Pathophysiology of meningococcal meningitis and septicaemia.

Neisseria meningitidis is remarkable for the diversity of interactions that the bacterium has with the human host, ranging from asymptomatic nasopharyngeal colonisation affecting virtually all members of the population; through focal infections of the meninges, joints, or eye; to the devastating and often fatal syndrome of meningococcal septic shock and purpura fulminans.     

Association between the DRD2 A1 allele and opium addiction in the Iranian population.

Dysfunction of the central dopaminergic neurotransmission has been suggested to play an important role in the etiology of certain neuropsychiatric disorders such as drug abuse. It has been shown that the dopamine D2 receptor (DRD2) gene dysfunction is associated with multi-drug addiction. Addiction to opium is the most common form of drug abuse in Iran. We studied the allelic association between DRD2 Taq I A polymorphism in 100 opium-dependent Iranian patients and 130 unrelated controls. A 310 bp (base pair) region surrounding Taq I site at the DRD2 locus was amplified by polymerase chain reaction (PCR) and the PCR product was incubated with Taq I restriction enzyme. The A1 allele remained intact while the A2 allele was cut. Significant association was observed between A1 allele and addiction in the patients group (P < 0.0001). Moreover, the frequency of A1A1 genotype was significantly higher in opium users than controls (P < 0.0001). Our result indicates that DRD2 might be involved in the pathophysiology of opium addiction.     

Shifting balance from neurodegeneration to regeneration of the brain： a novel therapeutic approach to Alzheimer＇s disease and related neurodegenerative conditions

<正>Neurodegeneration is one of the biggest public health problems in modern society.Age-associated neurodegeneration,which is accelerated several-fold in Alzheimer’s disease(AD)alone,is not only an enormous social and economic burden to the affected individuals and their families,but is also a great scientific challenge.     

Synthesis and preliminary evaluation of difluorinated 1,3-propanediones as potential agents in the treatment of breast cancer

A series of difluorinated propanediones were synthesized and evaluated for in vitro cytotoxic activity by Sulforhodamine B (SRB) assay against a panel of four human cancer cell lines. Though the compounds showed varying degrees of cytotoxicity in the tested cell lines, most marked effect was observed in breast cancer cell line (MCF7), wherein nine of the ten synthesized chalcones showed good antiproliferative activity.     

Molecular interactions of dioxins and DLCs with the ketosteroid receptors: an in silico risk assessment approach

Dioxins and dioxin-like compounds (DLCs) are the ones with poor water solubility and low volatility, resistant to physical, chemical and biological processes, persistent in the environment even under extreme conditions. Due to lipophilic nature, they get adhered to the fatty material and concentrate through biomagnification and bioaccumulation, thereby easily getting incorporated into food chains, paving the way to endocrine disruption via modulation of various human receptors. This in turn leads to certain adverse health effects. In the present study, a total of 100 dioxins and DLCs were taken and their binding pattern was assessed with the ketosteroid receptors, i.e. androgen (hAR), glucocorticoid (hGR), progesterone (hPR) and mineralocorticoid (hMR) in comparison to the corresponding natural steroids and a known endocrine disrupting xenobiotic, Bisphenol A (BPA). Most of the DLCs, particularly those bearing hydroxyl (-OH) group showed considerable affinities with ketosteroid receptors. On comparing D scores of all the dioxins and DLCs against all four receptors, compound 8-hydroxy-3,4-dichlorodibenzofuran(8-OH-DCDF) exhibited least D score of -9.549?kcal mol^?1 against hAR. 3,8-Dihydroxy-2-chlorodibenzofuran(3,8-DiOH-CDF), 4′-hydroxy-2,3,4,5-tetrachlorobiphenyl (4′-OH-TCB) and 4-hydroxy-2,2′,5′-trichlorobiphenyl(4-OH-TCB) also showed comparable molecular interactions with the ketosteroid receptors. These interactions mainly include H-bonding, π–π stacking, hydrophobic, polar and van der Waals’ interactions. In contrast, BPA and some natural ligands tested in this study showed lower binding affinities with these receptors than certain DLCs reported herein, i.e. certain DLCs might be more toxic than the proven toxic agent, BPA. Such studies play a pivotal role in the risk assessment of exposure to dioxins and DLCs on human health.