Dietary-feeding of grape seed extract prevents azoxymethane-induced colonic aberrant crypt foci formation in fischer 344 rats.

Chemoprevention by dietary agents/supplements has emerged as a novel approach to control various malignancies, including colorectal cancer (CRC). This study assessed dietary grape seed extract (GSE) effectiveness in preventing azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation and associated mechanisms in Fischer 344 rats. Six-week-old rats were injected with AOM, and fed control diet or the one supplemented with 0.

Reversed-phase liquid chromatographic resolution of diastereomers of protein and non-protein amino acids prepared with newly synthesized chiral derivatizing reagents based on cyanuric chloride.

Two new chiral monochloro-s-triazines (MCT) were synthesized [viz N-(4-chloro-6-piperidinyl-[1,3,5]-triazine-2-yl)-L-leucine amide and N-(4-chloro-6-piperidinyl-[1,3,5]-triazine-2-yl)-L-leucine) (CDR 1 and 2, respectively)] by the nucleophilic displacement of chlorine atoms in s-triazine moiety. One of the Cl atoms was replaced with piperidine, and the second Cl atom in the 6-piperidinyl derivative was replaced with amino acid amide (viz L-Leu-NH(2)) and amino acid (L-Leu). These reagents were characterized and used as CDRs for chiral separation of protein and non-protein amino acids, and were separated on a reversed-phase C(18) column.

Bilateral sudden sensorineural deafness with vertigo as the sole presenting symptoms of diabetes mellitus - a case report.

This Paper reports a late uncontrolled diabetic presenting to an otolaryngologist with sudden severe sensorineural hearing loss of immediate origin with vertigo and tinnitus as the symptoms. Appropriate investigative and treatment measure resulted in deterioration of hearing in the right ear and mild improvement of hearing in the left ear, with no recovery of imbalance.

Biological and molecular mechanisms of sulfur mustard analogue-induced toxicity in JB6 and HaCaT cells: possible role of ataxia telangiectasia-mutated/ataxia telangiectasia-Rad3-related cell cycle checkpoint pathway.

Effective medical treatment and preventive measures for chemical warfare agent sulfur mustard (HD)-caused incapacitating skin toxicity are lacking, because of limited knowledge of its mechanism of action. The proliferating basal epidermal cells are primary major sites of attack during HD-caused skin injury. Therefore, employing mouse JB6 and human HaCaT epidermal cells, here, we investigated the molecular mechanism of HD analogue 2-chloroethyl ethyl sulfide (CEES)-induced skin cytotoxicity.

Silibinin suppresses growth of human colorectal carcinoma SW480 cells in culture and xenograft through down-regulation of beta-catenin-dependent signaling.

Mutations in APC/beta-catenin resulting in an aberrant activation of Wnt/beta-catenin pathway are common in colorectal cancer (CRC), suggesting that targeting the beta-catenin pathway with chemopreventive/anticancer agents could be a potential translational approach to control CRC. Using human CRC cell lines harboring mutant (SW480) versus wildtype (HCT116) APC gene and alteration in beta-catenin pathway, herein we performed both in vitro and in vivo studies to examine for the first time whether silibinin targets beta-catenin pathway in its efficacy against CRC. Silibinin treatment inhibited cell growth, induced cell death, and decreased nuclear and cytoplasmic levels of beta-catenin in SW480 but not in HCT116 cells, suggesting its selective effect on the beta-catenin pathway and associated biologic responses.

Anion dependence of transport of mercury ion through Nafion-117 membrane.

Studies on isotopic and ion-exchange kinetics of mercury ions in Nafion-117 membrane have been carried out with (203)Hg radiotracer in the presence of Cl(-) and NO(3)(-) in solution. The results of isotopic-exchange kinetics indicate that mercury ions diffuse into the membrane as monovalent cation from HgCl(2) solution while as divalent ion from Hg(NO(3))(2) solution. The studies on the kinetics of ion exchange of Hg(2+) with Na(+) follow the prediction of the Nernst-Planck equation when NaNO(3) is used as an external salt solution.

Influence of gallate esterification on the activity of procyanidin B2 in androgen-dependent human prostate carcinoma LNCaP cells.

Purpose: Present study assessed the influence of gallate esterification on the anti-cancer activity of procyanidin B2 (B2) in androgen-dependent human prostate carcinoma LNCaP cells employing B2-3,3'-di-O-gallate (B2-G(2)), two mono-gallate esters B2-3-O-gallate (B2-3G) and B2-3'-O-gallate (B2-3'G) and the parent compound B2, all isolated from grape seed extract (GSE).

Materials And Methods: Study compounds were isolated from GSE by several chromatographic steps and structures determined by a combination of enzymatic hydrolysis, mass spectrometry and comparisons with standards. Cells, treated with these compounds, were assessed for viability and apoptosis and examined by western blotting.

Lactoferrin protects against concanavalin A-induced liver injury in mice.

Background: Liver diseases, caused by viral infection, autoimmune conditions, alcohol ingestion or the use of certain drugs, are a significant health issue, as many can develop into liver failure. Lactoferrin (Lac) is an iron-binding glycoprotein that belongs to the transferrin family. Owing to its multiple biological functions, Lac has been evaluated in a number of clinical trials to treat infections, inflammation and cancer.

The course of the frontal branch of the facial nerve in relation to fascial planes: an anatomic study.

Background: Despite a wealth of literature describing the anatomy of the temporal region, controversy still exists over the depth of the frontal branch of the facial nerve as it travels over the zygomatic arch. It is commonly stated that the frontal branch travels within the superficial musculoaponeurotic system (SMAS) as it crosses the zygomatic arch. Clinically, however, it is apparent that the nerve runs at a deeper level as it crosses the arch, allowing for safe elevation and division of the SMAS to a point at or above the superior border of the zygomatic arch.

Application of (S)-N-(4-Nitrophenoxycarbonyl) phenylalanine methoxyethyl ester as a chiral derivatizing reagent for reversed-phase high-performance liquid chromatographic separation of diastereomers of amino alcohols, non-protein amino acids, and PenA.

Indirect enantioresolution of 15 primary and secondary amino group containing compounds (amino alcohols, non-protein amino acids, PenA) was done using the reagent (S)-N-(4-Nitrophenoxycarbonyl) phenylalanine methoxyethyl ester [(S)-NIFE] by reversed-phase high-performance liquid chromatography. The diastereomeric derivatives were analyzed under reversed-phase conditions using linear gradient. The detection was at 205 nm and sharp peaks were obtained.

Dietary feeding of grape seed extract prevents intestinal tumorigenesis in APCmin/+ mice.

Chemopreventive effects and associated mechanisms of grape seed extract (GSE) against intestinal/colon cancer development are largely unknown. Herein, we investigated GSE efficacy against intestinal tumorigenesis in APC(min/+) mice. Female APC(min/+) mice were fed control or 0.

Two phosphodiesterases from ustilago maydis share structural and biochemical properties with non-fungal phosphodiesterases.

The dependence of Protein Kinase A (PKA) activity on cAMP levels is an important facet of the dimorphic switch between budding and filamentous growth as well as for pathogenicity in some fungi. To better understand these processes in the pathogenic fungus Ustilago maydis, we characterized the structure and biochemical functions of two phosphodiesterase (PDE) genes. Phosphodiesterases are enzymes involved in cAMP turnover and thus, contribute to the regulation of the cAMP-PKA signaling pathway.

Inositol hexaphosphate suppresses growth and induces apoptosis in prostate carcinoma cells in culture and nude mouse xenograft: PI3K-Akt pathway as potential target.

Constitutive activation of phosphoinositide 3-kinase (PI3K)-Akt pathway transmits growth-regulatory signals that play a central role in promoting survival, proliferation, and angiogenesis in human prostate cancer cells. Here, we assessed the efficacy of inositol hexaphosphate (IP6) against invasive human prostate cancer PC-3 and C4-2B cells and regulation of PI3K-Akt pathway. IP6 treatment of cells suppressed proliferation, induced apoptosis along with caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage, and inhibited constitutive activation of Akt and its upstream regulators PI3K, phosphoinositide-dependent kinase-1 and integrin-linked kinase-1 (ILK1).

Silibinin inhibits human nonsmall cell lung cancer cell growth through cell-cycle arrest by modulating expression and function of key cell-cycle regulators.

Recent studies show that silibinin possesses a strong antineoplastic potential against many cancers; however, its efficacy and underlying molecular mechanisms in nonsmall cell lung cancer (NSCLC) are not well defined. Herein, we assessed silibinin activity on prime endpoints and key molecular targets such as cell number, cell-cycle progression, and cell-cycle regulatory molecules in three cell lines representing different NSCLC subtypes, namely large cell carcinoma cells (H1299 and H460) and a bronchioalveolar carcinoma cell line (H322). Silibinin treatment (10-75 microM) inhibited cell growth and targeted cell-cycle progressing causing a prominent G(1) arrest in dose- and time-dependent manner.

A common polymorphism in the promoter of UCP2 is associated with obesity and hyperinsulenemia in northern Indians.

A polymorphism in the promoter region of uncoupling protein 2 gene -866 G/A has been associated with its expression levels, the risk of obesity, and metabolic abnormalities. We aimed to investigate the associations of uncoupling protein (UCP)2 gene variants with obesity and related traits. A total of 440 subjects, 200 obese, and 240 non-obese individuals were included in this case-control study.

Sulfur mustard analog induces oxidative stress and activates signaling cascades in the skin of SKH-1 hairless mice.

A monofunctional analog of the chemical warfare agent sulfur mustard (HD), 2-chloroethyl ethyl sulfide (CEES), induces tissue damage similar to HD. Herein we studied the molecular mechanisms associated with CEES-induced skin inflammation and toxicity in SKH-1 hairless mice. Topical CEES exposure caused an increase in oxidative stress as observed by enhanced 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid)-1-pyrroline N-oxide protein adduct formation and an increase in protein oxidation.

Anticancer and cancer chemopreventive potential of grape seed extract and other grape-based products.

With emerging trends in the incidence of cancer of various organ sites, additional approaches are needed to control human malignancies. Intervention or prevention of cancer by dietary constituents, a strategy defined as chemoprevention, holds great promise in our conquest to control cancer, because it can be implemented on a broader population base with less economic burden. Consistent with this, several epidemiological studies have shown that populations that consume diets rich in fruits and vegetables have an overall lower cancer incidence.

Silibinin suppresses growth and induces apoptotic death of human colorectal carcinoma LoVo cells in culture and tumor xenograft.

Colorectal cancer is one of the leading causes of cancer-related morbidity and mortality. The use of nontoxic phytochemicals in the prevention and intervention of colorectal cancer has been suggested as an alternative to chemotherapy. Here we assessed the anticancer efficacy of silibinin against advanced colorectal cancer LoVo cells both in vitro and in vivo.

Inositol hexaphosphate downregulates both constitutive and ligand-induced mitogenic and cell survival signaling, and causes caspase-mediated apoptotic death of human prostate carcinoma PC-3 cells.

Constitutively active mitogenic and prosurvival signaling cascades due to aberrant expression and interaction of growth factors and their receptors are well documented in human prostate cancer (PCa). Epidermal growth factor (EGF) and insulin-like growth factor-1 (IGF-1) are potent mitogens that regulate proliferation and survival of PCa cells via autocrine and paracrine loops involving both mitogen-activated protein kinase (MAPK)- and Akt-mediated signaling. Accordingly, here we assessed the effect of inositol hexaphosphate (IP6) on constitutive and ligand (EGF and IGF-1)-induced biological responses and associated signaling cascades in advanced and androgen-independent human PCa PC-3 cells.

Gallic acid, an active constituent of grape seed extract, exhibits anti-proliferative, pro-apoptotic and anti-tumorigenic effects against prostate carcinoma xenograft growth in nude mice.

Purpose: Gallic acid, a natural agent present in a wide-range of fruits and vegetables, has been of potential interest as an anti-cancer agent; herein, we evaluated its efficacy in androgen-independent DU145 and androgen-dependent-22Rv1 human prostate cancer (PCa) cells.

Materials And Methods: Cell viability was determined by MTT and apoptosis by Annexin V-PI assays. In vivo anti-cancer efficacy was assessed by DU145 and 22Rv1 xenograft growth in nude mice given normal drinking water or one supplemented with 0.

p21/Cip1 and p27/Kip1 Are essential molecular targets of inositol hexaphosphate for its antitumor efficacy against prostate cancer.

Inositol hexaphosphate (IP6) causes G(1) arrest and increases cyclin-dependent kinase inhibitors p21/Cip1 and p27/Kip1 protein levels in human prostate cancer (PCa) DU145 cells lacking functional p53. However, whether cyclin-dependent kinase inhibitor I induction by IP6 plays any role in its antitumor efficacy is unknown. Herein, we observed that either p21 or p27 knockdown by small interfering RNA has no considerable effect on IP6-induced G(1) arrest, growth inhibition, and death in DU145 cells; however, the simultaneous knockdown of both p21 and p27 reversed the effects of IP6.

Utility of fibronectin in immuocytochemial differentiation of reactive mesothelial cells from metastatic malignant cells in serous effusions.

Cytological evaluation of serous effusions often poses difficulties to the pathologists. This study was designed to assess the utility of fibronectin as a mesothelial cell marker and evaluate its use along with carcinoembryonic antigen (CEA) as a short panel to aid in the differentiation of reactive mesothelial cells from metastatic adenocarcinoma cells in serous effusions. Forty serous effusion cases from clinically benign cases and forty from clinically malignant cases with a known primary were included in the study.

Grape seed extract induces cell cycle arrest and apoptosis in human colon carcinoma cells.

One approach to control colorectal cancer (CRC) is its preventive intervention by dietary agents or those consumed as supplements. However, because most of these products are often consumed by patients as an complementary and alternative medicine practice, a scientific base such as efficacy, mechanism, and standardized preparation needs to be developed. Grape seed extract (GSE) is one such supplement widely consumed by humans for its several health benefits.

Safely navigating around the facial nerve in three dimensions.

Although much literature discusses the anatomy and injury of the facial nerve branches, the fascial plane of the nerves, particularly where they transition from one plane to another, is rarely emphasized and information is often contradictory. This article describes in three-dimensional, accurate surgical terms where the facial nerve branches are located and how they can be protected during dissection above and below the superficial musculoaponeurotic system-platysma plane.

Direct enantiomeric TLC resolution of dl-penicillamine using (R)-mandelic acid and l-tartaric acid as chiral impregnating reagents and as chiral mobile phase additive.

DL-Penicillamine has been resolved into its enantiomers by normal-phase TLC using L-tartaric acid as chiral impregnating reagent as well as chiral mobile phase additive, while (R)-mandelic acid has been found to be successful as a chiral impregnating reagent. The solvent system acetonitrile-methanol-water (5:1:1, v/v) was found to be successful when L-tartaric acid was used as impregnating agent while the solvent combination acetonitrile-methanol-(0.5% l-tartaric acid in water, pH 5)-glacial acetic acid (7:1:1.