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Mercury is an environmental neurotoxicant that triggers structural and physiological alterations in different brain parts. The hippocampus is associated with learning and memory, and injury to this brain part may lead to behavioural and cognitive changes. Phoenix dactylifera (date palm) has been demonstrated to possess a variety of medical benefits. This study comparatively assessed the neuroprotective property of aqueous and ethanol fruit pulp extracts of P. dactylifera in a rat model of mercury-triggered hippocampal changes using microscopic examinations. Twenty-eight Wistar rats were divided into seven groups (I-VII, n=4). Group I (control) was administered distilled water (2ml/kg); group II was administered mercuric chloride, HgCl2 (5mg/kg); group III was administered vitamin C (100mg/kg) as reference drug +HgCl2; groups IV and V were administered aqueous extract (250mg/kg and 500mg/kg, respectively) +HgCl2, while groups VI and VII were administered ethanol extract (250mg/kg and 500mg/kg, respectively) +HgCl2. Extracts' neuroprotective property were evaluated using histological and histometric assessments of CA1 and CA3 hippocampal sub-regions. Results revealed cytoarchitectural changes including karyopyknosis, basophilic necrosis and remarkably decreased histometric features of hippocampal pyramidal neurons in HgCl2-treated group relative to control. Administration of the extracts remarkably ameliorated mercury-induced degenerative changes by preservation of cytoarchitectural features comparable to reference drug. Comparatively, neuroprotective efficacies of the extracts are relatively similar, especially at doses of 500mg/kg and could be attributed to antioxidant activities of constituent phytochemicals. Results suggest that aqueous and ethanol fruit pulp extracts of P. dactylifera may prove efficacious in ameliorating mercury-triggered microscopic alterations in the hippocampus of Wistar rats.

Objective: Sitagliptin (ST) and Moringa oleifera (MO) Lam (Moringaceae) are used concomitantly by diabetic patients, with no study ascertaining for potential favorable or otherwise renal implications. We investigated the effect of coadministration of ST and MO leaf extract on functional and morphological biomarkers of alloxan-induced diabetic nephropathy (DN)., Materials and Methods: Diabetes was induced with a single dose of 150 mg/kg of alloxan intraperitoneally. Seven groups of eight rats per group were used, with Groups I, II, and VII as normal (NS), diabetic control (DC), and postprandial controls. Groups III, IV, V, and VI were diabetic rats on ST, MO, ST and MO (SM), for 42 days with 2 weeks delayed treatment in a postprandial hyperglycemic group (PPSM), respectively. Serum urea, albumin, electrolyte levels, lipid profile, and kidney tropism were determined in addition to histological examinations., Results: There was a significant increase ( P < 0.05) in kidney tropism comparing all drug-treated groups and DC to normal rats. Significant increases in serum urea were observed ( P = 0.02) in DC, MO-treated, and SM-treated rats compared to normal rats and also in serum triglyceride ( P < 0.05) in MO-treated and SM-treated rats compared to controls and other drug-treated groups. A mild reduction in severity of pathologic lesions was observed (glomerulosclerosis Grade 1) in SM-treated rats compared to a marked necrosis in DC (Grade 3)., Conclusion: The coadministration of ST-MO did not delay the progression of functional anomalies and renal injury nor ameliorated the lesions associated with chronic DN in Wistar rats., Competing Interests: There are no conflicts of interest.

Background: Leonotis nepetifolia Linn (Lamiaceae) is used in traditional medicine for its calming (tranquilizing) effects. The aim of this study was to determine whether there is any scientific justification for this use. To achieve this purpose, we investigated the behavioural effects of the methanol extract of Leonotis nepetifolia stem (37.5, 75 and 150 mg/kg) in mice., Methods: Acute toxicity studies were carried out on the methanol stem extract of Leonotis nepetifolia to determine the LD50. The behavioural tests employed were diazepam-induced sleep onset and duration, hole board assay for exploratory activity, mouse beam walk assay for motor coordination, and the staircase test for the detection of anxiolytic compounds. Preliminary phytochemical screening was also carried out on the extract., Results: The intraperitoneal LD50 value was found to be 3.8 g/kg. The results showed that the extract significantly prolonged the duration of diazepam-induced sleep at the highest dose (150 mg/kg). There was no observable effect on exploratory activity and motor coordination at the doses tested (37.5, 75 and 150 mg/kg). The extract, however, at 150 mg/kg elicited a significant decrease in the number of rearings in the staircase test, an effect also observed in the group of mice injected with an anxiolytic dose of diazepam. The preliminary phytochemical screening revealed the presence of alkaloids, saponins, glycosides and triterpenoids., Conclusion: The results obtained suggest that the crude methanol extract of Leonotis nepetifolia stem possesses some biologically active constituents with potential anxiolytic activity and thus may justify its traditional use as a tranquilizer.

Background: The co-morbidity of psychoactive substance use and other mental disorders is a major challenge to the management of both conditions in several parts of the world. There is relative dearth of information on co-morbidity and its predictors in Nigeria. This study determined the prevalence and socio-demographic risk factors associated with psychoactive substance use in the psychiatric out-patients of a tertiary hospital in Nigeria., Study Design: A cross-sectional study., Materials and Methods: From routine clinic visits over a 4-month period, each consecutive 4(th) adult patients (>18 years) who had previously attended the clinic at least for 1 year, completed a socio-demographic and semi-structured drug use questionnaires and interview with the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) to generate substance use diagnosis. Data was analysed using the statistical package for social sciences (SPSS), version 16. Level of significance was set at P < 0.05., Results: The lifetime prevalence for the use of substance was 29.3%, while that for multiple substances was 17.7%. The most commonly used substances were alcohol, cannabis and tobacco and they were also the ones mostly used in combination with one or the other. A total of 10.1% of the patients had a psychoactive substance use disorder. Being male, married with at least primary education and unemployed were significant risk factors for substance use., Conclusion: Psychoactive substance is common among the psychiatric outpatients of the hospital with males, those with formal education, the married and unemployed being at high risk of substance use.

Preliminary investigation of the in vitro and in vivo efficacies of different extracts from the leaves of Vernonia amygdalina (VA), a plant widely used in Nigeria was evaluated in Balb/C mice infected with a laboratory strain of Leishmania major (L. major). The ability of the methanol, hexane and aqueous extracts of the plant to suppress the infection rate and its cytotoxicity on macrophages and L929 cells were determined in the in vitro study. The in vivo study evaluated time course of infection, lesion progression and the histopathology of cutaneous lesions, liver and spleen after inoculation with metacyclic promastigotes. Methanolic extract of VA containing high levels of flavanoids, was the most potent extract as it showed the highest suppression on infectivity and viability of intracellular amastigotes at a concentration lower than that which elicited cytotoxicity on macrophages. Treatment of infected mice with methanolic extract of VA showed delayed onset of disease with a significant reduction in lesion size and attenuation of the histopathological outcome characterised by intact epidermis and less tissue destruction in skin, spleen and liver. In conclusion, these results demonstrate that VA has potent antileishmanial properties which warrants further investigation into the immunological mechanism.

Background: Lamivudine and artesunate are sometimes co administered in HIV-malaria co morbidity. Both drugs are used concurrently in presumptive malaria treatment and simultaneous HIV post exposure prophylaxis., Aim: The aim of this study was to investigate the effect of lamivudine-artesunate co administration on the histology of the liver of diseased adult Wistar rats., Materials and Methods: Five groups of rats of both sexes were used for the study and placed on feed and water ad libitum. Disease state consisted of immunosuppression with cyclophosphamide, and infection with Plasmodium berghei. Group 1 animals served as vehicle control, while group 2 were the diseased controls. Group 3 animals received 20 mg/kg lamivudine for three weeks, while group 4 similarly received 20 mg/kg Lamivudine but also received 10 mg/kg artesunate from day 12. Animals in group 5 received 10 mg/kg artesunate from day 12. All drugs were administered intraperitoneally. The animals were treated for twenty-one days, at the end of which they were sacrificed and their livers fixed in 10% formalin for histological studies., Result: Results from the study show the presence of regions of focal necrosis and perivascular cuffing with animals that received artesunate. Hemosiderosis was a common feature in all the parasitized groups, while fatty degeneration was observed in the group that received artesunate alone., Conclusion: Concurrent lamivudine-artesunate administration resulted in some histopathological changes in the liver. This study suggests there may be considerable histological changes with repeated occurrence of malaria and immunosuppression that may warrant intermittent lamivudine-artesunate administration, and may require evaluation as well as monitoring of liver function during such therapeutic interventions.

In the search for new plant-derived anti-malarial compounds, chromatographic fractions of chloroform extract of whole plants of Artemisia maciverae were tested in vivo using chloroquine resistant and chloroquine sensitive Plasmodium berghei NK 65 infected Swiss albino mice. One fraction and a sub-fraction of this were most active at 10/mg and cleared parasitemia in mice within 3 days. The different fractions and sub-fractions were tested with different reagents to determine the broad classes of compounds present. The active fraction tested positive for triterpenes and alkaloids, and the sub-fraction for only triterpenes. These tests suggest that the anti-malarial activities observed with these fractions may be due to these classes of compounds in the chloroform extract of the A. maciverae. Further chemical work is however required to characterize the active constituents.

Earlier pharmacological screening showed that siculine syrup (a traditional herbal remedy purported to be useful in the prevention and treatment of sickle cell pain - crises, due to sickle cell anaemia - SCA) had antisickling and analgesic activities as well as antimicrobial and diuretic effects. SCA is an important haemoglobinopathy in Africa and many other communities/countries worldwide, with relatively high morbidity and mortality. The present study was to determine the effects of the extract on various isolated muscle preparations - smooth, skeletal and cardiovascular. Siculine (4-20 microg/mL), like acetylcholine (40-400 microg/mL), contracted the isolated rat uterus concentration dependently. Similar effects were observed with the guinea-pig ileum and rabbit jejunum (2-20 microg/mL). In contrast to these effects, the direct (muscle) and indirect (nerve) stimulations of rat phrenic nerve-diaphragm were relaxed by siculine (4 and 8 microg/mL) and d-tubocurarine (0.8 microg/mL). Siculine also concentration-dependently decreased both the rate and force of contraction of guinea-pig atria and rabbit heart and also resulted in a fall in cat blood pressure in a manner similar to those of acetylcholine. The possible therapeutic and/or toxicological consequences of these effects including the hypotensive activity is noteworthy since siculine syrup is used by the local population for the prevention and treatment of sickle cell pain crises., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

Background: Solanum nigrum is claimed in traditional medical practice, to be useful in the treatment of epilepsy in some parts of Nigeria., Objectives: To study the anti-convulsant property of the aqueous extract of the leaves of S. nigrum in chicks, mice and rats., Method: Aqueous extracts were administered intraperitoneally, at a pre-treatment time of 30 minutes, at graded doses and animals were challenged with different types of proconvulsants., Results: The aqueous leaf extract produced a significantly (P<0.05) dose dependent protection against electrically-induced seizure in chicks and rats, pentylenetetrazole-induced seizure in mice and rats and picrotoxin-induced seizure in mice and rats. The anti-seizure property of the extract was potentiated by amphetamine., Conclusion: The result obtained in this study suggests that the leaves of this plant may possess anti-convulsant property in chicks, mice and rats.

Artemether (AM), a highly effective treatment for multidrug-resistant malaria and a component of artemisinin combination therapy, has been associated with some neurotoxicity following repeated high doses. This study was aimed at investigating the effect of AM on pentobarbitone sleep and electrical activities in rats. Wistar rats received AM i.p. at 3 dose levels: 1.5, 7.5, and 15 mg/kg, whereas control rats received 0.2 mL of the vehicle (3% v/v Tween 80). AM administered 20 min before pentobarbitone had no significant effect on the onset and duration of sleep. However, after a 7-day pretreatment, AM dose-dependently prolonged pentobarbitone sleep, as did chloramphenicol. Electroencephalogram and electromyogram recordings 20 min after pretreatment showed that AM (15 mg/kg) exhibited inhibitory activity similar to chlorpromazine as opposed to the excitatory effect of amphetamine. When pretreated for 7 days, rats receiving 1.5 mg/kg AM also showed inhibitory activity of the cortical centres, whereas desynchronization of the optic tectum and reticular formation was observed in rats pretreated with 7.5 and 15 mg/kg AM. The present data suggest that although the therapeutic equivalent dose of 1.5 mg/kg AM had no appreciable effects on pentobarbitone sleep but caused reduced electrical activity in rats, higher doses have more profound effects on both indices.

Artemether, highly effective in multi-drug-resistant malaria is not routinely available for use in pregnancy due to the lack of adequate research data in animals and man. This study was therefore aimed at investigating some pregnancy-related effects of artemether. Artemether (1.5, 7.5 and 15 mg/kg i.p. daily for 7 days) did not produce changes in rat oestrous cycle. The drug did not prevent or prolong the rate of conception or parturition, cause pre-term delivery and affect litter size. Birth weight and growth rate of pups from artemether-pretreated dams were within the normal range. Artemether (48-480 microg/ml) had no agonist effect on the isolated uterine smooth muscles of both non-pregnant and pregnant rats and guinea pigs. However, the drug (24- 240 microg/ml) reduced oxytocin-induced contraction of uterine tissues concentration-dependently, particularly in pregnant uteri., (Copyright (c) 2006 S. Karger AG, Basel.)

The antinociceptive activity of the methanolic extract of Neorautenania mitis was studied in mice and rats. Five experimental models of nociception employed were: acetic acid-induced abdominal constriction and hot-plate test in mice, formalin-induced pain, analgesy-meter and Randall-Selitto tests in rats. The antinociceptive action of the extract was tested against naloxone in the hot-plate test in a bid to further elucidate probable mechanisms of antinociception. Results showed that the extract at doses of 5, 10 and 20 mg/kg body weight caused significant (P<0.05) dose-dependent antinociceptive activity in all the nociceptive models. Naloxone (2 mg/kg), significantly (P<0.05) antagonised the antinociceptive activity at the highest dose of the extract (20 mg). The study showed that the methanolic extract of Neorautanenia mitis possesses both peripherally and centrally mediated antinociceptive activity. The peripherally mediated action may be linked partly to lipoxygenases and/or cyclo-oxygenases, while the central anti-nociception is likely to be mediated via opioid receptors in the CNS.

The leaves of Cassia tora Linn. (Family: Caesalpiniaceae) were soxhlet extracted with methanol. The spasmogenic effects of the extract were evaluated on guinea pig ileum, rabbit jejunum and mice intestinal transit. Antinociceptive activity of the extract was also evaluated in the mice. The LD(50) values of the extract in mice were >2000 mg/kg i.p. and p.o. The extract contracted smooth muscles of guinea pig ileum and rabbit jejunum in a concentration-dependent manner. Atropine reversibly blocked this activity. Mepyramine also reduced the contractile amplitude due to the extract in a concentration-dependent manner. The extract increased intestinal transit in mice dose dependently. C. tora extract significantly (P<0.05) reduced the number of acetic acid induced abdominal constrictions in mice and the effect was comparable to that of aspirin (150 mg/kg i.p.). The extract also significantly (P<0.05) reduced the nociceptive response of mice to increased force (g). The effects were dose-dependent. The studies suggest that the use of C. tora, traditionally, as a purgative and in the treatment of other ailments is justifiable.

Four calves infected with Trypanosoma vivax and four uninfected control calves were each injected intravenously with repeated doses of 0.5 g lactose kg-1 body weight, thrice daily at intervals of 4 h. Plasma samples were collected at specified time intervals and analysed for lactose. Pharmacokinetic parameters were calculated from the data. T. vivax infection delayed excretion of lactose from the body, thus leading to significantly (P < 0.001) increased biological half life (t1/2) and a significantly (P < 0.001) reduced elimination rate constant for lactose in the body. The apparent volume of distribution and total clearance of lactose were not affected by the infection. T. vivax infection also appeared to cause accumulation of lactose in the plasma after repeated intravenous administration.

Forty-eight BALB/C mice (30 males, 18 females) and 18 male Wistar rats were given Kargasok tea in their drinking water. Zero, 15, 25, 50, 75 or 100% concentrations were administered to mice for 2 or 8 w while the rats were given 0, 15 or 50% concentrations of the beverage for 12 w. Neither the mice nor rat's organ/body weight ratios were significantly affected by treatment. Rats receiving 15 or 50% concentrations of the tea had nephropathy and non-suppurative necrosis of the duodenum, pancreas and intestine. No significant microscopic lesions were found in any treated mice even when given 100% concentration of the tea. These findings suggest species variation in susceptibility to toxicity from the tea. The tea may be a cause of renal failure, diabetes mellitus and malabsorption syndrome and may not be safe for human or animal consumption.

The effects of cimetidine on drug metabolism were studied in male and female rat pups and compared to similar effects in adult rats. As in adult rats, cimetidine 50 mg/kg/day i.p. for 7 days in the 2nd, 3rd, 4th or 5th weeks of life resulted in prolonged pentobarbitone sleeping times (diminished pentobarbitone hydroxylase activities), particularly when administered during the 3rd week. These effects of cimetidine were reversible since they continued only up to 2 weeks in males and 4 weeks in females, but by the 6th week were no longer observed. Pretreatment with cimetidine 15, 25 and 50 mg/kg/day i.p. for 7 days, resulted in a dose-dependent inhibition of aminopyrine N-demethylase and aniline hydroxylase as well as a prolongation of pentobarbitone sleeping time in both pups and adults, aniline hydroxylase being the least affected. In general, female pups were more adversely affected than male pups and adults. The therapeutic and toxicological relevance of these results in man are discussed.

The effects of maternal cimetidine pretreatment at different dose levels during lactation, on drug metabolism, were investigated in mouse dams and recently weaned pups. Aminopyrine N-demethylase, aniline hydroxylase and pentobarbitone metabolism were inhibited in both dams and pups in a dose-dependent manner (15, 25 and 50 mg/kg/day, i.p.). Pretreatment at a dose level of 50 mg/kg/day resulted in comparable levels of inhibition of drug metabolism in dams and female pups while male pups were less affected. Of the three indices studied, aniline hydroxylase was the least influenced by cimetidine pretreatment. Thus, the effects of maternal cimetidine pretreatment on drug metabolism in the nursing pair varied with the dose, sex and substrate. The possible implications of these results for man are discussed.

Intraperitoneal injection of rats with 2 mg/kg ring labelled 14C AFB1 (spec. act. 110 mCi/mM/nmole) showed a higher level of radioactivity in the urine of test animals on diets containing 600 mg/kg vit. E 24 h after pretreatment. Analysis of the urine by chloroform extraction, thin layer chromatography and liquid scintillation counting of the various fractions showed less aflatoxin M1 (AFM1) and less unmetabolized AFB1 in test samples than in controls. Incubation of ring labelled 14C AFB1 with hepatic 10,000 g supernatant fractions, however, showed increased metabolism of AFB1 by fractions from test animals as compared with the controls. Rate of disappearance of 14C AFB1 and the consequent formation of AFM1 was greater in the test fractions than in the controls. At 30 days all test animals showed higher levels of serum vitamin E than the controls. Hepatic aniline hydroxylase and ethyl morphine N-demethylase activities of the liver fractions and blood glutathione reductase activity were greater in the tests. P-nitroanisole-O-demethylase activity was reduced while hepatic and serum reduced glutathione levels remained basically unaltered.