Behavioral, biochemical and histopathological toxic profiles induced by sub-chronic cannabimimetic WIN55, 212-2 administration in mice.

WIN55, 212-2 mesylate is a synthetic cannabinoid (SC) agonist of CB1 and CB2 receptors with much higher affinity to CB1 receptor than tetrahydrocannabinol and many potential therapeutic effects. Few studies have evaluated SCs effects on more complex animal behavior and sex differences in cannabinoids toxicology. The current study was undertaken for determination of behavioral (Open Field test), biochemical (liver and kidney function test plus GABA & Glutamate levels), histopathological and CB1 immunohistochemistry risks of sub-chronic administration of SC WIN55, 212-2 mesylate in male and female mice. A total of 40 healthy adult mice were randomly divided into four groups (5 mice each): a negative control group, a vehicle group, a low dose (0.05 mg/kg) group and a high dose group (0.1 mg/kg) for each gender.Open Field Test revealed dose and gender-dependent anxiogenic effect with reduced locomotor activity in both sexes especially the higher doses with female mice being less compromised. GABA and glutamate levels increased significantly in both dose groups compared to controls alongside female mice versus males. No significant biochemical alterations were found in all groups with minimal histopathological changes. The CB1 receptors immunohistochemistry revealed a significant increase in the number of CB1 positive neurons in both low and high dose groups against controls with higher expression in female brains.ConclusionsThere were sexual dimorphism effects induced by sub-chronic exposure to WIN55, 212-2 with lesser female mice affection and dose-dependent influences.

Hematological and immunological impairment following in-utero and postnatal exposure to aluminum sulfate in female offspring of albino rats.

Aim: Aluminum (Al) is a ubiquitous element extensively utilized in many products like food additives, pharmaceuticals, and vaccines, but its hematotoxic and immunotoxic effects are not entirely clarified. The present study explored the developmental hematotoxic and immunotoxic properties of aluminum sulfate (AS) in rats' offspring. Methods: Forty female offspring (10 rats each) were given three incremental AS doses plus a control group, from conception through lactation and after weaning until reached eight weeks old (near adults). Spleen relative weights along with total and differential blood counts were evaluated. Spectroscopic Al levels in spleen and brain were analyzed. Three immunoglobulins (IgG, IgM, and IgE) and two cytokines, interferon-γ and tumor necrosis factor-α, were measured through the ELISA technique. Results: The results revealed a significant relative increase in splenic weights mostly observed in the highest AS dose treated group. Reduction in the total leukocytic count was noticed in the three AS treated groups with relative lymphocytosis. Additionally, a significant decline in RBCs counts and hemoglobin concentrations were recorded. Tumor necrosis factor-α was significantly elevated in the three Al treated groups, while, interferon- γ showed a non-significant reduction compared to the control group. A significant increment in IgG and decline in IgE concentrations with no change in IgM level among groups were observed. Conclusion: Perinatal AS exposure caused mostly non-linear dose-dependent hematotoxicity and immunological impairment especially for the acquired immunity either cellular or humoral. Further studies can examine the immunotoxic effect of Al on male offspring during different stages of immune development.

Inhibition of brain oxidative stress and inducible nitric oxide synthase expression by thymoquinone attenuates the development of morphine tolerance and dependence in mice.

In this study, the effect of thymoquinone on morphine-induced tolerance and dependence in mice was investigated. Repeated administration of thymoquinone along with morphine attenuated the development of morphine tolerance, as measured by the hot plate test, and dependence, as assessed by naloxone-precipitated withdrawal manifestations. Concurrently, morphine-induced progressive increase in brain malondialdehyde (MDA) level and nitric oxide (NO) production as well as progressive decrease in brain intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity were inhibited by co-administration of thymoquinone. Morphine-induced progressive increase in brain glutamate level was not inhibited by concomitant administration of thymoquinone. Similarly, co-administration of thymoquinone inhibited naloxone-induced increase in brain MDA level, NO overproduction and decrease in brain intracellular GSH level and GSH-Px activities but it did not inhibit naloxone-induced elevation of brain glutamate level in morphine-dependent mice. The inhibitory effect of thymoquinone on morphine-induced tolerance and dependence on naloxone-induced biochemical alterations in morphine-dependent mice was enhanced by concurrent i.p. administration of the NMDA receptor antagonist, dizocilpine, the antioxidant, N-acetylcysteine or the NO synthase inhibitor, L-N (G)-nitroarginine methyl ester. On the other hand, this inhibitory effect of thymoquinone was antagonized by concurrent i.p. administration of NO precursor, L-arginine. In addition, concomitant administration of thymoquinone inhibited morphine tolerance and dependence-induced increase in inducible but not in neuronal NO synthase mRNA expression in mice brain. These results demonstrate that inhibition of morphine-induced oxidative stress, increase in the expression of brain inducible NO synthase and NO overproduction by thymoquinone can attenuate the development of morphine tolerance and dependence.

Genetic variation of 15 autosomal STR loci in Upper (Southern) Egyptians.

A sample of 265 unrelated individuals inhabiting five governorates in Upper (south) Egypt was collected with informed consent. The samples were amplified using the AmpFlSTR IdentifilerPCR Amplification Kit (containing 15 loci: D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA), and genotyped subsequent to capillary electrophoresis. Statistical analysis of the generated data indicated neither departure from expectation of Hardy-Weinberg Equilibrium (HWE) in most of the tested loci nor dependence of alleles between loci. All tested loci were polymorphic; the most discriminating is D18S51 while the least is TPOX. The combined power of exclusion was 0.99999868 and the combined match probability was 1.93x10(-18). The genetic diversity of the Upper Egyptians was compared with those of other populations at the local, regional and global levels.

Dynamic nature of the proximal AZFc region of the human Y chromosome: multiple independent deletion and duplication events revealed by microsatellite analysis.

The human Y chromosome shows frequent structural variants, some of which are selectively neutral, while others cause impaired fertility due to the loss of spermatogenic genes. The large-scale use of multiple Y-chromosomal microsatellites in forensic and population genetic studies can reveal such variants, through the absence or duplication of specific markers in haplotypes. We describe Y chromosomes in apparently normal males carrying null and duplicated alleles at the microsatellite DYS448, which lies in the proximal part of the azoospermia factor c (AZFc) region, important in spermatogenesis, and made up of "ampliconic" repeats that act as substrates for nonallelic homologous recombination (NAHR). Physical mapping in 26 DYS448 deletion chromosomes reveals that only three cases belong to a previously described class, representing independent occurrences of an approximately 1.5-Mb deletion mediated by recombination between the b1 and b3 repeat units. The remainder belong to five novel classes; none appears to be mediated through homologous recombination, and all remove some genes, but are likely to be compatible with normal fertility. A combination of deletion analysis with binary-marker and microsatellite haplotyping shows that the 26 deletions represent nine independent events. Nine DYS448 duplication chromosomes can be explained by four independent events. Some lineages have risen to high frequency in particular populations, in particular a deletion within haplogroup (hg) C(*)(xC3a,C3c) found in 18 Asian males. The nonrandom phylogenetic distribution of duplication and deletion events suggests possible structural predisposition to such mutations in hgs C and G.