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We have studied the entrance channel effects in the decay of Compound nucleus 240 Cf * formed in 34 S+ 206 Pb and 36 S+ 204 Pb reactions by using energy density dependent nuclear proximity potential in the framework of dynamical cluster-decay model (DCM). At different excitation energies, the fragmentation potential and preformation probability of decaying fragments are almost identical for both the entrance channels, which seem to suggest that decay is independent of its formation and entrance channel excitation energy. It is also observed that, with inclusion of deformation effects upto quadrupole within the optimum orientation approach, the fragmentation path governing potential energy surfaces gets modified significantly. Beside this, the fission mass distribution of Cf* isotopes is also investigated. The calculated fission cross-sections using SIII force for both the channels find nice agreement with the available experimental data for deformed choice of fragments, except at higher energies. In addition to this, the comparative analysis with Blocki based nuclear attraction is also worked out. It is observed that Blocki proximity potential accounts well for the CN decay at all energies whereas the use of EDF based nuclear potential suggests the presence of some non-compound nucleus process (such as quasi-fission (qf)) at higher energies.

Multilocular cystic renal cell carcinoma (MCRCC) is an uncommon low grade RCC with unique morphologic features. MCRCC also known as multilocular clear cell RCC is a rare cystic tumor of the kidney with an excellent outcome. MCRCC has been recognized as a separate subtype of RCC in the 2004 World Health Organization (WHO) classification of adult renal tumors. MCRCC is diagnosed on the basis of strict histological criteria according to 2004 WHO classification. It is usually included in the group of tumors of undetermined malignant potential with low nuclear grade. We present a case of MCRCC in a 43-year-old female patient who presented with pain in left lumbar region and hematuria. Left-sided radical nephrectomy was performed, and on histopathologic examination it was diagnosed as MCRCC with Fuhrman nuclear grade 1. Immunohistochemistry with epithelial membrane antigen and vimentin confirmed the diagnosis.

Introduction: Cone beam computed tomography is a new diagnostic innovation to dental imaging. Despite the use of CBCT in oral and maxillofacial imaging, reports on its use either by individual practitioners or referral patterns to CBCT centers is lacking. Hence, a study was conducted to determine incidental findings on CBCT and reasons for referral by dental practitioners in Indore city. Materials and Methods: A retrospective analysis of 795 records that were referred for CBCT imaging at Institutional and Oracal CBCT Centre, Indore was undertaken. Referrals from both within and outside institution, as well as from private practitioners were considered. The reason for CBCT referral, provision diagnosis, final diagnosis and any incidental diagnosis were recorded. Results: This retrospective chart audit revealed that 56.7 % were male and 43.3% were females. Greatest source of patients was referred by oral surgeons (21.9%) followed by oral and maxillofacial radiologist (14.2%) and prosthodontist (9.3%). The most common reason for referral was for implant analysis (24.2%) and the most common incidental finding diagnosed by CBCT was oral malignancies. Conclusion: In Institutional set-up, CBCT referrals were mostly for the reason of planning implant placement followed by trauma whereas private practitioners used CBCT mostly for implant placement followed by impaction. CBCT was being utilized more by Oral surgeons in private sector whereas it in an Institutional setup majority of referrals from Department of Oral Diagnosis and Radiology. Findings that were most commonly diagnosed incidentally on CBCT were Orofacial malignancies followed maxillary sinus pathologies.

KL(4)-surfactant contains the novel KL(4) peptide, sinapultide, which mimics properties of the hydrophobic pulmonary surfactant protein SP-B, in a phospholipid formulation and may be lung protective in experimental acute respiratory distress syndrome/acute lung injury. Our objective was to determine the protective role of airway delivery of KL(4)-surfactant in murine models of hyperoxic and lipopolysaccharide (LPS)-induced lung injury and further explore the mechanisms of protection. For the hyperoxic injury model, mice exposed to 80% O(2) for 6 days received an intranasal bolus of vehicle, beractant, or KL(4)-surfactant on days 3, 4, 5, and 6 of the exposure, and lungs were evaluated on day 7. Mice in the LPS-induced lung injury model received an intratracheal bolus of LPS followed by an intranasal bolus of KL(4)-surfactant or control at 1, 3, and 19 hr post-LPS challenge, and lungs were evaluated after 24 hr. To explore the mechanisms of protection, in vitro assays were performed with human and murine endothelial cell monolayers, and polymorphonuclear leukocyte (PMN) transmigration in the presence or absence of KL(4)-surfactant or lipid controls was evaluated. Based on morphology, histopathology, white blood cell count, percentage of PMNs, and protein concentration in bronchoalveolar lavage fluid, our data showed KL(4)-surfactant, unlike vehicle or beractant, blocked neutrophil influx into alveoli and suppressed lung injury. Furthermore, in vitro assays showed KL(4)-surfactant decreased neutrophil transmigration at the endothelial cell level. KL(4)-surfactant decreased inflammation and lung permeability compared with controls in both mouse models of lung injury. Evidence suggests the anti-inflammatory mechanism of the KL(4)-peptide is through inhibition of PMN transmigration through the endothelium.

The molecular mechanisms by which bradykinin induces excessive airway obstruction in asthmatics remain unknown. Transforming growth factor (TGF)-β has been involved in regulating airway inflammation and remodeling in asthma, although it is unknown whether TGF-β can modulate bradykinin-associated bronchial hyperresponsiveness. To test whether TGF-β directly modulates airway smooth muscle (ASM) responsiveness to bradykinin, isolated murine tracheal rings were used to assess whether TGF-β alters ASM contractile responsiveness to bradykinin. Interestingly, we found TGF-β-treated murine rings (12.5 ng/ml, 18 h) exhibited increased expression of bradykinin 2 (B2) receptors and became hyperreactive to bradykinin, as shown by increases in maximal contractile responses and receptor distribution. We investigated the effect of TGF-β on bradykinin-evoked calcium signals since calcium is a key molecule regulating ASM excitation-contraction coupling. We reported that TGF-β, in a dose- (0.5–10 ng/ml) and time- (2–24 h) dependent manner, increased mRNA and protein expression of the B2receptor in cultured human ASM cells. Maximal B2receptor protein expression that colocalized with CD44, a marker of membrane cell surface, occurred after 18 h of TGF-β treatment and was further confirmed using fluorescence microscopy. TGF-β (2.5 ng/ml, 18 h) also increased bradykinin-induced intracellular calcium mobilization in fura-2-loaded ASM cells. TGF-β-mediated enhancement of calcium mobilization was not attenuated with indomethacin, a cyclooxygenase inhibitor. These data demonstrate for the first time that TGF-β may play a role in mediating airway hyperresponsiveness to bradykinin seen in asthmatics by enhancing ASM contractile responsiveness to bradykinin, possibly as a result of increased B2receptor expression and signaling.

The role of surfactant protein-A (SP-A) in pulmonary uptake and metabolism of [3H]dipalmitoylphosphatidylcholine ([3H]DPPC) was studied in SP-A gene-targeted mice (SP-A −/−). Unilamellar liposomes were instilled into the trachea of anesthetized mice. Uptake was measured as dpm in lungs plus liver and kidney for in vivo experiments and in lungs and perfusate for isolated lung experiments. [3H]DPPC uptake increased with CO2-induced hyperventilation in wild-type mice (SP-A +/+) but was unchanged in SP-A −/−. Secretagogue treatment approximately doubled the uptake of [3H]DPPC in isolated lungs from SP-A +/+ but had no effect in SP-A −/−. Lungs degraded 23 ± 1.2% of internalized [3H]DPPC in SP-A +/+ and 36 ± 0.6% in SP-A −/−; degradation increased with 8-bromoadenosine 3′,5′-cyclic monophosphate in SP-A +/+ but was unchanged in SP-A −/−. Activity of lysosomal-type phospholipase A2(PLA2) was significantly greater in lungs from SP-A −/− compared with SP-A +/+. Thus SP-A is necessary for lungs to respond to hyperventilation or secretagogues with increased DPPC uptake and also modulates the PLA2-mediated degradation of internalized DPPC.

Background: In recent years basal cell markers (high molecular weight cytokeratin [HMWCK]) and prostate biomarker alpha-methyl acyl-coenzyme A racemase (AMACR) have been used as adjuvant to morphology in diagnostically challenging cases with a very high sensitivity and specificity. This has increased the diagnostic accuracy of prostate cancer worldwide. Materials and Methods: In this prospective study, total of 50 cases including 37 cases of malignant lesions and 13 cases of benign lesions of the prostate were taken. Tumor grade was determined according to Gleason's grading system. AMACR and HMWCK expressions were determined by immunohistochemical staining. The obtained results were analyzed and evaluated using Chi-square statistical test (SPSS version 20). Results: AMACR was not expressed in any of the 13 cases of benign lesions of the prostate while in malignant lesions of prostate it was expressed in 33 of 37 (89.18%) cases. All 4 (100%) cases of well-differentiated carcinoma were positive for AMACR expression. 21 of 25 (84%) moderately differentiated and all 10 (100%) cases of poorly differentiated tumors were positive for AMACR. There was statistically significant difference in expression of AMACR between benign and malignant lesions of the prostate, indicated byP = 0.001. In benign lesions, HMWCK was expressed in all the 13 (100%) cases while in malignant lesions of prostate it was not expressed in any of the (0%) case. All 13 benign lesions were positive for HMWCK only. AMACR expression was not seen in any of the benign lesion. Out of 37 malignant cases, 4 cases were negative for both, 33 cases were positive only for AMACR, but no case was positive only for HMWCK. Conclusions: As an adjunct to biopsy, AMACR and HMWCK have value for resolving diagnostically challenging cases.

Studies have shown that a single-item question might be useful in identifying patients with limited health literacy. However, the utility of the approach has not been studied in patients receiving maintenance peritoneal dialysis (PD). We assessed health literacy in a cohort of 31 PD patients by administering the Rapid Estimate of Adult Literacy in Medicine (REALM) and a single-item health literacy (SHL) screening question "How confident are you filling out medical forms by yourself?" (Extremely, Quite a bit, Somewhat, A little bit, or Not at all). To determine the accuracy of the single-item question for detecting limited health literacy, we performed sensitivity and specificity analyses of the SHL and plotted the area under the receiver operating characteristic (AUROC) curve using the REALM as a reference standard. Using a cut-off of "Somewhat" or less confident, the sensitivity of the SHL for detecting limited health literacy was 80%, and the specificity was 88%. The positive likelihood ratio was 6.9. The SHL had an AUROC of 0.79 (95% confidence interval: 0.52 to 1.00). Our results show that the SHL could be effective in detecting limited health literacy in PD patients.

The purpose of the present study was to find out the level of Anxiety among male and female adolescents. The local of the study was confined of Udaipur city of Rajasthan. The sample consisted of 60 subjects divided into two groups, 30 Male and 30 Female adolescents. Test anxiety scale by Dr. V. P Sharma (1971) was used to collect data. Mean, S.D and ‘t’ test was calculated to analyze the data. Result showed that male adolescents have higher anxiety in comparison to female adolescents.

The present study was carried out to determine the intracellular free calcium concentration ([Ca(2+)](i)) and the activity of its regulatory enzymes (Na(+),K(+)-ATPase and Ca(2+)-ATPase) in leucocytes. Levels of plasma lysophosphatidylcholine (LPC) were also measured. Then the relationship between these parameters and the clinical severity of asthma and bronchial reactivity was studied. Patients with asthma were divided into three groups: acute asthma (subjects in acute exacerbation), uncontrolled asthma (subjects currently symptomatic) and stable asthma (subjects currently asymptomatic). A group of normal subjects was also studied. Spirometry, specific airway conductance and bronchial reactivity measurements were carried out. The following biochemical parameters were studied in venous blood: leucocyte [Ca(2+)](i), Na(+), K(+)-ATPase and Ca(2+)-ATPase activities, and plasma LPC. Leucocyte [Ca(2+)](i) was increased and the activities of Na(+),K(+)-ATPase and Ca(2+)-ATPase were decreased in patients with asthma. Plasma levels of LPC were also increased. These changes were observed to be greatest among asthmatics in acute exacerbation of asthma, and lesser in magnitude in patients with less severe asthma. The activities of both ATPases were found to have a significant positive correlation, and [Ca(2+)](i) and the levels of plasma LPC a significant negative correlation, with predicted forced expiratory volume in 1 s (FEV(1)). No significant correlation was observed between the biochemical parameters and bronchial reactivity. It is concluded that intracellular calcium homoeostasis is abnormal in asthma; specifically, the activities of Na(+),K(+)-ATPase and Ca(2+)-ATPase are decreased. These abnormalities may modulate the clinical severity of asthma.

Monoclonal gammopathy is increasingly recognized as a common cause of membranoproliferative glomerulonephritis (MPGN); however, establishing this diagnosis can be challenging. We report the case of a 58-year-old asymptomatic woman who presented with proteinuria with protein excretion of 5,000mg/d, microscopic hematuria, and normal kidney function. Kidney biopsy was consistent with MPGN pattern of injury. Immunofluorescence studies were positive for nonspecific segmental immunoglobulin M (IgM) and C3 staining. Electron microscopy showed subendothelial, subepithelial, and mesangial electron-dense deposits. The workup excluded an infectious or autoimmune disease, but IgG κ monoclonal protein was detected in serum at a concentration of 0.4mg/dL. Because there was a mismatch between the serum monoclonal protein (IgG κ) and immunofluorescence staining pattern (nonspecific IgM, no light chain restriction), laser microdissection and mass spectrometry were performed on the kidney biopsy tissue. This identified the deposits as monoclonal IgG κ, thereby leading to the diagnosis of monoclonal gammopathy–associated MPGN. Our case emphasizes the importance of searching for an underlying cause of MPGN, reviews the technique of laser microdissection–mass spectrometry, and highlights its application as a pathology tool for the evaluation of monoclonal gammopathy–related glomerulonephritis.

The decay of various isotopes of Pt${}^{*}$ formed using stable and neutron-rich radioactive beams of Sn is studied by using the dynamical cluster-decay model (DCM). The entrance channel effect in ${}^{190}$Pt${}^{*}$ compound nuclei is investigated using different targets and projectiles. For both entrance channels, i.e., ${}^{132}$Sn+${}^{58}$Ni and ${}^{126}$Sn+${}^{64}$Ni, the fragmentation potential and preformation probability of decaying fragments are almost identical at comparable center-of-mass energies (${E}_{\mathrm{c}.\mathrm{m}.}$), enabling us to conclude that decay of ${}^{190}$Pt${}^{*}$ is independent of its formation effects. In order to check for the persistence of entrance channel independence in the decay of Pt${}^{*}$ compound nuclei, various versions of nuclear proximity potentials and different values of level density parameter are employed in the calculations, and the results are sustained. It is also observed that, with inclusion of deformation effects up to quadrupole (${\ensuremath{\beta}}_{2}$) within the optimum orientation approach, the structure of potential energy surfaces changes significantly. Besides this, the fission mass distribution of Pt${}^{*}$ isotopes is investigated and consequently the barrier modification is estimated to account for the phenomena of fusion hindrance. The ${}^{132}$Sn+${}^{58}$Ni reaction is also studied using four proximity potentials, i.e., Prox 1977, Prox 1988, mod-Prox 1988, and Denisov 2002 within the framework of the $\ensuremath{\ell}$-summed extended-Wong model for addressing the fusion hindrance phenomena. We find that Prox 77 and Prox 88 fit the total fusion cross-section data only at above-barrier energies, whereas Denisov 2002 underestimates the data at all energies due to being least sensitive towards asymmetry and isospin. So a stronger nuclear interaction potential mod-Prox 1988 that accounts for isospin effect and asymmetry of the colliding nuclei is employed, which fits the data with smooth variation of ${\ensuremath{\ell}}_{\mathrm{max}}$(${E}_{\mathrm{c}.\mathrm{m}.}$). Our calculations indicate that the isospin and asymmetry of colliding nuclei also play an important role in the fusion dynamics, particularly in the below-barrier region.

Pulsatile drug delivery systems (PDDS) have attracted attraction because of their multiple benefits over conventional dosage forms. They deliver the drug at the right time, at the right site of action and in the right amount, which provides more benefit than conventional dosages and increased patient compliance. These systems are designed according to the circadian rhythm of the body, and the drug is released rapidly and completely as a pulse after a lag time. These products follow the sigmoid release profile characterized by a time period. These systems are beneficial for drugs with chronopharmacological behavior, where nocturnal dosing is required, and for drugs that show the first-pass effect. This review covers methods and marketed technologies that have been developed to achieve pulsatile delivery. Marketed technologies, such as Pulsincap™, Diffucaps(®), CODAS(®), OROS(®) and PULSYS™, follow the above mechanism to render a sigmoidal drug release profile. Diseases wherein PDDS are promising include asthma, peptic ulcers, cardiovascular ailments, arthritis and attention deficit syndrome in children and hypercholesterolemia. Pulsatile drug delivery systems have the potential to bring new developments in the therapy of many diseases.

The entrance channel effects in the decay of compound nucleus 190Pt* formed using different incoming channels i.e. 132Sn+58Ni and 126Sn+64Ni is studied by using dynamical cluster-decay model (DCM). The neutron-rich radioactive beams of 132Sn and 126Sn are used here. We find that with the inclusion of deformation effects up to quadrupole (β2), the structure of potential energy surfaces changes a little bit at l = 0 and significantly at l = lmax. It is also observed that for both the entrance channels, the preformation probability of decaying fragments is almost identical at same lmax and comparable centre of mass energies. This identical potential energy surface behavior and same lmax values in either of entrance channels, enable us to conclude that decay of 190Pt* is independent of formation effects. The relevant role of level density parameter is also analyzed.

Since cancer is one of the leading causes of death worldwide, and there is an urgent need to find better treatment. In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. Treatment modalities comprise radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Currently, the use of chemotherapeutics remains the predominant option for clinical control. However, one of the major problems with successful cancer therapy using chemotherapeutics is that patients often do not respond or eventually develop resistance after initial treatment. This has led to the increased use of anticancer drugs developed from natural resources. The biodiversity of venoms and toxins makes them a unique source from which novel therapeutics may be developed. In this review, the anticancer potential of snake venom is discussed. Some of the included molecules are under clinical trial and may find application for anticancer drug development in the near future.

Mechanistic investigations coupled with epidemiology, case-control, cohort and observational studies have increasingly linked isocyanate exposure (both chronic and acute) with pulmonary morbidity and mortality. Though ascribed for impairment in endothelial cell function, molecular mechanisms of these significant adverse pulmonary outcomes remains poorly understood. As preliminary studies conducted in past have failed to demonstrate a cause-effect relationship between isocyanate toxicity and compromised pulmonary endothelial cell function, we hypothesized that direct exposure to isocyanate may disrupt endothelial structural lining, resulting in cellular damage. Based on this premise, we comprehensively evaluated the molecular repercussions of methyl isocyanate (MIC) exposure on human pulmonary arterial endothelial cells (HPAE-26). We examined MIC-induced mitochondrial oxidative stress, pro-inflammatory cytokine response, oxidative DNA damage response and apoptotic index. Our results demonstrate that exposure to MIC, augment mitochondrial reactive oxygen species production, depletion in antioxidant defense enzymes, elevated pro-inflammatory cytokine response and induced endothelial cell apoptosis via affecting the balance of mitochondrial-nuclear cross talk. We herein delineate the first and direct molecular cascade of isocyanate-induced pulmonary endothelial cell dysfunction. The results of our study might portray a connective link between associated respiratory morbidities with isocyanate exposure, and indeed facilitate to discern the exposure-phenotype relationship in observed deficits of pulmonary endothelial cell function. Further, understanding of inter- and intra-cellular signaling pathways involved in isocyanate-induced endothelial damage would not only aid in biomarker identification but also provide potential new avenues to target specific therapeutic interventions., Graphical abstract Highlights ► Pulmonary endothelial cells accomplish a vast variety of specialized functions. ► A balance in mitochondrial-nuclear cross talk is essential for endothelial integrity. ► Methyl isocyanate impairs redox balance in endothelial milieu. ► We profess a corollary between respiratory morbidities and methyl isocyanate exposure.

Health literacy is the capacity of an individual to understand information related to a disease in order to make an informed decision. In patients with kidney diseases, studies have reported increasing impact of limited health literacy on health outcomes. Our paper discusses current literature on health literacy in kidney diseases.

Application of Wong formula with explicit angular momentum and barrier modification effects is made to fit the fusion excitation function for 132Sn+64Ni→196Pt*→A;1+A2 reaction, with nuclear proximity potential obtained from the Skyrme Energy Density Formalism (SEDF) under Frozen approximation. The barrier modification effects, arising due to the use of different Skyrme forces, are studied in reference to fusion of neutron rich 132Sn with 64Ni target. It is observed that out of the three illustrated Skyrme forces i.e SIII, GSkI and SSk, the last two forces are able to fit the data with smooth variation of lmax with centre of mass energy whereas SIII force further requires barrier modifications at near and below barrier energies. Thus, it is clear that required modification of barrier by SIII can be supplemented by use of another suitable force.

Mucoadhesive nanosuspension of ciprofloxacin was designed in order to improve the solubility, bioavailability and efficacy for the treatment of typhoid fever. The identity and purity of drug was established. The compatibility of drug with various excipients was ascertained by FTIR techniques, which indicated no interaction between the drug and excipients. Four different formulations were prepared by optimizing various parameters using different polymers like soya lecithin, pluronic F68, polyvinyl alcohol, and polyvinylpyrrolidone K30. Particle size and polydispersity index were determined by photon correlation spectroscopy. Average particle size of different formulations was found to be between 503-1844 nm. The zeta potential of all formulations was found to be around +/- 20 My indicating satisfactory physical stability. Scanning electron microscopy showed that process parameters affect the crystal morphology. The promising formulations prepared from combination of soya lecithin and pluronic F68 and those based on soya lecithin alone were subjected to dissolution profile studies. The later formulation exhibited fast dissolution rate as compared to the former. Thus nanosus-pension based on soya lecithin was incorporated into hydrogels prepared using different grades of carbopol 934 and 971 as mucoadhesive polymers. After 10 h, mucoadhesive nanosuspensions showed 45-56% release. The developed mucoadhesive nanosuspensions exhibited satisfactory physical stability. The studies indicated potential of these formulations as novel gastroretentive systems.

Male reproductive health is exquisitely sensitive to environmental insults as evidenced by the rising incidence of testicular cancers and low and probably declining semen quality. Isocyanates, such as methyl isocyanate (MIC), with their wide industrial applications, are known to exert severe ill health effects. The present study was performed to find out the pathophysiological implications of isocyanate exposure on the male germ line. The investigations were performed in the cultured mouse spermatogonial GC-1 spg cell line using N-succinimidyl N-methylcarbamate, a surrogate chemical to MIC. DNA damage, oxidative stress and apoptosis response parameters increased with time of exposure and dose after treatment. Treated cells also displayed elevated levels of inflammatory cytokines as well as morphological transformation and stress-responsive senescence. Chromosomal aberrations, telomere anomaly, aneuploidy and variable amplification of microsatellite repeats additionally indicated induced genomic instability. This was accompanied by evidence of a deregulation of cell cycle progression, such as substantial fold-changes in the expression of proliferating cell nuclear antigen, Cyclin D1, Bcl-2 and Bax genes; and aberrant expression of p53, cyclin A, cyclin E, CDK-2 and aurora kinase-B proteins. Our results demonstrate that MIC in the form of N-succinimidyl N-methylcarbamate promotes germ-line genomic instability in vitro. We envisage that understanding the interplay between environmental toxin-induced signaling and predisposition to testicular cancers would spur identification of meaningful targets for useful therapeutic translational modalities.

We examined the possible molecular mechanisms underlying the cytotoxicity and anticarcinogenic potential of Mentha leaf extracts (petroleum ether, benzene, chloroform, ethyl acetate, methanol, and water extracts) on 6 human cancer (HeLa, MCF-7, Jurkat, T24, HT-29, MIAPaCa-2) and normal (IMR-90, HEK-293) cell lines. Of all the extracts tested, chloroform and ethyl acetate extracts of M piperita showed significant dose- and time-dependent anticarcinogenic activity leading to G1 cell cycle arrest and mitochondrial-mediated apoptosis, perturbation of oxidative balance, upregulation of Bax gene, elevated expression of p53 and p21 in the treated cells, acquisition of senescence phenotype, while inducing pro-inflammatory cytokines response. Our results provide the first evidence of direct anticarcinogenic activity of Mentha leaf extracts. Further, bioassay-directed isolation of the active constituents might provide basis for mechanistic and translational studies for designing novel anticancer drugs to be used alone or as adjuvant for prevention of tumor progression and/or treatment of human malignancies.

The purpose of this study was to design microsponge-based novel colon-specific drug delivery system bearing dicyclomine. Eudragit S-100-based microsponges containing the drug in varying amount were prepared using quasi-emulsion solvent diffusion method. The microsponges were prepared by optimizing various process parameters. Differential scanning calorimetry and Fourier transform infrared studies indicated compatibility and stability of the drug in various formulations. Shape and surface morphology of the microsponges were examined using scanning electron microscopy. The formulations were subjected to in vitro release studies, and the results were evaluated kinetically and statistically. In vitro release data showed a biphasic pattern with an initial burst effect. In the first hour, drug release from microsponges was found to be between 17% and 31%. The cumulative percent release at the end of eighth hour was noted to be between 53% and 83%. The release kinetics showed that the data followed Higuchi model and the main mechanism of drug release was diffusion. The colon-specific tablets were prepared by compressing the microsponges followed by coating with pectin:hydroxypropylmethylcellulose mixture. In vitro release studies exhibited that compression-coated colon-specific formulations started releasing the drug at the sixth hour corresponding to the arrival time at colon. The study presents a new approach for colon-specific drug delivery.

Dutasteride loaded liposomal system were developed for topical application in order to avoid the side effects associated with the oral administration of the drug. Drug-loaded multilamellar liposomes were prepared using thin-film hydration method followed by sonication and optimized with respect to entrapment efficiency, drug payload, size and lamellarity. The vesicular systems consisting of egg phosphatidylcholine (100 mg), cholesterol (50 mg), and dutasteride (5 mg) showed highest drug entrapment efficiency (94.6%) and drug payload (31.5 µg/mg of total lipids). Mean vesicle size of these liposomes was noted to be 1.82 ± 0.15 µm. Significantly higher skin permeation of dutasteride through excised abdominal mouse skin was achieved via the developed liposomal formulations as compared to hydro-alcoholic solution and conventional gels. The formulation exhibited about seven fold higher deposition of drug in skin. Stability studies indicated that the liposomal formulations were quite stable in the refrigerated conditions for 10 weeks with negligible drug leakage or vesicle size alteration. Results of the current studies exhibited improved and localized drug action in the skin and thus could be formulated as a better option to cure androgenetic alopecia.

Background/Aims: The impact of nebivolol therapy on the renal proximal tubular cell (PTC) structure and function was investigated in a transgenic (TG) rodent model of hypertension and the cardiometabolic syndrome. The TG Ren2 rat develops nephropathy with proteinuria, increased renal angiotensin II levels and oxidative stress, and PTC remodeling. Nebivolol, a β1-antagonist, has recently been shown to reduce albuminuria, in part, through reductions in renal oxidative stress. Accordingly, we hypothesized that nebivolol therapy would attenuate PTC damage and tubulointerstitial fibrosis. Methods: Young Ren2 (R2-N) and SD (SD-N) rats were treated with nebivolol (10 mg/kg/day) or vehicle (R2-C; SD-C) for 3 weeks. PTC structure and function were tested using transmission electron microscopy and functional measurements. Results: Nebivolol treatment decreased urinary N-acetyl-β-D-glucosaminidase, tubulointerstitial ultrastructural remodeling and fibrosis, NADPH oxidase activity, 3-nitrotyrosine levels, and increased megalin and lysosomal-associated membrane protein-2 immunostaining in PTCs. Ultrastructural abnormalities that were improved with therapy included altered canalicular structure, reduced endosomes/lysosomes and PTC vacuoles, basement membrane thickening, and mitochondrial remodeling/fragmentation. Conclusion: These observations support the notion that nebivolol may improve PTC reabsorption of albumin and other glomerular filtered small molecular weight proteins in association with the attenuation of oxidative stress, tubulointerstitial injury and fibrosis in this rat model of metabolic kidney disease.

This article present a mobile agent (MA) middleware, i.e., Multiagent System for distributed sensor networks (MASDSN) that generates an intelligent framework for deploying applications in distributed sensor network (DSNs). It provides high level middleware services such as object tracking, security, fault-tolerance, power management, and so on. It uses group aware conditions by varying either from service-to-service or according to system conditions (e.g., power level, connectivity, and bandwidth).

Campylobacter jejuni is the leading cause of gastroenteritis worldwide; cytolethal distending toxin (CDT) being an important virulence determinant. As its role in pathogenesis remains unclear, this study aims to investigate cell cycle arrest and apoptosis by CDT (+ve) and CDT (-ve) C. jejuni isolates on HeLa cells.Culture supernatants and lysates from 10 C. jejuni isolates [CDT (+ve) and CDT (-ve), five each] were incubated with HeLa cells. CDT activity on HeLa cells was confirmed by cell distension, cell cycle arrest by flowcytometry, and apoptosis by DNA fragmentation and flowcytometry.Culture supernatant and lysate of only CDT (+ve) C. jejuni isolates produced cell distension. For CDT (+ve) and CDT (-ve) isolates, the cells at G2/M phase after 24, 48 and 72 h were 25.8 +/- 3.79 per cent and 11.2 +/- 0.58 per cent, 72.9 +/- 2.44 and 14.3 +/- 1.88 per cent, 93.5 +/- 0.54 per cent and 18.0 +/- 1.80 per cent respectively (P0.001). All CDT (+ve) isolates induced DNA fragmentation. Apoptosis induced by CDT (+ve) C. jejuni was significantly greater than CDT (-ve) (26.3 +/- 3.49 % vs. 10.4 +/- 1.01% at 24 h, 43.9 +/- 2.40% vs. 17.6 +/- 0.88% at 48 h, 68.4 +/- 1.61% vs. 28.4 +/- 1.62% at 72 h); (P0.001).The present study shows that CDT (+ve) C. jejuni contributes to the pathogenesis through epithelial cell G2/M phase arrest and apoptosis.

The role of oxidative stress is often attributed in environmental renal diseases. Isocyanates, a ubiquitous chemical group with diverse industrial applications, are known to undergo bio-transformation reactions upon accidental and occupational exposure. This study delineates the role of isocyanate-mediated mitochondrial oxidative stress in eliciting chromosomal instability in cultured human kidney epithelial cells. Cells treated with 0.005 microM concentration of methyl isocyanate displayed morphological transformation and stress-induced senescence. Along the time course, an increase in DCF fluorescence indicative of oxidative stress, depletion of superoxide dismutase (SOD) and glutathione reductase (GR) and consistent accumulation of 8-oxo-dG were noticed. Thus, endogenous oxidative stress resulted in aberrant expression of p53, p21, cyclin E and CDK2 proteins, suggestive of deregulated cell cycle, chromosomal aberrations, centromeric amplification, aneuploidy and genomic instability.

The wireless sensor network is an emerging technology that may greatly facilitate human life by providing ubiquitous sensing, computing, and communication capability, through which people can more closely interact with the environment whenever required. One of the most important problems studied in any sensor network is data fusion. Client/server paradigm has been a commonly used computing model in traditional distributed wireless sensor networks (DWSNs). However, the deployment of wireless sensor networks (WSNs) and its ad hoc nature have brought new challenges to the fusion task. For example, the advances in sensor technology allow better, cheaper, and smaller sensors to be used, which results in a much larger number of sensors deployed. On the other hand, sensors communicate through wireless networks where the network bandwidth is much lower than for wired communication. In this article, we have presented mobile agent (MA) assisted data fusion in WSNs (MADFWs). In MADFWs, data stay at the local site, while the fusion process (code) is moved to the data sites. By transmitting the computing process instead of data, network bandwidth requirement is largely reduced and the performance of the fusion process is more stable. One of the key issue which is implemented in this model is how to plan the itinerary for a MA in order to achieve progressive fusion accuracy. We have presented a method to develop an optimal itinerary for MA to fulfill the integration task while consuming minimum amount of resources, including time and power. In MADFWs agent has freedom to invite some nearby slave sensors to cooperatively position the object and inhibit other irrelevant (i.e., farther) sensors from tracking the object. As a result, the communication and sensing overheads are greatly reduced.

Urokinase-type plasminogen activator (uPA) receptor (uPAR) is required for the recruitment of neutrophils in response to infection. uPA induces its own expression in lung epithelial cells, which involves its interaction with cell surface uPAR. Regulation of uPAR expression is therefore crucial for uPA-mediated signaling in infectious acute lung injury (ALI).To determine the role of uPA in uPAR expression during ALI caused by sepsis.We used Western blot, Northern blot, Northwestern assay, and immunohistochemistry. Phosphate-buffered saline- and lipopolysaccharide (LPS)-treated wild-type and uPA(-/-) mice were used.Biological activities of uPA, including proteolysis, cell adhesion, migration, proliferation, and differentiation, are dependent on its association with uPAR. Bacterial endotoxin (LPS) is a major cause of pulmonary dysfunction and infection-associated mortality. The present study shows that LPS induces uPAR expression both in vitro and in vivo, and that the mechanism involves post-transcriptional stabilization of uPAR mRNA by reciprocal interaction of phosphoglycerate kinase (PGK) and heterogeneous nuclear ribonucleoprotein C (hnRNPC) with uPAR mRNA coding region and 3' untranslated region determinants, respectively. The process involves tyrosine phosphorylation of PGK and hnRNPC. uPA(-/-) mice failed to induce uPAR expression after LPS treatment. In these mice, LPS treatment failed to alter the binding of PGK and hnRNPC protein with uPAR mRNA due to lack of tyrosine phosphorylation.Our study shows that induction of LPS-mediated uPAR expression is mediated through tyrosine phosphorylation of PGK and hnRNPC. This involves expression of uPA as an obligate intermediary.

Rationale: Surfactant protein D (SP-D) is a member of the collectin family of soluble, innate, host defense molecules with demonstrated immunomodulatory properties in vitro. Constitutive absence of SP-D in mice is associated with lung inflammation, alteration in surfactant lipid homeostasis, and increased oxidative-nitrative stress. Objectives: To test the hypothesis that SP-D would protect against acute lung injury from hyperoxia in vivo. Methods: Transgenic mice overexpressing rat SP-D constitutively (SP-D OE) or conditionally via regulation with doxycycline (SP-D Dox-on) were subjected to continuous hyperoxic challenge for up to 14 days. Measurements and Main Results: Compared with littermate control mice (wild-type [WT]), SP-D OE mice exposed to 80% O2 demonstrated substantially increased survival accompanied by significant reductions in wet to dry lung ratios and bronchoalveolar lavage (BAL) protein. Although SP-D OE and WT mice exhibited a twofold increase in total BAL cells and neutrophilia in response to hyperoxia, the SP-D OE group had lower levels of BAL proinflammatory cytokines and chemokines, including IL-6, tumor necrosis factor-α, and monocyte chemotactic protein-1; increased mRNA levels of the transcription factor NF-E2 related factor-2 (NRF-2) and phase 2 antioxidants hemoxygenase-1 (HO-1), glutathione peroxidase-2 (GPx-2) and NAD(P)H quinone oxidoreductase-1 (Nqo-1); and decreases in lung tissue thiobarbituric acid–reactive substances. As proof of principle, the protective role of SP-D on hyperoxic injury was confirmed as SP-D Dox-on mice exposed to 85% O2 demonstrated increased mortality upon withdrawal of doxycycline. Conclusions: Local expression of SP-D protects against hyperoxic lung injury through modulation of proinflammatory cytokines and antioxidant enzymatic scavenger systems.

Preceding infections and anti-ganglioside antibodies were assessed among 80 Guillain–Barré syndrome (GBS) patients and 125 controls. Previous infections were more frequent among GBS patients than among controls (p

Surfactant protein D (SP-D), a member of the collectin superfamily, modulates pulmonary inflammatory responses and innate immunity. Disruption of the SP-D gene in mice induces peribronchiolar inflammation, accumulation of large, foamy macrophages, increased bronchoalveolar lavage (BAL) phospholipid, and pulmonary emphysema. We hypothesized that absence of SP-D aggravates hyperoxia-induced injury. To test this, SP-D-deficient (SP-D−/−) and wild-type (SP-D+/+) mice were exposed to 80% or 21% oxygen. Paradoxically, during 14 days of hyperoxia, SP-D−/−mice had 100% survival vs. 30% in SP-D+/+. The survival advantage in SP-D−/−mice was accompanied by lower histopathological injury scores at days 5 and 14, although total BAL cells (8.2 ± 1.4 × 105in SP-D−/−vs. 4.04 ± 0.25 × 105in SP-D+/+mice) and neutrophils (1.2 ± 0.4 × 105vs. 0.03 ± 0.02 × 105in SP-D−/−and SP-D+/+, respectively) were increased. In addition, BAL protein and lung-to-body weight ratios were similarly elevated in both groups after 3, 5, and 14 days of continuous exposure. Biochemically, in contrast to SP-D+/+, SP-D−/−mice had higher levels of surfactant phospholipid and SP-B at baseline and 5 days after hyperoxia accompanied by a preservation of surfactant biophysical activity. From a multiplex assay of nine cytokines, we found elevated levels of IL-13 in BAL fluid of normoxic SP-D−/−mice compared with SP-D+/+. We conclude that the resistance of SP-D-deficient mice to hyperoxia reflects homeostatic changes in the SP-D−/−phenotype involving both phospholipid and SP-B-mediated induced resistance of surfactant to inactivation as well as changes in the immunomodulatory BAL cytokine profile.

The biochemical mechanisms underlying the development of sensitization-induced airway hyperresponsiveness (AHR) in asthma are poorly defined. Alterations in the regulation of intracellular calcium may play an important role in its pathogenesis. We carried out this study to see the effect of sensitization with ovalbumin on membrane ion fluxes and intracellular calcium in a guinea pig model.Airway reactivity to inhaled histamine was measured initially and after sensitization with ovalbumin in 28 guineapigs. Intracellular calcium [Ca(2+)]i was measured in tracheal smooth muscle cells and peripheral leukocytes using fluorescent dye FURA 2AM. Calcium and sodium ion influx across the cell membrane was measured in leukocytes. Ouabain-sensitive Rubidium ((86)Rb) influx was measured in tracheal smooth muscles cells. The activities of Na(+), K(+) ATPase and Ca(2+) ATPase were measured in tracheal smooth muscle cells. Lipid peroxides were measured in plasma.Airway responsiveness was significantly (P0.001) increased after sensitization along with an increase in [Ca2+]i levels in leukocytes and tracheal smooth muscle cells, higher rates of (45)Ca and (22)Na influx in leukocytes and higher (86)Rb influx rates in tracheal smooth muscle cells, and increased levels of lipid peroxides in plasma.In guineapig model of asthma sensitization to allergen increased the membrane permeability to calcium and sodium, and intracellular calcium levels. These alterations may play a role in the pathogenesis of airway hyper-responsiveness following sensitization.

The effect of dietary supplementation with Vitamin E was studied in sensitized guinea pigs. After measurement of baseline airway reactivity and sensitization with ovalbumin, the animals were randomized into two groups: Group A, on a commercial feed and Group B, on dietary supplementation with oral Vitamin E (0.7 IU/kg). These were challenged with inhaled ovalbumin after 4 weeks. The following outcomes were studied: airway responses to ovalbumin inhalation, airway reactivity, sodium and calcium ion influx in isolated tracheal cells, Na+ K+ ATPase and Ca2+ ATPase activity in tracheal homogenate and plasma malonaldehyde. Sensitization increased airway reactivity in Group A but not in Group B. The tracheal cells of animals in Group B showed significantly lower rates of 45Ca and 22Na influx and lower activities of tracheal Na+ K+ ATPase and Ca2+ ATPase as compared to Group A. Plasma malonaldehyde was similar between two groups. We concluded that Vitamin E suppresses the increase in airway reactivity following sensitization and has membrane stabilizing actions.

Campylobacter species are known as agents of enteritis worldwide. However, rural community-based studies on Campylobacter infections are lacking. We carried out a prospective case-control study from July to December 2002 to investigate the prevalence and socio-epidemiological determinants of Campylobacter infection in a rural community in north India and the drug resistance of Campylobacter strains isolated from the community. Stool specimens from 348 subjects with diarrhoea and 351 age- and gender-matched asymptomatic controls were cultured for Campylobacter, Salmonella and Shigella. All Campylobacter strains were identified and tested for antibiotic susceptibility. Campylobacter species were isolated from 47 (13.5%) subjects with diarrhoea and 2 (0.6%) asymptomatic controls respectively (P

Based on culture and serological evidence, a strong association between Campylobacter jejuni infection and Gullain-Barre syndrome (GBS) has been established. However, culture underestimates C. jejuni infection in GBS and the specificity of serology remains uncertain. Thus, a direct sensitive detection method for recent C. jejuni infection is required. We used the PCR technique in GBS patients to assess its role in the diagnosis of C. jejuni infection. From June 2001 to March 2003, stool specimens from 42 patients with GBS and an equal number of age- and gender-matched healthy controls were analysed for C. jejuni infection by culture and PCR. Gullain-Barre syndrome subtypes were classified by clinical and electrophysiological studies. Of the GBS patients, two (4.8%) and eight (19%) were positive by culture and PCR, respectively, and the difference was significant (P < 0.05). None of the controls were positive for C. jejuni by culture or PCR. All C. jejuni-positive GBS patients had axonal degeneration with or without sensory involvement. The incidence of C. jejuni-associated GBS cases was more frequent during summer than winter (7/19, 36.8% vs. 1/23, 4.3%, P < 0.01). Polymerase chain reaction appears to be a sensitive tool to detect preceding C. jejuni infection in GBS patients.

72 members of a pig farming community and 50 slaughtered pigs in Uttar Pradesh, India, were examined between November 2000 and June 2001 for Taenia solium infection. 27 of the human subjects (38%) had intestinal taeniasis and 7 (9.7%) had reported seizures. All 3 of the latter who were examined had neurocysticercosis. 13 of the pigs (26%) had cysticercosis. Such high prevalences indicate the need for detailed assessment of the disease burden in this community.

Introduction: Career is the progress and actions taken by a person throughout lifetime, especially those related to that person′s occupation and are often composed of the jobs held, titles earned and work accomplished over a long period of time. It plays a very important role in the success of once life. Aim: The aim was to compare the career satisfaction among medical and dental graduates in a private institution in Indore city, Madhya Pradesh. Materials and Methods: The study included a total of 100 medical graduates and 100 dental graduates and was carried out using a self-administered questionnaire. Chi-square test was performed for statistical analysis. Results: In medical profession, it was found that majority (87%) of the graduates were satisfied with their career. Majority (88%) of the graduates believed that their profession had a bright future 10 years from now and majority (74%) recommended joining medical profession as a safe and bright career alternative. On the contrary, in dental profession, it was found that more than half (53%) of the graduates were unsatisfied with their career. More than 50% of graduates believed that dental profession did not have a bright future 10 years from now and majority (66%) of the graduates recommended not to join dental profession. The differences were found to be significantly associated between the two groups (P < 0.05). Conclusion: The dental graduates were found to be dissatisfied with their career compared with medical graduates. Better job perspectives and better placements needs to be created. Endorsement of effective policies is required.

Intravascular papillary endothelial hyperplasia (IPEH) or reactive vascular endothelial lesion is a rare benign condition and is also known as Masson’s hemangioma. It may appear as a primary or pure form developing in a distended vessel, or it can be associated with hemangiomas, pyogenic granulomas, or lymphagiomas. It is usually confined to the lumen of preexisting vessels or vascular malformations. Nearly all the lesions are intimately associated with a thrombus in various stages of organization. The main significance of IPEH is its clinical and histological resemblance to soft-tissue sarcoma and possible misinterpretation as such. We hereby report a case of IPEH clinically and radiologically misdiagnosed as soft tissue sarcoma, in a 47-year-old man, presenting as a soft tissue mass in the left scapular region.

Introduction: Chemical substances used for prevention of dental caries are known to have many side-effects. Thus, natural products should be explored for their anticaries action. Objectives: To prepare 5% and 20% concentrations of ethanolic and water extracts of guava leaves and to assess their activity against Lactobacillus acidophilus. Materials and Methods: In vitro experimental study was conducted in Department of Biosciences. Ethanolic and water extracts of guava leaves were prepared using Soxhlet extractor. Two concentrations 5% and 20% weight/volume of both extracts were prepared. Test organism L. acidophilus Microbial Type Culture Collection 447 was obtained in lyophillized form. After revival in nutrient broth, bacteria were grown on Lactobacilli de Man, Rogosa, Sharpe agar for further experiment. Antimicrobial testing of extracts was done using Agar well-diffusion method. Ten plates each were prepared for both extracts. Chlorhexidine (0.2%) served as a positive control and distilled water as a negative control. Results: Mean zone of inhibition produced by 5% and 20% ethanolic extract was 11.2 mm and 14.1 mm respectively and by 5% and 20% water extract was 1.6 mm and 5.1 mm respectively. Statistical analysis of results using one-way ANOVA and post-hoc Tukey′s test revealed that activity of 5% ethanolic extract and 5%, 20% water extract was significantly less than that of 0.2% chlorhexidine. There was no statistical difference in efficacy of 20% ethanolic extract of guava and 0.2% chlorhexidine (P = 0.270). Conclusion: Ethanolic and water extracts of guava leaves possess antibacterial activity against L. acidophilus with 20% ethanolic extract being as efficacious as 0.2% chlorhexidine.

The present study was carried out to examine the relationship between intracellular free calcium ion concentrations and its regulatory enzymes, sodium potassium adenosine triphosphatase (Na(+),K(+)-ATPase) and calcium adenosine triphosphatase (Ca(2+)-ATPase), with airway reactivity to inhaled histamine in guinea pigs. Forty-nine guinea pigs were included in this study. Of these, 34 animals responded to histamine bronchoprovocation challenge in vivo with a greater than 35% fall in specific airways conductance and were labeled as "reactive," and the remaining 15 were "nonreactive." The dose of histamine producing a 35% fall in specific airways conductance was labeled as ED(35) SGaw. The animals were then sacrificed, and the following biochemical measurements were carried out: intracellular free calcium ion concentrations [Ca(2+)](i) in leukocytes and isolated tracheal smooth muscle cells, activities of Na(+),K(+)-ATPase and Ca(2+)-ATPase in tracheal homogenate, and plasma levels of lysophosphatidylcholine (LPC). Reactive guinea pigs showed significantly higher [Ca(2+)](i) and Na(+),K(+)-ATPase and Ca(2+)-ATPase activities. Airway reactivity (ED(35) SGaw) had significant negative correlation with [Ca(2+)](i), with activities of each of the ATPases and with plasma lysophosphatidylcholine. It is concluded that the level of [Ca(2+)](i) is an important determinant of airway reactivity. Intracellular calcium levels modulate airway response to histamine with higher levels being associated with greater reactivity.

Background During pregnancy asthma may remain stable, improve or worsen. The factors underlying the deleterious effect of pregnancy on asthma remain unknown. Oxytocin is a neurohypophyseal protein that regulates a number of central and peripheral responses such as uterine contractions and milk ejection. Additional evidence suggests that oxytocin regulates inflammatory processes in other tissues given the ubiquitous expression of the oxytocin receptor. The purpose of this study was to define the role of oxytocin in modulating human airway smooth muscle (HASMCs) function in the presence and absence of IL-13 and TNFα, cytokines known to be important in asthma. Method Expression of oxytocin receptor in cultured HASMCs was performed by real time PCR and flow cytomery assays. Responses to oxytocin was assessed by fluorimetry to detect calcium signals while isolated tracheal rings and precision cut lung slices (PCLS) were used to measure contractile responses. Finally, ELISA was used to compare oxytocin levels in the bronchoalveloar lavage (BAL) samples from healthy subjects and those with asthma. Results PCR analysis demonstrates that OXTR is expressed in HASMCs under basal conditions and that both interleukin (IL)-13 and tumor necrosis factor (TNFα) stimulate a time-dependent increase in OXTR expression at 6 and 18 hr. Additionally, oxytocin increases cytosolic calcium levels in fura-2-loaded HASMCs that were enhanced in cells treated for 24 hr with IL-13. Interestingly, TNFα had little effect on oxytocin-induced calcium response despite increasing receptor expression. Using isolated murine tracheal rings and PCLS, oxytocin also promoted force generation and airway narrowing. Further, oxytocin levels are detectable in bronchoalveolar lavage (BAL) fluid derived from healthy subjects as well as from those with asthma. Conclusion Taken together, we show that cytokines modulate the expression of functional oxytocin receptors in HASMCs suggesting a potential role for inflammation-induced changes in oxytocin receptor signaling in the regulation of airway hyper-responsiveness in asthma.