A study of serum Vitamin D level and its association with hypertension.

BACKGROUND: Evidence suggests that low levels of Vitamin D may adversely affect the cardiovascular (CV) system. Several studies have been done regarding the relation and possible causative role of Vitamin D in CV disorders and its well-known risk factors; however, there are limited studies in this part of the world. The aims were as follows: (1) To study the relation between serum Vitamin D level between nonhypertensive and hypertensive patients. (2) To study the relation of serum Vitamin D levels in patients with isolated systolic hypertension (ISH), isolated diastolic hypertension, systolo-diastolic hypertension, and their comparison vis-à-vis nonhypertensives. MATERIALS AND METHODS: A cross-sectional study was conducted with 154 patients attending medicine outpatient department of a tertiary care hospital of North Bengal from June 2012 to May 2013. The Vitamin D was measured by direct ELISA method. Blood pressure (BP) measurements were done. Statistical analysis was done by using SPSS 16.0 for Windows. RESULTS: The Vitamin D level in the hypertensive group was 22.36 ± 12.64; ISH Group was 22.04 ± 14.26; the isolated diastolic hypertension (IDH) Group was 18.82 ± 0.00; and the systolo-diastolic hypertensives (SDH) Group was 22.67 ± 12.51. Then, the mean value of Vitamin D in nonhypertensive Group (27.47 ± 13.43) was significantly (P < 0.05) higher than IDH, SDH, and the hypertensive as a whole groups. The relation with ISH Group also reached near significance (P = 0.074). There was a negative correlation with BP and serum Vitamin D. This remained statistically significant (P = 0.044) for systolic BP (SBP) and near significant (P = 0.075) for mean arterial pressure. In population having serum Vitamin D <30 ng/ml (deficient or insufficient), the negative correlation relationship between SBP and serum Vitamin D remains statistically significant (P = 0.010). CONCLUSION: Among the hypertensives, SDH shows significantly lower levels of serum Vitamin D. The patients with ISH show a trend, though not statistically significant, toward a lower level of Vitamin D compared to the nonhypertensive population.

The Drosophila Perlecan gene trol regulates multiple signaling pathways in different developmental contexts.

BACKGROUND: Heparan sulfate proteoglycans modulate signaling by a variety of growth factors. The mammalian proteoglycan Perlecan binds and regulates signaling by Sonic Hedgehog, Fibroblast Growth Factors (FGFs), Vascular Endothelial Growth Factor (VEGF) and Platelet Derived Growth Factor (PDGF), among others, in contexts ranging from angiogenesis and cardiovascular development to cancer progression. The Drosophila Perlecan homolog trol has been shown to regulate the activity of Hedgehog and Branchless (an FGF homolog) to control the onset of stem cell proliferation in the developing brain during first instar. Here we extend analysis of trol mutant phenotypes to show that trol is required for a variety of developmental events and modulates signaling by multiple growth factors in different situations. RESULTS: Different mutations in trol allow developmental progression to varying extents, suggesting that trol is involved in multiple cell-fate and patterning decisions. Analysis of the initiation of neuroblast proliferation at second instar demonstrated that trol regulates this event by modulating signaling by Hedgehog and Branchless, as it does during first instar. Trol protein is distributed over the surface of the larval brain, near the regulated neuroblasts that reside on the cortical surface. Mutations in trol also decrease the number of circulating plasmatocytes. This is likely to be due to decreased expression of pointed, the response gene for VEGF/PDGF signaling that is required for plasmatocyte proliferation. Trol is found on plasmatocytes, where it could regulate VEGF/PDGF signaling. Finally, we show that in second instar brains but not third instar brain lobes and eye discs, mutations in trol affect signaling by Decapentaplegic (a Transforming Growth Factor family member), Wingless (a Wnt growth factor) and Hedgehog. CONCLUSION: These studies extend the known functions of the Drosophila Perlecan homolog trol in both developmental and signaling contexts. These studies also highlight the fact that Trol function is not dedicated to a single molecular mechanism, but is capable of regulating different growth factor pathways depending on the cell-type and event underway.

The 2017 Academic College of Emergency Experts and Academy of Family Physicians of India position statement on preventing violence against health-care workers and vandalization of health-care facilities in India.

There have been multiple incidents where doctors have been assaulted by patient relatives and hospital facilities have been vandalized. This has led to mass agitations by Physicians across India. Violence and vandalism against health-care workers (HCWs) is one of the biggest public health and patient care challenge in India. The sheer intensity of emotional hijack and the stress levels in both practicing HCWs and patient relative's needs immediate and detail attention. The suffering of HCWs who are hurt, the damage to hospital facilities and the reactionary agitation which affects patients who need care are all together doing everything to damage the delivery of health care and relationship between a doctor and a patient. This is detrimental to India where illnesses and Injuries continue to be the biggest challenge to its growth curve. The expert group set by The Academic College of Emergency Experts and The Academy of Family Physicians of India makes an effort to study this Public Health and Patient Care Challenge and provide recommendations to solve it.

Perlecan signaling: helping hedgehog stimulate prostate cancer growth.

Perlecan, an extracellular matrix proteoglycan, regulates signaling by a variety of growth factors through protein-protein and protein-carbohydrate interactions. Recent evidence demonstrates that Perlecan modulates sonic hedgehog signaling during both development and neoplasia, in particular in prostate cancer. Perlecan directly binds to sonic hedgehog and is required for its signaling. Increased sonic hedgehog signaling due to Perlecan in aggressive and metastatic prostate cancer cells can be attributed to increased Perlecan expression or changes in Perlecan glycan structure. Additional co-localization studies suggest that other tumor types may also have a Perlecan-modulated hedgehog signaling pathway. Inhibitors of Perlecan function at either the protein or glycan level would be ideal drug candidates for anti-cancer therapies.

Perlecan, a candidate gene for the CAPB locus, regulates prostate cancer cell growth via the Sonic Hedgehog pathway.

BACKGROUND: Genetic studies associated the CAPB locus with familial risk of brain and prostate cancers. We have identified HSPG2 (Perlecan) as a candidate gene for CAPB. Previously we have linked Perlecan to Hedgehog signaling in Drosophila. More recently, we have demonstrated the importance of Hedgehog signaling in humans for advanced prostate cancer. RESULTS: Here we demonstrate Perlecan expression in prostate cancer, and its function in prostate cancer cell growth through interaction and modulation of Sonic Hedgehog (SHH) signaling. Perlecan expression in prostate cancer tissues correlates with a high Gleason score and rapid cell proliferation. Perlecan is highly expressed in prostate cancer cell lines, including androgen insensitive cell lines and cell lines selected for metastatic properties. Inhibition of Perlecan expression in these cell lines decreases cell growth. Simultaneous blockade of Perlecan expression and androgen signaling in the androgen-sensitive cell line LNCaP was additive, indicating the independence of these two pathways. Perlecan expression correlates with SHH in tumor tissue microarrays and increased tumor cell proliferation based on Ki-67 immunohistochemistry. Inhibition of Perlecan expression by siRNA in prostate cancer cell lines decreases SHH signaling while expression of the downstream SHH effector GLI1 rescues the proliferation defect. Perlecan forms complexes with increasing amounts of SHH that correlate with increasing metastatic potential of the prostate cancer cell line. SHH signaling also increases in the more metastatic cell lines. Metastatic prostate cancer cell lines grown under serum-starved conditions (low androgen and growth factors) resulted in maintenance of Perlecan expression. Under low androgen, low growth factor conditions, Perlecan expression level correlates with the ability of the cells to maintain SHH signaling. CONCLUSION: We have demonstrated that Perlecan, a candidate gene for the CAPB locus, is a new component of the SHH pathway in prostate tumors and works independently of androgen signaling. In metastatic tumor cells increased SHH signaling correlates with the maintenance of Perlecan expression and more Perlecan-SHH complexes. Perlecan is a proteoglycan that regulates extracellular and stromal accessibility to growth factors such as SHH, thus allowing for the maintenance of SHH signaling under growth factor limiting conditions. This proteoglycan represents an important central regulator of SHH activity and presents an ideal drug target for blocking SHH effects.

Deep vein thrombosis in a patient of adenomatous polyposis coli treated successfully with aspirin: A case report.

BACKGROUND: Deep vein thrombosis is an important cause of morbidity and mortality. However, its association with adenomatous polyposis coli is extremely rare. Here we present an interesting case of deep vein thrombosis associated with adenomatous polyposis coli. CASE PRESENTATION: A 15 year old female who was having fever and diarrhea for 5 months developed bilateral asymmetric painful swelling of lower limbs for 1 month. Doppler ultrasound of lower limbs revealed presence of thrombosis from inferior vena cava up to popliteal vein. Colonoscopy and biopsy were suggestive of adenomatous polyposis coli. However, she could not tolerate anticoagulant therapy and was put on aspirin therapy for 6 months to which she responded well with the resolution of thrombus. CONCLUSION: Role of aspirin therapy may be considered whenever a patient of venous thrombosis cannot tolerate anticoagulant therapy.

Concurrent meningitis and vivax malaria.

Malaria is an endemic infectious disease in India. It is often associated with other infective conditions but concomitant infection of malaria and meningitis are uncommon. We present a case of meningitis with vivax malaria infection in a 24-year-old lady. This case emphasizes the importance of high index of clinical suspicion to detect other infective conditions like meningitis when fever does not improve even after anti-malarial treatment in a patient of malaria before switching therapy suspecting drug resistance, which is quite common in this part of world.

Anterior segment dysgenesis and absent lens caused by amniotic bands.

A male infant is described with anterior segment dysgenesis and absent lens caused by amniotic bands.

Role of heparan sulfate 2-o-sulfotransferase in prostate cancer cell proliferation, invasion, and growth factor signaling.

Heparan-sulfate proteoglycans (HSPGs) are required for maximal growth factor signaling in prostate cancer progression. The degree of sulfate modification on the covalently attached heparan sulfate (HS) chains is one of the determining factors of growth factor-HSPG interactions. Sulfate groups are transferred to HS chains via a series of O-sulfotransferases. In the present study, we demonstrate that Heparan sulfate 2-O-sulfotransferase (2OST) is essential for maximal proliferation and invasion of prostate cancer cells in the LNCaP-C4-2B model. We also show that a decrease in invasion due to 2OST siRNA is associated with an increase in actin and E-cadherin accumulation at the cell surface. 2OST expression correlates with increasing metastatic potential in this model. We demonstrate that 2OST expression is upregulated by the stress-inducible transcription factors HIF1α, ATF2, and NFκB. Chromatin immunoprecipitation analysis suggests that HIF1α and ATF2 act directly on the 2OST promoter, while NFκB acts indirectly.

A case of psychogenic purpura in a female child.

Recurrent spontaneous cutaneous bruising or bleeding through intact skin may be due to underlying emotional stress which may be due to auto-erythrocyte sensitisation. A 9-year-old female child presented with recurrent episodes of oozing from the skin of both lower eyelids and lower peri-orbital areas along with bleeding from tongue which ceased spontaneously after a few minutes without having any induration or oedema at the sites. The child had no systemic abormality, but she was nervous and attention seeking. Psychologic assessment revealed that she was suffering from conversion anxiety and somatoform disorder. After twelve psychotherapeutic sessions she showed marked improvement and her symptoms did not recur.

Curable genetic instability of a gal4 transgene in Drosophila.

Transgenes, especially those driving production of the GAL4 transcription factor in a specific spatial pattern, are a critical and widely used tool in the Drosophila research community. We recently noticed loss of GAL4-driven reporter gene expression in a series of crosses, and traced that loss of reporter gene expression to stochastic physical loss of the GAL4 gene in the driver line. We have demonstrated that the instability of the GAL4 transgene can be "cured" by treatment of the line with tetracycline, suggesting that the causative agent is of bacterial origin. A PCR assay revealed that the line is not infected by Wolbachia, an intracellular parasite known to infect a large percentage of stocks in the public stock centers and to affect mutant phenotypes. Our data indicate that other tetracycline-sensitive agents can cause genetic instability of transgenes, and also provides a potential solution to the problem.

Arabidopsis vegetative storage protein is an anti-insect acid phosphatase.

Indirect evidence previously suggested that Arabidopsis (Arabidopsis thaliana) vegetative storage protein (VSP) could play a role in defense against herbivorous insects. To test this hypothesis, other AtVSP-like sequences in Arabidopsis were identified through a Basic Local Alignment Search Tool search, and their transcriptional profiles were investigated. In response to methyl jasmonate application or phosphate starvation, AtVSP and AtVSP-like genes exhibited differential expression patterns, suggesting distinct roles played by each member. Arabidopsis VSP2 (AtVSP2), a gene induced by wounding, methyl jasmonate, insect feeding, and phosphate deprivation, was selected for bacterial expression and functional characterization. The recombinant protein exhibited a divalent cation-dependent phosphatase activity in the acid pH range. When incorporated into the diets of three coleopteran and dipteran insects that have acidic gut lumen, recombinant AtVSP2 significantly delayed development of the insects and increased their mortality. To further determine the biochemical basis of the anti-insect activity of the protein, the nucleophilic aspartic acid-119 residue at the conserved DXDXT signature motif was substituted by glutamic acid via site-directed mutagenesis. This single-amino acid alteration did not compromise the protein's secondary or tertiary structure, but resulted in complete loss of its acid phosphatase activity as well as its anti-insect activity. Collectively, we conclude that AtVSP2 is an anti-insect protein and that its defense function is correlated with its acid phosphatase activity.

Induction of string rescues the neuroblast proliferation defect in trol mutant animals.

In trol mutants, neuroblasts fail to exit G1 for S phase. Increasing string expression in trol mutants rescues the number of S phase neuroblasts without an increase in M phase neuroblasts. Decreasing string expression further decreased the number of S phase neuroblasts. Coexpression of cyclin E and string did not produce additional S phase cells. Unlike cyclin E, cdk2, and cdk2AF, elevated expression of neither cyclin A, cyclin D, nor cdk1AF was able to promote S phase progression in arrested neuroblasts, indicating that String-induced activity of a Cyclin A or Cyclin D complex is unlikely to drive trol neuroblasts into S phase. Biochemical analyses revealed a rapid increase of Cyclin E-Cdk2 kinase activity to wild-type levels upon increased string expression. These results suggest that Drosophila Cdc25 may directly or indirectly increase the kinase activity of Cyclin E-Cdk2 complexes in vivo, thus driving arrested neuroblasts into cell division.

Drosophila perlecan modulates FGF and hedgehog signals to activate neural stem cell division.

Mutations in the Drosophila trol gene cause cell cycle arrest of neuroblasts in the larval brain. Here, we show that trol encodes the Drosophila homolog of Perlecan and regulates neuroblast division by modulating both FGF and Hh signaling. Addition of human FGF-2 to trol mutant brains in culture rescues the trol proliferation phenotype, while addition of a MAPK inhibitor causes cell cycle arrest of the regulated neuroblasts in wildtype brains. Like FGF, Hh activates stem cell division in the larval brain in a Trol-dependent fashion. Coimmunoprecipitation studies are consistent with interactions between Trol and Hh and between mammalian Perlecan and Shh that are not competed with heparin sulfate. Finally, analyses of mutations in trol, hh, and ttv suggest that Trol affects Hh movement. These results indicate that Trol can mediate signaling through both of the FGF and Hedgehog pathways to control the onset of stem cell proliferation in the developing nervous system.

Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling.

Prostate cancer is the most common solid tumor in men, and it shares with all cancers the hallmark of elevated, nonhomeostatic cell proliferation. Here we have tested the hypothesis that the SONIC HEDGEHOG (SHH)-GLI signaling pathway is implicated in prostate cancer. We report expression of SHH-GLI pathway components in adult human prostate cancer, often with enhanced levels in tumors versus normal prostatic epithelia. Blocking the pathway with cyclopamine or anti-SHH antibodies inhibits the proliferation of GLI1+/PSA+ primary prostate tumor cultures. Inversely, SHH can potentiate tumor cell proliferation, suggesting that autocrine signaling may often sustain tumor growth. In addition, pathway blockade in three metastatic prostate cancer cell lines with cyclopamine or through GLI1 RNA interference leads to inhibition of cell proliferation, suggesting cell-autonomous pathway activation at different levels and showing an essential role for GLI1 in human cells. Our data demonstrate the dependence of prostate cancer on SHH-GLI function and suggest a novel therapeutic approach.