RESUMO
Cimetidine, used as an anti-ulcer and adjuvant treatment in cancer therapy, causes disorders in the male reproductive tract, including steroidogenesis. However, its effect on sperm quality and male fertility has been poorly addressed. Since vitamin B12 has demonstrated to recover spermatogonia number and sperm concentration in cimetidine-treated rats, we evaluated the impact of cimetidine on sperm quality and fertility potential and whether vitamin B12 is able to prevent the harmful effect of this drug on steroidogenesis and sperm parameters. Adult male rats were treated for 52 consecutive days as follows: cimetidine group (100 mg/kg of cimetidine), cimetidine/vitamin B12 group (100 mg/kg of cimetidine + 3 µg vitamin B12), vitamin B12 group (3 µg vitamin B12) and control group (saline). Serum testosterone levels and immunofluorescence associated to western blot for detection of 17ß-HSD6 were performed. Sperm morphology and motility, mitochondrial activity, acrosome integrity, DNA integrity by Comet assay, lipid peroxidation as well as fertility potential were analyzed in all groups. Apoptotic spermatids were also evaluated by caspase-3 immunohistochemistry. In the cimetidine-treated animals, reduced serum testosterone levels, weak 17ß-HSD6 levels and impaired spermiogenesis were observed. Low sperm motility and mitochondrial activity were associated with high percentage of sperm tail abnormalities, and the percentage of spermatozoa with damaged acrosome and DNA fragmentation increased. MDA levels were normal in all groups, indicating that the cimetidine-induced changes are associated to androgenic failure. In conclusion, despite the fertility potential of rats was unaffected by the treatment, the sperm quality was significantly impaired. Therefore, considering a possible sperm-mediated transgenerational inheritance, the long term offspring health needs to be investigated. The administration of vitamin B12 to male rats prevents the androgenic failure and counteracts the damage inflicted by cimetidine upon sperm quality, indicating that this vitamin may be used as a therapeutic agent to maintain the androgenic status and the sperm quality in patients exposed to androgen disrupters.
RESUMO
Histamine [2-(4-Imidazolyl)-ethylamine] modulates different biological processes, through histamine H1 and H2 receptors, and their respective blockers are widely used in treating allergic and gastric acid-related disorders. Histamine H1 and H2 receptor crossdesensitization and cointernalization induced by its agonists have been previously described. In this study, we show how this crosstalk determines the response to histamine H1 and H2 receptor inverse agonists and how histamine H1 and H2 receptor inverse agonists interfere with the other receptor's response to agonists. By desensitization assays we demonstrate that histamine H1 and H2 receptor inverse agonists induce a crossregulation between both receptors. In this sense, the histamine H1 receptor inverse agonists desensitize the cAMP response to amthamine, a histamine H2 receptor agonist. In turn, histamine H2 receptor inverse agonists interfere with histamine H1 receptor signaling. We also determine that the crossdesensitization induced by histamine H1 or H2 receptor agonists alters the histamine inverse agonists receptor response: activation of histamine H1 receptor affects cAMP response induced by histamine H2 receptor inverse agonists, whereas histamine H2 receptor agonist induces a negative regulation on the anti-inflammatory response of histamine H1 receptor inverse agonists. Binding studies revealed that histamine H1 and H2 receptors cointernalize after stimulus with histamine receptor inverse agonists. In addition, the inhibition of the internalization process prevents receptor crossregulation. Our study provides new insights in the mechanisms of action of histamine H1 and H2 receptors that explain the effect of histamine H1 and H2 receptor inverse agonists and opens up new venues for novel therapeutic applications.
Assuntos
Agonistas dos Receptores Histamínicos/metabolismo , Antagonistas dos Receptores Histamínicos H1/metabolismo , Receptores Histamínicos H1/metabolismo , Receptores Histamínicos H2/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Células HEK293 , Histamina/metabolismo , Humanos , Transdução de Sinais/fisiologia , Células U937RESUMO
Despite the pivotal role GPCRs play in cellular signaling, it is only in the recent years that structural biology has begun to elucidate how GPCRs function and to provide a platform for structure-based drug design. It is postulated that GPCR activation involves the movement of transmembrane helices. The finding that many residues, which have been shown to be critical for receptor activation and are highly conserved among different GPCRs, are clustered in particular positions of transmembrane helices suggests that activation of GPCRs may involve common molecular mechanisms. In particular, phenylalanine 6.44, located in the upper half of TMVI, is highly conserved among almost all GPCRs. We generated Phe 2436.44 Ala/Ser mutants of histamine H2 receptor and found that while the substitutions do not affect receptor expression or ligand signaling, are able to specifically alter cimetidine and ranitidine mechanisms of action from simply inactivating the receptor to produce a ligand-induced G-protein sequestering conformation, that interferes with the signaling of ß2-adrenoceptor. Taking advantage of the cubic ternary complex model, and mathematically modeling our results, we hypothesize that this alteration in ligand mechanism of action is consequence of a change in ligand-induced conformational rearrangement of receptor and its effect on G-protein coupling. Our results show that receptor point mutations can not only alter receptor behavior, as shown for activating/inactivating mutations, but also can have more subtle effects changing ligand mechanism of action.
Assuntos
Cimetidina/farmacologia , Antagonistas dos Receptores H2 da Histamina/farmacologia , Ranitidina/farmacologia , Receptores Histamínicos H2/genética , Células HEK293 , Humanos , Modelos Moleculares , Mutação , Conformação ProteicaRESUMO
BACKGROUND: Histamine seems to act, via H2 receptor, on inflammatory processes by stimulating interleukin (IL)-6 and matrix metalloproteinase (MMP) release. As cimetidine is an H2 receptor antagonist, the authors hypothesize that this antiulcer drug reduces IL-6, MMP-1, and MMP-9 immunoexpression in gingiva with induced periodontal disease (PD). To confirm a possible modulatory role of IL-6 on MMPs, the relationship between IL-6/MMP-1 and IL-6/MMP-9 immunoexpression was evaluated. METHODS: Forty-six male rats were distributed into the cimetidine group (CimG: received daily intraperitoneal injections of 100 mg/kg of body weight of cimetidine) or the saline group (SG). PD was induced by cotton ligature around the maxillary left first molars (PDSG and PDCimG). The right molars were used as controls (SG and CimG). After 7, 15, 30, and 50 days, maxillary fragments were processed for paraffin embedding or for transmission electron microscopy. Tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in the alveolar process surface and number of IL-6, MMP-1, and MMP-9-immunolabeled cells in the gingival mucosa were quantified. Statistical analyses were performed (P ≤0.05). RESULTS: In PDSG and PDCimG, gingival mucosa exhibited few collagen fibers among numerous inflammatory cells. In PDCimG, the number of TRAP-positive osteoclasts and IL-6, MMP-1, and MMP-9-immunolabeled cells was significantly lower than in PDSG at all periods. A positive correlation between IL-6/MMP-1 and IL-6/MMP-9 was detected in PDSG and PDCimG. CONCLUSION: Cimetidine decreases bone loss through reduction of osteoclast number and induces reduction of IL-6, MMP-1, and MMP-9 immunoexpression, reinforcing the idea that the beneficial effect of cimetidine in PD may be due to reduction of IL-6 immunolabeling in the inflamed gingival mucosa.
Assuntos
Cimetidina/farmacologia , Gengiva/efeitos dos fármacos , Gengiva/metabolismo , Interleucina-6/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Doenças Periodontais/tratamento farmacológico , Doenças Periodontais/metabolismo , Animais , Técnicas Imunoenzimáticas , Masculino , Microscopia Eletrônica de Transmissão , RatosRESUMO
The amorphous state is of particular interest in the pharmaceutical industry due to the higher solubility that amorphous active pharmaceutical ingredients show compared to their respective crystalline forms. Due to their thermodynamic instability, drugs in the amorphous state tend to recrystallize; in order to avoid crystallization, it has been a common strategy to add a second component to hinder the crystalline state and form a thermally stable co-amorphous system, that is to say, an amorphous binary system which retains its amorphous structure. The second component can be a small molecule excipient (such as a sugar or an aminoacid) or a second drug, with the advantage that a second active pharmaceutical ingredient could be used for complementary or combined therapeutic purposes. In most cases, the compositions studied are limited to 1:1, 2:1 and 1:2 molar ratios, leaving a gap of information about phase transitions and stability on the amorphous state in a wider range of compositions. In the present work, a study of novel co-amorphous formulations in which the selection of the active pharmaceutical ingredients was made according to the therapeutic effect is presented. Resistance against crystallization and behavior of glass transition temperature ( T g were studied through calorimetric measurements as a function of composition and shelf time. It was found that binary formulations with T g temperatures higher than those of pure components presented long-term thermal stability. In addition, significant increments of T g values, of as much as 15 ∘ C, were detected as a result of glass relaxation at room temperature during storage time; this behavior of glass transition has not been previously reported for co-amorphous drugs. Based on these results, it can be concluded that monitoring behavior of T g and relaxation processes during the first weeks of storage leads to a more objective evaluation of the thermomechanical stability of an amorphous formulation.
Assuntos
Química Farmacêutica , Vidro , Varredura Diferencial de Calorimetria , Espectroscopia de Infravermelho com Transformada de Fourier , TemperaturaRESUMO
Exposure of cimetidine (CIM) to dry heat (160-180°C) afforded, upon cooling, a glassy solid containing new and hitherto unknown products. The kinetics of this process was studied by a second order chemometrics-assisted multi-spectroscopic approach. Proton and carbon-13 nuclear magnetic resonance (NMR), as well as ultraviolet and infrared spectroscopic data were jointly used, whereas multivariate curve resolution with alternating least squares (MCR-ALS) was employed as the chemometrics method to extract process information. It was established that drug degradation follows a first order kinetics. One of the products was structurally characterized by mono- and bi-dimensional NMR experiments. It was found to be the N3-enamino tautomer (TAU) of CIM, resulting from the thermal isomerization of the double bond of the cyanoguanidine moiety of the drug, from the imine form to its N3-enamine state. The thus generated tautomer demonstrated to be stable for months in the glassy solid and in methanolic solutions. A theoretical study of CIM and TAU revealed that the latter is less stable; however, the energy barrier for tautomer interconversion is high enough, precluding the process to proceed rapidly at room temperature.
Assuntos
Cimetidina/química , Antagonistas dos Receptores H2 da Histamina/química , Temperatura Alta , Isomerismo , Cinética , Análise dos Mínimos Quadrados , Espectroscopia de Ressonância Magnética , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The antiulcer drug cimetidine has shown to cause changes in the testicular microvasculature of adult rats. Since Leydig cells (LCs) produce the pro-angiogenic factor, EG-VEGF (endocrine gland-derived vascular endothelial growth factor), also known as prokineticin 1 (PK-1), this study examined the effect that cimetidine might have on LCs in testes with damaged vasculature. Rats received intraperitoneal injections of 100mg/kg of cimetidine (cimetidine group) or saline vehicle (control group) for 50 days. Serum testosterone levels were measured by chemiluminescence immunoassay and testicular sections were subjected to TUNEL and immunohistochemical reactions for caspase-3, 17ß-HSD6, CD163 (ED2 macrophage), PK-1 and androgen receptor (AR). LCs in the cimetidine group showed TUNEL and caspase-3 positive labeling and apoptotic ultrastructural features. Moreover, the presence of 17ß-HSD6-positive inclusions inside macrophages and the reduced number of LCs, AR immunoreactivity and serum testosterone levels correlated with a decrease in either the number of PK-1-immunostained LCs or PK-1 immunoreactivity. Although it is not clear which cell type is the primary target of cimetidine in the testicular interstitial compartment, these findings support a direct link between cimetidine-induced testicular vascular atrophy and LCs damage.
Assuntos
Antiulcerosos/toxicidade , Cimetidina/toxicidade , Testículo/efeitos dos fármacos , 17-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Apoptose/efeitos dos fármacos , Atrofia , Caspase 3/metabolismo , Masculino , Microscopia Eletrônica de Transmissão , Ratos , Receptores Androgênicos/metabolismo , Receptores de Superfície Celular/metabolismo , Testículo/metabolismo , Testículo/patologia , Testículo/ultraestrutura , Testosterona/sangue , Fator de Crescimento do Endotélio Vascular Derivado de Glândula Endócrina/metabolismoRESUMO
Different brain areas seem to be involved in the cardiovascular responses to stress. The medial amygdala (MeA) has been shown to participate in cardiovascular control, and acute stress activates the MeA to a greater extent than any of the other amygdaloid structures. It has been demonstrated that the brain histaminergic system may be involved in behavioral, autonomic and neuroendocrine responses to stressful situations. The aim of the present study was to investigate the role of the histaminergic receptors H1 and H2 in cardiovascular responses to acute restraint stress. Wistar rats (280-320g) received bilateral injections of cimetidine, mepyramine or saline into the MeA and were submitted to 45min of restraint stress. Mepyramine microinjections at doses of 200, 100 and 50nmol promoted a dose-dependent blockade of the hypertensive response induced by the restraint stress. Cimetidine (200 and 100nmol) promoted a partial blockade of the hypertensive response to stress only at the highest dose administered. Neither drugs altered the typical stress-evoked tachycardiac responses. Furthermore, mepyramine and cimetidine were unable to modify the mean arterial pressure or heart rate of freely moving rats under basal conditions (non-stressed rats). The data suggest that in the MeA the histaminergic H1 receptors appear to be more important than H2 receptors in the hypertensive response to stress. Furthermore, there appears to be no histaminergic tonus in the MeA controlling blood pressure during non-stress conditions.
Assuntos
Tonsila do Cerebelo/metabolismo , Hipertensão/fisiopatologia , Receptores Histamínicos H1/metabolismo , Receptores Histamínicos H2/metabolismo , Tonsila do Cerebelo/efeitos dos fármacos , Análise de Variância , Animais , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Histamínicos/farmacologia , Masculino , Microinjeções , Ratos , Ratos Wistar , Estresse Psicológico , Fatores de TempoRESUMO
The identity of the polymorphic form of an active pharmaceutical ingredient is an important parameter that may affect the performance of the drug formulation. This calls for special techniques, able to classify crystal forms or assign the polymorphic identity to a given solid in a mixture. In order to develop a method to determine which of the relevant polymorphs of Cimetidine (CIM) is present in commercial tablet samples, authentic forms A, B, D and M1 of the drug were prepared, structurally characterized and employed as standards. Thus, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was coupled to Principal Component Analysis (PCA) and used for the classification of physical mixtures of CIM and excipients, as well as laboratory-made and commercial tablets, according to their polymorphic composition. It was demonstrated that two principal components (PCs) suffice to classify the samples of the four forms of CIM into distinct groups, and that method performance is optimum when the second and third PCs are used for the classification process. The application of the method to commercial tablets of CIM also gave good results, confirming they were prepared employing the correct polymorph (form A).
Assuntos
Cimetidina/química , Comprimidos/química , Química Farmacêutica/métodos , Excipientes/química , Análise de Componente Principal/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodosRESUMO
Crystal polymorphism of active ingredients is relevant to the pharmaceutical industry, since polymorphic changes taking place during manufacture or storage of pharmaceutical formulations can affect critical properties of the products. Cimetidine (CIM) has several relevant solid state forms, including four polymorphs (A, B, C and D), an amorphous form (AM) and a monohydrate (M1). Dehydration of M1 has been reported to yield mixtures of polymorphs A, B and C or just a single form. Standards of the solid forms of CIM were prepared and unequivocally characterized by FTIR spectroscopy, digital microscopy, differential scanning calorimetry and solid state (13)C NMR spectroscopy. Multivariate curve resolution with alternating least squares (MCR-ALS) was coupled to variable temperature attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) to dynamically characterize the behavior of form M1 of CIM over a temperature range from ambient to 160°C, without sample pretreatment. MCR-ALS analysis of ATR-FTIR spectra obtained from the tested solid under variable temperature conditions unveiled the pure spectra of the species involved in the polymorphic transitions. This allowed the simultaneous observation of thermochemical and thermophysical events associated to the changes involved in the solid forms, enabling their unequivocal identification and improving the understanding of their thermal behavior. It was demonstrated that under the experimental conditions, dehydration of M1 initially results in the formation of polymorph B; after melting and upon cooling, the latter yields an amorphous solid (AM). It was concluded that the ATR-FTIR/MCR association is a promising and useful technique for monitoring solid-state phase transformations.
Assuntos
Cimetidina/química , Cristalização/métodos , Análise dos Mínimos Quadrados , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , TemperaturaRESUMO
BACKGROUND: There is evidence that histamine released during inflammation plays a role in bone metabolism via the H2 receptor, stimulating bone resorption. The purpose of this study is to evaluate whether cimetidine, a histamine H2-receptor antagonist, interferes with the initiation and progression of induced periodontal disease in rat molars. METHODS: Forty male rats received 100 mg/kg body weight of cimetidine (cimetidine group [CimG]) or saline solution (sham group [SG]). Periodontal disease was induced in the maxillary left first molars (PDSG and PDCimG); maxillary right molars were used as non-ligature controls. After 7, 15, 30, and 50 days, maxillary fragments were embedded in paraffin. The sections were stained with Masson trichrome and hematoxylin and eosin and subjected to the tartrate-resistant acid phosphatase (TRAP) method. The distances between the cemento-enamel junction (CEJ) and alveolar process (AP) crest, as well as between the CEJ and junctional epithelium (JE) level, were measured; the number of inflammatory cells was computed. Receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) immunohistochemistry was carried out, and the RANKL/OPG ratio was calculated. RESULTS: In PDSG and PDCimG, a significant increase (P ≤0.05) was observed in CEJ-AP and CEJ-JE distances. However, the increases in both distances were significantly less in PDCimG compared with PDSG at 15, 30, and 50 days. Numerous TRAP-positive osteoclasts were found in the PDSG and PDCimG. In PDCimG, the volume density of inflammatory cells and the RANKL/OPG ratio were significantly lower (P ≤0.05) than in PDSG. CONCLUSIONS: Cimetidine exerts a beneficial effect on periodontal disease in rats, decreasing the RANKL/OPG ratio in gingival connective tissue and reducing alveolar bone resorption.
Assuntos
Perda do Osso Alveolar/prevenção & controle , Cimetidina/uso terapêutico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Periodontite/prevenção & controle , Fosfatase Ácida/análise , Perda do Osso Alveolar/patologia , Processo Alveolar/efeitos dos fármacos , Processo Alveolar/patologia , Animais , Corantes , Tecido Conjuntivo/efeitos dos fármacos , Tecido Conjuntivo/patologia , Modelos Animais de Doenças , Progressão da Doença , Inserção Epitelial/efeitos dos fármacos , Inserção Epitelial/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Gengiva/efeitos dos fármacos , Gengiva/patologia , Isoenzimas/análise , Masculino , Maxila , Dente Molar , Osteoprotegerina/análise , Osteoprotegerina/efeitos dos fármacos , Periodontite/patologia , Ligante RANK/análise , Ligante RANK/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fosfatase Ácida Resistente a Tartarato , Fatores de Tempo , Colo do Dente/efeitos dos fármacos , Colo do Dente/patologiaRESUMO
JUSTIFICATIVA E OBJETIVOS: Avaliar a proteção gástrica do extrato hidroalcoólico da semente de girassol (EHSG) em relaçãoao estresse, ao uso de indometacina e etanol. MÉTODO: Foi realizado um estudo experimental envolvendo 90 ratas (Rattus norvegicus albinus), da linhagem Wistar, fêmeas, com peso corporal médio de 150-230 g, divididos em 18 grupos distintos os quais receberam os seguintes tratamentos: EHSG:250 mg/kg, 500 mg/kg, 1000 mg/kg e 2000 mg/kg; etanol 0,5mL; cimetidina 60 mg/kg; indometacina 20 mg/kg; água 1 mL. Os dados foram analisados utilizando o programa Grand PadPrism 5 com aplicação de testes estatísticos considerando o nível de significância de 5%. RESULTADOS: O EHSG apresenta proteção contra as lesões gástricas em ratas, nas doses de 250 e 1000 mg, tanto no modelo pelo estresse, quanto na indução por etanol e indometacina. CONCLUSÃO: Os dados obtidos no presente estudo mostram que o EHSG apresenta proteção gástrica em determinadas doses.
BACKGROUND AND OBJECTIVES: To evaluate the gastric protection hidroalcoólico extract the sunflower seed (EHSG) in relation to stress, the use of indomethacin and ethanol. METHOD: We conducted an experimental study involving 90 rats (Rattus norvegicus albinos), Wistar, females, mean body weight of 150-230 g were divided into 18 distinct groups which received the following treatments: EHSG: 250mg/kg , 500 mg/kg, 1000 mg/kg and 2000 mg/kg; 0.5 mL ethanol, cimetidine 60 mg/kg, 20 mg/kg indomethacin; 1 mL water. Data were analyzed using the GrandPad Prism 5 with application of statistical tests, the significance level of 5%. RESULTS: The EHSG has protective against gastric injury in rats at doses 250 mg and 1000, both in the model by stress, as in the induction by ethanol and indomethacin. CONCLUSION: The data obtained in this study show that has EHSG gastric protection in certain doses.
Assuntos
Animais , Feminino , Ratos , Cimetidina/efeitos adversos , Extratos Vegetais/uso terapêutico , Helianthus , Indometacina/efeitos adversos , Sementes , Úlcera Gástrica/terapia , Ratos WistarRESUMO
JUSTIFICATIVA E OBJETIVOS: Antagonistas de receptor de histamina apresentam efeitos sobre a dor. Antagonistas de receptor H1 apresentam efeito analgésico local, o papel de antagonistas de receptor H2 sobre a dor no sistema nervoso periférico ainda não está claro. Esse estudo teve como objetivo avaliar os efeitos de diferentes antagonistas H2 sobre a dor induzida pela administração de formalina na pata de ratos.MÉTODO: Foram estudados ratos machos divididos em grupos que receberam formalina na pata e diferentes antagonistas de receptor H2 - ranitidina, cimetidina e loxtidina, injetados na pata em diferentes concentrações (0,05 µmol, 0,25 µmol ou 1 µmol). Foi avaliado o número de elevações da pata pelo período de 45 minutos.RESULTADOS: A loxtidina inibiu o número de elevações da pata nas duas fases do teste a partir das três concentrações utilizadas, a ranitidina diminuiu o número de elevações da pata a partir da concentração de 0,25 µmol na fase II, a cimetidina não inibiu esse comportamento doloroso.CONCLUSÃO: De acordo com os resultados deste estudo,alguns antagonistas do receptor H2 apresentaram efeito analgésico local fármaco específico e não classe farmacológica específica.
BACKGROUND AND OBJECTIVES: Histamine receptor antagonists affect pain perception. H1 receptor antagonists present local analgesic effect, but the role of H2 receptor antagonists on pain in the peripheral nervous system is not clear yet. This study aimed at evaluating the effects of different H2 receptor antagonists on pain induced by formalin paw injection in rats.METHOD: Male rats were studied and divided into groups that received formalin and different H2 receptor antagonists - ranitidine, cimetidine and loxtidine, injected in the paw at different concentrations (0.05 mol, 0.25 mol or 1 mol). The number of flinches was evaluated during 45 minutes.RESULTS: Loxtidine inhibited the number of flinches in both phases of the test with the three different concentrations. Ranitidine decreased the number of flinches in phase II as from 0.25 mol. Cimetidine did not affectpain behavior.CONCLUSION: According to the results of this study,some H2 receptor antagonists presented local analgesic effects, which seem to be drug-related and not pharmacological class-specific.
RESUMO
JUSTIFICATIVA E OBJETIVOS: Avaliar a possível atividade gastroprotetora do extrato de raspa de juá (Ziziphus joazeiro) em relação ao estresse, ao uso de indometacina e etanol; verificar a acidez (pH) gástrica por meio da ligadura pilórica (resíduo gástrico puro e com adição de água) e comparar as diferenças dos valores do pH em ambos os modelos. MÉTODO: Foram utilizados 120 ratos (cinco em cada grupo), da espécie Rattus norvegicus albinus, com peso de 150 a 230 g, divididos em 24 grupos distintos, os quais receberam os seguintes tratamentos: extrato de raspa de juá: 250, 500, 1000 e 2000 mg/kg, etanol 0,5 mL; cimetidina (60 mg/kg); indometacina (20 mg/kg); água (1 mL); ligadura de piloro (água; cimetidina e extrato de raspa de juá). Os dados foram analisados pelo programa Grand Pad Prism 5 com aplicação de testes estatísticos. RESULTADOS: O extrato de raspa de juá nas doses de 250, 1000 e 2000 mg/kg sugeriu proteção gástrica no estresse. No modelo de indução de úlcera gástrica por etanol, as doses de 250 e 2000 mg/kg apresentaram proteção gástrica. No grupo do extrato de raspa de juá e indometacina as doses de 250, 1000 e 2000 mg/kg também sugeriram proteção gástrica. Em relação ao valor de pH, o resíduo gástrico, quando verificado puro, é mais ácido que pelo modelo da adição da água, significando que este modelo aumenta o pH, comprovando assim que o modelo do resíduo gástrico puro é mais indicado. CONCLUSÃO: Os dados obtidos no presente estudo mostraram que o extrato de raspa de juá apresentou provável proteção gástrica em determinadas doses.
BACKGROUND AND OBJECTIVES: To evaluate the possible gastroprotective activity of the extract of scrapings juá (Ziziphus joazeiro) by stress, indomethacin and ethanol; check the acidity (pH) through the gastric pylorus ligation (gastric residue pure and with added water) and compare differences in pH values in both models. METHOD: A total of 120 rats (5 in each group), Rattus norvegicus albinus, weighing 150-230 g were divided into 24 distinct groups, which received the following treatments: extract scrapings juá (250, 500 mg, 1000 and 2000 mg/kg), ethanol (0.5 mL), cimetidine (60 mg/kg), indomethacin (20 mg/kg), water (1 mL); ligation of pylorus (water, cimetidine and extract scrapings juá). The data were analyzed by Grand Pad Prism 5 with application of statistical tests. RESULTS: The extract of scrapings juá at doses 250, 1000 and 2000 mg/kg suggested gastric protection in stress. In the model of gastric ulcer induced by ethanol, the dosages of 250 and 2000 mg/kg showed gastric protection. In the group of extract scrapings juá and indomethacin dosages of 250, 1000 and 2000 mg/kg also suggested gastric protection. Regarding the pH, the gastric residue, occurred when pure, is more acidic than the model of the addition of water, meaning that this model increases the pH, thus proving that the model of pure gastric residue is indicated. CONCLUSION: The data obtained in this study show that the extract of scrapings has juá likely gastric protection in certain doses.
Assuntos
Animais , Ratos , Cimetidina , Indometacina , Physalis , Fitoterapia , Úlcera Gástrica/induzido quimicamente , Ratos EndogâmicosRESUMO
JUSTIFICATIVA E OBJETIVOS: Avaliar quantitativa e qualitativamente a provável proteção gástrica do extrato hidroalcoólico da semente de girassol (EHSG) em relação ao estresse, ao uso de indometacina e etanol; bem como verificar a acidez (pH) gástrica por meio da ligadura pilórica (resíduo gástrico puro e com adição de água) e comparar as diferenças dos valores do pH em ambos os modelos. MÉTODO: Foram estudados 120 ratos (5 em cada grupo) da espécie Rattus norvegicus albinus, com peso de 150-230g, divididos em 24 grupos distintos, os quais receberam os seguintes tratamentos: EHSG: 250 mg/kg, 500 mg/kg, 1000 mg/kg e 2000 mg/kg; etanol 0,5 mL; cimetidina 60 mg/kg; indometacina 20 mg/kg; água 1 mL; ligadura de piloro (água; cimetidina e EHSG). Os dados foram analisados utilizando o programa Grand Pad Prism 5 com aplicação de testes estatísticos considerando o nível de significância de 5%.RESULTADOS: O EHSG nas doses 250 e 1000 mg/kg sugeriu proteção contra as lesões gástricas no estresse. No modelo de indução de úlcera gástrica por etanol, as doses de 250 e 1000 mg/kg apresentaram provável proteção gástrica. No grupo utilizando EHSG 250 mg/kg e indometacina a dose de 250 mg/kg também sugere proteção gástrica. Em relação ao valor de pH, o resíduo gástrico, quando verificado puro, é mais ácido que pelo modelo da adição da água, significando que este último modelo está aumentando o pH, comprovando assim que o modelo do resíduo gástrico puro é mais indicado e prático. CONCLUSÃO: Os dados obtidos no presente estudo mostram que o EHSG apresenta provável proteção gástrica em determinadas doses.(AU)
BACKGROUND AND OBJECTIVES: To evaluate quantitatively and qualitatively the probable gastric protection of hydroalcoholic extract from sunflower seed (EHSG) in relation to stress, the use of indomethacin and ethanol; check the acidity (pH) through the gastric pylorus ligation (gastric residue pure and with added water), and compare differences in pH values in both models. METHOD: A total of 120 rats (5 in each group) of the type Wistar rats weighing 150-230g were divided into 24 distinct groups, which received the following treatments: EHSG: 250 mg/kg, 500 mg/kg, 1000 mg/kg and 2000 mg/kg, 0.5 mL ethanol, cimetidine 60 mg/kg, indomethacin 20 mg/kg, 1 mL water, ligation of pylorus (water, cimetidine and EHSG). The data were analyzed using the Grand Pad Prism 5 with application of statistical tests considering the significance level of 5%.RESULTS: The EHSG at doses 250 and 1000 mg/kg suggested protection against gastric lesions in stress. In the model of gastric ulcer induced by ethanol, the doses of 250 and 1000 mg/kg showed probable gastric protection. Group using EHSG 250 mg/kg and indomethacin dose of 250 mg/kg also suggests gastric protection. Regarding the pH, the gastric residue, occurred when pure, is more acidic than the model of the addition of water, meaning that the latter model is increasing the pH, thus proving that the model of pure gastric residue is more appropriate and more practical. CONCLUSION: The data obtained in this study show that has likely EHSG gastric protection in certain doses.(AU)
Assuntos
Animais , Ratos , Sementes , Úlcera Gástrica , Estresse Psicológico , Indometacina/farmacologia , Cimetidina/farmacologia , Etanol/farmacologia , Helianthus , Ratos EndogâmicosRESUMO
FUNDAMENTOS: Verrugas são proliferações epiteliais na pele e mucosas causadas por diversos tipos de HPV. Elas podem involuir espontaneamente ou aumentar em número e tamanho de acordo com estado imunitário do paciente. A cimetidina e o sulfato de zinco têm importante efeito no sistema imune, sendo usados como imunomoduladores no tratamento de diversas doenças. OBJETIVO:Comparar a eficácia terapêutica de cimetidina e sulfato de zinco no tratamento de verrugas cutâneas de difícil tratamento. MÉTODOS: Estudo prospectivo duplo-cego randomizado. Dezoito pacientes com verrugas múltiplas foram divididos em dois grupos, um recebeu cimetidina 35mg/kg/dia (máximo 1.200mg/dia), e o outro, sulfato de zinco 10mg/kg/dia (máximo de 600mg/dia) por três meses. RESULTADOS: Dos 18 pacientes do estudo, nove receberam cimetidina, e nove, sulfato de zinco; apenas um do grupo do sulfato de zinco não completou o tratamento devido a náuseas e vômitos. Cura foi obtida em cinco pacientes tratados com sulfato de zinco, e apenas um não obteve alteração das lesões. Do grupo da cimetidina cinco não apresentaram modificação, e quatro apresentaram diminuição inferior a 30% das lesões iniciais. CONCLUSÕES: Sulfato de zinco na dose de 10mg/kg/dia parece ser mais efetivo que cimetidina para o tratamento de crianças e adultos com verrugas múltiplas e de difícil manejo. A pequena casuística deste trabalho não permite, entretanto, conclusão categórica.
Background: Warts are epithelial proliferations on the skin and mucous membrane caused by various types of HPV. They can decrease spontaneously or increase in number and size according to patient's immune status. Cimetidine and zinc sulphate have important effects on the immune system and are used as immunomodulators in the treatment of various diseases. Objective: To compare the efficacy of cimetidine and zinc sulphate in the treatment of multiple and recalcitrant warts. Methods: A random double-blind prospective study. Eighteen patients with multiple warts were divided into two groups: one took 35mg/Kg/day of cimetidine (maximum 1200 mg/day) and the other 10 mg/Kg/day of zinc sulphate (maximum 600 mg/day) for three months. Results: Among the 18 patients who participated in the study, nine took cimetidine and nine zinc sulphate. Just one patient in the zinc sulphate group did not complete treatment due to nausea and vomiting. Five patients who were treated with zinc sulphate were cured and only one did not show modifications in lesions. Among the group who was treated with cimetidine, five did not show modifications in lesions and four showed decrease from baseline below 30%. Conclusions: 10 mg/Kg/day zinc sulphate dose seems to be more effective than cimetidine for the treatment of children and adults with multiple and difficult-to-handle warts. However, the small number of patients did not enable any definitive conclusion.
Assuntos
Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Cimetidina/uso terapêutico , /uso terapêutico , Verrugas/tratamento farmacológico , Sulfato de Zinco/uso terapêutico , Método Duplo-Cego , Estudos Prospectivos , Verrugas/patologia , Adulto JovemRESUMO
La creatinina sérica es un marcador poco sensible para identificar reducciones leves del índice de filtración glomerular (IFG); por ello resulta de gran importancia clínica disponer de métodos alternativos para estimar la función renal. Con este objetivo estudiamos la función renal de 41 pacientes -grupo completo y divididos según la creatinina sérica (menor o igual 1.2 mg/dl o mayores)- usando el clearance de creatinina modificado con cimetidina (Clcrc) como aproximación al IFG, las ecuaciones de Larsson y Hoek que incluyen el uso de cistatina C sérica y las tradicionales fórmulas de Cockroft-Gault y MDRD abreviada. En el grupo completo de pacientes y especialmente en aquellos con creatinina sérica menor o igual 1.2 mg/dl - con reducción de la función renal: Clcrc: 62.01 mas o menos 17.33 ml/min/1.73 m2-, las ecuaciones de Larsson y Hoek mostraron mejores correlaciones y menores diferencias promedio respecto a las fórmulas basadas en la creatinina sérica. La ecuación MDRD abreviada mostró buen rendimiento sólo en el grupo con evidente alteración de la función renal (creatinina sérica > 1.2 mg/dl). Concluimos que en pacientes con diferentes estadios de función renal, las fórmulas que emplean la cistatina C sérica detectan la reducción del IFG más precozmente respecto a aquellas basadas en la creatinina sérica.
Serum creatinine is an insensitive marker to identify early changes in glomerular filtration rate (GFR), for this reason alternative methods to estimate renal function result of great clinical importance. Forty-one patients were studied using creatinine clearance modified with cimetidina (Clcrc) as surrogate of GFR, cystatin C-based equations (i.e. Larsson and Hoek formulas), Cockroft-Gault and MDRD abbreviated equations. In the whole group, as well as in those patients with serum creatinine less than or equal to 1.2 mg/dl -but reduced renal function: Clcrc 62.01 more or less 17.33 ml/min/1.73 m2-, Larsson and Hoek equations showed higher correlations and lower bias than creatinine-based formulas. Abbreviated MDRD equation showed good performance just in those patients with evident alteration of renal function (serum creatinine > 1.2 mg/dl). We concluded that in patients with different stages of renal function, cystatin C-based equations detect reduction of renal function earlier than the serum creatinine-based formulas.