Monday, February 18, 2013

Dietary Mineral - Boron

Boron, a vital trace mineral found abundantly in Almond, Red Apple, Apricots, Avocado, Banana, Red kidneyBeans, etc., is necessary for the normal growth and health of the body. Boric acid has antiseptic and antiviral activity. Its aqueous solutions have been used as mouth-washes, eye-drops, skin lotions and cosmetics(1).

1. Boron and Osteoporosis
Osteoporosis and low bone mineral density affect millions of Americans. According to the study by Orlando Health, the majority of adults in North America have insufficient intake of vitamin D and calcium along with inadequate exercise. Physicians are aware that vitamin D, calcium and exercise are essential for maintenance of bone health. Physicians are less likely to be aware that dietary insufficiencies of magnesium, silicon, Vitamin K, and boron are also widely prevalent, and each of these essential nutrients is an important contributor to bone health(2). Other in the study to compare the possible relationship between urinary concentrations of boron, calcium, magnesium and phosphorus in serum and urine of postmenopausal women with and without osteoporosis of 45 postmenopausal women over 47 years of age, the preliminary results suggest the existence of a significant difference (p < 0.05) in boron and phosphorus concentrations in the urine of two hours between the groups. The model of linear regression analysis used showed a relationship between urinary concentrations of boron/creatinine index and calcium/ creatinine, magnesium/creatinine and phosphorus/creatinine indexes in the urine of postmenopausal women with osteoporosis(2a).

2. Dietary boron on mineral, estrogen, and testosterone metabolism in postmenopausal women
In the study to to examine the effects of aluminum, magnesium, and boron on major mineral metabolism in postmenopausal women, conducted by the  Grand Forks Human Nutrition Research Center, showed that boron supplementation markedly reduced the urinary excretion of calcium and magnesium; the depression seemed more marked when dietary magnesium was low. Boron supplementation depressed the urinary excretion of phosphorus by the low-magnesium, but not by the adequate-magnesium, women. Boron supplementation markedly elevated the serum concentrations of 17 beta-estradiol and testosterone; the elevation seemed more marked when dietary magnesium was low(3). Other study found that increase in dietary intake of B from 0.25 to 3.25 mg/d has been reported to increase plasma oestradiol and testosterone and decrease urinary Ca excretion in postmenopausal women. Changing B intake from 0.33 to 3.33 mg/d had no effect on minerals, steroids or crosslinks. However, the LBD (low-B diet) appeared to induce hyperabsorption of Ca since positive Ca balances were found in combination with elevated urinary Ca excretion. This phenomenon may have inhibited or obscured any effect of B(3a).

3. Plasma boron and the effects of boron supplementation in males
In the study to examine the effect of boron supplementation in 10 male bodybuilders, who  (aged 20 to 26) were given a 2.5-mg boron supplement, with nine male bodybuilders (aged 21 to 27) were given a placebo for 7 weeks. Plasma total and free testosterone, plasma boron, lean body mass, and strength measurements were determined on day 1 and day 49, found that bBoth groups demonstrated significant increases in total testosterone (p < 0.01), lean body mass (p < 0.01), and one repetition maximum (RM) squat (p < 0.001) and one RM bench press (p < 0.01). The findings suggest that 7 weeks of bodybuilding can increase total testosterone, lean body mass, and strength in lesser-trained bodybuilders, but boron supplementation affects these variables not at all(4).

4. Boron supplementation on lean body mass, plasma testosterone levels
In the study to evaluate the effect of boron supplementation in 19 male bodybuilders ages 20-27 years. Ten were given a 2.5-mg boron supplement while 9 were given a placebo every day for 7 weeks. Plasma total and free testosterone, plasma boron, lean body mass, and strength measurements were determined on Days 1 and 49, found that 7 weeks of bodybuilding can increase total testosterone, lean body mass, and strength in lesser trained bodybuilders, and that boron supplementation had no effect on these measures(5).

5. Boron and Fertility
In the study to investigate the consequences of exposure to three levels of boric acid on male rats reproduction, fertility, and progeny outcome, with emphasis on testicular DNA level and quality, by Ain Shams University, showed that the impact of boric acid exposure at dose 250 mg on male rats fertility was translated into increases in pre-implantation loss with a resulting decrease in the number of live fetuses/ litter. In addition to the significant alteration of biochemical measurements, observed at dose 250 mg, administration of boric acid at 500 mg caused testicular atrophy, severe damage of spermatogenesis, spermiation failure and significant reduction of Mg and Zn testicular levels. None of the male rats, treated with 500 mg/kg bwt, could impregnate untreated females, suggesting the occurrence of definitive loss of fertility(5a).

6. Dietary Boron and aging
Total boron concentrations in Drosophila changed during development and aging. In the study of mouses conducted by Masonic Medical Research Laboratory, found that  Adding excess dietary boron during the adult stage decreased the median life span by 69% at 0.01 M sodium borate and by 21% at 0.001 M sodium borate. Lower concentrations gave small but significant increases in life span. Supplementing a very low boron diet with 0.00025 M sodium borate improved life span by 9.5%. The boron contents of young and old mouse tissues were similar to those of Drosophila and human samples. Boron supplements of 4.3 and 21.6 ppm in the drinking water, however, did not significantly change the life span of old mice fed a diet containing 31.1 ppm boron(6).

7. Boron and hormonal regulation and cognitive function
in the study to review the scientific evidence of some studies on boron including expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing, found that there was a lack of systematic study on the safety and effectiveness of boron in humans. However, based on popular use and supportive scientific data, nine indications are discussed in this review: hormone regulation, improving cognitive function, osteoarthritis, osteoporosis, vaginitis (topical), bodybuilding aid (increasing testosterone), menopausal symptoms, prevention of blood clotting (coagulation effects), and psoriasis (topical). Although studies assessing the use of boron for osteoarthritis and osteoporosis are in preliminary stages, reports are promising. There is conflicting evidence to support the use of boron in hormonal regulation and cognitive function. Future randomized controlled trials are warranted. There is fair negative evidence regarding the use of boron as an anticoagulant, a bodybuilding aid, for menopausal symptoms, or for psoriasis. Excessive use may be harmful, and caution is advised(7).

8. Boron nutrition for brain and psychological function
Certain stuies indicated that Boron (B) nutriture has been related to bone, mineral and lipid metabolism, energy utilization, and immune function. In the study to consider possible relationships between B nutriture and brain and psychological function, indicated that assessments of brain electrical activity in both animals and humans found that B deprivation results in decreased brain electrical activity similar to that observed in nonspecific malnutrition. Assessments of cognitive and psychomotor function in humans found that B deprivation results in poorer performance on tasks of motor speed and dexterity, attention, and short-term memory. However, little support was found for anecdotal reports that supplementation with physiologic amounts of B helps alleviate the somatic and psychological symptoms of menopause. Parallels between nutritional and toxicological effects of B on brain and psychological function are presented, and possible biological mechanisms for dietary effects are reviewed. Findings support the hypothesis that B nutriture is important for brain and psychological function in humans(8).

9. Dietary boron and Magnessium
In the study with human volunteers conducted to test the hypothesis that naturally occurring inadequate intakes of magnesium induce negative magnesium balance and undesirable changes in calcium metabolism variables, and that these changes are influenced by dietary boron, indicated that consuming an ordinary diet deficient in magnesium, resulting in negative magnesium balance, can affect calcium, potassium, and cholesterol metabolism. Dietary boron did not have an obvious effect on the response to magnesium deprivation(9).

10. 2-aminoethoxydiphenyl borate (2-APB) and ORAI1
In the study to assess the influence of Orai1(ORAI calcium release-activated calcium modulator 1) intervention on mouse airway epithelium reactions in vivo and in vitro, found that administration of 2-aminoethoxydiphenyl borate (2-APB) into the nostrils suppressed Orai1 expression in nasal and tracheal mucosa of treated mice compared with that in control mice and restrained the mediators in nasal lavage fluid, bronchoalveolar lavage fluid, and airway mucosa of treated groups compared with those in control groups. Similarly, the 2-APB intervention also alleviated Orai1 and the production of the mediators in culture supernatant and cultured airway epithelium under allergic conditions(10).

11.  Boronic acid and Antimalarials
The high rate of mortality due to malaria and the worldwide distribution of parasite resistance to the commonly used antimalarial drugs chloroquine and pyrimethamine emphasize the urgent need for the development of new antimalarial drugs. According to the study to test Proteasome inhibitor bortezomib (Velcade: [(1R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl) amino]propyl]amino]butyl] boronic acid), which has been approved for treatment of patients with multiple myeloma, and a second boronate analog Z-Leu-Leu-Leu-B(OH)2 (ZL3B),  against four different strains of P. falciparum (3D7, HB3, W2 and Dd2) by University of Connecticut Health Center, found that the identification of bortezomib and its analog as potent antimalarial drugs will set the stage for the advancement of this class of compounds, either alone or in combination therapy, for treatment of malaria, and emphasize the need for large-scale screens to identify new antimalarials within the library of clinically approved compounds(11).

12. Boron and parasites
In the study of Balb/c mice fed either a low-B (0.2 microg B/g), marginal (2.0 microg B/g), or control (12.0 microg B/g) diet and to  explore whether low dietary B would: 1) alter survival or reproduction of Heligmosomoides bakeri (Nematoda); 2) modify the resulting cytokine response to this parasitic infection; or 3) influence liver mineral concentrations in the infected host, showed that parasite survival and cytokine and inflammatory responses are modified by dietary B intake but indicates that a GI nematode infection alters liver mineral concentrations(12). 

13. Boronic acids and Candida albicans
In the study of the inhibition of the beta-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Cryptococcus neoformans (Can2) and Candida albicans (Nce103) with a series of aromatic, arylalkenyl- and arylalkylboronic acids, found that the host human enzymes CA I and II were also effectively inhibited by these boronic acids. The B(OH)(2) moiety is thus a new zinc-binding group for designing effective inhibitors of the alpha- and beta-CAs.

14. Bortezomib and antibody-mediated diseases (lupus-like disease)
In the study of The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis conducted by Nikolaus Fiebiger-Center of Molecular Medicine, University Hospital Erlangen, found that treatment with bortezomib depleted plasma cells producing antibodies to double-stranded DNA, eliminated autoantibody production, ameliorated glomerulonephritis and prolonged survival of two mouse strains with lupus-like disease, NZB/W F1 and MRL/lpr mice. Hence, the elimination of autoreactive plasma cells by proteasome inhibitors might represent a new treatment strategy for antibody-mediated diseases(14). Other study showed that the proteasome inhibitor bortezomib, approved for the treatment of multiple myeloma, efficiently depletes short- and long-lived plasma cells and ameliorates lupus nephritis in mouse models. These novel therapies may improve the future treatment of SLE and other antibody-mediated diseases(14a).


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ources
(1) http://chemicalland21.com/industrialchem/inorganic/BORIC%20ACID.htm
(2) http://www.ncbi.nlm.nih.gov/pubmed/22523525
(2a) http://www.ncbi.nlm.nih.gov/pubmed/22524104 
(3) http://www.ncbi.nlm.nih.gov/pubmed/3678698
(3a) http://www.ncbi.nlm.nih.gov/pubmed/8329361
(4) http://www.ncbi.nlm.nih.gov/pubmed/7889885
(5) http://www.ncbi.nlm.nih.gov/pubmed/8508192
(5a) http://www.ncbi.nlm.nih.gov/pubmed/23301826
(6) http://www.ncbi.nlm.nih.gov/pubmed/7889879
(7) http://www.ncbi.nlm.nih.gov/pubmed/22433045
(8) http://www.ncbi.nlm.nih.gov/pubmed/10050926
(9) http://www.ncbi.nlm.nih.gov/pubmed/15724868
(10) http://www.ncbi.nlm.nih.gov/pubmed/22289729
(11) http://www.ncbi.nlm.nih.gov/pubmed/17956613
(12) http://www.ncbi.nlm.nih.gov/pubmed/17709446
(13) http://www.ncbi.nlm.nih.gov/pubmed/19375309
(14) http://www.ncbi.nlm.nih.gov/pubmed/18542049
(14a) http://www.ncbi.nlm.nih.gov/pubmed/19224224

Wednesday, February 13, 2013

Enteritis

Acute Enteritis, in most cases is defined as a condition of inflammation of the small intestine as a result of eating and drinking contaminated water and foods infected by virus and bacteria. But according to the study by the University Hospital Aintree, chronic radiation enteritis is an increasing problem, as more patients receive radiotherapy as part of their cancer therapy and as the long-term survival of these patients improves(a). Other study indicated that acute radiation enteritis is almost inevitable in the curative treatment of malignant tumors of the abdomen and pelvic area. It is frequently a self-limiting disorder of intestinal function associated with reversible mucosal changes of the intestine(b). The prevalence of the disease although is decreasing, it still affects millions (approx 1 in 83 or 1.20% or 3.3 million people in USA ) of people in the U.S alone, according to the statistic. Chronic enteritis is a condition of inflammation caused by other health conditions, such as Crohn's or celiac disease.

Types of Entertitis
1. Campylobacter enteritis (Campylobacter jejuni)
Campylobacter enteritis is the commonest form of infective diarrhoea in most developed countries of the world. According to the statistic from Wales laboratory, the an annual incidence of about 85/100,000, but the true rate is probably nearer 1100/100,000. Most infections are sporadic and believed to be foodborne; large outbreaks are infrequent and mostly as a result of the consumption of raw milk or unchlorinated water. Raw meats and animal products, notably broiler chickens, are the main source of campylobacters in food(c). Other indicated that Cross-contamination and improper handling and cooking of foods of animal origin account for the majority of disease. Hygienic measures must be applied in order to reduce the incidence of campylobacteriosis in humans(b).

2. E. coli enteritis (E. coli)
In an age cross sectional cohort analysis of 340 0-47 month old children and newborn cohort analysis of 144 newborns to determine the diarrheogenic Escherichia coli incidence in Santa Julia, a low socioeconomic community in Santiago, Chile, between December 1986 and February 1990, showed thatthe age cross sectional cohort had 1178 episodes of diarrhea and the newborn cohort had 674 episodes. No difference in the isolation rate of enteroaggregative E. coli existed between cases and controls. Since most households in Santa Julia have access to potable water (68%) and an indoor toilet (64%), food contamination were likely the vehicles of E. coli transmission because more than 50% of households do not have a refrigerator(e). Other in the review of the outbreak of E. coli O142 K86 H34, the enteritis of adults and children are due to enteroinvasive (EIEC) and enterotoxigenic (ETEC) strains, suggested that routine search for EPEC is suggested in cases of infantile enteritis in hospitals and other institutions(f).

3. Clostridium perfringens enteritis
Clostridium perfringens is an important anaerobic pathogen causing foodborne and non-foodborne gastrointestinal diseases in humans and animals. This pathogen is also the more common Clostridium species associated with bacteraemia. We report on a fatal case of C. perfringens infection in an adult with type 2 diabetes(g).

4. Staphylococcal enteritis (Food poisioning)
The disease is as reslt of eating or drinking substances contaminated with staph enterotoxin. The enterotoxins are fast acting, sometimes causing illness within one to six hours. Patients typically experience nausea, vomiting, stomach cramps, and diarrhea(h).

5. Radiation enteritis
Radiation therapy may damage the lining of the intestines (bowels) and cause inflammation.
The clinicopathologic features of radiation enteritis are reviewed in 44 children receiving whole abdominal radiation therapy between 1961-1972 at the Institut Gustave-Roussy. Five of 14 long-term survivors (36%) developed severe delayed radiation injury with small bowel obstruction, occurring within 2 months after completion of irradiation. All had previously had acute radiation reaction during therapy, according to the study by Dr. Donaldson SS and the research team(i).

6. Salmonella enteritis
Salmonella enterica and Campylobacter spp. cause a considerable number of human illnesses each year, and the vast majority of cases are foodborne(j). Other study indicated thatthe most common disease syndromes caused by Salmonella serotypes in humans, typhoid fever and enteritis, can be modeled using Salmonella enterica serotype Typhimurium infections in mice and calves, respectively(k).

7. Shigella enteritis
Shigella species cause bacillary dysentery in humans by invasion, intracellular multiplication, spread to adjacent cells, and induction of brisk inflammatory responses in the intestinal epithelium(l). According to the study, in August 2002, an outbreak of Shigella sonnei infection occurred in a Spanish town of 6343 inhabitants. In total, 756 people developed acute gastroenteritis and 181 cases were shigella-confirmed. The peak incidence was during 5-6 August 2002. The estimated primary attack rate was 9.97%; the attack rate for secondary cases was 38%. The <15 years ago group was most affected (16.49%)(m).

8. Etc.

I. Symptoms 
1. Abdomen Pain, diahrrea and fever
There is a report of a case of Cytomegalovirus ileitis with multiple small bowel perforations in a young man with human immunodeficiency virus (HIV) infection. The patient developed abdominal pain with diarrhea and fever, and eventually acute abdomen with pneumoperitoneum(1).

2. Post-infectious fatigue and abdominal symptoms
Some patients with Severity of Giardia infection after treatment may be experience Post-infectious fatigue and abdominal symptoms. According to the study by Haukeland University Hospital, Protracted and severe giardiasis seemed to be a risk factor for post-infectious fatigue and abdominal symptoms two years after clearing the Giardia infection(2).

3. Bloating, Iron and vitamin deficiency
Patient with Campylobacter jejuni enteritis may be experioence with symptoms of persistent diarrhea, new-onset bloating and the development of iron and vitamin deficiencies.
There is a report of  a young woman with no previous gastrointestinal complaints who was initially diagnosed with postinfective irritable bowel syndrome (IBS) after a confirmed case of Campylobacter jejuni enteritis. However, because of persistent diarrhea, new-onset bloating and the development of iron and vitamin deficiencies(3).

4. Hematochezia
Hematochezia is defined as a condition of passing fresh blood through the anus and in or with stools. In most cases it is caused by the bleeding of lower gastrointestine.

5. Dizziness
Patient with cryptogenic multifocal ulcerous stenosing enteritis, may be experiencerecurrent colicky abdominal pain and dizziness(4).

6. Acute intestinal obstruction or perforation
Although Acute intestinal obstruction or perforationare rare in patient with enteritis. There is a report of a case of a case of eosinophilic enteritis, hitherto unreported, presenting as an ileal obstruction, and followed by jejunal bleeding, which was visualized by capsule endoscopy. A 62-year-old man received a 15 cm single segmental ileal resection at a point 50 cm from the IC valve due to symptoms of obstruction, which were diagnosed as eosinophilic enteritis(5).

7. Constipation
There is a report of a case of mucosal Eosinophilic gastroenteris (EG) presenting as constipation and abdominal pain in a 43 year old female.  EG should be considered in the differential diagnosis of patients presenting with constipation and abdominal pain and can easily be diagnosed with mucosal biopsies and treated with steroid therapy(5a).

8. Others
Patients may be also experience to symptoms of loss of appetite, dehydration, vomiting, thirst, change in stool pattern, high CRP and leucocytosisetc, etc(5b).


II. Causes and Risk factors
A. Causes
1. Radiation-induced enteritis
Radiation enteritis is a severe problem in patients receiving irradiation of the abdomen or pelvis in the course of cancer treatment. According to the study by Fovárosi Onkormányzat Uzsoki Utcai Kórház Onkoradiológiai Központ Budapest Uzsoki u. 29. 1145, during the radiotherapy of tumors in the minor pelvis and abdomen intestinal inflammation of different degree may occur even if special attention is paid. Irradiation to the minor pelvis causes in half of the cases radiation induced acute enteritis, whereas in 25% chronic enteritis and colitis will develop(6).

2. Virus
Certain virus can induce entertitis including Cytomegalovirus and Norovirus. The Norovirus causes severe gastroenteritis requiring hospitalization especially in children less than five years of age both in developed and developing countries, according to the study to investigate the incidence of norovirus (NoV) in 0-5 years old children with acute gastroenteritis in two large hospitals in Ankara, Turkey. Stool samples were obtained from 1000 (413 female, 587 male) children between 0-5 years old with acute gastroenteritis by Gazi University Faculty of Medicine, Department of Medical Microbiology, Ankara, Turkey, indicated that  NoV detection rate was highest in 2007 (18.4%) and in 2009 (18%), and the difference regarding ELISA positivity among the study years was not statistically significant (p> 0.05). The prevalences of norovirus infection in spring, summer, autumn and winter were 13.8%, 17.7%, 14.7% and 11.2%, respectively. Therefore no seasonal variation was found in the incidence of norovirus infection. However when the monthly prevalence was analyzed, a statistically significant difference was found (p< 0.05) between the rate of norovirus infection in july (24.2%) and december (4.1%)(7).

3. Bacteria
Escherichia coli are ubiquitous bacteria from a wide variety of ecosystems including the gastrointestinal tract of humans and warm-blooded animals. E. coli can play a role as an opportunistic bacteria causing a variety of infectious diseases including, among many others, sepsis, urinary tract infections, meningitis, and wound infections. Moreover, these bacteria can also act as primary pathogens in the intestinal tract, according to the study by Universidad de Barcelona, Barcelona, España(8).

4. Crohn's disease
Crohn's disease is often considered an autoimmune condition, based on the observations of a histopathological inflammatory process in the absence of identifiable causal microorganism(s) and that immune-modulating therapeutics result in diminished host-directed inflammatory pathology(9). Cryptogenic multifocal ulcerous stenosing enteritis is a rare idiopathic disease of the small bowel, according to the study by, there is a report of a  44-year-old man complained of recurrent colicky abdominal pain and dizziness. Laboratory tests indicated iron-deficiency anemia. There was no evidence of bleeding on esophagogastroduodenoscopic and colonofiberscopic examination. With capsule endoscopy, multiple mucosal ulcers were visualized in the jejunoileal area. A small-bowel series revealed severe strictures and the capsule was retained in the stenotic focus without obstructive symptoms. Small bowel segmental resection with end-to-end anastomosis was performed, and the histologic examination indicated cryptogenic multifocal ulcerous stenosing enteritis(10).

5. Medication such as proton pump inhibitors
Gastric acid is a defense mechanism against gastrointestinal infections caused by ingested bacteria. According to the study by Centro Español de Investigación Farmacoepidemiológica, Madrid, Spain, gastric acid suppression induced by proton pump inhibitors (PPIs) but not H2RAs is associated with an increased risk of Campylobacter and Salmonella GE(11).

6. Drugs
There is a report of a 25-year-old woman who was hospitalized repeatedly during a 5-year period due to abdominal pain, change in stool pattern, high CRP and leucocytosis. A thorough interview revealed a recreational use of cocaine, and diary recordings confirmed the association between her abdominal pain and cocaine use(12).

B. Risk Factors
1. Intestinal illness
People who have a family memeber with intestinal illness are at increased risk to develop gastroenteritis.In the study to evaluate risk factors for childhood hemolytic-uremic syndrome (HUS) and gastroenteritis during an epidemic of Escherichia coli O157:H7 infection, showed that Patients with HUS and those with uncomplicated E. coli O157:H7 gastroenteritis differed only on measures of clinical severity. In the 7 days before the onset of gastrointestinal symptoms, children with HUS and those with uncomplicated gastroenteritis were more likely to have been exposed to a family member with diarrhea than were the healthy control subjects (odds ratio = 9 for HUS vs healthy control subjects; 95% confidence interval 2 to 43; p < 0.01)(13).

2. Undercooked ground meat and foods
Undercooked ground meat and foods traditionally consumed by the Inuit were not implicated as risk factors in E. coli O157:H7 infection(14).

3. Environmental risk
Campylobacter is a common cause of bacterial gastro-enteritis characterized by multiple environmental sources and transmission pathways. According to the study, regional characteristics associated with an increased regional risk of campylobacteriosis, for at least some geographical units, were high ruminant density, high poultry density, high population density, and presence of a large poultry slaughterhouse, whereas a reduction in risk was associated with a lower percentage of people with diplomas, a lower level of precipitation, and warmer temperature. Two clusters of elevated residual risk were observed, with different location and size depending on the geographical unit used(15).

4. Biologically plausible risk
In the study to to evaluate whether the increase in incidence of campylobacteriosis observed in humans in Norway from 1995 to 2001 was statistically significant and whether different biologically plausible risk factors were associated with the incidence of campylobacteriosis in the different counties in Norway, found that treated water was a protective factor against Campylobacter infections in humans with an IRR of 0.78 per percentage increase in people supplied. Campylobacter infections did not appear to be clustered in any particular county in Norway(16).

5. Immune dysfunction
Immune system is responsible in fighting against invasion of bacteria and virus. Cytomegalovirus infection of the gastrointestinal tract is common and is more often seen in patients with acquired immunodeficiency syndrome (AIDS)(17).

6. Aging
Elderly are more susceptible to bacterial and virus infection and inflammation, as a result of weakened immune system.

7. Etc.

II. Diseases associated to Entetitis
1. Functional gastrointestinal disorders (PI-FGID)
A Giardia outbreak was associated with development of post-infectious functional gastrointestinal disorders (PI-FGID) and chronic fatigue syndrome (PI-CFS). According to the study by the University of Bergen, Patients with PI-CFS and/or PI-FGID 5 years after Giardia lamblia infection showed alterations in NK-cell and CD8-cell populations suggesting a possible immunological abnormality in these conditions(18).

2. Small bowel perforation
There is a report of a  case of Cytomegalovirus ileitis with multiple small bowel perforations in a young man with human immunodeficiency virus (HIV) infection. The patient developed abdominal pain with diarrhea and fever, and eventually acute abdomen with pneumoperitoneum(19).

3. Severe intraluminal hemorrhage 
There is a report of 4  9-month-old Simmental male calves were presented with a history of sudden death. The necropsy and microscopic findings allowed a diagnosis of enteritis and severe intraluminal hemorrhage with blood clots in the jejunum, suggestive of jejunal hemorrhage syndrome, according to the study by Institute of Veterinary Medicine Belgrade(20).

4.  Chronic and recurrent occlusion events and multiple small intestinal ulcers
Cryptogenic multifocal ulcerous stenosing enteritis is a rare idiopathic disease of the small bowel. According to the study by Seoul Paik Hospital, Inje University, College of Medicine Seoul, there is a case of a 44-year-old man complained of recurrent colicky abdominal pain and dizziness. A small-bowel series revealed severe strictures and the capsule was retained in the stenotic focus without obstructive symptoms. Small bowel segmental resection with end-to-end anastomosis was performed, and the histologic examination indicated cryptogenic multifocal ulcerous stenosing enteritis. Cryptogenic multifocal ulcerous stenosing enteritis should be considered in cases of chronic or recurrent occlusion events and multiple small intestinal ulcers and strictures of unknown origin(21).

5. Hypereosinophilic syndrome
Hypereosinophilic syndrome is a blood disorder characterized by the overproduction of eosinophils in the bone marrow with persistent peripheral eosinophilia, associated with organ damage by the release of eosinophilic mediators. Although HES can involve multiple organ systems, GI tract involvement is very rare. Few cases of HES presenting with gastritis or enteritis have been reported worldwide(21a).

6. Systemic lupus erythematosus
There is a reprot of a  38-year-old Persian Iranian woman admitted with a five-month history of diarrhea and abdominal pain. A physical examination showed nothing abnormal. Initially, she had only lymphopenia and mild eosinophilia. No autoimmune or infectious etiology was detected to justify these abnormalities. A thorough evaluation was not helpful in finding the etiology, until she developed a scalp lesion similar to discoid lupus erythematosus. Computed tomography showed small bowel wall thickening. Briefly, she manifested full-blown SLE, and it was revealed that the diarrhea was caused by eosinophilic enteritis, according to the study by Tehran University of Medical Sciences(21b)


III. Complications
1. Chronic fatigue syndrome
A waterborne outbreak of Giardia lamblia gastroenteritis led to a high prevalance of long-lasting fatigue and abdominal symptoms. In the study to describe the clinical characteristics, disability and employmentloss in a case series of patients with Chronic Fatigue Syndrome (CFS) after the infection, showed that in a total of 58 (60%) out of 96 patients with long-lasting post-infectious fatigue after laboratory confirmed giardiasis were diagnosed with CFS. In all, 1262 patients had laboratory confirmed giardiasis(22).

2. Irritable bowel syndrome and chronic fatigue
Giardia lamblia is a common cause of gastroenteritis worldwide, but there is limited knowledge about the long-term complications. In the study to estimate the relative risk of irritable bowel syndrome (IBS) and chronic fatigue 3 years after acute giardiasis, indicated that Infection with Giardia lamblia in a non-endemic area was associated with a high prevalence of IBS and chronic fatigue 3 years after acute illness.This shows that the potential consequences of giardiasis are more serious than previously known. Further studies are needed, especially in areas where giardiasis is endemic(23).

3. Arthritis symptoms
According to the London Kidney Research Unit, Division of Nephrology, London Health Sciences Centre, Acute bacterial gastroenteritis necessitating medical attention was associated with a higher risk of arthritic symptoms, but not arthritic medications, up to 4 yrs afterwards(24).

4. Risk of pregnancy-related hypertension
In the study to  evaluate the risk of pregnancy-related hypertension (PRH) among previously healthy females from the Walkerton Health Study, Canada (2002-6), who conceived within five years of exposure to bacteria-contaminated drinking water, by the University of Western Ontario, London, indicated that of 148 eligible pregnancies, antenatal audits with blood pressure data were available for 135. PRH was detected in 20.7% pregnancies, of which 6.7% were chronic hypertension and 14.1% gestational hypertension. Although nonsignificant, we observed a consistent trend toward higher rates of PRH and mean arterial pressure, particularly prior to 20 weeks gestation, among women who reported symptomatic gastroenteritis compared to asymptomatic women. BP should be monitored closely in women after exposure to contaminated water(25).

5. Diabetes mellitus
Ingestion of Escherichia coli O157:H7 can cause a spectrum of acute illness, ranging from overt hemolytic-uremic syndrome (HUS), to gastroenteritis with bloody diarrhea, to no symptoms. According to the study by the University of Western Ontario, survivors with diarrhea-associated HUS have a significantly increased incidence of diabetes due to complete insulin deficiency, which may recur several years after the initial infection. However, less severe forms of infection, such as E. coli O157:H7 gastroenteritis without overt HUS, do not appear to result in an increased risk of type 2 diabetes(26).

6. Hypertension, Renal impairment, and Self reported cardiovascular disease
In the study to evaluate the risk for hypertension, renal impairment, and cardiovascular disease within eight years of gastroenteritis from drinking water contaminated with Escherichia coli O157:H7 and Campylobacter, showed that Gastroenteritis from drinking water contaminated with E coli O157:H7 and Campylobacter was associated with an increased risk for hypertension, renal impairment, and self reported cardiovascular disease. Annual monitoring of blood pressure and periodic monitoring of renal function may be warranted for individuals who experience E coli O157:H7 gastroenteritis(27).
Other study also indicated that acute bacterial gastroenteritis necessitating medical attention was associated with an increased risk of hypertension and reduced kidney function 4 years after infection(28).


7. Celiac disease
According to the study by the McMaster University Medical Centre, CD should be considered in the differential diagnosis of persistent IBS-like symptoms after an episode of infectious gastroenteritis(29).

8. Seizures and even GE encephalopathy
In the study to compare the demographic features, clinical manifestations including the incidence of afebrile seizure, and the outcomes in children with rotavirus and norovirus infections of a data of a retrospective review of children between age 1 month and 6 years admitted to the paediatric department of a regional hospital in Hong Kong with rotavirus and norovirus infections over a period of 3 years from 1 June 2006 to 31 May 2009, found that Afebrile seizure commonly occurred in norovirus infection (8.67% vs. 1.29%, P < 0.001). Children with rotavirus infection had higher temperature and more diarrhoea episodes, while more blood-stained stool was noted in the norovirus group. Rotavirus-infected patients stayed longer in hospital. All of them had full recovery without any complication. Among the 18 patients who developed afebrile convulsions, 17 of them had neuroimaging performed, which was normal. Fourteen of them had electroencephalogram (EEG) performed, demonstrating normal or non-specific findings. None of them developed subsequent seizure attack after the GE episode(29a).

9. Dehydration
According to the Department of Pediatrics, CHU Sainte-Justine, From April 2008 to March 2009, 150 patients with a mean (+/-SD) age of 22 (+/-14) months (range = 4 months to 4 years) were enrolled. Fifty-six patients had no dehydration, 74 had some dehydration, and 20 had moderate/severe dehydration. The median LOS in the ED after being seen by a physician was significantly longer as children appeared more dehydrated according to the CDS: 54 minutes (interquartile range [IQR] = 26-175 minutes), 128 minutes (IQR = 25-334 minutes), and 425 minutes (IQR = 218-673 minutes) for the no, some, and moderate/severe dehydration groups, respectively (p < 0.001)(29b).

10. Etc.

III. Misdiagnosis and diagnosis
A. Misdiagnosis
1. Primary NK/T cell lymphoma
Primary natural killer (NK) cell like T cell lymphoma of the terminal ileum is extremely rare. It most frequently occurs in the nasal or paranasal areas and less frequently in the skin, the soft tissue, and the gastrointestinal tract. NK/T cell lymphoma involving gastrointestinal tract has characteristic endoscopic features of Inflammatory bowel disease. According to the study by the Hallym University College of Medicine, there is a case of primary NK/T cell lymphoma misdiagnosed as Behcet's enteritis of the terminal ileum colonoscopically and complicated by cecal bleeding and perforation(30).

2. Acute appendicitis
Acute appendicitis is the most common cause of urgent surgery in children. Bacterial enteritis limited to the ileocecal region appears to be responsible for an appreciable number of unnecessary appendectomies. On the other hand, diagnostic errors in appendicitis may delay early appendectomy and result in the formation of appendiceal mass(31).

3. Acute abdomen pain
Enteritis cystica profunda, an uncommon condition, is characterized by nonneoplastic cystic spaces within the wall of the small bowel. The third case of enteritis cystica profunda in children is presented with special emphasis on diagnosis and treatment. This rare entity may mimic acute abdomen and should be kept in mind in the differential diagnosis(32).

4. Others
Eosinophilic enteritis is a rare condition of unknown aetiology, although it is generally believed to be due to intestinal allergy. It may mimic peptic ulcer, subacute (or chronic) intestinal obstruction, gastroenteritis, irritable bowel syndrome, and inflammatory bowel disease. According to the study by, there is a case of Eosinophilic enteritis in a 27 year old woman the symptoms of which appeared within six weeks of childbirth. With repeated episodes of abdominal pain, vomiting, occasional loose stools with weight loss, she was investigated and treated for many weeks in three hospitals without success. All investigations were inconclusive. Finally laparotomy revealed inflamed segments of small bowel, a biopsy of which showed Eosinophilic enteritis. The patient was subsequently treated successfully with Prednisolone(33).

B. Diagnosis
Diagnosis is depending to the underlined causes of the diseases
1. Stool culture
The aim of the test is to identify the bacteria and virus which cause the diseases. According to the study of "New methods for detection of campylobacters in stool samples in comparison to culture" by the University Hospital, Frankfurt/Main, current detection in stools is done essentially by culture on selective and nonselective media with filtration. These methods were compared to 2 molecular biology methods, an in-house real-time PCR and a multiplex PCR named Seeplex Diarrhea ACE Detection, and 3 immunoenzymatic methods, Premier Campy, RidaScreen Campylobacter, and ImmunoCard Stat!Campy. Out of 242 stool specimens tested, 23 (9.5%) fulfilled the positivity criteria, i.e., they were positive by one or both culture methods or, in case of a negative culture, by a positive molecular method and a positive immunoenzymatic method. The striking feature of this study is the low sensitivity of culture, in the range of 60%, in contrast to immunoenzymatic and molecular tests(34).

2.  [13]C-acetate breath test
[13C]acetate breath test is the measure of gastric emptying of the liquid phase both in liquid and semisolid test meals by simultaneous radioscintigraphy.There is a report of eosinophilic enteritis in which the (13)C-acetate breath test was effective(35).

IV. Preventions
A. The do and do not's list
In case of entertitis outbreak
A.1. The article by All Refer.com health(36) suggested the followings
1. Always wash hands after using the toilet and before eating or preparing food or drink.
2. You may also clean your hands with a 60% alcohol based product.
3. Avoid drinking from unknown sources, such as streams and outdoor wells, without boiling the water first.
4. Use only clean utensils for eating or handling foods, especially when handling eggs and poultry.
5. Cook food completely and properly.Store food appropriately in coolers.

A.2. Others according to the article of Viral Gastroenteritis by National Digestive Diseases Information Clearinghouse (NDDIC)(37) the following may increase the risk of virural entertitis
1. Touching contaminated surfaces or objects and then touching their mouths.
2. Sharing food, drink, or eating utensils with infected people
3. Eating foods that are contaminated with the virus, such as oysters from contaminated waters
4. Swallowing airborne particles that contain viruses.

B. Diet ot prevent Enteritis
1. Probiotic
Oral administration of a probiotic preparation was shown to be effective in preventing the recurrence of chronic pouchitis in a classic double-blind, placebo-controlled trial. According to the study by the East Carolina University, Greenville, dysbiosis, a condition of microbial imbalance, has been implicated in the pathogenesis of inflammatory bowel disease. Rather than administering antibiotics to treat the microflora with each relapse of pouchitis, the emphasis was placed on preventing chronic flare-ups by administering probiotics to correct dysbiosis. In addition, the choice of bacteria, optimal dose, and timing of administration have yet to be determined. Finally, the mechanisms by which probiotics provide their beneficial effects remain unresolved(38).

2. Green tea
In the study to investigate the  Green tea's repair fasting-induced mucosal damage in rat intestine, showed that use of green tea was associated with a significant increase in total plasma antioxidants (P < 0.001), and mucosal SOD (P < 0.001), catalase (P = 0.006) and GPx (P = 0.017), but a significant decrease in MPO activity (P < 0.001). Green tea reverses the fasting-induced damage to the intestinal mucosa by its antioxidant and anti-inflammatory effect(39).

3. Origanum vulgaris and Allium sativum
According to the study to  investigate the efficacy of Virbamix PE (Virbac SA, France) an appetite enhancer and feed flavouring material containing plant extracts of Origanum vulgaris and Allium sativum, added to the feed at one single dose in the control of proliferative enteropathy (PE) in weaning pigs,  in comparison to reference treatment with tiamulin (Tiamutine 6.5 Premix/Ceva Animal Health) group and a negative control group indicated that administration of Virbamix PE was found to be effective for the control of PE, as shown by the reduction of prevalence of Lawsonia intracellularis in the intestine at the end of the treatment period, as determined by PCR method comparatively with the T1 group, while no significant difference was found between T2 and T3 groups. The diarrhoea score (DS) was significantly higher (P < 0.05) in the control group in comparison with T2 and T3 groups. However, no significant differences were noticed between T2 and T3 groups during the treatment period (P > 0.05)(40).

4. Etc.

C. Phytochemicals to prevent Enteritis
1. Genistein
Genistein, a principal soy isoflavone, has been identified as a protein kinase inhibitor that possesses immunosuppressive and anti-inflammatory properties. According to the study by the Louisiana State University School of Medicine, Genistein, at low doses, also appeared to attenuate immunohistochemical staining for inducible nitric oxide synthase (iNOS) and nitrotyrosine. The beneficial effects of genistein were not apparent at doses above 0.1 mg/kg. Genistein also inhibited LPS-induced nitrite production by cultured macrophages and protected against LPS-induced necrosis despite its ability to cause apoptosis. These results indicate that genistein displayed mild anti-inflammatory properties which may, in part, involve an attenuation of nitric oxide release via inducible nitric oxide synthase, and the formation of peroxynitrite(41).

2. Resveratrol and curcumin
In the study to investigate the potential anti-inflammatory and immunomodulatory mechanisms of the above mentioned compounds in a murine model of hyper-acute Th1-type ileitis following peroral infection with Toxoplasma gondii conducted by the Charité-Universitätsmedizin Berlin, indicated that Oral treatment with Resveratrol, Curcumin or Simvastatin ameliorates acute small intestinal inflammation by down-regulating Th1-type immune responses and prevents bacterial translocation by maintaining gut barrier function. These findings provide novel and potential prophylaxis and treatment options of patients with inflammatory bowel diseases(42).

3. Beta-carotene
Beta-carotene is known as a potent free radical quencher and antioxidant. According to the study conducted by the B'nai Zion Medical Center, Haifa, Israel, the result demonstrate the effectiveness of beta-carotene in a rat model as a prophylactic dietary measure in reducing the effects of acid-induced enteritis and raise the possibility that patients with Crohn's disease may benefit from the consumption of natural beta-carotene(43).

D. Antioxidants to prevent Enteritis
1. Melatonin
In the study to tests the hypothesis that "the intake of melatonin can minimize the morphological features of cell damage associated with radiation enteritis", conducted by the Assuit University, Assuit, Egypt, found that Administration of melatonin prior to irradiation can protect the intestine against X-rays destructive effects, i.e. radiation enteritis(44).

2. Cu/Zn-superoxide dismutase (SOD1)
In the study to analyze the therapeutic value of Cu/Zn-superoxide dismutase (SOD1) supplementation in an experimental model of radiation-induced intestinal inflammation and explore its mechanistic effects, showed that Treatment with SOD1 decreases oxidative stress and adhesion molecule upregulation in response to abdominal irradiation. This is associated with an attenuation of the radiation-induced intestinal inflammatory response(45).

3. Vitamin A
Vitamin is a free radical scavenger. It emhances the immune system in fighting against forming of free radicals and foreign invasion. In the study to examine Serum retinol, retinyl palmitate, and total vitamin A concentrations, and jejunoileal morphology  in neonatal calves infected with Cryptosporidium parvum, showed that
Cryptosporidium parvum infection was associated with significant (P < or = 0.05) reduction in postadministration serum retinol, retinyl palmitate, and total vitamin A concentrations in calves of groups 2, 3, and 4. Cryptosporidium parvum infection caused significant (P < or = 0.05) reduction in villus height. Decreased villus height, villus blunting and fusion, and attenuation of the intestinal mucosa were associated with reduced absorption of vitamin A, as indicated by lower peak postadministration retinyl palmitate concentration in C parvum-infected calves(46).

4. Vitamin E
In the study to the effects of a nonenzymatic oxygen radical scavenger (vitamin E) and an exogenous PGE1 analog known to increase mucosal blood flow (misoprostol) on acute radiation enteritis in rats, showed that  ionizing radiation reduces in vivo intestinal fluid absorption without significant changes in histologic or morphometric appearance. Treatment with vitamin E, but not misoprostol, protects gastrointestinal mucosa against radiation-induced absorptive injury(47). Other study showed that selenium, vitamin E and selenium plus vitamin E pretreatments prior to whole abdominal irradiation on intestinal injury may have some beneficial effects against irradiation-induced intestinal injury(48).

V. Treatments
A. In conventional medicine perspective
Treatment depending to the underlined causes of the diseases.
Beside taking certain steps in relieving the symptoms of the patients by providing short-lived and  general supportive care(49), such as
Oral rehydration therapy for older children and adults:
  • Drink clear liquids only, such as water, sports drinks (best), fruit juice and dilute tea.
  • Drink small quantities of fluids frequently, such as 2 tablespoons of fluid every 5 minutes.
  • The absence of food allows the intestines to rest.
  • May be able to advance to full liquid diet once symptoms improve
  • Effective to treat mild to moderate dehydration




  • Intravenous fluids for severe dehydration
  • Clear liquid diet
  • BRAT diet (i.e. bananas, rice, applesauce, toast)
  • But according to the study by the Christiana Care Health System, probiotics reduce diarrheal duration from a number of etiologies. Professional nursing practice based on evidence and clinical expertise supports a diet-containing probiotics to manage acute diarrhea. Dietary limitations included in the BRAT (bananas, rice, applesauce, and toast) diet recommended by many nurses need to be reexamined in light of the newest evidence(48a).
  • Medications for nausea and vomiting:

    • Metoclopramide (Reglan) but side effects are not limit to hives, difficulty breathing, swelling of your face, lips, tongue, or throat.
    • Ondansetron (Zofran) but side effects are not limit to headache, fatigue, constipation, etc.
    • Olanzapine has been shown to be a safe and effective agent for the prevention of  nausea and vomiting  for patient with entertitis, but side effects are not limit to  hives; difficulty breathing; swelling, etc.
    • Prochlorperazine (Compazine, Compro) but side effects are not limit to Constipation, headaches, dizziness, etc.




  • Medications for diarrhea:

    • Loperamide (Imodium) but side effects are not limit to abdominal pain, constipation, drowsiness, dizziness, dry mouth, fatigue, nausea, vomiting, etc.
    • Diphenoxylate and Atropine (Lomotil) but side effects are not limit to thirst, decreased urination, muscle cramps, weakness, fainting, etc.
    A.1. Bacterial entertitis
    Atibiotic used are depending to types infectous organism, including Ciprofloxacin (Cipro),  Sulfamethoxazole and Trimethoprim (Bactrim, Septra, TMP-SMX),  Ceftriaxone (Rocephin) Cefotaxime (Claforan) Vancomycin (Vancocin, Lyphocin, etc., but side effects are not limit to rash, diarrhea, abdominal pain, nausea/vomiting, drug fever, hypersensitivity (allergic) reactions, etc.
    According to the study by Enterics laboratory, US Army Research Unit, Nairobi, in screening of the 651 patients screened, the highest prevalence of antimicrobial resistance was to ampicillin followed by trimethoprim/sulphamethoxazole and tetracycline. Though still at low levels, the major concern from our findings is the emerging resistance of enteric pathogens that was observed to quinolones (ciprofloxacin, nalidixic acid, norfloxacin) and gentamycin(49a).


    A.2. Viral entertitis
    There is no specific treatment for viral entertistis as antibiotic are not helpful in treating the diseasse. Make sure you are vaccinate against certain virus in a specific season.
    According to the study by Beijing Friendship Hospital Affiliate of Capital University of Medical Sciences,  clinical effective rate of Novalac AD in infantile rotavirus enteritis was 100%. All 20 subjects stool turned normal and systemic symptoms disappeared after treatment, with 17 within 48 h (85%,17/20) and 3 within 72 h (15%, 3/20)(50).

    A.3. Radiation-induced enteritis
    Radiation-induced enteritis van be prevented, according to the University Hospital Mannheim, Reduction of radiation dose and field size are still the most important factors in the prevention of acute and chronic radiation enteritis. Valid data particularly on the treatment of chronic radiation enteritis are lacking. A better understanding of the pathopysiology especially in chronic radiation enteritis might offer new therapeutic perspectives. Inhibition of TGF-beta, for example, might be a new promising therapy approach(50a).
    According to the study the Provincial Hospital affiliated to Shandong University, in the evaluation of the effect of actovegin (Nycomed, deproteinized hemoderivative of calf blood injection) on intestinal mucosa in rats with acute radiation enteritis, and observe the changes of expression of apoptosis-related bcl-2/bax genes, showed that Actovegin accelerates the recovery of the acute radiation-injured intestinal mucosal epithelium by decreasing apoptosis via down-regulation of the expression of activating apoptosis protein bax and up-regulation of inhibiting apoptosis protein bcl-2(51).
    B. In herbal medicine perspective
    1. Psidium guajava L (Guava)
    In the study to observe the clinical effect of olium Psidium guajava (PG) in treating infantile rotaviral enteritis in Sixty-two patients of rotaviral enteritis randomly divided into the treated group treated with PG and the control group treated with Gegen Qinlian decoction, showed that The rate of recovery in 3 days of the treated group was 87.1%, significantly higher than that of the control group (58.1%, P < 0.05). The time of ceasing diarrhea of the treated group (25.1 +/- 9.5 hr) was significantly shorter than that of the control group (38.7 +/- 15.2 hr, P < 0.01)(52).

    2. Gastritis-granule and Wei-Mei-Su
    According to the study by Dr. Pu CS., In the group treated with granule-gastritis, the effective rate for CP was 81.3% (26/32), and the improvement rates of the symptoms and histopathological lesion were 87.5% (28/32) and 40.6% (13/32) respectively. In the group treated with Wei-Mei-Su as the control group, the figures were 25%, 40% and 10% respectively. These differences were statistically significant (P less than 0.01-0.000). The results showed that the effect of granule-gastritis on chronic gastritis infected with CP was better than that of Wei-Mei-Su(53). 

    3. Etc.

    C. In traditonal Chinese medicine perspective
    1. Qiwei baizhu powder
    Sixty cases of rotaviral enteritis treated with Qiwei Baizhu Powder (QWBZP) revealed a better efficacy than that treated with Oral Rehydration solution (ORS, chi 2 = 6.07, P < 0.05), according to the study by the Hunan Academy of Traditional Chinese Medicine(54).

    2. Jiechang Mixture (JCM)
    In the study to evaluate the therapeutic effect and mechanism of Jiechang Mixture (JCM) in treating infantile mycotic enteritis, showed that the time of stool forming, diarrhea relieving and fungi vanishing in the treated group were significantly shorter than those in the control group (P < 0.01), and JCM also showed a better effect in improving clinical symptoms and signs of patients than the control. Results of experimental study showed that JCM could abate the ink evacuation of small intestine in mice. The fungi inhibitory test suggested that Candida albicans was susceptible to JCM(55).

    3. Zhixie buye mixture
    In the study to observe the therapeutic effect of Zhixie Buye mixture (ZXBYM) on infantile diarrhea patient with mild and middle degree of dehydration, indicated that the ZXBYM is an effective mixture in the treatment of diarrhea with dehydration. It has a good prospect of development and application(56).

    4. Fu-zheng qu-xie
    In the study of the of fu-zheng qu-xie on gastric disease infected with Campylobacter pyloridis] by Jiangsu Provincial Hospital of TCM, pointed out that the principle of Chinese herbal medicine treatment of gastric disease by campylobacter pyloridis was fu-zheng qu-xie. Fu-zheng was achieved by Astragalus membranaceus, Atractylodes macrocephala and Paeonia lactiflora, whereas qu-xie by Taraxacum monogolicum and Oldenlandia diffusa. Chinese herbal medicine for fu-zheng played an important role in modulating immune function. Qu-xie was directly disinfective and indirectly anti-bacterial. Chinese herbal medicine combined with western drugs will decrease the side effects and enhance the curative effect at the same time(57).
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    Saturday, February 9, 2013

    S-Allylcysteine (SAC)

    Allyl isothiocyanate (AITC) is organosulfur compounds found abundantly in cruciferous vegetables and responsible for the pungent taste of mustard, horseradish, wasabi, etc
    1. Allyl isothiocyanate (AITC) and prostate cancer
    In the study to demonstrate that allyl isothiocyanate (AITC), a constituent of cruciferous vegetables, significantly inhibits proliferation of cultured PC-3 (androgen-independent) and LNCaP (androgen-dependent) human prostate cancer cells in a dose-dependent manner with an IC(50) of approximately 15-17 micro, found that a 24 h exposure of PC-3 and LNCaP cells to an apoptosis-inducing concentration of AITC (20 micro M) resulted in a significant decrease (31-68%) in the levels of anti-apoptotic protein Bcl-2 in both cell lines, and approximately 58% reduction in Bcl-X(L) protein expression in LNCaP cells. In conclusion, it seems reasonable to hypothesize that AITC, and possibly other ITCs, may find use in the treatment of human prostate cancers(1).

    2. Allyl isothiocyanate (AITC) and Breast cancer
    Allyl isothiocyanate (AITC), a member of the isothiocyanate (ITC) family found in a constituent of cruciferous vegetables, possesses anticancer activity and induces apoptosis in various types of human cancer cell lines. According the China Medical University in the study on exploring the mechanisms underlying AITC-induced apoptosis in MDA-MB-468 human breast cancer cells in vitro, showed that
     AITC-promoted G2/M phase and AITC-triggered apoptosis correlate with the activation of phosphorylation of ERK in MDA-MB-468 cells. AITC is a potential agent for applcation in the treatment of human breast cancer(2).

    3. Antimicrobial Activities of Isothiocyanates
    Food-borne human infection with Campylobacter jejuni is a medical concern in both industrialized and developing countries. In the study to investigste the bacteriostatic and bactericidal activities of two phytochemicals, allyl-isothiocyanate (AITC), and benzyl isothiocyanate (BITC), against 24 C. jejuni isolates from chicken feces, human infections, and contaminated foods, as well as two reference strains NCTC11168 and 81-176. AITC and BITC displayed a potent antibacterial activity against C. jejuni, found that both compounds are bactericidal rather than bacteriostatic, and highlighted the role of GGT enzyme in the survival rate of C. jejuni exposed to ITC(3).

    4. DNA damage and repair in adults consuming allyl isothiocyanate
    Allyl isothiocyanate (AITC) is a dietary component with possible anticancer effects, though much information about AITC and cancer has been obtained from cell studies. In the study to assess the effect of AITC on DNA integrity in vivo, a crossover study was conducted. Adults (n=46) consumed AITC, AITC-rich vegetables [mustard and cabbage (M/C)] or a control treatment with a controlled diet for 10 days each, Indicated that DNA damage appeared to be induced in the short term by AITC and AITC-rich products, but that damage disappeared quickly, and neither AITC nor AITC-rich products affected DNA base excision repair(4).

    5. Allyl isothiocyanate as a cancer chemopreventive phytochemical
    Allyl isothiocyanate (AITC), which occurs in many common cruciferous vegetables, is widely and often frequently consumed by humans. According to the study by the Roswell Park Cancer Institute,
    AITC may be most effective in the bladder as a cancer chemopreventive compound. AITC at high-dose levels also exhibit a low degree of cytotoxicity and genotoxicity in animal studies, but such adverse effects are unlikely in humans exposed to dietary levels of AITC. Overall, AITC exhibits many desirable attributes of a cancer chemopreventive agent, and further studies are warranted in order to elucidate its mechanism of action and to assess its protective activity in humans(5).

    6. Allyl isothiocyanate and bladder cancer
    Bladder cancer is one of the common human cancers and also has a very high recurrence rate. According to the study by the Roswell Park Cancer Institute, a low oral dose of AITC (1 mg/kg) significantly inhibited the development and muscle invasion of the orthotopic bladder cancers but was ineffective against the subcutaneous xenografts of the same cancer cells in the same animals. This differential effect was explained by our finding that urinary levels of AITC equivalent were two to three orders of magnitude higher than that in the plasma and that its levels in the orthotopic cancer tissues were also three orders of magnitude higher than that in the subcutaneous cancer tissues. Moreover, we show that AITC is a multi-targeted agent against bladder cancer(6).

    7. Isothiocyanates and oxidative stress
    The choroid plexuses (CPs) form the blood-cerebrospinal fluid (CSF) barrier (BCSFB) and play an important role in maintaining brain normal function and the brain response to injury. According to the study by the University of Michigan, Sulforaphane (SF) significantly reduced H(2)O(2)-induced BCSFB disruption as assessed by transepithelial electrical resistance (29 ± 7% reduction vs. 92 ± 2% decrease in controls) and [(3)H]mannitol permeability. Allyl-isothiocyanate (AITC) had a similar protective effect. H(2)O(2)-induced epithelial cell death was also reduced by these isothiocyanates. In primary CP cells, SF and AITC reduced cell death by 42 ± 3% and 53 ± 10%, respectively. Similar protection was found in a CP cell line Z310. Protection was only found with pretreatment for 12-48 h and not with acute exposure (1 h). The protective effects of SF and AITC were associated with Nrf2 nuclear translocation and upregulated expression of antioxidative systems regulated by Nrf2, including heme oxygenase-1, NAD(P)H quinine oxidoreductase, and cysteine/glutamate exchange transporter(7).

    8. Anti-inflammatory potential of allyl-isothiocyanate
    In the study to investigate the underlying mechanisms of the potential anti-inflammatory properties of allyl-isothiocyanate (AITC) in vitro and in vivo, found that AITC was slightly less potent than sulforaphane (used as a positive control) in down-regulating inflammation in LPS-stimulated macrophages. A significant increase in nuclear Nrf2 and heme-oxygenase 1 gene expression and only a moderate down-regulation of interleukin-1β and microRNA-155 levels due to AITC was found in mouse liver. Present data suggest that AITC exhibits potent anti-inflammatory activity in cultured macrophages in vitro but has only little anti-inflammatory activity in mice in vivo(8).

    9. Allyl isothiocyanate (AITC) - the inducer of PON1
    In the study to test the ability of structure-related isothiocyanates to induce the antiatherogenic enzyme paraoxonase-1 (PON1) in cultured hepatocytes, conducted by the Christian-Albrechts-University of Kiel, Kiel, indicated that Allyl isothiocyanate (AITC), phenylethyl isothiocyanate (PEITC), and sulforaphane (SFN), but not butyl isothiocyanate (BITC) resulted in dose-dependent induction of PON1 transactivation in Huh7 cells in vitro. Induction of PON1 due to AITC was inhibited by the selective peroxisome proliferator-activated receptor γ-antagonist T0070907. AITC was used in a subsequent in vivo study in mice (n = 10 per group, Western-type diet) to test its PON1 inducing activity. Unlike in cultured hepatocytes, AITC supplementation (15 mg/kg body weight) did not increase hepatic PON1 mRNA and protein levels in mice. Thus, it is suggested that AITC may be a potent inducer of PON1 in vitro, but not in mouse liver in vivo(9).

    10. Allyl isothiocyanate (AITC) and the antioxidant enzymes in cultured fibroblasts
    The isothiocyanate sulforaphane (SFN) has been shown to induce phase 2 and antioxidant enzymes in cultured cells and in vivo via a Nrf2 dependent signal transduction pathway. According to the study by the Christian-Albrechts-University Kiel, not only SFN but also other aliphatic and aromatic isothiocyanates such as AITC, BITC and PEITC induce phase 2 and antioxidant enzymes in cultured fibroblasts(10).

    **11. Allyl isothiocyanate (AITC) toxicity
    In the study to assess the Subchronic toxicity of a horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate (AITC) and other isothiocyanates, with administration at concentrations of 0, 0.0125, 0.025 and 0.05% of HRE in drinking water for 13 weeks to male and female F344 rats, found that on histopathological assessment, papillary/nodular hyperplasia of bladder mucosa was observed in 0.05% HRE and AITC males and females, in addition to simple mucosal hyperplasia found in all treated groups. Based on the above findings, no-observed-adverse-effect levels (NOAELs) were estimated to be below 0.0125% of HRE for both males and females, corresponding to 9.4 and 8.0 mg/kg body weight/day, respectively, and there appeared to be comparable toxicological properties of HRE to AITC, such as the inductive effect of significant proliferative lesions in the urinary bladder(11).

    12. Allyl isothiocyanate and gastrointestinal contractility
    In the study to investigate  the effect of AITC on intestinal motility, conducted by the University of Naples Federico II, indicated that AITC, depending, in vitro, on the regions of gut examined and, in vivo, on the route of administration, exerted both stimulatory and inhibitory effects on intestinal motility, which were not sensitive to TRPA1 channel antagonists. The proposition that TRPA1 channels are the primary targets for AITC to induce contraction should be revised.(12).

    13. Allyl isothiocyanate (AITC) and cancers
    Allyl isothiocyanate (AITC)occurs in many commonly consumed cruciferous vegetables and exhibits significant anti-cancer activities. According to the study by the California Institute of Technology, AITC induced mitochondrion-mediated apoptosis, as shown by cytochrome c release from mitochondria to cytoplasm, activation of caspase-9 and caspase-3, and formation of TUNEL-positive cells. Inhibition of caspase-9 blocked AITC-induced apoptosis. Moreover, we found that apoptosis induction by AITC depended entirely on mitotic arrest and was mediated via Bcl-2 phosphorylation at Ser-70. Pre-arresting cells in G(1) phase by hydroxyurea abrogated both AITC-induced mitotic arrest and Bcl-2 phosphorylation. Overexpression of a Bcl-2 mutant prevented AITC from inducing apoptosis. We further showed that AITC-induced Bcl-2 phosphorylation was caused by c-Jun N-terminal kinase (JNK), and AITC activates JNK(13).

    14. Allyl isothiocyanate and human colorectal cancer
    Allyl isothiocyanate (AITC) is a constituent of cruciferous vegetables that exhibits antitumor activity. In this study, AITC was shown to inhibit the proliferation of human metastatic colorectal adenocarcinoma SW620 cells in vitro by inducing cell cycle arrest at the G2/M phase. According to the study by The Chinese University of Hong Kong, Shatin, upon prolonged exposure, AITC induced caspase-mediated apoptosis in SW620 cells. The apoptotic process was evidenced by the activation of initiator caspases (-8 and -9) and effector caspases (-3 and -7), and the cleavage of poly(ADP-ribose) polymerase (PARP). The antitumor activity of AITC was further demonstrated in a SW620 xenograft in vivo. Taken together, the results suggest that AITC is a potential candidate for future research in chemoprevention and chemotherapy(14).

    15. Allyl isothiocyanate and human brain malignant glioma
    Isothiocyanates (ITCs) are present as glucosinolates in various cruciferous vegetables. Allyl isothiocyanate (AITC) is one of the common naturally occurring isothiocyanates. According to the study by the National Chung Hsing University, AITC markedly reduced the CDK1/cyclin B activity and protein levels by CDK1 activity assay and Western blot analysis. AITC-induced apoptotic cell death and this evidence was confirmed by morphological assessment and DAPI staining. Pretreatment with specific inhibitors of caspase-3 (Z-DEVE-FMK) and -9 (Z-LEHD-FMK) significantly reduced caspase-3 and -9 activity in GBM 8401 cells. Western blot analysis and colorimetric assays also displayed that AITC caused a time-dependent increase in cytosolic cytochrome c, pro-caspase-9, Apaf-1, AIF, Endo G and the stimulated caspase-9 and -3 activity. Our results suggest that AITC is a potent anti-human brain malignant glioma drug and it shows a remarkable action on cell cycle arrest before commitment for apoptosis is reached(15).

    16. Allyl isothiocyanate and stress-responses
    The main pungent component of wasabi (Eutrema japonica) is known to be isothiocyanate and its derivatives, volatile substances. Allyl isothiocyanate (AITC) accounts for more than half of isothiocyanate derivatives.  According to the study posted in  J Toxicol Sci. 2010 Aug;35(4):583-9, showed that administration of AITC increased the number of neutrophil on days 8-10 by 61-112%. AITC did not change the number of eosinophil and basophil. Plasma corticosterone concentrations during the experimental period were 4.7-8.4 times significantly higher in the AITC group than in the control group, indicating that AITC induced stress-responses(16).

    17. Allyl isothiocyanate (AITC) hepaprotective effects
    In the study to investigate possible protective effect of allyl isothiocyanate (AITC) in nitrite- and nitrosamine-treated human hepatoma cells (HepG2) with the evaluation by cytotoxic effects and genotoxic effects determined by the single-cell gel electrophoresis (SCGE), found that Allyl isothiocyanate treatment enhanced cell viability and reduced intracellular reactive oxygen species (ROS) production in both nitrite- and nitrosamine-treated cells significantly. In SCGE, when compared to untreated control cells, all of the treated groups caused increases in the tail intensity (%) such as nitrite at 17%, N-nitrosodimethylamine (NDMA) at 279%, N-nitrosodiethylamine (NDEA) at 324%, and N-nitrosomorpholine (NMOR) at 288%. Allyl isothiocyanate reduced the tail intensity caused by nitrite 36%, by NDMA 36%, by NDEA 49%, and by NMOR 32%, respectively, when compared to each individual toxic compound-treated group. In conclusion, AITC protected HepG2 cells against cytotoxic and genotoxic effects caused by nitrite and the nitrosamines(17).

    18. Allyl isothiocyanate and pests
    In the study to investigate the effects of extraction of allyl isothiocyanate from horseradish (Armoracia rusticana) and its fumigant insecticidal activity on four stored-product pests of paddy, found that good insecticidal efficacy of AITC against the four stored-product pests, with non-gaseous residuals on stored products. AITC obtained from A. rusticana may be an alternative to phosphine and methyl bromide against the four pest species(18).

    19. Antiangiogenic and proapoptotic activities of allyl isothiocyanate
    In the studyt to investigate the antiangiogenic and proapoptotic effects of mustard essential oil containing allyl isothiocyanate (AITC) and explore its mechanism of action on Ehrlich ascites tumor (EAT) cells with Swiss albino mice transplanted with EAT cells, found that AITC significantly reduced ascites secretion and tumor cell proliferation by about 80% and inhibited vascular endothelial growth factor expression in tumor-bearing mice in vivo. It also reduced vessel sprouting and exhibited potent antiangiogenic activity in the chorioallantoic membrane and cornea of the rat. AITC arrested the growth of EAT cells by inducing apoptosis and effectively arrested cell cycle progression at the G1 phase(19).

    20. Allyl isothiocyanate and liver cancer
    Glucosinolates. Sinigrin, the predominant aliphatic glucosinolate in cruciferous vegetables, is hydrolyzed to yield allyl isothiocyanate (AITC)  to determine the inhibitory effects of AITC and its NAC conjugate on cell proliferation, the expression of matrix metalloproteinases (MMPs), adhesion, invasion, and migration in SK-Hep 1 human hepatoma cells, indicated that AITC and NAC-AITC suppress SK-Hep 1 cell proliferation in a dose-dependent manner; by 25% and 30% for 10 microM AITC and 10 microM NAC-AITC, respectively(20).

    21. Isothiocyanates and the immune system
    Administration of allyl isothiocyanate (AITC) and phenyl isothiocyanate (PITC) was found to stimulate the immunological response in Balb/c mice. According to the study by the Amala Cancer Research Centre, indicated that treatment with AITC and PITC along with the antigen sheep red blood cells (SRBC) produced an enhancement in the circulating antibody titer and the number of plaque forming cells (PFC) in the spleen. Maximum number of PFC (1329PFC/10(6) spleen cells) for AITC and PITC (1218PFC/10(6) spleen cells) was obtained on the 5th day. These results indicate the immunomodulatory activities of the two naturally occurring isothiocyanates namely, AITC and PITC(21).

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    (10) http://www.ncbi.nlm.nih.gov/pubmed/21109004
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    (12) http://www.ncbi.nlm.nih.gov/pubmed/21955242
    (13) http://www.ncbi.nlm.nih.gov/pubmed/21778226
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    (21) http://www.ncbi.nlm.nih.gov/pubmed/19180807