Microbiological, immunological, and histological changes in the gut of Salmonella Enteritidis-challenged rats fed goat cheese containing Lactobacillus rhamnosus EM1107.

Cheeses are able to serve as suitable matrices for supplying probiotics to consumers, enabling appropriate conditions for bacteria to survive gastric transit and reach the gut, where they are assumed to promote beneficial processes. The present study aimed to evaluate the microbiological, immunological, and histological changes in the gut of Salmonella Enteritidis-challenged rats fed goat cheese supplemented with the probiotic strain Lactobacillus rhamnosus EM1107. Thirty male albino Wistar rats were randomly distributed into 5 experimental groups with 6 animals each: negative (NC) and positive (PtC) control groups, control goat cheese (CCh), goat cheese added with L. rhamnosus EM1107 (LrCh), and L. rhamnosus EM1107 only (EM1107). All animals, except NC group were challenged with Salmonella Enteritidis (109 cfu in 1 mL of saline through oral gavage). Microbial composition was assessed with high-throughput 16S rRNA sequencing by means of Illumina MiSeq (Illumina, San Diego, CA). Nuclear factor kappa B (NF-κB) from the animal cecum tissue was determined by real-time PCR and interleukins (TNF-α, IL-1ß, IL-10, and IFN-γ) by means of ELISA. Myeloperoxidase and malondialdehyde levels were determined biochemically. The administration of the L. rhamnosus EM1107 probiotic strain, either as a pure culture or added to a cheese matrix, was able to reduce Salmonella colonization in the intestinal lumen and lessen tissue damage compared with rats from PtC group. In addition, the use of cheese for the probiotic strain delivery (LrCh) was associated with a marked shift in the gut microbiota composition toward the increase of beneficial organisms such as Blautia and Lactobacillus and a reduction in NF-κB expression. These findings support our hypothesis that cheeses might be explored as functional matrices for the efficacious delivery of probiotic strains to consumers.

Neuropharmacological Characterization of Dioclea altissima Seed Lectin (DAL) in Mice: Evidence of Anxiolytic-like Effect Mediated by Serotonergic, GABAergic Receptors and NO Pathway.

BACKGROUND: Plant lectins have shown promising biological activities in the central nervous system (CNS). OBJECTIVE: This study evaluated the effect of DAL, a lectin isolated from the seeds of the Dioclea altissima species, having binding affinity to D-glucose or D-mannose residues, on mice behavior. METHODS: Mice (n=6/group) were treated (i.p.) with DAL (0.25, 0.5 or 1 mg/kg) or vehicle and subjected to several tests (open field/OFT, marble-burying/MBT, hole-board/HBT, elevated plus maze/PMT, tail suspension/ TST, forced swimming/FST or rotarod/RRT). Pizotifen, cyproheptadine, flumazenil, L-NAME, 7-NI, Larginine or yohimbine were administered 15 min before DAL (0.5 mg/kg) and the animals were evaluated on PMT. It was also verified whether the DAL effect depended on its structural integrity and ability to interact with carbohydrates. RESULTS: The results showed there were no neurobehavioral changes in the mice at the RRT, FST and locomotion in the OFT. DAL (0.25, 0.5 or 1 mg/kg) increased the behavior of grooming and rearing in the OFT, head dips in the HBT, pedalling in the TST and decreased the number of marbles hidden in the MBT. In the PMT, DAL (0.25, 0.5 and 1 mg/kg) and Diazepam increased the frequency of entries in the open arms and the time of permanence in the open arms without affecting the locomotor activity. The effect of DAL was dependent on carbohydrate interaction and protein structure integrity and it prevented by pizotifen, cyproheptadine, flumazenil, L-NAME and 7-NI, but not by L-arginine or yohimbine. CONCLUSION: DAL was found to have an anxiolytic-like effect mediated by the 5-HT and GABAergic receptors and NO pathway.

Clinical and dermoscopic features of genital pigmented Bowen disease.

Pigmented Bowen disease (pBD) is an uncommon variant of squamous cell carcinoma in situ. Sometimes it can show clinical and dermoscopic features that are seen in other pigmented lesions of the skin and mucosa, making the diagnosis difficult. We report six cases of pBD occurring on the anogenital area, and discuss the importance of dermoscopy for improving the diagnostic accuracy in pBD.

Barriers associated with frequency of leisure-time physical activity among Brazilian adults of different income strata.

This study aimed to estimate the prevalence of the main perceived barriers to leisure-time physical activity (LTPA) and their associations with the frequency of LTPA in a representative sample of industrial workers from Brazil (n = 47,477), according to their income strata (low income: ≤$US280, middle income: $US281-$US1400, and high income: ≥$US1401). Data were collected between 2006 and 2008 via questionnaires about the main perceived barrier to LTPA and the frequency of LTPA. Multinomial logistic regression was performed to evaluate differences among groups. There was a lower prevalence of regular practice of LTPA in the low- (15.8%) and middle-income strata (18.2%) than among the individuals of the high-income stratum (27.6%). A large proportion of workers who regularly participated in LTPA reported no barriers (low: 43.1%; middle: 46.8%; high: 51.6%). Additional obligations and fatigue were the two most common perceived barriers in all family income strata among participants who engaged in different frequencies of LTPA. The odds for all perceived barriers showed a positive trend related to frequency of LTPA (from regular to no LTPA), with higher values according to income. In summary, the ordering of the main perceived barriers to LTPA differed according to workers' income stratum and frequency of engaging in LTPA.

New associations: INFG and TGFB1 genes and the inhibitor development in severe haemophilia A.

INTRODUCTION: The development of factor VIII (FVIII) inhibitor is the main complication of replacement therapy in patients with haemophilia A (HA). A ratio of 5-7% of individuals HA develops antibodies (inhibitors) against the FVIII infused during the treatment, thereby reducing their pro-coagulant activity. The immunomodulatory cytokine genes have been related to the risk of development of alloantibodies in several studies, mainly in HA with severe form. AIM: We investigated the polymorphisms in regulatory regions of cytokine genes (IL1A, IL1B, IL1R, IL1RA, IL4RA, IL12, INFG, TGFB1, TNF, IL2, IL4, IL6, IL10) that could influence the risk of developing inhibitors in patients with severe HA. METHODS: The genotyping of cytokine genes of 117 patients with HA was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP) using the protocol recommended by the manufacturer (Invitrogen kit Cytokines(®) , Canoga Park, USA) RESULTS: From the cohort of 117 patients with severe HA, 35 developed inhibitors. There was a higher frequency of +874 T allele in INFG and of +869 TT and TG/TG in TGFB1 genes on patients with inhibitors. CONCLUSION: This suggests that polymorphisms in INFG and in TGFB1 genes are related to risk of developing inhibitor, and could contribute to a genetic profile of the individual HA for the risk of inhibitors development to FVIII.

Clinical features of patients inappropriately undiagnosed of pulmonary embolism.

PURPOSES: The objective of this study was to identify clinical factors associated with delayed diagnosis of acute pulmonary embolism (PE) in the emergency department (ED). BASIC PROCEDURES: A retrospective observational study was performed at three University affiliated Hospitals; 436 consecutive patients who presented to the ED with an acute PE confirmed by chest computed tomography from 2008 to 2011 were included. Patients were divided into 3 groups: group 1, PE was diagnosed while the patient was still in the ED; group 2, PE was diagnosed during hospitalization; group 3, patients who were sent home with a wrong alternative diagnosis and returned to the ED and were diagnosed of PE. MAIN FINDINGS: One hundred forty-six patients (33.5%) had a delayed diagnosis of PE--21.5% belong to group 2 and 11.9% to Group 3. Chronic coexisting medical conditions like asthma or chronic obstructive pulmonary disease were independent predictors of a delayed diagnosis in patients who were admitted to hospital whereas non-specific and less severe symptoms like the presence of pleuro-mechanic thoracic pain, fever, hemoptysis, or the presence of a pulmonary infiltrate in chest x-ray were independent predictors of a delayed diagnosis in patients who were sent home. PRINCIPAL CONCLUSIONS: Delay in diagnosis of acute PE is frequent despite current diagnostic strategies. Patients are sent home or admitted to hospital with a wrong diagnosis depending on clinical presentation or coexisting medical conditions.

Influence of class I and II HLA alleles on inhibitor development in severe haemophilia A patients from the south of Brazil.

Congenital haemophilia A is a chromosome-linked recessive disorder caused by the deficiency or reduction of factor VIII (FVIII) pro-coagulant activity. During treatment, some patients develop alloantibodies (FVIII inhibitors) that neutralize the action of exogenously administered FVIII. Currently, the presence of these inhibitors is the most serious adverse event found in replacement therapy. Some studies have suggested that genetic factors influence the development of the FVIII coagulation inhibitors. To identify the class I and II alleles that may be influencing the formation of inhibitors in severe haemophilic patients. Genotyping of the class I (HLA-A, -B and -C) and class II (HLA-DRB1, -DQA1 and -DQB1) alleles of 122 patients with severe haemophilia A, including 36 who had developed antibodies to factor VIII, was performed. After the comparison of the group without inhibitors and the group with inhibitors, HLA-C*16 [Odds ratio (OR) = 7.73; P = 0.0092] and HLA-DRB1*14 (OR = 4.52; P = 0.0174) were found to be positively associated with the formation of the inhibitors. These results confirm that HLA alleles are involved in inhibitor production and could be used as a tool for recognition of groups at high risk of possible inhibitor development in Southern Brazilian haemophilic patients.

[The most frequent neurologic disturbances. A contribution to the definition of topics for the programmatic content to the program of neurology in medical graduation]. / Transtornos neurológicos mais frequentes: contribuição para a definição de temas do conteúdo programático do curso de neurologia, para a graduação médica.

INTRODUCTION: Knowledge accumulation is overfilling the thematic content of medical graduation. Medical Schools must be alert to define a minimal content related with the most frequent disturbs. We intent to suggest topics for the minimal content, to the program of Neurology in medical graduation. METHOD: 1. To identify the places where young doctors are working outside the School Hospital (SH): we analysed the answers of the letters sent to 6415 resident - doctors (RD) in São Paulo's State and we made personal interview with 201 RD. 2. To verify the most frequent neuropsychiatric disturbs (ND) in the population: we made the analysis of the patient's diagnostic records in emergency room of three institutions: Municipal of Taubaté-SP, Municipal of São José dos Campos-SP and Faculty of Medicine of São Paulo Santa Casa de Misericórdia. RESULTS: 1. The RD are young and, outside the SH, they work in other emergency services. 2. The most frequent diagnosis in institutions were listed: alcoholism, cerebrovascular disease, coma, cranial trauma, dementia, dizziness, epilepsy, facial paralysis, faint, headache, hemiplegia or paraplegia, meningitis, others paralysis, periferical neuropathy and psychiatric disorders. CONCLUSIONS: Those diagnostics most frequent are relevant topics of the programmatic content to the program of Neurology in medical graduation.

Iron mobilization by succinylacetone methyl ester in rats. A model study for hereditary tyrosinemia and porphyrias characterized by 5-aminolevulinic acid overload.

Accumulation of 5-aminolevulinic acid (ALA) is an event characteristic of porphyrias that may contribute to their pathological manifestations. To investigate effects of ALA independent of porphyrin accumulation we treated rats with the methyl ester of succinylacetone, an inhibitor of 5-aminolevulinic acid dehydratase that accumulates in the porphyric-like syndrome hereditary tyrosinemia. Acute 2-day treatment of fasted rats with succinylacetone methyl ester (SAME) promoted a 27% increase in plasma ALA. This increase in plasma ALA was accompanied by augmentation of the level of total nonheme iron in liver (37%) and brain (20%). Mobilization of iron was also indicated by 49% increase in plasma iron and a 77% increase in plasma transferrin saturation. Liver responded with a mild (12%) increase in ferritin. Under these acute conditions, some indications of oxidative stress were evident: a 15% increase in liver reactive protein carbonyls, and a 42% increase in brain subcellular membrane TBARS. Brain also showed a 44% increase in CuZnSOD activity, consistent with observations in treatment with ALA. Overall, the data indicate that SAME promotes ALA-driven changes in iron metabolism that could lead to increased production of free radicals. The findings support other evidence that accumulation of ALA in porphyrias and hereditary tyrosinemia may induce iron-dependent biological damage that contributes to neuropathy and hepatoma.

Coexistence of reef organisms in the Abrolhos Archipelago, Brazil.

The first study on coexistence of reef benthic organisms in Brazilian coral reefs was done in three localities of the Abrolhos Archipelago. Organisms were recorded in concentric circle samples (10 and 20 cm in diameter) randomly laid on transects. Type and frequency of "coexistence events" between pairs of organisms were determined. Most frequent organisms (massive and branched coralline algae, Favia gravida, and Agaricia agaricites) also had many significant positive coexistence events. These results might be related to the abundances of these organisms. The most frequent coral (Siderastrea stellata), however, exhibited only a few significant coexistence events (9% of 32 tests). Since the great majority of events were positive, and since there was high variation in the species/groups involved in significant events in different localities, benthic communities of Abrolhos Archipelago may well be structured primarily by abiotic rather than biotic factors.

Laparoscopy-assisted colonoscopic polypectomy.

One of the most feared complications in the removal of moderate-sized or large sessile polyps is colonic perforation. Complete colonoscopic total excision of these kinds of polyps can be safely undertaken using laparoscopic assistance, which enables prompt diagnosis and treatment of perforation. Laparoscopy-assisted endoscopic polyp excision can be safely performed, avoiding critical septic complications and can also help in the selection of patients to appropriate colonic resection without increasing morbidity or mortality.

High-repetition-rate femtosecond mid-infrared pulse generation.

Ultrashort mid-infrared pulses at a repetition rate of 82 MHz have been generated by difference-frequency mixing at the output of a single-cavity, two-color femtosecond Ti:sapphire laser. The center wavelengths of the midinfrared pulses are tunable from 7.5 to 12.5 microm. Their pulse durations range from 450 to 650 fs, as a function of the center wavelength.

[Prospective study of the effects of amiodarone on thyroid function in chagasic patients in an area of iodine deficiency]. / Estudo prospectivo dos efeitos da amiodarona na função tiroidiana de pacientes chagásicos em área de deficiência de iodo.

In order to evaluate the development of thyroid dysfunction during chronic amiodarone treatment in an area deficient in iodine and endemic for Chagas' disease, a group of 24 patients was prospectively studied. Clinical examination and measurement of serum T4, T3, rT3, TSH and antithyroglobulin antibodies were performed before and at 3 and 9 months of use of amiodarone. A TSH response 30 minutes after IV injection of 200 micrograms of TRH was also compared to TSH basal levels before and during amiodarone treatment. Thyroid radioactive uptake and scan were obtained before and nine months after amiodarone was started. Elevated rT3 concentrations were unexpectedly found in two thirds of the patients before treatment. Thyroid dysfunction developed during amiodarone administration in 20.8% of the patients; 12.5% became hyperthyroid and 8.3%, hypothyroid (with negative antithyroglobulin antibodies). Positive RAI uptake was seen in one patient with hyperthyroidism and diffuse goiter. Since T3 levels were not found to increase, the diagnosis of amiodarone-related hyperthyroidism was better evidenced by the reduced or blocked TSH response to TRH. Elevated TSH concentration was the best evidence of amiodarone-induced hypothyroidism. Increase in TSH levels since the beginning of amiodarone therapy may predispose to the growth of a goiter. In conclusion, amiodarone treatment in an iodine deficient area as above should be judiciously decided and thyroid function carefully monitored before and during the use of the drug.

Thresholds of electrically induced defence reaction of the rat: short- and long-term adaptation mechanisms.

The thresholds of electrically induced defence reaction of the rat were studied through the logistic fitting of the response output. When stepwise increasing stimuli were applied at the dorsal midbrain, hierarchically organized mean thresholds, spaced 10 microA apart, were observed for immobility, running and jumping defensive behaviours. The parallel threshold functions of these responses, ranked in the above order, denote that they have distinct output probabilities when induced with sequential stepwise increasing stimuli. In contrast, when single daily stimuli were given in a random order, virtually superimposed threshold functions were obtained for these defensive behaviours. In this case, since the same output probabilities would be expected for immobility, running and jumping behaviours, the defence system seems to operate in a state of maximum entropy. The above data suggest that the dorsal midbrain, including the deep collicular layers and the periaqueductal gray, may encode hierarchical or non-hierarchical defensive patterns which, respectively, mimic either the attentive behaviour of the prey watching the approaching predator or its chaotic behaviour when cornered by a sudden attack. On the other hand, whereas quite stable thresholds were observed for the somatic defensive responses when 5 stimulation sessions were repeated over 15 days, the defecation and micturition output underwent a marked and progressive lessening. Since these autonomic responses have long been considered as reliable indexes of fear, their attenuation throughout the repeated sessions could express the rat adaptation to fear by the recurrence of the aversive experience. Taken together, these data suggest that while short-term neuronal adaptation could be responsible for the hierarchical threshold structure of the short interval stepwise stimulation, long-term neuronal adaptation could underlie the selective decrease of defecation and micturition responses over repeated sessions of intracranial stimulation.

[Colonoscopy: experience in a general hospital]. / Colonoscopia: experiência de um hospital geral.

The authors emphasize the colonoscopy's importance and report their experience with the procedure in a general hospital. In a nearly 4 year period, 300 patients were submitted to the procedure, and the main indication was digestive bleeding, followed by alterations of bowels movements. The bowel preparation was done with mannitol ingestion except when contraindicated. The most frequent pathology were polyps and diverticular disease. Fifty three polypectomies were done in 22 patients.