Frequency of HLA-B27 and its alleles in patients with Reiter syndrome: comparison with the frequency in other spondyloarthropathies and a healthy control population

This retrospective study analyzed the HLA-B*27 alleles in a group of 20 consecutive patients with the diagnosis of Reiter syndrome (RS) followed in a tertiary referral university hospital in Brazil, during the period 1990-2006, and compared the data with that observed in other patients with spondyloarthropathies followed at the same institution. Eight cases were associated to gastrointestinal infection, eight cases to previous urethritis, and four cases presented no established preceding infection. HLA-B*27 alleles were typed by polymerase chain reaction-amplified DNA hybridized with sequence-specific oligonucleotide probes (HLA-B*2701 to HLA-B*2721). They were compared to a group of 108 patients with ankylosing spondylitis (AS), 40 with undifferentiated spondyloarthropathy (uSpA) and 111 healthy controls. Among the 20 patients, 17 were HLA-B*27 positive (85%). Two HLA-B*27 alleles were observed: HLA-B*2705 (65%) and HLA-B*2702 (35%). In the other spondyloarthropathies, the observed alleles were HLA-B*2705 (90% in AS and 92.5% in uSpA), HLA-B*2702 (8% in AS and 5% in uSpA), HLA-B*2704 (1% in AS and 2.5% in uSpA) and HLA-B*2713 (1% in AS). Among the 111 healthy controls, 80% presented HLA-B*2705, followed by HLA-B*2702 in 10%, HLA-B*2703 in 6%, HLA-B*2707 in 3% and HLA-B*2713 in 1%. Concluding, in the HLA-B*27 positive patients with RS in this study there was predominance of HLA-B*2705 allele, in a lower frequency than that observed in patients with other spondyloarthropathies and healthy controls.

Sildenafil inhibits duodenal contractility via activation of the NO-K+ channel pathway

Phosphodiesterase type-5 (PDE5) specifically cleaves cyclic guanosine monophosphate (cGMP), a key intracellular secondary messenger. The PDE5 inhibitor sildenafil is a well-known vasodilator that also has gastrointestinal myorelaxant properties. In the present study, we further investigated sildenafil-induced myorelaxation in rat isolated duodenum, assessing its interaction with nitric oxide (NO) synthase and K+ channel opening. The spontaneous contractions of duodenal strips were reversibly inhibited by sildenafil (0.1-300 mu M) in a concentration-dependent manner [mean (95% confidence interval); EC50 = 6.8 (2.7-17.3) mu M]. The sildenafil-induced myorelaxation was significantly decreased by the NO synthase inhibitor N-nitro-L-arginine methyl ester [increasing the EC50 value to 41.9 (26.1-67.3) mu M]. Sodium nitroprusside or forskolin pretreatments enhanced the sildenafil-induced myorelaxation. In isolated strips pretreated with BaCl2 (0.2 mM), 4-aminopyridine (4-AP, 3 mM), or glybenclamide (1 mu M), the sildenafil-induced EC50 value was significantly increased to 32.8 (19.1-56.4), 27.1 (15.2-48.3) and 20.1 (16.4-24.7) mu M, respectively. Minoxidil (50 mu M) or diazoxide (100 mu M) also significantly attenuated the sildenafil-induced potency. In conclusion, the NO synthase/cyclic nucleotide pathway activation is involved in sildenafil-induced inhibition of spontaneous duodenal contractions. Its pharmacological action seems to be influenced by K+ channel opening, especially the voltage-sensitive ones, being inhibited by 4-AP and K-ATP channels, sensitive to glybenclamide.

Validation of ACB in vitro and in vivo as a biomagnetic method for measuring stomach contraction

Background The aim of this study was to validate a biomagnetic method (alternate current biosusceptometry, ACB) for monitoring gastric wall contractions in rats. Methods In vitro data were obtained to establish the relationship between ACB and the strain-gauge (SG) signal amplitude. In vivo experiments were performed in pentobarbital-anesthetized rats with SG and magnetic markers previously implanted under the gastric serosa or after ingestion of magnetic material. Gastric motility was quantified from the tracing amplitudes and frequency profiles obtained by Fast Fourier Transform. Key Results The correlation between in vitro signal amplitudes was strong (R = 0.989). The temporal cross-correlation coefficient between the ACB and SG signal amplitude was higher (P < 0.0001) in the postprandial (88.3 +/- 9.1 V) than in the fasting state (31.0 +/- 16.9 V). Irregular signal profiles, low contraction amplitudes, and smaller signal-to-noise ratios explained the poor correlation between techniques for fasting-state recordings. When a magnetic material was ingested, there was also strong correlation in the frequency and signal amplitude and a small phase-difference between the techniques. The contraction frequencies using ACB were 0.068 +/- 0.007 Hz (postprandial) and 0.058 +/- 0.007 Hz (fasting) (P < 0.002) and those using SG were 0.066 +/- 0.006 Hz (postprandial) and 0.059 +/- 0.008 Hz (fasting) (P < 0.005). Conclusions & Inferences In summary, ACB is reliable for monitoring gastric wall contractions using both implanted and ingested magnetic materials, and may serve as an accurate and sensitive technique for gastrointestinal motility studies.

IL-4 regulates susceptibility to intestinal inflammation in murine food allergy

Cardoso CR, Provinciatto PR, Godoi DF, Ferreira BR, Teixeira G, Rossi MA, Cunha FQ, Silva JS. IL-4 regulates susceptibility to intestinal inflammation in murine food allergy. Am J Physiol Gastrointest Liver Physiol 296: G593-G600, 2009. First published January 8, 2009; doi:10.1152/ajpgi.90431.2008.-Allergies involve a state of immediate hypersensitivity to antigens, including food proteins. The mechanism underlying the initiation and development of allergic responses involves IL-4 that directly induces the differentiation of committed effector Th2 lymphocytes. Although it is clear that Th2 responses play a pivotal role in the development of allergic responses, it remains unclear which mechanisms are involved in the development of the intestinal damages observed in food allergy. Accordingly, this work aimed to study the role of Th2/IL-4-dependent responses in the development of food allergy and intestinal pathology. C57BL/6 wild-type (WT) and IL-4(-/-) mice were sensitized with peanut proteins, challenged with peanut seeds, and followed for the development of food allergy and intestinal inflammation. Results demonstrated that exposure to peanut seeds led to weight loss in WT but not in IL-4(-/-) mice that preserved gut integrity with no signs of mucosal inflammation. These animals presented increased levels of IgG2a in sera, suggesting a role for allergic antibodies in the pathogenesis of WT animals. Most importantly, results also showed that lack of IL-4 modulated gut mucosal response in food allergy through diminished expression of TNF-alpha mRNA, increased Th1 IFN-gamma, IL-12p40, regulatory cytokines, and Foxp3, demonstrating their relevance in the control of allergic inflammatory processes, especially in the intestine. Finally, this study highlighted some of the complex mechanisms involved in the pathogenesis of allergic responses to food antigens in the gut, thereby providing valuable tools for directing novel therapeutic or preventive strategies to the control of allergic enteropathy.

Modulation of mucosal immunity in a murine model of food-induced intestinal inflammation

Background Hypersensitivity or uncontrolled responses against dietary antigens can lead to inflammatory disorders like food allergy and current models reflect a variety of causes but do not reveal the detailed modulation of gut immunity in response to food antigens after breakdown in mucosal tolerance. Objective To develop and characterize a murine model for food-induced intestinal inflammation and to demonstrate the modulation of gut immune response by dietary allergenic antigens. Methods C57BL/6 mice were sensitized with peanut proteins, challenged with peanut seeds and their sera and gut segments were collected for subsequent analyses. Results Sensitization and challenged with peanut seeds led to alterations in gut architecture with inflammatory response characterized by oedema in lamina propria and cell infiltrate composed mainly by eosinophils, mast cells, phagocytes, natural killer and plasma cells, together with low percentage of gamma delta(+) and CD4(+)CD25(+)Foxp3(+) cells in Peyer`s patches. These animals also presented high levels of specific IgE and IgG1 in sera and modulation of mucosal immunity was mediated by increased expression of GATA-3, IL-4, IL-13 and TNF-alpha in contrast to low IFN-gamma in the gut. Conclusion A murine model for food-induced intestinal inflammation was characterized in which modulation of gut immunity occurs by peanut antigens in consequence of T-helper type 2 (Th2) allergic response and failure of regulatory mechanisms necessary for mucosa homeostasis, resembling food allergy. This work shed some light on the understanding of the pathogenesis of gastrointestinal disorders and intolerance in the gut and supports the development of therapies for food-related enteropathies like food allergy, focusing on gut-specific immune response.

Role of platelet-activating factor in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice

Gastrointestinal mucositis is a common side effect of cancer chemotherapy. Platelet-activating factor (PAF) is produced during gut inflammation. There is no evidence that PAF participates in antineoplastic-induced intestinal mucositis. This study evaluated the role of PAF in 5-fluorouracil (5-FU)-induced intestinal mucositis using a pharmacological approach and PAF receptor knockout mice (PAFR(-/-)). Wild-type mice or PAFR(-/-) mice were treated with 5-FU (450 mg/kg, i.p.). Other mice were treated with saline or BN52021 (20 mg/kg, s.c.), an antagonist of the PAF receptor, once daily followed by 5-FU administration. After the third day of treatment, animals were sacrificed and tissue samples from the duodenum were removed for morphologic evaluation. In addition, myeloperoxidase activity and the cytokine concentration were measured. 5-FU treatment decreased the duodenal villus height/crypt depth ratio, increased MPO activity, and increased the concentration of TNF-alpha, IL-1 beta and KC in comparison with saline-treated animals. In PAFR(-/-) mice and PAFR antagonist-treated mice, 5-FU-dependent intestinal damage was reduced and a decrease in duodenal villus height/crypt depth ratio was attenuated. However, the 5-FU-dependent increase in duodenum MPO activity was not affected. Without PAFR activation, 5-FU treatment did not increase the TNF-alpha, IL-1 beta and KC concentration. In conclusion, our study establishes the role of PAFR activation in 5-FU-induced intestinal mucositis. This study implicates treatment with PAFR antagonists as novel therapeutic strategy for this condition.

Hydrogen Sulfide Prevents Ethanol-Induced Gastric Damage in Mice: Role of ATP-Sensitive Potassium Channels and Capsaicin-Sensitive Primary Afferent Neurons

The aim of this study was to evaluate the protective effect of hydrogen sulfide (H(2)S) on ethanol-induced gastric lesions in mice and the influence of ATP-sensitive potassium (K(ATP)) channels, capsaicin-sensitive sensory afferent neurons, and transient receptor potential vanilloid (TRPV) 1 receptors on such an effect. Saline and L-cysteine alone or with propargylglycine, sodium hydrogen sulfide (NaHS), or Lawesson`s reagent were administrated for testing purposes. For other experiments, mice were pretreated with glibenclamide, neurotoxic doses of capsaicin, or capsazepine. Afterward, mice received L-cysteine, NaHS, or Lawesson`s reagent. After 30 min, 50% ethanol was administrated by gavage. After 1 h, mice were sacrificed, and gastric damage was evaluated by macroscopic and microscopic analyses. L-Cysteine, NaHS, and Lawesson`s reagent treatment prevented ethanol-induced macroscopic and microscopic gastric damage in a dose-dependent manner. Administration of propargylglycine, an inhibitor of endogenous H(2)S synthesis, reversed gastric protection induced by L-cysteine. Glibenclamide reversed L-cysteine, NaHS, or Lawesson`s reagent gastroprotective effects against ethanol-induced macroscopic damage in a dose-dependent manner. Chemical ablation of sensory afferent neurons by capsaicin reversed gastroprotective effects of L-cysteine or H(2)S donors (NaHS or Lawesson`s reagent) in ethanol-induced macroscopic gastric damage. Likewise, in the presence of the TRPV1 antagonist capsazepine, the gastroprotective effects of L-cysteine, NaHS, or Lawesson`s reagent were also abolished. Our results suggest that H(2)S prevents ethanol-induced gastric damage. Although there are many mechanisms through which this effect can occur, our data support the hypothesis that the activation of K(ATP) channels and afferent neurons/TRPV1 receptors is of primary importance.

Skin and oral lesions associated to imatinib mesylate therapy

Imatinib mesylate is a tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML) throughout all the phases of the disease. In most cases, this drug is well tolerated; however, some cases experience side effects. Skin rashes and oral lesions are uncommon and appear to be dose-dependent. The authors report two cases of CML Ph(+) in chronic phase patients who presented skin and oral lesions probably induced by imatinib therapy.

Case Report: Esophageal Histoplasmosis Associated with Disseminated Tuberculosis in Acquired Immunodeficiency Syndrome

Bacterial and fungal infections are common in acquired immunodeficiency syndrome (AIDS). Histoplasmosis is a common fungal disease in severely immunocompromised patients infected with human immunodeficiency virus (HIV) in endemic areas. In this population the most frequent form of presentation of histoplasmosis is disseminated, with the clinical manifestations being similar to those of disseminated tuberculosis. Esophageal histoplasmosis and the association of histoplasmosis with tuberculosis are infrequent. We report here a rare Case of esophageal histoplasmosis associated with disseminated tuberculosis in AIDS.

Nutrition Therapy in a Pediatric Intensive Care Unit: Indications, Monitoring, and Complications

Background: Nutrition therapy (NT) is essential for the care of critically ill children. Inadequate feeding leads to malnutrition and may increase the patient`s risk of morbidity and mortality. The aim of this study was to describe the NT used in a tertiary pediatric intensive care unit (PICU). Methods: The authors evaluated NT administered to 90 consecutive patients who were hospitalized for 7 days in the PICU of Instituto da Crianca, Hospital das Clinicas, Universidade de Sao Paulo, Brazil. NT was established according to the protocol provided by the institution`s NT team. NT provided a balance of fluids and nutrients and was monitored with a weekly anthropometric nutrition assessment and an evaluation of complications. Results: NT was initiated, on average, within 72 hours of hospitalization. Most children (80%) received enteral nutrition (EN) therapy; of these, 35% were fed orally and the rest via nasogastric or postpyloric tube. There were gastrointestinal complications in patients (5%) who needed a postpyloric tube. Parenteral nutrition (PN) was used in only 10% of the cases, and the remaining 10% received mixed NT (EN + PN). The average calorie and protein intake was 82 kcal/kg and 2.7 g/kg per day. Arm circumference and triceps skinfold thickness decreased. Conclusions: The use of EN was prevalent in the tertiary PICU, and few clinical complications occurred. There was no statistically significant change in most anthropometric indicators evaluated during hospitalization, which suggests that NT probably helped patients maintain their nutrition status. (JPEN J Parenter Enteral Nutr. 2011;35:523-529)

Short-Term Effects of Duodenocecostomy on Body Weight, Glucose Absorption, Serum Components, and Intestinal Histopathology in Four Normal Horses

The objective of this study was to evaluate duodenocecostomy in horses performed through a ventral midline laparotomy and report its influence oil body weight, glucose absorption, serum components, and characteristics of jejunum, cecum, and large colon histology. Four horses were submitted to the duodenocecostomy technique through a ventral midline laparotomy with animals in dorsal recumbency under inhalation anesthesia, followed by abdominal exploration. A side-to-side anastomosis was performed between the duodenojejunal flexure and the base of the cecum with two simple continuous suture lines of the serosal and muscular layers. The size of the opening created was approximately 2 cm in diameter. The mucosa layer was not Sutured. After 30 days, animals were submitted to a second laparotomy to check the patency of the duodenocaecal fistula. During both laparotomy procedures, excisional biopsies of different segments of the gastrointestinal tract were performed. Information on physical examination findings, results of hematologic and histopathologic evaluations, and oral glucose absorption test were recorded. The horses did not have significant weight loss from baseline, and absorption curve of glucose did not significantly vary from baseline. Only triglycerides had significant alterations. Histologic evaluation of jejunum, cecum, and large colon did not show alterations of intestinal structure and morphology. We concluded that the proposed technique, principally in relation to the fistula size and not suturing the mucosa layer, allowed partial or total Occlusion of the fistulae without the necessity of a second surgery and avoided the permanent bypass of ingesta and weight loss.

Phosphorus kinetics in calves experimentally submitted to a trickle infection with Cooperia punctata

Ten male Holstein calves (74.3 +/- 3.2 kg LW) were used for a trial with trickle infection with Cooperia punctata to evaluate phosphorus (P) kinetics. Five calves were inoculated with 10,000 L(3) stage larvae per week during 35 days, while the other group of five calves was kept as a control. On the 29th day each calf was intravenously injected with 29.6 MBq of a (32)p solution. Blood samples were taken at 24 h periods for 7 days, after which all calves were slaughtered and worms burdens. Faeces, urine and tissue samples were taken for analysis using isotopic dilution and modeling techniques. The number of eggs per gram of faeces (EPG)was 1920 +/- 168 on 28th day and the total number of worms burdens was 11,131 +/- 1500. Infected calves showed lower feed intake and live weight gain, as well as lower P intake, absorption and retention than control calves. The P flows between body compartments were lower for blood to gastrointestinal tract (TGI), TGI to blood, blood to soft tissues, bone balance and soft tissue balance in infected calves when compared to the control. The trickle infection of C punctata affected P metabolism due to the decrease in P retained and live weight due to fall in feed intake. (C) 2009 Elsevier B.V. All rights reserved.

Histologic and immunohistochemical evaluation of intestinal innervation in dogs with and without intussusception

Objective-To assess viability of innervation in bowel segments appearing macroscopically viable from dogs with intussusception. Animals-7 dogs without gastrointestinal dysfunction that had been euthanized for reasons unrelated to the study (control dogs) and 13 dogs with intussusception that underwent enterectomy and intestinal anastomosis (affected dogs). Procedures-A total of 31 samples of intestinal tissue were obtained from the control dogs; 28 samples were obtained from affected dogs during surgery. Samples were histologically and immunohistochemically prepared and subjectively scored for degree of vacuolization and staining, respectively. Other data collected included mean muscle cell density of circular and longitudinal muscular layers, ratio between areas of muscular layers, mean number of myenteric plexuses, mean ganglion cell density of myenteric plexuses, and degree of degeneration in neuronal plexuses as estimated through synaptophysin and neuron-specific enolase (NSE) immunoreactivity. Results-Mean muscle cell density of longitudinal muscular layers, ratio between areas of muscular layers, and synaptophysin immunoreactivity did not differ significantly between affected and control dogs; values of all other variables did. Correlations were evident between mean ganglion cell density in myenteric plexuses and mean muscle cell density in circular muscular layers, degree of neuronal degeneration in myenteric plexuses and NSE immunoreactivity, and degree of neuronal degeneration in myenteric plexuses and mean ganglion cell density of myenteric plexuses. Conclusions and Clinical Relevance-Innervation may be impaired in bowel segments that appear macroscopically viable. Therefore, careful evaluation of preserved surgical margins during enterectomy and enteroanastomosis and monitoring of digestive function after surgery are important. (Am J Vet Res 2010;71:636-642)

Helminths of Sotalia guianensis (Cetacea: Delphinidae) from the South and Southeastern Coasts of Brazil

From May 1997 to October 2000, 49 Sotalia guianensis (tucuxi dolphin) incidentally caught in fishing nets or stranded in Sao Paulo (SP) and Parana (PH) states in Brazil were necropsied. In total, 17 lungs, 35 stomachs, and 30 intestines were analyzed. Contents were washed through a sieve (mesh, 150 mm) and examined under a stereoscopic microscope for parasites. Histopathologic analyses were performed in the lungs of five infected dolphins. The nematode Halocereus brasiliensis was found in 88% of all lungs examined, inducing moderate-to-severe pneumonia. Braunina cordiformis, Anisakis sp., and acanthocephalans were found in the stomachs. The trematode Synthesium tursionis was the only parasite found in the intestines, and it was identified in 73% of the animals necropsied. No macroscopic lesions were seen due to parasites in the stomachs and intestines analyzed.

Tooth abnormalities and soft tissue alterations in patients with G/BBB syndrome

OBJECTIVE: The G/BBB syndrome is an X-linked recessive disorder characterized by eye anomalies, laryngotracheoesophageal cleft, congenital heart disease, genitourinary anomalies and gastrointestinal disorders. Patients may also present cleft lip and palate, high-arched palate and thin upper lip. This study aimed to investigate the occurrence of tooth abnormalities and soft tissue changes in patients with G/BBB syndrome. DESIGN: Cross-sectional. SUBJECTS AND METHODS: Twenty-one patients with G/BBB syndrome were analyzed as to the presence of tooth abnormalities and soft tissue alterations. MAIN OUTCOME MEASURES: The prevalence of tooth agenesis and supernumerary teeth was compared to patients without morphofunctional alterations, matched for gender and age. RESULTS: All patients had complete cleft lip and palate; 95.23% of patients presented tooth abnormalities, mainly hypoplastic alterations, with predominance of alterations of number, followed by alterations of structure, shape and position. The frequency of tooth agenesis and supernumerary teeth was significantly higher compared with the control group; 11 patients presented incisiform supernumerary teeth in the mandibular anterior region. Ankyloglossia was observed in 11 of 21 patients. CONCLUSION: The presence of mandibular anterior supernumerary teeth and ankyloglossia should be investigated in the clinical evaluation of patients with suspected diagnosis of the G/BBB syndrome. Oral Diseases (2008) 14, 747-753