A triple-masked, two-center, randomized parallel clinical trial to assess the superiority of eight weeks of grape seed flour supplementation against placebo for weight loss attenuation during perioperative period in patients with cachexia associated with colorectal cancer: a study protocol

BackgroundProgressive, involuntary weight and lean mass loss in cancer are linked to cachexia, a prevalent syndrome in gastrointestinal malignancies that impacts quality of life, survival and postoperative complications. Its pathophysiology is complex and believed to involve proinflammatory cytokine-mediated systemic inflammation resulting from tumor-host interaction, oxidative stress, abnormal metabolism and neuroendocrine changes. Therapeutic options for cachexia remain extremely limited, highlighting the need for clinical research targeting new interventions. Thus, this study primarily assesses the effects of grape-seed flour (GSF), rich in polyphenols and fibers, for attenuating perioperative weight loss in colorectal cancer.MethodsThis is a dual-center, triple-masked, placebo-controlled, parallel-group, phase II, randomized clinical trial designed to investigate GSF supplementation in subjects with pre- or cachexia associated with colorectal cancer during the perioperative period. Eighty-two participants will receive 8g of GSF or cornstarch (control) for 8 weeks. Assessments are scheduled around surgery: pre-intervention (4 weeks prior), day before, first week after, and post-intervention (4 weeks later). The primary endpoint is the difference in body weight mean change from baseline to week 8. The secondary endpoints describe the harms from 8-week supplementation and assess its superiority to improve body composition, post-surgical complications, quality of life, anorexia, fatigue, gastrointestinal symptoms, and handgrip strength. The study will also explore its effects on gut bacteria activity and composition, systemic inflammation, and muscle metabolism.DiscussionThe current trial addresses a gap within the field of cancer cachexia, specifically focusing on the potential role of a nutritional intervention during the acute treatment phase. GSF is expected to modulate inflammation and oxidative stress, both involved in muscle and intestinal dysfunction. The research findings hold substantial implications for enhancing the understanding about cachexia pathophysiology and may offer a new clinical approach to managing cachexia at a critical point in treatment, directly impacting clinical outcomes.Trial registrationThe Brazilian Registry of Clinical Trials (ReBEC), RBR-5p6nv8b; UTN: U1111-1285-9594. Prospectively registered on February 07, 2023

Influence of aerobic physical training in the motochondrial transport of long chain fatty acids in the skeletal muscle: role of the carnitine palmitoil transferase

O ácido graxo (AG) é uma importante fonte de energia para o músculo esquelético. Durante o exercício sua mobilização é aumentada para suprir as necessidades da musculatura ativa. Acredita-se que diversos pontos de regulação atuem no controle da oxidação dos AG, sendo o principal a atividade do complexo carnitina palmitoil transferase (CPT), entre os quais três componentes estão envolvidos: a CPT I, a CPT II e carnitina acilcarnitina translocase. A função da CPT I durante o exercício físico é controlar a entrada de AG para o interior da mitocôndria, para posterior oxidação do AG e produção de energia. Em resposta ao treinamento físico há um aumento na atividade e expressão da CPT I no músculo esquelético. Devido sua grande importância no metabolismo de lipídios, os mecanismos que controlam sua atividade e sua expressão gênica são revisados no presente estudo. Reguladores da expressão gênica de proteínas envolvidas no metabolismo de lipídios no músculo esquelético, os receptores ativados por proliferadores de peroxissomas (PPAR) alfa e beta, são discutidos com um enfoque na resposta ao treinamento físico.Fatty acids are an important source of energy for the skeletal muscle. During exercise, their mobilization is increased to supply the muscle energetic needs. Many points of regulation act in the fatty acids metabolism, where the carnitine palmytoiltransferase (CPT) complex is the main control system. Three compounds named CPT I, CPT II and carnitine acyl carnitine translocase (CACT) are components of this system. Its function is to control the influx of fatty acids inside the mitochondria for posterior oxidation and energy production. There is a pronounced increase in both activity and gene expression of CPT I in the skeletal muscle in response to exercise. Due to its importance in lipid metabolism, the controlling mechanisms are reviewed in the present study. The modulation of gene expression by peroxisome proliferator-activated receptors (PPARs) alpha and beta during the physical training is also discussed in this review

TERAPIA DE PRESSÃO NEGATIVA NO TRATAMENTO DE ÚLCERAS INFECTADAS COMPLEXAS DO PÉ: ESTUDOS DE CASO

Introdução: O pé diabético é uma das complicações mais graves dos doentes com Diabetes Mellitus. As feridas complexas do pé são um desafio muito comum na prática clínica e o tratamento clássico nem sempre se mostra eficaz. É, portanto, fundamental desenvolver terapêuticas alternativas para esta patologia. Objetivos: Analisar os resultados da aplicação de Terapia de Pressão Negativa (TPN) no tratamento de úlceras do pé em doentes diabéticos. Metodologia: Foi efetuado um estudo observacional, retrospetivo e únicentrico de doentes diabéticos com feridas complexas do pé tratadas com recurso a TPN durante o período de 1 fevereiro a 30 de novembro de 2019. As variáveis analisadas foram o encerramento completo da lesão, a recidiva de úlcera e a necessidade de amputação major. Resultados: Foram incluídos neste estudo de casos três doentes com lesões do pé classificadas como grau 4 (escala de Wegner). Nos três casos obteve-se encerramento completo da ferida, não tendo havido necessidade de amputação major. Durante os 15 meses de follow-up não se verificou recidiva ou outras intercorrências e todos os doentes referem ter uma qualidade de vida semelhante ao período prévio à patologia tratada. Discussão e conclusão: O recurso à TPN permitiu reduzir o edema local, remover o exsudato, estimular a neoangiogénese e reduzir a proliferação bacteriana. Esta técnica, quando comparada com o tratamento clássico parece proporcionar maior conforto para o doente. A TPN, com ou sem instilação, revelou-se uma ótima opção para o tratamento de feridas complexas do pé diabético. Pela facilidade de aplicação e pela sua eficácia, mostra-se promissora na redução da duração do tratamento e dos custos que este acarreta.N/

Antimicrobial Resistance and Extended-Spectrum Beta-Lactamase Production in Enterobacteriaceae Isolates from Household Cats (Felis silvestris catus)

Background: In Brazil, cats in households has recently increased dramatically, likely due to their lower space and care requirements. We need to know the health of these companion animal species, since they have behavioral patterns that make them an important link in the epidemiological chain. Extended spectrum beta-lactamase producer strains (ESBL) are resistant to penicillin, cephalosporin and monobactam, but they are susceptible to clavulanate. The goal of this study is to detect strains of Enterobacteriaceae that produce extended spectrum beta-lactamase (ESBL) and evaluate the bacterial resistance profile in isolated cats (Felis silvestris catus) that live in a city located at west of Parana state, Brazil.Materials, Methods & Results: Swabs were aseptically collected from the anal orifice and oral cavity of 49 female domestic cats that were healthy upon clinical and physical examination, a minimum age of one year, weighing up to 3 kg, and had attended a veterinary clinic specializing in cats, in order to, later, perform the isolation and bacterial identification, antimicrobial sensibility phenotypic test and the phenotypic test to detect ESBL producer strains. From the 98 swabs collected it was possible to perform the bacterial isolation in 68 samples; 40.81% isolated from anal orifice and 28.57% isolated from oral cavity. From rectal and oral cavities 77.50% and 71.42% of the isolated were identified as Escherichia coli respectively, being 2.94% considered ESBL producer strains. In relation to bacterial resistance the antibiotics that shown more resistance in anal orifice were ampicillin, amoxicillin, nalidixic acid, sulfazotrim, tetracycline and aztreonam. In oral cavity they were ampicillin, amoxicillin, cefoxitin, amoxicillin + clavulanate, aztreonam, ceftriaxone and nalidixic acid; and the bacterial resistance index shown that 39.70% were considered high level risk.Discussion: Household cats have a very important role in society, since the benefits they provide to their owners are clear, however, it is worth pointing out that these animals also pose risks to human health, caused by the transmission of zoonoses and also the possibility of transfer of antimicrobial resistance genes between bacteria of animal and human origin, as well as between bacteria of the normal microbiota and pathogenic microorganisms of diferents origins. Therefore, it is important to understand the health of these companion animal species, because they exhibit behavioral patterns that make them an important link in the epidemiological chain of potentially infectious microorganisms, which may show antimicrobial resistance. Extended spectrum beta-lactamase producer strains (ESBL) are resistant to penicillin, cephalosporin and monobactam, but they are susceptible to clavulanate. These enzymes hydrolyze the beta-lactam ring of the antibiotic structure, inactivating them. Nowadays bacterial resistance is considered to be one of the greatest problems in public health worldwide, as infections and diseases outbraks are caused by multiresistant bacteria are more and more frequent. The results of this study demonstrate the presence of strains of Enterobacteriaceae family associated to the high bacterial resistance, with samples that indicate ESBL producer strains in domiciled cats, in a city of west Parana state in Brazil. These results confirm that these cats can be considered as reservoirs of different microbial agents and resistance gens, being a health problem by the possibility of dissemination. The cat population is multiplying in a higher proportion compared to dogs and may probably became predominant in less than one decade. Due this situation and thinking about human, animal and environmental health new phenotypic studies to confirm the resistance gens and ESBL producers should be conducted in this specie

Toxoplasmosis seroepidemiology in pregnant women in a city in the Northwest region of the Paraná State, Brazil

Toxoplasmosis is a zoonosis caused by the Toxoplasma gondii protozoa. The congenital form happens when the parasite reaches the fetus through the placenta and causes damages of different intensities, which can be consequence of the strain virulence, of the immune response capability of the pregnant woman or even of the pregnancy stage, and can result in fetal death or severe clinical symptomatology. The aim of this paper was to determine the prevalence of antibodies to Toxoplasma gondii antibodies in pregnant woman seen at the Basic Health Units (BHU) in the city of Umuarama (PR) and check for possible toxoplasmosis associations with social-demographic characteristics, behavior and environmental variables. In this study, a total of 813 pregnant women who had their prenatal exams at the BHU in the city of Umuarama (PR) were included. Blood samples collected from these subjects were submitted to IgG and IgM anti-T. gondii antibody survey. Each pregnant woman answered an epidemiological questionnaire for the detection of variables, which were later analyzed by the EpiInfo program. The prevalence detected for IgG and IgM anti-T. gondii antibodies were 56.8% and 1.0%, respectively. The variables age group, education level, per capita income, number of pregnancies, ingestion of fresh sausage, presence of peridomiciliary cats in the backyard and the habit of ingesting farm milk showed association to the infection by T. gondii

Spectrum of molecular alterations detected in the CYP21A2 gene associated with 21-hydroxylase deficiency

A maioria dos doentes com hiperplasia suprarrenal congénita (HSC) apresenta alterações moleculares no gene CYP21A2, o qual codifica a enzima 21-hidroxilase (21-OH). Os doentes com a forma clássica de deficiência em 21-OH (21-OHD) apresentam a síntese de cortisol diminuída no córtex adrenal e, os casos mais graves, também apresentam deficiência de aldosterona. As mulheres com 21-OHD grave apresentam excesso de andrógenos desde a sua vida fetal conduzindo à virilização dos órgãos genitais externos. Tanto homens como mulheres com 21-OHD completa não sintetizam a aldosterona e, consequentemente, logo após o nascimento, podem desenvolver crises de perda de sal se não forem corretamente diagnosticados e tratados. A 21- OHD não clássica é devida à deficiência parcial em 21-OH, os fenótipos clínicos são menos graves, as mulheres não apresentam virilização dos genitais externos ao nascimento, e geralmente os sinais relativos a excesso de androgénios podem surgir durante a infância ou até mais tarde (durante ou após a puberdade). Neste trabalho descrevem-se as alterações e os genótipos mais frequentes encontrados em doentes portugueses não adultos com 21-OHD. As alterações mais frequentes encontradas na forma clássica da HSC são c.293-13C> G, diferentes deleções/quimeras/conversões génicas do gene CYP21A2 e c.518T> A, enquanto na 21-OHD não-clássica a variante c.844G> T é a mais frequente. Estes resultados contribuem para um diagnóstico correto e uma melhor gestão clínica dos doentes, para o seu aconselhamento genético e para oferecer o diagnóstico pré-natal a casais com risco de ter filhos afetados com a forma clássica de 21-OHD.Most of the patients with congenital adrenal hyperplasia (CAH) have molecular alterations in the CYP21A2 gene, which encodes the enzyme 21-hydroxylase (21-OH). Patients with the classic form of 21-OH deficiency (21-OHD) have the synthesis of cor tisol impaired in the adrenal cor tex and, the most severe cases also have aldosterone deficiency. Females with severe 21-OHD, star ting their fetal life have excess of androgens leading to external genitalia virilization at bir th. Both males and females with complete 21-OHD are not able to synthesize aldosterone, consequently soon af ter bir th may develop salt wasting crises if not correctly diagnosed and treated. Non-classic 21-OHD is due to par tial deficiency of 21-OH, the clinical phenotypes are less severe, females don’t present ambiguity of the external genitalia at bir th, usually signs of androgen excess may be present during childhood or even later in life (during or af ter puber ty). We present here the most frequent alterations and genotypes found in non adult Por tuguese patients with 21-OHD. The most frequent alterations found in the classic form of CAH are c.293-13C>G, dif ferent CYP21A2 deletions/quimeras/gene conversions and c.518T>A, while in non-classic 21-OHD the variant c.844G>T is the most frequent. These results contribute to a correct patient diagnosis, to a better clinical care, genetic counseling and to of fer pre-natal diagnosis to couples at risk of having af fected babies with the classic form of 21-OHD.info:eu-repo/semantics/publishedVersio