Saturday, December 28, 2013

Herbal Aloe Vera



Aloe Vera is species of succulent plant in the genus Aloe, belonging to the Family Xanthorrhoeaceae, native to Sudan. It has become very popular for commercial cultivation due to its health benefits. Aloe vera has been used in herbal medicine in treating many kinds of disease, including wound, burn healing, minor skin infections, sebaceous cysts, diabetes, and elevated of cholesterol, etc. It is also one of many popular herb studied in scientific ways with some conflicted results.
There are many types of skin diseases in this world, the most common one is acne. Most people know acne is caused by dirt in oily skin pores, but little is known that acne is also caused by the system of toxins in the body. If our liver and kidney can not cleanse all toxins in the body, then our skin become the third source for cleansing the remainder of toxins.

The Ingredients 
The ten main areas of chemical constituents of Aloe vera include: amino acids, anthraquinones, enzymes, minerals, vitamins, lignins, monosaccharide, polysaccharides, salicylic acid, saponins, and sterols. 

1. The benefits of Aloe vera against acne vulgaris
Ance vulgaris ,one of skin diseases with areas of  scaly red skin with seborrhea, blackheads and whiteheads.  aloe vera one of many herbs in the subject has been studied and researched in pharmaceutical world, because of it common problem to the young ages and commercial profits. The study to compare the efficacy and safety of the combination of tretinoin (TR) cream (0.05%) and Aloe vera topical gel (50%) with TR and vehicle, has been well tolerated and significantly more effective than TR and vehicle for the treatment of mild to moderate acne vulgaris and with less side effects. Other researchers in the observation of  traditional medicines  of many cultures used to treat skin diseases, indicated that certain ingredients, including aloe vera, have been identified  in the treatment of psoriasis and atopic dermatitis,

References
(1) Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat Model (PubMed)
(2)   ALOE VERA by Gertrude Baldwin, http://www.herballegacy.com/Baldwin_Chemical.html
(3) Effect of Aloe vera topical gel combined with tretinoin in treatment of mild and moderate acne vulgaris: a randomized, double-blind, prospective trial. by Hajheydari Z, Saeedi M, Morteza-Semnani K, Soltani A.(PubMed)
(4) Innovations in natural ingredients and their use in skin care. by Fowler JF Jr, Woolery-Lloyd H, Waldorf H, Saini R.(PubMed)
(5) Oral aloe vera-induced hepatitis(PubMed)
(6) Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study(PubMed)

2. Aloe Vera and Skin diseases
Skin diseases is defined as a condition of skin damage and classified according to each pathogenic causes of diseases.

The benefits of Aloe Vera against Skin diseases
In the a systematic review of Aloe vera's clinical effectiveness, topical application of aloe vera is not an effective preventative for radiation-induced skin injuries, but might be effective for genital herpes and psoriasis.In support to above, study by Feily A, Namazi MR. indicated that Topical application of aloe vera is not an effective in sunburn or suntan protection, but might be effective in treating genital herpes, psoriasis, human papilloma virus, seborrheic dermatitis, aphthous stomatitis, xerosis, lichen planus, frostbite, burn, wound healing and inflammation.

References
(1) Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat Model (PubMed)
(2)   ALOE VERA by Gertrude Baldwin, http://www.herballegacy.com/Baldwin_Chemical.html
(3) Aloe vera: a systematic review of its clinical effectiveness by Vogler BK, Ernst E. (PubMed)
(4) Aloe vera in dermatology: a brief review. by Feily A, Namazi MR (PubMed).
(5) Oral aloe vera-induced hepatitis(PubMed)
(6) Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study(PubMed)


 3. Aloe vera and Irritable bowel syndrome
Irritable bowel syndrome is defined as a condition, if a patient is diagnosed with abdominal pain or discomfort, bloating, and alteration of bowel habits at least three times a month for the last 3 months without preexistence of other disease.

The effects of Aloe vera in Irritable bowel syndrome
Aloe vera (AV) has long been suggested by herbal medicine in treating irritable bowel syndrome (IBS) symptoms. In the comparison of the effectiveness of a mixture of Aloe vera (AV) and Matricaria recutita (German chamomile, GC) in treating Irritable bowel syndrome, GC inhibited only small bowel transit while the AV/GC mixture delayed gastric emptying at the doses of 150 and 300 mg/kg. The AV/GC mixture also reduced colonic transit and small bowel transit at the dose of 150 mg/kg. In other Randomised double-blind placebo-controlled trial of to test the effects of aloe vera for irritable bowel syndrome, there was no evidence that AV benefits patients with IBS and superior to placebo in improving quality of life proven Irritable Bowel Syndrome patients., but in 49 completed the protocol to 1 month and 41 to 3 months. Eleven of thirty-one (35%) AV patients, and 6 of 27 (22%) placebo patients responded at 1 month (p = 0.763). Diarrhoea predominant patients showed a trend towards a response to treatment at 1 month (10/23 V 2/14, p = 0.07).

References
(1) Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat Model (PubMed)
(2)   ALOE VERA by Gertrude Baldwin, http://www.herballegacy.com/Baldwin_Chemical.html
(3) Benefit of Aloe vera and Matricaria recutita mixture in rat irritable bowel syndrome: Combination of antioxidant and spasmolytic effects by Asadi-Shahmirzadi A, Mozaffari S, Sanei Y, Baeeri M, Hajiaghaee R, Monsef-Esfahani HR, Abdollahi M.(PubMed)
(4) Randomised double-blind placebo-controlled trial of aloe vera for irritable bowel syndrome.
(5) A Randomised, Cross-Over, Placebo-Controlled Study of Aloe vera in Patients with Irritable Bowel Syndrome: Effects on Patient Quality of Life by Hutchings HA, Wareham K, Baxter JN, Atherton P, Kingham JG, Duane P, Thomas L, Thomas M, Ch'ng CL, Williams JG.(PubMed)
(7) Oral aloe vera-induced hepatitis(PubMed)
(8) Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study(PubMed)

4. Aloe Vera and psoriasis
Aloe Vera is species of succulent plant in the genus Aloe, belonging to the Family Xanthorrhoeaceae, native to Sudan. It has become very popular for commercial cultivation due to its health benefits. Aloe vera has been used in herbal medicine in treating many kinds of disease, including wound, burn healing, minor skin infections, sebaceous cysts, diabetes, and elevated of cholesterol, etc. It is also one of many popular herb studied in scientific ways with some conflicted results.
Psoriasis is defined as chronic condition of inflammatory skin disease, affecting the joins and mostly happens to people who are obese are predisposed to diabetes and heart disease.

The benefits
Many herbal extracts have been used as topical management of plaque psoriasis, including Aloe vera   based on multiple studies. Aloe vera gel is used in alternative medicine over the century for the treatment of skin diseases, including psoriasis, and recent study showed that ethanolic extract of Aloe vera leaf gel also produced a significant increase in relative epidermal thickness and an overall antipsoriatic activity of high effective rate. Other in the comparison of comparion to evaluate the efficacy of Topical aloe vera (AV) and 0.1% triamcinolone acetonide (TA) in mild to moderate plaque psoriasis, AV cream may be more effective than 0.1% TA cream  found to be more effective in reducing the clinical symptoms of psoriasis. Unfortunately, in diverse dermatologic conditions, even though there are some promising results with the use of aloe vera, but clinical effectiveness of oral and topical aloe vera may require further studies, according to the study of Dr. Feily A, and Dr. Namazi MR.

References
(1) Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat Model (PubMed)
(2)   ALOE VERA by Gertrude Baldwin, http://www.herballegacy.com/Baldwin_Chemical.html
(3) Evaluation of the antipsoriatic activity of Aloe vera leaf extract using a mouse tail model of psoriasis.
(4)A prospective, randomized clinical trial comparing topical aloe vera with 0.1% triamcinolone acetonide in mild to moderate plaque psoriasis by Choonhakarn C, Busaracome P, Sripanidkulchai B, Sarakarn P.(PubMed
(5) Aloe vera in dermatology: a brief review by Feily A, Namazi MR.(PubMed)
(7) Oral aloe vera-induced hepatitis(PubMed)(8) Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study(PubMed)


5. Aloe Vera and gingivitis
Aloe Vera is species of succulent plant in the genus Aloe, belonging to the Family Xanthorrhoeaceae, native to Sudan. It has become very popular for commercial cultivation due to its health benefits. Aloe vera has been used in herbal medicine in treating many kinds of disease, including wound, burn healing, minor skin infections, sebaceous cysts, diabetes, and elevated of cholesterol, etc. It is also one of many popular herb studied in scientific ways with some conflicted results.
Gingivitis is defined as a condition of Inflammation of Gum Diseases.

The benefits
Aloe Vera anti-inflammatory property may be the result of the plant used in treatment of gum diseases. In the sudy of 45 patients who were diagnosed with plaque-induced gingivitis were included, aloe mouth wash is proven to be the most potential in reduction in gingival inflammation caused by plagues. Other in the the randomized, controlled, and double-blind study, a total of 148 systemically healthy subjects, showed statistically significant decrease in PI, MGI, and BI scores after the rinse regimen began in comparison with the use of chlorhexidine. But Dr. de Oliveira SM, and the research team in comparison of  Aloe vera and fluoridated dentifrice, found that here was a significant reduction on plaque and gingivitis in both groups, but no statistically significant difference was observed among them (p>0.01), Aloe vera did not show any additional effect on plaque and gingivitis control compared to the fluoridated dentifrice.

References
(1) Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat Model (PubMed)
(2)   ALOE VERA by Gertrude Baldwin, http://www.herballegacy.com/Baldwin_Chemical.html
(3) Aloe vera: It's effect on gingivitis by Ajmera N, Chatterjee A, Goyal V.(PubMed)
(4) A randomized, double-blind clinical study to assess the antiplaque and antigingivitis efficacy of Aloe vera mouth rinse by Chandrahas B, Jayakumar A, Naveen A, Butchibabu K, Reddy PK, Muralikrishna T.(PubMed)
(5) Effect of a dentifrice containing Aloe vera on plaque and gingivitis control. A double-blind clinical study in humans by de Oliveira SM, Torres TC, Pereira SL, Mota OM, Carlos MX.(PubMed)
(7) Oral aloe vera-induced hepatitis(PubMed)(8) Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study(PubMed)

6. Aloe Vera and Gastric Ulcers
Aloe Vera is species of succulent plant in the genus Aloe, belonging to the Family Xanthorrhoeaceae, native to Sudan. It has become very popular for commercial cultivation due to its health benefits. Aloe vera has been used in herbal medicine in treating many kinds of disease, including wound, burn healing, minor skin infections, sebaceous cysts, diabetes, and elevated of cholesterol, etc. It is also one of many popular herb studied in scientific ways with some conflicted results.
Gastric ulcers is defined as a condition of a localized tissue erosion in the lining the stomach. as a result of bacteria Helicobacter pylori (H pylori) in most cases.

The benefits
Some people with gastric ulcers may be not experience any symptoms at all, while others may have burning pain, severe nausea, and vomiting. In the comparison of the effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing, treatment of Aloe vera found to reduce leukocyte adherence and TNF-alpha level, elevate IL-10 level and promote gastric ulcer healing. Because of its Anti-inflammatory effects, treatment of  A. vera process the enhancement in leukocyte-endothelium interaction are associated with reduction in TNF-alpha level. Other in the study of acute gastric mucosal lesions induced by 0.6 M HCl and acid outpu, indicated that Aloe vera is endowed with gastric acid anti-secretory activity and could protect the gastric mucosa at low concentrations against injurious agents. Other component of Aloe vera, the Polymer fraction (Avpf; molecular weight cut-off ≥50 kDa; 150 mg/kg body weight, p.o.), reduce 50% of the mRNA expressions of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS), according to the study.


References
(1) Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat Model (PubMed)
(2)   ALOE VERA by Gertrude Baldwin, http://www.herballegacy.com/Baldwin_Chemical.html
(3) Effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing in rats, by Eamlamnam K, Patumraj S, Visedopas N, Thong-Ngam D.(PubMed)
(4) Anti-inflammatory effects of Aloe vera on leukocyte-endothelium interaction in the gastric microcirculation of Helicobacter pylori-infected rats by Prabjone R, Thong-Ngam D, Wisedopas N, Chatsuwan T, Patumraj S.(PubMed)
(5) The effect of Aloe vera A. Berger (Liliaceae) on gastric acid secretion and acute gastric mucosal injury in rats by Yusuf S, Agunu A, Diana M.(PubMed)
(6) Polymer fraction of Aloe vera exhibits a protective activity on ethanol-induced gastric lesions.
(7) Oral aloe vera-induced hepatitis(PubMed)
(8) Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study(PubMed)

 
7. Aloe Vera and Wound Healing
Aloe Vera is species of succulent plant in the genus Aloe, belonging to the Family Xanthorrhoeaceae, native to Sudan. It has become very popular for commercial cultivation due to its health benefits. Aloe vera has been used in herbal medicine in treating many kinds of disease, including wound, burn healing, minor skin infections, sebaceous cysts, diabetes, and elevated of cholesterol, etc. It is also one of many popular herb studied in scientific ways with some conflicted results.
Wound healing is the natural process of skin repair after it was damaged

The Benefits 
In a systematic review, there are cumulative evidence support that aloe vera might be an effective interventions used in burn wound healing for first to second degree burns as the use of aloe vera shortens the healing time. In acute and chronic wounds, although there are an absence of high quality clinical trial evidence to support the use of Aloe vera topical agents or Aloe vera dressings as treatments for acute and chronic wounds, but some studies found the reduction in healing time with Aloe vera was noted after haemorrhoidectomy (RR 16.33 days, 95% CI 3.46 to 77.15) and application of Aloe vera cream on the surgical site is effective in reducing postoperative pain both on resting and during defecation. In a study of a herbal gel of Aloe vera extract containing Carbopol 93, shows a promising effect on the wound healing process.

References
(1) Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat Model (PubMed)
(2)   ALOE VERA by Gertrude Baldwin, http://www.herballegacy.com/Baldwin_Chemical.html
(3) The efficacy of aloe vera used for burn wound healing: a systematic review.
Maenthaisong R, Chaiyakunapruk N, Niruntraporn S, Kongkaew C.(PubMed)
(4) Aloe vera for treating acute and chronic wounds. by Dat AD, Poon F, Pham KB, Doust J.(PubMed)
(5) Effects of Aloe vera cream on posthemorrhoidectomy pain and wound healing: results of a randomized, blind, placebo-control study, by Eshghi F, Hosseinimehr SJ, Rahmani N, Khademloo M, Norozi MS, Hojati O.(PubMed)
(6) Formulation development, optimization and evaluation of aloe vera gel for wound healing.
Khan AW, Kotta S, Ansari SH, Sharma RK, Kumar A, Ali J.(PubMed)
(7) Oral aloe vera-induced hepatitis(PubMed)
(8) Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study(PubMed)

8. Aloe Vera and Immunity
Aloe Vera is species of succulent plant in the genus Aloe, belonging to the Family Xanthorrhoeaceae, native to Sudan. It has become very popular for commercial cultivation due to its health benefits. Aloe vera has been used in herbal medicine in treating many kinds of disease, including wound, burn healing, minor skin infections, sebaceous cysts, diabetes, and elevated of cholesterol, etc. It is also one of many popular herb studied in scientific ways with some conflicted results.
The immune system is the set of cells and their activity against antigens or infectious agents that comprises of the body's defense system against diseases. The immune system does a great job of keeping people healthy and preventing infections. Beside foods and nutritional supplements, herbs also play a important role in helping the immune system defend against viruses and bacteria attacks.


The benefits
Aloe Vera is best known for it anti-inflammatory effects, in the study to determine the effect of the inner gel on bacterial-induced pro-inflammatory cytokine production, Aloe vera suppresses bacterial-induced pro-inflammatory cytokines from human immune cells. In the pharmacological study of Aloe arborescens Miller leaf components, The Aloe extract (1.2 mg ml(-1)) acted as a powerful immune stimulant in LPS- or poly I:C-activated SAF-1 cells, inducing a synergic effect on interconnected genes that are expected to be involved in different aspects of the immune responses. Aloe polymannose, a chemical compound found in Aloe Vera, also enhances the cognitive and immune functioning in patients of Alzheimer's disease by decreasing tumor necrosis factor-α, vascular endothelial growth factor, and interleukins-2 and-4

References
(1) Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat Model (PubMed)
(2)   ALOE VERA by Gertrude Baldwin, http://www.herballegacy.com/Baldwin_Chemical.html
(3) The inner gel component of Aloe vera suppresses bacterial-induced pro-inflammatory cytokines from human immune cells. by Habeeb F, Stables G, Bradbury F, Nong S, Cameron P, Plevin R, Ferro VA.(PubMed)
(4) Immune modulatory effects of Aloe arborescens extract on the piscine SAF-1 cell line. by Picchietti S, Bernini C, Belardinelli MC, Ovidi E, Taddei AR, Guerra L, Abelli L, Fausto AM.(PubMed)
(5) The effect of an aloe polymannose multinutrient complex on cognitive and immune functioning in Alzheimer's disease. by Lewis JE, McDaniel HR, Agronin ME, Loewenstein DA, Riveros J, Mestre R, Martinez M, Colina N, Abreu D, Konefal J, Woolger JM, Ali KH.(PubMed)
(7) Oral aloe vera-induced hepatitis(PubMed)
(8) Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study(PubMed)

9. Aloe Vera and Type II Diabetes
Aloe Vera is species of succulent plant in the genus Aloe, belonging to the Family Xanthorrhoeaceae, native to Sudan. It has become very popular for commercial cultivation due to its health benefits. Aloe vera has been used in herbal medicine in treating many kinds of disease, including wound, burn healing, minor skin infections, sebaceous cysts, diabetes, and elevated of cholesterol, etc. It is also one of many popular herb studied in scientific ways with some conflicted results.
Diabetes is defined as a condition caused by insufficient insulin entering the bloodstream to regulate the glucose. It is either caused by cells in pancreas dying off or receptor sites clogged up by fat and cholesterol. In some cases, diabetes is also caused by allergic reactions of cells in the immune system.

The benefits
Many herbs have been proven in studies to be effective in treating type II diabetes, including Aloe vera. As a popular herbal remedy in the United Kingdom, oral administration of aloe vera might be a useful adjunct for lowering blood glucose in diabetic patients as well as for reducing blood lipid levels in patients with hyperlipidaemia. In other study of Aloe vera gel in a mouse model of non-insulin-dependent diabetes mellitus, Oral administration of PAG for 8 weeks was found to reduce circulating blood glucose concentrations to a normal level in these DIO mice. Its leaf is also found to be useful in treating diabetes, as study said A. vera leaf pulp extract showed hypoglycaemic activity on type I (IDDM) and type II (NIDDM) diabetic rats, the effectiveness being enhanced for type II diabetes in comparison with glibenclamide. On the contrary, A. vera leaf gel extract showed hyperglycaemic activity on NIDDM rats.

References
(1) Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat Model (PubMed)
(2)   ALOE VERA by Gertrude Baldwin, http://www.herballegacy.com/Baldwin_Chemical.html
(3) Aloe vera: a systematic review of its clinical effectiveness. by Vogler BK, Ernst E.(PubMed)
(4) Hypoglycemic and hypolipidemic effects of processed Aloe vera gel in a mouse model of non-insulin-dependent diabetes mellitus. by Kim K, Kim H, Kwon J, Lee S, Kong H, Im SA, Lee YH, Lee YR, Oh ST, Jo TH, Park YI, Lee CK, Kim K.(PubMed
(5) Effect of Aloe vera leaves on blood glucose level in type I and type II diabetic rat models.

(7) Oral aloe vera-induced hepatitis(PubMed)
(8) Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study(PubMed)

10. Aloe Vera and Cancers
 Aloe Vera is species of succulent plant in the genus Aloe, belonging to the Family Xanthorrhoeaceae, native to Sudan. It has become very popular for commercial cultivation due to its health benefits. Aloe vera has been used in herbal medicine in treating many kinds of disease, including wound, burn healing, minor skin infections, sebaceous cysts, diabetes, and elevated of cholesterol, etc. It is also one of many popular herb studied in scientific ways with some conflicted results.
Cancer is a class of diseases in which a group of cells growing and multiplying disordered and uncontrollable way in our body, have become progressively worse and damaged other healthy tissues, sometimes spreads to other organs in the body via lymph or blood and results may be in death.

The Benefits  
Aloe-Emodi, a chemical compound found in Aloe vera, specifically suppress breast cancer cell proliferation by targeting ER α protein stability through distinct mechanisms and may be used as a possible application of anthraquinones in preventing or treating breast cancer in the future. Also in other study, Aloe-Emodi is considered as a potential value for the treatment of gastric cancer and cervical cancer because of its mechanisms are by means of cell cycle interruption and induce differentiation and suppressed the expression of PKCalpha and c-myc. Radiotherapy are most often used to treat head and neck cancer patients. Ina study of Aloe Vera, Dr. Ahmadi A. found that oral Aloe vera mouthwash may not only prevent radiation-induced mucositis, but also may reduce oral candidiasis of patients undergoing head and neck radiotherapy due to its antifungal and immunomodulatory properties

References
(1) Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat Model (PubMed)
(2)   ALOE VERA by Gertrude Baldwin, http://www.herballegacy.com/Baldwin_Chemical.html
(3) Potential prevention: Aloe vera mouthwash may reduce radiation-induced oral mucositis in head and neck cancer patients. by Ahmadi A.(PubMed)
(4) Emodin and Aloe-Emodin Suppress Breast Cancer Cell Proliferation through ER α Inhibition.
Huang PH, Huang CY, Chen MC, Lee YT, Yue CH, Wang HY, Lin H.(PubMed)
(5) Growth inhibitory effects of gastric cancer cells with an increase in S phase and alkaline phosphatase activity repression by aloe-emodin. by Guo J, Xiao B, Zhang S, Liu D, Liao Y, Sun Q.(PubMed
(6) Anticancer effect of aloe-emodin on cervical cancer cells involves G2/M arrest and induction of differentiation. by Guo JM, Xiao BX, Liu Q, Zhang S, Liu DH, Gong ZH.(PubMed)
(7) Oral aloe vera-induced hepatitis(PubMed)
(8) Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study(PubMed)

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11. Aloe Vera and Skin Aging
A free radical is any atom or molecule that has a single unpaired electron in an outer shell and highly reactive to react with other cell, which in turn, causes oxidative damage to the enzymes, other protein, unsaturated fatty acid, phospho-lipids, DNA and RNA, etc., leading to aging of the organisms, as a result of widespread damage due to set of a chain reaction auto-catalytically after attacking the lipid bilayers of the cell walls. Free radicals oxidative effects can damage to skin and speed up the skin aging process.

The benefits 
Aging is a natural process, no one can stop but delay it. Aloe Vera Supplementation has long been promote by cosmetic industrial for reducing the progress of skin aging. The study of 30 healthy female subjects over the age of 45 received 2 different doses (low-dose: 1,200 mg/d, high-dose: 3,600 mg/d) of aloe vera gel supplementation for 90 days. to determine the effect of aloe gel on the clinical signs and biochemical changes of aging skin, researchers found that the facial wrinkles improved significantly (p<0.05) in both groups, and facial elasticity improved in the lower-dose group. In the photoprotected skin, the type I procollagen mRNA levels were increased in both groups, albeit without significance; the MMP-1 mRNA levels were significantly decreased in the higher-dose group. In UVB-Induced Skin Photoaging in vitro, aloe shoot extract (AE), which is from the four-month-old shoots of Aloe vera, have a protective effect on UVB-induced skin photoaging in normal human dermal fibroblasts (NHDFs). As a anti-inflammatory agent,  aloe vera, havs been identified as beneficial in the treatment of psoriasis and atopic dermatitis.

References
(1) Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat Model (PubMed)
(2)   ALOE VERA by Gertrude Baldwin, http://www.herballegacy.com/Baldwin_Chemical.html
(3) Dietary Aloe Vera Supplementation Improves Facial Wrinkles and Elasticity and It Increases the Type I Procollagen Gene Expression in Human Skin in vivo. by Cho S, Lee S, Lee MJ, Lee DH, Won CH, Kim SM, Chung JH.(PubMed)
(4) A Comparative Study of Baby Immature and Adult Shoots of Aloe Vera on UVB-Induced Skin Photoaging in vitro. by Hwang E, Kim SH, Lee S, Lee CH, Do SG, Kim J, Kim SY.(PubMed)
(5) Innovations in natural ingredients and their use in skin care.
Fowler JF Jr, Woolery-Lloyd H, Waldorf H, Saini R.(PubMed)
(5) Oral aloe vera-induced hepatitis(PubMed)
(6) Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study(PubMed)

12. Aloe Vera and Polycystic Ovarian Syndrome 
Polycystic Ovarian Syndrome is defined as endocrinologic diseases caused by undeveloped follicles clumping on the ovaries that interferes with the function of the normal ovaries as resulting of enlarged ovaries, leading to hormone imbalance( excessive androgen), resulting in male pattern hair development, acne,irregular period or absence of period, weight gain and effecting fertility. It effects over 5% of women population or 1 in 20 women. According to the study by Desai BN, Maharjan RH, Nampoothiri LP. almost 70% PCOS women have abnormal serum lipid levels (dyslipidemia) and 50% of these women are obese. Several classes of pharmacological agents have been used to manage dyslipidemia. However, studies have shown adverse effects associated with these drugs(1).

The Benefits
Aloe Vera may be a potential herb in treating Polycystic Ovarian Syndrome by enhancing the reductions of plasma triglyceride and LDL cholesterol levels, with an increase in HDL cholesterol or by restoring the ovarian steroid status. According to the study of PCOS was induced in Charles Foster female rats by oral administration of non-steroidal aromatase inhibitor letrozole (0.5 mg/kg body weight, 21 days), AVG treated PCOS rats exhibited significant reduction in plasma triglyceride and LDL cholesterol levels, with an increase in HDL cholesterol. The gel treatment also caused reversion of abnormal estrous cyclicity, glucose intolerance, and lipid metabolizing enzyme activities, bringing them to normal. Other study also indicated that Aloe vera gel formulation exerts a protective effect in against the PCOS phenotype by restoring the ovarian steroid status, and altering key steroidogenic activity. This can be attributed to phyto-components present in the extract.
Dr.Pérez YY and the research team in the study of Effect of a polyphenol-rich extract from Aloe vera gel on experimentally induced insulin resistance in mice also indicated that decreasing significantly both body weight (p < 0.008) and blood glucose levels of Aloe, calculated using the homeostasis model assessment for insulin resistance (HOMA-IR) formula by the polyphenol-rich extract from Aloe vera.
Also in the confirmation of aboce result, study of Aloe vera leaves on blood glucose level in type I and type II diabetic rat models, vera leaf pulp extract showed hypoglycaemic activity on IDDM and NIDDM rats, the effectiveness being enhanced for type II diabetes in comparison with glibenclamide. On the contrary, A. vera leaf gel extract showed hyperglycaemic activity on NIDDM rats. It may therefore be concluded that the pulps of Aloe vera leaves devoid of the gel could be useful in the treatment of non-insulin dependent diabetes mellitus. Where non-diabetic (ND), type I (IDDM) and type II (NIDDM) diabetic rats.

References
(1) Aloe barbadensis Mill. formulation restores lipid profile to normal in a letrozole-induced polycystic ovarian syndrome rat Model (PubMed)
(2)   ALOE VERA by Gertrude Baldwin, http://www.herballegacy.com/Baldwin_Chemical.html
(3) Effect of Aloe barbadensis Mill. formulation on Letrozole induced polycystic ovarian syndrome rat model (PubMed)
(4) Effect of a polyphenol-rich extract from Aloe vera gel on experimentally induced insulin resistance in mice (PubMed)
(5) Oral aloe vera-induced hepatitis(PubMed)
(6) Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study(PubMed)

13. Aloe vera and breast cancer
Breast cancer (malignant breast neoplasm) is a cancer that starts in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. there is also rare cases that breast cancer starts in other areas of the breast. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.

The benefits
Aloe-Emodin, chemical components found in Aloe-vera and other herbssuch as  rhubarb, have been researched for treamtns of certain kinds of diseases, including cancers. The efficacy of the conponents are found to inhibit breast cancer cell proliferation by downregulating ER α protein levels, thereby suppressing ER α transcriptional activation. In the study of another constituent, a natural anthracycline from Aloe plant found to exhibit the cytotoxic activity against two human breast cancer cell lines; without (MCF-7) and with (SKBR-3) erbB-2-topoIIalpha coamplification.
The above finding suggested that Aloe vera chemical constituents may be a potential new medicine to treat breast cancer

References
(1) Emodin and Aloe-Emodin Suppress Breast Cancer Cell Proliferation through ER α Inhibition.
Huang PH, Huang CY, Chen MC, Lee YT, Yue CH, Wang HY, Lin H.(PubMed)
(2) Cytotoxicity of a natural anthraquinone (Aloin) against human breast cancer cell lines with and without ErbB-2: topoisomerase IIalpha coamplification by Esmat AY, Tomasetto C, Rio MC.(PubMed)
(3) Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study(PubMed)
(4) Oral aloe vera-induced hepatitis(PubMed)
14. Aloe vera and prostate cancer
Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth which spread to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during the Physical (rectum) exams.
The benefitsAloe-amodin, is an anthraquinone present in aloe latex from the aloe plant has been found to suppress Breast Cancer Cell Proliferation through ER α Inhibition. In prostate cancer syudy, it found to  inhibited both proliferation and anchorage-independent growth of PC3 cells by by targeting mTORC2 as mTORC2  plays an important role in PC3 androgen refractory prostate cell proliferation and anchorage-independent growth.

References
(1) Aloe-emodin suppresses prostate cancer by targeting the mTOR complex 2 by Liu K, Park C, Li S, Lee KW, Liu H, He L, Soung NK, Ahn JS, Bode AM, Dong Z, Kim BY, Dong Z.(PubMed)
(2) Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study(PubMed)
(3) Oral aloe vera-induced hepatitis(PubMed)
15. Aloe vera and colon cancer
Colon Cancer is defined as a condition of the abnormal proliferation of cells in the colon.

The benefits
Aloe emodin (AE), found in Aloe vera has been suggested to have antiproliferative activity in various cancer cell lines in many studies. In the study of coplon cancer, AE appreciably induced cell death specifically through the induction of apoptosis and by activating caspases 9/6,  depending on caspase-
6. Other study on colon cancer also showed an efficacy of AE as it suppressed the nuclear translocation and DNA binding of NF-κB, which is an important transcription factor for controlling MMP-2/9 and VEGF gene expression.

References
(1) Effect of inhibition of aloe-emodin on N-acetyltransferase activity and gene expression in human malignant melanoma cells (A375.S2) by Lin SY, Yang JH, Hsia TC, Lee JH, Chiu TH, Wei YH, Chung JG.(PubMed)
(2) Aloe emodin induces G2/M cell cycle arrest and apoptosis via activation of caspase-6 in human colon cancer cells by Suboj P, Babykutty S, Srinivas P, Gopala S.(PubMed)
(3) Aloe emodin inhibits colon cancer cell migration/angiogenesis by downregulating MMP-2/9, RhoB and VEGF via reduced DNA binding activity of NF-κB by Suboj P, Babykutty S, Valiyaparambil Gopi DR, Nair RS, Srinivas P, Gopala S.(PubMed)

16.  Aloe vera and lung cancer
Aloe Vera is species of succulent plant in the genus Aloe, belonging to the Family Xanthorrhoeaceae, native to Sudan. It has become very popular for commercial cultivation due to its health benefits. Aloe vera has been used in herbal medicine in treating many kinds of disease, including wound, burn healing, minor skin infections, sebaceous cysts, diabetes, and elevated of cholesterol, etc. It is also one of many popular herb studied in scientific ways with some conflicted results.
Lung cancer is defined as a condition of the abnormal growth of the cells in the lung's tissue. Most common form of primary lung cancers are derived from epithelial cells. In Us, Lung cancer is the leading cause of cancer deaths, causing 158,683 people deaths, including 88,329 men and 70,354 women, according to 2007 statistic.
The Ingredients
The main areas of chemical constituents of Aloe vera include: Aloe-Emodin, amino acids, anthraquinones, enzymes, minerals, vitamins, lignins, monosaccharide, polysaccharides, salicylic acid, saponins, and sterols.

The benefits
Aloe-emodin has been studied extensively through our scientific community for their effects against cancer including induced apoptosis in lung carcinoma cell lines CH27 (human lung squamous carcinoma cell)  by breaking of DNA strands (DNA ladders and sub-G(1) formation) and regulating of the expression of Bcl-2 family proteins (a suppressor of apoptosis). Other in the study of the effects of aloe-emodin-induced cell death in the human lung nonsmall cell carcinoma cell line H460, indicated that aloe-emodin involved the regulating apoptotic cell death through the a class of mitogen-activated protein kinases(p38). These results suggested that aloe-amodin found in ALOE VERA may be a potential agent for preventing and treating lung cancer.

References
(1) Effects and mechanisms of aloe-emodin on cell death in human lung squamous cell carcinoma.
Lee HZ, Hsu SL, Liu MC, Wu CH.(PubMed)
(2) Signaling pathway for aloe-emodin-induced apoptosis in human H460 lung nonsmall carcinoma cell. by Yeh FT, Wu CH, Lee HZ(PubMed)
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Wednesday, July 10, 2013

Neutropenia

Written for my twitter friend

Neutropenia is defined as a condition of  abnormally low number of neutrophils, as a  result of granulocyte disorder of that leads to Immunodeficiency with lower than normal  circulating white blood cells. Patients with neutropenia are susceptible to bacterial infections causes of neutropenic sepsis.
Neutropenia is either problems in the production of the cells by the bone marrow and destruction of the cells from somewhere else in the body, if  neutrophil count falls below 1,000 cells per microliter of blood.
Neutropenia can be classified into acute and chronic types, depending to the duration of the illness. Some researchers divided severity of the disease, depending to the absolute neutrophil count (ANC) and is described as follows(a).
1. Mild neutropenia, when the ANC falls below a lower limit of 1500 per mm3 (1.5 x 109 /1), but remains higher than 1000 per mm3 (1.0 x 109 /1).
2. Moderate neutropenia, when the ANC falls between 500 per mm3 and 1000 per mm3 (0.5 x 109 /1 - 1.0 x 109 /1)
3. Severe neutropenia, when the ANC falls below 500 per mm3 (0.5 x 109 /1)
 A. Causes and Risk Factors
A.1.  Causes

1. Decreased production in the bone marrow
a. Aplastic anemia  
According to the study by the Jichi Medical University, patients with aplastic anemia (AA) or myelodysplastic syndrome (MDS) often have persistent severe neutropenia and are susceptible to infectious complications(1).

b. Arsenic poisoning   
There is a report of a case of the death by arsenic poisoning of a 62-year-old white man is presented. One year prior to death, he developed intermittent bouts of severe gastroenteritis with vomiting and diarrhea, hyperpigmentation and keratosis of the skin, neutropenia, and Guillain-Barré-like neuropathy for which he was hospitalized several time(2).

c. Cancers
In the study to determine the impact of primary prophylactic colony-stimulating factor (CSF) use on febrile neutropenia in a large patient population receiving contemporary chemotherapy regimens to treat breast cancer, colorectal cancer, or non-small cell lung cancer (NSCLC), showed that of the 998 patients with breast cancer, 72 (7.2%) experienced febrile neutropenia, 28 of whom received primary prophylactic CSF. In the patients with breast cancer, we observed that primary prophylactic CSF use was associated with reduced febrile neutropenia rates; however, the analysis may have been confounded by unmeasured factors associated with febrile neutropenia(3).

d. Hereditary disorders   
Certain prenatal conditions can be result of Neutropenia
d. 1. Homozygous G6PC3 mutations
Severe congenital neutropenia type 4 (SCN4) is an autosomal recessive disorder caused by mutations in the third subunit of the enzyme glucose-6-phosphatase (G6PC3). Its core features are congenital neutropenia and a prominent venous skin pattern, and affected individuals have variable birth defects, according to the study by the Memorial University of Newfoundland(4).

d.2. Hematologic condition
There is a report results for six patients with Severe congenital neutropenia (SCN) who underwent Hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) between 1997 and 2001 at two transplant centers. Two patients transplanted for MDS survived. Both of these patients were transplanted without being given induction chemotherapy. Four patients, who all received induction chemotherapy for AML prior to HSCT, died. Administering induction chemotherapy prior to HSCT resulted in significant morbidity(5).

d.3. Cyclic neutropenia
there is a report of a 22 years old patient presented with recurrent episodes of diarrhoea, pharyngitis, apthous ulcers and fever for the past 6 months. The patient was admitted and blood studies revealed neutropenia with increased number of Large Granular Lymphocytes.  Later on it was found out that his neutrophil count dropped to less than 0.2 x 10(9)/L after every 3 weeks. Bone marrow study revealed decreases neutrophil precursors during these episodes. He was diagnosed with adult onset cyclic neutropenia and his episodes were treated with G-CSF and Ceftriaxone, according to the Medical Ward-D, Khyber Teaching Hospita(6).

d.4, HAX1 deficiency
HAX1 is a major regulator of myeloid homeostasis and underline the significance of genetic control of apoptosis in neutrophil development.(6a).


e. Copper, Vitamin B12, Folate deficiency
e.1. Copper deficiency
Copper deficiency is an under-recognized cause of reversible refractory anemia and leukopenia, particularly neutropenia, often misdiagnosed as myelodysplastic syndrome (MDS)(7).

e.2. Vitamin B12 and Folate deficiency
Women with breast carcinoma were asked to complete a questionnaire that recorded their use of dietary supplements. Blood samples were obtained for the assessment of serum vitamin B12 and folate levels before and after the first cycle of chemotherapy and for weekly complete blood counts, according to the study by the University of Vermont(8).

2. Increased destruction in the bone marrow
a. Autoimmune neutropenia
Antineutrophil antibodies are well recognized causes of neutropenia, producing both quantitative and qualitative defects in neutrophils and increased risk for infection. In primary autoimmune neutropenia (AIN) of infancy, a moderate to severe neutropenia is the sole abnormality; it is rarely associated with serious infections and exhibits a self-limited course. Chronic idiopathic neutropenia of adults is characterized by occurrence in late childhood or adulthood, greater prevalence among females than among males, and rare spontaneous remission. Secondary AIN is more commonly seen in adults and underlying causes include collagen disorders, drugs, viruses and lymphoproliferative disorders, according to the study by the University of Milan(9).  
b. Chemotherapy-induced neutropenia
Thirty-two patients on treatment for solid cancers who were admitted with febrile neutropenia between January and December 2010, according to the Cambridge University Hospitals NHS FoundationTrust(2).
There is a study indicated that chemotherapy-induced febrile neutropenia in the inpatient and outpatient settings for a solid tumor or non-Hodgkin's lymphoma(10).

3. Medication induced neutropenia
According to the study by the University Hospital of Strasbourg, over the last 20 years, the incidence of idiosyncratic drug-induced agranulocytosis or acute neutropenia has remained stable at 2.4-15.4 cases per million, despite the emergence of new causative drugs: antibiotics (beta-lactam and cotrimoxazole), antiplatelet agents (ticlopidine), antithyroid drugs, sulfasalazine, neuroleptics (clozapine), antiepileptic agents (carbamazepine), nonsteroidal anti-inflammatory agents and dipyrone. Drug-induced agranulocytosis remains a serious adverse event due to the occurrence of severe sepsis with severe deep infections (such as pneumonia), septicemia and septic shock in around two thirds of patients(11).

4. Hemodialysis
Neutropenia and degranulation of neutrophils during hemodialysis with cellulosic membranes have been linked to complement activation, whereas in the synthetic polymethyl methacrylate (PMMA) membrane, degranulation occurs without notable complement activation, according to the study by the University of Freiburg(12).

5. Bacteria and viral infections
a. Bacteria infection
The College of Medicine, Korea University, reported of a 259 cases of febrile neutropenia occurring in 137 patients with hematologic disease(13). Also according to the Universidad Pontificia Bolivariana, in the study of 101 episodes of FN in 43 patients with the median age was 44 years. 63.5% of patients had no apparent clinical focus of infection at admission, 11.8% had soft tissue compromise and 8.9% urinary tract infection. Bacteremia was documented in 41.5% and catheter-associated bacteremia in 3.9%. The most common organisms were Escherichia coli 43.4%, Klebsiella pneumoniae 17.3% and Staphylococcus aureus 8.6%. Of those isolated in blood 84.7% were Gram negative rods and 15.2% were Gram positive bacteria. Piperacillin/tazobactam was the most common empirically prescribed antibiotic (81.1%). Mortality of FN episodes occurred in 8 (7.92%) patients, 5 (62.5%) attributable to infection and 3 (37.5%) due to progression of hematologic malignancy with a resolution of FN(14).

b. Viral infections 
Patients with hematological malignancies and therapy induced neutropenia (n = 159) were screened regarding a broad range of common respiratory viruses in the nasopharynx and for viruses commonly detected in severely immunosuppressed patients in peripheral blood. Quantitative PCR was used for detection of viruses. A viral pathogen was detected in 35% of the patients. The detection rate was rather similar in blood (22%) and NPA (18%) with polyoma BK virus and rhinovirus as dominating pathogens in blood and NPA, respectively. Patients with chronic lymphocytic leukemia (CLL) (p<0.01) and patients with fever (p<0.001) were overrepresented in the virus-positive group(15).

A.2. Risk factors
1. H-ficolin
According to the study by the Department of Pediatrics, University of Bern, Bern, low concentration of H-ficolin was associated with an increased risk of FN, particularly FN with bacteraemia, in children treated with chemotherapy for cancer. Low H-ficolin thus represents a novel risk factor for chemotherapy-related infections(16).

2. Deficiency of mannose-binding lectin
Mannose-binding lectin-associated serine protease-2 (MASP-2) is an essential component of the lectin pathway of complement activation. According to the study by the University of Bern, MASP-2 deficiency was associated with an increased risk of FN in children treated with chemotherapy for cancer. MASP-2 deficiency represents a novel risk factor for chemotherapy-related infections(17).

3. Poison
Exposure to certain poison are associated to the increased risk of the disease(18).
According to the article of Delaware physician care, an aetna health plan, indicated the following risk factors(19).


4. Chemotherapy Regimen 
The aggressiveness of the chemotherapy regimen can be taken into account by giving to each individual drug a score (ranging from 0 to 4), according to its expected hem atological toxicity . For combination drug regimens, the regimen’s score is calculated by taking the mean of the individual agent’s weights. (Example: vinblastine + carboplatin = 5 ÷ 2= 2.5). A score ≥3 is considered high risk for neutropenia

5. Pre-existing neutropenia
a. Age >65 of age
b. Previous chemotherapy or radiation therapy
c. Advanced disease or uncontrolled cancer
d. Pre - existing n eutropenia, anemia or other cytopenias, or b one marrow involvement of tumor
e. Act ive Infection/open wounds, pneumonia, sepsis o Poor performance status (e.g., poor nutritional status, low albumin)
f. Renal impairment (GFR<30 or age >65 and elevated creatinine)
g. Liver dysfunction (elevated bilirubin, alkaline phosphatase)
h. Other serious co - morbidities (heart disease, hypertension, COPD)
i. Previous episodes of FN
g. A previous neutropenic complication in the immediate previous cycle with no plan to reduce dose intensity(19).

B. Symptoms
Neutrophilic granulocytes form the major type of leukocytes with counts ranging from about 1500-5000 cells/ micro l of blood under normal conditions. Neutrophils protect our body against bacterial and fungal infections. For this purpose, these cells are equipped with a machinery to sense the site of an infection and, upon local extravasation, rapidly move towards the site with invading micro-organisms, to ingest and kill them(20). The most common symptoms are
1. Fever
Fever during neutropenia (FN) is a frequent and potentially life-threatening complication of the treatment of childhood cancer, according to the Royal Children's Hospital Melbourne, Peter MacCallum Cancer Centre, Federal University of Sao Paulo, Alcuin College and Leeds Teaching Hospitals Trust(21).

2. Frequent infection symptoms can be resulted as
a. Mouth ulcers
b. Diarrhea
c. Burning sensation when urinating
d. Unusual redness, pain, or swelling around a wound, or
e. Sore throat
f. Abscesses
g. Rashes

C. Complications and diseases associated to Neutropenia
C.1. Complications
1. Unstable hemodynamic status, respiratory distress, altered mental status, newly developed arrhythmia that required intervention, and death
In the study to evaluate associations between the risk factors and serious complications in patients presenting to the ED with febrile neutropenia by reviewing the health information system database to identify a retrospective cohort of patients with febrile neutropenia who visited the ED of a tertiary medical hospital from January to December 2008, showed that serious complications during hospitalization were defined as unstable hemodynamic status, respiratory distress, altered mental status, newly developed arrhythmia that required intervention, and death during hospitalization.  Only episodes of febrile neutropenia caused by chemotherapy for underlying cancer were included(22).

2. High risk for septic complications
In the study to evaluate pentraxin 3 as a marker for complications of neutropenic fever in 100 hematologic patients receiving intensive chemotherapy with Pentraxin 3 and C-reactive protein measured at fever onset and then daily to day 3, showed that in comparison to C-reactive protein, pentraxin 3 achieved its maximum more rapidly. Pentraxin 3 correlated not only with the same day C-reactive protein but also with the next day C-reactive protein. High pentraxin 3 on day 0 was associated with the development of septic shock (P=0.009) and bacteremia (P=0.046). The non-survivors had constantly high pentraxin 3 levels(23).

C.2. Diseases associated to Neutropenia
Chronic neutropenia with autoimmune diseases is associated mainly with rheumatoid arthritis (RA), as Felty's syndrome or large granular lymphocyte (LGL) leukemia, and with systemic lupus erythematosus (SLE)(23a).
1.  Rheumatoid arthritis (RA) 
T cell large granular lymphocyte leukemia (T-LGL) is a disease characterized by clonal expansion of cytotoxic T cells (CTLs). It generally follows an indolent course and is notable for an association with chronic inflammation, neutropenia and rheumatoid arthritis (RA), according to the study by the Duke University Medical Center(24).

2. Felty’ssyndrome or large granular lymphocyte (LGL) 
Large granular lymphocyte (LGL) leukemia is a clonal proliferation of cytotoxic cells, either CD3(+) (T-cell) or CD3(-) (natural killer, or NK). Both subtypes can manifest as indolent or aggressive disorders. T-LGL leukemia is associated with cytopenias and autoimmune diseases and most often has an indolent course and good prognosis. Rheumatoid arthritis and Felty syndrome are frequent, according to the study by Michal G. Rose, M.D., The Comprehensive Cancer Center (IIID), VA Connecticut Healthcare System(25).

3. Leukemia and related disorders
T-cell large granular lymphocyte (LGL) leukemia is a clonal proliferation of cytotoxic T cells, which causes neutropenia, anemia, and/or thrombocytopenia. This condition is often associated with autoimmune disorders, especially rheumatoid arthritis, and other lymphoproliferative disorders(26).

4. Systemic lupus erythematosus (SLE)
In the study of 89 SLE patients (92% females), with their mean (SD) age and disease duration at the study entry of 31.7 (12.2) years and 2.4 (2.9) months, leukopenia was found at the diagnosis in 51.6% of the cases. The cumulative prevalence of leukopenia, lymphopenia, and neutropenia was observed in 57.3%, 96.6%, and 60.7%, respectively(27).

5. Crohn's disease
There is a report of a 29-year-old woman with a 20-year history of Crohn's disease and neutropenia. Because of repeated complications of Crohn's disease, she has undergone three intestinal resections and also has had recurrent skin abscesses, sinusitis, and pneumonia. Persistent neutropenia has been noted throughout the course of her disease, and antineutrophil antibodies have been detected in her serum and that of her younger brother, who also has Crohn's disease and neutropenia(28)

6. Graves' disease
There is a report of a 38-year-old man with Graves' disease taking propylthiouracil (PTU) for 6 years developed neutropenia and marked splenomegaly(29). 

7. Poikiloderma
Poikiloderma with neutropenia (PN, OMIM 604173) is a rare autosomal-recessive genodermatosis. Mutations in the C16orf57 gene have been recently identified as the cause(29a).

8. without serious complications in children with acquired neutropenia
In the study to to identify the relationship of acquired neutropenia with childhood infections and to assess its clinical course, complications, and outcome of 161 previously healthy children with febrile neutropenia/leukopenia aged (mean ± SD) 3.02 ± 3.86 years (range, 0.1-14). One hundred and thirty-six out of 161 patients (84.5 %) had transient neutropenia (TN), while in 25 patients, neutropenia was chronic (CN) and persisted for ≥180 days, indicated that a infectious agent was isolated in 98/161 (60.9 %) cases, in 68.4 % patients with TN, and in 20 % of those with CN (p = 0.001). Among the patients with CN, seven had positive antineutrophil antibodies (autoimmune neutropenia) and four were eventually diagnosed with hematological malignancy. In all age groups, TN was of short duration (<1 month), of mild to moderate severity, and was predominantly associated with viral infections. Two years after diagnosis, 143/161 children (88.8 %) were available for follow-up. One hundred and thirty-seven of 143 (95.8 %) had recovered completely, while the rest remained neutropenic(30).
  
D. Misdiagnosis and Diagnosis
D.1. Misdiagnosis
1. Kikuchi's disease
Kikuchi's disease is usually a self limiting illness characterised by pyrexia, neutropenia, and cervical lymphadenopathy particularly in young women of Asian descent. This often leads to an initial misdiagnosis of lymphoma(31).

2. Myeloid sarcoma of the spleen
There is a report of a 58-year-old woman presented with a 3-day history of fever and abdominal pain. The results of hematological work-up were consistent with acute myeloblastic leukemia (M2, French-American-British classification). Being susceptible to infection in this leukemic patient with severe neutropenia, a diagnosis of splenic abscess was straightforward, plausibly supported by the radiographic findings. Despite empiric broad-spectrum antibiotic treatment, hyperleukocytosis with resultant pulmonary leukostasis supervened. Histological sections from ultrasound-guided percutaneous core-needle biopsy of the spleen confirmed the diagnosis of myeloid sarcoma. However, delayed leukemia-targeted therapy, unfortunately, resulted in catastrophic mortality(32).

3. Acute myeloblastic leukemia M3v
Splenic abscesses in therapy-resistant acute myeloblastic leukemia presenting as recurrent febrile neutropenia and unresolved splenomegaly, according to the study by the Ankara Oncology Hospital(33).

4. Appendicitis
There is a report of a 13-year-old boy with acute myelogenous leukemia developed 2 episodes of febrile neutropenia during induction therapy. The second one was treated with a 5-day course of parenteral antimicrobial therapy, but the patient then presented with right lower quadrant abdominal tenderness, guarding, and rebound tenderness. Abdominal ultrasonography and computed tomography revealed appendicitis. Conservative medical management was unsuccessful, and appendectomy was performed 5 days after appendicitis was diagnosed(34).

D.2. Diagnosis
If you are experience of certain symptoms above, after a complete physical examination and recording family and health history, the tests which your doctor order may include
1. A complete blood count, or CBC
It is also known as  also known as full blood count (FBC) or full blood exam (FBE) or blood panel with an aim to check for information of the concentration of white blood cells, red blood cells, and platelets in the blood of a patient's blood

2. Bone Marrow biopsy
The procedure of bone marrow biopsy involves the use of a syringe to withdraw a sample of liquid bone marrow (aspiration) from the hip bone and then checking the samples for any abnormality of neutrophils.

Other tests may also be necessary, depending to the underlined causes of the diseases of which include(35)
4. Test for antineutrophil antibodies
5. Autoantibody screen, 
6. Vitamin B12 and folate assays
7. Acidified serum test, and tests for detecting systemic lupus erythematosus.  

E. Preventions
E.1. Diet to prevent Neutropenia
a. The Neutropenic diet, according to the article of The Neutropenic diet from Non Hopkin's lymphoma cyberfamily(36)
FOOD GROUPS
ALLOWED NOT ALLOWED
Dairy All pasteurized, grade "A" milk and milk products.
Commercially-packaged cheese and cheese products made with pasteurized milk (i.e. mild and medium cheddar, mozzarella, parmesan, Swiss, etc.)
Pasteurized yogurt
Dry, refrigerated, and frozen pasteurized whipped topping
Ice cream, frozen yogurt, sherbet, ice cream bars, homemade milkshakes
Commercial nutritional supplements and baby formulas, liquid and powdered
Unpasteurized or raw milk, cheese, yogurt, and other milk products
Cheeses from delicatessens
Cheeses containing chili peppers or other uncooked vegetables
Cheese with molds (i.e. blue, Stilton, Roquefort, gorgonzola)
Sharp cheddar, brie, camembert, feta cheese, farmer's cheese
Vegetables All cooked frozen or canned vegetables.
All cooked herbs and spices (add at least 5 minutes before end of cooking)
Raw vegetables, salads
Caesar Salads with Caesar dressing
Pepper
Garnishes
Uncooked herbs and spices
Fruits and Nuts Canned and frozen fruit and fruit juices
Thick skinned fruits (oranges, bananas)
Melons cut up and used immediately
Canned or bottled roasted nuts
Nuts in baked products
Commercially packaged peanut butter
Dried fruits
Raw fruit; foods containing raw fruits
Unpasteurized fruit and vegetable juices
Raw nuts
Roasted nuts in the shell
Precut fresh fruits
Bread, Grain, and Cereal Products All breads, bagels, rolls, pan-cakes, sweet rolls, waffles, French toast
Potato chips, corn chips, tortilla chips, pretzels, popcorn
Cooked pasta, rice, and other grain
All cereals, cooked and ready-to-eat
Raw grain products
Bakery breads, cakes, donuts, muffins
Potato/macaroni salad
Entrees, Soups All cooked entrees and soups All miso products (i.e. miso soup)
Meat and Meat Substitutes All well-cooked or canned meats (beef, pork, lamb, poultry, fish, shellfish, game, ham, bacon, sausage, hot dogs)
Well-cooked eggs (white cooked firm with thickened yolk acceptable, i.e. hard boiled, over hard)
Pasteurized egg substitutes (i.e. Egg Beaters)
Commercially-packaged salami, bologna, and other luncheon meats
Canned and commercially-packaged hard smoked fish, refrigerated after opening
Cooked tofu (which must be cut into 1" cubes or smaller and boiled a minimum of five minutes in water or broth before eating or using in recipes)
Raw or undercooked meat,, poultry, fish, game, tofu
Meats and cold cuts from delicatessen
Hard cured salami in natural wrap
Cold smoked salmon, lox
Pickled fish
Tempe (tempeh) products
Sushi
Raw oysters/clams
 
 
Beverages Tap water
Commercial bottled distilled and natural waters
All canned, bottled, powdered beverages
Instant and brewed coffee, tea; cold brewed tea made with boiling water
Brewed herbal teas using commercially-packaged tea bags
Commercial nutritional supplements, liquid and powdered
Well water (unless tested yearly and found safe)
Cold-brewed tea made with warm or cold water sun tea
Egg nog
Fresh apple cider 
Homemade lemonade
Spring water
Fats Oil, shortening
Refrigerated lard, margarine, butter
Commercial shelf-stable mayonnaise and salad dressings (including cheese-based salad dressings, refrigerated after opening)
Fresh salad dressings containing aged cheese (i.e. blue, Roquefort) or raw eggs, stored in refrigerated case
Desserts Refrigerated commercial and homemade cakes, pies, pastries, and pudding
Refrigerated cream-filled pastries
Homemade and commercial cookies
Shelf-stable cream-filled cupcakes (i.e. Twinkies, Ding Dong), fruit pies (i.e. Poptarts, Hostess frit pies), and canned pudding
Unrefrigerated cream-filled pastry products (not shelf-stable)
Cream or custard filled donuts
Other Salt, granulated sugar, brown sugar
Jam, jelly, syrups (refrigerated after opening)
Commercially-packaged (pasteurized) honey 
Catsup, mustard, BBQ sauce, soy sauce, other condiments (refrigerated after opening)
Pickles, pickle relish, olives (refrigerated after opening)

Raw or unpasteurized honey
Herbal and non-traditional (health food store) nutritional supplements, Chinese herbs
Brewers yeast, if eaten uncooked
But according to the study by the New York University, despite improved survival of children with cancer, opportunistic infections remain a significant cause of morbidity and mortality in this population. Several interventions have been tried to decrease the incidence of infection by reducing patients' exposure to bacteria during neutropenia. The neutropenic diet is one such intervention that was intended to limit the introduction of bacteria into the host's gastrointestinal tract. The only studies evaluating this diet have used this strategy in combination with multiple other interventions, and the independent effect of this diet remains unknown(37). Other in the study to demonstrate a safe and feasible methodology to evaluate the infection rate in pediatric cancer patients randomized to the neutropenic diet or to Food and Drug Administration (FDA)-approved food safety guidelines with pediatric oncology patients receiving myelosuppressive chemotherapy randomized to the neutropenic diet or to FDA food safety guidelines and followed through one chemotherapy cycle found that four patients on each diet arm developed febrile neutropenia. The adherence rate was 94% for the neutropenic diet and 100% for the food safety guidelines. Although patients were able to tolerate both diets, there was more reported difficulty adhering to the neutropenic diet. Infection rates for children with cancer on the neutropenic diet were similar to those for patients following food safety guidelines(38).

b. Foods to enhance immune system
One of the most notable changes in the 2006 guidelines is that the level of risk when preventive use of blood cell growth factors is justified has been lowered. Previously, preventive use of blood cell growth factors was recommended for patients who had at least a 40% risk of developing febrile neutropenia. The 2006 guidelines recommend preventive use of blood cell growth factors for patients whose risk of febrile neutropenia is 20% or higher.
b.1. Green tea
Consuming green tea or its active ingredient, epigallocatechin-3-gallate (EGCG), has been shown consistently to benefit the healthy functioning of several body systems. In the immune system specifically, accumulating evidence has revealed an immunomodulating effect of green tea/EGCG. Several types of immune cells in both the innate and adaptive immune systems are known to be affected in varying degrees by green tea/EGCG. Among them, the dramatic effect on T cell functions has been repeatedly demonstrated, including T cell activation, proliferation, differentiation, and production of cytokines, according to the study by the Harvard Medical School(39).

b.2. Garlic
In the study to evaluate the immunostimulatory activities such as cell proliferation, tumor necrosis factor (TNF-α) and nitric oxides (NO) production of raw garlic and black garlic extracts on individual primary lymphocytes or macrophages isolated from the blood of 21 volunteers indicated that the immunostimulatory activities of RGE and BGE can be strongly correlated with the antioxidant and anticancer activities. Determination of immunostimulatory activities of different types of garlic using immune cells isolated from volunteers was dependent on the individual constituents due to changes in the composition of garlic during processing. Individual primary immune cells might be used as important tools to determine individual differences in all food ingredients for the development of personalized immunostimulatory active foods(40).

3. Turmeric and ginger
According to the study by the Assam University, polar fractions of C. longa and Z. officinale rhizomes boost the immune system by altering the cytokine milieu of the immunosuppressed macrophages, thus modulating their functional status. Therefore, it can be inferred that dietary intake of C. longa and Z. officinale potentiates the non-specific host defenses against opportunistic infections(41).

4.  Tomato
In the study to examine the effects of lycopene found abundantly in tomato, on the oxidative injury and immunity activities of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer rats, showed that dministration of lycopene to gastric carcinoma-induced rats largely up-regulated the redox status and immunity activities to decrease the risk of cancer. up-regulation of antioxidants and immunity by lycopene treatment might be responsible for the anticancer effect in gastric carcinoma(42).


E.2. Phytochemicals to prevent Neutropenia
1. Epigallocatechin-3-gallate
One of the proposed health benefits of consuming green tea is its protective effect on autoimmune diseases. Research on the immunopathogenesis of autoimmune diseases has made significant progression in the past few years and several key concepts have been revised. T cells, particularly CD4(+) T helper (Th) cells, play a key role in mediating many aspects of autoimmune diseases. Upon antigenic stimulation, naïve CD4(+) T cells proliferate and differentiate into different effector subsets. Th1 and Th17 cells are the pro-inflammatory subsets of Th cells responsible for inducing autoimmunity whereas regulatory T cells (Treg) have an antagonistic effect. Green tea and its active ingredient, epigallocatechin-3-gallate (EGCG), have been shown to improve symptoms and reduce the pathology in some animal models of autoimmune diseases(43)

2. Allicin 
Allicin treatment enhanced the production of pro-inflammatory mediators such as IFN-γ, TNF, IL-12p70 and NO. The absolute numbers of CD4+ T cells, DCs and macrophages were significantly higher in allicin-treated mice. In addition, allicin promoted the maturation of CD11c+ DCs, whereas it did not cause major changes in IL-4 and the level of anti-inflammatory cytokine IL-10(44).

3. Curcumin
In the study to investigate the bioavailablity of a well-established dietary antiinflammatory, curcumin, and examines its effect on adaptive immunity, found that long-term, low-dose, oral consumption of curcumin activates peroxisome proliferator-activated receptor-gamma, deactivates type 1 response, inhibits inducible nitric oxide synthase, and interferes with adaptive immunity to exacerbate the pathogenesis of Leishmania donovani infection in vivo. These in vivo effects can be correlated to activities on infected residential macrophages in vitro. Therefore, when reactive radicals generated from inflammation play the dominant role in elimination of pathogens, excessive use of the antioxidative supplements may compromise microbial defense(45).

4. Carotenoids
In the study to investigate the effects of orally administered carotenoids from natural sources on the non-specific defense mechanisms of rainbow trout in a nine-week feeding trial, showed that dietary carotenoids from both D. salina and P. rhodozyma can modulate some of the innate defense mechanisms in rainbow trout(46).

E.3. Antioxidant to prevent Neutropenia
1. Selenium  
Dietary selenium (]Se), mainly through its incorporation into selenoproteins, plays an important role in inflammation and immunity. Adequate levels of Se are important for initiating immunity, but they are also involved in regulating excessive immune responses and chronic inflammation. Evidence has emerged regarding roles for individual selenoproteins in regulating inflammation and immunity, and this has provided important insight into mechanisms by which Se influences these processes, according to the study by the University of Hawaii(47).

2. Vitamin D and C 
Inflammatory responses are operationally characterized by pain, redness, heat and swelling at the site of infection and trauma. Mast cells reside near small blood vessels and, when activated, release potent mediators involved in allergy and inflammation. Vitamin D modulates contraction, inflammation and remodeling tissue. Therapy targeting vitamin D3 signaling may provide new approaches for infectious and inflammatory skin diseases by affecting both innate and adaptive immune functions.  Vitamin C is also an anti-oxidant well-known as an anti-scurvy agent in humans. Vitamin C inhibits peroxidation of membrane phospholipids and acts as a scavenger of free radicals and is also required for the synthesis of several hormones and neurotransmitters. In humans, vitamin C reduces the duration of common cold symptoms, even if its effect is not clear. Supplementation of vitamin C improves the function of the human immune system, such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis and delayed-type hypersensitivity(48).

3. Zinc
T cell functions were affected adversely even when the deficiency of zinc was mild in humans. Characteristically during zinc deficiency, the serum thymulin activity (a thymic hormone) was decreased which was restored following zinc supplementation. Our studies also showed that zinc deficiency caused an imbalance between TH1 and TH2 functions. The production of IFN-g, IL-2, TNF-a (products of TH1 cells) were decreased, whereas the production of IL-4, IL-6 and IL-10 (products of TH2) were not affected during zinc deficiency. T cell subpopulation studies revealed that the CD4+ CD45RA+ to CD4+ CD45RO+ ratio was decreased as a result of zinc deficiency, suggesting that zinc may be required for the regeneration of new CD4+ T cells. zinc deficiency decreased NK cell lytic activity and caused a decrease in the percentage of CD8+ CD73+ T cells which are known to be predominantly precursors of cytotoxic T cells. In a suitable cell culture model our studies revealed that the gene expression of a DNA synthesizing enzyme TK was affected adversely which resulted in delayed cell cycle and decreased cell growth(49).

4. Resveratrol
In the study to evaluate the immune modulating effect of low dose of resveratrol by the
Chinese Academy of Sciences, showed that resveratrol (0.75-6 micromol/L) concentration-dependently promoted lymphocyte proliferation and IL-2 production induced by ConA. Sac induced IL-12 and IFN-gamma (interferon type II) production were also concentration-dependently enhanced by resveratrol, while IL-10 production was inhibited. Resveratrol (4 mg/kg, ig) promoted DTH response of mouse, which was suppressed by ethanol (16 %, w/v) consumption(50).

F. Treatments
F.1. In conventional medicine perspective
F.1.2. Treatments is depending to the underlined causes of the disease, patient with Neutropenia are advised to the lists of below
1. Good oral hygiene and dental care
According to the study in a report of clinical periodontal findings and microflora profiles of 2 children, 1 with severe congenital neutropenia (SCN, Kostmann type) and 1 with cyclic neutropenia (CN), by the Hiroshima University Faculty of Dentistry showed that Use of 1% povidone iodine solution and local antibiotic application under supervised oral hygiene were helpful to improve gingival conditions in patients with chronic neutropenia(51). Other study indicated that in the study of Benign familial neutropenia (BFN), it is a condition where there is a decrease in circulating neutrophils in the blood and patients suffer from oral manifestations which include: persistant periodontal disease, recurrent neutropenic ulceration and candidal infections(52).

2. Others according to the article of WebMD and Medscape include
2.1. WebMD(53)
a. Avoiding contact with sick people
b. Always wearing shoes
c. Cleaning cuts and scrapes, then covering them with a bandage
d. Using an electric shaver rather than a razor
e. Avoiding animal waste and, when possible, not changing infants' diapers
f. Avoiding unpasteurized dairy foods; undercooked meat; and raw fruits, vegetables, grains, nuts, and honey
g. Staying out of hot tubs, ponds, and rivers

2.2. Medscape(54)
a. Remove any offending drugs or agents in cases involving drug exposure: If the identity of the causative agent is not known, stop administration of all drugs until the etiology is established
b. Use careful oral hygiene to prevent infections of the mucosa and teeth
c. Avoid rectal temperature measurements and rectal examinations
d. Administer stool softeners for constipation
e. Use good skin care for wounds and abrasions: Skin infections should be managed by someone with experience in the treatment of infection in neutropenic patients.

F.2.2.  Types of therapy depending to the underlined causes of the disease but not limit to include
1. Corticosteroids 
Corticosteroids is the synthetic form of cortisol produced hat your adrenal glands produce naturally.
The aims of the medicine is to reduce autoantibody production, There is a report of a case of neutropenia in an infant, associated with repeated minor infections which responded to treatment with antibiotics. A granulocyte agglutinin was detected in the serum. Following treatment with prednisolone the neutropenia remitted, the antibody disappeared and the infections ceased(55).

2. Antibiotics 
There is a report by the Urmia University of Medical Sciences, of a 22-year-old male with idiopathic autoimmune thrombocytopenia whose diagnosis was made at age of eight. He underwent splenectomy at age ten and ITP recurred at age 21 with episodes of infection and severe neutropenia (absolute count around 170/μl). He showed no response to immunoglobulin, corticosteroids, danazol, cyclosporine and azathioprine. Anti-CD20 antibody was administered at a dose of 375 mg/m(2) once a week for 2 weeks. After the second infusion of rituximab, the platelet count increased from 4,000 to 516,000/mm(3) and neutrophils count raised from 180 to 545/mm(3). The response improvement persisted during follow up for 9 months (neutrophil count 4,390/mm(3))(56). 
 
3. Granulocyte colony-stimulating factor (G-CSF) 
Granulocyte colony-stimulating factor (G-CSF) also known as colony-stimulating factor 3 (CSF 3), is a proteins that contain oligosaccharide chains (glycans) used to stimulate the bone marrow in production of granulocytes and stem cells and release them into the bloodstream. In a report of a  treated a case of autoimmune neutropenia in a 57-year-old, by the  Kyushu University, because neutropenia persisted despite the administration of prednisolone for 30 days, daily subcutaneous injection of human recombinant granulocyte colony-stimulating factor (rhG-CSF) at a dosage of 100 micrograms was started. Neutrophil count increased gradually and reached a plateau of 5,000/microliters by day 25 after administration of rhG-CSF(57).

4.  Intravenous immunoglobulin therapy
Intravenous immunoglobulin (IVIG) is an immunomodulating agent that induces beneficial therapeutic responses in children and adults. IVIG is not only used for prophylaxis and therapy of infections in patients with primary and secondary immunodeficiencies associated with defective antibody production, but also used for treatment of patients with systemic inflammatory disorders, autoimmune diseases, and neuroimmunologic conditions(58).  There is a report of a young woman presenting respiratory infections, polyarthritis, severe neutropenia, and increased serum IgM was treated with intravenous immunoglobulin (IVIG) with good clinical and laboratory outcome followed by a loss of efficacy(59). Other in the study of performed serial hematology, including differentiation of white blood cells (WBC), before and after 22 instances of IVIG in 16 patients with neuroimmunologic disorders indicated that WBC and neutrophils showed a significant decrease with a nadir 2 days after IVIG, but returned to previous values by 14 days with no treatment except in 2 cases. No patient showed any infectious complication(60).

5. Supplements for patients with Copper, Vitamin B12, Folate deficiency
 
F.2.3. Treatment depending to types of Neutropenia
1. Severe autoimmune neutropenia
According to the study by the,in the study to systematically review the clinical presentations and management of periodontitis patients with neutropenia and present a patient with severe autoimmune neutropenia of twenty-four case reports describing a total of 33 patients, showed that improvements in periodontal condition were observed in 86% of patients who were administered adjuvant systemic antibiotics compared to 47% of patients who were not given supplemental therapy. Granulocyte-colony stimulating factor was administered to 67% of the neutropenic patients, and both improvement and progression of the hematological condition were monitored. Scaling and root planing, in combination with systemic antibiotics to supplement therapy for the underlying disease, have been successful in most cases(61).

2. Febrile neutropenia
Febrile neutropenic patients are at greater risk of getting bacterial and fungal infections. Empirical antifungal therapy is considered if the fever persists despite broad-spectrum antibiotics including vancomycin, According to the study by the Postgraduate Institute of Medical Education and Research,  to determine the response of empirical amphotericin B deoxycholate (dAMB) starting either on day 4 or day 8 in febrile neutropenic patients not responding to broad-spectrum antibiotics and without localisation of fever. Fifty-six patients with persistent neutropenic fever despite 72 h of antibiotic therapy were randomly assigned to receive dAMB either starting on day 4 (group A, n = 27, median age 23 years) or starting on day 8 (group B, n = 29, median age 25 years). Satisfactory response (patient remaining afebrile for 48 h and maintaining absolute neutrophil count >500 μl-1 ) occurred in 85.2% of patients in group A vs. 69.5% in group B (P = 0.209). Patients in group A took significantly fewer days to become afebrile than group B (5.4 ± 3.9 days vs. 11.3 ± 4.0 days, P = 0.0001). The adverse side effects of dAMB (nephrotoxicity, hypokalemia and hypomagnesemia) occurred at similar rates in both groups. Early addition of empirical dAMB in febrile neutropenic patients leads to their early defervescence and decreased dose requirement(62).

2. Treatment of Neutropenia as a result of chemotherapy in cancer patients
Cytotoxic chemotherapy suppresses the hematopoietic system, impairing host protective mechanisms and limiting the doses of chemotherapy that can be tolerated. Neutropenia, the most serious hematologic toxicity, is associated with the risk of life-threatening infections as well as chemotherapy dose reductions and delays that may compromise treatment outcomes.  According to the study by the University of Rochester School of Medicine and Dentistry, Neutropenia represents a major dose-limiting toxicity of chemotherapy and is associated with an increased risk of infection, impaired patient quality of life, and interference with the delivery of full-dose chemotherapy. These complications increase not only morbidity and mortality associated with cancer treatment but also the overall cost of care for cancer patients. Conversely, chemotherapy-induced neutropenia as a surrogate for delivered dose intensity has been associated with improved cancer survival. Administration of myeloid growth factors, such as filgrastim and pegfilgrastim, reduces the risk for neutropenic complications and facilitates the delivery of full-dose chemotherapy. There is an ongoing effort to identify patients at increased risk for developing neutropenic complications who would likely benefit from preemptive myeloid growth factor therapy. Appropriate use of myeloid growth factors is associated with reduced neutropenic complications, improved patient quality of life, and potentially improved disease control and long-term survival(63).

3. Cyclic neutropenia
In the study of six patients with cyclic neutropenia treated with recombinant human granulocyte colony-stimulating factor (G-CSF) for 3 to 15 months, found that uring the first 40 months of treatment, no typical mouth ulcers or bacterial infections occurred; recurrent gingivitis improved. We conclude that G-CSF is effective for the treatment of cyclic neutropenia in humans(64).

4. Congenital neutropenia
In recent years, the converging efforts of hematologists, immunologists and geneticists have led to the discovery of the genetic and biochemical basis of severe congenital neutropenia; cyclic neutropenia; warts, hypogammaglobulinemia, immunodeficiency, myelokathexis or WHIM syndrome and other rarer conditions associated to neutropenia. According to the study by the University of Brescia, although the diagnosis of congenital neutropenia includes many disorders of distinct origin and variable prognosis, their treatment is still based on granulocyte colony stimulating factor administration. Understanding the pathogenesis of these forms of neutropenia and their evolution will focus future studies on the mechanisms of normal and pathological myelopoiesis and on the development of the most appropriate treatment for each type of neutropenia(65). But other researchers indicated that the treatment with G-CSF is not sufficient to correct all of the functional deficiency of neutrophils, and this might account for the consistent risk of infections observed in SCN patients(66).

F.2. In Herbal medicine perspective
1. Glycyrrhizin
Glycyrrhizin is a ingredient found in liquorice (alt. licorice) rootIn the study to evaluate effect of glycyrrhizin on immunity function in allergic rhinitis (AR) mice, found that glycyrrhizin can improve immunity function in AR mice, suggesting a potential drug for the prevention and therapy of AR(67).

2. Bayberry bark extract, tea
Myricetin is a naturally occurring flavonoid that is found in many fruits, vegetables, teas and medicinal herbs, including Bayberry bark. In the study to evaluate the potential for myricetin to modulate lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs, showed that treatment with myricetin up to 10 µg mL(-1) does not cause cytotoxicity in cells. Myricetin significantly decreased the secretion of tumour necrosis factor-α, interleukin-6 and interleukin-12p70 by LPS-stimulated DCs. The expression of LPS-induced major histocompatibility class II, CD40 and CD86 on DCs was also inhibited by myricetin, and the endocytic and migratory capacity of LPS-stimulated DCs was blocked by myricentin. In addition, LPS-stimulated DC-elicited allogeneic T-cell proliferation was reduced by myricetin. Moreover, our results confirmed that myricetin attenuates the responses of LPS-stimulated activation of DCs via suppression of IκB kinase/nuclear factor-κB and mitogen-activated protein kinase-dependent pathways(68).

3. Rabdosia rubescens
According to the study of Shanghai Jiao Tong University School of Medicine, oridonin induced apoptosis of t(8;21) acute myeloid leukemic (AML) cells. Intriguingly, the t(8;21) product AML1-ETO (AE) fusion protein, which plays a critical role in leukemogenesis, The ectopic expression of AE enhanced the apoptotic effect of oridonin in U937 cells. Preincubation with caspase inhibitors blocked oridonin-triggered cleavage of AE, while substitution of Ala for Asp at residues 188 in ETO moiety of the fusion abrogated AE degradation. Furthermore, oridonin prolonged lifespan of C57 mice bearing truncated AE-expressing leukemic cells without suppression of bone marrow or reduction of body weight of animals, and exerted synergic effects while combined with cytosine arabinoside. Oridonin also inhibited tumor growth in nude mice inoculated with t(8;21)-harboring Kasumi-1 cells(68a).
 
F.3. In traditional Chinese medicine perspective 
1. Herbal extract granules
In the study applied the highest standard of clinical trial methodology to examine the role of CHM in reducing chemotherapy-induced toxicity, while maintaining a tailored approach to therapy with one hundred and twenty patients were accrued at the time of premature study termination. Enrolled patients were randomly assigned to one of three Chinese herbalists who evaluated and prescribed a combination of single-item packaged herbal extract granules. Patients received either CHM or placebo packages with a corresponding serial number. The placebo package contained nontherapeutic herbs with an artificial smell and taste similar to a typical herbal tea. The primary end points were hematologic and non-hematologic toxicity according to the National Cancer Institute Common Toxicity Criteria Version found that patient characteristics of the two groups were similar. The incidence of grade 3/4 anemia, leukopenia, neutropenia, and thrombocytopenia for the CHM and placebo groups were 5.4%, 47.3%, 52.7%, and 1.8% and 1.8%, 32.2%, 44.7%, and 3.6%, respectively (P = 0.27, 0.37, 0.63, and 0.13, respectively). Incidence of grade 2 nausea was the only non-hematologic toxicity that was significantly reduced in the CHM group (14.6% versus 35.7%, P = 0.04)(69). 

2. Lycium barbarum polysaccharide (LBP)
In the study to nvestigate the therapeutic effects of Lycium barbarum polysaccharide (LBP) on mitomycin C (MMC)-induced myelosuppressive mice, found that LBP at 100 mg/kg (LBP-L) on day 14 and LBP at 200 mg/kg (LBP-H) on days 10, 14, 17, 19 and 21, significantly ameliorated the decrease of peripheral RBC, HGB and hematocrit (HCT) of myelosuppressive mice compared to the control. LBP-L on days 12 and days 14 and LBP-H on days 10, 12, 14, 17, 19 and 21, significantly enhanced peripheral PLT recovery of myelosuppressive mice compared to the control. LBP-H on days 12, 17, 19 and 21, significantly inhibited the increase of mean platelet volume (MPV) of myelosuppressive mice compared to the control. LBP showed no obviously effect on neutropenia induced in mice by MMC(70).

3.  Fu Zheng and the Gong Xiao
In the study of observed the effect of chemotherapy combined with Chinese herbs and western drugs on white blood cell count in 31 patients with gastric cancer with patients were divided into 3 groups: (1) Fu Zheng (strengthen the body resistance) with invigorating the Spleen and Kidney recipe; (2) Fu Zheng with western drugs raising WBC and enhancing immunity; (3) Gong Xiao (eliminating the evil factors and mass) with promoting blood circulation to remove blood stasis recipe or eliminating the evil factors and mass recipe, suggested that invigorating the Spleen and Kidney recipe had specific effect on decreasing the toxicity and side effect of chemotherapy, preventing bone marrow suppression and leukopenia, and was better than western drugs used in group II. It showed in the treatment of cancer with TCM, we must pay attention to the relationship between the Fu Zheng and the Gong Xiao(71). 

3. Chinese herbal medicine
In the study to evaluate traditional Chinese medicine (TCM) in improving quality of life (QOL), reducing chemotoxicity and modulating immune function in patients undergoing chemotherapy, found that there was no significant difference in the GHS between the two groups. With adjustment for stage, chemotherapy type, disease status, age and baseline value, emotional function, cognitive function and nausea and vomiting were found to be worse or less improved in the TCM group compared with placebo group after six cycles of chemotherapy. The TCM group had less neutropenia after three cycles (0% grade 4 neutropenia versus 28.6%). There were no other significant differences in terms of chemotoxicity. Lymphocyte counts and cytokine activities decreased less in the TCM group(72).
 Other inthe searching of The Cochrane Breast Cancer Specialised Register (15/02/2007), The Cochrane Central Register of Controlled Trials (CENTRAL); (The Cochrane Library 2006, Issue 4); MEDLINE (1966 to December 2006); EMBASE (1990 to December 2006); and Chinese Biomedical Literature (2006, Issue 4), indicated that the searching provides limited evidence about the effectiveness and safety of Chinese medicinal herbs in alleviating chemotherapy induced short term side effects. Chinese medicinal herbs, when used together with chemotherapy, may offer some benefit to breast cancer patients in terms of bone marrow improvement and quality of life, but the evidence is too limited to make any confident conclusions(73).
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