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Cerebrovascular accident (CVA) is defined as the rapid development of localized or global clinical signs of neurological dysfunction with no apparent cause other than that of vascular origin. A variety of risk factors have been identified and associated with the occurrence of Ischemic CVA, including glucose and lipid metabolism disturbances. We conducted a retrospective study at the Clinic of Neurology, Fann. Our study focused on medical records of patients with ICVA confirmed by imaging, hospitalized from January 1 to December 31 2010. All patients underwent complete lipid profile (total cholesterol, triglycerides, HDL; LDL level was calculated using Friedwald formula), kidney function tests and fasting blood sugar test were performed within 48 hours of admission. Data were analysed using univariate technique and then using bivariate technique tanks to SPSS 16.0 software. We collected 235 files. We here report a case series of patients between ages 10-99 years, with an average age of 67,06 years. Males were 42,55%, sex-ratio was 0,74 in favour of women. 26% of cases had impaired fasting glucose levels during the acute phase of ICVA. The lipid profile showed an increase in total cholesterol level in 52.34% of patients. Low levels of HDL cholesterol were found in 34.47% of patients. Hypertriglyceridemia was only observed in 3% of patients. LDL levels were high in 12,76% of patients. Atherogenicity index was high in 25,53% of patients. Disturbances of blood glucose and lipid profile are often associated with ICVA and should be taken into account to ensure better secondary prevention., Competing Interests: Conflits d’intérêts Les auteurs ne déclarent aucun conflit d’intérêts.

Anti-SRP myopathy represents 4 to 6% of all the inflammatory myopathies. It has been described since the 80s and its influence on pregnancy and vice versa has been highlighted recently. We report two cases of anti-SRP myopathy associated with pregnancy. In the first case, the initial manifestations of the disease started in post partum and the second case was an anti-SRP myopathy patient before pregnancy. In both cases we objectified outbreaks during post-partum. Pregnancy seems to promote outbreaks. The inactive myopathy seems to presents no serious maternal-fetal complications as well as the usual dose of corticosteroids. The treatment (corticosteroid) during pregnancy is indicated given the risk of worsening during the post-partum., Competing Interests: The authors declare no competing interests.

We have shown that intravenous (i.v.) administration of anti-methotrexate (MTX) antibodies (AMAb) reduces the systemic exposure of intraperitoneal (i.p.) MTX therapy, and we have proposed that AMAb effects on MTX systemic exposure would allow a reduction in MTX-induced systemic toxicity (i.e., producing a desirable antagonistic effect). However, many literature reports have shown that anti-toxin antibodies occasionally demonstrate unexpected agonist-like activity, increasing the extent of toxicity induced by their ligand. In this report, we have utilized a pharmacokinetic-pharmacodynamic (PKPD) model to predict the potential of AMAb to increase or decrease the magnitude of MTX-induced body weight loss in mice. Simulations predicted that both anti-MTX immunoglobulin G (AMI) and anti-MTX Fab fragments (AMF) would lead to increases or decreases in MTX toxicity, with effects dependent on the dosing protocol used. Based on the computer simulations, two protocols were selected for in vivo evaluation of predicted agonistic or antagonistic effects. Murine monoclonal AMI and AMF were produced, purified, and characterized. Agonistic effects were tested after 24-h infusion of i.p. MTX (10 mg/kg) and i.v. administration of an equimolar dose of AMI. Antagonistic effects were tested after 72-h infusion of i.p. MTX (5 mg/kg) and i.v. infusion of an equimolar dose of AMF. Consistent with model predictions of agonist-like activity, the 24-h AMI protocol led to significantly increased animal mortality (all animals died, p < 0.005) and mean nadir weight loss (p < 0.005). Also consistent with the predictions of the PKPD model, the 72-h AMF protocol significantly decreased animal mortality and mean nadir body weight loss (p < 0.01). Thus, these studies demonstrate that agonistic and antagonistic effects of anti-toxin antibodies may be predicted through the use of an integrated PKPD model., (Copyright 2003 Wiley-Liss, Inc.)

1. Recent studies indicate that nitroglycerin (NTG) can produce beneficial clinical effects in healing anal fissures through the relaxation of the internal anal sphincter. The in vivo relaxation effects of NTG on the anorectal smooth muscle have not been studied and it is not known whether this tissue may also exhibit pharmacological tolerance toward NTG. 2. We have developed an in vivo procedure in the anaesthetized rat that permits continual monitoring of anorectal pressure after intravenous (i.v.) and intra-rectal application of NTG. The relaxant effects of NTG were quantified via the area-under-the-contraction-waveforms vs time curve (AUEC). 3. AUEC decreased significantly after intra-rectal bolus doses of NTG (5 - 25 microg), in a dose- and time-dependent manner. Sustained relaxation effects on anorectal pressure were also observed after continuous intra-rectal infusions of NTG. 4. Two-hours of i.v. NTG infusion led to a significant reduction in the mean arterial blood pressure (MAP) response toward a i.v. NTG (30 microg) bolus challenge. In contrast, relaxation of the anorectal pressure toward the challenge dose was not altered after NTG infusion. 5. In isolated tissues, cyclic GMP accumulation was significantly decreased after NTG pre-incubation in the rat aorta but not in the rat anorectal smooth muscle and anal sphincter. 6. These results indicate that the relaxation response toward NTG was not diminished in the anorectum under conditions that produced vascular tolerance. Thus, NTG causes significant and sustained in vivo relaxation of anorectal smooth muscle in the anaesthetized rat without evidence of tolerance development.

A study was conducted to determine if ice cream and sherbet interfered with the adsorption of aspirin onto activated charcoal both in vivo and in vitro. An aqueous suspension of 20 g activated charcoal decreased the absorption of 1 g aspirin by 65%; the same dose of activated charcoal with 50 g of ice cream reduced aspirin absorption by only 42% under otherwise identical conditions. In vitro tests showed that different ice creams and sherbet decrease the adsoprtion of aspirin onto activated charcoal. Thus, although ice cream is useful for preparing palatable suspensions of activated charcoal, it decreases appreciably the antidotal efficacy of the adsorbent.

The purpose of this investigation was to determine the effect of heparin-induced endogenous inhibitors of plasma protein binding on the plasma concentrations of total (free plus bound) and free bilirubin in rats with experimental hyperbilirubinemia. Adult male rats received constant-rate intravenous infusions of bilirubin and, after attaining steady state, were given either an intravenous injection of heparin, 500 units/kg, or this injection plus a maintenance infusion of hepatin. Control animals received normal saline solution instead of heparin. The free fraction of bilirubin in plasma increased substantially within 2 min after heparin injection and remained elevated when heparin concentrations were sustained by infusion of the anticoagulant. Despite the decreased plasma protein binding of bilirubin, the plasma concentration of total bilirubin did not decrease (as it does, consistent with pharmacokinetic theory, following injection or infusion of certain other inhibitors of bilirubin binding) and the plasma concentration of free bilirubin did not return to normal (as observed previously after administration of other binding inhibitors) but remained elevated. These results are consistent with the recently demonstrated rapid and extensive hepatic extraction of heparin-induced endogenous inhibitors of plasma protein binding. The heparin interaction with bilirubin may be particularly serious because of the sustained elevation of free bilirubin concentrations in plasma and the potential neurotoxicity of free bilirubin.

Inhibition of drug metabolism was studied in adult male Sprague-Dawley rats. A hydroxylated metabolite of phenylbutazone (oxyphenbutazone) inhibited the elimination of phenytoin, which is metabolized by oxidative pathways. The biotransformation of a relatively polar and only slightly plasma protein-bound drug, antipyrine, was subject to product inhibition by a hydroxylated metabolite, 4-hydroxyantipyrine. Neither oxyphenbutazone nor 4-hydroxyantipyrine measurably affected the elimination kinetics or metabolic fate of a drug (sulfanilamide) that is not metabolized by oxidative pathways.

The purpose of this study was to determine if certain physiologic parameters (plasma bilirubin concentration and urinary excretion rate of D-glucaric acid) can be used to predict a newborn infant's ability to eliminate a phenolic drug, and particularly to predict the ability to conjugate that drug with glucuronic acid. Tweleve healthy 2- to 3-day-old full-term infants with plasma bilirubin concentrations of 1.0 to 11.6 mg/100 ml and D-glucaric acid excretion rates of 0.131 to 0.345 mg/kg/day received a single oral dose of acetaminophen, 12 mg/kg. Urine was collected serially for 48 hours and analyzed for acetaminophen, acetaminophen glucuronide, acetaminophen sulfate, and D-glucaric acid. The biologic half-life of acetaminophen was 3.5 plus or minus 0.85 hours (average plus or minus SD) as compared to average values of 1.9 to 2.2 hours observed in five reported studies on a total of 39 adults. The rate constant for acetaminophen glucuronide formation in neonates was considerably smaller, on the average, than in adults but the average rate constant for acetaminophen sulfate formation was somewhat larger than in adults. There is not statistically significant colucaric acid excretion. The results of this study suggest that the limited ability of neonates to conjugate phenolic drugs with glucuronic acid is compensated to a degree by a well-developed capability for sulfate conjugation.