Comparison of the diagnostic yield of transbronchial lung biopsies by forceps and cryoprobe in diffuse parenchymal lung disease.

Background: Transbronchial lung cryobiopsy (TBLC) in the diagnosis of diffuse parenchymal lung disease (DPLD) has shown a promising yield in recent times, with low post-procedural mortality and morbidity. Objectives: To compare the yield of TBLC and conventional transbronchial forceps lung biopsy (TBLB). Methods: A prospective study was carried out in patients with DPLD over a period of 1 year in a tertiary respiratory care institute in New Delhi, India. All 87 patients enrolled underwent both TBLB and TBLC. The procedures were performed in the bronchoscopy suite under conscious sedation and local anaesthesia, with an attempt to take a minimum of three biopsy specimens by conventional TBLB followed by TBLC. A 1.9 mm cryoprobe with a freezing time of 4 - 5 seconds was used. An Arndt endobronchial blocker was used to control bleeding along with locally administered medications. Results: TBLB and TBLC led to a definitive diagnosis in 27 (31.0%) and 69 (79.3%) cases, respectively. The commonest diagnoses were hypersensitivity pneumonitis, sarcoidosis and pulmonary tuberculosis. TBLC led to additional diagnoses in 42 cases (48.3%). Pneumothorax was observed in 12 cases (13.8%), and moderate bleeding occurred in 63 (72.4%). There were no procedure-related deaths. Conclusion: TBLC had a better diagnostic yield than conventional TBLB in DPLD. It has the potential to become a safe day-care procedure in a resource-limited setting, if certain precautions are taken. Study synopsis: What the study adds. Compared with transbronchial forceps lung biopsy, transbronchial lung cryobiopsy (TBLC) led to additional diagnoses in 42 (48.3%) of 87 patients with clinicoradiological features of diffuse parenchymal lung disease. Pneumothorax was observed in 12 cases (13.8%) and moderate bleeding in 63 (72.4%). TBLC without rigid bronchoscopy or advanced airway devices under conscious sedation had a good diagnostic yield with an acceptable adverse events profile.Implications of the findings. TBLC under conscious sedation is not resource intensive and can be carried out in settings with limited resources.

Protective effect of quercetin and thymoquinone against genotoxicity and oxidative stress induced by ZnO nanoparticles in the Wistar rat model.

Zinc oxide nanoparticles (ZnO-NPs) are increasingly used in a variety of consumer and other commercial products. Hence, man faces the risk of exposure to ZnO-NPs and the consequent adverse health effects. Mitigation/prevention of such effects using natural products has drawn the attention of scientists. Therefore, the aim of the present study has been to find the toxic effects associated with exposure to ZnO-NPs, and the protective role of the phytochemicals thymoquinone (TQ) and quercetin (QCT) in the rat model. ZnO-NPs were administered to male Wistar rats through oral route; TQ / QCT was concurrently administered through intra-peritoneal route. The response in the animal was analyzed adopting chromosomal aberration test, micronucleus test, and comet assay of bone marrow cells to assess the genotoxicity, and biochemical assays of superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (LPO), total extractable protein of liver, and reduced glutathione (GSH) of liver homogenate to monitor the changes in the antioxidant defense mechanism in response to the oxidative stress. Treatment of 300 mg/kg body weight (bw) of ZnO-NPs produced adverse effects on all aspects analyzed viz., structural chromosomal aberrations, micronuclei formation, DNA damage, SOD, catalase, lipid peroxidation, GSH, and extractable total protein of liver. Co-treatment of TQ / QCT offered protection against the toxicity induced by ZnO-NPs. The most optimum doses of TQ and QCT that offered the best protection were 18 mg/kg bw and 500 mg/kg bw, respectively. The study reveals that TQ / QCT supplementation is beneficial in the context of toxic effects of ZnO-NPs.

Cardiac structural and functional abnormalities in primary hyperparathyroidism.

PURPOSE: Studies on cardiac structural and functional abnormalities in primary hyperparathyroidism (PHPT) have yielded conflicting and inconsistent results. In this prospective case-control study, we sought to compare cardiac structure and function in symptomatic PHPT patients and controls. METHODS: One hundred consecutive symptomatic PHPT patients and 113 matched controls underwent echocardiographic evaluation by the same operator. RESULTS: Left ventricular mass index (LVMI) was significantly higher in patients as compared to controls, (median of 90.95 g/m2 vs 86.5 g/m2, p = 0.041). Patients had significantly lower early trans-mitral diastolic flow (E velocity) as compared to controls (57.13 ± 14.88 vs 64.76 ± 15.45 cm/s, p < 0.001). Patients also had significantly lower early to late mitral annular velocity (E/A) as compared to controls (0.98 ± 0.37 vs 1.10 ± 0.34, p 0.013). Patients had higher frequency of aortic valve calcification (29% vs 2.65%, p < 0.001), mitral annular calcification (23% vs. 4.42%, p < 0.001), myocardial and septal calcifications (25% vs none, p < 0.001) as compared to controls. Serum PTH, calcium and uric acid significantly correlated with calcifications. Serum calcium showed a negative correlation with E/A ratio. CONCLUSIONS: Symptomatic patients with PHPT have substantial cardiac structural and functional abnormalities. These abnormalities include elevated LVMI, diastolic dysfunction, and aortic valve, mitral annular, septal and myocardial calcifications. We strongly suggest and conclude that the evaluation of PHPT patients should not only include traditional end organs like bones and kidneys but also the cardiovascular system in the form of echocardiography to detect subclinical cardiac dysfunction so that the cardiovascular health of such patients can be optimized.

Primary hyperparathyroidism and pancreatitis.

PURPOSE: The true association between primary hyperparathyroidism (PHPT) and pancreatitis continues to be controversial. In this study, we present clinical data, investigative profile, management and follow-up of PHPT patients with pancreatitis and compare this group with PHPT patients without pancreatitis. METHODS: Records of 242 patients with PHPT managed at our center over 24 years were retrospectively analyzed for demographic and laboratory data. The diagnosis of pancreatitis was entertained in the presence of at least two of the three following features: abdominal pain, levels of serum amylase greater than three times the normal or characteristic features at imaging. RESULTS: Fifteen (6.19%) of the 242 consecutive patients with PHPT had had pancreatitis. Fourteen patients (93.3%) had acute pancreatitis (AP), while one patient had chronic calcific pancreatitis. Over half (8 of 14) of the patients with AP had at least two episodes of pancreatitis. Pancreatitis was the presenting symptom in 14 (93.3%) patients. None of the pancreatitis cases had additional risk factors for pancreatitis. PHPT patients with pancreatitis had significantly higher serum calcium and ALP than PHPT patients without pancreatitis. After successful parathyroidectomy, 14 patients had no further attacks of pancreatitis during a median follow-up of 16 months (range 2-41 months), while recurrence of pancreatitis was seen in one patient. CONCLUSIONS: We conclude that pancreatitis can be the only presenting complaint of PHPT. Our study highlights the importance of fully investigating for PHPT in any pancreatitis patient with high normal or raised serum calcium level, especially in the absence of other common causes of pancreatitis.

Preoperative contrast-enhanced computed tomographic characterisation of pancreatic cystic lesions: A prospective study.

BACKGROUND: Characterisation of pancreatic cystic lesions has a direct role in their management and computed tomography is the mainstay of investigation for diagnosing and characterising them. OBJECTIVES: The aim of this study was to prospectively assess the diagnostic accuracy of contrast-enhanced computed tomography (CECT) in preoperative characterisation of pancreatic cystic lesions with histopathology as the reference standard. METHOD: A total of 38 patients with cystic pancreatic lesions diagnosed after clinical, laboratory and sonographic evaluation, irrespective of age, were preoperatively evaluated with CECT. Images were reviewed for the general characteristics of the lesions on pre-contrast and portal venous phase images and overall diagnostic accuracy calculated. Imaging findings were compared with histopathology, or cytology and/or intra-operative findings. RESULTS: Serous cystadenoma (SCA) was the most common cystic pancreatic lesion found in 31.6% of patients followed by mucinous cystadenoma (MCA) (26.3%), solid pseudo-papillary tumour (SPT) (21.1%) and intra-ductal papillary mucinous neoplasm (IPMN) (10.5%). Three patients (7.9%) had simple cysts and one patient (2.6%) had a lymphangioma. The diagnostic accuracy of CECT for pancreatic cystic lesions was found to be 72.5. CONCLUSION: The diagnostic accuracy of computed tomography (CT) was high for SCA, IPMN and pancreatic cysts, and low for MCA and SPT. Combination of a multiloculated cystic lesion with locule size of less than 20 mm, septal enhancement with relative lack of wall enhancement, central scar and lobulated outline are highly specific for SCA. Unilocular or macro-cystic pattern with locule size of more than 20 mm, female gender and wall enhancement with smooth external contour are pointers towards MCA. Solid cystic pancreatic head lesions in young females may be suggestive of SPT. A dilated main pancreatic duct in a cystic lesion with internal septations may point towards IPMN. Fluid attenuation lesions with imperceptible non-enhancing wall indicate pancreatic cysts. Lastly, pseudocysts and neuroendocrine tumours with cystic components are great mimickers of pancreatic cystic lesions, and a history of pancreatitis and hormonal profile of patients should always be sought.

Evaluation of various patient-, lesion-, and procedure-related factors on the occurrence of pneumothorax as a complication of CT-guided percutaneous transthoracic needle biopsy.

PURPOSE: To assess the influence of various patient-, lesion-, and procedure-related variables on the occurrence of pneumothorax as a complication of CT-guided percutaneous transthoracic needle biopsy. MATERIAL AND METHODS: In a total of 208 patients, 215 lung/mediastinal lesions (seven patients were biopsied twice) were sampled under CT guidance using coaxial biopsy set via percutaneous transthoracic approach. Incidence of post procedure pneumothorax was seen and the influence of various patient-, lesion-, and procedure-related variables on the frequency of pneumothorax with special emphasis on procedural factors like dwell time and needle-pleural angle was analysed. RESULTS: Pneumothorax occurred in 25.12% (54/215) of patients. Increased incidence of pneumothorax had a statistically significant correlation with age of the patient (p = 0.0020), size (p = 0.0044) and depth (p = 0.0001) of the lesion, and needle-pleural angle (p = 0.0200). Gender of the patient (p = 0.7761), emphysema (p = 0.2724), site of the lesion (p = 0.9320), needle gauge (p = 0.7250), patient position (p = 0.9839), and dwell time (p = 0.9330) had no significant impact on the pneumothorax rate. CONCLUSIONS: This study demonstrated a significant effect of the age of the patient, size and depth of the lesion, and needle-pleural angle on the incidence of post-procedural pneumothorax. Emphysema as such had no effect on pneumothorax rate, but once pneumothorax occurred, emphysematous patients were more likely to be symptomatic, necessitating chest tube placement. Gender of the patient, site of the lesion, patient position during the procedure, and dwell time had no statistically significant relation with the frequency of post-procedural pneumothorax. Surprisingly, needle gauge had no significant effect on pneumothorax frequency, but due to the small sample size, non-randomisation, and bias in needle size selection as per lesion size, further studies are required to fully elucidate the causal relationship between needle size and post-procedural pneumothorax rate. The needle should be as perpendicular as possible to the pleura (needle-pleural angle close to 90°), to minimise the possibility of pneumothorax after percutaneous transthoracic needle biopsy.

Preoperative contrast-enhanced computed tomographic characterisation of pancreatic cystic lesions: a prospective study

Background: Characterisation of pancreatic cystic lesions has a direct role in their management and computed tomography is the mainstay of investigation for diagnosing and characterising them. Objectives: The aim of this study was to prospectively assess the diagnostic accuracy of contrast-enhanced computed tomography (CECT) in preoperative characterisation of pancreatic cystic lesions with histopathology as the reference standard. Method: A total of 38 patients with cystic pancreatic lesions diagnosed after clinical, laboratory and sonographic evaluation, irrespective of age, were preoperatively evaluated with CECT. Images were reviewed for the general characteristics of the lesions on pre-contrast and portal venous phase images and overall diagnostic accuracy calculated. Imaging findings were compared with histopathology, or cytology and/or intra-operative findings. Results: Serous cystadenoma (SCA) was the most common cystic pancreatic lesion found in 31.6% of patients followed by mucinous cystadenoma (MCA) (26.3%), solid pseudo-papillary tumour (SPT) (21.1%) and intra-ductal papillary mucinous neoplasm (IPMN) (10.5%). Three patients (7.9%) had simple cysts and one patient (2.6%) had a lymphangioma. The diagnostic accuracy of CECT for pancreatic cystic lesions was found to be 72.5%. Conclusion: The diagnostic accuracy of computed tomography (CT) was high for SCA, IPMN and pancreatic cysts, and low for MCA and SPT. Combination of a multiloculated cystic lesion with locule size of less than 20 mm, septal enhancement with relative lack of wall enhancement, central scar and lobulated outline are highly specific for SCA. Unilocular or macro-cystic pattern with locule size of more than 20 mm, female gender and wall enhancement with smooth external contour are pointers towards MCA. Solid cystic pancreatic head lesions in young females may be suggestive of SPT. A dilated main pancreatic duct in a cystic lesion with internal septations may point towards IPMN. Fluid attenuation lesions with imperceptible non-enhancing wall indicate pancreatic cysts. Lastly, pseudocysts and neuroendocrine tumours with cystic components are great mimickers of pancreatic cystic lesions, and a history of pancreatitis and hormonal profile of patients should always be sought

Amelogenesis Imperfecta with Distal Renal Tubular Acidosis: A Novel Syndrome?

Amelogenesis imperfecta (AI) is a heterogeneous group of inherited dental enamel defects. It has rarely been reported in association with multiorgan syndromes and metabolic disorders. The metabolic disorders that have been reported in association with AI include hypocalciuria, impaired urinary concentrating ability, and Bartter-like syndrome. In literature, only three cases of AI and distal renal tubular acidosis (dRTA) have been described: two cases in adults and a solitary case in the pediatric age group. Here, we report a child with AI presenting with dRTA; to the best of our knowledge, our reported case is the only second such case in pediatric age group. Our case highlights the importance of recognizing the possibility of renal abnormalities in patients with AI as it will affect the long-term prognosis.

Is foliar spray of proline sufficient for mitigation of salt stress in Brassica juncea cultivars?

The effects of foliar application of proline (20 mM) on growth, physio-biochemical, and yield parameters were assessed in two Brassica juncea (L.) Czern & Coss cultivars, namely, Varuna and RH-30, at different levels (2.8, 4.2, or 5.6 dsm(-1)) of NaCl in soil. At 29 days after sowing (DAS), plants were sprayed with either 20 mM proline or water in the presence or absence of NaCl stress. The NaCl negatively affected parameters related to growth, photosynthesis, and yield in both varieties but more in RH-30 than in Varuna. Exogenous application of proline counteracted the effects of salt stress in Varuna only, by increasing the antioxidative capacity of the plants. Moreover, proline was not effective in alleviating the detrimental effects of higher salt concentrations on the studied parameters. Proline application to unstressed plants increased growth, photosynthesis, and yield parameters in both varieties; however, the effects were more prominent in Varuna than in RH-30.

Pattern of high voltage electrical injuries in the Kashmir valley: a 10-year single centre experience.

The objective was to study the clinical profile of high voltage electrical injuries in Kashmir, and various prevention and safety measures to bring down the incidence of such injuries in the future. All patients (176) with high voltage electrical injuries reporting to our centre from January 2001 to December 2010 were included in the study. The most common age group was 20-40 years, with mean age of 29.77 ± 8.98 years. Incidence was higher among the rural population (68.75%) than in urban areas (31.25%), and in the winter months. Electricians comprised 47.16% of victims. The most common mode of injury was touching a live wire directly or indirectly, and was seen in 63.64% of victims. Average total body surface burned was 15.27 ± 10.15 percent. Right upper limb was most commonly involved (64.20% of patients). Compartment syndrome was seen in 40.34% of patients, and fasciotomies on all the affected limbs saved around half of them. An average of 3.91 surgical procedures per patient were performed. Around one-third of the victims required major amputations. Reconstructive procedures were required in 49.43% of patients. Average hospital stay was 26.81 days. Average mortality rate was 2.27%. High voltage electrical injuries are not uncommon in the Kashmir Valley, and electrical workers are at higher risk. The incidence of high voltage injuries would not be so high if the workers were properly trained, hazards of high-tension lines were explained and the use of safety equipment was made mandatory.

L'objectif de ce travail était d'étudier l'épidémiologie des électrisations par haut voltage au Cachemire pour définir des axes de prévention. Les dossiers des 176 patients s'étant présentés dans notre CTB en raison de ce type de blessure entre janvier 2001 et décembre 2010 ont été étudiés. L'âge moyen était de 29,77 +/- 8,98 ans, avec une majorité de patients de la tranche 20-40 ans. Ils étaient en majorité (68,75%) ruraux et l'accident était plus fréquent en hiver. Les électriciens représentaient 47,16% des patients. Le contact, direct ou indirect, avec une ligne était le mécanisme le plus fréquent (63,64%). La surface brûlée était de 15,27 +/- 10,15% et le membre supérieur droit était atteint dans 64,2% des cas. Un syndrome compartimental a été observé dans 40,34% des cas, des aponévrotomies ayant permis de sauver la moitié des membres atteints. Les patients ont eu besoin d'une moyenne de 3,91 interventions chirurgicales, 1/3 d'entre eux ayant dû être amputés et presque la moitié (49,43%) du total ayant eu besoin de chirurgie reconstructrice. La durée moyenne d'hospitalisation a été de 26,81 jours, la mortalité de 2,27%. Les électrisations par haut voltage ne sont pas rares au Cachemire, les électriciens étant des sujets à risque. L'incidence serait moindre si les professionnels avaient une meilleure éducation sur les dangers de l'électricité et si l'utilisation des équipements de protection était rendue obligatoire.

Development of OMP based indirect ELISA to gauge the antibody titers in bovines against Pasteurella multocida.

Pasteurella multocida (P. multocida) is an important pathogen of various domestic animals. The outer membrane proteins (OMPs) play a major role in pathogenesis and immunogenicity of P. multocida. The aim of the study was to develop indirect enzyme linked immuno sorbant assay (ELISA) based on OMPs to ascertain the antibody titers in animals post-infection or to gauge the potency of vaccine. The OMPs were extracted and purified from P. multocida P:52 (vaccine strain) and P. multocida B:2 isolated from natural outbreak of Haemorrhagic septicaemia (HS) and analyzed on SDS PAGE and through western blot. The OMPs profile of the vaccine strain and the isolate from the natural outbreak of HS were found to be similar. Optimization of various components viz. coating antigens, anti-species conjugate, etc. were carried out against both anti-P. multocida hyper immune and pre immune serum. Validation of OMP based indirect ELISA assay to measure immune response against P. multocida in bovine revealed 91% diagnostic sensitivity (DSN) and about 100% diagnostic specificity (DSP) at 25% cut off. OMP based indirect ELISA was found to be more specific, but less sensitive as compared to WCL based assay.

Infectious lameness among migratory sheep and goats in north-west India, with particular focus on anaerobes.

Various bacterial species, particularly Dichelobacter nodosus, Fusobacterium necrophorum, Trueperella pyogenes (previously Arcanobacterium pyogenes) and Treponema spp., have been implicated in infectious conditions manifesting in lameness in sheep and goat populations. The current study reports the causes of infectious lameness in the north-western Himalayan region, particularly Himachal Pradesh (HP), where no such study has been conducted in the past. Among a total surveyed population of 27,586 animals, comprised of 15,006 sheep and 12,580 goats, 216 samples were collected from foot lesions. A total of 6.48% (14/216) samples were positive for D. nodosus, 20.83% (45/216) for F. necrophorum and 20.37% (44/216) for T pyogenes. In three instances, all of the three aforementioned bacteria were present in a single foot lesion. Most of the positive samples were from areas in the state of HP adjoining the state of Jammu and Kashmir (J&K), where footrot is endemic. The confirmation of footrot in HP and the fact that F. necrophorum and T pyogenes were detected from cases of foot/hoof infection in high numbers emphasises thatthese organisms play an important role in inducing morbidity in migratory sheep and goats. The present investigation also confirms the detection of D. nodosus from cases of footrot for the first time from HP. With new reports identifying F. necrophorum as a pathogen with a potential role in aggravating infection caused by footrot, the development of a combined vaccine to prevent lameness in sheep and goats in the north-western Himalayan region has been suggested.

USP7 modulates UV-induced PCNA monoubiquitination by regulating DNA polymerase eta stability.

DNA polymerase eta (Polη) has unique and pivotal functions in several DNA damage-tolerance pathways. Steady-state level of this short-lived protein is tightly controlled by multiple mechanisms including proteolysis. Here, we have identified the deubiquitinating enzyme (DUB), ubiquitin-specific protease 7 (USP7), as a novel regulator of Polη stability. USP7 regulates Polη stability through both indirect and direct mechanisms. Knockout of USP7 increased the steady-state level of Polη and slowed down the turnover of both Polη and p53 proteins through destabilizing their E3 ligase murine double minute 2 (Mdm2). Also, USP7 physically binds Polη in vitro and in vivo. Overexpression of wild-type USP7 but not its catalytically-defective mutants deubiquitinates Polη and increases its cellular steady-state level. Thus, USP7 directly serves as a specific DUB for Polη. Furthermore, ectopic expression of USP7 promoted the UV-induced proliferating cell nuclear antigen (PCNA) monoubiquitination in Polη-proficient but not in Polη-deficient XPV (Xeroderma pigmentosum variant) cells, suggesting that USP7 facilitates UV-induced PCNA monoubiquitination by stabilizing Polη. Taken together, our findings reveal a modulatory role of USP7 in PCNA ubiquitination-mediated stress-tolerance pathways by fine-tuning Polη turnover.

Persistence of metalaxyl and mancozeb on potato leaves and their residues in tubers.

The persistence of fungicides on two commercial cultivars of potato was determined under field conditions at Punjab Agricultural University, Ludhiana, Punjab. Initial deposits of mancozeb on potato leaves were found to be 26.9 and 38.7 mg kg(-1), following application of ready mixture of fungicide metalaxyl 8% + mancozeb 64% (Ridomil MZ) at the rate of 1260 and 2520 g a.i. ha(-1), whereas metalaxyl residues were found to be 35.1 and 49.5 mg kg(-1), respectively. The residue level of mancozeb in potato leaves 15 days after application at single and double doze were 19.0 and 27.0 mg kg(-1) showing a loss of 29.6 and 30.3%, whereas the values for metalaxyl at single and double doze were 0.40 and 0.80 mg kg(-1) showing a loss of 98.9 and 98.4%, respectively. Residues of mancozeb and metalaxyl were not detected at 0.04 and 0.02 mg kg(-1) level in potato tubers at harvest (PHI = 53 days) at both the dosages, respectively. The persistence and dissipation of mancozeb with the application of Ridomil MZ followed similar trend as in Indofil M-45. The rate of fungicide dissipation increased with time after application in both the potato cultivars 'Kufri Chandramukhi' and 'Chipsona'. No significant difference was observed on initial deposit, persistence and dissipation of the two molecules between the two potato cultivars.

Effect of post-harvest calcium chloride dip treatment and gamma irradiation on storage quality and shelf-life extension of Red delicious apple.

Freshly harvested Red delicious apples were dipped in calcium chloride solution of varying concentrations (0.5-2.0% w/v) for 1 h prior to irradiation at dose level of 0.4 kGy. Fruits after radiation treatment were stored at 2 ± 1°C, RH 90% and evaluated at intervals of 30 days for various quality parameters. Results revealed significant (p ≤ 0.05) retention in firmness, juice yield and ascorbic acid content in samples treated with combination of calcium chloride at 2.0% w/v and gamma irradiation (0.4 kGy) during storage. Water soluble pectin was inversely correlated with firmness (r = 0.88) and was significantly (p ≤ 0.05) lower in samples subjected to combination treatment of 2.0% w/v CaCl2 and 0.4 kGy irradiation throughout the storage. The combination treatment of 2.0% CaCl2 and 0.4 kGy irradiation gave about 4.3 log reduction in yeast and mold count of apple samples. Results of the post refrigeration weight loss, firmness and overall acceptability revealed that combination treatment was helpful in extending the shelf-life of Red Delicious apples by around 20-25 days at 17 ± 2°C, RH 75% following 90 days of refrigeration.

Integrin-linked kinase regulates melanoma angiogenesis by activating NF-κB/interleukin-6 signaling pathway.

Integrin-linked kinase (ILK) is a highly conserved serine-threonine protein kinase involved in cell-extracellular matrix interactions, cytoskeletal organization and cell signaling. Overexpression of ILK in epithelial cells leads to anchorage-independent growth with increased cell cycle progression. Previously, we have shown that ILK upregulation strongly correlates with melanoma progression, invasion and inversely correlates with 5-year survival of melanoma patients. However, the molecular mechanism by which ILK enhances melanoma progression is currently unknown. In the present study, we found that proangiogenic molecule interleukin-6 (IL-6) is the downstream target of ILK in melanoma cells. ILK overexpression increased IL-6, whereas silencing of ILK suppressed IL-6 expression at both messenger RNA and protein levels. ILK also altered the activity and subcellular localization of nuclear factor-kappaB (NF-κB) subunit p65. We further found that ILK enhanced the IL-6 gene transcription by promoting the binding of NF-κB p65 to IL-6 promoter. Moreover, ILK overexpression in melanoma cells enhanced the tube-forming ability of endothelial cells in vitro and microvessel formation in vivo. ILK-induced tube and blood vessel formation of endothelial cells was significantly reduced upon IL-6 inhibition in ILK-overexpressing melanoma cells. To delineate the mechanism by which ILK-induced IL-6 production can enhance angiogenesis, further analysis of the downstream targets of IL-6 signaling showed an increased activity of the signal transducer and activator of transcription 3 (STAT3) in ILK-overexpressing cells. As STAT3 binds to vascular endothelial growth factor (VEGF) promoter, we found that VEGF levels were elevated in ILK-overexpressing cells and declined upon transfection of IL-6 small interfering RNA, suggesting that ILK may regulate VEGF expression through IL-6 pathway by activating STAT3.

Physicochemical and dough-handling characteristics of Indian wheat and triticale cultivars.

Four bread wheat (PBW-138, PBW-299, PBW-343 and PBW-373), two durum wheat (PDW-215 and PDW-233) and two triticale cultivars (TL-419 and TL-1210) were investigated for physicochemical, milling and dough-handling properties for predicting end-use quality. Physical properties of durum wheat (PDW-215) and bread wheat (PBW-138, PBW-299 and PBW-343) cultivars were better than other wheat, durum and triticale cultivars. The compositional analysis revealed nonsignificant differences between the different cultivars; however, starch observed significant variation for different varieties. Particle size distribution indicated that triticale flours showed lower particle size than wheat and durum wheat. Dough-handling studies revealed triticale flours to be the weakest, while bread wheat flours were observed to be intermediate between durum and triticale. Among all the varieties, the bread wheat (PBW-138) variety was observed to be best, followed by PDW-215 durum wheat variety. Strong correlations were observed between physicochemical and dough-handling parameters, which can be used as quality parameter for suitable end-use.

Causes of mortality in diabetes mellitus: data from a tertiary teaching hospital in India.

BACKGROUND: Mortality studies can show the relative contribution of diabetes to mortality in the total population, and they can provide important descriptions of the changes in causes and frequency of diabetes mortality over time. OBJECTIVE: To find the mortality pattern in people with diabetes admitted to a tertiary care hospital in a developing country, using underlying/contributory causes of death. METHODS: In this retrospective study, mortality trends among people with diabetes admitted to Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India were reviewed by screening the hospital records of all people with diabetes who died over the last 9 years, carrying forward earlier observations from the same centre. RESULTS: Of 234 776 people admitted to the centre during the review period, 16 690 (7.11%) died; 741 (383 men) of these had diabetes mellitus mentioned on the death certificate. The mean (SD) age at death for people with diabetes was 60.07 (13.62) years in men and 57.36 (13.40) years in women. The leading contributory causes of death were infections (40.9%), chronic renal failure (33.6%), coronary artery disease (16.9%), cerebrovascular disease (13.2%), chronic obstructive pulmonary disease (6.9%), acute renal failure (6.2%), malignancy (4.2%), hypoglycaemia (3.5%) and diabetic ketoacidosis (3.4%). The cause of death could not be ascertained in 2.8% of cases; in 52.9%, 36.3% and 8.0% cases one, two and three or more causes, respectively, were recorded as the cause of death. CONCLUSIONS: The aetiological spectrum of mortality in people with diabetes at this Indian centre continues to be dominated by infections and renal failure, which is different from that in the developed world, where coronary artery disease and cerebrovascular disease are the principal causes of death in people with diabetes.