Clinical pertinence of neutrophil-to- lymphocyte ratio among hypertensives with different grades and duration of hypertension – an insight

Over the recent years, the pathophysiology of the inflammatory component in hypertension has been a challenge, because this inflammatory response is mainly contributed by an increased oxidative stress with the release of inflammatory mediators. Identification of a simple and early inflammatory marker such as the neutrophil-to-lymphocyte ratio (NLR) is the need of the hour. This study correlates the same specifically taking into account the duration and the grades of hypertension.

Objective: The response of the NLR among the hypertensives and its correlation with duration and stages of hypertension.

Method: Totally, 80 subjects and 40 controls of age between 20 and 60 years and both genders were included. Three recordings of blood pressure were measured with a standard mercury sphygmomanometer. The differential leukocyte count was estimated with an automated Beckman Coulter.

Objective: Variations in the neutrophil and lymphocyte counts were significant among the hypertensives with a p-value < 0.001. The NLR was also significantly altered among the hypertensives with a p-value = 0.001. The NLR showed a rise in value among the normotensives, prehypertensives, and stage 1 of systolic hypertension, though not statistically significant. An increase in the NLR was observed in hypertensives with duration of 1–2 years.

Conclusion: Our study gives a new insight with a rise in NLR in early years and even among prehypertensives and stage 1 systolic hypertension under strict criterion. This could be utilized as an early predictive tool, relating the inflammatory process and hypertension which on further intervention could slow the progression of the disease process.

Abbreviations: NLR: Neutrophil-to-lymphocyte ratio; BP: Blood pressure.     

Utility of CT oral contrast administration in the emergency department of a quaternary oncology hospital: diagnostic implications,turnaround times,and assessment of ED physician ordering

Abdominal Radiology - To compare studies with and without oral contrast on performance of multidetector computed tomography (CT) and the order to CT examination turnaround time in cancer patients...     

Antioxidants in prevention of cataracts in South India: methodology and baseline data*

PURPOSE: To describe the methodology and baseline data for the Antioxidants in Prevention of Cataracts (APC) study in South India. METHODS: The APC study is a prospective, 5-year, randomized, triple-masked, placebo-controlled, field-based clinical trial to examine the effect of antioxidants (combination tablet of vitamins A, C, and E) on progression of cataract. The primary outcome variable is cataract progression (nuclear opalescence), evaluated with the slit-lamp biomicroscope by the Lens Opacification Classification System III method. Secondary outcome variables are progression in cortical and posterior subcapsular opacity and nuclear color, change in best corrected visual acuity, myopic shift, and treatment failure (progression to cataract surgery or best corrected vision worse than 20/400 in an eye). Inclusion criteria are age between 35 and 50 years and best-corrected visual acuity of 20/40 or better. Exclusion criteria are a diagnosis of diabetes mellitus or nonfasting blood glucose level>7.8 mmol/L, history or presence of various ocular conditions or treatment forms, or current use of vitamin supplements. Baseline ophthalmic, demographic, and potential cataract risk factor data (such as smoking, sunlight, or alcohol exposure) were compared between groups on an intent-to-treat basis. RESULTS: Of 954 people screened, 798 were enrolled, a sample size which exceeded the required estimate. More than 80% of subjects had 20/20 or better vision in at least one eye, and baseline prevalence of significant cataract according to the LOCS III grading scale was high. The two treatment groups were comparable for all baseline measures except alcohol intake. CONCLUSION: The sample size and group baseline characteristics will provide sufficient power to detect a change in cataract progression within 5 years.     

Indole-3-carbinol in the maternal diet provides chemoprotection for the fetus against transplacental carcinogenesis by the polycyclic aromatic hydrocarbon dibenzo[a,l]pyrene

The fetus and neonate are sensitive targets for chemically induced carcinogenesis. Few studies have examined the risk/benefit of chemoprotective phytochemicals, given in the maternal diet, against transplacental carcinogenesis. In this study, B6129 SF1/J (AHR(b-1/d)) and 129Sv/ImJ (AHR(d/d)) mice were cross-bred. The polycyclic aromatic hydrocarbon, dibenzo[a,l]pyrene (DBP), was administered to pregnant mice (15 mg/kg, gavage) on gestation day 17, and 2000 p.p.m. indole-3-carbinol (I3C), a chemoprotective phytochemical from cruciferous vegetables, was fed to half of the mice from gestation day 9 until weaning. Offspring born to dams fed I3C exhibited markedly fewer mortalities (P < 0.0001). Maternal dietary exposure to I3C also significantly lowered lung tumor multiplicity (P = 0.035) in offspring surviving to 10 months of age. The I3C chemoprotection was independent of either maternal or fetal AHR genotype. The bioavailability of DBP to fetal target tissue was demonstrated by assessing DNA covalent adduction with a (33)P-post-labeling assay. The bioavailability of I3C was determined by dosing a subset of pregnant mice with [(14)C]-I3C. Addition of chemoprotective agents to the maternal diet during pregnancy and nursing may be an effective new approach in reducing the incidence of cancers in children and young adults.     

Effect of a standardized complex mixture derived from coal tar on the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons in human cells in culture

A complex mixture of polycyclic aromatic hydrocarbons (PAH) extracted from coal tar, standard reference material (SRM) 1597, has been shown to initiate tumor formation in mouse initiation-promotion assays in our laboratory [(2001) Carcinogenesis 22 (7), 1077-1086]. To determine the effects of SRM 1597 on PAH activation in human cells, we investigated the PAH-DNA adduct formation in the human mammary carcinoma-derived cell line MCF-7. We examined the effects of SRM 1597 on the metabolic activation to DNA binding derivatives of two carcinogenic PAHs, the bay region containing benzo[a]pyrene (B[a]P) and the more carcinogenic fjord region containing dibenzo[a,l]pyrene (DB[a,l]P). PAH-DNA adduct analysis by 33P-postlabeling and reversed phase high-performance liquid chromatography revealed a significant decrease in the levels of both B[a]P and DB[a,l]P DNA adduct formation on cotreatment with SRM 1597 in comparison to cells exposed to B[a]P or DB[a,l]P alone. However, the inhibition of PAH-DNA adduct formation only occurred within the first 48 h of exposure in cells cotreated with SRM 1597 and B[a]P. In contrast, SRM 1597 significantly inhibited the level of DB[a,l]P DNA adducts throughout the 120 h of exposure. Induction of human cytochrome P450 (P450) enzymes 1A1 and P4501B1 on treatment with SRM 1597 was observed by immunoblots. These results suggest that the important factors in determining the carcinogenic activity of PAH within a complex mixture would depend on the ability of other components of the mixture to promote or inhibit the activation of carcinogenic PAH by the induction of P450 enzymes followed by the formation of DNA adducts.     

Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia

Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet, the mechanisms for decreased hair growth in this disorder are unclear. We show that prostaglandin D(2) synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D(2) (PGD(2)), is similarly elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD(2) levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD(2) inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD(2) receptor G protein (heterotrimeric guanine nucleotide)-coupled receptor 44 (GPR44), but not the PGD(2) receptor 1 (PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD(2) in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD(2) as an inhibitor of hair growth in AGA and suggest the PGD(2)-GPR44 pathway as a potential target for treatment.     

African American and Latino patient versus provider perceptions of determinants of prenatal care initiation

Few studies have compared provider and patient perceptions of barriers, motivators and facilitators of prenatal care (PNC) initiation. The current study compared these perceptions in providers and patients in Washington, DC, a city characterized by infant mortality and low birth weight rates that are among the highest in the nation, and poor utilization of PNC, particularly among minority groups. The results reported here were part of a larger study of barriers, motivators and facilitators influencing PNC utilization in Washington, DC. A convenience sample of 331 African American and Latino patients and 61 providers were interviewed to identify which of 63 motivators, facilitators, and barriers significantly influenced PNC initiation. Both sample groups were recruited at 14 PNC facilities, selected to represent all sites in DC known to serve high-risk, low-income minority women, including hospital-based clinics, community-based clinics, and private practices. Data were analyzed using Fisher exact tests and Kendall's concordance tests. Results indicated that there was good agreement between patients and providers about the relative importance of the various barriers (especially psychosocial), motivators, and facilitators. However, differences were found between patients and providers in the response frequencies. Providers were more likely to report barriers while patients were more likely to report certain motivators (especially learning better health habits and how to protect health). These results indicate that despite widespread agreement on most issues, especially psychosocial barriers, patients rated health education higher than providers.     

Raised intracellular glucose concentrations reduce aggregation and cell death caused by mutant huntingtin exon 1 by decreasing mTOR phosphorylation and inducing autophagy

Huntington's disease is caused by a CAG trinucleotide repeat expansion that is translated into an abnormally long polyglutamine tract. This gain-of-function mutation is associated with huntingtin aggregation and cell death. Autophagy is an important clearance route for mutant huntingtin exon 1. While mammalian target of rapamycin (mTOR) is a key regulator of autophagy, the upstream modifiers of this process are poorly understood. Our previous expression profiling studies in HD cell models observed changes in four genes associated with glucose metabolism, including the GLUT1 glucose transporter. A role for intracellular glucose as a modulator for polyglutamine toxicity was suggested as cell death was reduced by GLUT1 overexpression. Here we show that the protective effect of GLUT1 is associated with decreased huntingtin exon 1 aggregation in cell models. Consistent with this result, we also observed reduced aggregation and enhanced clearance of mutant huntingtin when cells were cultured in raised glucose concentrations (8 g/l). These effects were mimicked by 8 g/l 2-deoxyglucose (2DOG) (transported, phosphorylated but not metabolized further), but not with 8 g/l 3-O-methyl glucose (transported but not metabolized further). Thus, this phenomenon is probably mediated by glucose-6-phosphate. Increased clearance of mutant huntingtin by raised glucose (8 g/l) and 2DOG correlated with increased autophagy and reduced phosphorylation of mTOR, S6K1 and Akt. Thus, raised intracellular glucose/glucose 6-phosphate levels reduce mutant huntingtin toxicity by increasing autophagy via mTOR and possibly Akt. As mTOR and Akt regulate a diversity of crucial cellular processes, our data also suggest a major new set of targets for intracellular glucose signalling.