A retrospective record review of tuberculous infections in rheumatoid arthritis patients on biologics in Malaysia.

INTRODUCTION: The aim of this study was to analyse the clinical characteristics of patients with rheumatoid arthritis receiving biologics therapy and investigate the association between types of biologics and tuberculosis (TB) infections in 13 tertiary hospitals in Malaysia. MATERIALS AND METHODS: This was a retrospective study that included all RA patients receiving biologics therapy in 13 tertiary hospitals in Malaysia from January 2008 to December 2018. RESULTS: We had 735 RA patients who received biologics therapy. Twenty-one of the 735 patients were diagnosed with TB infection after treatment with biologics. The calculated prevalence of TB infection in RA patients treated with biologics was 2.9% (29 per 1000 patients). Four groups of biologics were used in our patient cohort: monoclonal TNF inhibitors, etanercept, tocilizumab, and rituximab, with monoclonal TNF inhibitors being the most commonly used biologic. The median duration of biologics therapy before the diagnosis of TB was 8 months. 75% of patients had at least one co-morbidity and all patients had at least one ongoing cDMARD therapy at the time of TB diagnosis. More than half of the patients were on steroid therapy with an average prednisolone dose of 5 mg daily. CONCLUSION: Although the study population and data were limited, this study illustrates the spectrum of TB infections in RA patients receiving biologics and potential risk factors associated with biologics therapy in Malaysia.

Growth of 1D TiO2nanostructures on Ti substrates incorporated with residual stress through humid oxidation and their characterizations.

Different Ti substrates, such as particles (as-received and ball milled), plate and TEM grid were oxidized for the growth of one dimensional (1D) TiO2nanostructures. The Ti substrates were oxidized for 4 h at temperatures of 700 °C-750 °C in humid and dry Ar containing 5 ppm of O2. The effects of residual stress on the growth of 1D TiO2nanostructures were investigated. The residual stress inside the Ti particles was measured by XRD-sin2ψtechnique. The oxidized Ti substrates were characterized using field emission scanning electron microscope equipped with energy dispersive x-ray spectroscope, transmission electron microscope, x-ray diffractometer and x-ray photoelectron spectroscope. Results revealed that humid environment enhances the growth of 1D TiO2nanostructures. Four different types of 1D morphologies obtained during humid oxidation, e.g. stacked, ribbon, plateau and lamp-post shaped nanostructures. The presence of residual stress significantly enhances the density and coverage of 1D nanostructures. The as-grown TiO2nanostructures possess tetragonal rutile structure having length up to 10µm along the 〈1 0 1〉 directions. During initial stage of oxidation, a TiO2layer is formed on Ti substrate. Lower valence oxides (Ti3O5, Ti2O3and TiO) then form underneath the TiO2layer and induce stress at the interface of oxide layers. The induced stress plays significant role on the growth of 1D TiO2nanostructures. The induced stress is relaxed by creating new surfaces in the form of 1D TiO2nanostructures. A diffusion based model is proposed to explain the mechanism of 1D TiO2growth during humid oxidation of Ti. The 1D TiO2nanostructures and TiO2layer is formed by the interstitial diffusion of Ti4+ions to the surface and reacts with the surface adsorbed hydroxide ions (OH-). Lower valence oxides are formed at the metal-oxide interface by the reaction between diffused oxygen ions and Ti ions.

Induced in vitro adaptation for salt tolerance in date palm (Phoenix dactylifera L.) cultivar Khalas.

BACKGROUND: Soil salinity causes huge economic losses to agriculture productivity in arid and semiarid areas worldwide. The affected plants face disturbances in osmotic adjustment, nutrient transport, ionic toxicity and reduced photosynthesis. Conventional breeding approaches produce little success in combating various stresses in plants. However, non-conventional approaches, such as in vitro tissue culturing, produce genetic variability in the development of salt-tolerant plants, particularly in woody trees. RESULTS: Embryogenic callus cultures of the date palm cultivar Khalas were subjected to various salt levels ranging from 0 to 300 mM in eight subcultures. The regenerants obtained from the salt-treated cultures were regenerated and evaluated using the same concentration of NaCl with which the calli were treated. All the salt-adapted (SA) regenerants showed improved growth characteristics, physiological performance, ion concentrations and K+/Na+ ratios than the salt non-adapted (SNA) regenerants and the control. Regression between the leaf Na+ concentration and net photosynthesis revealed an inverse nonlinear correlation in the SNA regenerants. Leaf K+ contents and stomatal conductance showed a strong linear relationship in SA regenerants compared with the inverse linear correlation, and a very poor coefficient of determination in SNA regenerants. The genetic fidelity of the selected SA regenerants was also tested using 36 random amplified polymorphic DNA (RAPD) primers, of which 26 produced scorable bands. The primers generated 1-10 bands, with an average of 5.4 bands per RAPD primer; there was no variation between SA regenerants and the negative control. CONCLUSION: This is the first report of the variants generated from salt-stressed cultures and their potential adaptation to salinity in date palm cv. Khalas. The massive production of salt stress-adapted date palm plants may be much easier using the salt adaptation approach. Such plants can perform better during exposure to salt stress compared to the non-treated date palm plants.

Effect of LSR polymorphism on blood lipid levels and age-specific epistatic interaction with the APOE common polymorphism.

The lipolysis stimulated lipoprotein receptor (LSR) is an apolipoprotein (Apo) B and ApoE receptor that participates in the removal of triglyceride-rich lipoproteins during the postprandial phase. LSR gene is located upstream of APOE, an important risk factor for cardiovascular disease (CVD). Since the APOE common polymorphism significantly affects the variability of lipid metabolism, this study aimed to determine the potential impact of a functional SNP rs916147 in LSR gene on lipid traits in healthy subjects and to investigate potential epistatic interaction between LSR and APOE. Unrelated healthy adults (N = 432) and children (N = 328, <18 years old) from the STANISLAS Family Study were used. Age-specific epistasis was observed between APOE and LSR, reversing the protective effect of APOE ε2 allele on cholesterol, ApoE and low-density lipoprotein levels (ß: .114, P: .777 × 10-8 , ß: .125, P: .639 × 10-3 , ß: .059, P: .531 × 10-3 , respectively). This interaction was verified in an independent adult population (n = 1744). These results highlight the importance of the LSR polymorphism and reveal the existence of complex molecular links between LSR and ApoE for the regulation of lipid levels, revealing potential new pathways of interest in type III hyperlipidemia and its involvement in CVD pathology.

Floc Formation Reduces the pH Stress Experienced by Microorganisms Living in Alkaline Environments.

The survival of microorganisms within a cementitious geological disposal facility for radioactive wastes heavily depends on their ability to survive the calcium-dominated, hyperalkaline conditions resulting from the dissolution of the cementitious materials. The results from this study show that the formation of flocs, composed of a complex mixture of extracellular polymeric substances (EPS), provides protection against alkaline pH values up to 13.0. The flocs were dominated by Alishewanella and Dietzia spp., producing a mannose-rich carbohydrate fraction incorporating extracellular DNA, resulting in Ca2+ sequestration. EPS provided a ∼10-µm thick layer around the cells within the center of the flocs, which were capable of growth at pH values of 11.0 and 11.5, maintaining internal pH values of 10.4 and 10.7, respectively. Microorganisms survived at a pH of 12.0, where an internal floc pH of 11.6 was observed, as was a reduced associated biomass. We observed limited floc survival (<2 weeks) at a pH of 13.0. This study demonstrates that flocs maintain lower internal pHs in response to the hyperalkaline conditions expected to occur within a cementitious geological disposal facility for radioactive wastes and indicates that floc communities within such a facility can survive at pHs up to 12.0.IMPORTANCE The role of extracellular polymeric substances (EPS) in the survival of microorganisms in hyperalkaline conditions is poorly understood. Here, we present the taxonomy, morphology, and chemical characteristics of an EPS-based microbial floc, formed by a consortium isolated from an anthropogenic hyperalkaline site. Short-term (<2 weeks) survival of the flocs at a pH of 13 was observed, with indefinite survival observed at a pH of 12.0. Measurements from micro-pH electrodes (10-µm-diameter tip) demonstrated that flocs maintain lower internal pHs in response to hyperalkaline conditions (pH 11.0, 11.5, and 12.0), demonstrating that floc formation and EPS production are survival strategies under hyperalkaline conditions. The results indicate how microbial communities may survive and propagate within the hyperalkaline environment that is expected to prevail in a cementitious geological disposal facility for radioactive wastes; the results are also relevant to the wider extremophile community.

Tryptophan fluorescence quenching as a binding assay to monitor protein conformation changes in the membrane of intact mitochondria.

Intrinsic protein fluorescence is due to aromatic amino acids, mainly tryptophan, which can be selectively measured by exciting at 295 nm. Changes in emission spectra of tryptophan are due to the protein conformational transitions, subunit association, ligand binding or denaturation, which affect the local environment surrounding the indole ring. In this study, tryptophan fluorescence was monitored in intact mitochondria at 333 nm following excitation at 295 nm in presence of insecticides using spectrofluorometer. Methyl-parathion, carbofuran, and endosulfan induced Trp fluorescence quenching and release of cytochrome c when incubated with the mitochondria, except fenvalarate. Mechanism of insecticide-induced mitochondrial toxicity for the tested insecticides has been discussed. Reduction in the intensity of tryptophan emission spectra of mitochondrial membrane proteins in presence of an increasing concentration of a ligand can be used to study the interaction of insecticides/drugs with the intact mitochondria. Furthermore, this assay can be readily adapted for studying protein-ligand interactions in intact mitochondria and in other cell organelles extending its implications for pesticide and pharma industry and in drug discovery.

Electrochemical determination of folic acid: A short review.

Folic acid (FA) is an electroactive compound of biological origin. It helps our body to produce and maintain healthy cells. It can significantly reduce the occurrence of neural tube defects and also prevents change in DNA structure. FA deficiency can lead to various health risks. Therefore, a sensitive, specific, and reproducible way of FA detection is essential. A number of analytical methods are in practice for the quantification of FA. However, electroanalytical methods are attracting much attention because of their advantage over conventional methods, as they are fast, simple, sensitive, and cost effective. Moreover, modification of electrodes offers control over size and morphology which allows miniaturization for applicability in portable electrochemical devices.

Cellular accumulation of Cys326-OGG1 protein complexes under conditions of oxidative stress.

The common Ser326Cys polymorphism in the base excision repair protein 8-oxoguanine glycosylase 1 is associated with a reduced capacity to repair oxidative DNA damage particularly under conditions of intracellular oxidative stress and there is evidence that Cys326-OGG1 homozygous individuals have increased susceptibility to specific cancer types. Indirect biochemical studies have shown that reduced repair capacity is related to OGG1 redox modification and also possibly OGG1 dimer formation. In the current study we have used bimolecular fluorescence complementation to study for the first time a component of the base excision repair pathway and applied it to visualise accumulation of Cys326-OGG1 protein complexes in the native cellular environment. Fluorescence was observed both within and around the cell nucleus, was shown to be specific to cells expressing Cys326-OGG1 and only occurred in cells under conditions of cellular oxidative stress following depletion of intracellular glutathione levels by treatment with buthionine sulphoximine. Furthermore, OGG1 complex formation was inhibited by incubation of cells with the thiol reducing agents ß-mercaptoethanol and dithiothreitol and the antioxidant dimethylsulfoxide indicating a causative role for oxidative stress in the formation of OGG1 cellular complexes. In conclusion, this study has provided for the first time evidence of redox sensitive Cys326-OGG1 protein accumulation in cells under conditions of intracellular oxidative stress that may be related to the previously reported reduced repair capacity of Cys326-OGG1 specifically under conditions of oxidative stress.

Hepatic necroinflammation and severe liver fibrosis in patients with chronic hepatitis B with undetectable HBV DNA and persistently normal alanine aminotransferase.

Both consensus and controversy remains regarding surrogacy of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and alanine aminotransferase (ALT), however, these markers are used to ascertain the extent of liver damages and to guide therapeutic options in patients with chronic hepatitis B. However, little is known about liver histology of patients with chronic hepatitis B with undetectable HBV DNA and persistently normal ALT. Thirty-five incidentally-detected patients with chronic HBV infection (assessed by expression of hepatitis B surface antigen for more than 6 months) with undetectable HBV DNA and normal serum ALT were enrolled in this study. Liver biopsy specimens were taken from all patients and the extent of hepatic necroinflammation and liver fibrosis were evaluated. Moderate degree of hepatic necroinflammation was detected in 2 of 35 patients and severe hepatic fibrosis was seen in 6 of 35 patients. Two patients with undetectable HBV DNA and sustained normal ALT had moderate hepatic necroinflammation and severe hepatic fibrosis. In spite of undetectable HBV DNA for prolonged period and persistently normal ALT, some patients with chronic hepatitis B express evidences of progressive liver diseases. Large scale studies in different races and geographical regions should be accomplished to develop insights about management of these patients. Studies about extent of liver diseases in these patients should be accomplished in Treatment recommendation and management strategies should be developed for these patients.

Validity and reliability of Squegg device in measuring isometric handgrip strength.

OBJECTIVE: The quantitative measurement of handgrip strength is important in assessing and charting the progress of patients with neuromuscular diseases. The aim of this research was to determine the intra-rater and inter-rater reliability and the validity of the Squegg digital dynamometer. SUBJECTS AND METHODS: Twenty-one females and nine male participants with an age range between 18 and 40 years volunteered for the study. Three testers each took three measurements with a Squegg device and a Jamar dynamometer using standardized measurement techniques. Intra- and inter-tester reliability were calculated using the intra-class correlation coefficient (ICC). To investigate the relationship between hand measures and isometric handgrip strength, the Pearson correlation coefficient test was used. To determine the agreement between the two devices, a Bland Altman plot was constructed, and the concurrent validity of Squegg was calculated. RESULTS: The intra-rater reliability coefficients for both Jamar and Squegg were greater than 0.99 for all three testers, indicating excellent intra-rater reliability. The inter-rater reliability of Jamar (ICC=0.93) and Squegg (ICC=0.87) was excellent. With an ICC of 0.844 and an r-value of 0.720, Squegg with Jamar demonstrates good validity and statistical significance (p=0.001). CONCLUSIONS: The isometric handgrip strength and hand measures showed a moderate correlation in the study population. The Squegg isometric handgrip dynamometer has good concurrent validity and great intra- and inter-rater reliability in healthy individuals. The validity of Squegg in patients with neuromuscular diseases that affect hand function has to be investigated further.

Interaction of plant cell signaling molecules, salicylic acid and jasmonic acid, with the mitochondria of Helicoverpa armigera.

The cotton bollworm, Helicoverpa armigera is a polyphagous pest in Asia, Africa, and the Mediterranean Europe. Salicylic acid (SA) and jasmonic acid (JA) are the cell signaling molecules produced in response to insect attack in plants. The effect of these signaling molecules was investigated on the oxidative phosphorylation and oxidative stress of H. armigera. SA significantly inhibited the state III and state IV respiration, respiratory control index (RCI), respiratory complexes I and II, induced mitochondrial swelling, and cytochrome c release in vitro. Under in vivo conditions, SA induced state IV respiration as well as oxidative stress in time- and dose-dependent manner, and also inhibited the larval growth. In contrast, JA did not affect the mitochondrial respiration and oxidative stress. SA affected the growth and development of H. armigera, in addition to its function as signaling molecules involved in both local defense reactions at feeding sites and the induction of systemic acquired resistance in plants.

Some wounds are hard to heal: an interesting presentation of Ehlers-Danlos syndrome.

A 17-year-old female patient was admitted for an elective mini laparotomy and cystectomy of the right ovary for the treatment of chronic supra-pubic abdominal pain. The procedure went without complication and she was discharged the next day. She was re-admitted a month later as an acute case with wound dehiscence. HIV serology, thyroid function, immunoglobulin, protein electrophoresis and electrolyte levels were all normal. There were no obvious signs of infection and the bacterial swabs failed to culture an organism. Despite conservative measures with regular dressing, oral antibiotics and input from the tissue viability team the wound failed to epithelialise. The wound was debrided and re-sutured a total of three times and the patient received 24 days of intravenous antibiotics. After input from various teams a diagnosis of Ehlers-Danlos syndrome was made, allowing for appropriate management and wound healing.

Hepatitis B surface antigen-negative, but HBV DNA-positive patients in Bangladesh.

Hepatitis B surface antigen (HBsAg) is regarded as sole marker of hepatitis B virus (HBV) infection in Bangladesh and most other developing countries. However, some HBV-negative subjects may harbor HBV DNA and transfusion of their blood may cause HBV infection in recipients. HBV DNA was checked in 20 patients with cryptogenic liver cirrhosis, 10 patients with hepatocellular carcinoma without any known etiology, and 10 apparently healthy subjects with elevated levels of serum alanine aminotransferase (ALT). HBV DNA was detected in 8 of 20 patients with cryptogenic liver cirrhosis, 1 of 10 patients with hepatocellular carcinoma, and 2 of 10 apparent healthy subjects with elevated ALT. However, all of them were negative for HBsAg in the sera. This study indicates that some additional mechanisms should be developed for detection of HBsAg-negative HBV-infected subjects for efficient control and management of HBV infection in Bangladesh.

Brassica oleracea L. (Acephala Group) based zinc oxide nanoparticles and their efficacy as antibacterial agent.

Zinc oxide nanoparticles were synthesized from the leaf extract of Brassica oleracea L. Acephala group (collard green) followed by their characterization using Scanning Electron Microscope (SEM), and Energy Dispersive X-ray (EDX). The antibacterial properties of zinc nanoparticles were tested against Gram-negative bacteria, Pseudomonas aeruginosa (ATCC ® 9027™), Escherichia coli (ATCC ® 8739™), Klebsiella pneumoniae (ATCC® BAA-1705™) and Gram-positive bacteria, Staphylococcus aureus (ATCC ® 6538™) and Listeria monocytogenes (ATCC ® 13932™), at four different concentrations (50.00 µg/ml, 100.00 µg/ml, 500.00 µg/ml and 1 mg/ml) of zinc oxide nanoparticles suspension. Results revealed that the synthesized nanoparticles exhibit strong antibacterial effects against Pseudomonas aeruginosa, Listeria monocytogenes, Klebsiella pneumonia, Staphylococcus aureus and Escherichia coli at 500.00 µg/ml-1 mg/ml concentrations. An increase in efficacy of nanoparticles with the decrease of their size was also evident. This is a first ever report on Brassica oleracea, L. based nanoparticles which demonstrates that 500.00 µg-1 mg/ml conc. of zinc oxide nanoparticles have antibacterial activity against both Gram -ve and Gram +ve bacteria and have the potential to be considered as an antibacterial agent in future.

Immunosuppressive functions of hepatic myeloid-derived suppressor cells of normal mice and in a murine model of chronic hepatitis B virus.

The immunosuppressive state of tumour-bearing hosts is attributable, at least in part, to myeloid-derived suppressor cells (MDSC). However, the role of MDSC in physiological conditions and diseases other than cancer has not been addressed. As the liver is a tolerogenic organ, the present study attempted to localize and assess functions of hepatic MDSC in a normal liver and in a murine model of chronic hepatitis B virus (HBV) infection. MDSC was identified in the liver of normal mice and HBV transgenic mice (TM) as CD11b(+) Gr1(+) cells by dual-colour flow cytometry. Highly purified populations of MDSC and their subtypes were isolated by fluorescence-activated cell sorting. The functions of MDSC and their subtypes were evaluated in allogenic mixed lymphocyte reaction (MLR) and hepatitis B surface antigen (HBsAg)-specific T cell proliferation assays. Normal mice-derived liver MDSC, but not other myeloid cells (CD11b(+) Gr1(-) ), suppressed T cell proliferation in allogenic MLR in a dose-dependent manner. Alteration of T cell antigens and impaired interferon-γ production seems to be related to MDSC-induced immunosuppression. In HBV TM, the frequencies of liver MDSC were about twice those of normal mice liver (13·6±3·2% versus 6·05±1·21%, n=5, P<0·05). Liver-derived MDSC from HBV TM also suppressed proliferative capacities of allogenic T cells and HBsAg-specific lymphocytes. Liver MDSC may have a critical role in maintaining homeostasis during physiological conditions. As liver MDSC had immunosuppressive functions in HBV TM, they may be a target of immune therapy in chronic HBV infection.

Safety and immunogenicity of hepatitis B surface antigen-pulsed dendritic cells in patients with chronic hepatitis B.

The immune modulator capacity of antigen-pulsed dendritic cells (DC) has been documented in patients with cancers and in animal models of chronic viral infections. Cancer antigen-pulsed DC are now used for treating patients with cancer. But viral antigen-pulsed DC are not used in chronic viral-infected patients because safety of antigen-pulsed DC has not been evaluated in these patients. DC were isolated from human peripheral blood mononuclear cells by culturing with human-grade granulocyte-macrophage colony stimulating factor and interleukin-4. Human blood DC were cultured with hepatitis B surface antigen (HBsAg) for 8h to prepare HBsAg-pulsed DC. After immunogenicity assessment of HBsAg-pulsed DC in vitro, five million HBsAg-pulsed DC were administered intradermally to five patients with chronic hepatitis B (CHB) 1-3 times. HBsAg-pulsed DC were immunogenic in nature because they produced significantly higher levels of interleukin-12 and interferon-γ compared to unpulsed DC (P<0.05). Also, HBsAg-pulsed DC induced proliferation of HBsAg-specific T lymphocytes in vitro. CHB patients injected with HBsAg-pulsed DC did not exhibit generalized inflammation, exacerbation of liver damage, abnormal kidney function, or features of autoimmunity. Administration of HBsAg-pulsed DC induced anti-HBs in two patients and HBsAg-specific cellular immunity in 1 patient. This is the first study about preparation of antigen-pulsed DC using human consumable materials for treating patients with CHB. Because HBsAg-pulsed DC were safe for all patients with CHB and had immune modulation capacity in some patients, phase I and phase II clinical trials with antigen-pulsed DC in CHB and other chronic infections are warranted.

Mechanism of restoration of immune responses of patients with chronic hepatitis B during lamivudine therapy: increased antigen processing and presentation by dendritic cells.

Restoration of host immunity has been reported in patients with chronic hepatitis B (CHB) after treatment with lamivudine; however, the underlying mechanisms of this treatment have not been determined. This study examined the role of antigen-presenting dendritic cells (DC) in restoration of host immunity. Circulating DC were isolated from peripheral blood of 23 patients with CHB before and 1, 3, and 12 months after starting lamivudine therapy. The non-antigen-specific proliferation of DC was assessed in allogenic mixed leucocyte reaction. Dendritic cells were cultured with hepatitis B surface antigen (HBsAg) to prepare HBsAg-pulsed DC. Proliferative capacity and production of interleukin (IL)-12 and interferon (IFN)-γ of HBsAg-pulsed DC were evaluated. Circulating unpulsed DC and HBsAg-pulsed DC showed significantly higher levels of T-cell proliferation capacities 1 month after lamivudine therapy compared to proliferation levels before therapy (P<0.05). HBsAg-pulsed DC also produced significantly higher levels of IL-12 and IFN-γ with lamivudine therapy compared to levels before therapy (P<0.05). HBsAg-pulsed DC from lamivudine-treated patients induced proliferation of T cells of patients with CHB in an antigen-specific manner (P<0.05). However, T-cell stimulatory capacity of DC did not increase significantly 3 and 12 months after lamivudine therapy compared to 1 month after lamivudine therapy. Immune restoration as a result of lamivudine therapy is regulated at least in part by activation of DC. However, progressive activation of DC was not seen as treatment duration progressed, indicating the limitations of this mechanism of viral clearance.

Ethanolic Extract of Centella asiatica Treatment in the Early Stage of Hyperglycemia Condition Inhibits Glomerular Injury and Vascular Remodeling in Diabetic Rat Model.

BACKGROUND: Diabetes mellitus (DM) is marked by oxidative stress, inflammation, and vascular dysfunction that caused diabetic nephropathy that resulted in end-stage renal disease (ESRD). Vascular dysfunction is characterized by an imbalance in vasoconstrictor and vasodilator agents which underlies the mechanism of vascular injury in DM. Additionally, diminished podocytes correlate with the severity of kidney injury. Podocyturia often precedes proteinuria in several kidney diseases, including diabetic kidney disease. Centella asiatica (CeA) is known as an anti-inflammatory and antioxidant and has neuroprotective effects. This research aimed to investigate the potential effect of CeA to inhibit glomerular injury and vascular remodeling in DM. METHODS: The DM rat model was induced through intraperitoneal injection of streptozotocin 60 mg/kg body weight (BW), and then rats were divided into 1-month DM (DM1, n = 5), 2-month DM (DM2, n = 5), early DM concurrent with CeA treatment for 2 months (DMC2, n = 5), and 1-month DM treated with CeA for 1-month (DM1C1, n = 5). The CeA (400 mg/kg BW) was given daily via oral gavage. The control group (Control, n = 5) was maintained for 2 months. Finally, rats were euthanized and kidneys were harvested to assess vascular remodeling using Sirius Red staining and the mRNA expression of superoxide dismutase, podocytes marker, ACE2, eNOS, and ppET-1 using RT-PCR. RESULTS: The DM groups demonstrated significant elevation of glucose level, glomerulosclerosis, and proteinuria. A significant reduction of SOD1 and SOD3 promotes the downregulation of nephrin and upregulation of TRPC6 mRNA expressions in rat glomerular kidney. Besides, this condition enhanced ppET-1 and inhibited eNOS and ACE2 mRNA expressions that lead to the development of vascular remodeling marked by an increase of wall thickness, and lumen wall area ratio (LWAR). Treatment of CeA, especially the DMC2 group, attenuated glomerular injury and showed the reversal of induced conditions. CONCLUSIONS: Centella asiatica treatment at the early stage of diabetes mellitus ameliorates glomerulosclerosis and vascular injury via increasing antioxidant enzymes.

Preliminary findings of a study on the practice of self-medication of antibiotics among the practicing nurses of a tertiary care hospital.

OBJECTIVES: Antibiotic resistance is indeed a global concern. It is of significant concern especially in the low-middle income countries because of the ease of accessibility, affordability, and absence of regulations pertaining to the dispensing of non-prescription antibiotics. This study aims to estimate the frequency and factors associated with the self-medication of antibiotics found among the practicing nurses. METHODS: We conducted a descriptive cross-sectional study at a tertiary care hospital in Karachi, Pakistan from July 2016 to August 2016. RESULTS: Of the 48 recruited nurses, 60.4% (29/48) were practicing self-medication of antibiotics. There were slightly more male nurses (17/29) than their female counterparts. The most frequently used antibiotic was Amoxicillin/Clavulanic acid, which was reported by 72.4% (21/29) of the nurses. The most prominent factor urging the nurses for practicing self-medication of antibiotics was their perceived knowledge of antibiotics, as was the case with 72.4% (21/29) of the nurses. Fever (79.3%) and sore throat (65.5%) were the two most frequent health problems that prompted the nurses to practice antibiotics self-medication. An earlier experience of the use of antibiotics was reported by 51.7% (15/29) of the nurses. Only 20.7% (6/29) of the nurses completed the entire antibiotic course. The adverse effects of antibiotics were encountered by 41.4% (12/29) of the nurses, which included diarrhoea, nausea, and vomiting. CONCLUSIONS: The self-medication of antibiotics is a frequent practice found among the practicing nurses in Karachi. It is a pressing concern and needs considerable attention from the healthcare authorities.