Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies.

BACKGROUND: Body mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk. DESIGN: We conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood (ages 18-21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. RESULTS: Higher waist-to-hip ratio (HR = 1.09, 95% CI 1.02-1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00-1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11-1.25 per 5 kg/m(2)), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m(2), HR = 1.36, 95% CI 1.20-1.55 for BMI 25.0 < 27.5 kg/m(2), HR = 1.48, 95% CI 1.20-1.84 for BMI 27.5 to <30 kg/m(2), HR = 1.43, 95% CI 1.11-1.85 for BMI ≥30 kg/m(2)). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01-1.10 per 5 kg/m(2)). CONCLUSIONS: Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.

Reaction time in Stroop test in Nepalese Medical Students.

BACKGROUND: Stroop test is one of the widely used tests in cognitive psychology. It is used both in healthy population and also in patients to assess the selective attention. The selective attention as assessed by it is also found to be altered in bilinguals. In Nepal, most of the students are bilingual since most of the courses are in English language. Thus, they learn English language along with their native languages. This study is aimed to assess the selective attention in healthy Nepalese medical students. OBJECTIVE: To study the reaction time in stroop test in medical students of Nepal. MATERIALS AND METHODS: This study was conducted on 30 healthy male students aged 23.1±2.8 yrs. They were asked to read congruent (red printed in red ink) and incongruent (red printed in blue ink) tests in classical stroop cards. The reaction times for both the tests were calculated. Median with inter-quartile range was obtained for reaction time. Wilcoxon's Sign Rank Test was used to compare reaction time and errors between congruent and incongruent cards. RESULTS: The subjects took 82.10 (63.75-107.76) sec longer to read incongruent stroop test (p<0.001). The error made was 0 in congruent stroop test and 1.5 (0-3) in incongruent stroop test (p<0.001). No students made error in the congruent test but 60% (18) of students made error in incongruent test (p<.001) and interference percentage in incongruent was 157 (115.32-213.50)%. CONCLUSION: The reaction time and interferences were more in incongruent stroop test than congruent test. The interference was very high than that of previous literature's value. This indicates that Nepalese students have delayed attention while performing classical English version of stroop test.

An electro-physiological device to assess status of vitreous transparency.

INTRODUCTION: Evaluation of optical media is important in ophthalmic practice. OBJECTIVE: to design and tryout an electro-physiological device in order to assess the transparency of the vitreous. MATERIALS AND METHODS: A media-meter was designed where a light sensitive sensor was placed on the cornea and adjoining sclera during the process of trans-illumination. The trans-corneal (TC) and trans-scleral (TS) light transmittance were recorded objectively. By standardizing these readings on normal eyes, it was possible to suspect any cause of vitreous turbidity in eyes where the transmittance of light was observed to be less than the normal readings. STATISTICS: Media-meter values were compared using Student's unpaired t- test for comparison between both the groups. Pearson or Spearman correlation coefficients were calculated for pooled media-meter values obtained from patients with endophthalmitis. RESULTS: The readings were obtained by TC and TS media-metry with white light in 20 eyes that served to standardize the device. The mean values for the intensity recorded on the media-meter were 206 to 74 Lux and after log-values conversion were 2.14 (range 2.36 to 1.87) and 45 to 31 Lux and after log conversion 1.60 (range 1.66 to 1.49) for TC and TS media-meter respectively. There was a highly significant difference between normal eye readings and the corresponding values obtained for TC and TS media-meter values in eyes with endophthalmitis. CONCLUSION: The media-meter can be used to evaluate vitreous transparency.

Newer approaches for optimal bioavailability of ocularly delivered drugs: review.

Eye diseases can cause discomfort and anxiety in patients, with the ultimate fear of loss of vision and facial disfigurement. Many regions of the eye are relatively inaccessible to systemically administered drugs and, as a result, topical drug delivery remains the preferred route in most cases. Drugs may be delivered to treat the precorneal region for conjunctivitis and blepharitis, or to provide intraocular diseases such as glaucoma, uveitis, and cytomegalovirus retinitis. Most of the ophthalmic formulation strategies aim at maximizing ocular drug permeability through prolongation of the drug residence time in the cornea and conjunctival sac, as well as minimizing precorneal drug loss. The conventional topical ocular drug delivery systems show drawbacks such as increased precorneal elimination and high variability in efficacy. Attempts have been made to overcome these problems and enhance ocular bioavailability by the development of newer drug delivery systems. This review is concerned with classification, recent findings and applications and biocompatibility of newer drug delivery systems for the treatment of ocular diseases.

Chitosan coated PLA nanoparticles for ophthalmic delivery: characterization, in-vitro and in-vivo study in rabbit eye.

The objective of the present study is to develop a poly (D, L-lactic acid) (PLA) nano-carrier for topical ocular applications. PLA nanoparticles (PLA-NPs) with 5-fluorouracil were prepared using varying concentration and molecular weight of PLA to regulate the particle size. The dimension and shape of nanoparticles were verified by using dynamic light scattering (DLS), atomic force microscope (AFM) and scanning electron microscope (SEM). Ex-vivo permeation study was conducted by goat and rabbit excised cornea. In-vivo experiment was conducted in rabbit eye and 5-FU concentration was measured in aqueous and vitreous humor by HPLC. In-vitro experiments indicated a diffusion controlled release of 5-FU. No significant interaction was observed in between mucin and PLA NPs that measured in terms of viscosity change. Ex-vivo permeation was significantly higher with rabbit cornea as compared to goat cornea. PLA and CH-PLA DNPs showed increased level of 5-FU as comparison to 5-FU solution. In-vivo study showed significantly higher concentration in case of uncoated and CH coated PLA nanoparticles in rabbit eye as compared to free 5-FU solution. PLA nanoparticle was found non-irritant in nature by modified Draize test.

Polymeric nanoparticulate system: a potential approach for ocular drug delivery.

Various efforts in ocular drug delivery have been made to improve the bioavailability and to prolong the residence time of drugs applied topically onto the eye. The potential use of polymeric nanoparticles as drug carriers has led to the development of many different colloidal delivery vehicles. Drug loaded polymeric nanoparticles (DNPs) offer several favorable biological properties, such as biodegradability, nontoxicity, biocompatibility and mucoadhesiveness. These submicron particles are better than conventional ophthalmic dosage forms to enhance bioavailability without blurring the vision. DNPs have been shown to be amenable to targeting of the drug to the site of action, leading to a decrease in the dose required and a decrease in side effects. Additionally, DNPs can be fabricated by simple techniques with better physical stability than liposomes. This unique combination of properties makes DNPs a novel polymeric drug delivery device, which fulfils the requirements for ophthalmic application. This review discusses the polymeric nanoparticles, physiochemical characterization, fabrication techniques, therapeutic significances, patented technology of nanoparticles and future possibility in the field of ocular drug delivery.

Heart rate variability: Response to graded head up tilt in healthy men.

BACKGROUND: Heart rate variability is actually a misnomer for R to R variability in cardiac cycle. Variation in successive cycle length is called the heart rate variability (HRV). Head-up tilt is a model of studying cardiovascular haemodynamics, which reflects in heart rate variability (HRV). OBJECTIVES: To study the effect of 10 degrees and 70 degrees head-up tilt on HRV. MATERIALS AND METHODS: The study was done in the Department of Physiology using graded head up tilt (passive orthostatism). HRV measurement was done at 10 degrees and 70 degrees tilt and compared with supine using standardised methods on 30 consenting healthy males (age 25.37+/-3.89 years). The HRV variables across postures were compared by ANOVA and Bonferroni test. RESULTS: The heart rate increased at 70 degrees compared to 10 degrees and supine (70.48+/-8.17 Vs 70.22+/-8.67 and 88.51+/-12.84 bpm, p<0.001). The 70 degrees tilt decreased vagal HRV indicators compared to 10 degrees and supine: SDNN (31.13+/-8.12 Vs 38.07+/-11.29 and 38.13+/-10.89 ms, p<0.05), RMSSD (20.06 +/-8.47 Vs 34.23+/-14.22 and 36.16+/-12.22 ms, p<0.001), NN50 count (13.03+/-20.58 Vs 45.07+/-44.44 and 55.27+/-44.10, p<0.01), pNN50 (3.28+/-6.08 Vs 14.06+/-15.65 and 16.65+/-14.23, p<0.01), HF power (197.20+/-143.76 Vs 218.17+/-155.85 and 216.87+/-150.98 Hz, p<0.05), HFnu unit (24.28+/-14.16 Vs 45.48+/-16.34 and 47.67+/-19.89, p<0.001). The 70 degrees tilt increased LF power% (197.20+/-143.76 Vs 218.17+/-155.85 and 216.87+/-150.98, p<0.001). LFnu unit (75.72+/-14.76 Vs 54.52+/-16.34 and 52.32+/-19.89, p<0.001), LF: HF (4.96+/-4.08 Vs 1.53+/-1.138 and 1.69+/-1.67, p<0.001) compared to 10 degrees and supine. CONCLUSION: At 70 degrees tilt, HRV measures, reflecting vagal contribution to cardiac-cycle length, decreased with reciprocal increase in sympathetic activity compared to 10 degrees or supine leading to increase in sympathetic predominance. A 10 degrees tilt, which is almost equivalent to lying down with pillow, did not change HRV from supine. activity.

Antidiabetic activity of standardized extract of Picrorhiza kurroa in rat model of NIDDM.

The present study was undertaken to investigate the effect of standardized aqueous extract of Picrorhiza kurroa Royle ex Benth. on diabetes. Diabetes mellitus was induced with streptozotocinnicotinamide and rats found diabetic were orally administered standardized aqueous extract of Picrorhiza kurroa (100 and 200 mg/kg, p.o.) or glibenclamide (10 mg/kg, p.o.) or vehicle (0.3% carboxy methyl cellulose suspension) for 14 days. Fasting blood glucose levels and lipid profiles were measured in control as well as diabetic rats after two week treatment. In addition, liver glycogen level of Picrorhiza kurroa extract (PkE) treated diabetic rats were compared to that of control and diabetic control rats. Oral glucose tolerance test was also performed on nondiabetic normal rats. Statistical analyses were performed by one way analysis of variance followed by Tukey-Kramer multiple comparisons test. PkE treatment induced significant reduction (p < 0.001) in elevated fasting blood glucose level in streptozotocinnicotinamide induced type-2 diabetic rats. In oral glucose tolerance test, oral administration of PkE increased the glucose tolerance. PkE treatment also significantly (p < 0.001) reversed the weight loss associated with streptozotocin treatment. These findings provide in vivo evidence that standardized extract of Picrorhiza kurroa possess significant antidiabetic activity in streptozotocin-nicotinamide induced type-2 diabetes mellitus in rats.

Antiaggressive activity of hyperforin: A preclinical study.

The aim of present study was to investigate the in vivo antiaggressive activity of hyperforin using defensive and offensive behavioral models in rodents. Adult male rats and mice were used for the present study. Animals were divided into three groups, with 6 animals in each. Lorazepam was used as standard antiaggressive agent. Animals were treated once daily, for seven consecutive days. Hyperforin (10 mg/kg, i.p.) was injected in a volume of 10 mL/kg for seven consecutive days. Standard group was treated with lorazepam (2.5 mg/kg, i.p.). The control group was treated with equal volume of vehicle (0.3% carboxy methyl cellulose suspension, i.p.). Animals were screened for aggressive behavior before dividing them into groups. At the end of 7 days, experiments were performed. Antiaggressive activity was evaluated using following validated models of aggression viz. foot shock-induced aggression, isolation-induced aggression, resident-intruder aggression and water competition test. Hyperforin treatment significantly (p < 0.001) reduced various aggressive parameters viz. latency to first attack and number of fights in isolation induced aggression, resident intruder aggression and foot shock induced aggression tests. In water competition test, hyperforin treatment significantly (p < 0.001) reduced the duration of water consumption and frequency of water spout possession. We conclude that hyperforin, the major lipophilic compound contained in extracts of Hypericum perforatum, is thus responsible for the antiaggressive activity, suggesting the therapeutic potential of hyperforin as an antiaggressive agent.

Beneficial effects of a standardized Hypericum perforatum extract in rats with experimentally induced hyperglycemia.

The main aim of this study was to test the therapeutic potential of a standardized Hypericum perforatum extract in treating metabolic disturbances commonly associated with type-2 diabetes mellitus. Daily oral administration of the Hypericum perforatum extract (100, 200, and 300 mg/kg/day) for 14 consecutive days counteracted in a dose-dependent manner the alterations in blood glucose levels and lipid profile as well as liver glycogen content and body weight changes observed in a rat mode of nicotinamide-streptozotocininduced diabetes. In general, effects of the highest dose of the extract in this model were quite similar, but not identical, to those of a 10 mg/kg/day dose of glibenclamide. The effects of single oral doses of the extract in a rat oral glucose tolerance test conducted in fasted animals were also analogous to those of an antidiabetic drug therapeutic use. These observations not only further expand the therapeutic potentials of Hypericum extracts but also indicate that stimulation of insulin release could be involved in their modes of actions. The importance of an extract with diverse, therapeutically interesting pharmacological properties is also briefly discussed.

Cardiovascular effects of transdermally delivered bupranolol in rabbits: effect of chemical penetration enhancers.

Bupranolol is a promising candidate for transdermal drug delivery system (TDDS) development. The effect of permeation enhancers on the in vivo delivery and beta-blocking effect of reservoir type TDDS was studied in comparison with intravenous BPL in rabbits. The beta-blocking effect was quantified by measuring the inhibition of isoprenaline induced tachycardia in rabbits after BPL administration via transdermal and intravenous routes. The reservoir type TDDS containing a hydroxypropyl cellulose gel and polyethylene membrane was used as a control device. In comparison, the TDDS containing skin penetration enhancers, either 2-pyrrolidone or partially methylated beta cyclodextrin (PMbetaCD) were evaluated. The control device (no enhancer) produced about 52% inhibition of isoprenaline induced tachycardia at 2 h and the effect continued over 24 h application period, however, the devices with 2-pyrolidone or PMbetaCD produced about 85% inhibition of isoprenaline induced tachycardia at 3 h and the same effect continued over 24 h application period. Likewise, the AUC of these devices were significantly higher than that of control device. The intravenous bupranolol showed rapid decline in the pharmacodynamic effect with time indicating its rapid elimination. The in vivo delivery of bupranolol (as estimated by a mass balance study) from the devices made with pyrolidone or PMbetaCD was 3-fold higher than that of control. The results of this study strongly suggest that the penetration enhancers in the TDDS increased the in vivo delivery of BPL, thereby increased the beta-blocking activity of BPL by 50-60% higher than control, enabling the reduction of the TDDS patch size, accordingly.

Novel immunobiologics for psoriasis.

Psoriasis is one of the most common human skin diseases and is considered to have key genetic contributions. It is characterized by excessive growth and aberrant differentiation of keratinocytes, but is reversible with appropriate therapy with the possibilities of recurrence. The trigger of the keratinocyte response is thought to be the activation of the cellular immune system with T cells, dendritic cells and various immune related cytokines and chemokines being implicated in pathogenesis. Immunosuppressants like cyclosporine and methotrexate were used earlier in the treatment of psoriasis, however their use was associated with severe adverse effects due to down regulation of immune system. The most recent advances in therapies for psoriasis target specific immune components of psoriasis and promise to have high therapeutic efficacy with low adverse effects. This review focuses on the novel therapies aimed to specifically modulate the dysregulated immune system with minimal adverse effects.

Antinociceptive and antiarthritic activity of Cissampelos pareira roots.

In the present study, 50% aqueous ethanolic extract of Cissampelos pareira (Menispermaceae) roots (C. pareira) at the dose levels of 100-400 mg/kg, once daily for 3 days exhibited significant (P < 0.001) resistance against mechanical pain after 30 min in analgesymeter induced pain in mice. In acetic acid (0.6%; i.p.) inducing writhing, Cissampelos pareira significantly (P < 0.05) decreased the writhing episodes; the degree of percent protection at 200 and 400 mg/kg was 22.73 and 51.63. The hot plate reaction time was increased by 2.07 (P < 0.05) and 2.70 (P < 0.001) folds. respectively. Further Cissampelos pareira showed the dose dependent significant protective effect against complete Freund's adjuvant induced arthritis. The percentage protection on the 18th day was 40.54 (P < 0.01) and 71.52 (P < 0.001) at 200 and 400 mg/kg respectively. Lysosomal enzymes (acid phosphatase and N-acetyl glucosaminidase) were decreased by 50% (P < 0.01) and 26.26% (P < 0.05) by using Cissampelos pareira, dextramethasone decreased them 56.56% (P < 0.01) and 31.82% (P < 0.01) and the glycoprotein contents (total hexose and sialic acid) were increased by 1.55-folds (P < 0.01) and 1.51-folds (P < 0.05) by using Cissampelos pareira while dextramethasone increases them by 1.51-folds (P < 0.001) and 1.60-folds (P < 0.01) respectively in stomach homogenate with respect to arthritic group. The increased pain threshold and protective effect against CFE by Cissampelos pareira vindicated its medicinal value in treatment of pain and arthritis.

Evaluation of anti-inflammatory activity of Cissampelos pareira root in rats.

In the present study, 50% ethanolic extract of Cissampelos pareira roots (CPE) in acute, subacute and chronic models of inflammation was assessed in rats. Per os (p.o.) administration of CPE (200, 400 mg/kg) exhibited significant anti-inflammatory activity. In acute inflammation as produced by carrageenin 59.55% and 64.04%, by histamine 15.38% and 30.77%, by 5-hydroxytryptamine 17.78% and 31.11% and by prostaglandin E(2)-induced hind paw edema 19.23% and 30.77% protection was observed. While in subacute anti-inflammatory models using formaldehyde-induced hind paw edema (after 1.5 h) 38.36% and 47.95% and in chronic anti-inflammatory model using cotton pellet granuloma 15.02% and 19.19% protection from inflammation was observed. CPE did not show any sign of toxicity and mortality up to a dose level of 1000 mg/kg, p.o. in rats. Both acute as well as chronic administration of CPE (100, 200 and 400 mg/kg, p.o.) did not produce any gastric lesion in rats. These data indicate that CPE possesses significant anti-inflammatory activity without ulcerogenic activity suggesting its potential as an anti-inflammatory agent for use in the treatment of various inflammatory diseases.

Peak expiratory flow rate of children working in lock factories.

Peak expiratory flow rate (PEFR) of 106 children working in different units of lock factory was measured and compared with age and sex matched control group of same socio-economic status children. All the children worked for about ten hours per day. It was observed that there was a significant decrease in PEFR of children working in the different units of lock factories i.e. Hand press, Polishing, Lock fitting, Lock packing units as compared to control group (P>0.001). The reduction percentage of PEFR was maximum in children working in polishing unit (25.48%).

Hypolipidemic activity of aqueous extract of Withania coagulans Dunal in albino rats.

Administration of an aqueous extract of fruits of Withania coagulans (1 g/kg; p.o.) to high fat diet induced hyperlipidemic rats for 7 weeks, significantly reduced elevated serum cholesterol, triglycerides and lipoprotein levels. This drug also showed hypolipidemic activity in triton induced hypercholesterolemia. The histopathological examination of liver tissues of treated hyperlipidemic rats showed comparatively lesser degenerative changes compared with hyperlipidemic controls. The hypolipidemic effect of W. coagulans fruits was found to be comparable to that of an Ayurvedic product containing Commiphora mukkul.

Hypoglycemic activity of Withania coagulans Dunal in streptozotocin induced diabetic rats.

Administration of aqueous extract of fruits of Withania coagulans Dunal significantly lowered the blood sugar, serum cholesterol, serum LPO, and hepatic LPO levels at the highest concentration of 1g/kg; p.o. in streptozotocin induced diabetic rats. In normal rats as well the blood sugar levels were significantly decreased following treatment with the above drug. Withania coagulans also exhibited free radical scavenging activity in an in vitro system using DPPH.