RESUMO
OBJECTIVE: Periodontal diseases are inflammatory chronic infections. Sialic acid (SA) is an acute phase reactant by itself. The aim of this study is to investigate the relationship between salivary and serum SA levels and clinical parameters in different forms of periodontal diseases. SUBJECT AND METHODS: Systemically healthy subjects were included in the study; patients with chronic gingivitis (CG) (n = 10), chronic periodontitis (CP) (n = 10), and aggressive periodontitis (AgP) (n = 10), and ten volunteers with healthy periodontium as the control group. Total SA levels were determined by Warren's thiobarbituric acid method in whole saliva, parotis saliva, and serum samples of subjects before and 3 months after nonsurgical periodontal treatment. Full mouth clinical parameters including plaque index, gingival index, probing depth, and bleeding on probing were also recorded. RESULTS: Before treatment, in both periodontitis groups salivary and serum SA levels were higher than those of controls (P = 0.001). Both salivary and serum SA levels decreased significantly in the patient groups after treatment (P < 0.001). Multiple comparisons of baseline clinical parameters in all groups revealed significant differences (P = 0.001) and these parameters decreased significantly on the 90th day (P < 0.01). There were positive correlations between SA levels and periodontal indices of the CG, CP, and AgP groups (P < 0.05). CONCLUSION: Our results suggest that SA level in both saliva and serum may be a potentially useful marker to determine inflammatory changes and investigate different forms of periodontal diseases.
Assuntos
Biomarcadores/análise , Ácido N-Acetilneuramínico/sangue , Doenças Periodontais/sangue , Saliva/química , Adulto , Periodontite Agressiva/sangue , Biomarcadores/sangue , Periodontite Crônica/sangue , Feminino , Gengivite/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Índice PeriodontalRESUMO
The 17ß-estradiol plays a role in physiology of pancreas and may protect it from inflammation. To examine the possible anti-inflammatory effects of 17ß-estadiol in pancreaticobiliary duct ligated (PBDL) acute pancreatitis (AP) model, and the underlying mechanism that 17ß-estradiol acts on, via evaluating the direct and the receptor related effects by using 17ß-estradiol, ER-α and -ß agonists. In the study both sexes of rats (n = 88) were used. Animals were divided into two groups as PBDL and PBDL + ovariectomized. ER-α agonist propyl-pyrazole-triol (PPT; 1 mg/kg/day), ER-ß agonist diarylpropionitrile (DPN; 1 mg/kg/day) and 17ß-estradiol (10 mg/kg/day) were administered to the groups for 3 days following AP induction. On the 3rd day, lung and pancreas tissues and serum samples were taken for malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), superoxide dismutase (SOD) and interleukin (IL) assays, and histological analyses. In both tissues of male and female AP groups MPO, MDA, SOD levels were increased (P < 0.05 - 0.01) and GSH levels were decreased (P < 0.05). Pancreas and lung MDA and SOD levels were improved with all treatments in female, except lung MDA levels of PPT-treated ones, while lung MDA and SOD levels were improved by PPT and 17ß-estradiol in females and via PPT in males (P < 0.05 - 0.001). The increased MPO levels were inhibited with PPT in male pancreas and female lung and with 17ß-estradiol in female pancreas (P < 0.05). The increased pro-inflammatory ILs were declined by treatments (P < 0.05 - 0.001). 17ß-estradiol and ER-α and -ß agonists reduced oxidative pancreatic and pulmonary damage. Estrogen and agonists might have protective role in AP.
Assuntos
Estrogênios/farmacologia , Pulmão/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Pancreatite/metabolismo , Doença Aguda , Animais , Ductos Biliares/cirurgia , Citocinas/sangue , Estradiol/farmacologia , Feminino , Glutationa/metabolismo , Ligadura , Pulmão/metabolismo , Pulmão/patologia , Masculino , Malondialdeído/metabolismo , Nitrilas/farmacologia , Ovariectomia , Pâncreas/metabolismo , Pâncreas/patologia , Pâncreas/cirurgia , Peroxidase/metabolismo , Fenóis/farmacologia , Propionatos/farmacologia , Pirazóis/farmacologia , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismoRESUMO
The objective of the study was to determine the effects of a high fat (HF) diet alone or with high fructose (HF/F) on functional and structural changes in the basilar arteries and cardiovascular health parameters in rats. Male Sprague Dawley rats were fed either a HF (30%) or HF/F (30/40%) diet for 12 weeks. The basilar artery was cannulated in a pressurized system (90 cm H2O) and vascular responses to KCl (30 - 120 mM), endothelin (10(-11) - 10(-7) M), acetylcholine (ACh) (10(-10) - 10(-4) M), diethylamine (DEA)-NONO-ate (10(-10) - 10(-4) M), and papaverine (10(-10) - 10(-4) M) were evaluated. Rats were also monitored for food intake, body weight, blood lipids, blood pressure, and heart rate. At death, asymmetrical dimethyl arginine level (ADMA) and leptin were assayed in serum. Although there was no significant difference in weight gain and food intake, HF and HF/F diets increased body fat composition and decreased the lean mass. HF/F diet accelerated the development of dyslipidemia. Although resting blood pressure remained unchanged, stress caused a significant elevation in blood pressure and a modest increase in heart rate in HF fed rats. Both HF and HF/F diet resulted in decreased response to endothelium-dependent and -independent relaxation, whereas increased basilar artery wall thickness was observed only in HF group. Serum leptin levels positively correlated with wall thickness. Moreover serum ADMA was increased and eNOS immunofluorescence was significantly decreased with both diets. These data suggest that the presence of high fructose in a HF diet does not exacerbate the detrimental consequences of a HF diet on basilar artery function.
Assuntos
Artéria Basilar/efeitos dos fármacos , Dieta Hiperlipídica , Frutose/farmacologia , Animais , Artéria Basilar/patologia , Artéria Basilar/fisiologia , Glicemia/análise , Pressão Sanguínea/efeitos dos fármacos , Glutationa/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Leptina/sangue , Lipídeos/sangue , Masculino , Malondialdeído/metabolismo , Miocárdio/metabolismo , Ratos Sprague-Dawley , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
Mucosal balance impairment, bacterial over-proliferation, cytokines, inflammatory mediators are known as responsible for inflammatory bowel disease. Besides known anorexigenic, neuroprotective, and anti-apoptotic effects, the major effect of nesfatin-1 on colitis is unknown. Our aim was to investigate the possible anti-inflammatory effects of nesfatin-1 in acetic acid induced colitis model and potential underlying mechanisms. Male Spraque-Dawley rats were anesthetized by intraperitoneal ketamine (100 mg/kg) and chlorpromazine (0.75 mg/kg). For nesfatin-1 and antagonist applications some of the rats were intracerebroventricularly (i.c.v.) cannulated. In colitis group, intrarectally (i.r.) 4% acetic acid solution (1 ml) and 10 minutes later i.c.v. nesfatin-1 (0.05 µg/5 µl) or vehicle (5 µl) were administered. Treatments continued for 3 days. In control group, physiological saline solution was used intrarectally. To identify the underlying effective mechanism of nesfatin-1, rats were divided into 3 subgroups, 5 minutes following colitis induction; i.c.v. atosiban (oxytocin receptor antagonist), SHU9119 (melanocortin receptor antagonist) or GHSR-1a antagonist (ghrelin receptor antagonist) were administered, 5 minutes later nesfatin-1 was administered for 3 days. On the fourth day, rats were decapitated, and colon tissues were sampled. Macroscopic and microscopic damage scores of distal colon, and colonic tissue malondialdehyde, glutathione, myeloperoxidase, superoxide dismutase, catalase, luminol and lucigenin chemiluminescence measurements were analysed. The increased myeloperoxidase activity, malondialdehyde levels, luminol and lucigenin chemiluminescence measurements, macroscopic and microscopic damage scores with colitis induction (P < 0.05 - 0.001) were decreased with nesfatin-1 treatment (P < 0.05 - 0.001). Nesfatin-1 may show this effect by inhibiting neutrophil infiltration through tissues and by decreasing formation of free oxygen radicals. Atosiban and GHSR-1a administration alleviated the protective effect of nesfatin-1 from microscopic and oxidant damage parameters and lipid peroxidation (P < 0.05 - 0.001). The results of the study suggest that nesfatin-1 had a protective effect from colitis induction, and the anti-inflammatory and antioxidant effects of nesfatin-1 on colitis might occur via oxytocin and ghrelin receptors.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Proteínas de Ligação ao Cálcio/farmacologia , Colite/prevenção & controle , Proteínas de Ligação a DNA/farmacologia , Proteínas do Tecido Nervoso/farmacologia , Ácido Acético/toxicidade , Animais , Modelos Animais de Doenças , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Nucleobindinas , Peroxidase/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Valproic acid (VPA) is a drug used for the treatment of epilepsy, bipolar psychiatric disorders, and migraine. Previous studies have reported an increased generation of reactive oxygen species and oxidative stress in the toxic mechanism of VPA. Edaravone, a free radical scavenger for clinical use, can quench free radical reaction by trapping a variety of free radical species. In this study, effect of edaravone on some small intestine biochemical parameters in VPA-induced toxicity was investigated. Thirty seven Sprague Dawley female rats were randomly divided into four groups. The groups include control group, edaravone (30 mg(-1) kg(-1) day(-1)) given group, VPA (0.5 g(-1) kg(-1) day(-1)) given group, VPA + edaravone (in same dose) given group. Edaravone and VPA were given intraperitoneally for 7 days. Biochemical parameters such as malondialdehyde, as an index of lipid peroxidation(LPO), sialic acid (SA), glutathione levels and glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, catalase, myeloperoxidase, alkaline phosphatase (ALP), and tissue factor (TF) activities were determined in small intestine samples by colorimetric methods. Decreased small intestine antioxidant enzyme activities, increased LPO and SA levels, and increased activities of ALP and TF were detected in the VPA group. Based on our results edaravone may be suggested to reverse the oxidative stress and inflammation due to VPA-induced small intestine toxicity.
Assuntos
Antipirina/análogos & derivados , Sequestradores de Radicais Livres/farmacologia , Intestino Delgado/efeitos dos fármacos , Ácido Valproico/toxicidade , Fosfatase Alcalina/metabolismo , Animais , Antipirina/farmacologia , Edaravone , Feminino , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Intestino Delgado/metabolismo , Malondialdeído/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Peroxidase/metabolismo , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Tromboplastina/metabolismoRESUMO
The nitrergic system modulates cardiovascular functions of the central nucleus of amygdala (CeA) and the posterior hypothalamus (PH) which are involved in the central regulation of the cardiovascular system. The aim of this study was to investigate the contribution of nitric oxide (NO) in the PH in eliciting cardiovascular responses produced through electrical stimulation (ES) of the CeA. Rats were implanted with a stimulation electrode and a parenchymal cannula system into the CeA and a parenchymal cannula or a microdialysis probe into the PH. The next day, the femoral artery was cannulated for haemodynamic measurement. The CeA was electrically stimulated to produce cardiovascular response. The nitric oxide synthetase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 400 nmol/100 nl) or artificial cerebrospinal fluid were injected into the PH or the CeA before the ES of the CeA. The dialysates were collected from the PH to determine the L-citrulline and the L-glutamic acid levels. L-NAME injection into the CeA but not to the PH suppressed the increases in the mean arterial pressure produced by the ES of the CeA significantly; however, heart rate was not affected by L-NAME injection into either the PH or the CeA. L-citrulline and L-glutamic acid levels in the PH were shown to be increased by the ES of the CeA. NO is involved between the PH and the CeA which has a considerable role in the central regulation of the cardiovascular system.
Assuntos
Tonsila do Cerebelo/fisiologia , Pressão Sanguínea/fisiologia , Hipotálamo Posterior/fisiologia , Óxido Nítrico/fisiologia , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Citrulina/metabolismo , Estimulação Elétrica , Inibidores Enzimáticos/administração & dosagem , Feminino , Ácido Glutâmico/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Hipotálamo Posterior/efeitos dos fármacos , Masculino , Microdiálise , Microinjeções , NG-Nitroarginina Metil Éster/administração & dosagem , Óxido Nítrico Sintase/antagonistas & inibidores , Ratos , Ratos Sprague-DawleyRESUMO
The association between periodontal and cardiovascular disease has received considerable attention. Studies have demonstrated a higher incidence of atherosclerotic complications in patients with periodontal disease. Tissue factor (TF) has been known as a key initiator of the coagulation cascade, and the TF pathway is the primary physiological mechanism of initiation of blood coagulation. Recently, it has been shown that the circulating pool of TF in blood is associated with increased blood thrombogenicity in patients with coronary artery disease (CAD). Various tissues and saliva have been known to have TF activity. Consequently, the aim of this study was to investigate plasma TF levels and TF activity of saliva in periodontitis patients with and without diagnosed CAD. Twenty-six patients with a diagnosis of CAD and 26 systemically healthy patients were examined in the dental clinic, and the Community Periodontal Index Treatment Needs (CPITN) scores were recorded. Plasma TF levels were determined using commercially available ELISA kit. Salivary TF activities were determined according to Quick's one-stage method. Plasma TF levels were significantly increased in patients with CAD when compared with the control group. There was no difference in salivary TF activities between the 2 groups, but there was a strong and negative correlation between salivary TF activities and CPITN indexes in both groups. In order to determine the possible role of TF activity as a salivary marker in CAD and periodontitis and to fully understand the negative correlation between salivary TF activities and CPITN, TF activity of gingival crevicular fluid that may also affect saliva can be evaluated.
Assuntos
Doença da Artéria Coronariana/metabolismo , Periodontite/metabolismo , Saliva/metabolismo , Tromboplastina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Periodontite/complicaçõesRESUMO
Laboratory batch experiments were conducted at 20 degrees C to investigate the potential of primary sludge fermentation for the generation of readily biodegradable substrate and to evaluate the effect of fermentation products on mass balance for organic carbon, nitrogen and phosphorus, emphasizing COD fractionation. Fermentation converted between 18 to 30% of the initial volatile suspended solids in the sludge into soluble biodegradable COD. The volatile fatty fraction of the soluble COD was approximately 85% after the fermentation process. The average volatile fatty acid composition in fermentation involved 50% acetic acid, 33% propionic acid, 9% butyric acid and 8% valeric acid, indicating that the most important volatile fatty acid obtained during the biological fermentation process was acetate with more than half of total VFA concentration, which is one of the most important carbon sources for denitrification and biological nutrient removal processes. The recoverable fraction of the fermented sludge supernatant could potentially increase the readily biodegradable COD content of the primary effluent by 5%, together with a potential increase of the soluble nitrogen and phosphorus content by 2%.
Assuntos
Ácidos Graxos Voláteis/metabolismo , Fermentação , Nitrogênio/metabolismo , Fósforo/metabolismo , Esgotos , Eliminação de Resíduos Líquidos , OxigênioRESUMO
Mast cells are implicated in stress-induced inflammatory skin diseases such as psoriasis. Mechanisms of stress-induced mast cell degranulation however, are not entirely clear. Here we explore the role of activation of a Substance P (SP) receptor (NK-1) on mast cell degranulation upon exposure to stress in rats. A specific nonpeptide NK-1 antagonist, CP99994 was used to treat the rats either peripherally or intracerebroventricularly. Because increased SP activity in the brain may mediate the stress response, we also examined cutaneous mast cell degranulation after central injection of SP. Stress, as well as SP injected centrally, increased mast cell degranulation. Both central and peripheral injection of CP99994 prevented stress-induced mast cell degranulation. Surprisingly, the combination of stress with SP decreased mast cell degranulation, suggesting that high levels of SP may counteract the stress responses. Results in this animal model suggest that NK-1 antagonists may be used therapeutically to treat stress-induced inflammatory skin diseases; however, drug doses should be chosen carefully.
Assuntos
Degranulação Celular/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Antagonistas dos Receptores de Neurocinina-1 , Piperidinas/farmacologia , Estresse Psicológico/patologia , Animais , Temperatura Baixa , Relação Dose-Resposta a Droga , Privação de Alimentos , Imobilização , Mastócitos/fisiologia , Piperidinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptores da Neurocinina-1/fisiologia , Pele/patologia , Substância P/farmacologiaRESUMO
OBJECTIVE: The aim of this study was to compare rational pharmacotherapy decision-making competency of interns (final-year medical students) who had received rational pharmacotherapy education (RPE), with their classmates at another medical school and general practitioners (GPs) who had not been exposed to RPE. DESIGN: A written, objective, structured clinical examination (OSCE), consisting of open and structured questions, was given to all participants. The participants were expected to make a treatment plan and prescribe for simple, uncomplicated beta-hemolytic streptococcal tonsillitis and mild-to-moderate essential hypertension patients, explain their proposed treatment plans and reasons affecting their drug choice. After the OSCE, a questionnaire to assess knowledge of the rational use of drugs was given to the participants. RESULTS: Fifty RPE(+) interns, 54 RPE(-) interns and 53 GPs participated in the study. Mean scores of RPE(+) interns were higher than those of GPs, which were in turn found to be higher than those of RPE(-) interns for all cases. The RPE(+) interns scored the highest regarding all components of rational pharmacotherapy process for all cases of both indications. However, participants in all groups had higher scores for the structured questions compared with the corresponding open ones for both diseases. Prescription analysis also revealed better results for RPE(+) interns regarding the number of drugs/prescription and treatment costs. CONCLUSION: The present study demonstrated that the final-year medical students (interns) markedly benefited from undergraduate RPE at the medical school in developing rational prescribing skills compared with their classmates from a medical school with traditional pharmacology education. Interestingly, they got higher scores than not only RPE(-) interns, but also than the GPs participating in this study, indicating the urgent need for continuous medical education programs in this field throughout the country for practicing GPs.
Assuntos
Tomada de Decisões , Internato e Residência/estatística & dados numéricos , Médicos/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Prescrições de Medicamentos , Uso de Medicamentos , Educação de Graduação em Medicina , Educação em Farmácia , Humanos , Inquéritos e QuestionáriosRESUMO
The present study aims to assess the short- and mid-term post-graduation impact of a pharmacotherapy course in the fifth year at Marmara University School of Medicine by an objective (OSCE) and a subjective (questionnaires) evaluation. Statistical comparison of pretest, posttest-exposed case and posttest-unexposed case scores indicated both a retention and a transfer effect of training. The post-course questionnaire revealed that 95%of the students found the course useful and necessary; 97% reported that they will apply a rational pharmacotherapy approach using this model and communicate better with their patients. The post-graduation questionnaire also showed that the majority of them have learned general principles of rational pharmacotherapy(90%), gained good prescribing (90%) and communication skills (87.5%), and understood the importance of non-pharmacological treatment alternatives (100%). In general, they stated that they would apply the principles during their medical practice and they believed their colleagues would do too. In conclusion, the present study demonstrates the benefit of a clinical pharmacology programme focused on rational pharmacotherapy during the clinical years of medical education.
Assuntos
Estágio Clínico/métodos , Farmacologia Clínica/educação , Aprendizagem Baseada em Problemas , Análise de Variância , Atitude do Pessoal de Saúde , Tratamento Farmacológico , Avaliação Educacional , Seguimentos , Humanos , Relações Médico-Paciente , Avaliação de Programas e Projetos de Saúde , Estudantes de Medicina/psicologia , Inquéritos e Questionários , TurquiaRESUMO
In the present study, the effect of the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methylester (L-NAME), on the antishock actions of oxotremorine was investigated in rats subjected to hemorrhagic shock under urethane anesthesia. L-citrulline production in the AV3V region, as an indicator of nitric oxide (NO) synthesis, was assayed by high-performance liquid chromatography (HPLC) with fluorescent detection throughout the experiment. The rats were pretreated with either intravenous (i.v.) physiological saline or L-NAME (2.5 mg/kg) before bleeding. L-NAME potentiated the reversal of hypotension by oxotremorine (25 microg/kg, i.v.). However, oxotremorine either alone or in combination with L-NAME did not produce any significant change in 60-min survival rate at this low dose. Analysis of microdialysis samples collected from the AV3V region showed that L-citrulline concentration increased during bleeding and that this increase was abolished by L-NAME pretreatment. These results may suggest that nitric oxide production contributes to hypotension in rats bled to shock since nitric oxide levels in the AV3V region increased in response to bleeding and nitric oxide synthase (NOS) inhibition abolished this increase and potentiated the oxotremorine-induced reversal of hypotension.
Assuntos
Óxido Nítrico/fisiologia , Oxotremorina/farmacologia , Choque Hemorrágico/prevenção & controle , Animais , Pressão Sanguínea/efeitos dos fármacos , Ventrículos Cerebrais/efeitos dos fármacos , Ventrículos Cerebrais/metabolismo , Citrulina/efeitos dos fármacos , Citrulina/metabolismo , Inibidores Enzimáticos/farmacologia , Feminino , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Oxotremorina/uso terapêutico , Ratos , Ratos Sprague-Dawley , Choque Hemorrágico/mortalidade , Choque Hemorrágico/fisiopatologia , Taxa de Sobrevida , Fatores de TempoRESUMO
The watershed processes which control 129I/127I ratios, 129I and 127I concentrations, and speciation of iodine isotopes were studied through an investigation into the variability of these parameters in the Mississippi River near New Orleans, undertaken in 1996-1998. Analyses of suspended particulate matter (SPM) revealed a greater percent association of 127I than of 129I, resulting in lower 129I/127I ratios in SPM than in surrounding water. Furthermore, crossflow ultrafiltration showed that organo-iodine was the dominant form for both isotopes, with 70-85% of these isotopes found in the 0.45 microm filter-passing fraction associated with colloidal macromolecular organic matter. 129I showed a weak correlation, 127I no correlation, and 129I/127I ratios a strong inverse correlation with river flow rate. Inverse correlations between 129I/127I ratios and river flow rates can be best explained by rainwater and evapotranspiration dominated ratios at base flow and a lowering of the isotope ratios during higher flow due to extra inputs of 127I from soil weathering. We postulate that different equilibration times for 127I and 129I as well as for bomb-produced 129I and reprocessing-produced 129I are responsible for these fractionation effects and the differential mobilities of these isotopes in the Mississippi River watershed.
Assuntos
Radioisótopos do Iodo/análise , Iodo/análise , Poluentes Radioativos da Água/análise , Poluentes da Água/análise , Coloides , Monitoramento Ambiental , Filtração , Guerra Nuclear , Movimentos da ÁguaRESUMO
PURPOSE: We investigated the role of afferent C fibers in morphological changes of the rat bladder during stress. MATERIALS AND METHODS: Wistar albino rats were exposed to cold immobilization stress. Different routes of capsaicin administration before cold immobilization stress were studied. Capsaicin was given to neonates, around the vagus (perivagal) or celiac (periceliac), or perivagal plus periceliac. From each group samples of bladder were randomly chosen for morphological evaluation using electron microscopy. RESULTS: Stress exposure led to pathological changes, including an increased number of mast cells, degenerated urothelium and dilated tight junctions, in the bladder. Capsaicin given neonatally and around the vagal and celiac ganglia prevented these stress induced degenerative bladder changes. CONCLUSIONS: Activation of capsaicin sensitive afferent neurons locally and centrally may be involved in stress related pathological changes in the rat bladder.
Assuntos
Capsaicina/farmacologia , Fibras Nervosas/fisiologia , Neurônios Aferentes/fisiologia , Estresse Fisiológico/complicações , Bexiga Urinária/inervação , Bexiga Urinária/patologia , Animais , Animais Recém-Nascidos , Capsaicina/administração & dosagem , Temperatura Baixa , Imobilização , Microscopia Eletrônica , Fibras Nervosas/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Ratos , Ratos Wistar , Estresse Fisiológico/fisiopatologiaRESUMO
The role of capsaicin-sensitive afferent fibers on cold-restraint stress-induced gastric and hepatic injury was examined at the macroscopic and ultrastructural levels. Wistar albino rats were treated with capsaicin either locally (intragastric, perivagal, and periceliac) or systemically (neonatal, intraperitoneal). Perineural and neonatal treatment with capsaicin was used to denervate afferent fibers, while intragastric capsaicin treatment would have activated mucosal afferent fibers just before the stress exposure. Capsaicin decreased significantly the formation of macroscopic gastric lesions caused by stress in all treatment groups. At the electron microscopic level, however, denervation of vagal afferent fibers with capsaicin was most effective in prevention of cellular injury in gastric mucosa. In the liver, systemic denervation of afferent fibers completely inhibited stress-induced cellular damage, while denervation of afferent fibers in vagus and splanchnic nerve was partially effective. Central neural pathways sensitive to capsaicin may mediate formation of both gastric and hepatic injury resulting from stress.
Assuntos
Capsaicina/farmacologia , Hepatopatias/fisiopatologia , Fígado/inervação , Neurônios Aferentes/fisiologia , Úlcera Gástrica/fisiopatologia , Estômago/inervação , Estresse Fisiológico/fisiopatologia , Animais , Capsaicina/administração & dosagem , Temperatura Baixa , Denervação , Gânglios Simpáticos/efeitos dos fármacos , Gânglios Simpáticos/fisiopatologia , Mucosa Gástrica/patologia , Imobilização , Hepatopatias/etiologia , Hepatopatias/patologia , Neurônios Aferentes/efeitos dos fármacos , Ratos , Ratos Wistar , Úlcera Gástrica/etiologia , Úlcera Gástrica/patologia , Estresse Fisiológico/patologia , Nervo Vago/efeitos dos fármacos , Nervo Vago/fisiopatologiaRESUMO
Previous studies have suggested the presence of multiple muscarinic receptor subtypes in guinea pig gallbladder smooth muscle, although the relative abundance and functional role of these subtypes remains an area of significant research efforts. The present study utilized both radioligand kinetic and functional experiments to further probe the nature of the muscarinic receptors in gallbladder smooth muscle and their mode of coupling to intra- and extra-cellular Ca(2+) sources. Dissociation kinetic studies using [3H]N-methylscopolamine ([3H]NMS) indicated that the binding profile in guinea pig gallbladder smooth muscle could not be reconciled with that expected for a single muscarinic receptor subtype, the latter determined in parallel experiments conducted on the cloned muscarinic M(1)-M(5) subtypes in Chinese hamster ovary (CHO) cells. Furthermore, comparison of the gallbladder data with the dissociation characteristics of [3H]NMS in guinea pig urinary bladder revealed a significantly different kinetic profile, with the urinary bladder, but not the gallbladder, demonstrating biphasic radioligand dissociation kinetics. In functional experiments, carbachol caused a concentration-dependent contraction of guinea pig gallbladder smooth muscle strips in Ca(2+)-free or 5 mM Sr(2+)-substituted physiological salt solutions (PSS) with amplitudes of the maximal contractions corresponding to 45.8+/-8.0% and 33.2+/-6.6% of control responses in normal PSS, respectively. Furthermore, the stimulus-response characteristics of carbachol-mediated contraction appeared significantly altered in Ca(2+)-free PSS relative to normal or Sr(2+)-substituted PSS. The antagonist, methoctramine (1x10(-7)-3x10(-5) M), exerted only a slight inhibition of carbachol (10(-5) M)-induced contractions in 5 mM Sr(2+)-substituted medium, whereas it was significantly more potent in antagonizing gallbladder contractions in response to 10(-5) M carbachol in the absence of extracellular Ca(2+). Both atropine and tripitramine were equipotent in antagonizing carbachol-induced contractions in Ca(2+)-free (pIC(50): 6.85+/-0.11 for atropine and 5.75+/-0.32 for tripitramine) and Sr(2+)-substituted media (pIC(50): 6.88+/-0.25 for atropine and 5.70+/-0.16 for tripitramine), and pirenzepine was only slightly more potent in Ca(2+)-free PSS (pIC(50): 5.66+/-0.23) than in Sr(2+)-substituted PSS (pIC(50): 5.33+/-0.21). Taken together, our data indicate that carbachol contracts guinea pig gallbladder by stimulating two distinct muscarinic receptor subtypes linked to extracellular Ca(2+) influx and intracellular Ca(2+) release. These two subtypes may represent the muscarinic M(3) and M(4) receptors, although the presence of the muscarinic M(2) receptor subtype is also suggested from the binding data.
Assuntos
Vesícula Biliar/efeitos dos fármacos , Receptores Muscarínicos/efeitos dos fármacos , Animais , Células CHO , Cálcio/fisiologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Cricetinae , Feminino , Vesícula Biliar/metabolismo , Cobaias , Humanos , Masculino , Agonistas Muscarínicos/farmacologia , Antagonistas Muscarínicos/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , N-Metilescopolamina/farmacocinética , N-Metilescopolamina/farmacologia , Parassimpatolíticos/farmacocinética , Parassimpatolíticos/farmacologia , Ensaio Radioligante , Receptores Muscarínicos/metabolismo , Bexiga Urinária/efeitos dos fármacosRESUMO
OBJECTIVE: To evaluate the acute effects of a single dose of oral estrogen on left ventricular diastolic function in hypertensive postmenopausal women with diastolic dysfunction. DESIGN: Prospective, double-blind, placebo-controlled, clinical study. SETTING: Cardiology and postmenopausal outpatient clinics of a university hospital. PATIENT(S): Thirty postmenopausal women with hypertension (diastolic blood pressure of >90 mm Hg) and left ventricular diastolic dysfunction (mitral E/A ratio [the ratio of peak velocity of early mitral diastolic filling to late diastolic filling] of <1 and isovolumic relaxation time of >100 ms) were included in the study. Thirty normotensive postmenopausal women with normal left ventricular diastolic function served as the control group. INTERVENTION(S): Conjugated equine estrogen (0.625 mg) was given orally. Left ventricular diastolic function was assessed by Doppler echocardiography at baseline and 3 hours after the administration of estrogen. MAIN OUTCOME MEASURE(S): Left ventricular diastolic filling as assessed by Doppler echocardiography. RESULT(S): Estrogen had no effect on heart rate or blood pressure in either study group. The baseline E/A ratios were 0.72 +/- 0.26 and 1.22 +/- 0.30, and the isovolumic relaxation times were 122 +/- 18 ms and 89 +/-14 ms in the hypertensive and normotensive groups, respectively. Estrogen had no significant effect on any of the Doppler parameters in the normotensive group. In the hypertensive group, there was a trend toward normalization of the E/A ratio (from 0.73 +/- 0.11 to 0.84 +/- 20) and a significant improvement in the isovolumic relaxation time (from 124 +/- 20 ms to 105 +/- 13 ms) in response to the administration of estrogen compared with placebo. CONCLUSION(S): A single dose of oral estrogen caused a significant improvement in left ventricular diastolic filling in hypertensive postmenopausal women with diastolic dysfunction.
Assuntos
Diástole , Estrogênios Conjugados (USP)/uso terapêutico , Hipertensão/tratamento farmacológico , Pós-Menopausa , Disfunção Ventricular Esquerda/tratamento farmacológico , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Ecocardiografia Doppler , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Pessoa de Meia-Idade , Placebos , Estudos Prospectivos , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
AIMS: To evaluate the effects of simvastatin only or combined with continuous hormone replacement therapy on the serum lipid profile in hypercholesterolaemic post-menopausal women. METHODS AND RESULTS: One hundred hypercholesterolaemic post-menopausal women were given either simvastatin 10 mg daily together with oestrogen 0.625 mg and medroxyprogesterone 2.5 mg daily (HRT+simvastatin group) (n:50) or simvastatin 10 mg daily (simvastatin only group) (n:50) in a prospective manner. Serum total, low density lipoprotein, and high density lipoprotein cholesterol and triglyceride levels were measured at baseline, at 3 and 6 months. The initial mean (+/-SD) cholesterol values were as follows for the HRT+simvastatin group and the simvastatin only group, respectively: total cholesterol 240. 0+/-28.0 and 248.9+/-28.2 mg x dl(-1); low density lipoprotein cholesterol 174.7+/-25.6 and 175.1+/-25.9 mg x dl(-1); high density lipoprotein cholesterol 37.2+/-5.0 and 39.9+/-7.3 mg x dl(-1). Compared with the baseline, total and low density lipoprotein cholesterol levels decreased; and high density lipoprotein cholesterol levels increased significantly at 3 and 6 months in both groups. However, the mean percent reduction in total cholesterol and low density lipoprotein cholesterol was significantly greater in the HRT+ simvastatin group compared with the simvastatin only group both at 3 months (12.3+/-7.0% vs 8.9+/-6.2%;P<0.01; and 19.0+/-10.6% vs 13.2+/-10.4%;P< 0.005, respectively) and at 6 months (14.6+/-7.7% vs 11.3+/-7.4%;P<0.05 and 23.3+/-9.7% vs 15.8+/-12.3%;P<0.005, respectively). The mean percent increase in serum high density lipoprotein cholesterol concentrations was also significantly greater in the HRT+simvastatin group compared with the simvastatin only group at both times (14.6+/-11.8% vs 9.8+/-11.8%;P<0.005, at 3 months, and 21.3+/-15.2% vs 11.1+/-12.5;P<0.005, at 6 months, respectively). Furthermore, significantly more patients in the HRT+simvastatin group than in the simvastatin only group attained their target treatment goals dictated by the National Cholesterol Education Program Adult Treatment Panel II Guidelines. Although the mean percent decrease in triglyceride levels was significantly greater in the HRT+simvastatin group at 3 months, the significance disappeared at 6 months. CONCLUSION: The combination of simvastatin and continuous combined hormone replacement therapy seems to be more effective than simvastatin only in the treatment of hypercholesterolaemia in post-menopausal women.
Assuntos
Anticolesterolemiantes/administração & dosagem , Terapia de Reposição Hormonal , Hipercolesterolemia/tratamento farmacológico , Pós-Menopausa , Sinvastatina/administração & dosagem , Anticolesterolemiantes/uso terapêutico , Feminino , Humanos , Hipercolesterolemia/sangue , Lipídeos/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Sinvastatina/uso terapêutico , Fatores de TempoRESUMO
The presence of M(1)-M(4) receptors in guinea-pig gallbladder smooth muscle cells has been reported recently. The majority of these receptors are said to be of M(2) subtype. However, there are controversial reports about the functional muscarinic receptors that mediate contraction in this tissue. Similar to gallbladder, it was claimed that M(4) receptors mediate guinea-pig uterine contractions, but these receptors have appeared to be of M(2) subtypes later. Therefore, the antagonistic affinities of three M(2)-selective muscarinic antagonists were determined in contraction and radioligand binding experiments in guinea-pig gallbladder in the present study. The antagonistic affinity values (p K(i)) of gallamine, tripitramine and imperialine were as follows, respectively: 6.28+/-0.15, 8.65+/-0.10 and 6.55+/-0.07 against 0.250 n m [(3)H]QNB binding. All three antagonists displaced the concentration- response curves to carbachol to the right in parallel without affecting the maximum responses. The p A(2) values obtained from constrained Schild plots (-log K(B)) were 4.14+/-0.18 for gallamine, 6.79+/-0.09 for tripitramine, and 7.02+/-0.09 for imperialine. The antagonistic affinity values of gallamine, tripitramine and imperialine for M(2) receptors are reported to be 6. 3, 9.6, 7.7, respectively. The p A(2) values obtained in this study clearly indicate that the primary muscarinic receptors involved in carbachol-induced guinea-pig gallbladder contraction are not of M(2) subtype. The poor correlation between the antagonistic affinity values of these antagonists obtained at radioligand binding (p K(i)) and contraction (p A(2)) experiments also support the conclusion that the majority of muscarinic receptors which have been reported to be of M(2) do not mediate the contractile responses.