The impact of the association between Val16Ala-SOD2 SNP and SOD2 immunohistochemistry expression in the prognosis of patients with esophageal cancer.

INTRODUCTION: Esophageal cancer is an extensive public health issue worldwide, warranting the search for biomarkers related to its risk and progression. Previous studies have indicated an association between Val16AlaSOD2 single nucleotide polymorphism in the gene encoding the enzyme superoxide dismutase 2 and esophageal cancer. However, further investigations are needed to clarify its role in disease risk and progression. OBJECTIVE: To investigate the role of Val16AlaSOD2-SNP in esophageal cancer progression and in the survival of patients METHODS: Tumor samples were utilized for Val16Ala-SNP genotyping, while SOD2 expression levels in tissue were assessed using immunohistochemistry. A SOD2 Val16Ala-SNP database was used to obtain information on the genotype of healthy individuals. Risk and overall survival analyzes were performed. RESULTS: The Val16Ala SNP was associated with an increased risk of esophageal cancer (RR 2.18, 95%CI 1.23-3.86), regardless of age and gender, but did not have a significant effect on patient survival. In contrast, weak SOD2 expression demonstrated a significantly associated with poor overall survival after treatment, independent of other clinicopathological variables (HR, 0.41; 95% CI, 0.22-0.79 P = 0.007). CONCLUSIONS: Val16Ala SNP was positively associated with esophageal cancer, and the expression of SOD2 was an independent prognostic marker.

Insights for Alzheimer's disease pharmacotherapy and current clinical trials.

Over the years, the scientific community has sought improvements in the life quality of patients diagnosed with Alzheimer's disease (AD). Synaptic loss and neuronal death observed in the regions responsible for cognitive functions represent an irreversible progressive disease that is clinically characterized by impaired cognitive and functional abilities, along with behavioral symptoms. Currently, image and body fluid biomarkers can provide early dementia diagnostic, being it the best way to slow the disease's progression. The first signs of AD development are still complex, the existence of individual genetic and phenotypic characteristics about the disease makes it difficult to standardize studies on the subject. The answer seems to be related between Aß and tau proteins. Aß deposition in the medial parietal cortex appears to be the initial stage of AD, but it does not have a strong correlation with neurodegeneration. The strongest link between symptoms occurs with tau aggregation, which antecede Aß deposits in the medial temporal lobe, however, the protein can be found in cognitively healthy older people. The answer to the question may lie in some catalytic effect between both proteins. Amid so many doubts, Aducanumab was approved, which raised controversies and results intense debate in the scientific field. Abnormal singling of some blood biomarkers produced by adipocytes under high lipogenesis, such as TNFα, leptin, and interleukin-6, demonstrate to be linked to neuroinflammation worsens, diabetes, and also severe cases of COVID-19, howsoever, under higher lipolysis, seem to have therapeutic anti-inflammatory effects in the brain, which has increasingly contributed to the understanding of AD. In addition, the relationship of severe clinical complications caused by Sars-CoV-2 viral infection and AD, go beyond the term "risk group" and may be related to the development of dementia long-term. Thus, this review summarized the current emerging pharmacotherapies, alternative treatments, and nanotechnology applied in clinical trials, discussing relevant points that may contribute to a more accurate look.

Meningoencephalitis caused by Bovine alphaherpesvirus 5 in Pernambuco, Brazil / [Meningoencefalite causada pelo Bovine alphaherpesvirus 5 em Pernambuco, Brasil]

Objetivou-se descrever a ocorrência do Bovine alphaherpesvirus 5 (BoHV5) como causa de meningoencefalite não supurativa em bovinos do estado de Pernambuco, Brasil. Para tanto, 32 amostras de sistema nervoso embebidas em parafina foram obtidas de animais acometidos por doenças neurológicas atendidos na Clínica de Bovinos de Garanhuns da Universidade Federal Rural de Pernambuco (CBG-UFRPE), entre 2012 e 2016. As amostras foram analisadas quanto à presença do gene da glicoproteína C do BoHV5 por reação em cadeia da polimerase (PCR). Dois animais (6,25%) tiveram resultado positivo à PCR, e sua análise de sequenciamento indicou 100% de similaridade para o BoHV5. Os resultados histopatológicos desses dois animais revelaram lesões multifocais de meningoencefalite não supurativa associada à polioencefalomalácia, presença de corpúsculos de inclusão basofílicos, infiltração de células de Gitter e presença de manguitos perivasculares. A PCR se mostra uma importante ferramenta para diferenciação das infecções por BoHV5 de outras enfermidades neurológicas de bovinos, especialmente a raiva.(AU)

Systemic and Gastrohepatic Mucormycosis in Dogs.

We describe two cases of mucormycosis with systemic and gastrohepatic involvement in two male poodles. Respiratory, neurological and gastrointestinal signs progressed to death within 3 and 19 days of the onset of clinical signs, respectively. In case 1, there was systemic disease affecting the lungs, heart and brain. The lesions were characterized by yellow or red, raised, irregular areas that extended into deeper tissue from the surface. In case 2, there was gastric rupture; the margins of the rupture and the gastric mucosa were covered by a thick, white, friable material. In the liver, there were multiple yellow-white cavitated nodules. Histologically, pyogranulomas occurred in the affected organs and were associated with vasculitis, thrombosis and fungal hyphae. The diagnosis of mucormycosis was based on the characteristic microscopical lesions together with the morphology and staining features of the fungus. The hyphae were strongly labelled by monoclonal antibody specific for Rhizopus arrhizus on immunohistochemistry. Underlying immunosuppression was suspected in both cases.

Composition of fatty acids, tocopherols, tocotrienols and ß-carotene content in oils of seeds of Brazilian Sapindaceae and Meliaceae species.

This study analyzes the lipid composition and the oxidative stability of oils of Sapindaceae and Meliaceae seeds. The oil content ranged from 14.7% (Guarea guidonia) to 30.1% (Allophylus puberulus and Paullinia elegans). Ten fatty acids were identified in seed oils. Guarea guidonia seeds accumulated mainly oleic (44.9%) and linoleic (24.1%) acid, whereas the unusual gondoic and paullinic acids were identified in A. puberulus (15.8%; 8.9%) and P. elegans (14.4%; 44.2%), respectively. The oil of P. elegans had the highest oxidative stability (16.2 h.). Tocopherol predominated in A. puberulus (10.4 mg/100 g) and tocotrienol predominated in G. guidonea and P. elegans (2.6 mg/100 g). The vitamers α-tocopherol, γ-tocopherol, and γ-tocotrienol were found in the studied oils. ß-carotene was predominantly detected in the oil of A. puberulus seeds (22.4 µg/g). Guarea guidonia seed oil has a high potential in food due to richness in essential fatty acids. In turn, A. puberulus and P. elegans oils could be suggested for other industrial purposes (e.g., biodiesel, varnishes, paints, soaps, or oleochemicals) due to their content of long-chain fatty acids.

Toxin Gene Contents and Activity of Bacillus thuringiensis Strains Against Two Sugarcane Borer Species, Diatraea saccharalis (F.) and D. flavipennella (Box).

Bacillus thuringiensis (Berliner) bears essential characteristics in the control of insect pests, such as its unique mode of action, which confers specificity and selectivity. This study assessed cry gene contents from Bt strains and their entomotoxicity against Diatraea saccharalis (F.) and Diatraea flavipennella (Box) (Lepidoptera: Crambidae). Bioassays with Bt strains were performed against neonates to evaluate their lethal and sublethal activities and were further analyzed by PCR, using primers to identify toxin genes. For D. saccharalis and D. flavipennella, 16 and 18 strains showed over 30% larval mortality in the 7th day, respectively. The LC50 values of strains for D. saccharalis varied from 0.08 × 105 (LIIT-0105) to 4104 × 105 (LIIT-2707) spores + crystals mL-1. For D. flavipennella, the LC50 values of strains varied from 0.40 × 105 (LIIT-2707) to 542 × 105 (LIIT-2109) spores + crystals mL-1. For the LIIT-0105 strain, which was the most toxic to D. saccharalis, the genes cry1Aa, cry1Ab, cry1Ac, cry1B, cry1C, cry1D, cry1F, cry1I, cry2Aa, cry2Ab, cry8, and cry9C were detected, whereas for the strain LIIT-2707, which was the most toxic to D. flavipennella, detected genes were cry1Aa, cry1Ab, cry1Ac, cry1B, cry1D, cry1F, cry1I, cry2Aa, cry2Ab, and cry9. The toxicity data and toxin gene content in these strains of Bt suggest a great variability of activity with potential to be used in the development of novel biopesticides or as source of resistance genes that can be expressed in plants to control pests.

Intestinal intussusception secondary to enteritis caused by Pythium insidiosum in a bitch: case report / Intussuscepção intestinal secundária à enterite causada por Pythium insidiosum em uma cadela: relato de caso

We report a case of intestinal intussusception secondary to enteritis caused by Pythium insidiosum infection in a 1-year-old mixed breed bitch that died after a 30-day history of bloody diarrhea, anorexia, weight loss, listlessness, dehydration, and pale mucous membranes. Necropsy revealed two areas of intussusception, one jejunum-jejunal and one ileum-cecum-colic. The first intussusception showed slight congestion of the intestinal loop, which was resolved by manual traction, while the second intussusception exhibited thickening, irregular yellow spots, and transmural congestion. Histologically, the jejunum-jejunal segment had ischemic lesions secondary and ileum-cecum-colic intussusception there was also necrotizing, pyogranulomatous enteritis associated with negative images of intralesional fungal hyphae that were well visualized by silver impregnation. Immunohistochemistry identified the hyphae as Pythium insidiosum. The diagnosis was made based on the histological changes and confirmed by immunohistochemistry. We can conclude that enteritis by P. insidiosum in dogs can occasionally cause intestinal intussusception and result in acute death.(AU)

Relata-se um caso de intussuscepção intestinal secundária à enterite causada por Pythium insidiosusm em uma cadela, sem raça definida, com um ano de idade, que morreu após apresentar 30 dias de diarreia sanguinolenta, anorexia, perda de peso, apatia, desidratação e mucosas pálidas. Na necropsia verificaram-se duas áreas de intussuscepções, sendo uma jejuno-jejunal e outra íleo-ceco-cólica. Na primeira havia discreta congestão, que foi desfeita pela tração manual, e na segunda observou-se espessamento segmentar, focos amarelados irregulares e congestão transmural do intestino. Microscopicamente, no segmento jejuno-jejunal observaram-se moderadas lesões isquêmicas secundárias à intussuscepção, e no segmento íleo-ceco-cólica verificou-se enterite piogranulomatosa e necrosante, segmentar, associada a imagens negativas de hifas intralesionais, impregnadas pela prata. Pela imuno-histoquímica, as hifas foram imunomarcadas para Pythium insidiosum. O diagnóstico foi realizado com base nas características microscópicas das lesões e morfotintoriais das hifas e foi confirmado pela imuno-histoquímica. De acordo com esses dados, é possível concluir que a infecção intestinal por P. insidiosum em cães pode causar intussuscepção e morte.(AU)

Restless legs syndrome in Wilson's disease: frequency, characteristics, and mimics.

OBJECTIVE: To determine characteristics, clinical significance, frequency, and mimics of restless legs syndrome (RLS) in a cohort of Wilson's disease (WD, n = 42/f = 18), compared to healthy, matched controls. MATERIALS AND METHODS: Structured clinical interviews (patients and caregiving family members), repeated neurological examinations (afternoon and presleep), comprehensive laboratory tests, WD-, RLS-, and sleep-specific rating scales, and video-polysomnography. RESULTS: Thirteen patients with WD (13/42 = 31.0%) clearly fulfilled the five diagnostic criteria of RLS; in eight patients (19.1%), the burden of RLS was clinically significant. The RLS was of moderate severity, equally distributed among sexes, manifested mainly in the evening and before falling asleep, and had developed mostly after clinical manifestation of WD (time elapsed 10.2 ± 14.5 years), still at a young mean age (27.5 ± 11.5 years). The known RLS-associated features were absent (normal iron and kidney parameters) or rare (positive family history, polyneuropathy). Compared to WD patients without RLS, patients with RLS were significantly elder and had suffered longer from WD. WD-specific RLS mimics as well as RLS confounding motor comorbidities (dystonia, tremor, chorea) were frequent and a diagnostic challenge; in difficult cases, the differentiation was reached by clinical observation of the motor behavior in the evening or at nighttime. CONCLUSION: RLS was frequent in this cohort of WD and might be causally related to WD. RLS should be included in the diagnostic work-up of WD. In complex motor disorders, differential diagnosis of RLS might require evening/nighttime examination and video-polysomnography. In WD patients with a clinically significant RLS, treatment with dopaminergic substances may be considered.

Isoflavones in food supplements: chemical profile, label accordance and permeability study in Caco-2 cells.

Consumers nowadays are playing an active role in their health-care. A special case is the increasing number of women, who are reluctant to use exogenous hormone therapy for the treatment of menopausal symptoms and are looking for complementary therapies. However, food supplements are not clearly regulated in Europe. The EFSA has only recently begun to address the issues of botanical safety and purity regulation, leading to a variability of content, standardization, dosage, and purity of available products. In this study, isoflavones (puerarin, daidzin, genistin, daidzein, glycitein, genistein, formononetin, prunetin, and biochanin A) from food supplements (n = 15) for menopausal symptoms relief are evaluated and compared with the labelled information. Only four supplements complied with the recommendations made by the EC on the tolerable thresholds. The intestinal bioavailability of these compounds was investigated using Caco-2 cells. The apparent permeability coefficients of the selected isoflavonoids across the Caco-2 cells were affected by the isoflavone concentration and product matrix.

Lipid content and fatty acid profile of Senegalese sole (Solea senegalensis Kaup, 1858) juveniles as affected by feed containing different amounts of plant protein sources.

A growth trial with Senegalese Sole (Solea senegalensis Kaup, 1858) juveniles fed with diets containing increasing replacement levels of fishmeal by mixtures of plant protein sources was conducted over 12 weeks. Total fat contents of muscle, liver, viscera, skin, fins and head tissues were determined, as well as fatty acid profiles of muscle and liver (GC-FID analysis). Liver was the preferential local for fat deposition (5.5-10.8% of fat) followed by fins (3.4-6.7% fat). Increasing levels of plant protein in the diets seems to be related to increased levels of total lipids in the liver. Sole muscle is lean (2.4-4.0% fat), with total lipids being similar among treatments. Liver fatty acid profile varied significantly among treatments. Plant protein diets induced increased levels of C16:1 and C18:2 n-6 and a decrease in ARA and EPA levels. Muscle fatty acid profile also evidenced increasing levels of C18:2 n-6, while ARA and DHA remained similar among treatments. Substitution of fishmeal by plant protein is hence possible without major differences on the lipid content and fatty acid profile of the main edible portion of the fish - the muscle.

The effect of the Rochagan on radiolabeling with (99m)Tc.

Radionuclides are used in nuclear medicine by variety of diagnostic procedures. The labeling of red blood cells (RBC) with (99m)Tc is a current method applied in clinical nuclear medicine. Drugs can alter this labeling and modify the disposition of the radiopharmaceuticals. The influence of Rochagan on the labeling of blood constituents with (99m)Tc was reported. Samples of blood were incubated with different concentrations of Rochagan (0%; 6.25%; 12.5%; 25%; 50%; 100%). Stannous chloride and (99m)Tc (3.7MBq/mL) were added. Plasma (P) and (RBC) were isolated and precipitated with thricloroacetic acid 5%. The insoluble (IF) and soluble fractions (SF) were separated. The %ATI in RBC, IF-P and IF-RBC were calculated. The %ATI on RBC decreased significantly (p<0.05) from control to all concentrations of Rochagan, respectively: 90.15 + or - 0.14(control) to 70.80 + or - 4.21; to 64.36 + or - 0.33; to 57.30 + or - 1.56; to 50.28 + or - 2.71; to 42.41 + or - 2.24; on IF-RBC, respectively: 84.70 + or - 0.87(control) to 67.16 + or - 4.38; to 63.63 + or - 2.92; to 59.02 + or - 3.17; to 43.75 + or - 1.00; to 24.15 + or - 0.94 and also on IF-P, respectively: 83.46 + or - 1.09(control) to 50.90 + or - 3.36; to 35.46 + or - 4.13; to 35.78 + or - 2.31; to 28.74 + or - 3.09; to 19.66 + or - 1.34. The analyses were performed by T-Student and Mann Whitney tests, p<0.05. This effect was probably due to products present in Rochagan that may complex with ions or have a direct/indirect effect on intracellular stannous ion concentration.

Aerosols concentration in the Candiota area applying different gravimetric methods of sampling and numeric modelling.

The main purpose of the present work is to study the concentration of atmospheric particles in the Candiota region, in the state of Rio Grande do Sul, where the Presidente Médici coal power plant is located. Aerosol samples were collected at the studied locations between December 2000 and December 2001 during 24 h periods at 15 day intervals using HV PM10 and dichotomous samplers. Then, the values obtained with the ISCST (Industrial Source Complex Term) model, with the HV PM10 sampler at all studied stations, and with the dichotomous sampler at the 8 de Agosto station were compared with each other. The results show that the values for the model had been underestimated in relation to the HV PM10 data for the studied stations, but agreed with the values obtained with the dichotomous sampler.

A single strain of Mycobacterium bovis bacillus Calmette-Guérin (BCG) grown in two different media evokes distinct humoral immune responses in mice.

Two attenuated bacillus Calmette-Guérin (BCG) preparations derived from the same Moreau strain, Copenhagen but grown in Sauton medium containing starch and bacto-peptone (onco BCG, O-BCG), or asparagine (intradermal BCG, ID-BCG), exhibited indistinguishable DNA sequences and bacterial morphology. The number of viable bacilli recovered from spleen, liver and lungs was approximately the same in mice inoculated with the vaccines and was similarly reduced (over 90%) in mice previously immunized with either BCG vaccine. The humoral immune response evoked by the vaccines was, however, distinct. Spleen cell proliferation accompanying the growth of bacilli in tissue was significantly higher in mice inoculated with O-BCG. These cells proliferated in vitro upon challenge with the corresponding BCG extract. Previous cell treatment with mAb anti-CD4 T cells abolished this effect. Anti-BCG antibodies, as assayed either in serum by ELISA or by determining the number of antibody-producing spleen cells by the spot-ELISA method, were significantly higher in mice inoculated with ID-BCG. Anti-BCG antibodies were detected in all immunoglobulin classes, but they were more prevalent in IgG with the following distribution among its isotypes: IgG1>(IgG2a = IgG2b)>IgG3. When some well-characterized Mycobacterium tuberculosis antigens were used as substitutes for BCG extracts in ELISA, although antibodies against the 65-kDa and 96-kDa proteins were detected significantly, antibodies against the 71-kDa, 38-kDa proteins and lipoarabinomannan were only barely detected or even absent. These results indicate that BCG bacilli cultured in Sauton-asparagine medium permitted the multiplication of bacilli, tending to induce a stronger humoral immune response as compared with bacilli grown in Sauton-starch/bacto-peptone-enriched medium.

A single strain of Mycobacterium bovis bacillus Calmette-Guérin (BCG) grown in two different media evokes distinct humoral immune responses in mice

Two attenuated bacillus Calmette-Guérin (BCG) preparations derived from the same Moreau strain, Copenhagen but grown in Sauton medium containing starch and bacto-peptone (onco BCG, O-BCG), or asparagine (intradermal BCG, ID-BCG), exhibited indistinguishable DNA sequences and bacterial morphology. The number of viable bacilli recovered from spleen, liver and lungs was approximately the same in mice inoculated with the vaccines and was similarly reduced (over 90 percent) in mice previously immunized with either BCG vaccine. The humoral immune response evoked by the vaccines was, however, distinct. Spleen cell proliferation accompanying the growth of bacilli in tissue was significantly higher in mice inoculated with O-BCG. These cells proliferated in vitro upon challenge with the corresponding BCG extract. Previous cell treatment with mAb anti-CD4 T cells abolished this effect. Anti-BCG antibodies, as assayed either in serum by ELISA or by determining the number of antibody-producing spleen cells by the spot-ELISA method, were significantly higher in mice inoculated with ID-BCG. Anti-BCG antibodies were detected in all immunoglobulin classes, but they were more prevalent in IgG with the following distribution among its isotypes: IgG1>(IgG2a = IgG2b)>IgG3. When some well-characterized Mycobacterium tuberculosis antigens were used as substitutes for BCG extracts in ELISA, although antibodies against the 65-kDa and 96-kDa proteins were detected significantly, antibodies against the 71-kDa, 38-kDa proteins and lipoarabinomannan were only barely detected or even absent. These results indicate that BCG bacilli cultured in Sauton-asparagine medium permitted the multiplication of bacilli, tending to induce a stronger humoral immune response as compared with bacilli grown in Sauton-starch/bacto-peptone-enriched medium

Coinfection by Strongyloides stercoralis in blood donors infected with human T-cell leukemia/lymphoma virus type 1 in São Paulo City, Brazil.

The frequency of coinfection with Strongyloides stercoralis and human T-cell leukemia/lymphoma virus type 1 (HTML-1) was determined in 91 blood donors examined at the blood bank of a large hospital in São Paulo city, Brazil. As control group 61 individuals, not infected by HTLV-1, were submitted to the same techniques for the diagnosis of S. stercoralis infection. In HTLV-1 infected patients the frequency of S. stercoralis infection was 12.1%; on the other hand, the control group showed a frequency significantly lower of S. stercoralis infection (1.6%), suggesting that HTLV-1 patients should be considered as a high risk group for strongyloidiasis in São Paulo city.

Role of cytokines and nitric oxide in the induction of tuberculostatic macrophage functions.

The aim of this study was to determine phenotypic differences when BCG invades macrophages. Bacilli prepared from the same BCG primary seed, but produced in different culture media, were analysed with respect to the ability to stimulate macrophages and the susceptibility to treatment with cytokines and nitric oxide (NO). Tumour necrosis factor (TNF) activity was assayed by measuring its cytotoxic activity on L-929 cells, interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) were assayed by enzyme-linked immunosorbent assay (ELISA), whereas NO levels were detected by Griess colorimetric reactions in the culture supernatant of macrophages incubated with IFN-gamma, TNF or NO and subsequently exposed to either BCG-I or BCG-S. We found that BCG-I and BCG-S bacilli showed different ability to simulate peritoneal macrophages. Similar levels of IL-6 were detected in stimulated macrophages with lysate from two BCG samples. The highest levels of TNF and IFN-gamma were observed in macrophages treated with BCG-S and BCG-I, respectively. The highest levels of NO were observed in cultures stimulated for 48 h with BCG-S. We also found a different susceptibility of the bacilli to exogenous treatment with IFN-gamma and TNF which were capable of killing 60 and 70% of both bacilli, whereas NO was capable of killing about 98 and 47% of BCG-I and BCG-S, respectively. The amount of bacilli proportionally decreased with IFN-gamma and TNF, suggesting a cytokine-related cytotoxic effect. Moreover, NO also decreased the viable number of bacilli. Interestingly, NO levels of peritoneal macrophages were significantly increased after cytokine treatment. This indicates that the treatment of macrophages with cytokines markedly reduced bacilli number and presented effects on NO production. The results obtained here emphasize the importance of adequate stimulation for guaranteeing efficient killing of bacilli. In this particular case, the IFN-gamma and TNF were involved in the activation of macrophage bactericidal activity.

Evaluation of the polarographic technique for assay of the viability of freeze-dried BCG vaccine: II. Viability of the vaccine assessed by polarography, Warburg respirometry and colony counting.

A comparative study of the viability of 34 lots of freeze-dried BCG vaccine has been carried out using an oxygen electrode polarographic technique, Warburg respirometry and colony counting. There were no statistical differences between the results obtained with the polarographic and Warburg techniques. Both methods gave reliable and similar results and showed a positive correlation (r = 0.8615). Comparison between the polarographic and colony-counting methods showed a positive correlation (r = 0.6530); for comparison between the Warburg and colony-counting methods, the correlation value was r = 0.6868. All the tests were significant at the level of alpha = 0.05. The advantages of the polarographic technique are that it is much less time- and material-consuming than other methods. It is a reliable, inexpensive and convenient method for BCG vaccine quality control.

Implicacoes medicas e socio-economicas do tabagismo em familias de baixa renda em Sao Paulo (Capital). / Medical and socio-economic involvements of smoking in low-income families in Sao Paulo (Capital)

Foi realizada uma pesquisa entre as puerperas de duas maternidades de Sao Paulo, procurando-se determinar algumas implicacoes medicas e socio-economicas do tabagismo em familias de baixa renda. Concluiu-se que uma parcela significativa do orcamento familiar e destinada ao tabagismo (media de 9,8%), sendo superior as fatias orcamentarias destinadas aos gastos com transporte (media 5,8%) e com a compra de leite (media de 8,3%)