Evaluation of the use of coconut to treat chronic diarrhea in rhesus macaques (Macaca mulatta)

Background Chronic diarrhea can be challenging to manage in captive rhesus macaques (Macaca mulatta) leading to ongoing diagnostics, medications, monitoring, and potential euthanasia. Coconut has been used as a dietary supplement for people with inflammatory bowel disease, with anecdotal reports of decreased diarrhea following the dietary addition. A dietary trial in rhesus macaques was initiated to evaluate the hypothesis that dietary coconut decreases symptoms of chronic diarrhea in rhesus macaques. Methods Ten rhesus macaques with chronic diarrhea were selected for the trial. Five of the subjects were fed coconut macaroons and five of the subjects were fed a sham cookie. Stool consistency was monitored daily for both groups. Results and conclusions Data of chi‐squared analysis obtained from eight rhesus macaques with chronic diarrhea showed that the use of coconut macaroons as a dietary supplement did not have a statistically significant effect on their diarrhea.     

Effect of weaning time and associated management practices on postweaning chronic diarrhea in captive rhesus monkeys (Macaca mulatta)

OBJECTIVE: Our purpose was to assess the extent to which early weaning and other weaning-management factors affect development of postweaning chronic diarrhea in captive rhesus monkeys at the California Regional Primate Research Center between 1992 and 1995. METHODS: Data for weaning, management, and onset of diarrhea were obtained from daily records. The Cox proportional hazard model was used to assess whether the risk of chronic diarrhea was related to early weaning. RESULTS: Monkeys that were lighter at weaning had a threefold increase in risk of postweaning chronic diarrhea (P = 0.07), compared with that in heavier monkeys. An episode of preweaning diarrhea increased the risk of postweaning chronic diarrhea twofold (P = 0.08). Relocation of monkeys to outdoor facilities in the fall was associated with a fivefold decrease in risk (P < 0.001), compared with that of other seasons, and weaning in 1993 was associated with a twofold decrease in risk, compared with that of other years (P = 0.04). CONCLUSIONS: Multiple factors need to be considered for prevention of postweaning chronic diarrhea, including weaning weight, preweaning diarrhea, season weaned, and weaning conditions that change from year to year.     

Isolation and characterization of a new simian retrovirus type D subtype from monkeys at the Tsukuba Primate Center, Japan

Exogenous type D simian retroviruses (SRV/D) are prevalent in captive and feral populations of various macaque monkeys. Thus far, five subtypes of SRV/Ds have been reported, three of which (SRV-1, -2 and -3) have been molecularly characterized. Two SRV/D strains (N27 and T150) were isolated from seropositive cynomolgus macaques at the Tsukuba Primate Center (TPC) in Japan, showing clinical signs of SRV/D infection, including anemia and persistent unresponsive diarrhea. Electron microscopy demonstrated that both SRV/D isolates have a virion morphology typical of type D retrovirus. The SRV/D N27 and T150 isolates were essentially the same based on sequence analysis. From homology analysis of the entire gag sequence, the N27 isolate is closely related to the other known SRV/Ds but is distinct from the three molecularly characterized SRV/Ds. Thus, we have tentatively designated the N27 and T150 viruses isolated from TPC cynomolgus macaques as SRV/D-Tsukuba (SRV/D-T).     

MHC haplotype frequencies in a UK breeding colony of Mauritian cynomolgus macaques mirror those found in a distinct population from the same geographic origin

Background  Mauritian cynomolgus macaques have greatly restricted genetic diversity in the MHC region compared to other non-human primates; however, the frequency of common MHC haplotypes among captive-bred populations has not been reported.
Methods  Microsatellite PCR was used to determine MHC haplotype frequencies among captive macaques at a UK breeding facility. Allele-specific PCR and reference strand conformational analysis were used to determine the allele expression profile of a subset of animals.
Results  Haplotypes H3 (21%) and H1 (19%) were most common in the captive population of Mauritian cynomolgus macaques. Predicted alleles were detected by allele-specific PCR-SSP in 98% of animals. Allele expression profiles were similar in animals with identical haplotypes.
Conclusions  Mauritian cynomolgus macaques in the UK breeding facility have restricted MHC diversity comparable to a previously described population. Microsatellite-derived haplotypes are highly predictive of allele expression. A selective breeding program has been established to produce MHC-identical animals for biomedical research.     

Nutritional investigations and management of captive moose

Historically, moose have been difficult to maintain in captivity when on diets of grass or legume hays and grain due to enteritis that frequently leads to chronic diarrhea/wasting disease. The development of wood-fiber diets has increased the lifespan of moose in captivity, but these diets do not completely prevent chronic wasting. Purina Mills (St. Louis, MO) hypothesized that captive moose are unable to digest starch that escapes the rumen, and therefore abnormal bacterial fermentation in the hindgut causes chronic diarrhea. An earlier study found no evidence of a digestive problem, so we tested the hypothesis that moose have difficulty metabolizing excess propionate produced from the fermentation of starch found in traditional cervid rations and high-grain wood-fiber diets. When challenged with an i.v. propionate load, moose metabolized propionate similar to healthy mule deer and domestic livestock. We then tested the hypothesis that grass forage is an initiating factor to chronic diarrhea/wasting and further hypothesized that grass, alfalfa, and other agriculture-based forages in association with an anaerobic bacteria produce inflammatory bowel disease (IBD) in moose. Captive moose that had ad libitum access to a wood-fiber pelleted moose diet and grazed in grass pastures developed chronic wasting symptoms at 2–4 years of age and died at 4.7 ± 0.3 years unless restricted from grass before the development of advanced symptoms. We isolated Bacteroides vulgatus in the feces and successfully treated a moose with chronic diarrhea/wasting disease with long-term metronidazole therapy, suggesting that the chronic enteritis causing wasting disease arises from a bacteria-associated defective immunosuppressive response similar to IBD in other species. Further support for the IBD cause of wasting in moose is that this animal will relapse within hours if the metronidazole treatment is discontinued even after many months. We developed a highly palatable high-fiber, low-starch moose ration that can be fed as the sole source of nourishment, although additional research and dietary improvements are required. Zoo Biol 16:479–494, 1997. © 1997 Wiley-Liss, Inc.     

A non-human primate model for gluten sensitivity

Background and Aims

Gluten sensitivity is widespread among humans. For example, in celiac disease patients, an inflammatory response to dietary gluten leads to enteropathy, malabsorption, circulating antibodies against gluten and transglutaminase 2, and clinical symptoms such as diarrhea. There is a growing need in fundamental and translational research for animal models that exhibit aspects of human gluten sensitivity.

Methods

Using ELISA-based antibody assays, we screened a population of captive rhesus macaques with chronic diarrhea of non-infectious origin to estimate the incidence of gluten sensitivity. A selected animal with elevated anti-gliadin antibodies and a matched control were extensively studied through alternating periods of gluten-free diet and gluten challenge. Blinded clinical and histological evaluations were conducted to seek evidence for gluten sensitivity.

Results

When fed with a gluten-containing diet, gluten-sensitive macaques showed signs and symptoms of celiac disease including chronic diarrhea, malabsorptive steatorrhea, intestinal lesions and anti-gliadin antibodies. A gluten-free diet reversed these clinical, histological and serological features, while reintroduction of dietary gluten caused rapid relapse.

Conclusions

Gluten-sensitive rhesus macaques may be an attractive resource for investigating both the pathogenesis and the treatment of celiac disease.     

An outbreak of salmonellosis in newly imported cynomolgus monkeys

Serious salmonellosis occurred in groups of cynomolgus monkeys newly imported into Tsukuba Primate Center for Medical Science from the Philippines in 1985. During the quarantine period, Salmonella typhimurium (29 strains) and S. stanley (1 strain) were isolated from 30 of 130 imported monkeys. Twenty-eight of the 30 infected monkeys excreted mainly watery diarrhea, and occasionally bloody mucous stool. Seven of the 28 clinical cases infected with S. typhimurium resulted in death or in moribund state. In both the small and large intestines of autopsied monkeys, acute inflammatory changes were observed.     

Experimental group A rotaviral infection in cynomolgus monkeys raised on formula diet

Rotaviral infections in cynomolgus monkeys (Macaca fasicularis) were studied to ascertain its suitability as a model of infection and diarrhea caused by group A human rotaviruses. Formula-fed monkeys were used as they could be observed closely. Experimental rotaviral infection of cynomolgus monkeys was age-dependent; only young monkeys were readily infected. Formula-fed newborns were readily infected with cell-culture-adapted human (WA) and simian (SA11) viruses and with a rotavirus from a human fecal specimen. However, diarrhea was detected only in very young animals. A number of rotaviral shedding patterns as a function of time were observed. Although there was no typical viral shedding pattern which represented exclusive association of viral infection with diarrhea, the initial level of viral excretion and the maximum level of viral shedding attained were much higher in animals with diarrhea. Seroconversion occurred in less than half of the inoculated animals. The presence of maternal rotaviral antibodies did not prevent infection or diarrhea.     

Clinical pathology data from cynomolgus monkeys from China in which diarrhea was observed during quarantine.

Shin Nippon Biomedical Laboratories, Ltd. (SNBL) imported and quarantined 3,148 cynomolgus monkeys (aged 2.5 to 6.5 years) from China in 2002. The hematology and blood biochemistry data obtained from these monkeys on Day 32 of quarantine were analyzed separately by sex [2,890 animals in which no abnormalities were observed during the 35-day quarantine period (normal group), and 258 animals which exhibited diarrhea 1 to 12 times (diarrhea group)]. The values obtained for all parameters were within the normal range (mean +/- SD), and no significant abnormalities were noted in either sex. The clinical pathology data from 11 animals (6 males and 5 females) exhibiting diarrhea repeatedly (10 to 12 times) were statistically analyzed, and significant differences were noted in PLT and ALP in both sexes. The PLT values of these animals were within the normal group mean +/- 2 SD, and were considered within the normal range. A significant difference was noted in some individual ALP values (males: Nos. 2 and 3, females: Nos. 1, 3, and 4). The clinical pathology data obtained from the normal group in this study basically correspond to the widely reported results already obtained from healthy cynomolgus monkeys, from which it can be concluded that the cynomolgus monkeys from China were generally healthy and presenting no particular abnormality. The clinical pathology data from the normal group will serve as valuable baseline data for experimenters using cynomolgus monkeys.     

A survey of the prevalence of Anatrichosoma sp. in nasal cavities of cynomolgus monkeys

Microscopic examination of 45 nasal swab samples of cynomolgus monkeys revealed that three of them were positive for Anatrichosoma sp. In the tissue sections of nasal mucosa collected from positive monkeys, female worms were consistently seen in the stratified squamous epithelial layer of the nasal mucosa. Epithelial layer thickening and parakeratosis were evident in nasal mucosa adjacent to female worms. Male worms were consistently seen in the submucosa and chronic inflammatory reactions was observed around them.     

The Fecal Microbiome in Dogs with Acute Diarrhea and Idiopathic Inflammatory Bowel Disease

Background

Recent molecular studies have revealed a highly complex bacterial assembly in the canine intestinal tract. There is mounting evidence that microbes play an important role in the pathogenesis of acute and chronic enteropathies of dogs, including idiopathic inflammatory bowel disease (IBD). The aim of this study was to characterize the bacterial microbiota in dogs with various gastrointestinal disorders.

Methodology/Principal Findings

Fecal samples from healthy dogs (n = 32), dogs with acute non-hemorrhagic diarrhea (NHD; n = 12), dogs with acute hemorrhagic diarrhea (AHD; n = 13), and dogs with active (n = 9) and therapeutically controlled idiopathic IBD (n = 10) were analyzed by 454-pyrosequencing of the 16S rRNA gene and qPCR assays. Dogs with acute diarrhea, especially those with AHD, had the most profound alterations in their microbiome, as significant separations were observed on PCoA plots of unweighted Unifrac distances. Dogs with AHD had significant decreases in Blautia, Ruminococcaceae including Faecalibacterium, and Turicibacter spp., and significant increases in genus Sutterella and Clostridium perfringens when compared to healthy dogs. No significant separation on PCoA plots was observed for the dogs with IBD. Faecalibacterium spp. and Fusobacteria were, however, decreased in the dogs with clinically active IBD, but increased during time periods of clinically insignificant IBD, as defined by a clinical IBD activity index (CIBDAI).

Conclusions

Results of this study revealed a bacterial dysbiosis in fecal samples of dogs with various GI disorders. The observed changes in the microbiome differed between acute and chronic disease states. The bacterial groups that were commonly decreased during diarrhea are considered to be important short-chain fatty acid producers and may be important for canine intestinal health. Future studies should correlate these observed phylogenetic differences with functional changes in the intestinal microbiome of dogs with defined disease phenotypes.     

Seroprevalence of SV40-like polyomavirus infections in captive and free-ranging macaque species

BACKGROUND AND METHODS: To investigate the seroprevalence of polyomavirus infections in macaques, we analyzed 1579 sera from nine different species for antibodies cross-reactive with simian virus 40 (SV40) in an enzyme-linked immunosorbent assay. Most samples were collected from captive animals, but we also investigated a colony of free-ranging Barbary macaques (Macaca sylvanus). RESULTS: High seropositive rates were found in rhesus macaques (Macaca mulatta; 74.7%), cynomolgus macaques (Macaca fascicularis; 44.8%) and Tonkean macaques (Macaca tonkeana; 41.7%), especially in animals imported from China. Low rates were measured in cynomolgus macaques from Mauritius (8.8%), and in Barbary macaques (1.4%). Seropositivity was age-dependent increasing to >70% in animals of 5 years and older. CONCLUSIONS: High seroprevalence rates were found in different species of macaques, dependent on their origin. Very low infection rates found in Barbary macaques and cynomolgus macaques from Mauritius suggest that these animals in the wild are not commonly infected by SV40-like viruses.     

Procyanidin A1 alleviates DSS-induced ulcerative colitis via regulating AMPK/mTOR/p70S6K-mediated autophagy

Journal of Physiology and Biochemistry - Ulcerative colitis (UC) is a recurrent chronic inflammatory disease. The symptom of UC is mainly diarrhea including bloody stools. Increasing evidence has...     

Idiopathic hypoparathyroidism with impaired vitamin B12 absorption and neuropathy

A 68-year-old man presenting with chronic intermittent diarrhea and progressive ataxia was found to have idiopathic hypoparathyroidism. Intrinsic factor-resistant vitamin B₁₂ malabsorption was demonstrated. Both the diarrhea and vitamin malabsorption were reversed by correction of hypocalcemia.His neurological profile was a combination of peripheral nerve, posterior column and cerebellar deficits. He had calcifications in the dentate nuclei of the cerebellum. Possible etiological factors such as vitamin B₁₂ deficiency, folic acid deficiency and steatorrhea have been excluded. Posterior column and cerebellar abnormalities improved with treatment. It is postulated that hypocalcemia causes functional, reversible spinal cord and cerebellar dysfunction.     

Antioxidants and mucosa protectives: realistic therapeutic options in inflammatory bowel disease?

Oxidative damage is involved in the pathogenic process of idiopathic chronic inflammatory bowel disease. Although specific intervention in the oxidative cascade showed promising results in animal models and preliminary patient trials, the clinical efficacy of antioxidants still has to be established. Mucosa protection, for example by dietary fatty acids, seems to attenuate the intestinal inflammatory process as well but awaits definite clinical proof for the treatment of inflammatory bowel disease.     

儿童慢性腹泻病因分析

目的探讨儿童慢性腹泻的病因,以提高临床诊治水平。方法选择2005年12月至2010年12月在重庆医科大学附属儿童医院住院的141例慢性腹泻患儿为研究对象,对患儿的临床资料进行回顾性分析。结果本组病例中常见致病因素依次为过敏因素46.2%(24/52)、肠道内感染28.4%(40/141)、乳糖不耐受28.3%(26/92)。共109例明确病因诊断,55.1%(60/109)为多因素共同致病,以肠道内感染合并继发乳糖不耐受,过敏合并继发乳糖不耐受,免疫缺陷合并肠道内感染多见。前4位主要病因诊断为感染性腹泻(24.1%)、过敏性腹泻(17.0%)、乳糖不耐受(7.1%)、炎症性肠病(6.4%)。结论除肠道内感染外,过敏因素、乳糖不耐受等也是儿童慢性腹泻常见致病因素。儿童慢性腹泻常由多因素共同致病,主要病因除感染性腹泻外,过敏性腹泻、乳糖不耐受、炎症性肠病等也是常见病因。儿童慢性腹泻重在病因诊断,针对病因治疗。     

Pathogenesis and treatment of autoimmune hepatitis and chronic viral hepatitis B and C.

Immune mechanisms play a role in autoimmune hepatitis which is considered as "idiopathic" inflammatory liver disease of unknown etiology. However, even chronic viral hepatitis B and C have also features suggesting the importance of immunopathogenesis in their development. This paper discusses the major genetical and immunological factors in the above-mentioned chronic liver diseases and briefly summarizes their therapeutic modalities.     

Low rates of transmission of SRV-2 and STLV-I to juveniles in a population of Macaca fascicularis facilitate establishment of specific retrovirus-free colonies

Background  Prevalence of simian retrovirus-2 (SRV-2) and simian T lymphotropic virus type I (STLV-I), was unknown in 337 captive cynomolgus macaques.
Methods and Results  Molecular assays identified 29% of animals as SRV-2 mono-infected, 4% of animals as STLV-I mono-infected and 9% of animals as dual-infected. Of 108 juvenile animals, 83% were SRV-2-negative and no juvenile animal was STLV-I-positive. A subsequent study of juvenile macaques over a period of 2.5 years detected no STLV-I and 10 SRV-2 infections, six of which occurred between testing and day of colony formation. The study also highlighted that an anti-SRV-2 serological response does not presuppose infection. Tissue reservoirs of latent SRV-2 were not identified in suspected SRV-2 infections.
Conclusions  Low transmissibility of the viruses present in the parental cohort and improved knowledge of the host response to SRV-2 has facilitated the creation of specific-retrovirus-free colonies of cynomolgus macaques.     

Blood eosinophils and serum eosinophil cationic protein in patients with acute and chronic urticaria

We have analysed the relationship of blood eosinophil count and serum eosinophil cationic protein (ECP) levels in patients with acute and chronic idiopathic urticaria. The ECP levels and eosinophil counts were measured in the peripheral blood of 15 patients with acute urticaria, 25 with chronic idiopathic urticaria and 10 normal healthy subjects. Blood eosinophil counts and serum ECP levels increased in all patients with acute urticaria. Concerning patients affected by chronic urticaria, taking into account the recrudescence of the disease at the moment of taking the blood sample, only symptomatic patients showed increased eosinophil blood values whereas serum ECP levels were increased both in symptomatic and asymptomatic patients. Furthermore, serum ECP levels in chronic urticaria did not correlate with the peripheral eosinophil counts, as they did in acute urticaria. The results of the present study indicate that eosinophils may play a role in the inflammatory mechanisms in patients with acute and chronic urticaria showing a positive correlation between serum ECP levels and disease activity.     

食蟹猴经股静脉导管长期给药方法的建立

目的建立一种可靠的食蟹猴经股静脉导管长期给药的方法.方法选取20只雄性食蟹猴,麻醉后经股静脉造口,插入静脉导管,将植入式通道与导管连接并将其埋植于背部皮下,通过与植入式通道相连的输液泵进行给药.分别于术前1周、术后1周及术后2周测定血常规、血凝、生化等值.结果全部动物都能完成为期3个月的给药,手术感染率、导管堵塞率较低,分别为10%和5%.术后两周89.5%的生理指标与术前相比,差异无统计学意义(P>0.05).结论该实验采用的食蟹猴经股静脉插管并通过输液泵进行长期给药是一种安全、有效的方法,可广泛用于药理学及毒理学实验.