Arecoline inhibits pineal-testis function in experimentally induced hypothyroid rats.

DARK Classics in Chemical Neuroscience: Arecoline.

Abstract: Arecoline is a naturally occurring psychoactive alkaloid from areca (betel) nuts of the areca palm ( Areca catechu) endemic to South and Southeast Asia. A partial agonist of nicotinic and muscarinic acetylcholine receptors, arecoline evokes multiple effects on the central nervous system (CNS), including stimulation, alertness, elation, and anxiolysis. Like nicotine, arecoline also evokes addiction and withdrawal symptoms (upon discontinuation). The abuse of areca nuts is widespread, with over 600 million users globally. The importance of arecoline is further supported by its being the world's fourth most commonly used human psychoactive substance (after alcohol, nicotine, and caffeine). Here, we discuss neuropharmacology, pharmacokinetics, and metabolism of arecoline, as well as social and historical aspects of its use and abuse. Paralleling clinical findings, we also evaluate its effects in animal models and outline future clinical and preclinical CNS research in this field.

Hypothyroidism: morphological and metabolic changes in the testis of adult albino rat and the amelioration by alpha-lipoic acid

Abstract: Background: The objective of this study is to evaluate the influence of carbimazole- induced hypothyroidism on the testes of adult albino rats and the probable protective effect of alpha-lipoic acid (ALA). Materials and methods: The rats were divided into four groups; control group, ALA group, carbimazole, and carbimazole + ALA groups. Rats were exposed to ALA (60 mg/kg body weight) or carbimazole (1.35 mg/kg body weight), or both, administered via gavages for 30 days. Results: Morphometric analysis revealed a significant decrease in tubular diameter, germinal epithelium thickness, and interstitial space as compared to the controls. Also, rats exposed to carbimazole showed a significant decline in testicular weight, sperm motility, and count. Additionally, deterioration of the testicular architecture was observed. ALA supplementation resulted in a significant improvement in the tubular diameter and germinal epithelium thickness, but no significant improvement regarding interstitial space was observed. Another observation was the significant decline in serum testosterone and follicle-stimulating hormone (FSH) in the carbimazole group, indicating reduced steroidogenesis. A significant reduction in reduced glutathione content was detected in the testes of the carbimazole group compared with the controls, while malonaldehyde concentration significantly increased. Conversely, ALA supplementation ameliorated the toxicity induced by hypothyroidism as illustrated by enhanced reproductive organ weights, testosterone, luteinizing hormone, and FSH levels, testicular steroidogenesis, and oxidative stress parameters. Conclusions: Hypothyroidism altered testicular antioxidant balance and negatively affected spermatogenesis. On the other hand, ALA through its antioxidant properties alleviated testicular toxicity in carbimazole-exposed rats.

ENHANCED p53-DEPENDENT GROWTH INHIBITION OF HUMAN GLIOBLASTOMA CELLS BY COMBINATORIAL TREATMENT OF TEMOZOLOMIDE AND NOVEL PURIFIED NATURAL CARBOHYDRATE OF PLEUROTUS FLORIDA

Abstract: Objective: This study was designed to analyze the combinatorial chemotherapeutic effect of temozolomide (TMZ), the most common drug in glioblastoma treatment and a purified carbohydrate (Fr-II) from the edible mushroom Pleurotus florida , on human glioblastoma cell lines Methods: Fr-II was purified by size-exclusion chromatography and characterised by different mass spectroscopy analysis Human glioblastoma cells were treated with TMZ, Fr-II, and combination of TMZ and Fr-II Cell cytotoxicity was measured by MTT assay, cell cycle phase distribution was determined by cell cycle analysis and followed by the relative p53 protein expression was analyzed by western blot analysis Results: Chemical analysis of Fr-II confirmed the glycosidically linked two units of glucose with terminally attached mannitol with mass of 506 Da Fr-II treatment exhibited cytotoxicity in both the cell lines in a dose-dependent manner with most effective dose at 200µg/ml When Fr-II (200µg/ml) was combined with a dose range of TMZ it showed a more cellular cytotoxicity compared to the cytotoxicity of TMZ alone with most oppressive combinatorial dose at 400µM (TMZ)+200µg/ml (Fr-II) In compliance, with the above results, both cell lines showed a 10% increase in no of cells (p<005) in G 2 /M phase indicating an arrest of cell cycle and increased p53 protein expression (p<005) at the combinatorial dose than TMZ alone at 400µM, but Fr-II alone didn’t show any cell cycle arrest nor did it show increased p53 expression Conclusion: Therefore it confirms that Fr-II synergizes with TMZ to significantly intensify its anti-proliferative properties, thereby emerging as an effective element for combinatorial treatment of glioblastoma

Identification of novel biomarkers and candidate small molecule drugs in rheumatoid arthritis and osteoarthritis based on bioinformatics analysis of high-throughput data.

Abstract: Background Rheumatoid arthritis (RA) and osteoarthritis (OA) are two major types of joint diseases. The present study aimed to identify hub genes involved in the pathogenesis and further explore the potential treatment targets of RA and OA. Methods The gene expression profile of GSE12021 was downloaded from Gene Expression Omnibus (GEO). Total 31 samples (12 RA, 10 OA and 9 NC samples) were used. The differentially expressed genes (DEGs) in RA versus NC, OA versus NC and RA versus OA groups were screened using limma package. We also verified the DEGs in GSE55235 and GSE100786. Functional annotation and protein-protein interaction (PPI) network construction of OA- and RA-specific DEGs were performed. Finally, the candidate small molecules as potential drugs to treat RA and OA were predicted in CMap database. Results 165 up-regulated and 163 down-regulated DEGs between RA and NC samples, 73 up-regulated and 293 down-regulated DEGs between OA and NC samples, 92 up-regulated and 98 down-regulated DEGs between RA and OA samples were identified. Immune response and TNF signaling pathway were significantly enriched pathways for RA- and OA-specific DEGs, respectively. The hub genes were mainly associated with 'Primary immunodeficiency' (RA vs. NC group), 'Ribosome' (OA vs. NC group), and 'Chemokine signaling pathway' (RA vs. OA group). Arecoline and Cefamandole were the most promising small molecule to reverse the RA and OA gene expression. Conclusion Our findings suggest new insights into the underlying pathogenesis of RA and OA, which may improve the diagnosis and treatment of these intractable chronic diseases.

The thiobarbituric acid assay of sialic acids.

Abstract: Publisher Summary This chapter discusses the different aspects of thiobarbituric acid assay of sialic acid. Periodate oxidation of the neuraminic acid backbone of sialic acids results in the formation of β -formylpyruvic acid from carbon atoms 1 to 4. The N -acetyl or N -glycolyl group of sialic acids apparently does not interfere with periodate oxidation. β -Formylpyruvic acid is coupled with 2-thiobarbituric acid to form a red chromophore with a maximum absorption at 549 mμ. It is found that as only free sialic acids are reactive in the assay, hydrolysis of sialic acid-containing material must be carried out for the measurement of total sialic acids. The assay is suitable for measuring the release of bound sialic acid by sialidase. A series of 2-keto, 3-deoxy sugar acids, found in bacteria, also react in the thiobarbituric acid assay. These produce a chromogen with a peak at 549 mμ. They can be readily distinguished from sialic acids because they are not reactive in the orcinol or direct Ehrlich assays for sialic acids. The hydrolysis frees all the sialic acids from several mucoproteins that have been tested except for brain tissue where release of sialic acids takes place for several hours.

Williams Textbook of Endocrinology

Abstract: Williams textbook of endocrinology , Williams textbook of endocrinology , کتابخانه الکترونیک و دیجیتال - آذرسا