Hypothalamic free fatty acid receptor-1 regulates whole-body energy balance.

OBJECTIVE: Free fatty acid receptor-1 (FFAR1) is a medium- and long-chain fatty acid sensing G protein-coupled receptor that is highly expressed in the hypothalamus. Here, we investigated the central role of FFAR1 on energy balance. METHODS: Central FFAR1 agonism and virogenic knockdown were performed in mice. Energy balance studies, infrared thermographic analysis of brown adipose tissue (BAT) and molecular analysis of the hypothalamus, BAT, white adipose tissue (WAT) and liver were carried out. RESULTS: Pharmacological stimulation of FFAR1, using central administration of its agonist TUG-905 in diet-induced obese mice, decreases body weight and is associated with increased energy expenditure, BAT thermogenesis and browning of subcutaneous WAT (sWAT), as well as reduced AMP-activated protein kinase (AMPK) levels, reduced inflammation, and decreased endoplasmic reticulum (ER) stress in the hypothalamus. As FFAR1 is expressed in distinct hypothalamic neuronal subpopulations, we used an AAV vector expressing a shRNA to specifically knockdown Ffar1 in proopiomelanocortin (POMC) neurons of the arcuate nucleus of the hypothalamus (ARC) of obese mice. Our data showed that knockdown of Ffar1 in POMC neurons promoted hyperphagia and body weight gain. In parallel, these mice developed hepatic insulin resistance and steatosis. CONCLUSIONS: FFAR1 emerges as a new hypothalamic nutrient sensor regulating whole body energy balance. Moreover, pharmacological activation of FFAR1 could provide a therapeutic advance in the management of obesity and its associated metabolic disorders.

Activation of G protein-coupled estrogen receptor stimulates placental human chorionic gonadotropin expression through PKA-CREB signaling.

The placenta-secreted human chorionic gonadotropin (hCG) is a hormone that plays a critical role in inducing ovarian progesterone production, which is required for maintaining normal pregnancy. The bioavailability of hCG depends on the expression of the beta-subunit of hCG (hCG-ß) which is encoded by the chorionic gonadotropin beta (CGB) gene. G protein-coupled estrogen receptor (GPER) is a membrane estrogen receptor involved in non-genomic estrogen signaling. Estradiol (E2) has been shown to stimulate hCG production. However, the role of the GPER in regulating CGB expression remains unknown. In the present study, our results revealed that treatment with G1 upregulated CGB expression in two human choriocarcinoma cell lines, BeWo and JEG-3, and primary human cytotrophoblast cells. In addition, G1 treatment activated the cAMP-response element binding protein (CREB). Using a pharmacological inhibitor and siRNA-mediated knockdown approach, we showed that the stimulatory effect of G1 on CGB expression is mediated by the protein kinase A (PKA)-CREB signaling pathway. This study increases the understanding of the role of GPER in the human placenta. In addition, our results provide important insights into the molecular mechanisms that mediate hCG expression, which may lead to the development of alternative therapeutic approaches for treating placental diseases.

Role of hysterectomy in the management of patients with gestational trophoblastic neoplasia: importance of receiving treatment in reference centers.

OBJECTIVE: To evaluate hysterectomy prevalence, indications and impact on clinical outcomes in a reference center in southern Brazil. STUDY DESIGN: Institutional Ethical Committee approval was granted for this study. In a cohort study spanning 21 years, all patients who underwent hysterectomy for gestational trophoblastic neoplasia (GTN) were included, and technical differences between hysterectomy performed in the reference center and those performed elsewhere were evaluated as well. RESULTS: Of 1,023 patients with gestational trophoblastic disease, 57 (5.6%) underwent hysterectomy (95% CI, 4.3-7.1). Hysterectomy incidence in 230 GTN patients was 17.7% (95%CI, 15.1-23.3). Indications for 41 hysterectomies in the reference center were as follows: primary treatment in 14 (34.1%) cases and secondary treatment in 27 (65.9%); of these, the main indications were GTN recurrence (7 [25.9%] cases), hemorrhage (6 [22.2%]), resistance to single-agent chemotherapy in patients who refused more aggressive treatment (6 [22.2%]), and tumor mass reduction (5 [18.5%]). Twelve (92.3%) of the 13 hysterectomies with bilateral oophorectomy were performed elsewhere (p < 0.001). Thirty-five (85.4%) patients had no complications, and median hospitalization time was short (3 +/- 4 days). None of the 4 deaths were associated with hysterectomy. In the reference center, when associated with hysterectomy, GTN cure rates reached 93% after 63 +/- 87 months of follow-up. CONCLUSION: When treatment is in a reference center, hysterectomy frequency and morbidity may be low, and indications due to hemorrhage are significantly lower. Furthermore, at a reference center there is significantly greater ovarian preservation at the time of hysterectomy, and significantly more patients who undergo hysterectomy have low-risk GTN.

Effect of exercising in water on the fibrocartilage of the deep digital flexor tendon in rats with induced diabetes.

Individuals with diabetes mellitus (DM) are affected four times more by tendinopathies than non-diabetics. On the other hand, physical activity helps to DM control. However, the effects of physical exercise in water (PEW) on the fibrocartilages present in the tendons of animals affected by DM are unknown. In this sense, the aim of this study was to analyze the structural organization and chemical composition of fibrocartilage present in the intermediate region of the deep digital flexor tendon (DDFT) of Wistar rats with alloxan-induced DM. Diabetic and non-diabetic animals were randomly separated into four experimental groups (n = 10): Non-Trained Control (NTC), Trained Control (TC), Non-Trained Diabetic (NTD), and Trained Diabetic (TD). TC and TD animals underwent the exercise protocol (total weekly training load - week 1: 14,375; 2: 16,500; 3: 18,375; 4: 20,000) and then were euthanized to collect tendon samples for analysis. The matrix basophilia was more intense in the TC and TD groups. The Decorin immunohistochemical test results showed greater intensity in the NTD and TD groups. The wet weight of the fibrocartilaginous region of the tendon (NTC:19.9 ± 0.06; TC:22.3 ± 0.05; NTD:20.3 ± 0.08; TD:21.8 ± 0.04 mg - p = 0.048), glycosaminoglycan amounts (NTC:3.21 ± 0.18; TC:3.98 ± 0.44; NTD:3.32 ± 0.19; TD:3.79 ± 0.28 µg/mg of fresh tissue - p = 0.046), and intumescence in water (NTC:13.8 ± 3.8; TC:24.3 ± 3.9; NTD:14.9 ± 3.9; TD:28.2 ± 5.3 % w/w - p = 0.042) were higher in the TC and TD groups. The TD group showed the highest levels of type I collagen and matrix metalloproteinase (MMP)-13. The TC group showed the highest and TD the lowest TGF-ß1 levels. In conclusion, the PEW was able to stimulate the deposition of proteoglycans, without inducing chemical changes that would cause histopathological modifications in fibrocartilage in the DDFT of adult rats. Thus, PEW preserves the structural organization of these tissues in tendons of animals affected by DM.

Lapatinib Inhibits Amphiregulin-induced BeWo Choriocarcinoma Cell Proliferation by Reducing ERK1/2 and AKT Signaling Pathways.

BACKGROUND: Human choriocarcinoma is the most aggressive type of gestational trophoblastic neoplasia. The expression of epidermal growth factor receptor (EGFR) in choriocarcinomas is significantly higher than those of trophoblastic cells in healthy placentas. Lapatinib is a potent EGFR and human epidermal growth factor receptor 2 (HER2) inhibitor that inhibits cell proliferation and induces apoptosis in various human cancer cells. Amphiregulin (AREG) is the most abundant EGFR ligand in amniotic fluid during human pregnancy. AIM: To explore the role of AREG in human choriocarcinoma cell proliferation. MATERIALS AND METHODS: The effect of lapatinib and AREG on cell proliferation was examined by the MTT assay. Western blots were used to investigate EGFR and HER2 expression, and the activation of caspase-3, extracellular signal-regulated kinases 1/2 (ERK1/2) and phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT) signaling pathways. RESULTS: Treatment with lapatinib reduced BeWo cell proliferation by inducing apoptosis. Moreover, AREG treatment stimulated BeWo cell proliferation by activating ERK1/2 and PI3K/AKT signaling pathways, which was blocked by lapatinib. CONCLUSION: Targeting EGFR/HER2 might be a useful therapeutic strategy for human choriocarcinoma.

Cross-cultural adaptation of the Brazilian-Portuguese version of the Perceived Nutrition Environment Measures Survey / Adaptação transcultural da versão brasileira do Perceived Nutrition Environment Measures Survey

ABSTRACT Objective The objective of this study was to cross-culturally adapt the Perceived Nutrition Environment Measures Survey for use in the Brazilian context. Methods Independent translations into Portuguese of the original version and respective back-translations into English were performed. The steps were evaluated by an expert committee and the translated version was applied in a group of both genders, of different ages and education. Results After suggested modifications in the translation processes, the expert committee considered that the translated and adapted version presented conceptual and semantic equivalence. The translated version was applied to a sample of twenty people and only one question related to the amount of fat in the food required a new round to obtain understanding and clarity. Conclusion We present an adapted version of Perceived Nutrition Environment Measures Survey for the Brazilian context, which has adequate conceptual, cultural, and semantic equivalence, being objective and comparable to the original version. Future studies should confirm clarity, reliability, and validity.

RESUMO Objetivo O objetivo deste estudo foi adaptar transculturalmente o Perceived Nutrition Environment Measures Survey para uso no contexto brasileiro. Métodos Foram realizadas traduções independentes da versão original para o português e respectivas retrotraduções para o inglês. As etapas foram avaliadas por um comitê de especialistas e a versão traduzida foi aplicada em um grupo com pacientes de ambos os sexos, de diferentes idades e níveis de escolaridade. Resultados Após modificações sugeridas nos processos de tradução, o comitê de especialistas considerou que a versão traduzida e adaptada apresentou equivalência conceitual e semântica. A versão traduzida foi aplicada a uma amostra de 20 pessoas e apenas uma questão, relacionada à quantidade de gordura no alimento, requereu nova rodada para obter compreensão e clareza. Conclusão Uma versão do Perceived Nutrition Environment Measures Survey adaptada ao contexto brasileiro, a qual possui equivalências conceitual, cultural e semântica adequadas, sendo objetiva e comparável à versão original, é apresentada. Futuros estudos devem confirmar a clareza, confiabilidade e validade.

Achados clínicos e radiológicos, perfil e evolução de pacientes internados com COVID-19 em uma enfermaria de referência em Salvador - BA / Clinical and radiological findings, profile and evolution of patients hospitalized for COVID-19 in a reference nurse in Salvador - BA

COVID-19 é a doença causada pelo coronavírus SARS-CoV-2. Esta doença foi responsável por uma pandemia no ano de 2020, que resultou em uma grande quantidade de óbitos. Nesse contexto, os exames radiológicos de pacientes com COVID-19 comumente demonstram distribuição bilateral de opacidades em vidro fosco, podendo existir consolidação periférica. Tais achados variam com a idade do paciente, progressão da doença, status da imunidade, comorbidades e intervenção médica inicial. Ademais, existem casos em que a sintomatologia do paciente não condiz com a gravidade das manifestações pulmonares. Objetivo: Analisar o perfil clínico radiológico e evolução de pacientes internados com diagnóstico de COVID-19, em uma enfermaria de um hospital de referência em Salvador-BA. Métodos: Estudo observacional, descritivo e analítico. Os dados foram coletados, por meio de análise de prontuário, acessados pelo computador (banco de dados) do Hospital Geral Ernesto Simões Filho (HGESF). Resultados: Foram coletados dados de um total de 70 pacientes. Destes, 29 (41,4%) participantes do sexo feminino e 41 (58,6%) do sexo masculino com idade variando entre menor que 60 anos (32,9%) e maior ou igual a 60 anos (67,1%), havendo 31 (44,3%) portadores de Diabetes Mellitus. Com relação aos sintomas apresentados, 59 (84,3%) pacientes cursaram com dispneia, 50 (71,4%) manifestaram tosse e 36 (51,4%) tiveram febre. Outros parâmetros clínicos como leucocitose foram evidenciados em 50 (71,4%) participantes, além da dessaturação (<90% spO2) presente em 25 (35,7%) participantes. Durante o internamento, 46 (65,7%) pacientes receberam tratamento com Azitromicina, 60(85,7%) pacientes foram transferidos para Unidade de Terapia Intensiva (UTI), 34 (48,6%) evoluíram com necessidade de intubação orotraqueal (IOT) e 32 (45,7%) foram a óbito. Tais variáveis foram analisadas junto ao percentual de acometimento pulmonar tomográfico que variou entre menor ou igual a 25% em 19 (27,1%) participantes, 26-49% em 19 (27,1%) participantes, 50-74% em 23 (32,9%) participantes e maior ou igual a 75% em 9 (12,9%) participantes. O envolvimento pulmonar foi preditor de óbito e acarretou mudança de conduta quanto ao tempo de internamento. Além disso, a presença de tosse foi constatada como um fator de alerta para o acometimento pulmonar mais grave. Ademais, o uso de azitromicina não predispôs menores percentuais de acometimento pulmonar.

COVID-19 is the disease caused by the coronavirus SARS-CoV-2. This disease was responsible for a pandemic in the year 2020, which resulted in a large number of deaths. In this context, it was noticed that the radiological examinations of patients with COVID-19 commonly demonstrate bilateral distribution of ground glass opacities, with the possibility of peripheral consolidation. Such findings vary with the patient's age, disease progression, immunity status, comorbidities and initial medical intervention. In addition, there are cases in which the patient's symptoms do not match the severity of the pulmonary manifestations. Objective: To analyze the clinical-radiological findings, profile and evolution of patients hospitalized with COVID-19 in a referral ward in Salvador-BA. MethodS: Observational, descriptive and analytical study. Data were collected through medical record analysis, accessed by the computer (database) of the Hospital Geral Ernesto Simões Filho (HGESF). Results: Data were collected from a total of 70 patients. Of these, 29 (41.4%) female participants and 41 (58.6%) male participants, aged between less than 60 years (32.9%) and greater than or equal to 60 years (67.1%), with 31 (44.3%) patients with Diabetes Mellitus. Regarding the symptoms presented, 59 (84.3%) patients had dyspnea, 50 (71.4%) had cough and 36 (51.4%) had fever. Other clinical parameters such as leukocytosis were evidenced in 50 (71.4%) participants, in addition to desaturation (<90% spO2) present in 25 (35.7%) participants. During hospitalization, 46 (65.7%) patients received treatment with Azithromycin, 60 (85.7%) patients were transferred to the intensive care unit (ICU), 34 (48.6%) envolved with the need for cheal intubation and 32 (45.7%) they died. These variables were analyzed along with the percentage of tomographic pulmonary involvement, which ranged from less than or equal to 25% in 19 (27.1%) participants, 26-49% in 19 (27.1%) participants, 50-74% in 23 (32.9%) participants and greater than or equal to 75% in 9 (12.9%) participants. Pulmonary involvement was a predictor of death and led to a change in conduct regarding the length of stay. In addition, the presence of cough was found to be an alert factor for the most severe pulmonary involvement. Furthermore, the use of azithromycin did not predispose lower percentages to pulmonary involvement

Prevalência do "Helicobacter pylory" na hipertençäo portal / Incidence of \"Helicobacter pylory\" in portal hypertension

Estudou-se a prevalência do Helicobacter pylori (Hp) em 50 pacientes com hipertensao portal (HP) de origem cirrótica (26), esquistossomótica (17) e outras causas (7) e sua posível relaçao com episódios prévios de hemorragia alta (HDA) e gastropatia congestiva (GC). Cem pacientes com dispepsia nao-ulcerosa constituíram o grupo controle. O Hp foi positivo em 81 por cento nos controles e em 56 por cento do grupo com HP (P<0,05) nao houve diferença significativa em relaçao à presença do Hp nas diferentes etiologias da HP. Foram positivos para o Hp 62,5 por cento dos pacientes com sangramento prévio de 44,4 por cento dos sem sangramento (p>0,05-NS). Cinqüenta por cento dos pacientes com GC e 66,6 por cento dos sem GC foram positivos para o Hp (p>0,05-NS). Nossos resultados sugerem que o Hp nao se relaciona com a HDA da HP nem com a GC; dessa forma, nao deve estar envolvido com as complicaçoes da síndrome. Acreditamos que nao há indicaçao para o tratamento do Hp como forma de prevenir ou atenuar o risco de sangramento na HP.