Defining the interaction of HIV-1 with the mucosal barriers of the female reproductive tract

Worldwide, HIV-1 infects millions of people annually, the majority of whom are women. To establish infection in the female reproductive tract (FRT), HIV-1 in male ejaculate must overcome numerous innate and adaptive immune factors, traverse the genital epithelium, and establish infection in underlying CD4(+) target cells. How the virus achieves this remains poorly defined. By utilizing a new technique, we define how HIV-1 interacts with different tissues of the FRT using human cervical explants and in vivo exposure in the rhesus macaque vaginal transmission model. Despite previous claims of the squamous epithelium being an efficient barrier to virus entry, we reveal that HIV-1 can penetrate both intact columnar and squamous epithelial barriers to depths where the virus can encounter potential target cells. In the squamous epithelium, we identify virus entry occurring through diffusive percolation, penetrating areas where cell junctions are absent. In the columnar epithelium, we illustrate that virus does not transverse barriers as well as previously thought due to mucus impediment. We also show a statistically significant correlation between the viral load of inocula and the ability of HIV-1 to pervade the squamous barrier. Overall, our results suggest a diffusive percolation mechanism for the initial events of HIV-1 entry. With these data, we also mathematically extrapolate the number of HIV-1 particles that penetrate the mucosa per coital act, providing a biological description of the mechanism for HIV-1 transmission during the acute and chronic stages of infection.

Blocking HIV-1 transmission in the female reproductive tract: from microbicide development to exploring local antiviral responses

The majority of new HIV-1 infections are transmitted sexually by penetrating the mucosal barrier to infect target cells. The development of microbicides to restrain heterosexual HIV-1 transmission in the past two decades has proven to be a challenging endeavor. Therefore, better understanding of the tissue environment in the female reproductive tract may assist in the development of the next generation of microbicides to prevent HIV-1 transmission. In this review, we highlight the important factors involved in the heterosexual transmission of HIV-1, provide an update on microbicides' clinical trials, and discuss how different delivery platforms and local immunity may empower the development of next generation of microbicide to block HIV-1 transmission in the female reproductive tract.

Histopathology findings in common marmosets (Callithrix jacchus Linnaeus, 1758) with chronic weight loss associated with bile tract obstruction by infestation with Platynosomum (Loos, 1907)

Chronic weight loss in marmosets is often associated with wasting marmoset syndrome (WMS), an important disease that occurs in callitrichid colonies around the world. Even though its etiology is very difficult to determine, particular variables, such as weight loss, diarrhea and alopecia, associated or not with infestation in the pancreatic ducts with Trichospirura leptossoma (Nematoda: Thelazioidea), seem to be linked with the syndrome. This study investigated the histopathology of the lungs, duodenum, liver, gallbladder, extrahepatic bile ducts and pancreatic ducts of six common marmosets (Callithrix jacchus) suffering from severe non-diarrheic weight loss. Three individuals died naturally and the other three were euthanized. Microscopic findings showed the presence of adult flukes (Platynosomum) in the liver. These flukes, which provoke common infection in cats, were also observed inside the gallbladder as well as in the intra and extrahepatic bile ducts in common marmosets. Portal fibrosis was observed in two animals, which developed chronic fibrosing hepatopathy (biliary pattern, grade 3). The disease progresses without diarrhea and without pancreatic lesions or infestation. With the rogression, the animals presented with ascending cholangitis, cholestasis and portal fibrosis, sometimes culminating in secondary biliary cirrhosis. Therefore, this nfirmity, associated with chronic weight loss in common marmosets, could be another tiological factor linked with WMS

Influence of chlorine added to drinking water during the preslaughter feed withdrawal on microbiology and morphology of the broiler gastrointestinal tract

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of egg pre-storage heating period and storage length on the digestive tract of newly-hatched broiler chicks

An experiment was carried out to evaluate the effect of different heating times of settable eggs of Cobb 500® broiler breeders before submitting them to different storage periods on body weight, digestive tract organ weights, and intestinal mucosa morphology of newly-hatched chicks. Settable eggs were distributed in a completely randomized experimental design with a 3 x 3 factorial arrangement: pre-storage heating periods (0, 6, 12 hours at 36.92°C) and storage periods (4, 9, 14 days at 12.06°C). Body weight and relative weights of the yolk sac, heart, liver, proventriculus+gizzard, and intestinal segments were measured in chicks hatching at 480 and 498 hours of incubation. Villi height, width and perimeter, and crypt depth (ìm) were measured in duodenal histological sections. It was concluded that pre-storage heating for six hours of eggs stored for four or nine days increases small intestine weight of newly-hatched chicks, but does not influence the morphology of the duodenal mucosa. Pre-storage heating for 12 hours negatively influences body weight and duodenal mucosa development, and therefore this practice is not recommended. Storage length does not have consistent effect on body weight and development of the gastrointestinal tract.

Phenotypical characterization and adhesin identification in Escherichia coli strains isolated from dogs with urinary tract infections

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Qualitative feed restriction for heavy swines: effect on digestibility and weight of organs of digestive tract, and environmental impact of feces

Foram utilizados 50 suínos machos castrados para avaliar o efeito da restrição alimentar qualitativa sobre a digestibilidade dos componentes dietéticos, os órgãos do trato digestório, a composição e a produção fecal. Foram utilizadas cinco dietas experimentais, com níveis de restrição qualitativa de 0, 5, 10, 15 e 20%. Houve redução linear (P<0,001) para todos os coeficientes de digestibilidade, com exceção da fibra em detergente ácido, que apresentou resposta quadrática (P<0,05). Os teores de sólidos totais (P<0,01) e voláteis (P<0,05), e minerais totais (P<0,001) nas fezes aumentaram com os níveis de restrição alimentar, enquanto os níveis de K (P<0,05), Cu (P<0,01) e de N, P, Na, Ca, Mg, Fe e Zn (P<0,001), apresentaram resposta quadrática. A excreção diária de fezes, sólidos totais e voláteis, minerais totais, N, P, K, Mn e Cu (P<0,001), Ca, Na, Mg e Fe (P<0,05) apresentaram aumento em função do nível da restrição alimentar qualitativa. A restrição qualitativa pode ser alternativa para destinação de resíduos da agroindústria, conferindo boas propriedades às fezes suínas, no que diz respeito à utilização para adubação de culturas.

Carcinogenesis of the upper gastrointestinal tract induced by N-methyl-N '-nitro-nitrosoguanidine and reflux of duodenal contents in the rat

Purpose: To investigate the combined effects of reflux of duodenal contents through the pylorus and treatment with N-methyl-N'-nitro-nitrosoguanidine ( MNNG) on the development of lesions in the glandular stomach, at the gastrojejunal anastomosis and in the forestomach of rats. Methods: Eighty Male Wistar rats were divided into 4 groups: G1: MNNG + Reflux, G2: Reflux, G3: MNNG and G4: Gastrostomy. MNNG was given in the drinking water ( 100 mg/ml) for 12 weeks and then two groups ( G1 and G2) were submitted to a gastrojejunal anastomosis followed by section of the afferent loop and suture of both stumps to allow reflux of duodenal contents through the pylorus. The animals were sacrificed 18 and 36 weeks after surgery. The lesions obtained in the antral mucosa, at the gastrojejunal anastomosis and in the forestomach were analysed histologically. Results: Duodenal reflux induced proliferative lesions at both glandular and squamous mucosa of the stomach. In the antrum, adenomatous hyperplasia (AH) was observed in 20% and 50% of the animals at the 18(th) and 36(th) weeks respectively. Aditionally 85% of the animals presented AH at the gastrojejunal anastomosis and 60% developed squamous hyperplasia at the squamous portion of the stomach. MNNG treatment plus duodenal reflux enhanced the development of malignant tumors at both glandular and squamous mucosa, since there were 30% of antral adenocarcinomas and 45% of squamous carcinomas at the 18th week and the frequency of these malignant tumors rose to 50% in the antrum and 65% in the squamous mucosa at the 36th week. Conclusion: The reflux of duodenal contents through the pylorus enhanced the development of proliferative lesions, benign and malignant, in the glandular stomach and in the forestomach of rats.

Biliary tract reconstruction using jejunal tube: an experimental study in dogs

BACKGROUND: To physiologically reconstruct the biliary tract, Crema et al suggested the application of the Monti principle to the biliary tract, already used in humans for the urinary tract. With this technique, a jejunal segment is transversely retubularized. This study aimed to evaluate the efficacy of jejunal tube interposition between the common bile duct and duodenum in dogs.METHODS: Thirteen dogs underwent a laparoscopic common bile duct ligature, followed by a biliodigestive connection by jejunal tube interposition after one week. The levels of glutamic-pyruvic and glutamic-oxalacetic transaminases, total bilirubins, alkaline phosphatase and gamma-glutamyltransferase were assessed before surgery and thereafter weekly until euthanasia, which was performed 6 weeks after biliodigestive connection.RESULTS: Data on 9 dogs were analyzed statistically. The dogs presented with obstructive jaundice after common bile duct ligature, as confirmed by biochemical examination. They showed a statistically significant reduction in cholestasis after biliodigestive connection by jejunal tube interposition and were healthy until the end of the experiment.CONCLUSION: A statistically significant reduction was seen in total bilirubin and canalicular enzymes (alkaline phosphatase and gamma-glutamyltransferase) in the 9 dogs 6 weeks after biliodigestive conviction by jejunal tube interposition.

Enteric coated magnetic HPMC capsules evaluated in human gastrointestinal tract by AC biosusceptometry

Purpose. To employ the AC Biosusceptometry (ACB) technique to evaluate in vitro and in vivo characteristics of enteric coated magnetic hydroxypropyl methylcellulose (HPMC) capsules and to image the disintegration process.Materials and Methods. HPMC capsules filled with ferrite (MnFe2O4) and coated with Eudragit (R) were evaluated using USP XXII method and administered to fasted volunteers. Single and multisensor ACB systems were used to characterize the gastrointestinal (GI) motility and to determine gastric residence time (GRT), small intestinal transit time (SITT) and orocaecal transit time (OCTT). Mean disintegration time (t (50)) was quantified from 50% increase of pixels in the imaging area.Results. In vitro and in vivo performance of the magnetic HPMC capsules as well as the disintegration process were monitored using ACB systems. The mean disintegration time (t (50)) calculated for in vitro was 25 +/- 5 min and for in vivo was 13 +/- 5 min. In vivo also were determined mean values for GRT (55 +/- 19 min), SITT (185 +/- 82 min) and OCTT (240 +/- 88 min).Conclusions. AC Biosusceptometry is a non-invasive technique originally proposed to monitoring pharmaceutical dosage forms orally administered and to image the disintegration process.

Identification of Staphylococcus saprophyticus isolated from patients with urinary tract infection using a simple set of biochemical tests correlating with 16S-23S interspace region molecular weight patterns

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Prevalence and Risk Factors of Chlamydia trachomatis Cervicitis in Pregnant Women at the Genital Tract Infection in Obstetrics Unit Care at Botucatu Medical School, São Paulo State University - UNESP, Brazil

Objective. To evaluate the prevalence of and risk factors for Chlamydia trachomatis cervicitis in pregnant women seen at the Genital Tract Infection in Obstetrics Unit Care in Botucatu Medical School, São Paulo State University - UNESP.Materials and Methods. Between June 2006 and February 2008, 101 pregnant women were included in this study. During the gynecologic examination, cervical secretions were collected using cytobrush Plus GT (CooperSurgical Inc) to assess C. trachomatis using polymerase chain reaction. Vaginal flora were examined by Gram stain, and socio-demographic data were extracted from medical records.Results. of the 101 patients, 26 (25.7%) were positive for C. trachomatis. The median age of the infected group was 24 years (range = 13-40 y), and 48.5% of them had abnormal vaginal flora. The presence of chlamydial infection was associated with smoking (odds ratio [OR] = 2.67, 95% confidence interval [CI] = 1.01-7.19), residing in a city with fewer than 100,000 inhabitants (OR = 2.86, 95% CI = 1.03-7.94), presence of condyloma acuminatum (p = .03), and presence of discreet inflammation on Pap smear (p = .02).Conclusions. The prevalence of C. trachomatis is high in pregnant women seen at the Genital Infection Unit Care, UNESP, and is related to many risk factors. Therefore, its screening is extremely important in reducing obstetrical and neonatal complications.

The impact of physical exercise on the gastrointestinal tract

Purpose of reviewPhysical exercise can be both beneficial and harmful for the gastrointestinal tract in a dose-effect relationship between its intensity and health. Mild-to-moderate intensity exercises play a protective role against colon cancer, diverticular disease, cholelithiasis and constipation, whereas acute strenuous exercise may provoke heartburn, nausea, vomiting, abdominal pain, diarrhea and even gastrointestinal bleeding. This review focuses on mechanisms involved in those symptoms and their associations with type of exercises in humans.Recent findingsOne quarter to one half of elite athletes are hampered by the gastrointestinal symptoms that may deter them from participation in training and competitive events. Vigorous exercise-induced gastrointestinal symptoms are often attributed to altered motility, mechanical factor or altered neuroimmunoendocrine secretions. Training, lifestyle modifications, meal composition, adequate hydration and avoidance of excessive use of some medications are the recommendations.SummaryStrenuous exercise and dehydrated states would be the causes of gastrointestinal symptoms referred by 70% of the athletes. Gut ischemia would be the main cause of nausea, vomiting, abdominal pain and (bloody) diarrhea. The frequency is almost twice as high during running than during other endurance sports as cycling or swimming and 1.5-3.0 times higher in the elite athletes than the recreational exercisers.