RESUMEN
BACKGROUND: Definition of Cardiac Syndrome X (CSX) refers to groups of patients with positive exercise stress test and normal epicardial coronary arteries on coronary angiography accompanied by chest pain. Although the etiology of CSX is not completely understood, there is a common consensus that its pathophysiology may be associated with endothelial dysfunction resulting in impaired coronary flow. Some polymorphisms observed on the MTHFR gene cause inactivation of the MTHFR enzyme, leading to hyperhomocysteinemia and homocysteinuria, which are prominent risk factors of cardiovascular and cerebrovascular diseases. It was aimed to explain the association of the endothelial dysfunction, which is thought to play a role in the pathophysiology of CSX, with C677T polymorphism on MTHFR gene based on genetic basis. METHODS: A total of 176 CSX patients and 196 healthy subjects with similar age and clinical features were compared in terms of C677T polymorphism of the MTHFR gene. RESULTS AND CONCLUSION: There was no significant difference in terms of MTHFR gene C677T polymorphism between CSX patients and controls. When genotypic distribution was compared based on gender in both patients and controls, no significant difference was found between male and female subjects (P>.05). As fasting blood sugar and urea values were significantly higher, alanine aminotransferase and gamma-glutamyl transferase levels were significantly lower in the patients than the controls (P<.05). Described family story of the patients was significantly higher than the controls (P<.05). These suggest that homocysteine metabolism in CSX is not directly related to the endothelial dysfunction and thus the effect on the microvascular circulation.
Asunto(s)
Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Angina Microvascular/epidemiología , Angina Microvascular/genética , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genéticaRESUMEN
BACKGROUND: Drug-induced conditioned place preference (CPP) is linked to the addictive properties of the drug used. The number of studies that have investigated the effects of propofol on CPP is limited. Research findings suggest that nitric oxide (NO) might play an important role in substance use disorders. OBJECTIVES: The present study sought to investigate the role of the nitrergic system on the rewarding effects of propofol by using the CPP protocol in rats. METHODS: The experiment followed habituation, pre-conditioning, conditioning, and post conditioning sessions. Male Wistar albino rats weighing 240-290 g were divided into eight groups: control (saline), propofol (10, 20, and 40 mg/kg), the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) alone (30 and 60 mg/kg), and in combination with propofol (30 and 60 mg/kg L-NAME plus 40 mg/kg propofol) (n = 8 for each group). The CPP effects of propofol, L-NAME, saline, and their combinations were evaluated. All the drug and saline administrations were performed by intraperitoneal (ip) injections. RESULTS: Propofol (10-40 mg/kg) produced CPP that was statistically significant relative to saline. Propofol-induced CPP was significantly reversed by pretreatment with L-NAME. When administered alone, L-NAME did not produce CPP and also did not produce any significant change on locomotor activity of naïve rats. CONCLUSION: Our results suggest that propofol produces CPP effects in rats and that NO-related mechanisms may be responsible for propofol-induced CPP. Thus, propofol might have the potential to be addictive, and this possibility should be considered during clinical applications of this drug.
Asunto(s)
Condicionamiento Psicológico/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Propofol/farmacología , Animales , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Locomoción/efectos de los fármacos , Masculino , Propofol/antagonistas & inhibidores , Ratas , RecompensaRESUMEN
Dexmedetomidine (DEX) is an alpha-2 adrenergic agonist drug recently introduced to anesthesia practice. Certain agents used in anesthesia practice have been associated with abuse and addiction problems; however, few studies have investigated the role of DEX on addictive processes. Here, the effects and possible mechanisms of action of DEX on conditioned place preference (CPP), a model used for measuring the rewarding effects of drug abuse in rats, was investigated. The CPP apparatus was considered "biased" as the animals preferred the grid side to the mesh side. Male Wistar albino rats weighing 250-300 g were divided into several groups, including control (saline), morphine (10mg/kg), DEX (2.5-20 µg/kg), naloxone alone (0.5mg/kg) and a combination (0.5mg/kg naloxone plus 20 µg/kg DEX) (n=7-8 for each group). The CPP effects of morphine, DEX, saline and the combination were evaluated. All the drug and saline administrations except naloxone were performed by intraperitoneal (ip) injections. Naloxone was injected subcutaneously (sc) when given alone or in combination with DEX. Morphine (10mg/kg) and DEX (5-20 µg/kg) produced CPP that were statistically significant relative to saline-injected rats. DEX-induced CPP was significantly reversed by pretreatment with naloxone, an opioid antagonist. Naloxone alone treatment did not cause any significant effect on CPP. Our results suggest that DEX produces CPP effects similar to morphine in rats and that opioidergic mechanism may be responsible for DEX-induced CPP. Thus, DEX might have the potential to be addictive, and this possibility should be considered during clinical application of this drug.