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Estrogen Receptor-β (ER-β), a tumor-suppressor in prostate cancer, is epigenetically repressed by hypermethylation of its promoter. DNA-methyltransferases (DNMTs), which catalyze the transfer of methyl-groups to CpG islands of gene promoters, are overactive in cancers and can be inhibited by DNMT-inhibitors to re-express the tumor suppressors. The FDA-approved nucleoside DNMT-inhibitors like 5-Azacytidine and 5-Aza-deoxycytidine carry notable concerns due to their off-target toxicity, therefore non-nucleoside DNMT inhibitors are desirable for prolonged epigenetic therapy. Disulfiram (DSF), an antabuse drug, inhibits DNMT and prevents proliferation of cells in prostate and other cancers, plausibly through the re-expression of tumor suppressors like ER-β. To increase the DNMT-inhibitory activity of DSF, its chemical scaffold was optimized and compound-339 was discovered as a doubly potent DSF-derivative with similar off-target toxicity. It potently and selectively inhibited cell proliferation of prostate cancer (PC3/DU145) cells in comparison to normal (non-cancer) cells by promoting cell-cycle arrest and apoptosis, accompanied with inhibition of total DNMT activity, and re-expression of ER-β (mRNA/protein). Bisulfite-sequencing of ER-β promoter revealed that compound-339 demethylated CpG sites more efficaciously than DSF, restoring near-normal methylation status of ER-β promoter. Compound-339 docked on to the MTase domain of DNMT1 with half the energy of DSF. In xenograft mice-model, the tumor volume regressed by 24% and 50% after treatment with DSF and compound-339, respectively, with increase in ER-β expression. Apparently both compounds inhibit prostate cancer cell proliferation by re-expressing the epigenetically repressed tumor-suppressor ER-β through inhibition of DNMT activity. Compound-339 presents a new lead for further study as an anti-prostate cancer agent. © 2015 Wiley Periodicals, Inc.

Background: Traditional approach to predicting trauma-related mortality utilizes scores based on anatomical, physiological, or a combination of both types of criteria. However, several factors are reported in literature to predict mortality independent of severity scores. The objectives of the study were to identify predictors of 1 year mortality and determine their magnitude and significance of association in a resource constrained scenario. Materials and Methods: Prospective observational study enrolled 572 patients. Information regarding factors known to affect mortality was recorded. Other factors which may be important in resource constrained settings were also included. This included referral from a peripheral hospital, number of surgeries performed on the patient, and his socioeconomic status (below poverty line (BPL) card). Patients were followed till death or upto a period of 1year. Logistic regression, actuarial survival analysis, and Cox proportionate hazard model were used to identify predictors of 1year mortality. Limited estimate of external validity of the study was obtained using bootstrapping. Results: Age of patient, Injury Severity Score (ISS), abnormal activated partial thromboplastin time (APTT), Glasgow Coma Scale (GCS) score at admission, and systolic blood pressure (BP) at admission were found to significantly predict mortality on logistic regression and Cox proportionate hazard models. Abnormal respiratory rate at admission was found to significantly predict mortality in the logistic regression model, but no such association was seen in Cox proportionate hazard model. Bootstrapping of the logistic regression model and Cox proportionate hazard model provide us with a set of factors common to both the models. These were age, ISS, APTT, and GCS score at admission. Conclusion: Multivariate analysis (logistic and Cox proportionate hazard analysis) and subsequent bootstrapping provide us with a set of factors which may be considered as valid predictors universally. However, since bootstrapping only provides limited estimates of external validity, there is a need to test these factors against the well accepted requirements of external validity namely population, ecological, and temporal validity.

Readily accessible pyrazolylchalcones (III) suffer an iodine-mediated cyclization in DMSO leading to the title compounds (IV) in almost quantitative yield.

In the last few years Digital controllers are widely used because of their excellent qualities of simplicity, effectiveness and they are applicable for broad class of systems. At present their involvement in industrial processes is more than 95%. They generally relate to accuracy, relative stability and speed of the response so as to yield an optimal control system for the given purpose. In this paper, the control of gimbal has been stated for the defence application mounted on the tank. A gimbal is a mechanical arrangement, which is used to isolate the payload from the moving vehicle. This is particularly used in line of stabilization systems and inertial guidance systems [1]. These systems require very fast and accurate control within a particular bandwidth. In the present problem, the digital controller is implemented using frequency domain approach in order to control the rate of motion of platform, meeting the stringent requirements of disturbance attenuation and robust stability.

1-Azido-2-nitro-2-azapropane (1) was synthesized in high yield from 1-chloro-2-nitro-2-azapropane and sodium azide. 1-Nitrotetrazolato-2-nitro-2-azapropane (2) was synthesized in high yield from 1-chloro-2-nitro-2-azapropane and silver nitrotetrazolate. The highly energetic new compounds (1 and 2) were characterized using vibrational (IR and Raman) and multinuclear NMR spectroscopy (1H, 13C, 14N), elemental analysis and low-temperature single crystal X-ray diffraction. 1-Azido-2-nitro-2-azapropane (1) represents a covalently bound liquid energetic material which contains both a nitramine unit and an azide group in the molecule. 1-Nitrotetrazolato-2-nitro-2-azapropane (2) is a covalently bound room-temperature stable solid which contains a nitramine group and a nitrotetrazolate ring unit in the molecule. Compounds 1 and 2 are hydrolytically stable at ambient conditions. The impact sensitivity of compound 1 is very high (

The aim of this study was to describe the incidence of cardiac chamber collapse assessed by echocardiography and explore possible mechanisms in a clinical population of 116 patients with pleural effusion in the absence of pericardial effusion. We found that the frequency of chamber collapse was 18% in patients with pleural effusion in the absence of pericardial effusion, thus cardiac chamber collapse occurs in patients with pleural effusion. (ECHOCARDIOGRAPHY, Volume 20, April 2003)

We report a sporadic case of progressive osseous heteroplasia (POH) in a 10-year-old male child who developed progressive ossification of the skin and deep connective tissue. The condition needs to be distinguished from other causes of childhood heterotopic ossification, such as fibrodysplasia ossificans progressiva, pseudohypoparathyroidism, and pseudopseudohypoparathyroidism. The cause of POH is an inactivating GNAS1 (guanine nucleotide-binding protein alpha-stimulating activity polypeptide 1) mutation caused only by paternal inheritance of the mutant allele. Most cases are sporadic and only 2 instances of familial transmission have been documented, suggesting an autosomal dominant mode of inheritance with possible somatic mosaicism. The condition is associated with progressive superficial to deep ossification, progressive restriction of range of motion, bleak prognosis, and recurrence if excised.

Dietary consumption of phytoestrogens like genistein has been linked with lower incidence of prostate cancer. The estradiol-like benzopyran core of genistein confers estrogen receptor-β (ER-β) selectivity that imparts weak anti-proliferative activity against prostate cancer cells. DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran (BP), a SERM designed with benzopyran core, targeted androgen independent prostate cancer (PC-3) cells 14-times more potently than genistein, ~25% more efficiently than tamoxifen and 6.5-times more actively than ICI-182780, without forfeiting significant specificity in comparison to genistein. BP increased apoptosis (annexin-V and TUNEL labeling), arrested cell cycle, and significantly increased caspase-3 activity along with mRNA expressions of estrogen receptor (ER)-β and FasL (qPCR) in PC-3 cells. In classical ERE-luc reporter assay BP behaved as a potent ER-α antagonist and ER-β agonist. Accordingly, it decreased expression of ER-α target PS2 (P

The predominant estrogen-receptor (ER)-β signaling in normal prostate is countered by increased ER-α signaling in prostate cancer (CaP), which in association with androgen-receptor (AR) signaling results in pathogenesis of the disease. However CaP treatments mostly target AR signaling which is initially effective but eventually leads to androgen resistance, hence simultaneous targeting of ERs has been proposed. A novel series of molecules were designed with multiple sex-steroid receptor modulating capabilities by coalescing the pharmacophores of known anti-CaP molecules that act via modulation of ER(α/β) and/or AR, viz. 3,3′diindolylmethane (DIM), mifepristone, toremifene, tamoxifen and raloxifene. N,N-diethyl-4-((2-(4-methoxyphenyl)-1H-indol-3-yl)methyl) aniline (DIMA) was identified as the most promising structure of this new series. DIMA increased annexin-V labelling, cell-cycle arrest and caspase-3 activity, and decreased expression of AR and prostate specific antigen in LNCaP cells, in vitro. Concurrently, DIMA increased ER-β, p21 and p27 protein levels in LNCaP cells and exhibited ∼ 5 times more selective binding for ER-β than ER-α, in comparison to raloxifene. DIMA exhibited a dose-dependent ER-β agonism and ER-α antagonism in classical gene reporter assay and decreased hTERT (catalytic subunit of telomerase) transcript levels in LNCaP at 3.0 μM (P < 0.05). DIMA also dose-dependently decreased telomerase enzyme activity in prostate cancer cells.more » It is thus concluded that DIMA acts as a multi-steroid receptor modulator and effectively inhibits proliferation of prostate cancer cells through ER-β mediated telomerase inhibition, by countering actions of ER-α and AR. Its unique molecular design can serve as a lead structure for generation of potent agents against endocrine malignancies like the CaP.« less

To increase the security of messages sent over internet steganography is used. Various steganography techniques have been proposed so far. Least Significant Bit steganography is one such technique in which least significant bit of pixels of the image is replaced with data bits. This approach has the advantage that it is simplest one to understand, easy to implement and results in stego-images that contain embedded data as hidden. The disadvantage of Least Significant Bit is that it is vulnerable to steganalysis and is not secure at all. So as to make it more secure, the least significant bit algorithm is modified to work in different way. This proposed approach simply does not pick up least significant bits of pixel in a sequence but is combined with midpoint circle approach to choose which pixels are used to hide message. The goals of this paper are to present theoretic analysis of Least Significant Bit approach and to propose an advanced LSB embedding scheme that exhibits not only the advantages of LSB but also provides additional level of security. The scheme breaks the regular pattern of LSB, resulting in increased difficulty of steganalysis and thereby raising the security level.

A new series of 2-(alkoxy(hydroxy)phosphoryloxy)ethyl dialkylcarbodithioate derivatives was synthesized and evaluated against endocrine related cancers, acting via modulation of Akt-pathway. Eighteen compounds were active at 7.24–100 μM against MDA-MB-231 or MCF-7 cell lines of breast cancer. Three compounds ( 14 , 18 and 22 ) were active against MCF-7 cells at IC 50 significantly better than miltefosine and most of the compounds were less toxic towards non-cancer cell lines, HEK-293. On the other hand, twelve compounds exhibited cell growth inhibiting activity against prostate cancer cell lines, either PC-3 or DU-145 at 14.69–95.20 μM. While nine of these were active against both cell lines. The most promising compounds 14 and 18 were about two and five fold more active than miltefosine against DU-145 and MCF-7 cell lines respectively and significantly down regulated phospho-Akt. Possibly anti-cancer and pro-apoptotic activity was mostly due to blockade of Akt-pathway.

STUDY QUESTION: Can a specifically acting synthetic spermicide (DSE-37) be combined with a natural microbicide (saponins) for safe prophylactic contraception? SUMMARY ANSWER: A 1:1 (w/w) combination of DSE-37 and Sapindus saponins can target sperm and Trichomonas vaginalis precisely without any noticeable off-target effects on somatic cells at effective concentrations. WHAT IS KNOWN ALREADY: Broad-spectrum vaginal agents like nonoxynol-9 (N-9) and cellulose sulfate have failed clinically as microbicides due to non-specific off-target effects whereas agents that specifically target retroviruses have shown promise in clinical trials. DSE-37 and Sapindus saponins respectively specifically target human sperm and T. vaginalis in vitro. STUDY DESIGN SIZE DURATION: A comprehensive study of efficacy and safety was undertaken using in vitro (human cells) and in vivo (rabbit) models. The 1:1 combination of DSE-37 and Sapindus saponins was based on the in vitro spermicidal and anti-Trichomonal activities of the two components. N-9 the spermicide in clinical use served as reference control. Free sperm thiols were fluorescently glinted to reveal differences in the targets of the test agents. PARTICIPANTS/MATERIALS SETTING METHODS: On/off-target effects were evaluated in vitro against human sperm T. vaginalis HeLa Vk2/E6E7 End1/E6E7 and Lactobacillus jensenii using standard assays of drug susceptibility cell viability flow cytometric assessment of cell apoptosis and qPCR for expression of pro-inflammatory cytokine mRNAs. The spermicidal effect was also recorded live and free thiols on sperm were fluorescently visualized using a commercial kit. In vivo contraceptive efficacy (pregnancy/fertility rates) and safety (vaginal histopathology and in situ immune-labeling of inflammation markers VCAM-1 E-selectin and NFkB) were evaluated in rabbits. MAIN RESULTS AND THE ROLE OF CHANCE: A 0.003% drug combination containing 0.0015% each of DSE-37 and Sapindus saponins in physiological saline irreversibly immobilized 100% human sperm in approximately 30 s and eliminated 100% T. vaginalis in 24 h without causing any detectable toxicity to human cervical (HeLa) cells and Lactobacilli in 24-48 h in vitro. N-9 at 0.003% exhibited lower microbicidal activity against Trichomonas but failed in spermicidal assays while causing severe toxicity to HeLa cells and Lactobacilli in 12-24 h. The combination of DSE-37 and Sapindus saponins completely prevented pregnancy in rabbits at a vaginal dose of 20 mg (1% in K-Y Jelly) while application of 5% combination in K-Y Jelly for 4 consecutive days caused negligible alterations in epithelial lining of rabbit vagina with only minor changes in levels of inflammation markers. N-9 at a 20 mg vaginal dose prevented pregnancy in 33% animals and a 4-day repeat application of 2% N-9 gel caused severe local toxicity to vaginal epithelium with molecular expression of acute inflammation markers. LIMITATIONS REASONS FOR CAUTION: The number of animals used for the in vivo efficacy study was limited by the approval of the animal ethics committee. WIDER IMPLICATIONS OF THE FINDINGS: Anti-Trichomonal contraceptives with specifically acting synthetic component and clinically-proven safe natural component may define a new concept in empowering women to control their fertility and reproductive health. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by CSIR-Network Project PROGRAM (BSC0101) and partly by the Ministry of Health and Family Welfare Government of India (GAP0001). The funding agencies did not play any role in this study and none of the authors had any competing interest(s).

Unlike somatic cells, sperm have several-fold more available-thiols that are susceptible to redox-active agents. The present study explains the mechanism behind the instant sperm-immobilizing and trichomonacidal activities of pyrrolidinium pyrrolidine-1-carbodithioate (PPC), a novel thiol agent rationally created for prophylactic contraception by minor chemical modifications of some known thiol drugs. PPC, and its three derivatives (with potential active-site blocked by alkylation), were synthesized and evaluated against live human sperm and metronidazole-susceptible and resistant Trichomonas vaginalis, in vitro. Sperm hexokinase activity was evaluated by coupled enzyme assay. PPC irreversibly immobilized 100% human sperm in ∼30 seconds and totally eliminated Trichomonas vaginalis more efficiently than nonoxynol-9 and metronidazole. It significantly inhibited (P

Fruit extract of Cupressus sempervirens (CS), which is used traditionally to treat Benign Prostatic Hyperplasia (BPH)-like urinary symptoms in patients, was scientifically validated for anti-BPH activity. The ethanolic fruit extract of CS inhibited proliferation of human BPH-stromal cells and the activity was localized to its chloroform-soluble, diterpene-rich fraction. Eight major diterpenes isolated from this fraction exhibited moderate to potent activity and the most active diterpene (labda-8(17),12,14-trien-19-oic acid) exhibited an IC50 of 37.5 μM (antiproliferative activity against human BPH-stromal cells). It significantly inhibited activation (phosphorylation) of Stat-3 in BPH-stromal cells and prevented transactivation of androgen sensitive KLK3/PSA and TMPRSS2 genes in LNCaP cells. Labda-8(17),12,14-trien-19-oic acid-rich CS fraction prevented prostatic hyperplasia in rat model and caused TUNEL labeling of stromal cells with lower expressions of IGF-I, TGF-ß and PCNA, and bcl-2/bax ratio. Human BPH tissues exhibited precise lowering of stromal component after incubation in labda-8(17),12,14-trien-19-oic acid, ex vivo. We conclude that labda-8(17),12,14-trien-19-oic acid contained in CS exhibits anti-BPH activity through inhibition of stromal proliferation and suppression of androgen action in the prostate, presenting a unique lead structure for further optimization of anti-BPH activity.

A series of novel symmetrically (II) as well as unsymmetrically (VI) diaryl-substituted 1H-naphtho[1,2-e][1,3]oxazines are synthesized and screened for their antimicrobial and cytotoxic activities.

With increased environment dynamism, firm agility has grabbed the attention of both researchers and practitioners. Firm agility has been conceptualised as dynamic capability comprising of sensing capability, responding capability and alignment between sensing and responding capability. Agility has often been compared with absorptive capacity, another dynamic capability. However, these comparisons lack depth. We compare and contrast agility with absorptive capacity. For this, we trace back the evolution of the two concepts which leads us to the emergence of convergence between the two. We then compare the two at construct level. We show how the sensing and responding components of agility are similar to potential and realised absorptive capacity components of Absorptive capacity. Through a review of alignment literature, we propose that agility could be a special case of absorptive capacity where potential and realised absorptive capacities are aligned for superior firm performance in dynamic environment. This convergence between agility and absorptive capacity could enrich dynamic capabilities frameworks for a dynamic environment.

A series of new 1,3-disubstituted-1H-naphtho[1,2-e][1,3]oxazines (3 and 7) was synthesized in good yields and the structure was determined with the help of NMR, 2D-NMR, HRMS studies and X-ray crystallography. These compounds were tested in vitro for their antibacterial activity against Gram-positive and Gram-negative bacteria and as well as for antifungal activity. The compounds 3c, 3e, 7a, 7d and 7k showed significant antibacterial activity and 7l showed moderate antifungal activity. The cytotoxicity of 1,3-disubstituted-1H-naphtho[1,2-e][1,3]oxazines showed that 3e and 7e are more effective against breast, lung and colon cell proliferation.

Metronidazole, the U.S. Food and Drug Administration-approved drug against trichomoniasis, is nonspermicidal and thus cannot offer pregnancy protection when used vaginally. Furthermore, increasing resistance of Trichomonas vaginalis to 5-nitro-imidazoles is a cause for serious concern. On the other hand, the vaginal spermicide nonoxynol-9 (N-9) does not protect against sexually transmitted diseases and HIV in clinical situations but may in fact increase their incidence due to its nonspecific, surfactant action. We therefore designed dually active, nonsurfactant molecules that were capable of killing Trichomonas vaginalis (both metronidazole-susceptible and -resistant strains) and irreversibly inactivating 100% human sperm at doses that were noncytotoxic to human cervical epithelial (HeLa) cells and vaginal microflora (lactobacilli) in vitro . Anaerobic energy metabolism, cell motility, and defense against reactive oxygen species, which are key to survival of both sperm and Trichomonas in the host after intravaginal inoculation, depend crucially on availability of free thiols. Consequently, molecules were designed with carbodithioic acid moiety as the major pharmacophore, and chemical variations were incorporated to provide high excess of reactive thiols for interacting with accessible thiols on sperm and Trichomonas . We report here the in vitro activities, structure-activity relationships, and safety profiles of these spermicidal antitrichomonas agents, the most promising of which was more effective than N-9 (the OTC spermicide) in inactivating human sperm and more efficacious than metronidazole in killing Trichomonas vaginalis (including metronidazole-resistant strain). It also significantly reduced the available free thiols on human sperm and inhibited the cytoadherence of Trichomonas on HeLa cells. Experimentally in vitro , the new compounds appeared to be safer than N-9 for vaginal use.

Hepatitis C virus (HCV) has emerged as a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. Genotyping and assessment of the viral load in HCV patients is important for designing the therapeutic strategies. Thus the present study was designed to determine the distribution pattern of HCV genotypes in chronic hepatitis patients and their association with the viral load and biochemical profiles.Seventy one HCV RNA positive patients were included in the study. HCV genotyping was carried out by restriction fragment length polymorphism (RFLP) followed by the direct sequencing of the core region. Viral load estimation was carried out by Taqman real time PCR system.Sixty three per cent (45/71) of cases were infected with genotype 3 followed by genotype 1 in 30.98 per cent (22/71) and genotype 2 in 5.63 per cent (4/71) of cases. Genotype 1 was associated with a significantly (P0.001) higher viral load as compared to genotypes 3 and 2. There was no significant difference seen in the biochemical profile between the three groups of genotypes except in the levels of SGOT. The commonest mode of transmission was parenteral which accounted for 68 per cent of all the infected cases.The present study revealed that HCV genotype 3 and 1 accounted for approximately 95 per cent of the HCV infection in Delhi and surrounding areas. Also two atypical subtypes like 3i and 3f were identified. Genotype 1 was associated with more severity of liver disease as compared to genotypes 3 and 2 as assessed by viral load.

Rotavirus gastroenteritis is a major cause of severe dehydrating diarrhea in children worldwide. Rotavirus G and P genotyping is essential for epidemiological surveillance and for better formulation of candidate rotavirus vaccines. Out of 862 diarrheal stool samples collected from hospitalized children aged2 years during February 2005 - March 2007, 318 (36.9%) were positive for rotavirus by ELISA. G and P genotyping was performed on 100 randomly selected positive samples using a seminested multiplex RT-PCR assay. The result of G genotyping indicates G1 (60%) was the most predominant VP7 type, followed by G2 (16%), G9 (8%) and G3 (3%). Two cases of G12 genotype were also observed. P genotypes identified were P[8] (40%) followed by P[4] (26%) and P[6] (17%). The most common G-P combinations were G1P[8] (26%), followed by G1P[4] and G1P[6]. Mixed infection involved 28% of strains. In this study the G1 and P[8] genotypes were the leading G and P types. Two cases with G12 genotype were also observed during the study.

background: We have attempted to identify structural, physiological and other targets on human sperm vulnerable to the spermicidal action of two novel series of non-detergent molecules, reported to irreversibly immobilize human sperm in ,30 s, apparently without disrupting plasma membrane. methods: Three sperm samples were studied. Scanning and transmission electron microscopy were used to assess structural aberrations of sperm membrane; plasma membrane potential and intracellular pH measurements (fluorometric) were used to detect changes in sperm physiology; reactive oxygen species (ROS, fluorometric) and superoxide dismutase activity (colorimetric) were indicators of oxidative stress; and sperm dynein ATPase activity demonstrated alterations in motor energy potential, in response to spermicide treatment. Post-ejaculation tyrosine phosphorylation of human sperm proteins (immunoblotting) was a marker for functional integrity. results: Disulfide esters of carbothioic acid (DSE compounds) caused complete sperm attenuation at � 0.002% concentration with hyper-polarization of sperm membrane potential (P , 0.001), intracellular alkalinization (P , 0.01), ROS generation (P , 0.05) and no apparent effect on sperm (n ¼ 150) membrane structure. Isoxazolecarbaldehyde compounds required � 0.03% for spermicidal action and caused disrupted outer acrosomal membrane structure, depolarization of membrane potential (P , 0.001), intracellular acidification (P , 0.01) and ROS generation (P , 0.01). Detergent [nonoxynol-9 (N-9)] action was sustainable at � 0.05% and involved complete breakdown of structural and physiological membrane integrity with ROS generation (P , 0.001). All spermicides caused functional attenuation of sperm without inhibiting motor energetics. Unlike N-9, DSE-37 (vaginal dose, 200 mg) completely inhibited pregnancy in rats and vaginal epithelium was unchanged (24 h,10 mg). conclusions: The study reveals a unique mechanism of action for DSE spermicides. DSE-37 holds promise as a safe vaginal

Combination of dietary phytoestrogens with diverse molecular mechanisms may enhance their anticancer efficacy at physiological concentrations, as evidenced in epidemiological studies. A select combination of three dietary phytoestrogens containing 8.33 μM each of genistein (G), quercetin (Q) and biochanin A (B) was found to be more potent in inhibiting the growth of androgen-responsive prostate cancer cells (LNCaP) as well as DU-145 and PC-3 prostate cancer cells in vitro than either 25 μM of G, B or Q or 12.5+12.5 μM of G+Q, Q+B or G+B. Subsequent mechanistic studies in PC-3 cells indicated that the action of phytoestrogens was mediated both through estrogen receptor (ER)-dependent and ER-independent pathways as potent estrogen antagonist ICI-182780 (ICI, 5 μM) could not completely mask the synergistic anticancer effects, which were sustained appreciably in presence of ICI. G+Q+B combination was significantly more effective than individual compounds or their double combinations in increasing ER-β, bax (mRNA expression); phospho-JNK, bax (protein levels); and in decreasing bcl-2, cyclin E, c-myc (mRNA expression); phospho-AKT, phospho-ERK, bcl-2, proliferating cell nuclear antigen (protein levels) in PC-3 cells. Phytoestrogens also synergistically stimulated caspase-3 activity. Our findings suggest that selectively combining anticancer phytoestrogens could significantly increase the efficacy of individual components resulting in improved efficacy at physiologically achievable concentrations. The combination mechanism of multiple anticancer phytochemicals may be indicative of the potential of some vegetarian diet components to elicit chemopreventive effects against prostate cancer at their physiologically achievable concentrations, in vivo.

Twenty seven derivatives (2-28) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanol were synthesized and evaluated for anti-trichomonas, spermicidal and antifungal activities. Twenty six compounds were active against Trichomonas vaginalis at MIC ranging from 1-42 microM and seven compounds (9,18,19,22,24,26,28) immobilized 100% human spermatozoa at 1% concentration (w/v). Twenty three compounds (2,3,5,8-26,28) exhibited antifungal activity at 25-50 microg/mL concentration. Seven compounds (9,18,19,22,24,26,28) showed significant anti-trichomonas and spermicidal activities and also exhibited mild antifungal activity. All the compounds were highly safe towards human cervical cell line (HeLa) as shown by the cell-viability assay of HeLa cells at 200 microg/mL concentration, whereas nonoxynol-9 (N-9, the marketed spermicidal microbicide) was highly cytotoxic. Therefore, it may be concluded that introduction of the pharmacophore responsible for spermicidal activity into a proven anti-trichomonas structure may lead to a potent dual function microbicide better and safer than N-9.

Objective: The co-infection of Hepatitis B and C viruses with HIV accelerates disease progression and also has an effect on the management of patients infected with HIV. The prevalence of HIV co-infection with hepatitis viruses varies widely. This study is planned to evaluate the prevalence of HIV co-infection with Hepatitis B and C viruses in North India. Materials and Methods: A total of 1178 patients enrolled in the ART center were retrospectively analyzed for the presence of HBV and HCV on the basis of the presence of HBsAg and anti-HCV markers. Results: In patients infected with HIV, the prevalence of co-infection with HBV was 9.9% (117/1178), the prevalence of co-infection with HCV was 6.3% (74/1178) and the prevalence co-infection with both HBV and HCV was ~1% (12/1178). Discussion: The prevalence rate of HBV and HCV are increasing in patients infected with HIV. Having acquired the knowledge about the importance of such a co-infection, it is essential that all the patients infected with HIV be screened for HBV and HCV co-infection.

Background: Congenital adrenal hyperplasia (CAH) is a disorder wherein female babies are born with masculinized external genitalia characterized by hyperpigmented or fused labioscrotal tissue, a urogenital sinus, and clitoromegaly. Feminizing genitoplasty (clitoroplasty, labioplasty, and vaginoplasty) is necessary to make the patient consistent with gender identity and to ensure adequate sexual function in pubertal age. Patients and Method: We performed feminizing genitoplasty in which reduction clitoroplasty was done by a ventral approach in 6 patients of CAH, with a mean age of 3.8 years. Excessive erectile tissue was excised by giving incisions into Buck's fascia at 8 and 4 o'clock position on the clitoral shaft and Byar's flaps created from the degloved clitoral shaft were used for labial and vaginal reconstruction. The glans clitoris was left as such and anchored to proximal 1–1.5 cm clitoral shaft. Results: All patients had good cosmetic female appearance of external genitalia. In 5 patients, the clitoroplasty was done along with labioplasty and vaginal introitus exteriorization. However, in 1 patient, the vaginal confluence into urogenital sinus was high and hence only clitoral reduction as well as labioplasty was done and the urogenital sinus opening was left as such. The maximum follow-up is up to 6 years with good result. Conclusion: The reduction clitoroplasty by present approach of 8 and 4 o'clock incision into the Buck's fascia is a good option for clitoral girth and length reduction as it preserves approximately two-third of Buck's fascia with intact neuromuscular bundle and glans. Postoperatively, patients have good vascularity and sensation of the glans clitoris and acceptable cosmetic outcome. However, the long-term results are difficult to comment as no patient of the present study achieved puberty.

In the present study two types of composite were developed - Al-Al2O3 composite by direct metal oxidation (DIMOX) and by reinforcements using both ex situ and in situ approaches together by a dispersing powder mixture of Al2O3 and MnO2 in a ratio of 1:1, through stir casting route in aluminium matrix. Al-Al2O3 composites were synthesised successfully under ambient conditions and it was found that the particles increased as the holding time and the number of stirrings was increased resulting in improved mechanical properties. Generation of Al2O3 particles in the matrix was confirmed by X-ray diffraction (XRD) and energy dispersive spectroscopy (EDS) examination. Hence, oxidation, which is known as a major problem in composite preparation by liquid metallurgy route, can be used for preparation of composites and for improving the properties. In Al-Al2O3/MnO2 composites the mechanical properties as well as particle distribution improved as Al2O3 + MnO2 were introduced and also with their increasing weight percent.

Cytokines play a key role in regulation of immunity and inflammation. The aim of the study was to detect serum levels of TGF-beta, IL-10, and sTNFalphaRII in patients with type C chronic liver disease (CLD) and to correlate these with biochemical and histopathological parameters used to assess the severity of the disease. Blood samples were aseptically collected from 90 CLD patients. Cytokine levels were also followed up in 39 chronic hepatitis cases. Levels of the cytokines in 90 CLD patients were significantly higher than in controls. In the follow up patients, 12 were non-responders and the serum levels of cytokines were still elevated after therapy whereas in 27 responders cytokine levels were significantly reduced after therapy and correlated well with biochemical and histopathological parameters. It is inferred that cytokine levels reflect the level of inflammation in chronic hepatitis C virus (HCV) infection and can be used as indirect markers to assess the severity of liver disease.

The molecular detection of HCV RNA by using primers from the 5′ noncoding region (5′NCR) is universally accepted and preferred for diagnosis; however, insufficient sequence variation limits its usefulness for differentiating various subtypes—such as 1a/1b and newer subtypes, such as 1c—which cannot be distinguished by analysis of this region alone. Determination of genotypes and subtypes has important implications in the clinical management and epidemiologic investigations. The present study was designed to develop a reverse transcription-polymerase chain reaction (RT-PCR) assay using degenerate primers from the 5′ noncoding-core region (5′NCR-core region) for detecting as well as subtyping HCV isolates. 5′NCR-core region and 5′NCR were amplified by nested PCR. Genotyping of HCV isolates was carried out using restriction fragment length polymorphism (RFLP) assay from the 5′NCR-core region using restriction enzymes AccI, MboI, and BstNI. The accuracy of the RFLP method was also evaluated using direct sequencing.

The major causes of chronic liver disease (CLD) are infection with Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) either alone or together. The clinical course of the disease varies in cases ofcoinfection with HCV and HBV as compared to single infection. The present study was carried out to determine the occurrence of coinfection of HCV with HBV in CLD patients and to look for the presence of suppressive effect of the two viruses on each other. The severity of liver disease was also assessed and correlated with biochemical profiles. Sera from 150 patients of CLD were tested serologically for the presence of HBsAg, IgG anti HBc and anti-HCV antibodies. HBV DNA and HCV RNA were also detected by amplifying surface region and 5' noncoding-core region respectively by polymerase chain reaction. Forty-seven (31.3%) cases showed the presence of HBsAg or anti IgG-HBc or HBV DNA either alone or together (Group A). Thirty-nine (26%) cases were found to be positive for HCV by detecting either anti-HCV antibodies or HCV RNA (Group B). Coinfection ofHCV with HBV (Group C) could be detected in twenty-four (16%) cases, of these twenty-one cases (87.5%) were positive both for HCV RNA and IgG anti-HBc without the presence of HBV DNA whereas in none of the cases could HBV DNA be detected in the absence of HCV RNA. Forty (26.6%) cases had neither HCV or HBV related CLD. Amongst, the biochemical parameters, the liver function test profiles were altered and found to be statistically significantly in HCV positive cases (Group B) when compared to the negative ones while in case of HBV (Group A) and coinfected (Group C) cases none of the parameters was statistically significant when compared with non-HBV and non-coinfected cases respectively. Thus, coinfection of HCV with HBV is seen in a substantial number of CLD cases. It is also revealed from the present study that HCV infection has a suppressive effect on the replication of HBV as seen by the loss of replicative markers like HBV DNA.

This study was carried out to extend the quality and shelf life of ber fruits by low-cost effective packaging materials. There were 48 treatment combinations consisting oftwo packing materials (Card Board Box; Polythene Net bag) three size of the retail packing units (250 g; 500 g; - 1 kg; - 2kg) and six storage periods (Initial; 2 days; 4 days; 6 days; 8 days; 10 days). The fruits of ber cultivar Umran were harvested at optimum maturity from Horticulture Research Centre, Patharchatta, Pantnagar, Udham Singh Nagar, Uttarakhand. Ber is one of the commercial fruit crops grown in the tropical and sub-tropical region. It is considered to be“poor man's apple” due to its high nutritional, medicinal value and low cost. Ber fruits have an advantage that fruits areavailable in market during lean period and to ensure remunerative prices to growers. However, the storage life of ber is extremely short, hardly 2–4 days at ambient conditions and thus early perishability of fruit poses a problem. Among the various packaging materials evaluated for packing of berfruits, cardboard boxes were found suitable and economically viable containers involving least cost ( 3.00). Although physico-chemical properties were concerned during 10 days storage, the maximum acidity and ascorbic acid along with minimum physiological loss in weight and spoilage percentage were found in cardboard boxes packed fruits. However, maximum physiological loss in weight, spoilage, TSS, total sugars of fruits were obtained in fruits packed in polythene netbags. Sensory scores for overall acceptability were better infruits packed in cardboard boxes. Therefore, storage of 100 kg ber fruits packed in cardboard boxes showed better quality as compared to polythene net bags under ambient storage. Economics computed showed feasibility as on a total input of Rs. 1363.32 and Rs. 3000 is earned as gross returns with a netreturn of Rs. 1637. 68 with 2.20 B: C ratio.

According to the literature, the prevalence of supernumerary teeth is 1% to 4% of permanent dentitions; and among these, the presence of fifth mandibular incisor - a supernumerary eumorphic tooth - has rarely been described in literature, and its association with localized aggressive periodontitis is an even more rare entity. This paper reports a very rare case of unusual association of supernumerary eumorphic fifth mandibular incisor with aggressive periodontitis in a Muslim individual, so that these findings generate curiosity and inspire others to carry out further studies and investigations.