Background: The prevalence of osteoarthritis among elderly is high and it majorly affects the quality of life. Knee osteoarthritis is the most common form of osteoarthritis. Timely diagnosis using clinical criteria and effective intervention is of utmost importance.
Aim: To estimate the prevalence and determinants of osteoarthritis of knee joint among elderly persons residing in an urban slum of Delhi using ACR clinical criteria.
Materials and Methods: We did a community-based cross-sectional study among 496 elderly (>= 60 years) persons residing in urban slum of Delhi, India from December 2009 to February 2010. The American College of Rheumatology (ACR) criteria was used to clinically diagnose osteoarthritis knee.
Statistical Analysis: Bivariate analysis using Chi-square test and multivariate analysis was done to identify the determinants. Sensitivity and specificity of individual factors to diagnose osteoarthritis knee was calculated.
Results: The prevalence of osteoarthritis was estimated to be 41.1% (95% C.I., 36.7-45.6). Female sex and age >= 70 y were found to be independent risk factor for osteoarthritis knee. Among those having knee pain, presence of crepitus and tenderness were the most sensitive factors whereas bone overgrowth and bone warmth were most specific factors.
Conclusion: The prevalence of osteoarthritis knee was high among this elderly population and increased with age. Overall, individual factors of ACR criteria were both sensitive and specific in diagnosing osteoarthritis knee. In resource constrained setting of urban India, it can be an effective tool in clinical diagnosis of osteoarthritis knee.
Aged; Diagnosis; Osteoarthritis
The world of Dermatology is flooded with inflexions among clinical conditions and signs and syndromes; making it interesting, but a tougher subject to remember. Signs and syndromes have always fascinated residents, but simultaneously burdened their minds, as these attractive names are difficult to remember. This work was undertaken to review dermatological conditions and signs based on commonly encountered daily words and objects like animals, etc. Fifty dermatological conditions were found to be based on animal eponyms. For example, the usage of animal terminology in dermatology like leonine facies is present in leprosy, sarcoidosis, mycosis fungoides (MF), and airborne contact dermatitis (ABCD).
Animal eponyms; signs and syndrome; simpler associations
Glucose and oxygen deprivation during ischemia is known to affect the homeostasis of the endoplasmic reticulum (ER) in ways predicted to activate the unfolded protein response (UPR). Activation of UPR signalling due to ER stress is associated with the development of myocardial infarction (MI). MicroRNAs (miRNAs) are key regulators of cardiovascular development and deregulation of miRNA expression is involved in the onset of many cardiovascular diseases. However, little is known about the mechanisms regulating the miRNA expression in the cardiovascular system during disease development and progression. Here we performed genome-wide miRNA expression profiling in rat cardiomyoblasts to identify the miRNAs deregulated during UPR, a crucial component of ischemia.
We found that expression of 86 microRNAs changed significantly during conditions of UPR in H9c2 cardiomyoblasts. We found that miRNAs with known function in cardiomyoblasts biology (miR-206, miR-24, miR-125b, miR-133b) were significantly deregulated during the conditions of UPR in H9c2 cells. The expression of miR-7a was upregulated by UPR and simulated in vitro ischemia in cardiomyoblasts. Further, ectopic expression of miR-7a provides resistance against UPR-mediated apoptosis in cardiomyoblasts. The ample overlap of miRNA expression signature between our analysis and different models of cardiac dysfunction further confirms the role of UPR in cardiovascular diseases.
This study demonstrates the role of UPR in deregulating the expression of miRNAs in MI. Our results provide novel insights about the molecular mechanisms of deregulated miRNA expression during the heart disease pathogenesis.
Unfolded protein response; ER stress; MicroRNAs; Myocardial infarction; Mir-7a; Apoptosis
Identification by molecular imaging of key processes in handling of transition state metals, such as copper (Cu), will be of considerable clinical value. For instance, the ability to diagnose Wilson’s disease with molecular imaging by identifying copper excretion in an ATP7B-dependent manner will be very significant. To develop highly effective diagnostic approaches, we hypothesized that targeting of radiocopper via the asialoglycoprotein receptor will be appropriate for positron emission tomography, and examined this approach in a rat model of Wilson’s disease. After complexing 64Cu to asialofetuin we studied handling of this complex compared with 64Cu in healthy LEA rats and diseased homozygous LEC rats lacking ATP7B and exhibiting hepatic copper toxicosis. We analyzed radiotracer clearance from blood, organ uptake, and biliary excretion, including sixty minute dynamic positron emission tomography recordings. In LEA rats, 64Cu-asialofetuin was better cleared from blood followed by liver uptake and greater biliary excretion than 64Cu. In LEC rats, 64Cu-asialofetuin activity cleared even more rapidly from blood followed by greater uptake in liver, but neither 64Cu-asialofetuin nor 64Cu appeared in bile. Image analysis demonstrated rapid visualization of liver after 64Cu-asialofetuin administration followed by decreased liver activity in LEA rats while liver activity progressively increased in LEC rats. Image analysis resolved this difference in hepatic activity within one hour. We concluded that 64Cu-asialofetuin complex was successfully targeted to the liver and radiocopper was then excreted into bile in an ATP7B-dependent manner. Therefore, hepatic targeting of radiocopper will be appropriate for improving molecular diagnosis and for developing drug/cell/gene therapies in Wilson’s disease.
ATP7B; diagnosis; metal complex; positron emission tomography; radiocopper; therapy; Wilson’s disease
Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection.
Coagulopathy in acute promyelocytic leukemia (APL) is a very complex disorder and is believed to result from interplay of various factors. Usually patients present with bleeding tendencies which can be life threatening. However, a few present with thromboses. Here, we report a young male with APL who presented with ischemic stroke in young.
Mesenchymal stem cells (MSCs) have been reported to preserve renal function in various models of acute kidney injury (AKI). Different routes were used to transplant MSCs but the role of cell transplantation routes in directing outcomes has been unknown. In the present study, we evaluated organ bio-distributions of transplanted MSCs, and correlated survival of transplanted cells with outcomes in mice with cisplatinum-induced AKI. We found that after intravenous administration MSCs were largely localized in pulmonary capillaries and only a minute fraction of MSCs entered kidneys and the cells survived only transiently. Therefore, we also transplanted MSCs via intraperitoneal and renal subcapsular routes. Transplanted MSCs survived longer in peritoneal cavity and renal subcapsular space. Interestingly, when MSCs transplantation was followed by cisplatinum-induced AKI, renal morphology and renal functions were better preserved, irrespective of the cell transplantation route. As transplanted MSCs did not migrate to kidneys from either peritoneal cavity or renal subcapsular space, this finding suggested that migration of cells was not required for the beneficial response. The possibility of indirect mechanisms was confirmed when administration of the conditioned medium from MSCs also protected renal tubular cells from cisplatinum-induced cytotoxicity. We identified presence of over forty regulatory cytokines in the conditioned medium obtained from MSCs. Since paracrine factors released by transplanted cells accounted for improvements, it appears that the route of cell transplantation is not critical for realizing benefits in AKI of cell therapy with MSCs. Studies of specific cytokines secreted by MSCs will help to obtain new therapeutic mechanisms for renal protection.
Data on the knowledge of cardiovascular risk factors among Indian school children are limited. Aim of the study was to assess the prevalence of cardiovascular risk factors and its knowledge among school children of Delhi.
We performed a cross-sectional survey among 485 school children studying in classes 6, 7 and 8 in two government and one private school in New Delhi using convenience sampling. Cardiovascular risk factors (physical activity, diet and smoking), knowledge about risk factors and family profile were assessed using a structured self report questionnaire. Weight, height and blood pressure measurements were taken.
The mean age of the studied school children was 12.8 ± 1.6 years. The prevalence of overweight and obesity was 9.5% and 11.5% respectively. The prevalence of prehypertension, stage 1 hypertension and stage 2 hypertension was 12.4%, 6.8% and 1.4% respectively. Of the total, 43.8% were physically active for at least 1 hour per day on all 7 days of the previous week. Daily consumption of fruits and vegetables was reported by 42% and 76% of the school children respectively. Nearly 5% of the school children reported to have used any form of tobacco. One fifth of the school children had a family history of cardiovascular disease. Of the total, 25.4% had adequate knowledge regarding cardiovascular risk factors.
Cardiovascular risk factors are highly prevalent among school children. Importantly, school children lack adequate knowledge regarding cardiovascular risk factors. School based interventions are required for cardiovascular risk reduction in childhood.
Cardiovascular risk factors; Knowledge; School children; Delhi
Intraperitoneal infection known as peritonitis is a major killer in the practice of clinical surgery. Tertiary peritonitis (TP) may be defined as intra-abdominal infection that persists or recurs ³48 h following successful and adequate surgical source control. A planned or on-demand relaparotomy after an initial operation is probably most frequent way to diagnose TP, but is a late event to occur. Hence it is desirable to have timely and nonoperative diagnosis of TP after the initial operation and subsequent initiation of an appropriate therapy to reduce the complications and to improve the outcome.
Mannheim peritonitis index; simplified acute physiology score II; tertiary peritonitis
To optimize strategies for liver-directed cell therapy prevention of initial transplanted cell losses is particularly important for subsequent liver repopulation. After cell transplantation in hepatic sinusoids, perturbations in hepatic microcirculation along with changes in various liver cell types are among the earliest changes. Therefore, for advancing further concepts in cell engraftment, we studied vascular and related events in the liver after transplanting syngeneic hepatocytes into dipeptidyl peptidase IV-deficient rats. We treated rats with vascular drugs to define whether deleterious cell transplantation-induced events could be controlled followed by improvements in transplanted cell engraftment and proliferation. We found cell transplantation altered liver gene expression related to vessel tone, inflammation, cell adhesion, thrombosis, or tissue damage/remodeling. This was due to hepatic ischemia, endothelial injury and activation of neutrophils, Kupffer cells and hepatic stellate cells. Treatment of rats before cell transplantation with angiotensin converting enzyme blocker, lisinopril, or angiotensin II receptor blocker, losartan, did not improve cell engraftment. By contrast, direct-acting nitroglycerine or prostacyclin improved cell engraftment and also kinetics of liver repopulation. These drugs lowered hepatic ischemia and inflammation. Whereas pretreatment of rats with the dual endothelin-1 receptor blocker, bosentan, improved cell engraftment independently of hepatic ischemia or inflammation, without improving liver repopulation. However, incubation of hepatocytes with bosentan protected cells from cytokine toxicity in vitro and produced superior cell engraftment and proliferation in vivo. We concluded that cell transplantation-induced changes in hepatic microcirculation contributed to transplanted cell clearances from liver. Vascular drugs, such as nitroglycerine, prostacyclin and bosentan, offer opportunities for improving cell therapy results through superior cell engraftment and liver repopulation. Ongoing clinical use of these drugs will permit rapid translation of the findings in people.
Cell therapy; Inflammation; Ischemia; Vascular; Drugs
Persistent inflammation and impaired neovascularization in type 2 diabetes mellitus (T2DM) patients may lead to development of macro- and microvascular complications. Diabetic retinopathy (DR) is one of the secondary microvascular complications of T2DM. Improper activation of the innate immune system may be an important contributor in the pathophysiology of DR. Toll-like receptor 4 (TLR4) is an important mediator of innate immunity, and genetic alterations in TLR4 support inflammation in the hyperglycemic condition. The present work was designed to investigate whether the TLR4 single nucleotide polymorphisms (SNPs) rs4986790, rs4986791, rs10759931, rs1927911, and rs1927914 are associated with DR in a north Indian population.
The study group of 698 individuals (128 DR, 250 T2DM, 320 controls) was genotyped by PCR-RFLP. Haplotype and linkage disequilibrium between SNPs were determined using Haploview software.
Combined risk genotypes of TLR4 SNPs rs10759931 (odds ratio [OR] 1.50, p = 0.05) and rs1927914 (OR 1.48, p = 0.05) were found to be significantly associated with pathogenesis of DR. A total of 14 haplotypes with frequency >1% were obtained using Haploview software. Haplotypes ACATC (37.5%) and ACATT (14.8%) were the two most common haplotypes obtained.
Results of the present case-control study that included 698 north Indian subjects suggested that TLR4 SNPs rs10759931 and rs1927914 modulate the risk of DR in T2DM cases. Association analysis using haplotypes showed none of the haplotypes were associated with either susceptibility or resistance to DR in a north Indian population.
Dicer, an RNase III-type endonuclease, is the key enzyme involved in RNA interference and microRNA pathways. Aberrant expression of Dicer is reported in several human cancers. Our aim was to assess the prognostic role of Dicer in breast cancer.
The entire series comprised 666 invasive breast cancers (IBCs), 480 DCIS cases (397 associated with IBC and 83 pure DCIS) and 305 lymph node metastases. Cytoplasmic Dicer expression by immunohistochemistry was scored as negative (no staining) and positive (weak, moderate or strong staining).
Dicer staining was assessable in 446 IBC, 128 DCIS and 101 lymph node metastases. Expression of Dicer was observed in 33% (145/446) of IBCs, 34% (44/128) of DCIS and 57% (58/101) of lymph node metastases. Dicer expression was increased in nodal metastases compared to primary tumours (p<0.001); and was associated with ER negativity (p<0.001), HER2 positivity (p<0.001), high Ki67 labeling index (p<0.001) and expression of basal-like biomarkers (p = 0.002). Dicer positivity was more frequent in the HER2 overexpressing (p<0.001) and basal-like (p = 0.002) subtypes compared to luminal A subtype. Dicer expression was associated with reduced overall survival (OS) on univariate analysis (p = 0.058) and remained an independent predictor of OS on multivariate analysis (HR 2.84, 95% CI 1.43–5.62, p = 0.003), with nodal status (HR 2.61, 95% CI 1.18–5.80, p = 0.018) and PR (HR 0.28, 95% CI 0.13–0.59, p = 0.001). Further, moderate or strong expression of Dicer was associated with improved disease-free survival in the HER2-overexpressing subtype compared to negative or weak expression (p = 0.038).
Deregulated Dicer expression is associated with aggressive tumour characteristics and is an independent prognostic factor for OS. Our findings suggest that Dicer is an important prognostic marker in breast cancer and that its prognostic role may be subtype specific.
Necrotizing soft tissue infections (NSTIs) are fulminant infections of any layer of the soft tissue compartment associated with widespread necrosis and systemic toxicity. Delay in diagnosing and treating these infections increases the risk of mortality. Early and aggressive surgical debridement with support for the failing organs significantly improves the survival. Although there are different forms of NSTIs like Fournier's gangrene or clostridial myonecrosis, the most important fact is that they share common pathophysiology and principles of treatment. The current paper summarizes the pathophysiology, clinical features, the diagnostic workup required and the treatment principles to manage these cases.
Hepatocyte transplantation; Injury; Rescue; Stem cells; Tissue engineering
Nanotechnology (nano: One billionth) is a novel arena with promising applications in the field of medicine, especially pharmaceuticals for safe and targeted drug delivery. The skin is a phenomenal tool for investigation of nanocarriers for drug delivery for topical and dermatological application. The physicochemical characteristics of the nanoparticles, such as rigidity, hydrophobicity, size and charge are crucial to the skin permeation mechanism. Many nanocarriers such as polymeric, inorganic and lipid nanoparticles and nanoemulsions have been developed and some like carbon nanotubes and fullerenes still need further exploration for future use in skin care and dermatological treatments. Risks of nanopollution and cytotoxicity also need to be kept in mind while exploring various nanoparticles for medical use.
Nanocarriers; nanodermatology; nanomedicine; nanopollution nanotechnology
Objectives. To compare the outcome of dorsal buccal mucosal graft (BMG) substitution urethroplasty by dorsal urethrotomy approach with ventral urethrotomy approach in management of stricture urethra. Methods and Materials. A total of 40 patients who underwent dorsal BMG substitution urethroplasty were randomized into two groups. 20 patients underwent dorsal onlay BMG urethroplasty as described by Barbagli, and the other 20 patients underwent dorsal BMG urethroplasty by ventral urethrotomy as described by Asopa. Operative time, success rate, satisfaction rate, and complications were compared between the two groups. Mean follow-up was 12 months (6–24 months). Results. Ventral urethrotomy group had considerably lesser operative time although the difference was not statistically significant. Patients in dorsal group had mean maximum flow rate of 19.6 mL/min and mean residual urine of 27 mL, whereas ventral group had a mean maximum flow rate of 18.8 and residual urine of 32 mL. Eighteen out of twenty patients voided well in each group, and postoperative imaging study in these patients showed a good lumen with no evidence of leak or extravasation. Conclusion. Though ventral sagittal urethrotomy preserves the blood supply of urethra and intraoperative time was less than dorsal urethrotomy technique, there was no statistically significant difference in final outcome using either technique.
Leukemia cutis is the term used for cutaneous manifestations of leukemia, which can have varied clinical presentations. A skin biopsy can help in diagnosing such condition and differentiating it from other skin diseases. We present a case where a 45 years old man presented with diffuse papulovesicular skin lesions mimicking dessiminated herpes. Further workup revealed patient having acute myeloid leukemia (AML-M2) and skin biopsy showed infiltration by myeloblasts. With chemotherapy patient went into remission and skin lesions healed.
Acute myeloid leukemia; Leukemia cutis; Myeloperoxidase
Transplanting pancreatic islets is of significant interest for type 1 diabetes mellitus. After intraportal injection of islets, inferior engraftment and eventual loss of transplanted islets constitute major limitations. Therefore, alternative approaches will be helpful. Here, we evaluated in animals whether an isolated venous sac would support survival of transplanted islets, along with correction of hyperglycemia.
Pancreatic islets isolated from adult Lewis rats were transplanted either into an isolated venous sac made from lumbar vein or into the portal vein of syngeneic rats. The integrity and vascular organization of the venous sac was determined by studies of the local microcirculation. The engraftment, survival, and function of transplanted islets were analyzed by histology, including endocrine function in situ and by glycemic control in rats with streptozotocin-induced diabetes.
Transplanted islets showed normal morphology with insulin expression in isolated venous sac during the long term. Transplanted islets received blood supply from vasa vasorum and had access to drainage through venous tributaries in the venous sac. This resulted in restoration of euglycemia in diabetic rats. Removal of islet graft-bearing venous sac in diabetic rats led to recurrence of hyperglycemia. By contrast, euglycemia was not restored in rats treated by intraportal transplantation of islets.
We demonstrated that pancreatic islets successfully engrafted and functioned in the isolated venous sac with ability to restore euglycemia in diabetic rats. Therefore, the isolated venous sac offers a new site for transplantation of pancreatic islets. This would be clinically beneficial as an alternative to intrahepatic islet transplantation.
Islets; Pancreas; Intravascular transplantation
Global downregulation of microRNAs (miRNAs) is a common feature of human tumors and has been shown to enhance cancer progression. Several components of the miRNA biogenesis machinery (XPO5, DICER and TRBP) have been shown to act as haploinsufficient tumor suppressors. How the deregulation of miRNA biogenesis promotes tumor development is not clearly understood. Here we show that loss of miRNA biogenesis increased resistance to endoplasmic reticulum (ER) stress-induced cell death. We observed that HCT116 cells with a DICER hypomorphic mutation (Exn5/Exn5) or where DICER or DROSHA were knocked down were resistant to ER stress-induced cell death. Extensive analysis revealed little difference in the unfolded protein response (UPR) of WT compared to Exn5/Exn5 HCT116 cells upon ER stress treatment. However, analysis of the intrinsic apoptotic pathway showed that resistance occurred upstream of the mitochondria. In particular, BAX activation and dissipation of mitochondrial membrane potential was attenuated, and there was altered expression of BCL-2 family proteins. These observations demonstrate a key role for miRNAs as critical modulators of the ER stress response. In our model, downregulation of miRNA biogenesis delays ER stress-induced apoptosis. This suggests that disrupted miRNA biogenesis may contribute to cancer progression by inhibiting ER stress-induced cell death.
The Toll-Like receptor 4 (TLR4) plays an important role in immunity, tissue repair, and regeneration. The objective of the present work was to evaluate the association of TLR4 single nucleotide polymorphisms (SNPs) rs4986790, rs4986791, rs11536858 (merged into rs10759931), rs1927911, and rs1927914 with increased diabetic foot ulcer (DFU) risk in patients with type 2 diabetes mellitus (T2DM). PCR-RFLP was used for genotyping TLR4 SNPs in 125 T2DM patients with DFU and 130 controls. The haplotypes and linkage disequilibrium between the SNPs were determined using Haploview software. Multivariate linear regression (MLR) and artificial neural network (ANN) modeling was done to observe their predictability for the risk of DFU in T2DM patients. Risk genotypes of all SNPs except rs1927914 were significantly associated with DFU. Haplotype ACATC (P value = 9.3E − 5) showed strong association with DFU risk. Two haplotypes ATATC (P value = 0.0119) and ATGTT (P value = 0.0087) were found to be protective against DFU. In conclusion TLR4 SNPs and their haplotypes may increase the risk of impairment of wound healing in T2DM patients. ANN model (83%) is found to be better than the MLR model (76%) and can be used as a tool for the DFU risk assessment in T2DM patients.