Ontogenetic and sexual differences in the venom of Bothrops moojeni: insights from a litter and its mother.

Variability in snake venom composition is well-documented and crucial for understanding snake ecology and predicting snakebites. In this study, we characterize the venom composition and biological activities of newborn female and male Bothrops moojeni and their mother. Our results reveal significant differences between the venom of newborn females and males, demonstrating a broad and diverse range of proteins. The venoms of newborn females showed higher serine protease effects, increased hemorrhagic activity, and greater lethality compared to the venom of newborn males. However, no differences were observed in phospholipase A2 and coagulant activity. The differences in protein composition and toxic activities between maternal and neonatal venom, as well as between the venoms of newborn females and males, contribute to understanding the diverse outcomes of snakebites. These results underscore the importance of considering sex and ontogeny in understanding venom composition in snakes.

Improving a herbicide risk assessment model in paddy rice cultivation.

Herbicides play a pivotal role in paddy rice cultivation by effectively controlling weeds, thus ensuring optimal resource utilisation and higher crop yields, making them indispensable for efficient rice production systems. However, herbicide applications could be related to potential environmental impacts such as water contamination and harm to non-target species, requiring special attention in their management to ensure the long-term sustainability of rice farming practices. The development and utilisation of robust risk assessment indicators for pesticides are essential tools in evaluating and mitigating potential environmental and human health hazards associated with pesticide use in agricultural practices. The Environmental Potential Risk Indicator for Pesticides (EPRIP) is not suitable for rice paddy cultivation due to its limitations in accurately assessing pesticide risk in this specific agricultural context. This is primarily attributed to the unique hydrological characteristics and ecosystem dynamics of paddy fields, which significantly differ from other agricultural systems. To address this issue and to enhance the accuracy of pesticide risk assessment in rice paddy fields, EPRIP has been improved and validated in two agricultural seasons. A synergistic approach involving field experiments and enhanced EPRIP model simulations was employed to assess the risk associated with the application of two herbicides in Italian paddy rice systems. The observed and model-predicted surface water (SW) concentrations exhibited a close alignment, though an overestimation was observed for groundwater (GW). In general, the estimated Risk Points (1 for SW and 4 for GW) were largely in accord with those derived from the field experiments (1 for SW and 3 for GW), suggesting that the refined EPRIP model holds promise for conducting reliable risk assessments following herbicide applications in such contexts.

Treatment patterns and outcomes in metastatic castration-resistant prostate cancer patients with and without somatic or germline alterations in homologous recombination repair genes.

BACKGROUND: Although germline BRCA mutations have been associated with adverse outcomes in prostate cancer (PC), understanding of the association between somatic/germline alterations in homologous recombination repair (HRR) genes and treatment outcomes in metastatic castration-resistant PC (mCRPC) is limited. The aim of this study was to investigate the prevalence and outcomes associated with somatic/germline HRR alterations, particularly BRCA1/2, in patients initiating first-line (1L) mCRPC treatment with androgen receptor signalling inhibitors (ARSi) or taxanes. PATIENTS AND METHODS: Data from 729 mCRPC patients were pooled for CAPTURE from four multicentre observational studies. Eligibility required 1L treatment with ARSi or taxanes, adequate tumour samples and biomarker panel results. Patients underwent paired normal and tumour DNA analyses by next-generation sequencing using a custom gene panel including ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2, RAD51B and RAD54L. Patients were divided into subgroups based on somatic/germline alteration(s): with BRCA1/2 mutations (BRCA); with HRR mutations except BRCA1/2 (HRR non-BRCA); and without HRR alterations (non-HRR). Patients without BRCA1/2 mutations were classified as non-BRCA. Radiographic progression-free survival (rPFS), progression-free survival 2 (PFS2) and overall survival (OS) were assessed. RESULTS: Of 729 patients, 96 (13.2%), 127 (17.4%) and 506 (69.4%) were in the BRCA, HRR non-BRCA and non-HRR subgroups, respectively. BRCA patients performed significantly worse for all outcomes than non-HRR or non-BRCA patients (P < 0.05), while PFS2 and OS were significantly shorter for BRCA than HRR non-BRCA patients (P < 0.05). HRR non-BRCA patients also had significantly worse rPFS, PFS2 and OS than non-HRR patients. Exploratory analyses suggested that for BRCA patients, there were no significant differences in outcomes associated with 1L treatment choice (ARSi or taxanes) or with the somatic/germline origin of the alterations. CONCLUSIONS: Worse outcomes were observed for mCRPC patients in the BRCA subgroup compared with non-BRCA subgroups, either HRR non-BRCA or non-HRR. Despite its heterogeneity, the HRR non-BRCA subgroup presented worse outcomes than the non-HRR subgroup. Screening early for HRR mutations, especially BRCA1/2, is crucial in improving mCRPC patient prognosis.

Correlação entre as atividades antiradical, antiacetilcolinesterase e teor de fenóis totais de extratos de plantas medicinais de farmácias vivas / Correlation between the anti-radical, anti-acetylcholinesterase activities and phenolic content of some extracts of live herbal pharmacies in the Northeast of Brazil

O objetivo deste trabalho foi avaliar a correlação entre o conteúdo de fenóis de extratos de 18 plantas medicinais comuns nas Farmácias Vivas com a atividade sequestradora do radical livre DPPH e com a inibição da enzima acetilcolinesterase. Maiores conteúdos de fenóis totais foram encontrados nas plantas: Eugenia uniflora, Lippia alba, Lippia microphylla, Mentha x villosa, Ocimum gratissimum e Ocimum selloi. As espécies que apresentaram maior atividade antioxidante, semelhante a quercetina, foram: Spondias mombim, Malphigia glabra, L. alba e Croton zenhtneri,. As plantas Cecropia pachystachia, L. alba, L. microphylla, M. glabra, O. gratissimum e Plectranthus ornatus mostraram maiores halos de inibição da enzima acetilcolinesterase. Combinando as duas ações, as plantas mais ativas foram a M. glabra e a L. alba e somente a segunda correlaciona-se diretamente com o maior teor de fenóis totais. Através deste estudo, M. glabra e L. alba foram consideradas as plantas mais promissoras para estudos subsequentes a fim de encontrar novos compostos com ação potencial contra a doença de Alzheimer.

The purpose of this study was to evaluate the phenolic content of 18 medicinal plant extracts of "Live Pharmacies" and correlate them with their free radical scavenging activity and inhibition of the acetylcholinesterase enzyme. Higher amounts of phenolic compounds were found in the following plants: Eugenia uniflora, Lippia alba, Lippia microphylla, Mentha x villosa, Ocimum gatissimum, and Ocimum selloi. The species that showed higher anti-radical activity were Croton zenhtneri, Lippia alba, Malphigia glabra, and Spondias mombim, similar to quercetin. The plants Cecropia pachystachia, L. alba, L. microplylla, M. glabra, O. gratissimum, and Plectranthus ornatus showed larger inhibition zones of the acetylcholinesterase enzyme. By correlating the two actions L. alba and M. glabra are common as more active to both tests and only L. alba correlates directly with the phenolic content. Through this study, L. alba and M. glabra are considered the most promising plants for further studies to find new compounds with potential action against Alzheimer's disease.

Comparison of blood neoangiogenesis and lymphatic vascularization in colorectal adenomas from patients with and without concomitant colorectal cancer

Blood and lymphatic vessel proliferation is essential for tumor growth and progression. Most colorectal carcinomas develop from adenomas (adenoma-carcinoma sequence) in a process due to accumulation of molecular genetic alterations. About 5% of adenomatous polyps are expected to become malignant, but data on the differential angiogenic patterns of these lesions in patients with and without concomitant cancer are missing. The aim of the present study is to compare the angiogenic and lymphatic patterns of adenomatous polyps from patients with and without sporadic cancer. Thirty adenomatous polyps (15 from patients with another principal malignant lesion, and 15 from patients without cancer) were submitted to immunohistochemical staining for CD105 (marker for neoangiogenesis) and D2-40 (marker for lymphatic endothelium). Microvessel density and total vascular area were determined by computer image analysis to quantify the immunostained and total areas, and to assess the number of microvessels. Adenomas from patients with carcinoma showed significantly higher values of total vascular area determined by immunostaining for CD105 (cutoff value = 4386 µm²; P = 0.019) and of lymphatic microvessel density determined by immunostaining with D2-40 (cutoff value = 11.5; P = 0.041) when compared with those from patients without cancer. The present data indicate a significant increase in blood microvascular area and in lymphatic microvascular counts in adenomas removed from patients with cancer.

Paraganglioma gangliócítico do duodeno: relato de um caso / Gangliocytic paraganglioma of the duodenum: a case report

É apresentado um caso de paraganglioma gangliocítico da região da papila duodenal em paciente masculino de 51 anos, com queixa de dor epigástrica e empachamento pós-prandial. O paraganglioma gangliocítico é neoplasia rara no trato gastrointestinal, onde o local mais acometido é a região periampular do duodeno. A constituição por três tipos celulares permite sua identificação bem como diagnóstico diferencial com outros tumores um pouco mais comuns no local, como o carcinóide duodenal, o ganglioneuroma e o tumor estromal gastrointestinal (GIST).

CagA y erradicación de Helicobacter pylori en pacientes con dispepsia / CagA status and Helicobacter pylori eradication among dyspeptic patients

Objetivo: El tratamiento triple parece tener una eficacia mayor en la curación de la infección por Helicobacter pylori en los pacientes con úlcera péptica, en comparación con los pacientes que presentan dispepsia de origen no ulceroso. Se ha señalado que esta diferencia depende de la expresión de la proteína CagA, que es más frecuente en los primeros. El objetivo de este estudio ha sido la investigación de una posible asociación entre la positividad sérica para CagA, la intensidad de la inflamación de la mucosa gástrica y el buen resultado de la erradicación de la infección por H. pylori en pacientes con úlcera péptica y en pacientes con dispepsia de origen no ulceroso. Material y método: El estudio se realizó en pacientes atendidos entre marzo de 2000 y marzo de 2001 en el Department of Gastroenterology, Hospital Vera Cruz; en todos los pacientes se había indicado la realización de endoscopia gastrointestinal alta como parte del estudio de un cuadro de dispepsia. Los participantes presentaron positividad para H. pylori, tanto en la prueba rápida de la ureasa como en el estudio histológico. Se determinó la intensidad de la inflamación de la mucosa gástrica y se evaluó la positividad sérica para CagA mediante el uso de una técnica de ELISA comercializada, todo ello antes de la administración de un ciclo de tratamiento de 7 días para la erradicación de H. pylori con lansoprazol, claritromicina y amoxicilina (30 mg, 500 mg y 1 g cada 12 h, respectivamente). El resultado de la erradicación se estableció a las 8-24 de semanas de la finalización del tratamiento. Resultados: En el estudio participaron 74 pacientes (edad media, 40,8 años; rango, 18-67 años; número de mujeres, 28). Se detectó positividad para CagA en el 48% de los pacientes. El 54% de ellos presentaba úlcera péptica gastroduodenal. La positividad sérica para CagA fue significativamente mayor en los pacientes con úlcera péptica (62,5%), mientras que la negatividad sérica para CagA fue significativamente mayor en los pacientes con dispepsia de origen no ulceroso (67,7%). La intensidad de la infiltración por linfocitos y eosinófilos fue significativamente mayor en los pacientes con positividad para CagA, a pesar de que dicha intensidad fue similar entre los pacientes con úlcera péptica y en los pacientes con dispepsia de origen no ulceroso. En un análisis de protocolo individualizado, la erradicación de la infección tuvo éxito en el 93,2% de los pacientes, con independencia de la positividad o negatividad para CagA. En este tipo de análisis, el buen resultado respecto de la erradicación de la infección fue comparable en los pacientes con úlcera péptica y en los pacientes con dispepsia de origen no ulceroso, con independencia de la positividad o negatividad para CagA. Conclusión: Nuestros resultados apoyan la posibilidad de que la positividad para CagA esté asociada a la enfermedad ulcerosa péptica y a una intensidad mayor de la infiltración por linfocitos y eosinófilos. La eficacia del tratamiento de erradicación de la infección por H. pylori puede no estar influida por la positividad o negatividad sérica para CagA

Aim: Triple therapy seems more effective in curing Helicobacter pylori infection in patients with peptic ulcer than in those with non-ulcer dyspepsia. It has been suggested that this difference depends on the expression of CagA protein that is more frequent in the former. The objective of this study was to investigate a potential association between serum CagA positivity, severity of gastric mucosal inflammation and eradication success among peptic ulcer and non-ulcer dyspepsia patients. Material and method: Patients undergoing upper gastrointestinal endoscopy for investigation of dyspepsia at the Department of Gastroenterology, Hospital Vera Cruz, between March, 2000 and March 2001 were screened. H. pylori positive patients, as diagnosed by rapid urease test and histology were included. Severity of gastric mucosal inflammation was determined and serum CagA positivity was assessed using a commercially available ELISA assay prior to H. pylori 7-day eradication therapy with lansoprazole, clarithromycin and amoxicillin (30 mg, 500 mg and 1 g b.i.d., respectively). Eradication success was determined 8-24 weeks following completion of therapy. Results: Seventy-four patients were included in the study (mean age 40.8, range 18-67, female = 28). CagA positivity was observed in 48% of patients. Gastroduodenal peptic ulceration was found in 54% of patients. Serum CagA positivity was significantly higher among peptic ulcer patients (62.5%), while CagA negativity was significantly higher among non-ulcer dyspepsia patients (67.7%). Lymphocyte and eosinophil infiltration was significantly higher among CagA + patients, despite being comparable when distributed among peptic ulcer and non-ulcer dyspepsia patients. Eradication was successful in 93.2% of patients, regardless of CagA status on a per protocol analysis. Based on a per protocol analysis, eradication success was comparable among peptic ulcer and non-ulcer dyspepsia patients, regardless of CagA status. Conclusion: Our results support the concept that CagA positivity is associated to peptic ulcer disease and to a higher severity of lymphocyte and eosinophil infiltration. Efficacy of treatment eradication of H. pylori may not be affected by serum CagA status

Immunoexpression of CD95 in chronic gastritis and gastric mucosa-associated lymphomas

CD95 (Fas/APO-1)-mediated apoptosis plays an important role in immunological regulation and is related to the pathogenesis of autoimmune diseases. Immunoexpression of CD95 has been reported to frequently occur in low grade non-Hodgkin lymphomas, especially of post-germinal center histogenesis, among which those originating in mucosa-associated lymphoid tissue (MALT lymphomas). However, there is no report comparing in situ immunoexpression of this marker in lymphomas and the hyperplastic lymphoid reaction (chronic gastritis) related to Helicobacter pylori infection. The purpose of the present research was to compare the intensity of lymphoid CD95 immunoexpression in 15 cases of H. pylori-related chronic gastritis and 15 gastric MALT lymphomas. CD95 (anti-CD95) was detected by an immunoperoxidase technique in paraffin sections using the catalyzed amplification system. Graduation of reaction intensity (percentage of CD95-positive cells) was semiquantitative, from 1+ to 4+. Nine cases of chronic gastritis were 4+, five 2+ and one 1+. Three lymphomas were 4+, three 3+, four 2+, four 1+, and one was negative. Although 14 of 15 lymphomas were positive for CD95, the intensity of the reaction was significantly weaker compared to that obtained with gastric tissue for patients with gastritis (P = 0.03). The difference in CD95 immunoexpression does not seem to be useful as an isolated criterion in the differential diagnosis between chronic gastritis and MALT lymphomas since there was overlapping of immunostaining patterns. However, it suggests the possibility of a pathogenetic role of this apoptosis-regulating protein in MALT lymphomas.

Gastrite crônica associada ao Helicobacter pylori em pacientes com dispepsia näo ulcerosa e com úlcera duodenal / Chronic gastritis associated to Helicobacter pylori in patients with non-ulcerating dyspepsia and with duodenal ulcer

Prevalência da gastrite crônica e da infecçäo da mucosa gástrica por Helicobacter pylori em pacientes com dispepsia näo ulcerosa e com úlcera duodenal. Tipo de estudo, local, pacientes: Foram estudados, prospectivamente, 48 pacientes consecutivos com dispepsia näo ulcerosa (DNU) do tipo dismotilidade e 13 pacientes consecutivos com úlcera duodenal (UD) em atividade, selecionados no ambulatório de Gastrenterologia do Hospital das Clínicas da Universidade Estadual de Campinas (Unicamp). Intervençöes: Em cada um dos pacientes, foram realizadas oito biópsias endoscópicas (quatro do corpo e quatro do antro gástrico), para identificaçäo do H. pylori, utilizando-se três testes: urease, gram e exaqme histopatológico. Medidas e resultados: Nos 48 pacientes com DNU, o teste de urease foi postivo em 89,6% no antro e 81,2% no corpo; o gram foi positivo em 81,2% no antro e em 77,1% no corpo; e o H. pylori foi identificado no exame histopatológico em 79,2% no antro e em 70,8% no corpo gástrico. Na mucosa do antro gástrico de todos os 48 pacientes com DNU, pelo menos um dos três testes empregados foi positivo. Em todos os 13 pacientes com UD, os três testes foram positivos no antro gástrico, todos com gastrite crônica do antro no exame histopatológico. Gastrite crônica do corpo gástrico, com presença do HY. pylori no exame histopatológico, foi encontrada em 10 dos 13 pacientes. O teste de urease foi positivo na mucosa do corpo gástrico em todos os casos de UD. Conclusöes: Os autores acreditam que a alta prevalência dos testes empregados para identificaçäo fo H. pylori nos pacientes com DNU possa ser explicada pelo grupo selecionado de pacientes pertencentes a uma classe socioeconômica menos favorecida. A presença do H. pyloru na mucosa gástrica de todos os pacientes com UD está de acordo com algums trabalhos já publicados

Neurinoma da ampola de Vater. / Neurinoma of Vater's ampulla

Os autores relatam um caso de neurinoma ou shwannoma da ampola de Vater associado a neurofibromatose cutanea de Von Recklinghausen. Fazem revisao da literatura e discutem a conduta cirurgica nos tumores benignos desta localizacao

A biopsia do endometrio e a dosagem da progesterona plasmatica na avaliacao da funcao lutea. / Biopsy of the endometrium and plasma progesterone dosage in the evaluation of luteal function

Em 35 pacientes da clinica de esterilidade foi colhida uma biopsia do endometrio e, no mesmo dia,foi feita uma dosagem da progesterona plasmatica pela tecnica de radioimunoensaio, com o objetivo de avaliar a funcao lutea. Compararam-se os resultados e concluiu-se que a biopsia do endometrio traz mais subsidios para o diagnostico da ovulacao e para uma avaliacao geral do orgao onde deve ocorrer a nidacao.A dosagem unica da progesterona plasmatica nao permite uma avaliacao correta da funcao lutea quando o resultado obtido fica abaixo da faixa de variacao normal, porem acima de 2 ng/ml

A citologia hormonal seriada na pratica ginecologica. / Serial hormonal cytology in gynecological practice

A citologia hormonal seriada de 35 pacientes estereis foi comparada a respectiva biopsia de endometrio e a concordancia diagnostica foi de 88,5%. Os autores tiveram dois casos inconclusivos e dois erros diagnosticos, todos em pacientes que nao ovularam. A dosagem unica de progesterona pela tecnica de radioimunoensaio nao mostrou correlacao com a graduacao subjetiva da intensidade das alteracoes morfologicas vistas nos esfregacos colhidos no mesmo dia do ciclo (em torno do 24o. dia apos a ultima menstruacao). Do mesmo modo, a dosagem unica de estradiol por radioimunoensaio nao mostrou correlacao direta ou inversa com os indices picnoticos dos esfregacos colhidos no mesmo dia do ciclo (em torno do 24 dia apos a ultima menstruacao)

Desempenho de um laser do CO2 nacional para uso em cirurgias otorrinolaringologicas. / Performance of a national CO2 laser for use in otorhinolaryngologic surgery

No presente trabalho, apresentamos os resultados de cirurgias experimentais em mucosa oral de cobaias, realizadas com um laser de CO2 inteiramente construido no Instituto de Fisica da UNICAMP. Mostramos que o efeito da radiacao laser sobre o tecido e fundamentalmente dependente da densidade de energia da radiacao, a qual e inversamente proporcional ao quadrado da distancia focal da lente utilizada para concentracao do feixe laser. No caso, utilizamos lentes de 60 mm e 260 mm e para cada uma utilizamos potencias de 9, 6 e 3 Watt com tempo de exposicao de 1, 0,5 e 0,2 segundos

Actinomicose das amigdalas palatinas.Valor do exame histopatologico de rotina / Actinomycosis of the palatine tonsils.Value of routine histopathological examination

Os autores apresentam tres casos de actinomicose amigdaliana que foram achados de exames anatomo-patologicos realizados de rotina. E salientada a importancia desse diagnostico e a necessidade do exame microscopico de todas as amigdalas retiradas cirurgicamente

Colangiodisplasia intrahepatica em dois irmaos. Conceituacao da entidade. / Intrahepatic cholangiodysplasia in 2 brothers. Concept of the entity

Sao apresentados os aspectos histopatologicos da displasia das vias biliares intrahepaticas (colangiodisplasia) diagnosticada em dois irmaos, um deles assintomatico. Caracteriza-se pela proliferacao de ductos biliares interlobulares anomalos e fibrose portal, sem colestase, mas acompanhados de colangite cronica ativa. Sao discutidos diagnosticos diferenciais e a possivel genese dessas colangiodisplasia