Potent MCH-1 receptor antagonists from cis-1,4-diaminocyclohexane-derived indane analogs.

Benzimidazole and indane are the two key fragments in our potent and selective MCH-1 receptor (MCHR1) antagonists. To identify novel linkers connecting the two fragments, we investigated diamino-cycloalkane-derived analogs and discovered highly potent antagonists with cis-1,4-diaminocyclohexane as a unique spacer in this chemical class. Structural overlay suggested that cis-1-substituted-4-aminocyclohexane functions as a bioisostere of 4-substituted-piperidine and that the active conformation adopts a U-shaped orientation.

A review on extraction, composition, structure, and biological activities of polysaccharides from different parts of Nelumbo nucifera.

Nelumbo nucifera (lotus plant) is an important member of the Nelumbonaceae family. This review summarizes the studies conducted on it since the past 15 years to provide an understanding on future areas of focus. Different parts of this plant, that is, leaves, roots, and seeds, have been used as food and for the treatment of various diseases. Polysaccharides have been extracted from different parts using different methods. The manuscript reviews the methods of extraction of polysaccharides used for leaves, roots, and seeds, along with their yield. Some methods can provide better yield while some provide better biological activity with low yield. The composition and structure of extracted polysaccharides have been determined in some studies. Although monosaccharide composition has been determined in various studies, too little information about the structure of polysaccharides from N. nucifera is available in the current literature. Different useful biological activities have been explored using in vivo and in vitro methods, which include antioxidant, antidiabetic, antitumor, anti-osteoporotic, immunomodulatory, and prebiotic activities. Antitumor activity from polysaccharides of lotus leaves is yet to be explored, besides lotus root has been underexplored as compared to other parts (leaves and seeds) according to our literature survey. Studies dedicated to the successful use of combination of extraction methods can be conducted in future. The plant provides a therapeutic as well as nutraceutical potential; however, antimicrobial activity and synergistic relationships of polysaccharides from different parts of the plant need further exploration.

Potent, selective MCH-1 receptor antagonists.

This paper describes the lead optimization of a new series of potent, selective, orally bioavailable, brain-penetrant MCH-1 receptor antagonists. A major focus of the work was to achieve a selectivity profile appropriate for in vivo efficacy studies and safety.

Association between Tooth Loss and Opium Addiction: Results of a Community-Based Study on 5900 Adult Individuals in South East of Iran in 2015.

BACKGROUND: Like any other drug abuse, opium use is known to have detrimental effects on oral health. Oral hygiene neglect in opium users can lead to tooth loss resulting in further functional, esthetic, and dieting problems. Therefore, the aim of this study was to assess the association between tooth loss and opium addiction in a large-scale population. MATERIALS AND METHODS: This study was part of an extensive study related to the risk factors of cardiovascular disease and conducted by the center for physiological research during 2012-2015 in Kerman. A total of 5900, 15-75-year-old individuals, were recruited by a single-stage random cluster sampling method. Factors including opium and smoking consumption, factors related to oral health, hygiene, and the number of missing teeth were examined. Data were collected through questionnaires, interviews, and physical examination. RESULTS: Of 5900 individuals, 2662 (45.1%) were men and the rest were women, which 1011 individuals (17.1%) consumed opium. The prevalence of opium abuse was significantly higher in men. Regarding the oral dental indicators, the numbers of missing teeth (P < 0.001), decayed (P = 0.01), and the total index of decayed, missing, and filled teeth (P < 0.001) were significantly higher in addicts as compared to nonaddicts. The gingival index and community periodontal index scores were significantly lower in addicts. Addicted women had a higher prevalence of tooth loss. CONCLUSIONS: Opium addiction is associated with higher tooth loss, especially, in women opium users. Dental practitioners and health politicians should pay special attention to the oral health of addicts before tooth loss occurs.

Liquid chromatography determination of residue levels on apples treated with cetylpyridinium chloride.

Cetylpyridinium chloride (CPC) has been found to be effective in reducing microbial contamination in apples. A sensitive and specific HPLC method was developed to determine CPC residues in apples treated with CPC. This method involves ion exchange solid-phase extraction, and the use of stearylpyridinium chloride (SPC) as internal standard. Limit of quantitation, was 0.5 microg/ml of CPC for the apple ethanolic extracts. The observed residues in apple (2.35-4.35 microg/g of apple) were lower than those previously reported for chicken and beef. The method is specific, sensitive, reproducible and accurate.

Pharmacokinetic distribution of 67Cu(II)2[3,5-diisopropyl(carboxy-14C)salicylate]4 among murine tissues.

Non-toxic doses of tetrakis-mu-3,5-diisopropylsalicylatodicopper(II) [Cu(II)2(3,5-DIPS)4] have been found to have anti-inflammatory, analgesic, anti-ulcer, anti-colitis, anti-convulsant, anti-cancer, anti-mutagenic, anti-carcinogenic, and anti-diabetic activities and, in addition, facilitates recovery from lethal irradiation and ischemia-reperfusion injuries. The goal of this research was to determine the time-dependent tissue distribution and persistence of 67Cu and the 14C labeled salicylate ligand, carboxy-14C-3, 5-diisopropylsalicylate [3,5-DIP(carboxy-14C)S], following subcutaneous administration of a 50 micromole per kilogram of body mass dose of double labeled tetrakis-mu-3,5-diisopropyl[carboxy-14C]salicylatodiaquo [67Cu]dicopper(II) 67Cu(II)4[3,5-DIP(carboxy-14C)S]4. This compound was administered to nine groups of six 20 gram female C57BL/6 mice and blood, liver, kidney, intestine, lung, thymus, femur, muscle, spleen, and brain tissues removed and analyzed for 67Cu and 14C at 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hours after treatment. These data were then analyzed using a pharmacokinetic model simulation program. Both 67Cu and 14C were found in all tissues as well as urine and feces at 0.5 hour after administration. As anticipated, 67Cu entered the liver storage pool; it was conserved by the kidneys, and subsequently underwent release in maintaining 67Cu levels in all other tissues. While the presence of 67Cu correlated with the presence of the salicylate ligand, 3,5-DIP (carboxy-14C)S, early in the course of this experiment, the ligand was lost via ligand exchange and could not be measured in blood, kidney, intestine, lung, thymus, spleen, and brain after 24 hours following administration. However, 3,5-DIP(carboxy-14C)S persisted in liver, femur, and muscle throughout the 5-day period of study. It is suggested that marked lipophilicity accounts for its very rapid distribution to all tissues wherein it undergoes ligand exchange as 67Cu is incorporated into Cu-dependent enzymes and proteins and persists in tissues based upon physiological demand for Cu in meeting normal biochemical requirements.

Elimination of Salmonella Contamination from Poultry Tissues by Cetylpyridinium Chloride Solutions.

The effects of cetylpyridinium chloride (CPC) on the inhibition and reduction of viable Salmonella typhimurium cells were studied. In these experiments skin excised from chicken drumsticks was treated with solutions of CPC. At the CPC concentrations used, the ability of this compound to reduce bacterial contamination was clearly demonstrated. This effect was both CPC concentration- and exposure-time-dependent. A 4.87-log reduction of viable S. typhimurium cells was achieved at a CPC concentration of 4 mg/ml at the treatment time of 3 min. Moreover, CPC was effective in preventing bacterial contamination, as shown by a 4.9-log inhibition of S. typhimurium cell attachment at a CPC concentration of 8 mg/ml and a treatment time of 10 min.