Involvement of opioidergic and GABAergic systems in the anti-nociceptive activity of the methanolic extract of Cuscuta Epithymum Murr. in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Cuscuta epithymum Murr. (CE) is a parasitic plant used as a traditional medicine to treat various diseases such as muscle and joint pains and headache different parts of the world, Europe in the north, Asia in the east. AIM OF THE STUDY: In this study, we aimed to investigate the anti-nociceptive effect of the methanolic extract of the aerial parts of CE and its probable mechanism(s) in mice. MATERIALS AND METHODS: The anti-nociceptive activity of different doses of CE methanolic extract (2.5, 5, 10, 25, 50 and 100 mg/kg, i.p.) was assessed using tail flick, formalin and writhing tests. Morphine (5 mg/kg, s.c.) was used as positive control drug. The possible mechanisms were evaluated by using naloxone (4 mg/kg, i.p.), ondansetron (4 mg/kg, i.p.), picrotoxin (0.6 mg/kg, i.p.) and MK-801 (0.03 mg/kg, i.p.). RESULTS: GC-MS analysis indicated that one of the main components of CE extract was terpenoid compounds. The CE extract (25-100 mg/kg), like morphine, reduced tail flick latency and nociceptive response in both phases of the formalin test. We also observed that the extract significantly decreased the number of abdominal contractions dose-dependently from 5 to 100 mg/kg. The results of tail flick and the first phase of formalin test proved that unlike ondansetron and MK-801, naloxone and picotroxin were able to reverse the anti-nociceptive effect of CE extract. CONCLUSION: Our observations showed the anti-nociceptive potential of the CE extract, which may be mediated by opioidergic and GABAergic systems.

Efficacy of Preoperative Administration of Acetaminophen and Melatonin on Retrobulbar Block Associated Pain in Cataract Surgery.

BACKGROUND: Retrobulbar block is one of the chosen methods for local anesthesia in cataract surgery. Since it is a painful procedure, using analgesic and sedative drugs is recommended. Current medications have side effects and evaluating of new drugs or new uses of existing safer drugs is necessary. OBJECTIVES: The aim of this study was to compare the administration of melatonin and acetaminophen on pain and hemodynamic changes during retrobulbar block. METHODS: In a double-blinded randomized trial, 180 patients undergoing cataract surgery were randomly divided into three groups: Melatonin group (received melatonin 6 mg), acetaminophen group (received acetaminophen 500 mg), and control group (received placebo). All drugs were administered orally 60 min before arrival to the operating room by nurses blinded to the drugs administered. All patients received fentanyl 0.5 µg/kg before retrobulbar block intravenously. Hemodynamic variables and pain score in each patient were evaluated on arrival in the operating room, during retrobulbar block, during surgery, 20 min after operation, at the end of surgery, and in the recovery room. In case of pain score more than three, additional fentanyl was administered. All data were recorded in structured data sheets. RESULTS: Data analysis indicated no significant differences among the groups at baseline on any of the demographic variables. Both acetaminophen and melatonin reduced the pain score significantly compared with control during retrobulbar block (P < 0.05 and P < 0.01, respectively). Administration of additional fentanyl was significantly lower in the melatonin group than the control group (P < 0.05). Hemodynamic changes were not significantly different among all groups. CONCLUSIONS: For the first time, as far as we have studied, the analgesic effect of acetaminophen on the retrobulbar block was indicated. We also showed that melatonin can reduce pain during retrobulbar block leading to reduction of additional fentanyl during operation. It seems that both melatonin and acetaminophen may have a beneficial effect on pain control in the retrobulbar block.

Iron overload is associated with perihematoma edema growth following intracerebral hemorrhage that may contribute to in-hospital mortality and long-term functional outcome.

Iron overload may contribute to brain damage that involves delayed brain atrophy, edema, and neuronal cell death as well as unfavorable outcome following ischemic stroke and intracerebral hemorrhage (ICH). This prospective study was performed to determine the association of serum ferritin level, an iron storage protein, with perihematoma edema (PHE) growth as well as in-hospital mortality and long-term clinical outcome of patients with ICH. Data was collected from patients with ICH from February 2011 to April 2012. Demographic and clinical data were recorded and serum ferritin was measured on admission. Brain CT scan was performed on admission and 72 hours later. Volume of hematoma and PHE was calculated using ABC/2 formula. Functional outcome was assessed using modified Rankin Scale. A total of 63 patients were included in this study, of those 11 (17.5%) patients died during the first 72 hours of admission. There was a significant correlation between PHE growth during first 72 hours of hospitalization and serum ferritin (P<0.001) as well as history of diabetes mellitus (P<0.001). PHE growth during the first 72-hours of hospitalization and baseline hematoma volume were both predictors of in-hospital mortality and poor outcome (P=0.026 and P=0.035, respectively). These results indicate the role of iron overload in the development of PHE following ICH. However, it seems that serum ferritin level is not directly associated with in-hospital mortality and long-term functional outcome.

Smoking as a risk factor for development of Secondary Progressive Multiple Sclerosis: A study in IRAN, Guilan.

BACKGROUND: Cigarette smoking seems to contribute to susceptibility and progression of multiple sclerosis (MS).Although the incidence of MS in Iranian population has increased during recent years, the effects of smoking on progression of MS have not been studied. The aim of this study was to investigate the association between cigarette smoking and development of secondary progressive MS (SPMS) in Iranian patients with MS. METHODS: This study was carried out on patients registered in the MS Society (Guilan, Iran) database. Using a structured questionnaire, information on smoking status of 400 of patients could be obtained. The association between cigarettes smoking and SPMS was analyzed by Cox regression model. RESULTS: The relationship between smoking and development of SPMS was still evident after adjusting for age at disease onset, gender and number of relapses per year (P =0.004). Smoking more than 10 cigarettes per day increased risk of development of SPMS (HR: 2.43; 95% CI: 1.28 to 4.6; P =0.007). CONCLUSIONS: Our results indicated that smokers have an increased risk for progression of relapsing-remitting MS (RRMS) to SPMS compared with non-smokers. We also showed that the disease progression may be influenced by increase of cigarette smoking.

Nitric oxide involvement in pancreatic beta cell apoptosis by glibenclamide.

Glibenclamide as a second-generation compound of sulfonylurea has widely been used in the treatment of type 2 diabetes patients. It has been shown that it induces apoptosis in beta cells, which is partially mediated by Ca(2+) influx. Here, we investigated the role of nitric oxide (NO) and nitric oxide synthase (NOS) isoforms on glibenclamide-induced apoptosis in rat insulinoma cells. Our results showed that glibenclamide induces NO generation (measured as nitrite) that is accompanied with decrease of cell viability in a defined concentration of glibenclamide. The effects of glibenclamide on cell viability were partially inhibited after treatment with N(G)-nitro-L-arginine methyl ester (L-NAME), inhibitor more selective for constitutive nitric oxide synthase, and in the presence of D600--a blocker of voltage-gated L-type Ca(2+) channels inhibited Ca(2+) influx into beta cells, whereas aminoguanidine (AG), a preferential inhibitor of inducible NOS, was significantly less effective. Analysis of DNA fragmentation by electrophoresis and staining with Hoechest 33342 and propidium iodide showed that L-NAME, but not AG, prevented DNA fragmentation and decreased the number of cells with condensed and fragmented nuclei. It revealed that the effects of glibenclamide on apoptosis were partially inhibited by treatment with L-NAME. In conclusion, we have shown that NO production in glibenclamide treated cells may be involved in the induction of apoptotic cell death in pure beta cell line and it may be due to Ca(2+) dependent activation of constitutive NOS isoforms.