Methods and findings in experimental and clinical pharmacology最新文献

The main biologically active constituents of Aronia melanocarpa fruit juice (AMFJ) are polyphenolics, amongst them flavonoids, mainly anthocyanins. The aim of the present study was to investigate the effects of AMFJ (5 and 10 mL/kg) on anxiety using the social interaction test, on locomotor activity in the open field test and on working memory in the object recognition test in rats. AMFJ showed an anxiolytic-like effect which was demonstrated by a dose-dependent increase in the time of active social contacts between the test partners. The effects of both AMFJ doses were comparable to the effect of diazepam (1 mg/kg). AMFJ neither changed significantly horizontal and vertical locomotor activity, nor did it adversely affect working memory.

Combinations of caffeine with L-arginine or with taurine can enhance the effect of caffeine, but the mechanisms remain elusive. This study was designed to test the hypothesis that stimulant effects of central nervous system nitric oxide (NO) may explain the beneficial effect of caffeine on combinations with amino acid, L-arginine or taurine. Caffeine increased the spontaneous locomotor activity dose-dependently (2-10 mg/kg) in mice. The locomotor activity induced by caffeine at a dose of 2 mg/kg was enhanced by combined administration of L-arginine at a dose of 600 mg/kg, or taurine at a dose of 400 mg/kg, respectively. For both combinations, enhancement was significantly inhibited by pretreatment with N-nitro-L-arginine methyl ester (L-NAME) at a dose of 40 mg/kg. These results suggest that the enhancement induced by combining caffeine with amino acid might be regulated at least in part by NO in the central nervous system.

The genus Ecballium only comprises the Ecballium elaterium (EE) (L.) A.Rich species which is a wild medicinal plant found in the Mediterranean region. EE fruit juice is widely used in Turkish folk medicine for the relief of sinusitis and for several illnesses. Up to date, there has been no report on the genotoxicity of EE fruit juice. Thus, the aim of this study was to investigate the potential genotoxic effects of EE fruit juice using the Allium test system. Allium cepa (A. cepa) bulbs were treated with four concentrations (10 ml/L, 20 ml/L, 50 ml/L and undiluted) of EE fruit juice for 72 h and tap water (pH 7.3) was used as a control. The results showed significant dose-dependent (P < 0.05) inhibition of root growth and mitodepressive effects on cell division in A. cepa root tip cells after the EE fruit juice treatments. Also, EE fruit juice significantly increased the dose-dependent frequency of chromosome aberrations (breaks, stickiness and pole deviations) in root tip cells and micronucleus formations. There was no dividing cell in the undiluted EE fruit juice treated group, but there were pyknotic/apoptotic cells with varying frequency.

Abacavir sulfate/lamivudine, Adalimumab, AdCD40L, Adefovir, Adefovir dipivoxil, Ambrisentan, Amlodipine, Amlodipine besylate/olmesartan medoxomil, AN-2728, Apixaban, Aripiprazole, Armodafinil, Atazanavir sulfate, Atomoxetine hydrochloride, Atrasentan, Azacitidine, Bevacizumab, Blinatumomab, Bortezomib, Bosentan, Carfilzomib, Caspofungin acetate, Cediranib, Cetuximab, Choriogonadotropin alfa, Clevudine, Clindamycin phosphate/benzoyl peroxide, Clofarabine, Daidzeol, Darunavir, Dasatinib, Decitabine, Deferasirox, Deforolimus, Degarelix acetate, Denenicokin, Dexlansoprazole, Duloxetine hydrochloride, Elacytarabine, Enfuvirtide, Enoxaparin, Entecavir, Eribulin mesilate, Erlotinib hydrochloride, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Ezetimibe/simvastatin, Forodesine hydrochloride, Fosamprenavir calcium, Gefitinib, Gemtuzumab ozogamicin, Golimumab, Imatinib mesylate, Imetelstat, Insulin gl'argine, Insulin glulisine, Interferon alfa-2b XL, Ivabradine hydrochloride, Lacosamide, Lenalidomide, Lintuzumab, Liposomal adriamycin, Liposomal belotecan, Liposome-encapsulated fentanyl, Lopinavir/ritonavir, Lutropin alfa, LY-207320, Maraviroc, Mecasermin, MKC-253, MP-470, NGR-TNF, Nilotinib hydrochloride monohydrate, Ofatumumab, Olmesartan medoxomil, Omacetaxine mepesuccinate, PAN-811, Panobinostat, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pemetrexed disodium, Perospirone hydrochloride, PF-734200, Phentermine/topiramate, Pimecrolimus, Pitavastatin calcium, Plerixafor hydrochloride, Pregabalin, Raltegravir potassium, Ramelteon, Ranibizumab, Recombinant Bet V1, Recombinant human insulin, Regadenoson, rhITF, Romidepsin, Rosuvastatin calcium, Ruboxistaurin hydrochloride, Rufinamide, Sapropterin dihydrochloride Saracatinib, SB-73, SC-599, Seliciclib, Sirolimus-eluting stent, Sorafenib, Sunitinib malate, Tadalafil, Tanespimycin, Tapentadol hydrochloride, Tegaserod maleate, Telbivudine, Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tenofovir disoproxil fumarate/emtricitabine/efavirenz, Ticlopidine hydrochloride, Tigecycline, TST-10088, Tularemia vaccine, Valsartan/amlodipine besylate, Vandetanib, Vardenafil hydrochloride hydrate, Vincristine, Vorinostat, Yttrium 90 (90Y) ibritumomab tiuxetan.

The folklore medicine of primitive people has been greatly appreciated for centuries. Many researchers study the curative efficiency and mode of action of various medicinal plants. Serum glucose level, lipid profile, glucose tolerance, hepatic and muscle glycogen contents as well as the activities of hepatic hexokinase and glucose-6-phosphatase recovered significantly after oral administration of ethyl acetate fractions of Eugenia jambolana (E. jambolana) or Musa paradisiaca (M. paradisiaca) in separate (E. jambolana L.: 200 mg/kg of body weight and M. paradisiaca: 100 mg/kg of body weight) or combined form for 90 days (twice a day through gavage) to streptozotocin-induced diabetic rats. The loss in body weight of diabetic animals was reversed and serum levels of insulin as well as C-peptide, which were found to be reduced in diabetic rats, increased significantly after oral administration of the fractions. A histological study of the rats' pancreas revealed that after 90 days of oral treatment with the plant fractions in separate or combined form, the size and volume of pancreatic islets in diabetic treated rats increased significantly compared with the diabetic control group. Treatment of diabetic rats with the combined dose (300 mg/kg of body weight) of plant fractions (200 mg E. jambolana and 100 mg M. paradisiaca) was found to be more effective than treatment with the individual fraction. The doses of E. jambolana and M. paradisiaca selected for this study are the optimum antihyperglycemic doses of the plant fractions, which were determined after conducting a dose-dependent study at various dose levels (50-500 mg/kg) in our pilot experiments. The plant fractions were found to be free from metabolic toxicity. Through HPTLC finger printing, three different compounds were noted in the ethyl acetate fraction of E. jambolana L. and eight different compounds in the ethyl acetate fraction of M. paradisiaca L.

Recent clinical studies have indicated that grapefruit juice (GFJ) improves insulin resistance and reduces weight gain in humans. The effect of GFJ on glucose tolerance and metformin-induced lactic acidosis in normal, non-diabetic in rats is hereby investigated. Three groups (A, B, C) of 20 male Wistar rats each, were treated with stepwise, escalated oral doses of 0, 1.0, 2.0, 3.0 (group A), and 3.0 ml/kg body weight (groups B and C) of GFJ. Group C rats additionally received 250 mg/kg body weight of metformin. All the animals were sacrificed after 14 days of treatment. Fasting blood glucose levels were significantly (P < 0.0001) lower in GFJ-treated test (2.9 +/- 0.4 mmol/L) compared with control (3.7 +/- 0.39 mmol/L) rats, but 1.5-hr plasma insulin levels were similar. GFJ alone or in combination with metformin, significantly (P < 0.05) lowered blood glucose levels compared with control animals. Blood lactic acid levels were similar in GFJ-treated test (2.81 +/- 1.4 mmol/L) and control (2.54 +/- 0.7 mmol/L) rats, respectively, but were significantly increased (P = 0.0079) in rats that were treated with either metformin alone (5.38 +/- 2.53 mmol/L) or in combination with GFJ (8.31 +/- 3.48 mmol/L). Metformin concentration in liver tissue was significantly higher (P < 0.05) in GFJ-treated (397 +/- 19 microg/g) than in control (280 +/- 15 microg/g) rats, respectively. Plasma metformin levels were comparable between the control (95 +/- 8.1 microg/ml) and GFJ-treated test (108 +/- 20 microg/ml) rats, respectively. Liver tissue metformin concentrations and plasma lactic acid levels showed significant correlation in both control (P = 0.0122; r(2) = 0.9080) and GFJ-treated test rats (P = 0.0005; r(2) = 0.9893). Although GFJ may be beneficial to diabetic patients, it may exacerbate lactic acidosis in diabetic patients taking metformin concurrently.

The present study was carried out to examine the effect of administration of vineatrol in the middle cerebral artery (MCA) occlusion model of stroke in rats. Rats were anesthetized using chloral hydrate (400 mg/kg i.p.) and subjected to 2 h of transient MCA occlusion. Vineatrol was administered at doses of 10, 20 and 40 mg/kg i.p. to different groups. In total, four injections of vineatrol were given, i.e., at the time of MCA occlusion, 1 h after MCA occlusion, at the time of reperfusion and 30 min after reperfusion. Neurological deficit and motor performance tests (grip, foot fault, rotarod performance, spontaneous locomotor activity tests) were carried out 24 h after MCA occlusion. Thereafter, the rats were sacrificed to estimate markers of oxidative stress: malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD). A vehicle-treated group was also run in parallel. Vineatrol at the dose of 10 mg/kg i.p. neither improved neurological deficits nor decreased the elevated level of MDA compared with vehicle-treated MCA-occluded rats. However, higher doses of vineatrol (20 and 40 mg/kg i.p.) afforded significant protection, as shown by the increase in scoring on motor performance tests and significant attenuation of the elevated MDA level observed after MCA occlusion. Levels of GSH and SOD were significantly increased. The results demonstrate that administration of vineatrol is able to reduce the neuronal damage caused by focal ischemia in the MCA occlusion model of stroke in rats.

In the process of evolution a number of complicated mechanisms have developed to protect the gastric mucous membrane, e.g., angiogenesis and stimulation of mucosal growth. The aim of this study was to determine the role of vascular endothelial growth factor (VEGF) administered intraperitoneally in the gastroprotective response to stress-induced acute gastric ulcers in rats. A dramatic increase in the number of blood vessels was observed when VEGF was injected 24 h before stress exposure. Gastric secretion, depth of ulceration and ulceration index decreased significantly after VEGF application. The results demonstrate the gastroprotective effect of VEGF on stress-induced ulceration.

This study investigated the immunopotentiating effect of Khamira Marwarid (KM), an herbo-mineral Unani preparation, in an animal model. KM was administered to mice orally at a dose level of 2 g/kg body weight for 5, 10, 15 or 30 days, following which the animals were sacrificed for hematology and immune function testing, including lymphoid organ weight and cellularity. The group of animals receiving KM showed a significant increase (P < 0.05) in the relative organ (spleen and thymus) weight. Cellularity of the spleen and bone marrow also increased significantly (P < 0.01). Groups receiving KM for 10 and 15 days showed an increase in hemoglobin, red blood cells (RBCs) and total white blood cells (WBCs) (P < 0.01). The humoral immune response, evaluated by the plaque-forming cell (PFC) assay after challenging the mice with goat RBCs, was better in all treated groups when compared to controls. Maximum hemagglutination titer was obtained in mice treated with KM for 15 days. Ovalbumin-specific serum IgG levels in the treated mice also increased significantly (P < 0.01), suggesting an immunopotentiating effect for the preparation. Administration of KM resulted in elevated levels of IgG2a and IgG2b. A comparison of anti-ovalbumin IgE and IgG was also done; anti-ovalbumin IgE decreased, with a concomitant increase in anti-ovalbumin IgG. Administration of KM for 10 or 15 days elicited an increase in the delayed-type hypersensitivity (DTH) response. Taken together, the results suggest an immunostimulatory effect for KM through a mechanism leading to a Th1-dominant immune state.

Recently, new concerns on the safety profile of nonsteroidal anti-inflammatory drugs (NSAIDs) have been raised by the European Medicines Agency (EMEA) and other regulatory authorities. The safety profile of oral dexketoprofen trometamol for the treatment of acute mild to moderate pain of different causes in actual conditions of use in the primary care setting was assessed. A prospective cohort study was designed to evaluate the tolerability of dexketoprofen compared with other commonly prescribed analgesics. Medications were given according to specifications in the summary of product characteristics. The intensity of pain was assessed at baseline and at days 1 and 7 of drug treatment using a 100-mm visual analog scale (VAS). Adverse events (AEs) were recorded. A total of 7,337 patients (median age [IQR] = 46 [33-61] years) were included in the study comparing dexketoprofen (n = 5,429), diclofenac (n = 485), ibuprofen (n = 479), paracetamol (n = 459), metamizole (n = 207), aceclofenac (n = 103), naproxen (n = 74), piroxicam (n = 69) and dexibuprofen (n = 32). The reasons for use were: musculoskeletal disorders, headache, dysmenorrhea and odontalgia. Treatment compliance was very high. Metamizole-paracetamol and dexketoprofen showed the lowest prevalence of AEs (2.7% and 3.6%, respectively), while aceclofenac-diclofenac showed the highest prevalence (8.2%) (P < 0.0001). AEs most frequently observed during NSAID treatment were those related to the gastrointestinal tract (3.5% of subjects, 84% of all AEs), followed by AEs related to the nervous system (0.4%) and skin (0.1%). Most of the reported AEs (91.3%) were of mild to moderate intensity (303 of 332) and only 3.3% of them were considered severe (11 of 332). Risks for gastrointestinal AEs were adjusted for age, gender, history of previous NSAID intake, gastroprotective drugs and reason for prescription. Taking metamizole-paracetamol as the reference group, the odds ratios (OR, 95%) were: 1.30 (0.77-2.19) for dexketoprofen, 1.57 (0.79-3.13) for ibuprofen and dexibuprofen, 2.31 (0.64-8.27) for naproxen, 2.63 (0.85-8.15) for piroxicam and 3.37 (1.87-6.06) for aceclofenac-diclofenac. These results confirm the safety of oral treatment with dexketoprofen in patients with acute pain of various etiologies observed in previous studies and support the use of dexketoprofen as a first-line drug for the approved therapeutic indications.