Ultrasonographic evaluation of femoral cartilage thickness in patients with ankylosing spondylitis.

OBJECTIVE: To evaluate femoral cartilage thickness in patients with ankylosing spondylitis (AS) by using ultrasonography. METHODS: Eighty-four patients (55 M, 29 F) with a diagnosis of AS and 84 age-, gender- and body mass index-matched healthy subjects were enrolled. Demographic and clinical characteristics of the patients including disease duration, morning stiffness and medications were recorded. The femoral cartilage thicknesses of both knees were measured with a 7-12 MHz linear probe while subjects' knees were held in maximum flexion. Three mid-point measurements were taken from both knees (lateral femoral condyle (LFC), intercondylar area (ICA) and medial femoral condyle (MFC)). RESULTS: Concerning both ICA (p < 0.001) and left MFC (p = 0.013), cartilage measurements were significantly thicker in AS patients than control subjects. In a subgroup analysis (anti-tumour necrosis factor (TNF) users vs anti-TNF naive), cartilage thickness measurements - bilateral ICA (p = 0.000) and left MFC (p = 0.017) - were found to be greater in AS patients under anti-TNF treatment (n = 65) when compared with those of healthy controls. CONCLUSION: We imply that AS patients seem to have thicker femoral cartilage, which could be related to anti-TNF treatment.

Inhibitory effect of agmatine on naloxone-precipitated abstinence syndrome in morphine dependent rats.

Effects of agmatine, which is an endogenous polyamine metabolite formed by decarboxylation of L-arginine, were investigated on the morphine abstinence syndrome in rats. Two pellets containing 75 mg morphine base (total 150 mg) were implanted subcutaneously on the back of rats. Seventy-two hours after morphine implantation, agmatine sulphate (20, 30 and 40 mg/kg) or saline was injected intraperitoneally. Forty-five min later, naloxone (2 mg/kg) was injected intraperitoneally to induce precipitated withdrawal. Immediately after naloxone injection, rats were observed for 15 min, and abstinence syndrome signs, which included jumping, wet dog shake, writhing, defecation, ptosis, teeth chattering and diarrhea were counted or rated. Agmatine attenuated all of the signs of the morphine abstinence syndrome dose dependently and significantly. Our results suggest that agmatine prevents naloxone-precipitated abstinence syndrome in morphine dependent rats; thus, this drug may be beneficial in the treatment of opioid dependence.

In vitro microsomal [correction of mircosomal] metabolism of N-benzyl and N-benzoylnornicotine derivates by rat.

The in vitro hepatic microsomal metabolism of N-1'-benzylnornicotine, N-l'-(p-chlorobenzyl)nornicotine, N-1'-benzoylnornicotine and N-1'-(p-chlorobenzoyl) nornicotine was studied using hepatic washed rat microsomal preparations fortified with NADPH. Substrates and their potential metabolites were synthesized, characterised by spectral methods, and separated using a reverse phase HPLC system consisted of a C18 column and a mobile phase composition of acetonitrile: phosphate buffer. Substrates and their potential metabolites were extracted from biological systems with dichloromethane. Metabolites detected were compared with retention times and uv spectra of authentic standards. Metabolic experiments indicated that oxidative dealkylation leading to the formation of nornicotine and the corresponding aldehydes was a major route of metabolism for N-alkylnornicotine substrates. In addition, N-1'-(p-chlorobenzyl)nornicotine produced the corresponding lactam and amide metabolites. N-Acylnornicotines were hydrolysed to nornicotine.

In vivo metabolism of 4-fluorobenzoic acid [(5-nitro-2-furanyl)methylene] hydrazide in rats.

It is known that substituted hydrazide hydrazone derivatives have several biological and pharmacological activities; there is limited literature on the metabolism of hydrazide hydrazones in rats. In our previous study, 4-fluorobenzoic acid [(5-nitro-2-furanyl)methylene]hydrazide (S) was found active against Staphylococcus aureus ATCC 29213. Therefore, we planned to study the in vivo metabolism of S in rats. The substrate was administered in doses of 50 mg/kg or 100 mg/kg intraperitoneally. Blood samples were collected at 0, 5, 15, 30, 45 min and 1, 1.5, 2, 4, 8, 12, 24, 48 h after administration. The substrate and its potential metabolites were separated using HPLC on a reverse phase system. 4-Fluorobenzoic acid and one unidentified metabolite were detected together with substrate.

Gamma-vinyl-GABA potentiates the severity of naloxone-precipitated abstinence signs in morphine-dependent rats.

Effects of gamma-vinyl-GABA (GVG), an antiepileptic drug that inhibits GABA transaminase and increases extracellular GABA concentrations in the brain, were investigated on the morphine abstinence syndrome (AS) in male Wistar rats. Two morphine pellets (75 mg morphine base in each) were implanted subcutaneously on the back of the rats. Seventy-two hours after the morphine implantation, naloxone (NL, 2 mg kg-1) was injected intraperitoneally (i.p.) to induce precipitated morphine AS. GVG was administered at the doses of 250 mg kg-1 (n = 11) and 500 mg kg-1 (n = 11) i.p. 24 h prior to AS and at the dose of 500 mg kg-1 (n = 13) i.p. 6 h prior to AS. Immediately after NL injections, rats were observed for 5 min and AS signs (jumping, teeth chattering, wet dog shake, diarrhoea, ptosis and defecation) were assessed. The behavioural signs of GVG-treated rats were compared with the control groups (n = 10) during the AS. Jumping, wet dog shake, teeth chattering were found to be significantly increased in all of the GVG-treated groups. Ptosis was found to have increased in only 500 mg kg-1 GVG groups. GVG potentiated the severity of morphine AS signs. GVG does not seem to have any therapeutic potential for treatment of morphine abstinence unlike some other drugs that enhance GABAergic transmission.

Investigation of extracellular L-citrulline concentration in the striatum during alcohol withdrawal in rats.

In this study, changes in striatal extracellular L-citrulline concentrations were investigated hourly for 5 h following alcohol withdrawal in chronic alcohol feeding Wistar rats. Alcohol (7.2% ethyl alcohol, v/v) was given to rats as modified liquid diet for 20 days. Signs of alcohol withdrawal appeared from the 1st h of alcohol withdrawal and the total alcohol withdrawal scores remained higher during the course of experiments. The mean of basal levels of L-citrulline in the microdialysis samples collected in conscious rat model from the striatum of control and alcoholized rats were found to be 1.28 +/- 0.48 microM and 0.35 +/- 0.08 microM, respectively. L-citrulline levels in the striatum of alcoholized rats increased by 4 folds significantly within 1 h following alcohol withdrawal. The increased striatal L-citrulline concentration was blocked by NG-nitro-L-arginine methyl ester (L-NAME; 60 mg/kg), a nitric oxide synthase inhibitor, pretreatment. Our results indicate an increased L-citrulline level in the rat striatum during early alcohol withdrawal and this situation may be related to an increased nitric oxide production.