Light and electron microscopic study of the effect of sodium valproate on the quadriceps femoris muscle of rat and the possible protective role of L-carnitine

Sodium valproate [VPA] is a broad spectrum antiepileptic drug. Patients especially children who receive VPA for a long time present with myalgia and exercise intolerance. The aim of the present study was to elicit the effect of VPA on the skeletal muscle and the possible protective role of L-carnitine. Fifty male albino rats were used in this study. The animals were divided into two groups: group A [control group] and group B [experimental group] which was subdivided into 4 subgroups: group B1 and B2 received VPA only [50 mg/kg/day], for 1 and 2 months respectively. Group B3 and B4 received VPA and L-carnitine [300 mg/kg/day] for 1 and 2 months respectively. At the end of the experiment blood samples were collected to evaluate serum VPA levels. Quadriceps femoris muscles [QFM] were dissected and processed for light and electron microscopic [EM] study. In group B1, some QFM fibers showed loss of their striation or longitudinally splitted. Some intermediate muscle fibers appeared to be deficient in succinic dehydrogenase enzyme[S-DH] activity. EM study revealed many lipid droplets and enlarged degenerated mitochondria in-between the myofibrils. The mean serum VPA level was 101.6 +/- 7.88 micro g/ml. In group B2 the majority of muscle fibers were degenerated with mononuclear cellular infiltration and marked decrease in S-DH activity in all types of muscle fibers. Disorganized myofibrils, megamitochondria and lysosomes were seen. The lipid and glycogen granules were increased. There was a non significant increase in the mean serum VPA level [105.01 +/- 6.34 micro g/ml]. On the other hand, there was a highly significant decrease in the mean serum VPA level in group B3 [85.39 +/- 5.93 micro g/ml] and B4 [86.23 +/- 8.39 micro g/ml]. No histological changes were observed in these two groups except that some mitochondria were enlarged in group B4. In conclusion, the use of L-carnitine has a great role in protection against VPA-induced myopathy and it should be prescribed for all patients treated with VPA for long time

Qualitative and quantitative analysis of morphone and phenobarbitone in dried human blood stains

This study was conducted to evaluate the relationship between the age of the dried human bloodstains and the degree of detectability of morphine and phenobarbitone present in bloodstains. Detection of the drugs was studied in bloodstains at different time intervals [1, 14 days 1, 2, 3, 4, 5 months] by using thin layer chromatography [TLC] and enzyme multiplied immunoassay [EMIT]. Furthermore, the effect of storage temperature [25C and 20C] on detectability of these drugs was investigated. The results showed that both phenobarbitone and morphine could be detected by TLC from recent and old blood stains up to 5 months at both 25C by using EMIT, the percentages of both phenobarbitone and morphine concentrations were 48.39% and 82.59%, respectively, after 5 months of storage at room temperature [25C]. Thus, the decrease in morphine concentrations was less marked than that of phenobarbitone indicating that morphine was more stable in bloodstains. On the other hand, storage of blood stain samples at-20C showed slight insignificant variation in the concentrations of both phenobarbitone and morphine at all the time intervals up to 5 months. It became 98.98% and 98.80%, respectively, after 5 months. Thus, storage of bloodstains at 20C had a stability effect on the tested drugs. Statistical regression equation was used to predict the concentrations and percentages of both phenobarbitone and morphine in the dried bloodstains provided that the age of bloodstain is known at the time of assay

Deliberate self-poisoning A toxicological study

The present work was designed to detect drugs and chemicals commonly ingested by suicidal patients. This study was carried out on 100 male and female patients treated from deliberate self- poisoning. Biological samples [20 ml blood, 50 ml urine and 100 ml gastric contents] were collected from every patient. Toxicological analysis was done by enzyme multiplied immunoassay technique [EMIT] and fluorescent immunoassay system [TDX-FLX] for qualitative and quantitative detection. Thin layer chromatography [TLC] was used for the confirmation of EMIT negative results and the detection of insecticides and drugs, which can not be detected by EMIT ad TDX- FLX. From the results obtained it was concluded that the detection of drugs and chemicals used by self-poisoned patients needs more than one analytical method to give accurate results

Vitreous / blood concentration ratio in drug overdoses an experimental study

Serum and vitreous concentrations in three drug overdoses [phenobarbitone,morphine and theophylline] were measured in albino rats after 1, 2, 4 and 12 hours of i.p. injection. Vitreous/blood ratio was determined for every drugoverdose. It was found that this ratio remained constant regardless of thetime passed since injection. The study demonstrated that vitreous is a cleanbiological fluid that can be used for the detection of drug overdose by EMIT and can predict the blood concentration of the drug as long as vitreous/bloodratio is known

Relationship between lead in breast milk and lead in blood of urban and rural mothers

Lead levels in breast milk and maternal blood of 60 lactating women were determined using Perkin-Elmer 2380 atomic absorption spectrophotometer. The mean lead concentration in breast milk was 4.13 +/- 0.89 micro g/dl and 3.06 +/- 0.76 micro g/dl for urban and rural mothers respectively. The mean lead concentration in blood was 6.19 +/- 1.09 micro g/dl and 4.61 +/- 0.93 micro g/dl for urban and rural mothers respectively. Urban women showed higher lead concentrations of both breast milk lead and blood lead than that of rural women [P < 0.0001]. In this study, lead concentrations in both milk and blood were affected by maternal age and exposure to smoking. The most important factors used to predict lead concentrations of breast milk in the studied samples were maternal age and maternal blood lead concentration. According to the daily permissible intake value established by WHO which is 5.0 micro g/kg/day in mother's milk, the mean value for lead in breast milk of urban and rural mothers was higher than the permissible level [6.3 micro g/kg/day and 6.1 micro g/kg/day respectively]

Evaluation of the effect of gastrointestinal dialysis by multiple doses of activated charcoal on the toxicokinetics of drug overdose in rats

This study was performed to evaluate the effect of multiple oral doses ofactivated charcoal [MDAC] on the toxicokinetics of intraperitoneallyadministered drug overdoses [phenobarbitone, salicylate, theophylline anddiazepam] in albino rats. Four groups of rats [310 rats] were injected withthe previous 4 drugs, respectively [0 time]. Each group was divided intotest animals [received multiple doses of oral activated charcoal] and controlanimals [received distilled water orally]. Ten animals were sacrificed fromeach group [five from controls and five from test animals] after one hour from zero time, then at different subsequent hours according to every drug groupregimen. Blood samples were analyzed for plasma drug concentration, by enzymemultiplied immunoassay technique for phenobarbitone, theophylline anddiazepam, and fluorescence polarization immunoassay [FPIA] by TDx-FLx for theestimation of salicylate. Significant reduction in half life and enhancedclearance were found in phenobarbitone and theophylline groups. In salicylategroup, the reduction in half life and enhancement of clearance wereinsignificant. No effect of MDAC was found on the plasma concentration ofdiazepam

Rapid analysis of some drugs of abuse in human blood by using EMIT and TLC techniques

A recent method for direct and rapid extraction of some drugs of abuse inwhole human blood was evaluated. Methanolic extraction of 2ml blood with 4mlmethanol yielded 0.3-3.5 ml clear extract after vigorous vortexing for 30seconds followed by centrifugation at 3000 rpm for 3 minutes. Analysis ofblood samples were done by using 2 techniques; Enzyme Multiplied Immunoassay[EMIT] and Thin Layer Chromatography [TLC] for the presence of morphine,amphetamine, phenobarbitone and methaqualone. The time taken from the startof the extraction procedure up to the point, at which the EMIT-apparatus wasinjected with the extract or TLC plates were spotted, was 10 minutes, i.e. rapid extraction. Values of detection of the four assayed drugs in the methanolic extract proved that this method of extraction is very sensitive and gives a potent, i.e. it can be used to detect drugs concentration ranges [subtherapeutic to therapeutic] for all assays

Toxicity of methotrexate on fertility and internal organs of male albino rats

Fifty male adult albino rats with average weight of 220 - 250 gm were used in this study. Animals were divided into four test groups and a control group each comprised of ten rats. Test animals received methotrexate [MTX] in a therapeutic constant low dose of 7.5 mg/kg/ week for eight weeks. The effects of the drug were assessed by histopathological, biochemical and spermatozoal examination immediately after its stoppage and within one month recovery period. Significant histopathological changes in internal organs of albino rats associated with marked functional biochemical abnormalities were observed. Also there was marked alteration in sperm count, motility and increased percentage of abnormal forms. Gradual improvement was observed during the recovery period

Percutaneous toxicity of ethylene glycol and 1,2 propylene glycol in rats

Forty albino rats were divided into four equal groups. The three test groups were applied percutaneously with 1000 mg /kg of ethylene glycol, 1, 2-propylene glycol and a mixture of equal amounts of both ethers respectively, while the fourth group served as a control. The application was done 6 days / week for 8 weeks. Results of the ethylene glycol and combined [ethylene and propylene glycols] groups revealed depression of bone marrow cellularity with significant changes in the Hb concentration and the blood cell counts. Histopathological findings of liver, lungs and kidneys showed marked evidences of toxicity whereas the testes were slightly affected and the application site of the skin was found normal. Minimal changes were observed in the propylene glycol group

Osteometry and sexual dimorphism of the human hip bone

Fifty-six human hip bones of 14 males and 14 females were used in this study. Measurements of 15 variables were taken for each hip bone. Among thesevariables, statistically high significant differences related to sex weredetected for the mean values of the total pelvic height and pelvic width. Inanterior border measurements, statistically significant differences weredetected between mean values for 4 variables [distance from the anteriorinferior iliac spine to the iliopubic eminence and to the pubic tubercle, aswell as the depth of the anterior border and the index of the anterior borderlength to the total pelvic height]. These variables could be used for sexdetermination from the human hip bone or its fragments

Postmortem biochemical changes of the vitreous humor in relation to the cause of death and premortal suffering period

Lactic acid, albumin, total proteins, sodium, chloride and potassium wereestimated in the vitreous humor of 30 female albino rats. Animals weredivided into five equal groups, one of them used as a control group, while theother groups were classified according to the cause of death. In thestrangulation groups, insignificant changes of lactic acid and potassiumconcentrations were observed, while other investigated items revealed highlysignificant increase. Concentrations of all the estimated materials showedsignificant increase in the bleeding and hypothermic groups. Increasingconcentrations of lactic acid and most of the estimated items seem to berelated to the increased permeability of brain cells and blood brain barrierfollowing stressful death. Also, this reflects the intensity of the braindamage and the induced effects of prolonged hypoxia caused by respiratorydepression preceding death