NAPROXEN INDUCED ERYTHEMA MULTIFORME-A RARE CASE REPORT

Erythema multiforme (EM) is a hypersensitivity reaction characterized by varying degrees of blisters and ulcerations. We report a case of 4 y old girl child born for Non-custodial parents who has a history of seizures and a known case of carbamazepine-induced SLE (Systemic Lupus Erythematosus) when treated with anti-inflammatory drugs developed EM. The offending drug was identified and withdrawn. Steroid was given as a part of symptomatic treatment. Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed groups of drugs for a variety of indications. The patient gradually improved and got discharged

Alpha-synuclein aggresomes inhibit ciliogenesis and multiple functions of the centrosome.

Protein aggregates are the pathogenic hallmarks of many different neurodegenerative diseases and include the accumulation of α-synuclein, the main component of Lewy bodies found in Parkinson's disease. Aggresomes are closely-related, cellular accumulations of misfolded proteins. They develop in a juxtanuclear position, adjacent to the centrosome, the microtubule organizing centre of the cell, and share some protein components. Despite the long-standing observation that aggresomes/Lewy bodies and the centrosome sit side-by-side in the cell, no studies have been done to see whether these protein accumulations impede organelle function. We investigated whether the formation of aggresomes affected key centrosome functions: its ability to organise the microtubule network and to promote cilia formation. We find that when aggresomes are present, neuronal cells are unable to organise their microtubule network. New microtubules are not nucleated and extended, and the cells fail to respond to polarity cues. Since neurons are polarised, ensuring correct localisation of organelles and the effective intracellular transport of neurotransmitter vesicles, loss of centrosome activity could contribute to functional deficits and neuronal cell death in Parkinson's disease. In addition, we provide evidence that many cell types, including dopaminergic neurons, cannot form cilia when aggresomes are present, which would affect their ability to receive extracellular signals

Impact of hyperglycaemia on molecular markers of oxidative stress and antioxidants in type 2 diabetes mellitus

Introduction. The pathogenesis of type 2 diabetes mel­litus (T2DM) is strongly linked to oxidative stress mainly caused by chronic hyperglycaemia. The present study investigates the association between hyperglycaemia with oxidative stress markers, antioxidants and lipid profile. Materials and methods. The case-control study in­volved two groups, T2DM patients (n = 83) and age and sex matched controls (n = 81). Serum levels of various molecular markers malondialdehyde (MDA), reactive oxygen species (ROS) and nitric oxide (NO), su­peroxide dismutase (SOD), catalase (CAT), glutathione (GSH), vitamin C, total antioxidant capacity (TAC) and lipid parameters total cholesterol, triglycerides, low density lipoprotein (LDL) and high density lipoprotein (HDL) were measured using spectrophotometric as­says. Results were analysed to compare and correlate glycaemic levels with these molecular markers. Results. T2DM patients had a higher body mass index (BMI) and body fat percentage. 2 hour blood glucose, glycated haemoglobin A1c % (HbA1c), total cholesterol, triglycerides and LDL were higher in diabetics, HDL was found to be lower in diabetics than in controls. Mean levels of enzymatic and non-enzymatic antioxi­dants SOD, CAT, GSH, vitamin C and TAC were signifi­cantly lower while oxidative stress markers NO, ROS and MDA were higher in T2DM patients. NO showed a positive correlation (r = 0.3993, p < 0.0001) whereas TAC showed a negative correlation with glycaemia (r = –0.4796, p < 0.0001). Conclusions. Poor glycaemic control in T2DM causes elevated ROS and NO levels with increased lipid peroxi­dation and lowered antioxidant capacity. MDA and NO being the major risk factors could be used as a param­eter along with antioxidants to assess oxidative stress in T2DM patients

Distribution of chromosomal abnormalities commonly observed in adult acute myeloid leukemia in Pakistan as predictors of prognosis

Objective: The heterogenous response to treatment in acute myeloid leukemia (AML) can be attributed largely to the difference in cytogenetic features identified in between cases. Cytogenetic analysis in acute leukemia is now routinely used to assist patient management, particularly in terms of diagnosis, disease monitoring, prognosis and risk stratification. Knowing about cytogenetic profile at the time of diagnosis is important in order to take critical decisions in management of these patients. The study was conducted to determine the distribution of cytogenetic abnormalities in Pakistani adult patients with AML in order to have insights regarding behavior of the. method: A retrospective analysis of all the cases of AML (≥15years old) diagnosed at Aga Khan University from January 2011 to December 2016 was performed. Cytogenetic analysis was made for all cases using the trypsin-Giemsa banding technique. Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature (ISCN) criteria. Result: A total of 321 patients were diagnosed with AML during the study period, of which 288 samples successfully yielded metaphase chromosomes. The male to female ratio was 1.7:1. A normal karyotype was present in 61% (n=176) of the cases whereas, 39% (n=112) had an abnormal karyotype. Of the abnormal cases, t (8;21) (q22;q22) and t (15;17) (q22;q12) were identified in 8.3% and 4.9% cases respectively. Adverse prognostic cytogenetic subgroups including complex karyotype, monosomy 7 and t(6;9)(p23;q34) were identified in 9%, 1% and 0.7% patients respectively. Conclusion: This largest cytogenetic data in adult AML from Pakistan showed comparable prevalence of favorable prognostic karyotype to international data. The prevalence of specific adverse prognostic karyotype was low

Momordica charantia (bitter melon) inhibits primary human adipocyte differentiation by modulating adipogenic genes

<p>Abstract</p> <p>Background</p> <p>Escalating trends of obesity and associated type 2 diabetes (T2D) has prompted an increase in the use of alternative and complementary functional foods. <it>Momordica charantia </it>or bitter melon (BM) that is traditionally used to treat diabetes and complications has been demonstrated to alleviate hyperglycemia as well as reduce adiposity in rodents. However, its effects on human adipocytes remain unknown. The objective of our study was to investigate the effects of BM juice (BMJ) on lipid accumulation and adipocyte differentiation transcription factors in primary human differentiating preadipocytes and adipocytes.</p> <p>Methods</p> <p>Commercially available cryopreserved primary human preadipocytes were treated with and without BMJ during and after differentiation. Cytotoxicity, lipid accumulation, and adipogenic genes mRNA expression was measured by commercial enzymatic assay kits and semi-quantitative RT-PCR (RT-PCR).</p> <p>Results</p> <p>Preadipocytes treated with varying concentrations of BMJ during differentiation demonstrated significant reduction in lipid content with a concomitant reduction in mRNA expression of adipocyte transcription factors such as, peroxisome proliferator-associated receptor γ (PPARγ) and sterol regulatory element-binding protein 1c (SREBP-1c) and adipocytokine, resistin. Similarly, adipocytes treated with BMJ for 48 h demonstrated reduced lipid content, perilipin mRNA expression, and increased lipolysis as measured by the release of glycerol.</p> <p>Conclusion</p> <p>Our data suggests that BMJ is a potent inhibitor of lipogenesis and stimulator of lipolysis activity in human adipocytes. BMJ may therefore prove to be an effective complementary or alternative therapy to reduce adipogenesis in humans.</p

Induction of apoptosis of human primary osteoclasts treated with extracts from the medicinal plant Emblica officinalis

<p>Abstract</p> <p>Background</p> <p>Osteoclasts (OCs) are involved in rheumatoid arthritis and in several pathologies associated with bone loss. Recent results support the concept that some medicinal plants and derived natural products are of great interest for developing therapeutic strategies against bone disorders, including rheumatoid arthritis and osteoporosis. In this study we determined whether extracts of <it>Emblica officinalis </it>fruits display activity of possible interest for the treatment of rheumatoid arthritis and osteoporosis by activating programmed cell death of human primary osteoclasts.</p> <p>Methods</p> <p>The effects of extracts from <it>Emblica officinalis </it>on differentiation and survival of human primary OCs cultures obtained from peripheral blood were determined by tartrate-acid resistant acid phosphatase (TRAP)-positivity and colorimetric MTT assay. The effects of <it>Emblica officinalis </it>extracts on induction of OCs apoptosis were studied using TUNEL and immunocytochemical analysis of FAS receptor expression. Finally, <it>in vitro </it>effects of <it>Emblica officinalis </it>extracts on NF-kB transcription factor activity were determined by gel shift experiments.</p> <p>Results</p> <p>Extracts of <it>Emblica officinalis </it>were able to induce programmed cell death of mature OCs, without altering, at the concentrations employed in our study, the process of osteoclastogenesis. <it>Emblica officinalis </it>increased the expression levels of Fas, a critical member of the apoptotic pathway. Gel shift experiments demonstrated that <it>Emblica officinalis </it>extracts act by interfering with NF-kB activity, a transcription factor involved in osteoclast biology. The data obtained demonstrate that <it>Emblica officinalis </it>extracts selectively compete with the binding of transcription factor NF-kB to its specific target DNA sequences. This effect might explain the observed effects of <it>Emblica officinalis </it>on the expression levels of interleukin-6, a NF-kB specific target gene.</p> <p>Conclusion</p> <p>Induction of apoptosis of osteoclasts could be an important strategy both in interfering with rheumatoid arthritis complications of the bone skeleton leading to joint destruction, and preventing and reducing osteoporosis. Accordingly, we suggest the application of <it>Emblica officinalis </it>extracts as an alternative tool for therapy applied to bone diseases.</p

Development and evaluation of introgression lines with yield enhancing genes of the Indian mega-variety of rice, MTU1010

MTU 1010 is an early maturing and high-yielding mega rice variety widely grown in an area of 3 Mha. It is characterised by limited grain number and panicle branching. To improve the grain number in MTU 1010, an IRRI breeding line, IR121055-2-10-5 was utilized as donor to transfer yield-enhancing genes Gn1a and OsSPL14 (associated with increased grain number and better panicle branching, respectively) into MTU1010 by Marker-Assisted Backcross Breeding (MABB). At each backcross generation, foreground selection was carried out with Gn1a and OsSPL14- specific molecular markers, whilst background selection was done with a set of SSR markers polymorphic between the IR121055-2-10-5 and MTU1010. With the use of a gene-specific marker, homozygous BC2 F2 plants carrying the yield-enhancing gene were identified and advanced through pedigree-method of selection till BC2 F6 and best performing ten lines were selected and evaluated in replicated station trials for yield contributing traits, where grain number and brancing per panicle exhibited high significant and positive correlation with single plant yield. Three promising lines namely RP6353-5-8-13-24, RP6353-26-13-39-5 and RP6353-32-12-8-16 with higher grain number and yield than MTU1010 were identified and nominated for evaluation in Initial Varietal Trial-Aerobic (IVT-Aerobic) of All India Crop Improvement Programme on Rice (AICRP), of which RP6353-26-13-39-5 (IET28674), was promoted for further testing

Fine mapping and sequence analysis reveal a promising candidate gene encoding a novel NB-ARC domain derived from wild rice (Oryza officinalis) that confers bacterial blight resistance

Bacterial blight disease of rice caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most serious constraints in rice production. The most sustainable strategy to combat the disease is the deployment of host plant resistance. Earlier, we identified an introgression line, IR 75084-15-3-B-B, derived from Oryza officinalis possessing broad-spectrum resistance against Xoo. In order to understand the inheritance of resistance in the O. officinalis accession and identify genomic region(s) associated with resistance, a recombinant inbred line (RIL) mapping population was developed from the cross Samba Mahsuri (susceptible to bacterial blight) × IR 75084-15-3-B-B (resistant to bacterial blight). The F2 population derived from the cross segregated in a phenotypic ratio of 3: 1 (resistant susceptible) implying that resistance in IR 75084-15-3-B-B is controlled by a single dominant gene/quantitative trait locus (QTL). In the F7 generation, a set of 47 homozygous resistant lines and 47 homozygous susceptible lines was used to study the association between phenotypic data obtained through screening with Xoo and genotypic data obtained through analysis of 7K rice single-nucleotide polymorphism (SNP) chip. Through composite interval mapping, a major locus was detected in the midst of two flanking SNP markers, viz., Chr11.27817978 and Chr11.27994133, on chromosome 11L with a logarithm of the odds (LOD) score of 10.21 and 35.93% of phenotypic variation, and the locus has been named Xa48t. In silico search in the genomic region between the two markers flanking Xa48t identified 10 putatively expressed genes located in the region of interest. The quantitative expression and DNA sequence analysis of these genes from contrasting parents identified the Os11g0687900 encoding an NB-ARC domain-containing protein as the most promising gene associated with resistance. Interestingly, a 16-bp insertion was noticed in the untranslated region (UTR) of the gene in the resistant parent, IR 75084-15-3-B-B, which was absent in Samba Mahsuri. The association of Os11g0687900 with resistance phenotype was further established by sequence-based DNA marker analysis in the RIL population. A co-segregating PCR-based INDEL marker, Marker_Xa48, has been developed for use in the marker-assisted breeding of Xa48t