Erratum: Azimuthal Anisotropy at the Relativistic Heavy Ion Collider: The First and Fourth Harmonics [Phys. Rev. Lett. 92, 062301 (2004)].

This corrects the article DOI: 10.1103/PhysRevLett.92.062301.

Work-exposure to PM10 and aromatic volatile organic compounds, excretion of urinary biomarkers and effect on the pulmonary function and heme-metabolism: A study of petrol pump workers and traffic police personnel in Kolkata City, India.

This study focused work-exposure to particulate matter ≤ 10 µm (PM10), volatile organic compounds (VOCs) and biological monitoring of major VOCs (BTEX) to observe the significant effects of traffic related pollutants on respiratory and hematological systems of workers engaged in two occupational settings, petrol pumps and traffic areas of Kolkata metropolitan city, India. PM10 was assessed by personal sampling and particle size distribution by 8-stage Cascade Impactor. VOCs were analysed by gas chromatography-flame ionization detector (GC-FID) and five urinary metabolites, trans trans- mercapturic acid (tt-MA), S-phenyl mercapturic acid (SPMA), hippuric acid (HA), mandelic acid (MA) and methyl hippuric acid (MHA) of VOCs, benzene, toluene, ethyl benzene and xylenes (BTEX) by reverse phase high performance liquid chromatography (HPLC). Pulmonary functions test (PFT) was measured Spirometrically. ∂-aminoleavulinic acid (ALA) and porphobilinogen (PBG) in lymphocytes were measured spectrophometrically following column chromatographic separation. High exposure to PM10, having 50% of particles, ≤ 5.0 µm in both the occupational settings. Exposure to toluene was highest in petrol pumps whereas benzene was highest (104.6 ± 99.0 µg m-3) for traffic police personnel. Workplace Benzene is found many fold higher than the National ambient standard. Air-benzene is correlated significantly with pre- and post-shift tt-MA (p < 0.001) and SPMA (p < 0.001) of exposed workers. Blood cell counts indicated benzene induced hematotoxicity. ALA and PBG accumulation in lymphocytes indicated alteration in heme-metabolism, especially among traffic police. Significant reduction of force exploratory volume in one second (FEV1) and forced vital capacity (FVC) of fuel fillers are observed with increased tt-MA and SPMA. Study revealed PFT impairments 11.11% (6.66% restrictive and 2.22% obstructive and combined restrictive and obstructive type, each) among petrol pumps and 8.3% obstructive type among traffic police.

One-stage breast reconstruction using the inferior dermal flap, implant, and free nipple graft.

BACKGROUND: An inferior dermal flap with implant is a useful option for women hoping for immediate breast reconstruction. This one-stage procedure uses autologous tissue as an inferolateral local sling, avoiding the costs and potential morbidity of prosthetic mesh and reducing valuable operating time. Patient comorbidity or choice may restrict autologous reconstruction options available. Many patients will still require a second procedure for subsequent nipple reconstruction and further appointments and costs for tattooing. METHOD: A prospective database was kept of a single surgeon's experience with 16 patients (19 breasts) from 2010 to 2012. Reconstruction was performed following a Wise pattern skin incision. An inferior, deepithelialized dermal sling was sutured to the pectoralis major to form a pocket for a silicone implant or tissue expander. A free nipple graft was sited at the time of reconstruction, with biopsies taken from retroareolar tissue. RESULTS: Patient average age was 54 years (range 36-66). Six mastectomies were for ductal carcinoma in situ, 6 for invasive carcinoma, 2 for lobular carcinoma, and 5 of 19 mastectomies were prophylactic. Average operative time was 165 min. There were no immediate complications requiring reoperation. All retroareolar biopsies were benign and no locoregional recurrences have occurred. Two nipples had partial necrosis of the lower pole but healed with conservative treatment. No patients required any subsequent procedures to their reconstructed breast. CONCLUSION: The inferior dermal flap with implant and free nipple graft is an excellent single-stage reconstruction option. This method offers a potentially safe, reliable, and aesthetically acceptable outcome for women with larger, ptotic breasts. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Carbapenem-resistant Acinetobacter ventilator-associated pneumonia: Clinical characteristics and outcome.

OBJECTIVE: To study the clinical characteristics and 28-days mortality in patients with ventilator-associated pneumonia (VAP) due to carbapenem-resistant Acinetobacter (CRA). DESIGN: Retrospective, observational, cohort study. SETTING: Intensive care unit (ICU) of a university hospital. MATERIALS AND METHODS: Microbiologically confirmed VAP due to CRA infection. INTERVENTION: None. RESULTS: Out of 87 patients with VAP due to CRA, 60 (69%) were male; whose median age was 51 years; 73 (84%) patients were medical; 26 (30%) had history of hospitalization in last 3 months; median acute physiology and chronic health evaluation (APACHE) II was 15 and median SOFA 9 at admission; primary reason for ICU admission was respiratory failure (34%); 46 (53%) patients had more than 2 organ failure at ICU admission; median length of ICU stay was 19 days; 66 (76%) patients need vasoactive agents during ICU stay, whereas 55 (63%) patients had renal failure; median duration of mechanical ventilation was 17 days; 22 (25%) patients had acute respiratory distress syndrome (ARDS) during ICU stay; 72 (83%) patients had exposure to carbapenem before inclusion in the study; 33 (38%) patients had same organism at other sites. In the follow-up, 47 (54%) patient survived at 28 days after having VAP; whereas only 40 (46%) patients were discharged from the hospital. CONCLUSIONS: CRA-VAP has high crude mortality. Advanced age; severity of illness and presence of pneumonia at ICU admission; and presence of shock, ARDS and renal failure have impact on outcome in these patients.

Neglected Bilateral Facet Dislocation of the Cervical Spine with Intact Neurology: Reduction Technique.

Bilateral cervical facet dislocation is a serious injury that in majority cause neurologic deficit requiring prompt medical attention. Rarely, they retain normal neurology due to spontaneous decompression even though patients can have objective myelopathic or root compression signs. Neglected cases with normal neurology are uncommon with only few of them reported in the literature but their management is still a matter of debate. Here, we report a case of a 26-year-old female who had neglected bilateral facet dislocation with neck stiffness that was operated with posteroanterior approach with near-complete reduction and intact neurology. We describe the technique employed and discuss the literature.

Exopolysaccharides directed embellishment of diatoms triggered on plastics and other marine litter.

In the present study, embellishment or beautification of diatoms on substrates like plastics, polydimethylsiloxane, graphite, glass plate, and titanium dioxide, triggered by exopolysaccharides was examined under laboratory conditions. Exopolysaccharides are secreted mainly by primary colonisers, bacteria, which is succeeded by secondary colonisers i.e. diatoms. Both diatom (Nitzschia sp.4) and bacteria (Bacillus subtilis) were exposed with substrates separately for 30 days. Diatoms adhere on substrates strongly, not only because of surface roughness of different substrates but also the nanoporous architecture of diatoms which enhanced their embellishment. This study attempted to identify the substrates that adhere to diatoms strongly and was mainly analyzed by scanning electron microscope and further the observations are well supported by math work software (MATLAB). The variation of diatom's binding on different substrates is due to the influence of marine litters on diatom population in ocean beds where they undergo slow degradation releasing macro, micro and nanoparticles besides radicals and ions causing cell death. Therefore a proof-of-concept model is developed to successfully deliver a message concerning benefit of using different diatom species.

Effect of sweet flag rhizome oil (Acorus calamus) on hemogram and ultrastructure of hemocytes of the tobacco armyworm, Spodoptera litura (Lepidoptera: Noctuidae).

Effect of the essential oil of Acorus calamus L. rhizomes, was studied on hemocytes of the tobacco armyworm, Spodoptera litura. The oil was administered in oral application at concentration of 500 and 1000 ppm to last instar larvae of S. litura and its effect on ultrastructure of hemocytes and hemogram was evaluated. The oil was administered in topical application at 250 microg dose to pupae to ascertain its effect on total and differential hemocyte counts. At both scanning (SEM) and transmission electron microscopic (TEM) levels, the major effect of oil treatment was observed on plasmatocytes (PLs) and granular hemocytes (GRs). SEM study revealed that the cytoplasmic projections of granular hemocytes were reduced, while the filopods of plasmatocytes remained unaffected. The vacuolization in the cytoplasm and degeneration of the organelles in both plasmatocytes and granular hemocytes was observed by TEM. However, no such deformities were observed in prohemocytes (PRs), spherulocytes (SPs), and oenocytoids (OEs). A concentration-dependent decrease has been observed in the larval body weight and hemolymph volume (HV), 24-72 h after treatment. In comparison to the controls, the maximum percentage growth inhibition (GI) was recorded to be 58.28 and 66.48, respectively at 500 and 1000 ppm after 72 h treatment. Similarly after 72 h treatment, the percentage reduction in hemolymph volume was 61.38 and 69.05, respectively at 500 and 1000 ppm. Total hemocyte count (THC), in larvae computed from five recorded hemocyte types viz. PRs, PLs, GRs, SPs and OEs, decreased only after 48-72 h of treatment. The maximum decrease in THC was recorded to be 29.15 and 49.05% at 500 and 1000 ppm, respectively, after 72 h of treatment. There was continuous decline in THC in pupae after 24-72 h treatment. DHC study revealed that both the concentrations of oil in 6th instar larvae of S. litura caused a decrease in PRs, PLs and SPs and increase in GRs and OEs after 24-72 h of treatment. Since A. calamus oil treatment causes the injury to both PLs and GRs and also affects the hemogram, it can be inferred that cellular defence reactions of S. litura are impaired.

Actinobacterial community structure in the Polar Frontal waters of the Southern Ocean of the Antarctica using Geographic Information System (GIS): A novel approach to study Ocean Microbiome.

Integration of microbiological data and geographical locations is necessary to understand the spatiotemporalpatterns of themicrobial diversity of an ecosystem. The Geographic Information System (GIS) to map and cataloguethe data ontheactinobacterial diversity of the Southern Ocean waterswas completed through sampling and analysis. Water samples collectedat two sampling stations viz.Polar Front 1(Station 1) andPolar Front 2(Station2)during7thIndian Scientific Expedition to the Indian Ocean Sector of the Southern Ocean (SOE-2012-13)were used for analysis. At the outset, two different genera of Actinobacteria were recorded at both sampling stations.Streptomyces was the dominantedwiththehigh score (> 60%), followed by Nocardiopsis (< 30%)at both the sampling stations-Polar Front 1 and Polar Front 2-along withother invasive genera such as Agrococcus, Arthrobacter, Cryobacterium, Curtobacterium,Microbacterium, Marisediminicola, Rhodococcus and Kocuria. This data will help to discriminate the diversity and distribution pattern of the Actinobacteria in the Polar Frontal Region of the Southern Ocean waters.Itis a novel approachusefulfor geospatial cataloguing of microbial diversityfromextreme nichesand in various environmental gradations.Furthermore,this research work will act as the milestone for bioprospecting of microbial communities and their products having potential applications in healthcare, agriculture and beneficial to mankind. Hence, this research work would have significance in creating a database on microbial communities of the Antarctic ecosystem.

Exposure to varying concentration of fungal spores in grain storage godowns and its effect on the respiratory function status among the workers.

Grain storage depot workers suffer from different respiratory problems after getting the exposure to storage grain dust. Which is a mixture of pesticides, fungi, silica, bacteria, spores, storage mites, animal hairs, pollens etc. The present study was undertaken to evaluate the fungal spore concentration in summer and winter season as well as the pulmonary function status of the workers; studies are limited in our country. In summer and winter seasons, air sampling was done to measure the airborne fungal spore concentration inside the godowns by Rotorod sampler, UK. Aspergilla, Alternaria, Drechslera, Epicoccum, Nigrospora, Periconia were very much common and found higher in winter compared to summer. The respiratory functional status was assessed in two groups of workers of the same storage grain depot (total n=316) in summer (n=136) and in winter (n=180). List of the workers was collected from the authority and randomly selected every alternate worker and divide them for the studies in summer and winter seasons. Slow Vital Capacity (SVC), Forced Vital Capacity (FVC), and Peak Expiratory Flow Rate (PEFR) were recorded and Forced Expiratory Volume in one second (FEV1), FEV1% and different flow rates were calculated. The Immunoglobulin- E (IgE) level in the blood serum was assessed on post shift pulmonary function tests (PFT) decreased workers. The age, height and weight of the same categories of workers of both studies are highly comparable. Mean PFT values in summer found higher than winter. A gradual decrement of values were found as age was increased but not with duration of exposure. Post-shift PFT was carried in 21.8% (69) workers of which 46.4% (32) workers showed the decrement of values. The serum IgE level of the post-shift PFT decreased subjects was found more than 250 IU/ml in 53.1% (17) workers. Restrictive, obstructive and combined types of respiratory impairments were noticed among the workers. Presence of different spores in varying concentration in the working atmosphere may be responsible for the post shift decrement of PFT, allergic symptoms, high IgE level and respiratory impairments among the workers.

A strain-induced exciton transition energy shift in CdSe nanoplatelets: the impact of an organic ligand shell.

We study the influence of surface passivating ligands on the optical and structural properties of zinc blende CdSe nanoplatelets. Ligand exchange of native oleic acid with aliphatic thiol or phosphonic acid on the surface of nanoplatelets results in a large shift of exciton transition energy for up to 240 meV. Ligand exchange also leads to structural changes (strain) in the nanoplatelet's core analysed by wide-angle X-ray diffraction. By correlating the experimental data with theoretical calculations we demonstrate that the exciton energy shift is mainly caused by the ligand-induced anisotropic transformation of the crystalline structure altering the well width of the CdSe core. Further the exciton reduced mass in these CdSe quantum wells is determined by a new method and this agrees well with the expected values substantiating that ligand-strain induced changes in the colloidal quantum well thickness are responsible for the observed spectral shifts. Our findings are important for theoretical modeling of other anisotropically strained systems and demonstrate an approach to tune the optical properties of 2D semiconductor nanocrystals over a broad region thus widening the range of possible applications of AIIBVI nanoplatelets in optics and optoelectronics.

Bacterial extracellular polymeric substance (EPS): a carrier of heavy metals in the marine food-chain.

The ecological implications of metal binding properties of bacterial EPS and its possible role in the bioaccumulation of pollutants in the marine food-chain was investigated using a partially purified and chemically characterized microbial EPS isolated from a species of Marinobacter. Various factors influencing metal sorption by the EPS including the influence of initial metal concentrations, incubation time, pH and sodium chloride concentrations on binding of lead (Pb2+) and copper (Cu2+) were evaluated. The bacterial EPS selectively bound more amount of Cu2+ per mg of EPS than Pb2+. Both copper and lead were sorbed more at near neutral pH than acidic pH. The sorption of Cu2+ increased with increasing copper concentration. The estimated maximum binding ability (MBA) of the EPS was 182 nmol copper and 13 nmol lead mg(-1) EPS. However, the sorption of these metals decreased with the increase in sodium chloride concentration. Furthermore, up to 35% of 14C-labeled Marinobacter was ingested by a benthic polychaete Hediste diversicolor. On an average, 29% of the ingested EPS was absorbed into tissues and 49% of the EPS was respired. It was apparent that the animals used the EPS as a source of energy and nutrition. The labile nature of the bacterial EPS and its ability to bind heavy metals might route the bound metals through the marine food chain, thereby transferring and aiding bioaccumulation of metal pollutants in the higher trophic animals.

Efficacy and safety of the intensive dose of rosuvastatin 40mg/day in patients with acute coronary syndrome and at high risk of cardiovascular disease-ROSUVEES-2.

BACKGROUND: Randomized clinical trials have established the benefits of statin therapy in acute coronary syndromes (ACS) via their pleiotropic effects. AIM OF THE STUDY: This was a 12-week, open-label, multicenter, postmarketing observational study evaluating the efficacy and safety of rosuvastatin 40 mg/day in very high-risk or high-risk Indian patients according to NCEP ATP III guidelines. METHODOLOGY: One hundred and sixty two patients (age: 30 to 69 years) with evidence of coronary artery disease, hospitalized with chest pain with/without electrocardiogram changes and with non-ST segment elevation ACS and ST segment elevation ACS who received optimal reperfusion therapy were enrolled. The primary endpoint was the percent change from baseline in low-density lipoprotein cholesterol (LDL-C) levels at 6 and 12 weeks of treatment. Other lipid parameters, high sensitive C-reactive protein (hsCRP), glycosylated hemoglobin, and clinical biochemical parameters were also assessed. RESULTS: At 12 weeks, intensive therapy with rosuvastatin 40mg/day significantly reduced LDL-C (p<0.001), total cholesterol (TC) (p<0.001), triglyceride (p<0.01), TC/high density lipoprotein cholesterol (HDL-C) ratio (p<0.001), non-HDL-C (p<0.001), LDL-C/HDL-C ratio (p<0.001), and hsCRP (p=0.034) in very high-risk and high-risk patients with ACS. Overall, 54.5% (61/112) patients achieved LDL-C goal of <70mg/dL. However, the change in HDL-C and very low density lipoprotein cholesterol (VLDL-C) were not significant. Few adverse events including myalgia were reported during the study. CONCLUSION: Results of this study showed that 40mg dose of rosuvastatin, initiated early and continued for 12 weeks, was effective in terms of reducing LDL cholesterol and was well tolerated.

Production of macroaggregates from dissolved exopolymeric substances (EPS) of bacterial and diatom origin.

Exopolymeric substances (EPS) isolated from a pure culture of the marine bacterium Marinobacter sp. and the marine diatom Skeletonema costatum (axenic) were partially purified, chemically characterized and used as dissolved organic matter (DOM) for the production of macroaggregates. The role of organic particles such as transparent exopolymeric particles (TEP) and Coomassie stained particles (CSP) in the production of macroaggregates was experimentally assessed. Three experimental rolling tanks containing sterile medium with: (1) EPS, (2) EPS + live diatom cells and (3) EPS + killed bacteria, and three control tanks without any added EPS were used for macroaggregate production. Changes in abundance and average size of macroaggregates were monitored using image analysis, whereas TEP and CSP were enumerated microscopically. In the presence of microbial EPS, macroaggregates of a size of 23-35 mm(2) were produced. Aggregate size and abundance considerably varied with both time and source of EPS. No correlation was observed for macroaggregate size and abundance with either TEP or CSP. One-way ANOVA demonstrated significant differences in the variance of particle abundance and size in tanks having only EPS or EPS in combination with live diatom cells. Our data suggest that production of macroaggregates was influenced by polymer chemistry and surface properties of colliding particles, whereas TEP and CSP concentrations were influenced by molecular weight of EPS and the presence of growing cells. Interestingly, macroaggregates were formed in the near absence of TEP and CSP, highlighting the role of other unknown processes in the transformation of DOM to particulate organic matter (POM) in aquatic environments.

The prevalence and characteristics of colorectal neoplasia in acromegaly.

An increased prevalence of colorectal neoplasia has been reported in acromegalic patients, and recommendations have been made for early colonoscopic screening and regular surveillance. This assumption, however, is frequently drawn from studies using selected control populations. To clarify colonoscopic management in these patients, we undertook a 2-center prospective screening colonoscopy study in 122 acromegalics (age range, 25-82 yr). In the absence of ideal age-matched controls, we calculated prevalence rates of occult adenocarcinomas and adenomas in the general population using cumulative data in the published literature from 8 autopsy studies (model 1, n = 3,559) and 4 screening colonoscopy studies (model 2, n= 810), applying linear regression models. Of the 115 patients with complete examinations, adenocarcinomas were discovered in 3 (2.6%), and at least 1 adenoma was found in 11, giving an overall prevalence of neoplasia of 12% (14 of 115). Prevalence rates for age bands 30-40, 40-49, 50-59, 60-69, and 70+ yr were 0%, 8%, 12%, 20%, and 21%, respectively. Compared with the 2 control models, the prevalence of occult colorectal cancer was not significantly increased (acromegalics vs. models 1 and 2, 2.6% vs. 2.3% and 0.9%), nor was there an increase in the prevalence of adenomas in any age band. Pathological characteristics showed some differences, in that adenomas in acromegalics tended to be right sided (68% vs. 57% and 56%), larger (for > or =10 mm, 27% vs. 13% and 9%), and of advanced histology (for tubulovillous, 27% vs. 4% and 22%). No associations were found between the presence of colonic neoplasia and the duration of disease, total GH exposure, cure status, and serum insulin-like growth factor I. This study has failed to demonstrate an increased prevalence of neoplasia in acromegalic patients compared with the expected prevalence in the general population and questions the need for an aggressive colonoscopic screening policy.

Effect of L-dopa on visual evoked potential in patients with Parkinson's disease.

In 47 patients with Parkinson's disease, we studied the visual evoked potential (VEP) using the pattern-reversal checkerboard (CBVEP) and the grating (GVEP) stimuli before and after 3 months of L-dopa therapy. The P100 latency in both CBVEP and GVEP was prolonged before L-dopa therapy, usually commensurate with the degree of motor disability. Clinical improvement of the parkinsonian state after L-dopa therapy was associated with shortening of the P100 latency in CBVEP, but not significantly in GVEP.

Bioavailability studies on guar gum-based three-layer matrix tablets of trimetazidine dihydrochloride in human volunteers.

Guar gum-based three-layer matrix tablets of a highly water-soluble drug, trimetazidine dihydrochloride, were evaluated for their in vivo release in healthy volunteers in comparison with commercially available conventional immediate release tablets. Six healthy volunteers participated in the study and a two-way crossover design was followed. The plasma concentration of trimetazidine dihydrochloride was estimated by reverse-phase HPLC. The pharmacokinetic parameters were calculated from the plasma concentration of trimetazidine dihydrochloride versus time data. The delayed T(max), decreased C(max) and K(a), unaltered bioavailability, and prolonged t(1/2) and MRT indicated a slow and prolonged release of trimetazidine dihydrochloride from guar gum three-layer matrix tablets in comparison with the immediate release tablet dosage form. The guar gum three-layer matrix tablets of trimetazidine dihydrochloride may be useful in providing constant drug delivery with minimum fluctuations.

Development of colon targeted drug delivery systems for mebendazole.

The objective of the present study is to develop colon targeted drug delivery systems for mebendazole using guar gum as a carrier. Matrix tablets containing various proportions of guar gum were prepared by wet granulation technique using starch paste as a binder. The tablets were evaluated for drug content uniformity, and were subjected to in vitro drug release studies. The amount of mebendazole released from the matrix tablets at different time intervals was estimated by a high-performance liquid chromatography method. Guar gum matrix tablets released 8-15% of the mebendazole in the physiological environment of stomach and small intestine depending on the proportion of guar gum used in the formulation. When the dissolution study was continued in simulated colonic fluids the matrix tablets containing 20% of guar gum released another 83% of mebendazole after degradation into 2-3 pieces. The matrix tablets containing 30% of guar gum also released about 50% of mebendazole in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that matrix tablets containing either 20% or 30% of guar gum are most likely to provide targeting of mebendazole for local action in the colon. The mebendazole matrix tablets containing either 20% or 30% of guar gum showed no change either in physical appearance, drug content or dissolution pattern after storage at 45 degrees C/75% relative humidity for 3 months. Differential scanning calorimetry indicated no possibility of interaction between mebendazole and guar gum.

Pharmacokinetic evaluation of guar gum-based colon-targeted drug delivery systems of mebendazole in healthy volunteers.

The pharmacokinetic evaluation of guar gum-based colon-targeted tablets of mebendazole against an immediate release tablet was carried out in human volunteers. Six healthy volunteers participated in the study and a crossover design was followed. Mebendazole was administered at a dose of 50 mg both in immediate release tablet and colon-targeted tablets. On oral administration of colon-targeted tablets, mebendazole started appearing in the plasma at 5 h, and reached the peak concentration (C(max) of 25.7+/-2.6 ng/ml) at 9.4+/-1.7 h (T(max)) whereas the immediate release tablets produced peak plasma concentration (C(max) of 37.2+/-6.8 ng/ml) at 3.4+/-0.9 h (T(max)). Colon-targeted tablets showed delayed t(max) and absorption time, and decreased C(max) and absorption rate constant when compared to the immediate release tablets. The results of the study indicated that the guar gum-based colon-targeted tablets of mebendazole did not release the drug in stomach and small intestine, but delivered the drug to the colon resulting in a slow absorption of the drug and making the drug available for local action in the colon.

Influence of menthol and pressure-sensitive adhesives on the in vivo performance of membrane-moderated transdermal therapeutic system of nicardipine hydrochloride in human volunteers.

A membrane-moderated transdermal therapeutic system of nicardipine hydrochloride was developed using 2% w/w hydroxypropylcellulose (HPC) gel as a reservoir system containing 5% w/w of menthol as a penetration enhancer. The permeability flux of nicardipine hydrochloride through the ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38 or TACKWHITE A 4MED on the permeability of nicardipine hydrochloride through EVA 2825 membrane (28% w/w vinyl acetate) or EVA 2825 membrane/skin composite was also studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE A 4MED/skin composite was higher than that coated with MA-31 or MA-38. Thus, a new transdermal therapeutic system for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE A 4MED, and 2% w/w HPC gel as reservoir containing 5% w/w of menthol as a penetration enhancer. In vivo studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady-state plasma concentration of the drug with minimal fluctuations for 26h with improved bioavailability in comparison with the immediate release capsule dosage form.