Adverse effects associated with favipiravir in patients with COVID-19 pneumonia: a retrospective study

ABSTRACT BACKGROUND: Favipiravir is generally used in treating coronavirus disease 2019 (COVID-19) pneumonia in Turkey. OBJECTIVE: To determine the side effects of favipiravir and whether it is a good treatment option. DESIGN AND SETTING: Retrospective study conducted in Atatürk Chest Diseases and Chest Surgery Training and Research Hospital, Ankara, Turkey. METHODS: 357 patients who completed favipiravir treatment at the recommended dose were included. 37 patients with drug side effects and 320 patients without drug side effects were examined in two groups. RESULTS: Side effects were observed in 37 (10.36%) out of 357 patients using favipiravir. The most common side effect was liver dysfunction, in 26 (7.28%) of the patients. The following other side effects were also observed: diarrhea (1.4%), nausea (0.84%), abdominal pain (0.28%) and thrombocytopenia (0.28%). One patient (0.28%) presented both increased transaminases and nausea. CONCLUSION: In this study, it was determined that favipiravir may constitute an alternative for treating COVID-19 pneumonia given that its side effects are generally well tolerated and not serious.

Eficácia e segurança da tripla terapia com Selexipague comparada à dupla terapia para tratamento de hipertensão arterial pulmonar: revisão rápida de evidências / Effectiveness and safety of triple therapy with Selexipag compared dual therapy for treatment of pulmonary arterial hypertension: rapid response review of evidence

Selexipague e outros medicamentos de controle da Hipertensão Arterial Pulmonar grupo 1. Indicação: Tratamento de Hipertensão Arterial Pulmonar grupo 1. Pergunta: Há superioridade em eficácia e segurança da tripla terapia com selexipague, comparado a dupla terapia, disponível no SUS, no tratamento de Hipertensão Arterial Pulmonar grupo 1? Métodos: Revisão rápida de evidências (overview) de ensaios clínicos randomizados e revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada pela ferramenta risco de viés da Cochrane. Resultados: Foi selecionado um ensaio clínico randomizado, especificamente um artigo contendo análise de subgrupo de dados desse estudo. Conclusão: As evidências demonstraram redução do número de hospitalizações relacionadas à HAP e de eventos de progressão da doença no tratamento de selexipague em tripla terapia em pacientes na classe funcional II, quando comparada à dupla terapia sem selexipague. A tripla terapia é tão segura quanto a dupla terapia, pois tem riscos similares de eventos adversos e eventos adversos sérios. A tripla terapia não é diferente da dupla terapia no risco da mortalidade geral

Selexipag and other drugs for the control of Pulmonary Arterial Hypertension group 1. Indication: Treatment of Pulmonary Arterial Hypertension group 1. Question: Is there superiority in efficacy and safety of triple therapy with selexipag, compared to dual therapy, available in the SUS, in the treatment of ulmonary Arterial Hypertension group 1? Methods: Rapid review of evidence (overview) of randomized clinical trials and systematic reviews, with a bibliographic survey carried out in the PUBMED database, using a structured search strategy. Results: A randomized clinical trial was selected, specifically an article showing a subgroup analysis of data from this study. Conclusion: Evidence showed a reduction in the number of Pulmonary Arterial Hypertension related hospitalizations and disease progression events in the treatment of selexipag in triple therapy in patients in functional class II, when compared to dual therapy without selexipag. Triple therapy is as safe as dual therapy, as it has similar risks of adverse events and serious adverse events. Triple therapy is no different from dual therapy in the risk of overall mortality

The effects of favipiravir on hematological parameters of covid-19 patients

SUMMARY INTRODUCTION This study aims to evaluate changes in hematological parameters after the follow-up of patients who received treatment with favipiravir due to COVID-19 infections. METHODS Sixty-two cases receiving favipiravir treatment for at least five days due to COVID-19 infection were evaluated retrospectively. Parameters including age, gender, nasopharyngeal swab positivity, and chronic diseases were analyzed. Hematologic parameters were analyzed before and after the treatment. RESULTS The mean age of the patients receiving treatment with favipiravir was 63.7±12.3 years. Nasopharyngeal swab positivity was detected in 67.7%. The most common comorbid conditions detected in patients were hypertension in 25 cases (40.3%) and diabetes in 16 cases (25.8%). In the statistical analysis of the hematological parameters before and after treatment with favipiravir, WBC, PT-PTT-INR levels were found to be unaffected; the mean RBC was found to have decreased from 4.33 ± 0.58 M/uL to 4.16 ± 0.54 M/uL (p:0.003); the median hemoglobin level was found to have decreased from 12.3 g/dl to 11.9 g/dl (p:0.041); the hematocrit level decreased from 38.1% ± 4.8 to 36.9% ± 4.2 (p:0.026); the median neutrophil count decreased from 4.57 K/uL to 3.85 K/uL (p:0.001); the mean lymphocyte count increased from 1.22 ± 0.53 K/uL to 1.84 ± 1.19 K/uL (p:0.000); and the mean platelet count increased from 244.1 ± 85.1 K/uL to 281.9 ± 103.3 K/uL (p:0.005). CONCLUSION We concluded that the pathological effect of treatment with favipiravir on the hematologic system was the suppression in the erythrocyte series, and there were no adverse effects in other hematologic parameters.

RESUMO INTRODUÇÃO Este estudo tem como objetivo avaliar as alterações nos parâmetros hematológicos após o acompanhamento de pacientes que receberam tratamento com favipiravir devido à infecção por Covid-19. MÉTODOS Sessenta e dois casos em tratamento com favipiravir por pelo menos cinco dias devido à infecção por Covid-19 foram avaliados retrospectivamente. Parâmetros como idade, sexo, positividade do swab nasofaríngeo e doenças crônicas foram analisados. Os parâmetros hematológicos foram analisados antes e após o tratamento. RESULTADOS A idade média dos pacientes que receberam tratamento com favipiravir foi de 63,7±12,3 anos. A positividade do swab nasofaríngeo foi detectada em 67,7%. As condições comórbidas mais comuns detectadas nos pacientes foram hipertensão em 25 casos (40,3%) e diabetes em 16 casos (25,8%). Na análise estatística dos parâmetros hematológicos antes e após o tratamento com favipiravir, os níveis de leucócitos, PT-PTT-INR não foram afetados. Verificou-se que o RBC médio diminuiu de 4,33±0,58 M/uL para 4,16±0,54 M/uL (p=0,003); o nível médio de hemoglobina foi reduzido de 12,3 g/dl para 11,9 g/dl (p=0,041); o nível de hematócrito diminuiu de 38,1%±4,8 para 36,9%±4,2 (p=0,026); a contagem mediana de neutrófilos diminuiu de 4,57 K/uL para 3,85 K/uL (p=0,001); a contagem média de linfócitos aumentou de 1,22±0,53 K/uL para 1,84±1,19 K/uL (p=0,000); a contagem média de plaquetas aumentou de 244,1±85,1 K/uL para 281,9±103,3 K/uL (p=0,005). CONCLUSÃO Concluiu-se que o efeito patológico do tratamento com favipiravir no sistema hematológico foi a supressão na série eritrocitária e que não houve efeitos adversos em outros parâmetros hematológicos.

Beneficial effects of Oltipraz, nuclear factor - erythroid - 2 - related factor 2 (Nrf2), on renal damage in unilateral ureteral obstruction rat model

ABSTRACT Introduction: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. Materials and Methods: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration. Transforming growth factor beta-1 (TGF-β1), E-cadherin, nitric oxide (NO) and hydroxyproline levels were measured. Histopathological and immunohistochemical examinations were carried out. Results: TGF-β1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group. In rats treated with UUO + OPZ, despite the presence of mild tubular degeneration and less severe tubular necrosis, glomeruli maintained a better morphology when compared to the UUO group. Expressions of α-SMA in immunohistochemistry showed that the staining positivity decreased in the tubules of the OPZ-treated group. Conclusions: While the precise mechanism of action remains unknown, our results demonstrated that OPZ exerted a protective role in the UUO-mediated renal fibrosis rat model highlighting a promising therapeutic potency of Nrf2-activators for alleviating the detrimental effects of unilateral obstruction in kidneys.

Hydrogen sulfide in posthemorrhagic shock mesenteric lymph drainage alleviates kidney injury in rats

Posthemorrhagic shock mesenteric lymph (PHSML) is a key factor in multiple organ injury following hemorrhagic shock. We investigated the role of hydrogen sulfide (H2S) in PHSML drainage in alleviating acute kidney injury (AKI) by administering D,L-propargylglycine (PPG) and sodium hydrosulfide hydrate (NaHS) to 12 specific pathogen-free male Wistar rats with PHSML drainage. A hemorrhagic shock model was established in 4 experimental groups: shock, shock+drainage, shock+drainage+PPG (45 mg/kg, 0.5 h prehemorrhage), and shock+drainage+NaHS (28 µmol/kg, 0.5 h prehemorrhage). Fluid resuscitation was performed after 1 h of hypotension, and PHMSL was drained in the last three groups for 3 h after resuscitation. Renal function and histomorphology were assessed along with levels of H2S, cystathionine-γ-lyase (CSE), Toll-like receptor 4 (TLR4), interleukin (IL)-10, IL-12, and tumor necrosis factor (TNF)-α in renal tissue. Hemorrhagic shock induced AKI with increased urea and creatinine levels in plasma and higher H2S, CSE, TLR4, IL-10, IL-12, and TNF-α levels in renal tissue. PHSML drainage significantly reduced urea, creatinine, H2S, CSE, and TNF-α but not TLR4, IL-10, or IL-12. PPG decreased creatinine, H2S, IL-10, and TNF-α levels, but this effect was reversed by NaHS administration. In conclusion, PHSML drainage alleviated AKI following hemorrhagic shock by preventing increases in H2S and H2S-mediated inflammation.

Effect of treatment with sitagliptin on somatosensory-evoked potentials and metabolic control in patients with type 2 diabetes mellitus / Efeito do tratamento com sitagliptina sobre os potenciais evocados somatossensoriais e controle metabólico de pacientes com diabetes melito tipo 2

Objective: To evaluate the effect of sitagliptin on somatosensory-evoked potentials (SEPs) and metabolic control in patients with type 2 diabetes mellitus without clinical diabetic neuropathy. Materials and methods: Interventional, prospective, and open study. Patients with less than six months from the diagnosis were included. Examinations of SEPs and laboratory tests at fasting and after food stimulation were performed before and after three months of treatment with sitagliptin (100 mg/day). Results: There was a reduction in the mean levels of HbA1c (P < 0.0001), fasting glucose (P = 0.001), total cholesterol (P = 0.019), and ALT (P = 0.022). An increase in active GLP-1 was found at the end of the study (P = 0.0025). Several SEPs showed statistically significant differences when analyzed before and after treatment with sitagliptin. Conclusion: The results give a glimpse of the possible use of sitagliptin in the treatment of some neurodegenerative conditions of the peripheral nervous system, in addition to its already established role in glycemic control. .

Objetivo: Avaliar o efeito da sitagliptina nos potenciais evocados somatossensoriais (PESS) e controle metabólico de pacientes com diabetes melito tipo 2, sem neuropatia diabética. Materiais e métodos: Estudo de intervenção, prospectivo e aberto. Os pacientes com menos de seis meses de diagnóstico foram incluídos. Exames dos PESS e testes laboratoriais em jejum e após a estimulação com alimentos foram realizados antes e depois de três meses de tratamento com sitagliptina (100 mg/dia). Resultados: Houve redução nos níveis médios de HbA1c (P < 0,0001), glicemia de jejum (P = 0,001), colesterol total (P = 0,019) e ALT (P = 0,022). Verificou-se aumento de GLP-1 ativo (P = 0,0025). Vários PESS mostraram diferenças estatisticamente significativas quando os valores foram analisados antes e após o tratamento com sitagliptina. Conclusão: Os resultados vislumbram a possível utilização de sitagliptina no tratamento de algumas condições neurodegenerativas do sistema nervoso periférico, em adição ao seu papel no controle glicêmico. .

Tetramethylpyrazine potentiates arsenic trioxide activity against HL-60 cell lines

The objective of this study was to evaluate the effects of tetramethylpyrazine (TMP) in combination with arsenic trioxide (As2O3) on the proliferation and differentiation of HL-60 cells. The HL-60 cells were treated with 300 µg/mL TMP, 0.5 µM As2O3, and 300 µg/mL TMP combined with 0.5 µM As2O3, respectively. The proliferative inhibition rates were determined with MTT. Differentiation was detected by the nitroblue tetrazolium (NBT) reduction test, Wright’s staining and the distribution of CD11b and CD14. Flow cytometry was used to analyze cell cycle distribution. RT-PCR and Western blot assays were employed to detect the expressions of c-myc, p27, CDK2, and cyclin E1. Combination treatment had synergistic effects on the proliferative inhibition rates. The rates were increased gradually after the combination treatment, much higher than those treated with the corresponding concentration of As2O3 alone. The cells exhibited characteristics of mature granulocytes and a higher NBT-reducing ability, being a 2.6-fold increase in the rate of NBT-positive ratio of HL-60 cells within the As2O3 treatment versus almost a 13-fold increase in the TMP + As2O3 group. Cells treated with both TMP and As2O3 expressed far more CD11b antigens, almost 2-fold compared with the control group. Small doses of TMP potentiate As2O3-induced differentiation of HL-60 cells, possibly by regulating the expression and activity of G0/G1 phase-arresting molecules. Combination treatment of TMP with As2O3 has significant synergistic effects on the proliferative inhibition of HL-60 cells.

In vitro assessment of reproductive toxicity of cigarette smoke and deleterious consequences of maternal exposure to its constituents

Cigarette smoke is known to be a serious health risk factor and considered reproductively toxic. In the current study, we investigated whether constituents of cigarette smoke, pyrazine, 2-ethylpyridine, and 3-ethylpyridine, adversely affect reproductive functioning such as oocyte maturation and sperm capacitation. Our findings indicated that three smoke components were involved in retardation of oocyte maturation in a dose-dependent manner and the lowest-observed-adverse-effect level (LOAEL) was determined to be 10-10M. However, individual smoke components administrated at the LOAEL did not attenuate oocyte maturation, demonstrating that all three toxicants were equally required for the observed growth impairment. When exposed to all three components at 10-10M during in vitro capacitation, murine sperm lost forward progression and were unable to show adequate hyperactivation, which is indicative of the incompletion of the capacitation process. Only sperm administrated with 3-ethylpyridine alone showed significant reduction in capacitation status, suggesting the chemical is the one responsible for disrupting sperm capacitation. Taken together, this is the first report that documents the effect of cigarette smoke components on oocyte maturation and sperm capacitation. The present findings demonstrate the adverse effects of smoke constituents of mammalian reproduction and the differences in sensitivity to smoke components between male and female gametes. Since both processes take place in the female reproductive system, our data provide new insights into deleterious consequences of maternal exposure to cigarette smoke.

Sitagliptina, un inhibidor de la enzima DPP-IV, aumenta el colesterol plasmático total, altera el perfil de colesterol lipoproteico y disminuye el transporte reverso de colesterol en ratones / Sitagliptine, an DPP-IV enzyme inhibitor, raises total cholesterol and decreases reversal cholesterol transport in mice

Antecedentes: Las hormonas insulina y glucagón regulan la expresión de proteínas claves en el metabolismo lipídico. En pacientes diabéticos, la enfermedad cardiovascular ateroesclerótica es la principal causa de muerte, siendo la dislipidemia un importante factor de riesgo patogénico. La sitagliptina, un inhibidor de la enzima dipeptidilpeptidasa tipo IV (DPP-IV) que controla el metabolismo de las incretinas, es una nueva droga hipogli-cemiante utilizada para el tratamiento de la diabetes tipo 2, aunque sus implicancias en el metabolismo lipídico no han sido establecidas claramente. Objetivo: Estudiar el efecto de la sitagliptina sobre algunos parámetros relacionados con el metabolismo del colesterol en el ratón. Material y Métodos: Se utilizaron ratones C57BL6/J silvestres, siendo un grupo alimentado con dieta estándar y el otro con dieta estándar suplementada con sitagliptina (0,6 por ciento P/Pde dieta) por 8 semanas. La actividad plasmática de DPP-IV y el colesterol plasmático total y lipoproteico fueron medidos por métodos enzima-ticos. La expresión hepática de SR-BI y LDLR se cuantificó por western blot. El transporte reverso de colesterol (TRC) fue evaluado inyectando intraperitonealmente macrófagos cargados con colesterol-14C y midiendo posteriormente los niveles de 14C en plasma y deposiciones en los ratones controles o tratados con sitagliptina. Resultados: La sitagliptina inhibió en un 38 por ciento la actividad de DPP-IV medida en plasma de los ratones. El colesterol plasmático aumentó significativamente (+60 por ciento) con una elevación preferente del colesterol HDL en los ratones tratados con sitagliptina versus los animales controles. Con respecto al TRC, la sitagliptina indujo una mayor recuperación (+20 por ciento) en el plasma y una menor excresión (-30 por ciento) en las deposiciones del 14C-colesterol inyectado versus el grupo control. Finalmente, la sitagliptina disminuyó la expresión hepática de los receptores lipoproteicos ...

Background: Insulin and glucagon regulate the expression of key lipoprotein metabolism enzymes. Dyslipidemia is a significant risk factor for cardiovascular disease, the main cause of death in diabetic patients. Sitagliptine, an inhibitor of type IV dipep-tidil-peptidase (DPP-IV), controlling the metabolism of incretins, is a new hypoglycemic agent used for treatment of type II diabetes. Its effects on lipid metabolism are not clearly defined. Aim: to study the effects of sitagliptine upon parameters of cholesterol metabolism in mice. Methods: C5BL6/J mice were assigned to receive either a standard diet or one with sitagliptine supplementation (0.6 percent P/P) for 8 weeks. DPP-IV plasma, total and lipoprotein cholesterol were measured using enzyme methods. Reverse cholesterol transport was evaluated through the peritoneal injection of cholesterol loaded macrophages followed by measurement of plasma and fecall4C labeled cholesterol. Results: compared to controls, sitagliptine treated mice exhibited a 38 percent decrease in plasma DPP-IV Total plasma cholesterol increased by 60 percent with a marked increase in HDL cholesterol. Also, an increased HDL cholesterol recovered from plasma along with a 30 percent decrease in fecal cholesterol was observed Finally, sitagliptine administration was associated to a decreased LDL and SR-BI hepatic receptors. Conclusion: Sitagliptine administration is associated to increased levels of plasma cholesterol, mainly the HDL fraction, and decreased reverse cholesterol transport and fecal excretion. This effects seem to be mediated by a decreased expression of SR-BI in the liver. The expected increase in atherosclerosis associated to the atherogenic changes induced by sitagliptine should be the subject for further studies in mice.

Incretin mimetics and dipeptidyl peptidase-4 inhibitors: innovative treatment therapies for type 2 diabetes / Incretinomiméticos e inibidores da dipeptidil peptidase-4: terapias inovadoras para o tratamento do diabetes tipo 2

The prevalence of diabetes and impaired glucose tolerance is predicted to dramatically increase over the next two decades. Clinical therapies for type 2 diabetes mellitus (T2DM) have traditionally included lifestyle modification, oral anti-diabetic agents, and ultimately insulin initiation. In this report, we review the clinical trial results of two innovative T2DM treatment therapies that are based on the glucoregulatory effects of incretin hormones. Incretin mimetics are peptide drugs that mimic several of the actions of glucagon-like peptide-1 (GLP-1) and have been shown to lower glycated hemoglobin (A1C) levels in patients with T2DM. Additionally, incretin mimetics lower postprandial and fasting glucose, suppress elevated glucagon release, and are associated with progressive weight reduction. Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous GLP-1 levels by inhibiting the enzymatic degradation of GLP-1. Clinical studies in patients with T2DM have shown that DPP-4 inhibitors reduce elevated A1C, lower postprandial and fasting glucose, suppress glucagon release, and are weight neutral. Collectively, these new drugs, given in combination with other antidiabetic agents, such as metformin, sulfonylureas, and/or thiazolidinediones, can help restore glucose homeostasis in poorly controlled patients with T2DM.

É previsto que a prevalência de diabetes e a intolerância à glicose aumente dramaticamente ao longo das próximas duas décadas. As terapias clínicas para diabetes melito tipo 2 (DM2) têm tradicionalmente incluído modificação do estilo de vida, agentes antidiabéticos orais e, por último, o início da insulina. Neste artigo, revisamos os resultados dos estudos clínicos de duas terapias inovadoras no tratamento do DM2 baseadas nos efeitos glicorregulatórios dos hormônios incretina. Os incretinomiméticos são medicamentos peptídeos que mimetizam várias das ações do peptídeo semelhante ao glucagon-1 (GLP-1) e têm demonstrado reduzir níveis de hemoglobina glicada (A1C) em pacientes com DM2. Adicionalmente, incretinomiméticos reduzem as glicemias pós-prandial e de jejum, suprimem a liberação elevada do glucagon, e são associados com redução de peso. Os inibidores da dipeptidil peptidase-4 (DPP-4) aumentam os níveis de GLP-1 endógeno pela inibição da degradação enzimática do GLP-1. Estudos clínicos em pacientes com DM2 têm demonstrado que inibidores da DPP-4 reduzem A1C elevada, reduzem as glicemias pós-prandial e de jejum, suprimem a liberação elevada do glucagon e são neutros quanto ao peso. Coletivamente, estas novas medicações, administradas em combinação com outros agentes antidiabéticos, como metformina, sulfoniluréias e/ou tiazolidinedionas (TZDs), podem ajudar a recuperar a homeostase glicêmica de pacientes com DM2 não-controlados.

Evoluçäo do teor dos compostos pirazínic durante a torraçäo de cacau (Theobroma cacao L.), da variedade forasteiro / Evolution of pyrazines during the roasting of cacao beans (Theobroma cacao, L.)variety forastero

Durante a torraçäo do cacau ocorre o desenvolvimento de aromas, principalmente pela Reaçäo de Malliard, a partir dos precursores formados durante a fermentaçäo. Dentre os compostos aromáticos formados predominam em um número as pirazinas, as quais säo compostos heterecíclicos que aumentam de concentraçäo gradualmente com o decorrer da torraçäo, sendo que a diminuiçäo do teor de algumas pirazinas na amêndoa é coincidente com o início da sobretorraçäo. Considerando-se que o aroma é formado por um grande número de constituintes orgânicos de diferentes estruturas químicas, propriedades e concentraçöes, sua quantificaçäo é bastante complexa, requerendo equipamentos modernos e sofisticados. Estudou-se entäo a utilizaçäo da cromatografia gasosa (CG) para separaçäo dos compostos aromáticos do cacau torrado onde, fizeram-se a identificaçäo e a quantidade de alguns importantes componentes voláteis: 2-metilprazina; 2,5-dimetilprazina; 2,6-dimetilprazina; etilprazina; 2,3 dimetilprazina; 2,3,5,6-tetrametilprazina. Alguns autores destacam que possivelmente a reduçäo na concentraçäo de certos compostos aromáticos pode ser indicadora de que a etapa de torraçäo do cacau esteja atingindo seu ponto final. Com o objetivo de avaliar se realmente tal fato ocorre, fizeram-se testes de torraçäo em amêndoas inteiras e em nibs (cotilédones fragmentados), utilizando-se quatro diferentes tempos de torraçäo para cada tipo de amostra (36,40,42 e 44 minutos para amêndoas inteiras e 30,34,36 e 38 minutos para os nibs, com temperatura da camisa do forno elétrico fixada em 150C, em ambos os casos. Avaliou-se o perfil aromático de cada uma das amostras testadas e os resultados obtidos demonstraram que a 2,3,5,6-tetrametilprazina parece realmente ser um indicador de que a torraçäo esteja atingindo seu ponto final.

Central serotonergic modulation of drinking behavior induced by water deprivation: effect of a serotonergic agonist (MK-212) administered intracerebroventricularly

The present study was carried out to evaluate the participation of the serotonergic system (5-HT) in the modulation of the drinking response induced by water deprivation. Male Wistar rats implanted with a cannula in the 3rd ventricle were injected with the 5-HT1C/5-HT2 agonist 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) at doses of 0.5, 5, 25, 50 and 125 nmol/2 µl. MK-212 induced a significant reduction (p < ou = 0.05) in water intake over a period of 300 min. This result indicates that the central 5-HT system plays an important role, probably at the level of the periventricular hypothalamus, in the modulation of drinking behavior induced by water deprivation

Central serotonergic modulation of drinking behavior induced by angiotensin II and carbachol in normally hydrated rats: effect of intracerebroventricular injection of MK-212

The objective of the present study was to evaluate the role of the central erotonergic (5-HT) system in the modulation of drinking behavior induced angiotensin II (Ang II) and carbachol. Male Wistar rats implanted with a delay cannula in the 3 rd ventricle were injected with the 5-HT1C/5-HT2 agonist 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) (50 nmol/2 µl) before receiving an intracerebro-ventricular (icv) injection of Ang II or carbachol (100 ng/2 µl). MK-212 induced a significant reduction in the drinking response evoked by Ang II or carbachol which was more marked in the case of the cholinergic agonist. The results obtained suggest that thirst and water intake produced by angiotensinergic or cholinergic activation are modulated by the action of 5-HT, possibly at the level of the periventricular hypothalamus

Thyroidectiomy reduces stress-induced prolactin secretion in rats. Participation of brain serotonergic systems

Plasma prolactin levels were measusred in thyroidectomized and sham-operated rats under immobilization stress. thyroidectomy significantly reduced prolactin secretion during stress. The pretreatment of thyroidectomized rats with 6-chloro-2[1-piperazinyl]-pyrazine (MK 212), a serotinin agonist that easily penetrates the blood-brain barrier, reversed the reduction in stress-induced prolactin release in the thyroidectomized group

Participation of the serotonergic system in the regulation of water and electrolyte balance

To determine the possible participation of the serotonergic (5-Ht system in the regulation of water and electrolyte balance, rats were submitted to two sessions of water overloading and the 5-HT agonist MK 212 was administered intracerebroventricularly (icv) in 1.0 micronl 20 min after the second session. Urine volume and sodium and potassium excretion were measured over a priod of 120 min. Microinjection of MK-212 (1 microng/animal) caused a significant reduction (24 to 57%; mean, 43%) in natriuresis throghout the experimental period, and the administration of 10 microng/animal caused a 26-41% reduction (mean, 33%) in kaliuresis. At 20 microng/ animal, MK-212 did not change any of the parameters investigated. No significant change in urine volume was detected after any of the reatments used

Ascaris lumbricoides en vías biliares / Ascaris lumbricoides in the bile ducts

El Ascaris Lumbricoides, es un helminto endémico de los países de clima cálido, como los es el nuestro. La infestación masiva de diversos órganos por este parásito es mundialmente conocida. Incluyendo el alojamiento de grandes cantidades de Ascaris Lumbricoides de las vías biliares, sobre todo en pacientes pediátricos, siendo ésto más infrecuente en pacientes adultos. En el Servicio de Cirugía General del C.H.M. nos tocó operar una paciente de 38 años, residente en la capital por 29 años, quien ingresó con un cuadro típico de Colecistitis aguda. Durante su estudio se evidenció la presencia de un Ascaris Lumbricoides en el interior del colédoco. Fue llevada al salón de operaciones, donde se le practicó coledocotomía lagrándose extraer el helminto del radical izquierdo hepático. Efectuándose drenaje del colédoco con tubo en "T" número 18 y a continuación una colecistectomía de cuello a fondo. Se evolución fue satisfactoria y se complementó con tratamiento a base de Piperazina oral. El objeto de este trabajo es llamar la atención de los colegas, sobre todo de los que trabajan en áreas rurales, ya que siendo un parásito muy conocido en nuestro medio, no se reportan muchos casos similares. Nos llama la atención que en el Continente Africano la segunda causa de abdómenes agudos son las complicaciones por la presencia masiva del Ascaris en diversos órganos abdominales

Failure at inducing resistance to schistosomicidal drugs in a brazilian human strain of Schistosoma mansoni

No presente estudo, realizou-se uma tentativa de induçäo de resistência a 3 drogas esquistossomicidas em uma cepa brasileira de S. mansoni, segundo o esquema de induçäo de resistência tipo II preconizado por Jansma et al. em 1977. Houve insucesso nas 3 tentativas realizadas. A geraçäo parental tratada com a droga durante o estágio imaturo do verme mostrou-se menos suscetível aos quimioterápicos do que as geraçöes F1 e F2 do verme. Uma hipótese é levantada para a explicaçäo do fato

Avaliaçäo terapêutica do oltipraz na infecçäo humana pelo S. mansoni / Therapeutic evaluation of oltipraz in human infection due to S. monsoni

Foram tratados com oltipraz, dose oral única de 30 mg/kg de peso, 72 indivíduos com esquistossomose mansoni, matriculados na Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de Säo Paulo. As idades dos pacientes variaram de 7 a 58 anos, sendo que 8 (11,1%) eram menores de 15 anos. Os principais efeitos colaterais consistiram em tonturas 22,2%, sonolência 22,2%, naúseas 22,2%, cefaléia, 9,7%, astenia 9,7%, parestesia 8,3%, vômitos 8,3%, cólicas 7,0%, diarréia 4,2%, escotomas 2,8%, sialosquese 2,8%, nódulos dolorosos em extremidades 2,8% e outras manifestaçöes clínicas em menor frequência. A toxicidade do medicamento foi avaliada mediante a realizaçäo pré e pós-tratamento, de exames hamatimétricos, de funçäo renal (uréia e creatinina), hepática (enzimas de liberaçäo hepato-canalicular e bilirrubinas), cardíaca (ECG) e neuropsiquiátrica (EEG). Näo foram encontrados nos controles laboratoriais alteraçöes relevantes ou que determinasse alguma repercussäo clínica. O controle de cura verificou-se em 49 indivíduos, através de 8 coproscopias (no período de 6 meses subseqüente ao tratamento) utilizando-se duas técnicas (Hoffman e Kato/Katz) para cada amostra de fezes. Dos 29 indivíduos que tiveram as 8 coproscopias negativas, 20 realizaram biopsia retal, mostrando-se positiva em uma oportunidade, indicando 5% de "falsos negativos" com relaçäo às coproscopias. O índice de cura para todas as faixas etárias foi de 59,2%. Os resultados obtidos demonstraram ser o oltipraz de relativa eficácia e determinante de efeitos tóxicos-colaterais sistêmicos no tratamento da esquistossomose mansoni

Estudio de la eficacia y seguridad de un tratamiento a largo plazo con acipimox en hiperlipogroteinemia / Efficacy and security of a long-term treatment with acipimox in hyperlipoproteinemia

Diseño experimental: Abierto, no controlado. Número de pacientes: 117 pacientes externos (64 varones, 53 mujeres) con hiperlipoproteinemia tipo 2a, (35), 2b (38) y 4 (44). Horario de tratamiento: Los pacientes fueron instruidos para que tomaran una cápsula de 250 mg. o 400 mg. t. i. d. por un período de 6 - 24 meses. Evaluación: Mensualmente los primeros dos meses y de allí en adelante bi-mensualmente: peso corporal, ritmo cardíaco, presión sanguínea sistólica y diastólica, lípidos plasmáticos, (colesterol) total y triglicéridos). Con el mismo horario mencionado para el primer año y luego por lo menos una vez cada seis meses hemograma y bioquímica sanguínea (glicemia, uricemia, BUN, creatinina, proteínas totales, bilirrubina total, SGOT, SGPT, fosfatasa alcalina, RBC, hemoglobina, hematocrito, WBC total y diferencial, trombocitos, tiempo de protrombina), urianálisis. La electroforesis lipoproteína se hizo sólo en el momento de admisión y en algunos controles durante el estudio. Resultados: 15 pacientes interrumpieron el tratamiento: 10 debido a motivos adversos, 1 debido a enfermedad intercurrente, 1 por mejoramiento definitivo, 1 debido a empeoramiento de enfermedad concomitante y 2 se perdieron en el seguimiento. De los pacientes restantes 45, 18 y 39 completaron 6, 12 y 24 meses de tratamiento, respectivamente. Durante la prueba el peso corporal de los pacientes no cambió significativamente. a) Eficacia. Los niveles medios de triglicéridos bajaron alrededor de 57% en pacientes hiperlipoproteinémicos del tipo 4 y casi 39% en pacientes del tipo 2b con diferencias muy significativas en comparación con los valores básicos. En los pacientes del tipo 2a. la trigliceridemia bajó alrededor de 13%. Los niveles medios de colesterol total bajaron 17% en pacientes de tipo 2a y 2b y 16% en pacientes de tipo 4 con diferencias muy significativas en comparación con los valores básicos...