Duodenitis

Duodenitis is defined as a condition of inflammation in the lining of the duodenum, the first section of the small intestine.

I. Symptoms
1. Abdominal pain
In a report of Thirty nine children with recurrent abdominal pain aged between 5.5 and 12 years, underwent endoscopic duodenal biopsy. Duodenal inflammation was graded by the duodenitis scale of Whitehead et al (grade 0, 1, 2, and 3). In 13 out of 39 patients (33%) definite signs of inflammation were found (grade 2 and 3). Intestinal permeability to 51Cr-EDTA in patients with duodenitis (grade 1, 2, and 3) was significantly higher (4.42 (1.73)%) than in patients with normal (grade 0) duodenal biopsy appearances (3.3 (0.9)%)(1).

2. Loss of appetite, epigastric pain and weight loss
Parasitic infection cause of  Duodenitis can lead to loss of appetite and weight loss, according to the study of An extremely uncommon case of parasitic infection presenting as eosinophilic ascites in a young patient, by thye research team at the GATA Haydarpasa Training Hospital(2).

3. Other symptoms
In the study of over a 15 month period, 124 referred patients were evaluated in a prospective cohort analysis with a standardised investigation including duodenal biopsies and aspirate, blood tests and faecal parasite and calprotectin tests. Recovered subjects were recruited for symptom analysis, researchers at the Haukeland University Hospital, found that There were significant associations between persistent Giardia positivity, microscopic duodenal inflammation and a positive calprotectin test. In patients with persisting symptoms after metronidazole treated Giardia infection we commonly found chronic Giardia infection and microscopic duodenal inflammation, especially in illness duration less than 7 months. Both these findings subsided over time. Increasingly, investigations could not determine a definite cause for the persistent symptoms. The very long-term post-giardiasis diarrhoea, bloating, nausea and abdominal pain documented here need further study(3). 

4. Etc.

II. Causes and Risk factors 
A. Causes
1. Medication
Prolonged use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin), naproxen (Aleve), or aspirin, in some people, it can lead to irritation causes of  inflammation in the lining of the duodenum. There is a report of a 40-year-old previously healthy white man presented to the emergency department at American University of Beirut Medical Center, Beirut, Lebanon, with developed symptomatic severe transmural duodenitis and periduodenal mesenteric streaking, consistent with a complicated ulcer, probably associated with very short-term exposure to tiaprofenic acid(3a).

2. Bacteria infections (Helicobacter pylor)
In the study of 138 (92 males, 46 females) patients aged 4.5-85 years [mean (7) = 45+/-SD 17.8 years] who had upper gastrointestinal endoscopy were analyzed for presence of H. pylori, found that eighty-three had histopathology alone, while 55 others had both histology and culture. Endoscopic diagnosis included duodenal ulcer (DU) (n=35, 23%); gastric ulcer (n=4, 3%); gastric cancer (n=14, 9%); NUD, including gastritis (n=49, 32%); duodenitis (n=47, 31%); and normal (n=16, 11%). Overall, H. pylori was positive in 107 of 138 (77.5%) patients. There was a significant association of H. pylori with DU and NUD (p<0.000). Three-quarters of cases of normal endoscopy harbored H. pylori. The finding of 80% and 85% H. pylori in gastritis and duodenitis, respectively, was of interest(4).

3. Gastroesophageal reflux disease
In the study to determine the relationship between symptoms and H. pylori eradication and to determine whether H. pylori eradication results in symptoms or endoscopic findings of GERD, researchers at the University of Wisconsin Medical School, Milwaukee, showed that he presence of epigastric pain was significantly associated with persistent H. pylori infection 1 month after therapy (odds ratio 2.3, 95% CI: 1.02-5.2; P=0.041), as was nausea (OR 7.1, 95% CI: 0.93-55.6; P=0.029). The presence of epigastric pain was significantly associated with ulcer relapse at 6 months (OR 7.5, 95% CI: 3.6-15.7; P < 0.001) as was nausea (OR 5.1, 95% CI: 1.7-16.0; P=0.002). Heartburn was not associated with eradication of H. pylori or ulcer relapse. New onset reflux symptoms were reported by 17% (17 of 101 patients) at 6 months and were not significantly different in patients with (15%) and without (22%) persistent H. pylori infection (P=0.47)(5).

4. Parasitic infection
There is a report of a case of a 24-year-old male patient admitted for recent ascites and splenomegaly of unknown origin. The patient was referred to our institution with complaints of diarrhea, epigastric pain, abdominal cramping and weight loss over the past three weeks, Upper gastrointestinal system endoscopy performed a few days later revealed diffuse severe erythematous pangastritis and gastroduodenal gastric reflux. Duodenal biopsies showed chronic nonspecific duodenitis. Antrum and corpus biopsies showed chronic gastritis. The final diagnosis was consistent with parasitic infection while the clinical, sonographic and histological findings suggested an eosinophilic ascites(6).

5. Nucleic acids by phases of cavitary secretion
In the study of the concentration of nucleic acids in the cavitary secretion phase reflects the state of the gastroduodenal mucosa and physicochemical properties of the mucus of Sixty patients with gastroduodenal diseases (chronic gastritis, chronic duodenitis from surface to atrophic and during exacerbation), sgowed that changes in the distribution of nucleic acids by phases of cavitary secretion were revealed. A decrease in the total content of nucleic acids in cavitary contents was paralleled by decreased activity of chronic gastritis and duodenitis and normalization of colloid and gel-forming properties of the mucus(7)
6. Viral infection
In the study to investigate endoscopic and histopathological findings in the duodenum of patients with Strongyloides stercoralis (S. stercoralis) hyperinfection, reseachers at the indicated that twenty-four (96%) of the patients investigated were under immunocompromised condition which was mainly due to a human T lymphotropic virus type 1 (HTLV-1) infection. The abnormal endoscopic findings, mainly edematous mucosa, white villi and erythematous mucosa, were observed in 23 (92%) patients. The degree of duodenitis including villous atrophy/destruction and inflammatory cell infiltration corresponded to the severity of the endoscopic findings(8).

7. Celiac disease, Whipple's disease and Crohn's disease
In studied the count and identification of inflammatory cells in duodenal biopsies of specific duodenitis. In celiac disease there is an increase of lymphocytes in the epithelial layer, and rich population of plasmacells in the lamina propria of duodenal mucosa. In Whipple's disease the reticulum cell component of lamina propria is increased, while total inflammatory cells are within normal limits, and both lymphocytes and plasmacells are decreased. The comparison between duodenal and jejunal findings shows similar data in celiac and Whipple's disease. In Crohn's disease the inflammatory cell count differs from controls only in presence of radiological or endoscopical features of duodenal involvement(9).

8. Toothpick ingestion
There is a report of  two patients with duodenal inflammation secondary to toothpick ingestion. In the first patient, there was acute onset of severe abdominal pain, with findings on computed tomography consistent with marked duodenal inflammation. Endoscopy revealed a toothpick embedded in the wall of the duodenum with associated ulceration. In the second patient, 4 months of chronic abdominal pain was evaluated by upper endoscopy which revealed a toothpick embedded in a 1-cm ulcer found in the third portion of the duodenum(9a).



9. Etc.

B. Risk Factors 
1. Smoking and gender
In the study of the extent of duodenitis on the site opposite the ulcer determined by histological examination, showed that Sixty per cent of the duodenal ulcers were healed after three weeks. By univariate analysis, the following factors affect the healing; pain radiation to back and pain duration during treatment (p less than 0.001), multiple or deep ulcers, narrowing of duodenal bulb (p less than 0.01), number of pain attacks and poor appetite (p less than 0.05). By the stepwise logistic regression model, the following factors were selected as predictors for healing of duodenal ulcer with 76% correct classification: pain radiation to back (p = 0.002), deep ulcer (p = 0.013), multiple ulcers (p = 0.028). Number of cigarettes/day (p less than 0.007) and male sex (p = 0.036). By this model, the prediction of healing could be accurately assessed in 78% in a new sample. Individual treatment should be carried out on the basis of these factors(10).

2. Alcohol abuse 
Even though, there is  no any relation existing between the percentage of cases with atrophic inflammation and the kind of drinks or the content of ethanol in them, but examinations concerning the secretory function of the stomach showed lower values of hydrochloric acid secretion, both in basic conditions and after pentagastrin stimulation, in patients addicted to alcohol as compared to the control. Continuous abuse of alcohol predisposes to atrophic inflammation of the gastric mucosa, and the appearance of this type of inflammatory changes is related to the duration of addiction. The longer the addiction, the lower the secretion of hydrochloric acid is(11).

3. Stress
GDD in the young is a very frequent pathology, which may be triggered off by abrupt changes in life style, especially in those patients who are unable to react positively to changes in the outer world. GD pathology arises most frequently during the first five months of military service, especially within the third and the fourth month(12). 

4. Etc.
 
III. Diagnosis 
After taking the family history, recording the symptoms and a complete physical examination, the most common test which your doctor order is Endoscopy.
The aim of the test is to allow your doctor to visualize the duodenum and it surrounding area to check for any abnormality, including shallow, eroded areas in the wall of the intestine, bleeding, etc. 
In the study of 50 patients with endoscopically diagnosed duodenitis who had undergone double-contrast upper gastrointestinal (GI) examinations. Duodenitis was diagnosed on the original radiographic reports in six of 37 patients (16%) with mild-to-moderate duodenitis, five of 13 patients (38%) with severe duodenitis, and 11 of 50 patients (22%) with all grades of duodenitis on endoscopy. Subsequent analysis of the films revealed one or more radiologic signs of duodenitis (including folds more than 4 mm in thickness, mucosal nodularity, bulbar deformity, and erosions) in 18 of 37 patients (49%) with mild-to-moderate duodenitis, eight of 13 patients (62%) with severe duodenitis, and 26 of 50 patients (52%) with all grades of duodenitis on endoscopy(13),

IV. Complications
1. Hemorrhage
Inflammation of the stomach lining may lead to the formation of an ulcer (lesion) in the  the duodenum or stomach. In the study to investigate epidemiological, clinical, and etiological characteristics of acute upper gastro-intestinal bleeding between January 2003 and December 2008, researchers at the Medical Unit C, Ibn Sina Hospital, found that in 1389 registered cases, 66% of the patients were male, 34% were female. Mean age was 49. 12% of patients had a history of previous hemorrhage, and 26% had a history of NSAID and aspirin use. Endoscopy was performed in 96%. The gastroduodenal ulcer was the main etiology in 38%, followed by gastritis and duodenitis in 32.5%(14).

2. Iron deficiency anemia
Iron deficiency anemia is a result of internal bleeding. Men and postmenopausal women with iron deficiency anemia are routinely evaluated to exclude a gastrointestinal source of suspected internal bleeding. Forty-three of the 45 women fulfilled the entry criteria and were enrolled. Their mean age was 35 +/- 15 years and their mean hemoglobin level 9.3 +/- 2.3 g/dl. Twenty-eight upper gastrointestinal lesions were demonstrated in 24 of the 43 patients (55.8%): erosive gastritis in 12 (27.9%), erosive duodenitis in 4 (9.3%), erosive esophagitis in 3 (7.0%), hiatus hernia (with Cameron lesions) in 3 (7.0%), active duodenal ulcer in 1 (2.3%) and hyperplastic polyp (10 mm) in 1 (2.3%)(15).

3. Peritonitis
There is a report of a  case of a 62-year-old man with Candida krusei peritonitis secondary to duodenal perforation due to Candida duodenitis that was successfully treated with a 14-day course of caspofungin, according to Department of Human Pathology, University of Messina(16).

4. Etc.


IV. Prevention
A. The do`s and do not`s list
1. Avoiding spicy foods
Prolonged intake spicy foods incinerates the risk of irritation and inflammation of the lining of stomach and duodenum. 

2. Changes in food tolerance and lifestyle
If you develop Duodenitis as result of bacterial infection, changes in food tolerance and lifestyle can be helpful. The prevalence of food intolerance decreased from 71% to 44% among patients with peptic ulcer disease (PUD) (P < 0.0001) and from 76% to 63% among patients with  duodenitis (G/D) (P = 0.09). Tolerance improved for coffee, orange juice, fried foods, spicy foods and fruits, according to the study by Haukeland University Hospital(17).

3. Quit smoking
In the study to  investigate whether cigarette smoking has an additive effect on the clinical presentation and course of disease in Helicobacter pylori-positive dyspeptic patients, researchers at the  Tel Aviv University, indicated that Gastric and duodenal ulcers were significantly less prevalent in non-smokers than in current or past smokers (gastric 1.8%, 4.1%, 6.3%; duodenal 39.8%, 50%, 51.4%, respectively) (P < 0.05). The incidence of gastrointestinal bleeding was significantly lower in non-smokers than in current or past smokers (7.1%, 8.1% and 20.7%, respectively) (P < 0.05). Bacterial density, as assessed by the UBT value in 244 patients, was higher in non-smokers (mean 352.3 +/- 273 units) than in past smokers (mean 320.8 +/- 199) or current-smokers (mean 229.9 +/- 162) (P < 0.05)(18).

4.  Excessive alcohol drinking and stress
Excessive drinking and stress are associated with the risk of  Duodenitis(19)(20).

5. Avoiding prolonged use  of anti-inflammatory drugs, such as Ibuprofen and Aspirin
Prolonged use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin), naproxen (Aleve), or aspirin, in some people, it can lead to irritation causes of  inflammation in the lining of the duodenum(21).

6. Moderate exercise
Exercises can reduce stress at work and at home(22), thus, reducing the risk of Duodenitis.

7. Etc.

B. Phytochemicals to prevent Duodenitis
The aim of phytochemicals is to enhance the inmmue function ain fighting against invasion as result of  bacterial, viral and parasitic causes of inflammation
1. Gingerole
Gingerole, is also known as gingerol, a phytochemical of Flavonoids (polyphenols) found in fresh ginger. and in variety of other plants. The herb has been used to treat nausea and vomiting of pregnancy, motion sickness, rheumatoid arthritis, relieve migraine, etc. In the investigation of the effectiveness of chemical constituents of Zingiber officinale Rosc. (Zingiberaceae)in treating oxidative stress found that compounds [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol of the herb scavenges of 1,1-diphenyl-2-picyrlhydrazyl (DPPH), superoxide and hydroxyl radicals, inhibitsof N-formyl-methionyl-leucyl-phenylalanine (f-MLP) induced reactive oxygen species (ROS) production in human polymorphonuclear neutrophils (PMN), lipopolysaccharide induced nitrite and prostaglandin E(2) production in RAW 264.7 cells, according to the study of "Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol" by Dugasani S, Pichika MR, Nadarajah VD, Balijepalli MK, Tandra S, Korlakunta JN(23).

2. Rutin
Rutin also known as rutoside, quercetin-3-O-rutinoside and sophorin is a Flavonols, belong to Flavonoids (polyphenols) of Phenolic compounds found orange, grapefruit, lemon, lime, berries mulberry, cranberries, buckwheat etc. In the investigation of Rutin, a natural flavone derivative and its anti inflammatory effect found that Oral administration of rutin reduced rat paw swelling starting 2 hours after lambda-carrageenan injection. Rutin reduced significantly (p < 0.05) and in a dose-dependant manner the polymorphonuclear neutrophils chemotaxis to fMet-Leu-Phe, according to the study of "Anti-inflammatory effect of rutin on rat paw oedema, and on neutrophils chemotaxis and degranulation" by Selloum L, Bouriche H, Tigrine C, Boudoukha C.(24).

3. Catechin
Catechin is phytochemical of Flavan-3-ols, in the group of Flavonoids (polyphenols), found abundantly in white tea, green tea, black tea, grapes, wine, apple juice, cocoa, lentils, etc. In the research on polyphenolic compounds (included catechins) in the berries of edible honeysuckle and their biological effects, including recommended utilization, are reviewed found that These berries seem to be prospective sources of health-supporting phytochemicals that exhibit beneficial anti-adherence and chemo-protective activities, thus they may provide protection against a number of chronic conditions, e.g., cancer, diabetes mellitus, tumour growth or cardiovascular and neurodegenerative diseases, according to "Phenolic profile of edible honeysuckle berries (genus lonicera) and their biological effects" by Jurikova T, Rop O, Mlcek J, Sochor J, Balla S, Szekeres L, Hegedusova A, Hubalek J, Adam V, Kizek R.(25). Also in the preparation of the gel of Chinese medicine catechu, and to observe the release mechanism in vitro and anti-inflammatory activity in rats, found that the optimum condition of extraction from catechu was as follows, the concentration of ethanol, ratio of raw material to solvent, ultrasonic time, and extraction temperature were 50% , 1: 12, 35 min and 60 degrees C, respectively. The formulation of catechu gel was carbomer-9 400.5 g, glycerol 5.0 g, the extracts of catechu 50.0 mL, and triethanomine 0.5 mL The gel was semitransparent and stable. The drugs released quickly. The catechu gel reduced the paw edema considerably in dose-dependent manner compared to carrageenan-induced rat, according to "[Preparation and pharmacodynamics studies on anti-inflammatory effect of catechu gel].[Article in Chinese]" by Zheng X, Zheng C.(26).

4. Cinnamic acid
Cinnamic acid is a phytochemical in the class of Hydroxycinnamic acids, found abundantly in cinnamon, aloe. etc. In the sudy of the ulcer-preventive properties of aqueous extract of ginger rhizome (GRAE) belonging to the family Zingiberceae, found that compositional analysis favored by determination of the efficacy of individual phenolic acids towards their potential ulcer-preventive ability revealed that between cinnamic (50%) and gallic (46%) phenolic acids, cinnamic acid appear to contribute to better H(+), K(+)-ATPase and Helicobacter pylori inhibitory activity, while gallic acid contributes significantly to anti-oxidant activity, according to "Gastroprotective Effect of Ginger Rhizome (Zingiber officinale) Extract: Role of Gallic Acid and Cinnamic Acid in H+, K+-ATPase/H. pylori Inhibition and Anti-oxidative Mechanism" by Nanjundaiah SM, Annaiah HN, M Dharmesh S.(27).

5. Resveratrol
Resveratrol is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, nuts, peanuts, etc. In the observation of Resveratrol's effects in exhibition of several physiological activities including anticancer and anti-inflammatory activities in vitro and in experimental animal models, as well as in humans, found that Anticancer activity of this compound is mainly due to induction of apoptosis via several pathways, as well as alteration of gene expressions, all leading to a decrease in tumor initiation, promotion, and progression. Resveratrol exhibits anti-inflammatory activity through modulation of enzymes and pathways that produce mediators of inflammation and also induction of programmed cell death in activated immune cells. Resveratrol has been shown to produce no adverse effects, even when consumed at high concentrations, according to "Potential of resveratrol in anticancer and anti-inflammatory therapy" by Udenigwe CC, Ramprasath VR, Aluko RE, Jones PJ.(28). Also in the study of implantation and growth of metastatic cancer cells at distant organs is promoted by inflammation-dependent mechanism, found that resveratrol remarkably inhibited hepatic retention and metastatic growth of melanoma cells by 50% and 75%, respectively. The mechanism involved IL-18 blockade at three levels: First, resveratrol prevented IL-18 augmentation in the blood of melanoma cell-infiltrated livers. Second, resveratrol inhibited IL-18-dependent expression of VCAM-1 by tumor-activated hepatic sinusoidal endothelium, preventing melanoma cell adhesion to the microvasculature. Third, resveratrol inhibited adhesion- and proliferation-stimulating effects of IL-18 on metastatic melanoma cells through hydrogen peroxide-dependent nuclear factor-kappaB translocation blockade on these cells, according to "Resveratrol prevents inflammation-dependent hepatic melanoma metastasis by inhibiting the secretion and effects of interleukin-18" by Salado C, Olaso E, Gallot N, Valcarcel M, Egilegor E, Mendoza L, Vidal-Vanaclocha F.(29).

6. Etc.
C. Antioxidant to prevent Duodenitis
The aim of antioxidants is to enhance the inmmue function ain fighting against invasion as result of bacterial, viral and parasitic causes of inflammation.
1. Quercetin
Since it contains high amount of antioxidants, onion enhances the immune system in fighting against the forming of free radicals and foreign invasion, thus eeducing the symptoms of inflammatory conditions such as arthritis and gout and infection caused by bacteria, including E.coli and salmonella,etc., according to the study of Antibacterial and antioxidant activities of quercetin oxidation products from yellow onion (Allium cepa) skin.(30).

2. Bromelain
Today Pineapple is widely cultivated for commercial and its rich of vitamins and mineral and digesting enzyme bromelin which seems to help digestion at the end of a high protein meal. It is second only to banana as America's most favourite tropical fruit. In the classification of bromelain is a mixture of proteinases derived from pineapple stem and its effect in gastrointestinal tract, found that bromelain enzymes can remain intact and proteolytically active within the murine gastrointestinal tract. They provide further support for the hypothesis that oral bromelain may potentially modify inflammation within the gastrointestinal tract via local proteolytic activity within the colonic microenvironment, according to "Proteolytic activity and immunogenicity of oral bromelain within the gastrointestinal tract of mice" by Hale LP.(31). Also Bromelain also increases the immune function in fighting the invasion of foreign substances such as bacteria and virus, thus decreasing the risk of inflammation and infection according to the study of "Bromelain treatment reduces CD25 expression on activated CD4+ T cells in vitro" by Secor ER Jr, Singh A, Guernsey LA, McNamara JT, Zhan L, Maulik N, Thrall RS., posted in PubMed(32).

3. Polyphenols
Polyphenols, one of more powerful form of antioxidant not only helps to improve the immune system fighting against the forming of free radicals and guarding our body from foreign invasion, such as virus and bacteria, thus reducing the risk of inflammation and lessening the risk of oxidation of low-density lipoprotein (LDL) cause coronary heart disease, according to the study of "Plant polyphenols as dietary antioxidants in human health and disease" by Kanti Bhooshan Pandey and Syed Ibrahim Rizvi, posted in PubMed Central(33).

4. Catechins
Catechins are a category of polyphenols contained epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) and 25-100 times more potent than vitamins C and E that help to protect the body from oxidative damage by enhancing the immune function in fighting against forming of free radicals cause of cancer, according to the study of "Green tea catechins augment the antitumor activity of doxorubicin in an in vivo mouse model for chemoresistant liver cancer" by Liang G, Tang A, Lin X, Li L, Zhang S, Huang Z, Tang H, Li QQ.(34).

5. LycopeneLycopene, one of the powerful antioxidant in tomatoes, not only helps the immune system in neutralizing the forming of free radicals in the body and according to Harvard investigation as it found that men who ate more than 10 servings tomato-based foods daily (like cooked tomatoes and tomato sauce,) had a 35 percent lower risk of developing prostate cancer than those who ate the least amount of these foods. The benefits of lycopene was more pronounced with advanced stages of prostate cancer. Also according to the study of "Chemoprevention of prostate cancer with lycopene in the TRAMP model" by Konijeti R, Henning S, Moro A, Sheikh A, Elashoff D, Shapiro A, Ku M, Said JW, Heber D, Cohen P, Aronson WJ.(35),.

6. Etc.

D. Diet to prevent Duodentitis
1. Purple grape juices
In the evaluation of the protection of organic and conventional purple grape juices and theirs effect against the oxidative damage provoked by carbon tetrachloride (CCl(4)) found that in the alkaline version of the comet assay performed on whole blood, it was observed that CCl(4) was capable of inducing mainly DNA damage class 4 and 3 frequencies, which was significantly reduced in groups that received both purple grape juices. This implies that both grape juices have an important antigenotoxic activity, according to "Antioxidant and antigenotoxic activities of purple grape juice--organic and conventional--in adult rats" by Dani C, Oliboni LS, Umezu FM, Pasquali MA, Salvador M, Moreira JC, Henriques JA(36).

2. Garden strawberry
In the observation of Ethanolic extract of Fragaria vesca (EFFV) of Fragaria vesca L. and its effect on Ulcerative colitis and Crohn's disease (chronic recurrent inflammatory bowel disease (IBD)) found that EFFV at 500 mg/kg showed significant amelioration of experimentally induced IBD, which may be attributed to its antioxidant and anti-inflammatory properties, according to "Effect of fruit extract of Fragaria vesca L. on experimentally induced inflammatory bowel disease in albino rats" by Kanodia L, Borgohain M, Das S.(37).

3. Lime
Since it contains high amount of flavonoid, it helps to improve the immune system fighting against forming of free radical causes of tumor and cancer, according to the study of "Dietary intake of selected flavonols, flavones, and flavonoid-rich foods and risk of cancer in middle-aged and older women" by Wang L, Lee IM, Zhang SM, Blumberg JB, Buring JE, Sesso HD.(38).

4. Papaya leaves
In the assessment of ethanolic extract of Carica papaya leaves and its anti-inflammatory activity effect found that the extracts significantly reduced the persistent oedema from the 4th day to the 10th day of the investigation. The extracts also produced slight mucosal irritation at high doses. The study establishes the anti-inflammatory activity of Carica papaya leaves, according to "Anti-inflammatory activities of ethanolic extract of Carica papaya leaves" by Owoyele BV, Adebukola OM, Funmilayo AA, Soladoye AO.(39).

5. Celery
High amount of vitamin C in celery helps to increase the immune function infighting against the forming of free radicals, and irregular cell growth causes of tumor and cancer, according to the study of "Vitamin C and cancer: what can we conclude--1,609 patients and 33 years later?" by Cabanillas F.(40). Also High amount of flavonoid in celery helps to reduce the risk of oxidative stress as a result of its antioxidant activity, according to the study of "Influence of flavonoid extracts from celery on oxidative stress induced by dichlorvos in rats" by Cao J, Zhang X, Wang Q, Jia L, Zhang Y, Zhao X.(41).

6. Etc.
 
V. Treatment
A. In conventional medicine perspective
A.1. Antibiotics
If the causes of the disease is as a result of bacterial infection, then antibiotic is the primary choice of treatment such as, Amoxicillin, Clarithromycin (Biaxin), Metronidazole (Flagyl), etc. for 14 days to prevent re-infection or recurrence. In the study to assess the duodenal infection by Mycobacterium avium-intracellulare is a common opportunistic disease in HIV-infected patients (Individuals with CD4 counts <50 cells/mm3 are at highest risk) found that the patient was treated with rifampicine, isoniazide, ethambutol, and pyrazinamide in association with stavudine, lamuvidine and efavirenz. Despite improvement of general condition, fever persisted and the patient died after 40 days of treatment. The main symptoms are diarrhea, abdominal pain, weight loss, and fever(41a).
 Other in the study of the prevalence of Helicobacter pylori infection in patients with erosive duodenitis (ED), the associated gastric histological lesions and their response to eradication therapy with omeprazole plus two antibiotics, showed that a 1-week twice daily therapy with omeprazole plus two antibiotics (clarithromycin plus amoxycillin or metronidazole) was very effective in H. pylori eradication, duodenal erosion healing, symptomatic improvement, and in disappearance of associated histological gastritis. These observations suggest that ED should be considered a variant form of duodenal ulcer disease and treated accordingly(41b).
Side effects include yeast overgrowth,  gastrointestinal trouble, etc.

A.2. Of the causes of the disease is as a result of elevated stomach acid, then  medication include
1. Proton pump inhibitors
 According to the study by Uniwersytet Mikołaja Kopernika w Toruniu, Collegium Medicum w Bydgoszczy, Proton pump inhibitors (PPI), are characterized by high effectiveness, selectivity and few adverse events. Development of PPI was an important issue in aspect of acid-related diseases treatment. Nowadays following PPI are available on the market: omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole. In children these drugs are the most frequently use in gastritis and duodenitis, ulcer disease with coexistence of Helicobacter pylori infection and gastroesophageal reflux disease. Pharmacokinetics of PPI is slightly different in children than in adults and so far there is a lack of randomised studies assessing the efficacy of PPI i developmental period medicine on numerous groups of patients(41c).
Side effects include nausea, diarrhea, abdominal pain, fatigue, dizziness, etc.

2. Histamine H2-receptor antagonists
Histamine H2-receptor antagonists, such as, Cimetidine (Tagamet), Famotidine (Pepcid), Nizatidine (Axid), etc.
According to the study by Dr. Mackinnon M and research team, treatment with cimetidine for 6 weeks resulted in a significant improvement in symptoms and in the endoscopic appearance of the duodenitis when compared to treatment with placebo. The symptomatic and endoscopic improvement, however, was not associated with any significant change in the histological grading of the duodenitis.
Side effects include headache, tiredness, dizziness, confusion, diarrhea, constipation, rash, etc(41d).

According to the Department of Family Medicine, Cathay General Hospital, Taipei, Taiwan, in the study of all the patients aged ≥ 20 years with a diagnosis of cirrhosis hospitalized for variceal bleeding and non-variceal upper GI adverse events (oesophageal, gastric, duodenal ulcer, bleeding; gastritis and duodenitis) in 2006, using ICD-9-CM diagnosis codes from inpatient claims from the Taiwan National Health Insurance Database, found that Concomitant use of proton pump inhibitors and histamine-2 receptor antagonists tended to decrease the upper GI toxicity associated with non-selective NSAIDs and celecoxib(41f).

3. Proton pump inhibitors and low-dose aspirin
In the study to investigate the effect of histamin H₂ receptor antagonist (H₂RA) or proton pump inhibitor (PPI) for the prevention of upper gastrointestinal lesions associated with low-dose aspirin, found that suggest that the combined administration of low-dose aspirin and PPI is effective for the prevention of upper gastrointestinal lesions associated with low-dose aspirin. Also, the pharmacists should be especially careful for upper gastrointestinal lesions development within two years after administration of low-dose aspirin, regardless of combined whether H₂RA or PPI(41e).

B. In herbal medicine perspective
1. Herbal combination of Symphitum officinalis and Calendula officinalis
In a study of a total of 170 patients were treated--137 only with the herb combination of Symphitum officinalis and Calendula officinalis of (78 with duodenal ulcer and 59 with gastroduodenitis), 33--with the herb combination together with antacid (21 with duodenal ulcer and 12 with gastroduodenitis), Dr. Chakŭrski I and the team found that the spontaneous pains disappeared in 90 per cent of the patients--in the group with and in the group without antacid, the dyspeptic complaints faded in over 85 per cent but in the patients, treated with herbs and antacid the mentioned complaints disappeared several days earlier. The palpitation pains, in both groups, disappeared in more than 90 per cent of the patients within the same time. Gastric acidity, in both groups, showed a statistically insignificant tendency to decrease prior and post treatment. The gastroscopically control revealed that the ulcer niche, in both groups, was healed in almost the same percentage of the patients(42)

2. Suggested Starting Formula(43)
Aloe vera juice 70 wt%
Cabbage juice 20 wt%
Honey 10 wt%
Dosage: 3 times a day before meal

C. In traditional Chinese medicine perspective
According to the article of Herbs and Foods to Help Cure Naturally by NFA clinic of Oriental Medicine, epigastric pain including peptic ulcers is mostly the result of metabolic imbalance among liver, stomach and spleen. The function of one organ is depending on the function of another organs in Oriental medicine. They are understood not only by its function but also by its relationship with others. The article also suggested that Lu Hui, Yi Tang are ideal herbs to treat peptic ulcers
1. Lu Hui (Aloe Vera), the bitter and cold herb has been used in TCM to drain fire and guides out accumulation: for (chronic) constipation, strengthens the Stomach and kills parasites, clears heat and cools the Liver: for epigastric discomfort, enhancinmg the functions of Large Intestine, Liver, Stomach channels. Cautions: due to its cold property, dosage should be made considering the constitution of each patients. Some persons show allergy reaction to aloe vera

2. Yi tang (Honey), the sweet, slightly warm herb has been sued in TCM to tonifie the Spleen,  the middle burner Qi (stomach and spleen), alleviate pain, moisten the Lungs and stops cough by enhancing the functions of Lung, Spleen, Stomach channels.

3. Gan Cao (Licorice) the sweet and neutral herb has been used in TCM to tonifie the Spleen, moisten the Lungs, stop coughing, clear heat and relieves fire toxicity, moderates spasms and alleviates pain, by enhancing the functions of all 12 channels(42).
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Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/2125404
(2) http://www.ncbi.nlm.nih.gov/pubmed/21552435
(3) http://www.ncbi.nlm.nih.gov/pubmed/17964658
(3a) http://www.ncbi.nlm.nih.gov/pubmed/18158085 
(4) http://www.ncbi.nlm.nih.gov/pubmed/17304966
(5) http://www.ncbi.nlm.nih.gov/pubmed/10632644
(6) http://www.ncbi.nlm.nih.gov/pubmed/21552435 
(7) http://www.ncbi.nlm.nih.gov/pubmed/12132379
(8) http://www.ncbi.nlm.nih.gov/pubmed/18350608
(9) http://www.ncbi.nlm.nih.gov/pubmed/71989
(9a) http://www.ncbi.nlm.nih.gov/pubmed/8792719
(10) http://www.ncbi.nlm.nih.gov/pubmed/3356359
(11) http://www.ncbi.nlm.nih.gov/pubmed/12898897
(12) http://www.ncbi.nlm.nih.gov/pubmed/9479996 
(13) http://www.ncbi.nlm.nih.gov/pubmed/2016037
(14) http://www.ncbi.nlm.nih.gov/pubmed/21991509 
(15) http://www.ncbi.nlm.nih.gov/pubmed/16544728
(16) http://www.ncbi.nlm.nih.gov/pubmed/20632210
(17) http://www.ncbi.nlm.nih.gov/pubmed/12737441 
(18) http://www.ncbi.nlm.nih.gov/pubmed/11344768
(19) http://www.ncbi.nlm.nih.gov/pubmed/12898897
(20) http://www.ncbi.nlm.nih.gov/pubmed/9479996 
(21) http://www.ncbi.nlm.nih.gov/pubmed/18158085
(22) http://www.ncbi.nlm.nih.gov/pubmed/22988262
(23)  http://www.ncbi.nlm.nih.gov/pubmed/19833188
(24) http://www.ncbi.nlm.nih.gov/pubmed/12710715
(25) http://www.ncbi.nlm.nih.gov/pubmed/22269864
(26) http://www.ncbi.nlm.nih.gov/pubmed/22256752
(27) http://www.ncbi.nlm.nih.gov/pubmed/19570992 
(28) http://www.ncbi.nlm.nih.gov/pubmed/18667005
(29) http://www.ncbi.nlm.nih.gov/pubmed/21569399
(30) http://www.ncbi.nlm.nih.gov/pubmed/19127724
(31) http://www.ncbi.nlm.nih.gov/pubmed/14996417
(32) http://www.ncbi.nlm.nih.gov/pubmed/19162239
(33) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835915/
(34) http://www.ncbi.nlm.nih.gov/pubmed/20514403
(35) http://www.ncbi.nlm.nih.gov/pubmed/20687227)
(36) http://www.ncbi.nlm.nih.gov/pubmed/19857077
(37) http://www.ncbi.nlm.nih.gov/pubmed/19160185
(38) http://www.ncbi.nlm.nih.gov/pubmed/19158208
(39) http://www.ncbi.nlm.nih.gov/pubmed/18759075
(40) http://www.ncbi.nlm.nih.gov/pubmed/20799507
(41) http://www.ncbi.nlm.nih.gov/pubmed/22045891
(41a) http://www.ncbi.nlm.nih.gov/pubmed/20099679  
(41b) http://www.ncbi.nlm.nih.gov/pubmed/9391784 
(41c) http://www.ncbi.nlm.nih.gov/pubmed/17598663
(41d) http://www.ncbi.nlm.nih.gov/pubmed/7042248 
(41e) http://www.ncbi.nlm.nih.gov/pubmed/21372542
(41f) http://www.ncbi.nlm.nih.gov/pubmed/22226322 
(42) http://www.ncbi.nlm.nih.gov/pubmed/7336704
(43) http://www.needlefreeacupuncture.net/peptic_ulcer.pdf

Nephritis

Nephritis is defined as a condition of inflammation of the nephrons in the kidneys.

Types of Nephritis
Depending to the locations of inflammation, Nephritis can be classified as follows
I. Glomerulonephritis 
 Glomerulonephritis is defined as the condition of inflammation of the tiny filters in  kidneys (glomeruli), which filter blood by removing excess fluid, electrolytes and waste and pass them through urination.
1.. Acute Glomerulonephritis
A sudden onset of inflammation of glomeruli.
2. Chronic Glomerulonephritis
This is a graduated progression of kidney diseases. It can be primary or as a result of certain diseases 

II. Interstitial nephritis (Tubulo-interstitial nephritis) 
Interstitial nephritis is defined as a condition of inflammation of the spaces between renal tubules, affecting the interstitium of the kidneys and kidney function in wast removal.
1,  Acute Interstitial nephritis
A sudden onset of the inflammation of the diseases
2. Chronic Interstitial nephritis
In most case, it ends in kidney failure

I. Glomerulonephritis 
Glomerulonephritis is defined as the condition of inflammation of the tiny filters in  kidneys (glomeruli), which filter blood by removing excess fluid, electrolytes and waste and pass them through urination.
A. Signs and Symptoms
A.1. Acute Glomerulonephritis 
According to the study by Movchan EA, in the study of Evolutionary trends in symptoms of acute glomerulonephritis in adult population of the Novosibirsk region, indicated that AGN occurs not often but with stable rate. It is encountered more frequently in young men. The last decade is characterized by higher morbidity after streptococcal infection, high percentage of women at reproductive age, aggravation of the clinical course with marked edemas, severe arterial hypertension, renal dysfunction (acute renal failure in 10.4%), cases of left ventricular failure (5.2%) and eclampsia (1.7%) not registered earlier(1).

A.2. Chronic Glomerulonephritis 
In the study of Incidence and characteristics of the hypertension syndrome in chronic glomerulonephritis, by Dr. Stefanov G. showed that in the random group, 65.1 per cent had renoparenchymal hypertension (RPH), 34.8 per cent of the patients had RPH among the patients with normal renal function, and with various degrees of chronic renal insufficiency (ChRI) - 95.4 per cent..... In 48 per cent but patients with ChGN without RPH also had the same complaints--26 per cent. Complaints as dizziness, tinnitus and insomnia were rare. The hypertension was with a short duration (according to anamnestic data)--in 2/3 less than three years and 40 per cent of the patients had hypertonic crises or/and acute left cardiac insufficiency in spite of the relatively little alterations in ECG and fundus of the eye(2).

3. Other symptoms include 
a. Hematuria
Hematuria is condition of the presence of red blood cells in the urine.
There is a report of a a 16 year old male with a history of recurrent synpharyngitic macroscopic hematuria presented with severe loin pain, macroscopic hematuria and oliguric acute renal failure, according to the study by Dr. Kincaid-Smith P and the research team(3).

b. Proteinuria (The presence of an excess of proteins in the urine)
Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney(4)

c. Cold sweating, general fatigue, and somnolence
  There is a report of a 66-year-old woman, who has been under hemodialysis due to antineutrophil cytoplasm autoantibody (ANCA)-associated glomerulonephritis since 2003, was hospitalized because of cold sweating, general fatigue, and somnolence, According to the research team at the Divisions of Endocrinology and Metabolism(5).

B. Causes and Risk factors
B.1. Causes
1. Infections
In the study of Glomerulonephritis causing acute renal failure during the course of bacterial infections of of four male patients, aged 53-71 years, who developed GN and ARF following bacterial infections, showed that
a. The first two patients developed GN with immunoglobulin A (IgA) deposits after infections with hospital-acquired methicillin resistant Staphylococcus aureus (MRSA). Clinical, serologic and histological features, classification of GN and treatment differed between the two patients.
b. The third patient developed simultaneous acute rheumatic fever and post-streptococcal GN causing severe ARF requiring hemodialysis. Complete recovery of ARF and migratory polyarthritis followed initiation of corticosteroids.
c. The fourth patient developed ARF and cerebral vasculitis following a prolonged course of Streptococcus mutans endocarditis with delayed diagnosis. He also developed multiple serological abnormalities including elevated titers of antineutrophil cytoplasmic antibodies (ANCA), antinuclear antibodies (ANA), anti-phospholipid antibodies, rheumatoid factor, and modest hypocomplementemia(6).

2. Lupus
In the study of Distinct roles for complement in glomerulonephritis and atherosclerosis revealed in mice with a combination of lupus and hyperlipidemia by Dr. Lewis MJ and the research team at the Imperial College London showed that accelerated atherosclerosis and renal inflammation in SLE are closely linked via immune complex formation and systemic complement depletion. However, whereas hyperlipidemia will enhance renal immune complex-mediated complement activation and the development of nephritis, accelerated atherosclerosis is, instead, related to complement depletion and a reduction in the uptake of apoptotic/necrotic debris(7).

3. Goodpasture's disease
In the study of the Progression from Goodpasture's disease to membranous glomerulonephritis, according to the research team at the Department of Renal Medicine, Concord Hospital, Sydney, thwew is report of an unusual case of a patient with Goodpasture's disease presenting with hemoptysis, severe iron deficiency anemia and microscopic hematuria and proteinuria.... Nine months after presentation he developed nephrotic range proteinuria and a repeat renal biopsy revealed membranous glomerulonephritis with no evidence of his original disease(8).

4.  IgA nephropathy
IgA nephropathy is an autoimmune disease, affecting the kidneys
IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23(9).

5. Polyarteritis nodosa (PAN)
Polyarteritis nodosa (PAN) is defined as a vasculitis of medium & small-sized arteries
There is a report of a 53-year-old man with hepatitis C virus (HCV) infection underwent cholecystectomy for presumed cholecystitis. Gallstones were not present, and histological examination demonstrated medium-sized arteritis, consistent with polyarteritis nodosa (PAN). The patient later developed rapidly progressive glomerulonephritis. Kidney biopsy demonstrated cryoglobulinemic glomerulonephritis(10).

6. Polyangiitis (Wegener's granulomatosis)
Polyangiitis is defined as a vasculitis of small-sized blood vessels. Granulomatosis with polyangiitis (GPA), is the recently proposed, new alternative name for Wegener's granulomatosis. It defines a systemic small-vessels vasculitis, characterized by frequent involvement of upper and lower respiratory tract. According to Dr. Karras A, and the research team at hôpital Européen Georges-Pompidou, service de néphrologie(11).

7. Other causes
a. Homozygous C1q deficiency
According to the study of in mice, Dr. Botto M and the research team at the Imperial College School of Medicine, indicated that among mice without glomerulonephritis, there were significantly greater numbers of glomerular apoptotic bodies in C1q-deficient mice compared with controls. The phenotype associated with C1q deficiency was modified by background genes. These findings are compatible with the hypothesis that C1q deficiency causes autoimmunity by impairment of the clearance of apoptotic cells(12).

b.  Deficiency of factor H
Factor H is a member of the regulators of complement activation family, a complement control protein. Factor H, the main regulator of this activation, prevents formation and promotes dissociation of the C3 convertase enzyme, and, together with factor I, mediates the proteolytic inactivation of C3b. Factor H deficiency, described in 29 individuals from 12 families and in pigs, allows unhindered activation of fluid-phase C3 and severe depletion of plasma C3 (ref. 11). Membranoproliferative glomerulonephritis (MPGN) occurs in factor H-deficient humans and pigs(13).
 
B.2. Risk factors
1. Age, hypertension, and presence of nephrotic range proteinuria
The risk factors for renal dysfunction were the age, hypertension, and nephrotic range proteinuria during the follow-up period. By multivariate analysis only the, hypertension, and presence of nephrotic range proteinuria during the follow-up period were the significant risk factors(14).

2. Hepatitis C virus (HCV)
People with the infection of hepatitis C virus (HCV) are at increased risk to develop glomerulonephritis(15).

3. Genetic passing through 
Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome(16)

4. Diabetes
There is a report of an 88-year-old man with a 30-year history of type 2 diabetes and a 3-year history of chronic renal failure was admitted for evaluation of anasarca. On admission, findings of nephrotic syndrome and microscopic hematuria were observed. During the course of therapy, rapid deterioration of renal function occurred with the appearance of pneumonia. Irrespective of the therapy with hemodialysis and antibiotics, he died of respiratory failure. The autopsy showed a rare case of rapidly progressive glomerulonephritis (crescentic glomerulonephritis) superimposed on membranous nephropathy(17)

4. Other risk factors
History of cancer, Blood or lymphatic system disorders, Exposure to hydrocarbon solvents are associated to higher risk to develop glomerulonephritis(17)

C. Complications 
1.  Heart failure (HF), acute renal failure (ARF), hypertensive encephalopathy and nephrotic range proteinuria
In the study of Systemic complications of acute glomerulonephritis in Nigerian children, by Dr. Olowu WA at the Obafemi Awolowo University Teaching Hospitals Complex, showed that majority of the patients (18/29) were under 6 years of age, with peak age incidence of 3 years. The hospital incidence of AGN and prevalence of systemic complications were 10 new cases per year and 41.38%, respectively. Heart failure (HF) and acute renal failure (ARF) were sole systemic complications in 7 and 2 AGN patients, respectively. Three patients had double systemic complications: one each of hypertensive encephalopathy (HTE)+HF, HTE+ARF and ARF+HF. Ten of 29 patients (34.48%) had nephrotic range proteinuria. None of the AGN patients except those with ARF had FeNa >1%, plasma bicarbonate <15 mmol/l, urea 225 mmol/l and creatinine 2400 mmol/l. Two of the patients died: one each of ARF and ARF+HF, giving a case fatality and mortality rate of 6.90% and 0.08%(18).


2. Chronic kidney failure
In most cases of glomerulonephritis (GN),  long-term course can lead to chronic renal failure(19).
 
3. Etc.

D. Diagnosis
After completing the physical exam and family history, the tests which your doctor orders include 
1. Urinalysis 
The aim of the test is to check
a. Damage to the glomeruli
If the test shows the presence of red blood cells and red cell in the urine.
b. Infection or inflammation
If the white blood cells are presented in the urine, in mmost case.
c.  Nephron damage
If the presence of protein is found in the urinary test.

2. Blood tests
The aim of the test is to check for the presence of wast products which will provide the information of kidney damage and impairment of the glomeruli

3. Imaging tests
Image test such as an ultrasound examination or a computerized tomography (CT) scan will provide visualization of the the damage of the patient kidneys.  

4. Kidney biopsy
The diagnosis of glomerulonephritis can be confirmed by performing a kidney biopsy. A small sample is extracted from the small pieces of kidney tissue for microscopic examination. The procedure is important in predicting the likely progress, response to treatment and outcome of  glomerulonephritis.

 In the analyzing whether histological diagnosis of glomerulonephritis (GN) at an early stage of chronic kidney disease (CKD) associated with different outcome and compared to diagnosis at a more advanced stage. Patients with CKD stage 1 and 2 at kidney biopsy had fewer endpoints compared to patients with a GFR of <60 ml/min (p < 0.001). Kidney function at the time point of histological glomerulonephritis (GN) diagnosis is associated with clinical outcome, likely due to early initiation of specific drug treatment. This suggests that selection of therapy yields greatest benefit before renal function is impaired in GN(20).

E. Prevention
E.1. The do`s and do not`s list
1. Diet to enhance your immune to prevent infection and inflammation caused by bacteria and virus, including HIV and hepatitis.

2.  Mediterranean diet
On the most healthy diet in the Southern Italy and Northern Greek. MeDiet score was created based on the intake of ten food components: vegetables; whole grains; nuts; legumes; fruits; ratio of monounsaturated:saturated fat; red and processed meat; dairy products; fish; alcohol. researchers at the University of Minnesota, in the study of Relationships of the Mediterranean dietary pattern with insulin resistance and diabetes incidence in the Multi-Ethnic Study of Atherosclerosis (MESA), showed that ahigher MeDiet score was also associated with significantly lower glucose levels after basic adjustment, but was attenuated after adjustment for waist circumference. During the follow-up, 412 incident diabetes events accrued. The MeDiet was not significantly related to the risk of incident diabetes (P for trend = 0·64). In summary, greater consistency with a Mediterranean-style diet, reflected by a higher a priori MeDiet score, was cross-sectionally associated with lower insulin levels among non-diabetics, and with lower blood glucose before adjustment for obesity, but not with a lower incidence of diabetes(21).

3. Stop smoking
Cigarette contains many harmful  chemicals, including cadmium. There is a significant association between blood cadmium levels and elevated blood pressure regardless of the type of variable (continuous or categorical) in women and men with a lower blood cadmium level compared to previous Korean studies, according to the study by the Soonchunhyang University(22),

4. Safe sex
Safe sex to prevent infection caused by sexual transmitting diseases.

5. Eat well to prevent fluctuation of insulin levels of that can increase the risk of diabetic nephropathy

6. Reduce intake of salt to prevent fluid retention, swelling and hypertension

7. Maintain healthy weight to prevent complications due to obesity

8. Etc.


E.2. Phytochemicals to prevent glomerulonephritis
1. (-)-epigallocatechin-3-gallate (EGCG)
In the study of Glomerulonephritis therapy: is there a role for green tea?, researchers at the Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, showed that (-)-epigallocatechin-3-gallate (EGCG) treatment ameliorates renal inflammation, tissue damage, and loss of renal function and might therefore represent a novel therapeutic approach for human glomerulonephritis(23).

2. Resveratrol
Mesangioproliferative glomerulonephritis is associated with overactive PDGF receptor signal transduction. We show that the phytoalexin resveratrol dose dependently inhibits PDGF-induced DNA synthesis in mesangial cells with an IC(50) of 10 microM without inducing apoptosis(24).

3. Isoflavones genistein and genistin 
In the study to evaluate the Male Wistar rats with glomerulonephritis caused by a single intravenous injection of nephrotoxic serum,with 5 mg of genistein or 8 mg of genistin/d/100 g body weight for 12 d given orrally, found that these isoflavones suppressed nephritis-induced severe hypercholesterolemia and hypertriglyceridemia, and their hypolipidemic action was almost identical. Fecal steroid excretion was unchanged by administration of the two isoflavones. Genistein inhibited the incorporation of [1-14C]acetate into cholesterol and FA in liver slices from nephritic rats when added to an incubation buffer, whereas genistin did not(25).

4. Etc.


E3. Diet to prevent Glomerulonephritis
1. Flaxseed
In the study to evaluate Flaxseed: a potential treatment for lupus nephritis, showed that 30 g flaxseed/day was well tolerated and conferred benefit in terms of renal function as well as inflammatory and atherogenic mechanisms important in the pathogenesis of lupus nephritis(26).

2. Green tea
In the study to investigate whether the anti-inflammatory and antioxidant properties of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) favorably affect the development of immune-mediated GN, researchers at the Shanghai Tenth People's Hospital of Tongji University, found that levels of glutathione peroxidase and peroxisome proliferator-activated receptor-γ (PPARγ), both reduced in the vehicle-pretreated diseased mice, were normalized. This renoprotective effect was reversed by concomitant administration of the PPARγ antagonist GW9662 throughout the EGCG pretreatment period. Importantly, mortality and renal dysfunction were significantly attenuated even when the polyphenol treatment was initiated 1 week after the onset of GN. Thus, EGCG reversed the progression of immune-mediated GN in mice by targeting redox and inflammatory pathways(27).

3. Soy
According to the study of Beneficial effects of soy protein consumption for renal function by Anderson JW. at the University of Kentucky, substituting soy protein for animal protein usually decreases hyperfiltration in diabetic subjects and may reduce urine albumin excretion. Limited data are available on effects of soy peptides, isoflavones, and other soy components on renal function on renal function in diabetes(28).


4. Etc.

F. Treatment 
F.1. In conventional medicine perspective
Treatment depends on the underlined causes, symptom and types of glomerulonephritis (Acute or chronic)
F.1.1. If the causes of the disease is the result of hypertension
Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. High blood pressure means raising pressure in your heart and staying high over time, damaging the body in many ways.
1. Diuretics
Thiazide diuretics were the first tolerated efficient antihypertensive drugs that significantly reduced cardiovascular morbidity and mortality in placebo-controlled clinical studies. Although these drugs today still are considered a fundamental therapeutic tool for the treatment of hypertensive patients. Thiazide diuretics must be used at appropriate and/or optimal doses to achieve the optimal antihypertensive effect with the smallest occurrence of side effects, including alterations in glucose and lipid profiles and hypokalemia. Moreover, because thiazide diuretics can increase the incidence of new-onset diabetes, especially when combined with beta blockers, caution is advised in using these drugs above all in patients who are at high risk for developing diabetes(29), according to the study by Department of Internal Medicine, University of Pisa(29).

2. Angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II receptor agonists
In the study of a total of 25,035 hypertensive patients newly prescribed an ACE inhibitor or angiotensin II receptor blockers (ARBs), no differences were found in risk of death, coronary disease, chronic kidney disease, or stroke between those prescribed ACE inhibitors and those prescribed ARBs. Patients prescribed ARBs had a greater rate of new-onset diabetes (hazard ratio [HR], 1.28; confidence interval [CI], 1.08-1.52), and this was especially true for women (HR, 1.93; CI, 1.22-3.07). Within a large medical-practice based population, there was no evidence of differential effectiveness between ACE inhibitors and ARBs for most outcomes, with diabetes being the notable exception(30).

3. Etc.

A.2. If the causes of the disease is the result of infection due to invasion of bacteria
Corticosteroid therapy with antibiotics 

There is a report of a 24-years old man who presented to the hospital with fever, fatigue, and rapidly progressive glomerulonephritis. Although renal function in the case worsened despite therapy with antibiotics, a short-term and low dose of corticosteroid therapy with antibiotics was able to recover renal function and the patient finally underwent tricuspid valve-plasty and VSD closure, according to the study by Shiga University of Medical Science, Seta(31). 

A.3. Lupus or vasculitis
Lupus is a chronic, autoimmune disease as as a result of the development of autoantibodies that attack the systems and organs in the body.researchers at the indicated that saturated fatty acid palmitate, but not unsaturated oleate, induces the activation of the NLRP3-ASC inflammasome, causing caspase-1, IL-1β and IL-18 production. Immune-suppressing drugs can be prescribed to control inflammation. 
Immune-suppressing drugs
Tacrolimus, an immune-suppressing drug, at low dosage and serum level to be potentially effective and safe for treatment in patients with LN resistant to sufficient CYC therapy. A tacrolimus dosage of 2-3 mg daily appears to be effective and safe, according to the study by Peking Union Medical College Hospital, Chinese Academy of Medical Sciences(32)

A.4. IgA nephropathy
Treatment strategies have included management of blood pressure and lipids, improvement or stabilization of kidney function, and reduction of proteinuria. Supportive therapies, including angiotensin blockade, should be considered as first-line therapy for patients with urine protein >0.5 g/day and/or blood pressure >140/90 mm Hg. Corticosteroids could be considered as add-on or monotherapy for patients with urine protein >1 g/day with preserved renal function, but conclusive data are lacking for general treatment recommendations for the use of other therapies for IgAN(33).

A.5. Etc.
 B. In herbal medicine perspective
According to the research of Herbal treatments of glomerulonephritis and chronicrenal failure: Review and recommendations by Rainer Nowack, Felipe Flores-Suarez, Rainer Birck, Wilhelm Schmitt and Urs Benck(34), some herbs below may have certain effects in treating glomerulonephritis.
1. Astragalus
In the study to evaluate the effect of APS on glomerulonephritis rats induced by cationic Bovine Serum Albumin(C-BSA) by flow cytometry using Nuclear Transcription Factor-kappaB (NF-kappaB) as marker, showed that the expression of NF-kappaB and the concentration of IL-2, IL-6 and TNF-alpha were significantly decreased in the treatment group. This study clearly suggests that APS is effective in protecting against glomerulonephritis induced by C-BSA through the inhibition of NF-kappaB mediated-cytokine pathway(35).



2. Rhubarb
In the study of  the evidence of the effect of Rhubarb in immune complex GN induced in rats by injection of anti-thymocyte serum (ATS), researchers at the Department of Nephrology, Drum Tower Hospital, indicated that Rhubarb-treated anti-Thy-1 animal model should develop significantly less matrix expansion. Rhubarb also inhibited synthesis and secretion of fibronectin, an important component of mesangial extracellular matrix. Decreased IL-1 activity might be involved in the therapeutic effect of Rhubarb on mesangioproliferative glomerulonephritis(36).

3. Perilla frutescens
In the study to evaluate the anti-nephritic effects of perilla in HIGA mice that spontaneously develop high levels of serum immunoglobulin A (IgA) along with mesangial IgA deposition, researchers at the Graduate School of Pharmaceutical Sciences, Kyoto University, showed that Perilla suppressed proteinuria, proliferation of glomerular cells, serum levels of IgA, glomerular IgA and IgG depositions in HIGA mice. Cultured Peyer's patch cells and spleen cells from perilla-treated mice produced significantly less IgA than controls. Rosmarinic acid, by itself, suppressed serum IgA levels and glomerular IgA deposition in HIGA mice. Cultured spleen cells from RsA-treated mice produced less IgA than controls(37).


4. Dan Shen and Sheng Mai Ye
In the study to investigate the effects of danshen(Salvia plectranthoides Griff.) and shengmaiye (Panax ginseng C. A. Mey, Ophiopogon japonicus Ker-Gawl and Schisandra chinensis Baill) on glomerulosclerosis induced by adriamycin in SD rats, showed that Dansheng and shengmaiye may play an important role in the treatment of glomerulosclerosis in rats(38).

5. Arctium lappa
In the study of the ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats, researchers at the School of Pharmacy, Second Military Medical University, found that the ameliorative effects of arctiin on glomerulonephritis is carried out mainly by suppression of NF-kappaB activation and nuclear translocation and the decreases in the levels of these pro-inflammatory cytokines, while SOD is involved in the inhibitory pathway of NF-kappaB activation. Arctiin has favorable potency for the development of an inhibitory agent of NF-kappaB and further application to clinical treatment of glomerulonephritis, though clinical studies are required(39).

6. Etc. 


C. In Traditional Chinese medicine perspective 
 C.1. HTCM herbal formula: Huang Dan decoction (HDD) and Tripterygium Wilfordii (TW)
In the study to investigate the therapeutic effects of huangdan decoction (HDD) and Tripterygium Wilfordii (TW) compound tablet on membranous glomerulonephritis in rats, researchers at the Tongji Medical University, indicated that HDD and TW may alleviate the pathological lesions of MGN, prevent or retard its progression, and have remarkable therapeutic effects on MGN(40).

C.2. Shen Yan Yi Qi Ye 
In the study using cationic bovine serum albumin (C-BSA) for duplicating experimental animal model of membranous glomerulonephritis with chronic renal failure, found that in the therapeutic group, the urine protein and serum creatinine were reduced as compared with those in pathological group, P < 0.01. The parameter of morphometric analysis of glomeruli such as mean diameter, mean perimeter, mean surface area, mean volume, mean cross sectional area were all decreased, P < 0.01, the number of glomerular proliferative cells and thickness of glomerular capillary wall were all attenuated, P < 0.01, as compared with those in the pathological group. It suggested that SYYQY might alleviate the glomeruli lesions and benefit the renal functions, according to the study by Beijing University of TCM(41).

C.3. Etc,

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(13) http://www.ncbi.nlm.nih.gov/pubmed/12091909
(14) http://www.ncbi.nlm.nih.gov/pubmed/16307349
(15) http://www.ncbi.nlm.nih.gov/pubmed/22310786
(16) http://www.ncbi.nlm.nih.gov/pubmed/17018561
(17) http://www.ncbi.nlm.nih.gov/pubmed/16293921
(18) http://pennstatehershey.adam.com/content.aspx?productId=117&pid=1&gid=000484 
(19) http://www.ncbi.nlm.nih.gov/pubmed/8754411
(20) http://www.ncbi.nlm.nih.gov/pubmed/22682295
(21) http://www.ncbi.nlm.nih.gov/pubmed/22932232
(22) http://www.ncbi.nlm.nih.gov/pubmed/22692952
(23) http://www.ncbi.nlm.nih.gov/pubmed/21878951 
(24) http://www.ncbi.nlm.nih.gov/pubmed/18567737
(25) http://www.ncbi.nlm.nih.gov/pubmed/11942476 
(26) http://www.ncbi.nlm.nih.gov/pubmed/7564115
(27) http://www.ncbi.nlm.nih.gov/pubmed/21544063
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(31) http://www.ncbi.nlm.nih.gov/pubmed/15610562
(32) http://www.ncbi.nlm.nih.gov/pubmed/22935463
(33) http://www.ncbi.nlm.nih.gov/pubmed/21954446
(34) http://www.academicjournals.org/jpp/PDF/Pdf2011/Oct/Nowack%20et%20al.pdf 
(35) http://www.ncbi.nlm.nih.gov/pubmed/17161813 
(36) http://www.ncbi.nlm.nih.gov/pubmed/9812565 
(37) http://www.ncbi.nlm.nih.gov/pubmed/12584268 
(38) http://www.ncbi.nlm.nih.gov/pubmed/12080639
(39) http://www.ncbi.nlm.nih.gov/pubmed/19524415
(40) http://www.ncbi.nlm.nih.gov/pubmed/7783260  
(41) http://www.ncbi.nlm.nih.gov/pubmed/7950217   

II. Interstitial nephritis (Tubulo-interstitial nephritis) 
Interstitial nephritis is defined as a condition of inflammation of the spaces between renal tubules, affecting the interstitium of the kidneys and kidney function in wast removal.
A. Signs and symptoms 
In the study of Symptoms in patients with tubulo-interstitial nephritis, researchers at the School of Medicine, Juntendo University, indicated that in patients with acute TIN, marked
1. Fever,
2. Back or flank pain
3. CVA tenderness
4. Skin rash
5. Arthralgia
6. Cosinophilia and
7. Eosinouria are observed.
Clinical symptoms might be induced by glomerular, proximal tubular or distal tubular dysfunction in chronic TIN. Mild to moderate
8. Proteinuria
9. Edema
10. Hypertension
11. Azotemia
12. Glucosuria
13. Aminoaciduria
14. Polyuria and
15. Polydipsia are characteristic findings in patients with chronic TIN(1).


B. Causes and Risk factors
1. In the study of The outcome of acute interstitial nephritis: risk factors for the transition from acute to chronic interstitial nephritis, researchers at the Department of Nephrology, MHH, Hannover, Germany, in determination of risk factors for the development of chronic renal insufficiency, and thus, the transition from acute to chronic interstitial nephritis, showed that acute interstitial nephritis was found in 6.5% of all biopsies (64 patients with 68 episodes of acute interstitial nephritis); it was infection-induced in 10%, idiopathic in 4%, and drug-induced in 85% of the cases (antibiotics in 13 cases, analgesics in 17, non-steroidal anti-inflammatory drugs (NSAIDs) in 16, diuretics in 5, and various other drugs in 7). Renal insufficiency was reversible in 69% and permanent in 31% (12% partially reversible, 19% irreversible). The infection-induced and idiopathic types of acute interstitial nephritis were always reversible. Drug-related acute interstitial nephritis caused permanent renal insufficiency in 36% with a maximum of 56% in NSAID-induced cases. In drug-induced cases, intake of the suspected drug for more than a month prior to diagnosis caused permanent renal insufficiency in 88% and interstitial granuloma in 31%(2).

2. Impaired potassium and magnesium homeostasis and urinary losses are associated with the increased risk of acute tubulo-interstitial nephritis(3)

3. Hypercalcemia is a life-threatening disorder and is related primarily to neoplastic diseases and primary and secondary hyperparathyroidism and associated to the risk of Interstitial nephritis(4).

4. Allergic effect
A severe generalized multisystem allergic reaction occurred in a 16-month-old infant following the use of trimethoprim-sulfamethoxazole. Acute interstitial nephritis developed three weeks following the onset of this reaction and resolved after three months. This is the first description of this renal toxicity with TMP-SMX in a child(4a).

5. Etc.


C. Diseases associated with interstitial nephritis
1. Crohn's Disease
There is a report of s case of of granulomatous interstitial nephritis (GIN) associated with Crohn's disease (CD) was reported. GIN is a rare pathological finding in renal biopsy specimens. In a patient affected by CD, granulomas may be found in various tissues and organs such as lymph nodes, mesentery, liver, and lungs and occasionally in bones, joints, and skeletal muscle. Few cases of granuloma have been reported in the kidney, and it is not always possible to relate the presence of granuloma to CD, to other interstitial granulomatosis diseases, or to a drug-induced reaction(5).

2. Sjögren's syndrome
In the study of the tissue distribution of cellular adhesion molecules (ICAM-1, ELAM-1, VCAM-1) was studied in specimens from six normal human kidneys and in six biopsies from kidneys with tubulointerstitial nephritis associated with Sjögren's syndrome, researchers at the Toho University School of Medicine, showed that adhesion molecules were thought to play a role in the pathogenesis of tubulointerstitial nephritis and sialoadenitis associated with Sjögren's syndrome. It was thus concluded that the same inflammatory process that took place in the salivary glands to induce the characteristic tissue change of Sjögren's syndrome likely was operative in the renal tubulointerstitial tissue as well(6).

3. Uveitisa
There is a report of Clinical features and natural course of acute tubulointerstial nephritis and uveitis (TINU syndrome) in five adolescent patients (3 girls and 2 boys), according to Dr. Nikolić V, and reseach team(7)

4. Tuberculosis
Tuberculosis (TB) is a common disease worldwide, but kidney affection, i.e. tubulointerstitial nephritis (TIN) caused by Mycobacterium tuberculosis is rare. More frequent in patients with TB is drug induced TIN, i.e. the result of intensive antitubercular treatment(8). 

5. Castleman's disease
There is a report of a case of mesangial proliferative glomerulonephritis with interstitial nephritis associated with multicentric Castleman's disease (MCD) successfully treated with an anti-interleukin-6 receptor antibody (tocilizumab)(9).

6. Feline morbillivirus
Feline morbillivirus, a previously undescribed paramyxovirus associated with tubulointerstitial nephritis in domestic cats(10)

7.  Etc.   

D. Diagnosis
Dr. Nikolić V and the research team in the review of the data between 1986 and 1997 of 21 patients, aged 7-16 years (mean, 12.8), with acute tubulointerstitial nephritis, including eight with tubulointerstitial nephritis and uveitis (TINU syndrome). Laboratory studies included urinalysis, complete blood count, erytrocyte sedimentation rate (ESR), plasma creatinine, glomerular filtration rate (GFR), electrolytes, proteins, IgG, C3, C4 antinuclear-antibodies (ANA), antistreptolysin-O and antibodies to hantaviruses. Renal ultrasound was done in all patients. Renal biopsy was performed in 5 children(11).


E. Prevention
1. Avoid overdose of medication and vitamins
Overdose of certain medication indicated above and some vitamins are associated to the increased risk of the diseases.
2. Eat well to enhance the immune system to prevent bacterial and viral causes of inflammation.
3. Use herbs with caution
Overdose of herb can damage to kidney of that can lead to interstitial nephritis(11a).
4. Avoid extreme Exercise
There is a report of a A 45-year-old man presented with abdominal pain, vomiting, and oliguria after severe exercise as a result of Familial renal hypouricemia with exercise-induced acute renal failure (ARF)(12).
5. Reduce in take of animal fat to prevent waste to the kidney
6. Reduce intake of salt to reduce the risk of hypertension and kidney overload.
7. Etc.
 
F. Treatment 
F.1. In conventional medicine perspective
1. Acute tubulointerstitial nephritis
In the study to evaluate the controversial effects of steroids in acute tubulointerstitial nephritis (ATIN), showed that steroid treated (StG) patients had a greater degree of improvement in their renal function; however there was no correlation between the degree of improvement in eGFR and delay in starting steroids. PPIs were second commonest implicated drug category among drug induced cases(13).

2. Chronic tubulointerstitial nephritis
Chronic tubulointerstitial nephritis has no cure. Many patients may require dialysis. In younger patient,  kidney transplant may be the only choice. 

F.2. In herbal medicine perspective
1. Soy
In the study to evaluate the effects of soy protein isolate (SPI) on severe kidney damage in deoxycorticosterone acetate (DOCA) salt-treated obese Zucker rats, researchers at the Food Science Research Institute, Fuji Oil Company Ltd., Izumisano-shi, showed that that consecutive treatment of SPI protects against renal dysfunction, particularly tubulointerstitial nephritis, in DOCA salt-treated obese Zucker rats(14).

2.  Flaxseed
In the study to determine if flaxseed would also modify clinical course and renal pathology in the Han:SPRD-cy rat, showed that Flaxseed ameliorates Han:SPRD-cy rat polycystic kidney disease through moderation of the associated chronic interstitial nephritis. The diet alters renal content of polyunsaturated fatty acids in a manner that may promote the formation of less inflammatory classes of renal prostanoids(15).

3. Etc.
 
F.3. In traditional Chinese medicine perspective 
1. Traditional Chinese medicine with immunosuppressant
In an  experimental study combined on traditional Chinese medicine with immunosuppressant for treatment and prevention of tubular interstitial nephritism researchers at the Department of Nephrology, First Affiliated Hospital, showed that the infiltration of cells was inhibited in the "Chinese herbs combined with prednisone" group, the infiltration of cells, TGF-beta expression and interstitial fibrosis were all inhibited in the cyclophosphamide and prednisone" group. But in the prednisone group, interstitial fibrosis was not inhibited. These data suggest that the combined use of Chinese herbs, immunosuppressant and prednisone can inhibit the interstitial cell infiltration and prevent the interstitial fibrosis in diffuse proliferative glomerulonephritis(16).

2. Astragali Radix and Angelicae Sinensis Radix (AS-IV)with ferulic acid
Other researchers suggested that AS-IV synergizes with FA to alleviate renal tubulointerstitial fibrosis; this was associated with inhibition of tubular epithelial-mesenchymal transdifferentiation (EMT) and fibroblast activation, as well as an increase in NO production in the kidney(17).
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