Effect of incident angle on weld microstructure and mechanical properties of laser beam welded nitronic -50 austenitic stainless steel joints.

3 mm thick nitronic-50 stainless steel sheets were successfully butt-joined using a 2 kW fiber laser beam welding. Three weld joints were fabricated for different incident angles, namely, 70°, 80° and 90° for the other constant welding process parameters. The effect of incident angle on the weld bead geometry, microstructure evolution, and strength of the laser beam welded joints was studied in detail. The incident angle significantly affected the bead geometry and its orientation. Lowering the incident angle beyond a limit caused the beam shift near the weld root of the joint, where the bead was formed away from the joint line resulting in improper fusion and a defective weld occurred. The microstructure transformed from columnar to an equiaxed dendritic structure at the center of the weld nugget for lower incident angles. Skeletal and lathy ferrite was observed in the joints' weld zone. However, the fraction of lathy ferrite was higher at lower incident angles due to a faster cooling rate. A higher weld joint strength of 1010 MPa (97% of the base metal UTS) was achieved at an 80° incident angle, owing to the formation of more equiaxed dendritic grains and the absence of the secondary phases. All of the tensile test samples showed evidence of ductile failure, and overall, an acceptable level of elongation was achieved.

Neuroprotective effects of Tongtian oral liquid, a Traditional Chinese Medicine in the Parkinson's disease-induced zebrafish model.

Traditional Chinese medicine (TCM) is used in the treatment of Parkinson's disease (PD) worldwide. Tongtian Oral Liquid (TTKFY) is one such patented TCM, and a poly-herbal formulation, composed of 11 herbal constituents, which possess neuroprotective, antioxidant, pain-relieving properties. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP), a neurotoxicant is used to induce PD in animal models. The present study was aimed to evaluate the neuroprotective effects of TTKFY, on dopaminergic neuron development, antioxidant activities, and gene expression involved in the dopaminergic pathway in the MPTP-treated zebrafish model. Zebrafish larvae were treated with MPTP (70 µM) to induce PD and then by different concentrations (0.5, 1, 2, 4 ml/L) of TTKFY. Transgenic zebrafish Vmat: GFP at 5 dpf were used to observe the development of dopaminergic neurons. The activities of T-Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malonaldehyde (MDA) and mRNA gene expression of dopamine pathway were quantified. MPTP-treated zebrafish larvae showed degeneration of dopaminergic neurons, locomotion dysfunction, diminished activities of antioxidant enzymes, MDA accumulation, and altered gene expression of dopamine pathway. In contrast, TTKFY protected dopaminergic neurons, ameliorated behavioral impairments, antioxidant activities and mRNA gene expression of dopamine pathway in a dose-dependent manner. Thus, TTKFY confers protective effects against MPTP-induced neurotoxicity and the mechanisms of protection may be related to the recovery of dopaminergic neurons by reducing oxidative stress via restoring cellular defense mechanisms and thereby highlighting its therapeutic potential to prevent the progression of PD. Further studies are necessary to elucidate the mechanism of action of TTKFY on neuroprotection in the MPTP-induced PD model.

Isoliquiritigenin triggers developmental toxicity and oxidative stress-mediated apoptosis in zebrafish embryos/larvae via Nrf2-HO1/JNK-ERK/mitochondrion pathway.

Isoliquiritigenin (ISL) is an emerging natural flavonoid found in the roots of licorice, exhibits antioxidant, anti-cancer, anti-inflammatory, anti-allergic, cardioprotective, hepatoprotective and neuroprotective properties. However, the effect of ISL in embryonic development is yet to be elucidated, and the mechanisms underlying its target-organ toxicity and harmful side effects are still unclear. In the present study, we employed zebrafish embryos to study the developmental toxicity effect of ISL and its underlying mechanisms. Zebrafish embryos upon treatment with either vehicle control (0.1% DMSO) or ISL solutions for 4-96 h post fertilization (hpf) showed that ISL exposure instigated severe developmental toxicity in heart, liver, and nervous system. Mortality and morphological abnormalities were also observed. High concentrations of ISL exposure resulted in abnormal phenotypes and embryonic malformations including pericardial edema, swim bladder defects, yolk retention, curved body shape and shortening of body length. Moreover, ISL exposure led to significant loss of dopaminergic neurons accompanied by reduced locomotor behaviour. Apoptotic cells were predominantly located in the heart area of 96 hpf embryo. Additionally, ISL significantly increased the levels of reactive oxygen species, lipid peroxidation content and decreased antioxidant enzyme activities. The expressions pattern of apoptosis-related genes Bad, Cyto c, Caspase-9, Caspase-3 and Bax/Bcl-2 indicated that the oxidative stress-induced apoptosis triggered by ISL suggest involvement of Nrf2-HO1/JNK-ERK/mitochondrion pathways. In conclusion, here we provide first evidence that demonstrate ISL-induced dose-dependent developmental toxicity in zebrafish embryos. Furthermore, gene expression patterns in the embryos correlate the above and reveal potential genetic mechanisms of developmental toxicity.

Synthesis of platinum nanoparticles using seaweed Padina gymnospora and their catalytic activity as PVP/PtNPs nanocomposite towards biological applications.

In the recent years, synthesis of nanomaterials using seaweeds and their diverse applications is escalating research in modern era. Among the noble metals, platinum nanoparticles (PtNPs) are of great importance owing to their catalytic property and less toxicity. The significance of this work is a simple one-step synthesis of PtNPs using aqueous extract of Indian brown seaweed Padina gymnospora and their catalytic activity with a polymer Polyvinylpyrrolidone (PVP) as PVP/PtNPs nanocomposite towards antimicrobial, haemolytic, cytotoxic (Artemia salina) and antioxidant properties. Fourier Transform Infrared (FT-IR) spectrum results showed diversified functional groups (biomoeities such as carbohydrates and proteins) present in the seaweed extract is responsible for the reduction of platinum ions (Pt+) to PtNPs. The seaweed mediated PtNPs was characterized by UV-vis spectrophotometer, X-ray diffraction (XRD) pattern, Field Emission Scanning Electron Microscopy (FESEM) equipped with Energy Dispersive X-ray (EDX) spectroscopy and High Resolution Transmission Electron Microscopy (HRTEM) analysis. The synthesized PtNPs was found to be truncated octahedral in shape with the range of 5-50nm. Crystalline nature of the nanoparticles was evidenced by Selected Area Electron Diffraction (SAED) pattern with bright circular spots corresponding to (111), (200), (220) and (311) Bragg's reflection planes. The size of the PtNPs was further evidenced by Dynamic Light Scattering (DLS) analysis and it is originate to be stable at -22.5mV through Zeta Potential (ZP) analysis. The present study shows that the catalytic behavior of PtNPs as polymer/metal nanocomposite (PVP/PtNPs) preparation for an antibacterial activity against seven disease causing pathogenic bacterial strains with the maximum activity against Escherichia coli (15.6mm) followed by Lactococcus lactis (14.8mm) and Klebsiella pneumoniae (14.4mm). But no haemolytic activity was seen at their effective bactericidal concentration, whereas increase in the haeomyltic activity was seen only in higher concentrations (600, 900 and 1200µgmL-1). On the other hand, PVP/PtNPs nanocomposite has shown cytotoxic activity at 100±4µgmL-1 (LC50) against Artemia salina nauplii. Furthermore, PVP/PtNPs nanocomposite showed an enhanced scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide, nitric oxide and hydroxyl radicals.

Impact of the Diabetes Inpatient Care and Education (DICE) project and the DICE Care Pathway on patient outcomes and trainee doctor's knowledge and confidence.

AIM: To evaluate the impact of the Diabetes Inpatient Care and Education project and a comprehensive diabetes care pathway, the Diabetes Inpatient Care and Education Care Pathway, on patient outcomes and on the knowledge and confidence of trainee doctors. METHODS: The effect on patient outcomes was evaluated by comparing the National Diabetes Inpatient Audit data before (2012) and after (2013) implementing the Diabetes Inpatient Care and Education project. The impact on trainee doctors was evaluated using the Modified Kirkpatrick model. Just before the project began and again 3 months later, trainee doctors were surveyed to assess their knowledge and confidence in inpatient diabetes care. RESULTS: Patient harm was found to have been reduced significantly when National Diabetes Inpatient Audit data for 2012 and 2013 were compared. Severe hypoglycaemia decreased from 15.4 to 9.7%, medication errors from 56.9 to 21.1% and insulin errors from 31 to 7%. Across the 96 trainee doctors surveyed, the mean (sd) knowledge and confidence scores increased significantly (P < 0.001 for both) from 57.1 (16.8) and 61.8 (14.9) to 68.4 (13.3) and 74.3 (11.7), respectively. CONCLUSION: The Diabetes Inpatient Care and Education project and the Diabetes Inpatient Care and Education Care Pathway improved patient outcomes and the knowledge and confidence of trainee doctors in this hospital. The impact of a similar project in other hospitals needs to be evaluated.

Bioassay guided fractionation and identification of active anti-inflammatory constituent from Delonix elata flowers using RAW 264.7 cells.

CONTEXT: Delonix elata (L.) Gamble (Fabaceae) has been used in the Indian traditional medicine system to treat rheumatism and inflammation. AIM: To assess the anti-inflammatory effect of Delonix elata flowers and to isolate the active principle. MATERIALS AND METHODS: The prompt anti-inflammatory constituent was isolated from Delonix elata flower extracts using bioassay guided fractionation in liposaccharide (LPS) stimulated RAW 264.7 macrophage cell line. The anti-inflammatory activity of extracts/fractions/sub-fractions/compounds (10, 25, and 50 µg/ml) was evaluated by estimating the levels of nitric oxide (NO), TNF-α, and IL-1ß after 24 h of LPS induction (1 µg/ml). The isolated active compound was subjected to NMR, IR, and UV analyses for structure determination. RESULTS: In an attempt to search for anti-inflammatory constituents, the active pure principle was isolated and crystallized as a white compound from Delonix elata flowers methanol extract. This active compound (50 µg/ml) decreased the release of inflammatory mediators levels such as NO (0.263 ± 0.03 µM), TNFα (160.20 ± 17.57 pg/ml), and IL-1ß (285.79 ± 15.16 pg/ml) significantly (p < 0.05); when compared to the levels of NO (0.774 ± 0.08 µM), TNFα (501.71 ± 25.14 pg/ml), and IL-1ß (712.68 ± 52.25 pg/ml) from LPS-stimulated macrophage cells. The active compound was confirmed as hesperidin with NMR, IR, and UV spectroscopy data. This is the first report of this compound from Delonix elata flowers. CONCLUSION: The findings of the study support the traditional use of Delonix elata flowers to treat inflammation.

Late effects of childhood cancer treatment: severe hypertriglyceridaemia, central obesity, non alcoholic fatty liver disease and diabetes as complications of childhood total body irradiation.

BACKGROUND: Childhood cancer survivors may develop a number of endocrine complications linked to organ failure, such as hypogonadism, diabetes and growth hormone deficiency. However, increasing evidence now suggests that total body irradiation treatment, specifically, is linked with future risk of insulin resistance, hepatic steatosis and dyslipidaemia, possibly because total body irradiation affects adipocyte differentiation and impairs subcutaneous adipose tissue depot expansion during times of positive energy balance. CASE REPORT: We describe a 20-year-old woman who developed pancreatitis with severe hypertriglyceridaemia (serum triglycerides > 300 mmol/l) that required plasmapheresis. She had received total body irradiation prior to her bone marrow transplant at age 6 years for relapsed acute lymphoblastic leukaemia. She developed ovarian failure at age 12 years. At age 15 years she was noted to have hyperglycaemia, increased blood pressure, hepatic steatosis and mild hypertriglyceridaemia. She presented with severe hypertriglyceridaemia and eruptive xanthoma, and developed pancreatitis 12 h after admission. She was treated with plasmapheresis and intravenous insulin and made an excellent recovery. We implicate and discuss total body irradiation as the major contributing factor to her severe hypertriglyceridaemia, compounded by worsening glycaemic control, oestrogen deficiency and a changing adult lifestyle. CONCLUSION: Children who have received total body irradiation are at risk of diabetes and an exaggerated form of the metabolic syndrome with hypertriglyceridaemia, which can be life-threatening. We suggest that survivors of total body irradiation treatment require careful lifelong monitoring of their metabolic status.

Editorial. Oral submucous fibrosis: revised hypotheses as to its cause.

Oral submucous fbrosis (OSF), being a prototype of pathological fbrosis, remains enigmatic as regards its causation. The connective tissue production is permanent and there is no reversal of the condition even after cessation of the habit of areca-nut usage; prime suspect in its causation.(1) The bulk of the connective tissue consists of type-1 collagen(2) and its formation does not appears to be caused by excessive proliferation of fbroblasts.(3) The effect of areca nut extract on in vitro fbroblasts varies on a concentration gradient, predominantly suppressing rather than stimulating the growth of the cells.(4) Based on morphological characteristics, the fbroblast population in the diseased mucosa has been classifed in to types F1, F2 and F3 with F3 cells producing signifcantly more collagen than the other two cell types. It was concluded that a change of fbroblast population has occurred in OSF and that this relative increase of F3 cells in humans, could be committed to the production of large quantities of collagen formation in OSF. It has been proposed that fbroblasts are functionally heterogeneous, the composition of any given normal or diseased connective tissue being a consequence in part of its particular mixture of fbroblast subtypes and density. Subtype deletion or amplifcation can result from selective cytotoxic or mitogenic responses induced by the binding environmental ligands.(5) Against this backdrop, we propose few de-novo attributes, hitherto unreported, and seem to be of relevance in the pathogenesis of OSF; namely the role of autophagy in basic cellular homeostatic process, important to cell fate decisions under conditions of stress and also ECM producing cells (fbroblasts, myofbroblasts and smooth muscle cells) derived from epithelial and endothelial cells through process termed epithelial and endothelial-mesenchymal transition.

Osteosarcoma of the mandible masquerading as a dental abscess: report of a case.

An aggressive and fatal case of osteosarcoma of the mandible in a 19-year-old female is reported. Six weeks after the clinical appearance of the swelling, the patient died. This paper is unique in that the age of occurrence and the biologic behavior of the tumor were not consistent with the reported literature. The case report is followed by a brief review of osteosarcoma of the jaw with a note on its clinical presentation, diverse radiologic appearance, varied histopathologic picture, and prognosis.

Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in zebrafish.

BACKGROUND: Obesity is a complex, multifactorial disorder influenced by the interaction of genetic, epigenetic, and environmental factors. Obesity increases the risk of contracting many chronic diseases or metabolic syndrome. Researchers have established several mammalian models of obesity to study its underlying mechanism. However, a lower vertebrate model for conveniently performing drug screening against obesity remains elusive. The specific aim of this study was to create a zebrafish obesity model by over expressing the insulin signaling hub of the Akt1 gene. METHODOLOGY/PRINCIPAL FINDINGS: Skin oncogenic transformation screening shows that a stable zebrafish transgenic of Tg(krt4Hsa.myrAkt1)(cy18) displays severely obese phenotypes at the adult stage. In Tg(krt4:Hsa.myrAkt1)(cy18), the expression of exogenous human constitutively active Akt1 (myrAkt1) can activate endogenous downstream targets of mTOR, GSK-3α/ß, and 70S6K. During the embryonic to larval transitory phase, the specific over expression of myrAkt1 in skin can promote hypertrophic and hyperplastic growth. From 21 hour post-fertilization (hpf) onwards, myrAkt1 transgene was ectopically expressed in several mesenchymal derived tissues. This may be the result of the integration position effect. Tg(krt4:Hsa.myrAkt1)(cy18) caused a rapid increase of body weight, hyperplastic growth of adipocytes, abnormal accumulation of fat tissues, and blood glucose intolerance at the adult stage. Real-time RT-PCR analysis showed the majority of key genes on regulating adipogenesis, adipocytokine, and inflammation are highly upregulated in Tg(krt4:Hsa.myrAkt1)(cy18). In contrast, the myogenesis- and skeletogenesis-related gene transcripts are significantly downregulated in Tg(krt4:Hsa.myrAkt1)(cy18), suggesting that excess adipocyte differentiation occurs at the expense of other mesenchymal derived tissues. CONCLUSION/SIGNIFICANCE: Collectively, the findings of this study provide direct evidence that Akt1 signaling plays an important role in balancing normal levels of fat tissue in vivo. The obese zebrafish examined in this study could be a new powerful model to screen novel drugs for the treatment of human obesity.

α4ß1 integrin-dependent cell sorting dictates T-cell recruitment in oral submucous fibrosis.

AIM: The biological mechanism(s) that guide the immunological effectors of lymphocytes to sites of inflammatory response, a feature consistently seen in oral submucous fibrosis (OSF) was evaluated. It is envisaged that endothelial/lymphocyte adhesion cascades involving VCAM-1/α4ß1 integrins control the migration of lymphocytes across the vascular endothelium resulting in their homing in these locales. MATERIALS AND METHODS: The study group comprised 28 OSF cases (M:F = 12:16, age range 18-65 years; mean 55.4 ± 8.5 SD) divided into early (n=17) and advanced (n=11) disease groups. Biopsy specimens of normal buccal mucosa (site compatible) were obtained from 10 healthy volunteers (age and sex matched) who served as control. All the samples were fixed in 10% neutral-buffered formalin and embedded in paraffin. Immunolocalization of ß1 subunit associated with α4 integrin was performed by a mouse heterodimer (clone 4B7R, Ig G, R & D Systems Inc., dilution 1:100) using a peroxidase labeled streptavidin-biotin technique. The immunocompetent cell density was expressed as the number of positive cells per mm(2). The Mann-Whitney U-test and Fischer exact test were used to evaluate differences. P<0.05 was considered to be significant. RESULTS: The median percentage of "T" lymphocytes with positive integrin α4ß1 expression was 77.7 (an interquartile range of 73.3-83.4) for the test cases and for the controls, it was 28.2 (IQR 24.0-38.3). This difference was significant at 0.001 level. For the endothelial cells the positive expression was 82.8 (IQR 77-90.6) and 22.3 (IQR 18.3-29.2) respectively (P<0.001). When the intensity of integrin expression was considered 26/28 cases (96%) and 2/10 (20%) of controls showed intense expression of integrins α4ß1 on T lymphocytes (P<0.001). Similarly, 27/28 cases (92.9%) and 2/10 (20%) of controls showed intense expression on endothelial cells (P<0.001). T lymphocyte-endothelial cell interactions were assessed by evaluating the overexpression of integrins on both the endothelial cells and lymphocytes together. The interaction was positive in 15/17 and 11/11 early and advanced OSF cases respectively (P=0.51). CONCLUSION: Following leukocyte activation, the interaction between leukocyte integrin heterodimers and endothelial superfamily adhesion ligands results in a firm adherence of leukocytes to endothelium, leading to leukocyte migration and homing to sites of mucosal inflammation consistently seen in OSF.

Dental pulp stem cells from primary teeth quality analysis: laboratory procedures.

OBJECTIVES: To present details of isolation, processing and differentiation of stem cells from inflamed dental pulp of primary teeth. MATERIALS AND METHODS: Tissue sample was collected from teeth indicated for a single visit pulp therapy. Samples were transported and processed in the laboratory which included culturing of cells, isolation and in vitro differentiation into multiple lineages. The results for the analysis of various cell surface markers used for dental pulp were compared with bone marrow. RESULTS: There was no statistically significant difference found in the expression of various surface markers between dental pulp and bone marrow. The stem cells from dental pulp were differentiated into multiple lineages. CONCLUSION: Isolation of cells from oral tissues is technique sensitive.

Prevalence of Ascogregarina spp. in the container breeding Aedes albopictus from Chikungunya fever affected areas of Kerala State, India.

The prevalence of protozoan, Ascogregarina sp. had been determined in the container breeding mosquitoes, Aedes albopictus. Since, the cyst of Ascogregarina might play role in the maintenance of the Chik virus during silent period, the presence of Ascogregarina has gained importance in recent days. The prevalence was found to be 71.62.

Helicobacter pylori coinfection is a confounder, modulating mucosal inflammation in oral submucous fibrosis.

UNLABELLED: The oral cavity has been considered a potential reservoir for Helicobacter pylori (H pylori) , from where the organism causes recurrent gastric infections. AIM: With this case-control study we tried to evaluate the role of H pylori in the etiology of mucosal inflammation, a condition that compounds the morbid state associated with oral submucous fibrosis (OSF). MATERIALS AND METHODS: Subjects ( n = 150) were selected following institutional regulations on sample collection and grouped into test cases and positive and negative controls based on the presence of mucosal fibrosis and inflammation. The negative controls had none of the clinical signs. All patients underwent an oral examination as well as tests to assess oral hygiene/periodontal disease status; a rapid urease test (RUT) of plaque samples was also done to estimate the H pylori bacterial load. We used univariate and mutivariate logistic regression for statistical analysis of the data and calculated the odds ratios to assess the risk posed by the different variables. RESULTS: The RUT results differed significantly between the groups, reflecting the variations in the bacterial loads in each category. The test was positive in 52% in the positive controls (where nonspecific inflammation of oral mucosa was seen unassociated with fibrosis), in 46% of the test cases, and in 18% of the negative controls (healthy volunteers) (chi2 = 13.887; P < 0.01). A positive correlation was seen between the oral hygiene/periodontal disease indices and RUT reactivity in all the three groups. CONCLUSIONS: The contribution of the H pylori in dental plaque to mucosal inflammation and periodontal disease was significant. Logistic regression analysis showed gastrointestinal disease and poor oral hygiene as being the greatest risk factors for bacterial colonization, irrespective of the subject groups. A positive correlation exists between RUT reactivity and the frequency of mucosal inflammation.

Generation, long-term persistence, and neuronal differentiation of cells with nuclear aberrations in the adult zebrafish brain.

Zebrafish, like other teleosts, continuously produce new cells in numerous regions of the adult brain. Immunolabeling employing antisera against phosphorylated histone-H3 and 5-bromo-2'-deoxyuridine revealed that approximately 6%-7% of such cells exhibited nuclear aberrations. These aberrations, presumably the result of mitotic segregation defects, included single and multiple laggards (both during metaphase and anaphase) and anaphase bridges. Cells with such aberrations persisted long-term and comprised, when examined 7.5 months after their generation, approximately 2.5% of the total population of adult-born cells. The drop in relative frequency of aberrations in the course of further development appears to be caused by elimination of cells with nuclear aberrations, presumably by apoptotic cell death. The cells with nuclear aberrations that persisted long-term were capable of neuronal differentiation, as demonstrated by combining anti-5-bromo-2'-deoxyuridine immunohistochemistry with immunostaining against the neuronal marker protein Hu or the enzyme tyrosine hydroxylase, a marker of catecholaminergic neurons. We hypothesize that the alterations in chromosome number and/or chromosome structure caused by nuclear aberrations do not necessarily result in loss of vital functions or in tumorigenesis. Instead, cells with such aberrations are able to undergo what appears to be normal development.

Apoptotic cell death, long-term persistence, and neuronal differentiation of aneuploid cells generated in the adult brain of teleost fish.

Aneuploidy, caused by segregation defects during mitosis, has previously been identified in adult-born cells of mammals and teleosts. In the present study, we have examined the fate of these cells in the brain of the teleost fish Apteronotus leptorhynchus. By immunostaining against active caspase-3, we have shown that both cells with normal nuclear morphology and cells with mitotic segregation defects undergo apoptosis, but the relative number of apoptotic cells is higher among cells of the latter category. Long-term survival of cells with mitotic segregation defects could be demonstrated by incorporation of 5-bromo-2'-deoxyuridine into newly synthesized DNA during the S-phase of mitosis, and by employment of postadministration survival times of up to 860 days. Moreover, by combining 5-bromo-2'-deoxyuridine immunolabeling with immunostaining against the neuron-specific marker protein Hu, we have shown that among the long-term persistent cells with mitotic segregation defects a similar portion develops into neurons as does among the long-term persistent cells without such defects. It is possible that aneuploid cells play a role in the regulation of gene expression by somatic genomic alterations during postnatal development.

PCAF is an HIF-1alpha cofactor that regulates p53 transcriptional activity in hypoxia.

The p53 tumour suppressor is involved in several crucial cellular functions including cell-cycle arrest and apoptosis. p53 stabilization occurs under hypoxic and DNA damage conditions. However, only in the latter scenario is stabilized p53 capable of inducing the expression of its pro-apoptotic targets. Here we present evidence that under hypoxia-mimicking conditions p53 acetylation is reduced to a greater extent at K320 site targeted by P300/CBP-associated factor (PCAF) than at K382 site targeted by p300/CBP. The limited amounts of acetylated p53 at K320 are preferentially recruited to the promoter of the p21(WAF-1/CIP-1) gene, which appears to be unaffected by hypoxia, but are not recruited to the BID promoter and hence p53 is incapable of upregulating pro-apoptotic BID in hypoxic conditions. As the K320 p53 acetylation is the site predominantly affected in hypoxia, the PCAF histone acetyltransferase activity is the key regulator of the cellular fate modulated by p53 under these conditions. In addition, we provide evidence that PCAF acetylates hypoxia-inducible factor-1alpha (HIF-1alpha) in hypoxic conditions and that the acetylated HIF-1alpha is recruited to a particular subset of its targets. In conclusion, PCAF regulates the balance between cell-cycle arrest and apoptosis in hypoxia by modulating the activity and protein stability of both p53 and HIF-1alpha.

Fulminant myocarditis: a rare but life-threatening association of Crohn's disease.

Myocarditis is an uncommon association of Crohn's disease. It has been reported to occur independently of inflammatory bowel disease activity. The case history is presented of a young woman admitted to hospital with acute small bowel obstruction as a presentation of active Crohn's disease which was further complicated by fulminant myocarditis leading to cardiogenic shock. This could have proved fatal if not recognised and managed appropriately. Myocarditis is rare, but it can be a life-threatening association of inflammatory bowel disease which needs early recognition and prompt treatment.

Effect of topical nasal steroid spray in the treatment of non-specific recurrent / chronic pharyngitis - a trial study.

OBJECTIVE: Non-Specific Chronic/Recurrent Pharyngitis is a diagnosis with no definite effective treatment. An array of drugs and therapies has been tried from local applications like Mandl's paint and throat gargles to anxiolytics. None have proved of therapeutic benefit. This trial study is a Pilot study of its kind in to the effectiveness of nasal steroid spray in the treatment of non-specific chronic pharyngitis. This is a prospective randomized study. SETTING: Study done in medical college with ambulatory patients centre. PATIENTS: 53 patients were taken up for the study though only 42 could be followed up for a period of 1-2.5 years. Selection done on the basis of symptoms avoiding extreme age groups and subjective persistent relief was central to be considered proof of effectiveness of the treatment. Fluticasone Nasal Spray was used in the study. RESULTS: 35 patients (83.3%) reported some degree of relief in symptoms. 68% had >90% relief of symptoms with only a total of 1-2 sprays. There were 7 failures. Side effects were negligible. CONCLUSION: Nasal steroid spray is therefore recommended as a most cost-effective, safe treatment method for well-selected cases of Chronic Non-Specific Pharyngitis.

Inducible nitric oxide synthase expression is upregulated in oral submucous fibrosis.

OBJECTIVE: We tested the hypothesis that inducible nitric oxide synthase (iNOS) modulates angiogenesis in human models and this information could be extrapolated in elucidating the pathophysiology of oral submucous fibrosis (OSF). A hypothesis which looks inadequate, but is deep rooted in literature is the epithelial alteration ("atrophy") seen in OSF and the events that lead to its causation. This aspect was tried to be addressed and an alternative pathogenetic pathway for the disease is proposed. MATERIALS AND METHODS: This immunohistochemical study sought to investigate the expression of iNOS in OSF samples (n=30) a using monospecific antibody (SC- 2050, Santa Cruz Biotechnology, Inc) to the protein and also to correlate it with different grades of epithelial dysplasia associated with the disease. Twenty (20) healthy adults acted as controls. RESULTS: iNOS staining was not demonstrated in normal oral epithelium. In oral epithelial dysplasia, staining was seen in all cases (100%) in the basal layers of the epithelium and in 30% of cases it extended into the parabasal compartments as well. iNOS staining was uniformly positive in moderate dysplasia with an increase in intensity and distribution noted as the severity of dysplasia progressed. There were highly significant differences in overall positivity for iNOS in epithelium between cases and controls (Mann-Whitney U=11.000, Wilcoxon W=221.00, P=0.000). Significant comparisons were made of mild Vs moderate dysplasia (Mann-Whitney U=48.000, P=0.014) CONCLUSIONS: This study supports our earlier morphological assessment (image analysis) of the nature of vascularity in OSF mucosa. The significant vasodilation noticed in these cases argues against the concept of ischemic atrophy of the epithelium. This observation of vascularity and iNOS expression helped to explain the vasodilation noticed (sinusoids) in this disease; NO being a net vasodilator. The mechanism of activation of iNOS in dysplasia is difficult to explain. The role of contingent paracrine-activating factors on keratinocytes and macrophages is discussed.