Correlation of renin angiotensin system (RAS) candidate gene polymorphisms with response to Ramipril in patients with essential hypertension.

BACKGROUND: The renin-angiotensin system (RAS) is an important facet of blood pressure regulation physiology. Treatment of essential hypertension targets the RAS using Angiotensin Converting Enzyme Inhibitors (ACEIs). However, ACEIs are not uniformly effective and show inter-individual pharmacodynamic variations. AIM: To assess the correlation between genetic polymorphisms in the genes coding for RAS components (angiotensin converting enzyme (ACE I/D), α-adducin (ADD1) and ß1 -adrenoreceptor (ß1-ADR)) and response to Ramipril. MATERIALS AND METHODS: We recruited 120 patients with essential hypertension who were administered Ramipril monotherapy initially, followed by combination therapy, if needed, based on their responses. Relationship between genotypes of the three candidate genes and decrease in the blood pressure (BP) was analyzed. RESULTS: One hundred and six patients were evaluable at the end of the study period and 21 different genotypes were observed among them. Seven of them were classified as responders after 8 weeks and at the end of 12 weeks, an additional 77 (72.64%) were deemed responders. 19/22 non-responders were treated with combination therapy and 7/19 (36.84%) showed a response to the same. There was a significant difference between the proportions of responders and non-responders among the genotypes of the ADD1 and ß1-ADR genes (P=0.005 and 0.003, respectively). The best predictors of response to Ramipril 5 mg daily were the II/GG/SS, II/TG/SS, II/GG/SG, ID/GG/SS, ID/GG/SG and ID/TT/SS and DD/GG/SS; II/GG/GG, II/TT/SG, ID/TG/SG, ID/TT/SG, DD/GG/SG and DD/GG/GG were moderately predictive and II/TT/SS, II/TG/GG, ID/TG/GG, DD/TG/SG and DD/TG/GG were poorly predictive of response. DISCUSSION: Variable responses to Ramipril may be the result of genetic factors. CONCLUSION: Pre-prescription genotyping may help individualize treatment.

Determining the density content of symmetry energy and neutron skin: an empirical approach.

The density dependence of nuclear symmetry energy remains poorly constrained. Starting from precise empirical values of the nuclear volume and surface symmetry energy coefficients and the nuclear saturation density, we show how in the ambit of microscopic calculations with different energy density functionals, the value of the symmetry energy slope parameter L along with that for neutron skin can be put in tighter bounds. The value of L is found to be L=64±5 MeV. For 208Pb, the neutron skin thickness comes out to be 0.188±0.014 fm. Knowing L, the method can be applied to predict neutron skin thicknesses of other nuclei.

Antioxidant status and smoking habits: relationship with diet.

INTRODUCTION: The present study was conducted to assess the association between smoking, dietary intake of antioxidants and plasma indices of oxidative stress and antioxidant defences in male smokers (cigarette and bidi smokers). METHODS: The study sample consisted of 100 healthy men, including 50 non-smokers and 50 smokers, who were subclassified into 25 cigarette smokers and 25 bidi smokers, aged 18-55 years. Erythrocyte superoxide dismutase and plasma ascorbic acid were measured as antioxidants and erythrocyte malondialdehyde as an oxidative stress index, by colorimetric methods. RESULTS: Smokers ate less fruits and vegetables than non-smokers, leading to them having a lower antioxidant level. Erythrocyte superoxide dismutase was significantly lower in cigarette smokers (0.193 U/mgP, p-value is less than 0.05) and bidi smokers (0.169 U/mgP, p-value is less than 0.001) as compared to non-smokers (0.231 U/mgP). Plasma ascorbic acid was also significantly lower in cigarette smokers (1.45 mg/100 ml, p-value is less than 0.05) as well as in bidi smokers (1.38 mg/100 ml, p-value is less than 0.001) as compared to non-smokers (1.73 mg/100 ml). There was a significant increase in erythrocyte malondialdehyde concentration levels in cigarette smokers (171.47 micromol/gHb, p-value is less than 0.05) as well as in bidi smokers (231.04 micromol/gHb, p-value is less than 0.001) as compared to non-smokers (127.30 micromol/gHb). CONCLUSION: These results provide enough evidence of increased oxidative stress and a compromised antioxidant defence system in smokers, and they are more profound in bidi smokers than in those smoking cigarettes. This study also revealed that the diet and nutrient intake of smokers are different from that of non-smokers.

Oscillatory metallic behaviour of carbon nanotube superlattices-an ab initio study.

We study the structural, electronic and optical properties of the (n,n)/(2n,0);n = 3 and 6 superlattices of carbon nanotubes (CNs) by employing the first principles pseudo-potential method within density functional theory (DFT) in the generalized gradient approximation (GGA). There occur pentagon-heptagon defects along the circumference of the heterojunction of these superlattices. The role of the length of the superlattice unit cell on the electronic and optical properties has been investigated. The curvature effects on the various properties are also discussed. The heterojunctions of the small diameter n(3,3)/n(6,0) superlattices which possess a threefold rotational symmetry exhibit an oscillatory behaviour in terms of the fundamental energy bandgaps which vanish whenever the integer n is a multiple of 3. These results indicate that a similar oscillatory behaviour in the fundamental gap energy having a periodicity of 6 may be observed in the case of the large diameter n(6,6)/n(12,0) superlattices whose heterojunctions reveal a sixfold symmetry. The system energy of the 3(6,6)/3(12,0) superlattice shows a minimum. The electronic structure and optical absorption of a superlattice are quite different from those of its constituent carbon nanotubes. The present results obtained after employing all the s-, p- and d-orbitals of the atoms (although the d-orbital contributions are quite small) are quite different from the findings of earlier workers who have employed a phenomenological tight-binding formulation considering only one pi orbital or four orbitals. We find that most of the states are extended resonance states and are quite delocalized in contrast to the earlier finding of the occurrence of the completely localized states in sections of the constituent nanotubes. The metallic superlattices exhibit a high density of states (DOS) at the Fermi level (E(F)). For the large diameter n(6,6)/n(12,0) superlattices, the electron energy gap vanishes for n = 1 and 2 but increases up to a maximum value of 0.344 eV for n = 3 and decreases thereafter for larger n, a result which is in disagreement with earlier workers. These new facts have not been reported in the literature so far.

Effect of lycopene from tomatoes (cooked) on plasma antioxidant enzymes, lipid peroxidation rate and lipid profile in grade-I hypertension.

BACKGROUND: Results from observational studies suggest that the oxidative stress and hyperlipidemic status, which prevails in hypertension, plays an important role in causation of secondary complications. So the aim of the present study is to evaluate the beneficial effect of tomatoes, which are a rich source of lycopene, a relatively new carotenoid known to play an important role in human health and disease. METHODS: In this study lipid peroxidation rate was measured by estimating malondialdehyde (MDA) and the activity of plasma enzymes involved in antioxidant activities like superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GR), reduced glutathione (GSH), and serum lipid profile which includes total cholesterol and triglycerides were estimated in a grade I hypertensive group (n = 40) and an age-matched control group (n = 50). RESULTS: Significantly lower plasma antioxidant enzyme activity, very high lipid peroxidation rate and very high serum total cholesterol, triglycerides in the grade I hypertensive group was observed when compared to the control group (p < 0.001). Sixty days of tomato supplementation in the hypertensive group (n = 30) showed a significant improvement in the levels of serum enzymes involved in antioxidant activities and decreased lipid peroxidation rate (F value highly significant), but there were no significant changes in lipid profile (F value insignificant). CONCLUSION: These findings suggest that tomato lycopene may have considerable natural therapeutic potential as an antioxidant but may not be used as a hypolipidemic agent in hypertension.

Effect of lycopene from cooked tomatoes on serum antioxidant enzymes, lipid peroxidation rate and lipid profile in coronary heart disease.

INTRODUCTION: This present study aims to evaluate the beneficial effect of tomatoes, a rich source of lycopene, which is a relatively new carotenoid known to play an important role in human health and disease. METHODS: We investigated the lipid peroxidation rate by estimating malondialdehyde (MDA), levels of serum enzymes involved in antioxidant activities such as superoxide dismutase, glutathione peroxidase, glutathione reductase, reduced glutathione and lipid profile, which includes total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein and very low density lipoprotein in a coronary heart disease (CHD) group and an age-matched control group. RESULTS: We observed significantly lower levels of serum antioxidant enzymes and very high lipid peroxidation rate in the CHD group, when compared to the controls (p-value is less than 0.001). At the same time, we observed significantly higher levels of lipids in the CHD group, when compared to the controls (p-value is less than 0.001). 60 days of tomato supplementation in the CHD group showed a significant improvement in the levels of serum enzymes involved in antioxidant activities and decreased lipid peroxidation rate (p-value is less than 0.001), but there were no significant changes in lipid profile (p-value is greater than 0.10). CONCLUSION: These findings suggest that tomato lycopene may have considerable therapeutic potential as an antioxidant but may not be used as a hypolipidaemic agent in CHD.

Structural, electronic and vibrational properties of small Ga(x)N(y) (x+y = 2-5) nanoclusters: a B3LYP-DFT study.

An ab initio study of the stability, structural and electronic properties has been made for 49 gallium nitride nanoclusters, Ga(x)N(y) (x+y = 2-5). Among the various configurations corresponding to a fixed x+y = n value, the configuration possessing the maximum value of binding energy (BE) is named as the most stable structure. The vibrational and optical properties have been investigated only for the most stable structures. A B3LYP-DFT/6-311G(3df) method has been employed to optimize the geometries of the nanoclusters fully. The binding energies (BEs), highest-occupied and lowest-unoccupied molecular orbital (HOMO-LUMO) gaps and the bond lengths have been obtained for all the clusters. We have considered the zero-point energy (ZPE) corrections ignored by the earlier workers. The adiabatic and vertical ionization potentials (IPs) and electron affinities (EAs), charge on atoms, dipole moments, vibrational frequencies, infrared intensities (IR Int.), relative infrared intensities (Rel. IR Int.) and Raman scattering activities have been investigated for the most stable structures. The configurations containing the N atoms in majority are seen to be the most stable structures. The strong N-N bond has an important role in stabilizing the clusters. For clusters containing one Ga atom and all the others as N atoms, the BE increases monotonically with the number of the N atoms. The HOMO-LUMO gap and IP fluctuate with the cluster size n, having larger values for the clusters containing odd number of N atoms. On the other hand, the EA decreases with the cluster size up to n = 3, and shows slow fluctuations thereafter for the larger clusters. In general, the adiabatic IP (EA) is smaller (greater) than the vertical IP (EA) because of the lower energies of the most stable ground state of the cationic (anionic) clusters. The optical absorption spectrum or electron energy loss spectrum (EELS) is unique for every cluster, and may be used to characterize a specific cluster. All the predicted physical quantities are in good agreement with the experimental data wherever available. The growth of these most stable structures should be possible in experiments.

Effect of short term supplementation of tomatoes on antioxidant enzymes and lipid peroxidation in type-II diabetes.

The objective of the present study is to evaluate the beneficial effect of tomatoes, which are rich source of Lycopene, relatively a new carotenoid known to play an important role in human health and disease. In this study lipid peroxidation rate was measured by estimating Malondialdehyde and the levels of serum enzymes involved in antioxidant activities like Super Oxide Dismutase, Glutathione Peroxidase, Glutathione Reductase, Reduced Glutathione, in type-II diabetic group (n=40) and age matched control group (n=50), and observed significantly lower levels of antioxidant enzymes and very high lipid peroxidation rate in type-II diabetes when compared to control group (p<0.001). Short term supplementation with tomatoes (cooked) to diabetic group for a period of 30 days, showed a significant improvement in antioxidant enzyme levels (p<0.001) and decreased lipid peroxidation rate (p<0.001) suggesting the supplementation with tomato lycopene may serve as the best method of preventing the oxidative stress in diabetic patients.

Effect of long term supplementation of tomatoes (cooked) on levels of antioxidant enzymes, lipid peroxidation rate, lipid profile and glycated haemoglobin in Type 2 diabetes mellitus / Efectos de la suplementación a largo plazo con tomates (cocidos) en los niveles de enzimas antioxidantes, el indice de peroxidación lipídica, el perfil lipídico, y la hemoglobina glicada en la diabetes de tipo 2

The objective of the present study is to evaluate the beneficial effect of tomatoes, which are a rich source of lycopene, a relatively new carotenoid known to play an important role in human health. In this study, the lipid peroxidation rate was investigated by estimating malondialdehyde (TBARS) levels of antioxidant enzymes like SOD, GSH-Px, GR, GSH, lipid profile, which includes total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, very low density lipoprotein, and glycated haemoglobin HbA1c in (n = 40) the Type 2 diabetic group (n = 40) and an age-matched control group (n = 50). Significantly lower levels of antioxidant enzymes and very high lipid peroxidation rate in the Type 2 diabetic group were observed when compared to controls (p 0.10). These findings suggest that tomato lycopene may have considerable therapeutic potential as an antioxidant but there was no significant lipid lowering effect in Type 2 diabetes mellitus.

El objetivo del presente estudio es evaluar el efecto beneficioso del tomate como fuente rica en licopeno – un carotenoide relativamente nuevo, del cual se sabe que juega un importante papel en la salud humana. En este estudio, investigamos el índice de peroxidación lipídica, estimando los niveles MDA (TBARS) de las enzimas antioxidantes como SOD, GSH-Px, GR, GSH, el perfil lipídico, que incluye el colesterol total, los triglicéridos, los HDL, LDL, VLDL, y la hemoglobina glicada (HbA1c) en (n = 40) en el grupo diabético tipo 2 (n = 40) y el grupo de control pareado por edad (n = 50). En este estudio, observamos niveles significativamente más bajos de enzimas antioxidantes e índices de peroxidación lipídica muy altos en el grupo diabético tipo 2, en comparación con el grupo control (p < 0.001). Asimismo observamos niveles significativamente más altos de perfil lipídico y hemoglobina glicada (HbA1c) en el grupo diabético al comparársele con el grupo control (p < 0.001).

Effect of long term supplementation of tomatoes (cooked) on levels of antioxidant enzymes, lipid peroxidation rate, lipid profile and glycated haemoglobin in Type 2 diabetes mellitus.

The objective of the present study is to evaluate the beneficial effect of tomatoes, which are a rich source of lycopene, a relatively new carotenoid known to play an important role in human health. In this study, the lipid peroxidation rate was investigated by estimating malondialdehyde (TBARS) levels of antioxidant enzymes like SOD, GSH-Px, GR, GSH, lipid profile, which includes total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, very low density lipoprotein, and glycated haemoglobin HbA1c in (n = 40) the Type 2 diabetic group (n = 40) and an age-matched control group (n = 50). Significantly lower levels of antioxidant enzymes and very high lipid peroxidation rate in the Type 2 diabetic group were observed when compared to controls (p < 0.001). Likewise, significantly higher levels of lipid profile and glycated haemoglobin (HbA1c) in the diabetic group were observed when compared with control (p < 0.001). Long term tomato supplementation in diabetes mellitus showed a significant improvement in the levels of antioxidant enzymes and decreased lipid peroxidation rate (p < 0.001), but there were no significant changes in lipid profile and glycated haemoglobin HbA1c levels (p > 0.10). These findings suggest that tomato lycopene may have considerable therapeutic potential as an antioxidant but there was no significant lipid lowering effect in Type 2 diabetes mellitus.

Ab-initio study of the structural and electronic properties of very thin silver nanowires.

An ab initio study of the energetics, structural, and electronic properties of thin silver nanowires of Ag(n) with n = 1 to 6 has been made in density functional theory in local density approximation. The present study reveals that all of the wires are stable except the wire with 3 silver atoms per unit cell. The linear chain is comparatively less stable. The binding energies of the most stable wires lie in the range 2.60-3.18 eV/atom with maximum values for the 5-Ag pentagonal and the two 6-Ag (hexagonal and pyramidal) nanowires. The nearest neighbor Ag-Ag separations in all of the most stable wires up to n=6 is quite the same and is equal to 2.634 +/- 0.03 A. For the most stable 6-Ag pyramidal wire, the bond length increases to 2.75 or 2.81 A. The cross-sectional dimension of these wires are around 5.0 A. All of the studied silver wires are metallic. A majority of the sd mixed states cross the Fermi level. The density of state is maximum for the 5-Ag pentagonal and 6-Ag pyramidal nanowires, and so is the number of channels (5 or 6) crossing the E(F) which would be available for high electrical conduction.

Structural and vibrational properties of small carbon clusters.

An ab-initio comprehensive study of the stability and structural and vibrational properties of small carbon clusters, CN for N = 1-10, has been made. We use a self-consistent pseudopotential method within density functional theory in the generalized gradient approximation considering spin polarization. The estimated values of binding energies for the various clusters are overestimated in the non-spin-polarized calculations. On the other hand, for the spin-polarized case, the computed binding energies are in very good agreement with the available experimental data. Also, the calculated vibrational frequencies for CN, N = 2-5, are in reasonable agreement with the available experimental values.

A study of metopic sutures in human skulls.

The present study has been carried out in fifty-one adult human skulls for metopic sutures in the department of anatomy, Nepalgunj Medical College, Chisapani. Metopic sutures were found in six skulls (11.46%) This study showed higher incidences of incomplete metopic sutures (7.84%). One skull showed double incomplete sutures (one to right of bregma and other in the middle of the frontal bone in the mid line), which was of, a very rare variety seen in frontal bone of (1.96%), three skulls showed incomplete sutures (3.92%). Though the number of the skulls was small, the study showed a rare morphological variety, which was well correlated with earlier workers.

Study of fifty human tali for calcaneal articular facets.

Fifty adult dry human tali from the Department of anatomy, Nepalgunj Medical College Chisapani, were studied. Observations were made on different types of articular facets of calcaneus for the tali. They were classified into four groups and their percentages of incidences were calculated. These findings were well correlated and compared with the literatures available.

Triple-drug therapy of Helicobacter pylori infection in duodenal ulcer disease.

OBJECTIVE: To evaluate the efficacy of triple-drug therapy for Helicobacter pylori infection and the effect of its eradication on relapse of ulcer in patients with duodenal ulcer (DU) disease. METHODS: Patients with uncomplicated DU who were H. pylori-positive on urease test or histology were given triple-drug therapy (metronidazole, tetracycline, colloidal bismuth subcitrate). Ulcer healing and H. pylori status were assessed one month after completion of therapy. Those with healed ulcers were followed up endoscopically for ulcer recurrence at 3-month intervals for one year or more. RESULTS: Fifty seven of 60 consecutive DU patients (95%) who were H. pylori-positive were taken up for the study; 46 patients (36 men; median age 40 years, range 13-70) completed the study. Thirty one of them (67%) eradicated H. pylori and had healed ulcers at one month post therapy; of 15 patients with persistent H. pylori infection, ulcers healed in 12 (p = ns). After an average follow up of 11 months, 8 of 12 H. pylori-positive patients had relapse of DU compared to 5 of 31 (16%) H. pylori-negative patients (p < 0.01). CONCLUSIONS: Triple-drug therapy was effective and safe for H. pylori infection, the lower rate of eradication observed compared to results elsewhere probably being related to bacterial resistance. Eradication of H. pylori was associated with healing of ulcers, resolution of antral gastritis and a significant fall in the rate of ulcer relapse.

Bifid pancreas: an endoscopic retrograde pancreaticographic curiosity.

Bifid pancreas, representing a major bifurcation of the main pancreatic duct, has rarely been reported. We report four such cases where this condition was picked up incidentally.

End point for sclerosis of esophageal varices.

BACKGROUND: Small esophageal varices are difficult to inject intravariceally and complete eradication of varices may not be therapeutically necessary. METHODS: A prospective study designed to compare the use of different end points of sclerotherapy ie (i) total eradication (grade 0) (ii) grade I varices or (iii) grade II white (IIw) varices, by stopping variceal injection when one of these was reached. The patients were followed endoscopically and clinically at 3-4 mo intervals. OUTCOME MEASURES: Variceal recurrence and rebleeding rates. RESULTS: Of 266 patients with portal hypertension (147 cirrhosis, 51 non-cirrhotic portal fibrosis, 68 extra-hepatic portal venous obstruction), 232 (87.2%) reached one of the three end points--six to grade 0, 96 to grade I and 130 to grade IIw. Among 212 patients followed up for a mean post-sclerotherapy period of 12.2 mo (range 3-48 mo), variceal recurrence rates, time intervals to recurrence and rebleed rates were comparable in patients with endpoints of grade I and grade II (white) varices (28.5% vs 38.9%, 10.8 mo vs 9.2 mo, and 7.7% vs 7.8%, respectively; all p = ns). Overall, 51 patients had interval bleed before reaching the end point--50 (98%) of them bled from grade III and IV varices while only one patient (2%) bled with grade IIw varices. CONCLUSION: Grade I or grade IIw varices should be acceptable as the end points for endoscopic sclerotherapy of esophageal varices.

Combination of anticholinergic agent and H2 receptor antagonist in duodenal ulcer treatment--a randomized, double blind multicenter study.

BACKGROUND: The acid suppressive abilities of H2 receptor antagonists and anticholinergics have been claimed to be additive. METHODS: A multicenter, double-blind, randomized trial comparing ranitidine (150 mg) plus propantheline bromide 15 mg at bedtime to ranitidine 300 mg alone at bedtime was conducted in 161 patients with endoscopically confirmed uncomplicated duodenal ulcer. RESULTS: After six weeks of therapy, ulcer healing rates in the two groups were comparable ie 80% in the combination group (ranitidine + propantheline) and 79.4% in the ranitidine group. Pain relief after one, two and four weeks of treatment was also comparable in the two groups. Side effects to drugs were minor and comparable in both the groups. CONCLUSION: A combination of 150 mg ranitidine and 15 mg propantheline bromide is as efficacious as 300 mg ranitidine in inducing healing of uncomplicated duodenal ulcers, with similar side-effects but at greatly reduced cost.