Trends of acute poisoning: 22 years experience from a tertiary care hospital in Karachi, Pakistan.

Objective: To determine the trends of acute poisoning in terms of frequency, nature of poisoning agent, clinical presentation and its outcome. Methods: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of patients who presented with poisoning between January 1989 and December 2010.The patients were randomly selected , and demographic, chemical information, clinical feature, treatment and outcome were analysed using SPSS 16. Results: Of the total hospital admissions during the period, 3,189(0.3%) were cases of poisoning. Of them, medical records of 705(22%) cases were reviewed; 462(65.5%) adult and 243(34.5%) paediatric cases below 16 years of age. The overall median age was 21 years (interquartile range: 4-32 years)Moreover, 544(87%) were critical at the time of presentation. In 647(92%) cases, the poisoning occurred at home. Psychiatric drugs were found involved in 205(29%) cases, followed by prescription drugs 172(24.4%), pesticides 108(15.3%), hydrocarbons 71(10%), analgesics 59(8.7%), household toxins 59(8.7%), alcohol and drug abuse 21(2.97%) and others 47(6.67%). Conclusion: Poisoning was a serious cause of morbidity in children and young adults. Medications were the leading cause and home was the most common place of incident

Interleukin-10 (IL-10) mediated suppression of IL-12 production in RAW 264.7 cells also involves c-rel transcription factor

Interleukin-10 (IL-10) is known to inhibit IL-12 production in macrophages primarily at the transcriptional level with the involvement of p50 and p65 nuclear factor-kB (NF-kB). We demonstrate that the c-rel transcription factor also plays a major role in IL-10-mediated IL-12 suppression. Treatment of macrophages with recombinant IL-10 inhibited nuclear c-rel levels, whereas addition of neutralizing anti-IL-10 antibody up-regulated both nuclear c-rel levels and IL-12 production by macrophages. Decreased nuclear c-rel was associated with a reduction in phosphorylation of inhibitory kappa B alpha (IkBα ) in the cytoplasm, indicating that IL-10 prevents degradation of IkBα and the subsequent translocation of c-rel into the nucleus. Treatment with leptomycin B, a known inhibitor of c-rel at a concentration of 10 nm, when used with anti-IL-10 antibody, resulted in reduced expression of IL-12. In a complementary experiment, in vitro transient expression of p65 NF-kB could not rescue the inhibitory effect of IL-10 on IL-12 production, suggesting that NF-kB alone was not sufficient to restore IL-12 production during IL-10 treatment. However, over-expression of c-rel resulted in IL-12 restoration upon stimulation with lipopolysaccharide plus interferon-γ - during IL-10 treatment. Our studies highlight the involvement of c-rel in IL-10-mediated IL-12 regulation

Anti-B7-1/B7-2 antibody elicits innate-effector responses in macrophages through NF-kB-dependent pathway

Blocking T cell co-stimulatory signals by anti-B7-1/B7-2 mAb is an attractive approach to treat autoimmune diseases. However, anti-B7-1/B7-2 mAb treatment is known to exacerbate autoimmune diseases through mechanisms not fully understood. Tumor necrosis factor alpha (TNF-α) and reactive oxygen species (ROS) also play important roles in determining the clinical outcome of autoimmune diseases. In this study, we demonstrate that the anti-B7-1 and the anti-B7-2 mAbs activate macrophages for higher induction of TNF-α and other effector responses such as bacterial cytotoxicity and production of ROS. Nuclear factor-kappaB (NF-kB) was found to be increased with anti-B7-1/B7-2 mAb treatment. Inhibition of NF-kB activity by over-expression of phosphorylation-defective I-kappaB alpha in anti-B7-1/B7-2 mAb-treated macrophages decreased TNF-α production. These data indicate that anti-B7-1 and anti-B7-2 mAbs can trigger innate-effector responses in macrophages by activating NF-kB-signaling pathway. Our results suggest that the B7 molecules are not only essential for induction of adaptive immune responses but also play roles in activation of innate immune responses

Cellular stress response and immune signaling in retina ischemia-reperfusion injury

Ischemia-reperfusion injury is a well-known pathological hallmark associated with diabetic retinopathy, glaucoma and other related retinopathies that ultimately can lead to visual impairment and vision loss. Retinal ischemia pathogenesis involves a cascade of detrimental events that include energy failure, excitotoxic damage, calcium imbalance, oxidative stress and eventually cell death. Retina for a long time has been known to be an immune privileged site; however, recent investigations reveal that retina, as well as the central nervous system (CNS), elicits immunological responses during various stress cues. Stress condition such as reperfusion of blood supply post-ischemia results in the sequestration of various immune cells, inflammatory mediators including cytokines, chemokines etc., to the ischemic region, which in turn facilitates induction of inflammatory conditions in these tissues. The immunological activation during injury or stress per se is beneficial for repair and maintenance of cellular homeostasis but whether the associated inflammation is good or bad, during ischemia-reperfusion injury, hitherto remains to be explored. Keeping all these notions in mind the current review tries to address the immune response and host stress response mechanisms involved in ischemia-reperfusion injury with the focus on the retina

Amino Acid Sensing via General Control Nonderepressible-2 Kinase and Immunological Programming

Metabolic adaptation to the changing nutrient levels in the cellular microenvironment plays a decisive role in the maintenance of homeostasis. Eukaryotic cells are equipped with nutrient sensors, which sense the fluctuating nutrients levels and accordingly program the cellular machinery to mount an appropriate response. Nutrients including amino acids play a vital role in maintaining cellular homeostasis. Therefore, over the evolution, different species have developed diverse mechanisms to detect amino acids abundance or scarcity. Immune responses have been known to be closely associated with the cellular metabolism especially amino acid sensing pathway, which influences innate as well as adaptive immune-effector functions. Thus, exploring the cross-talk between amino acid sensing mechanisms and immune responses in disease as well as in normal physiological conditions might open up avenues to explore how this association can be exploited to tailor immunological functions toward the design of better therapeutics for controlling metabolic diseases. In this review, we discuss the advances in the knowledge of various amino acid sensing pathways including general control nonderepressible-2 kinase in the control of inflammation and metabolic diseases

Characteristics of treatment naive chronic hepatitis B in Bangladesh: Younger populations are more affected; HBeAg-negatives are more advanced

<b>Background/Aim:</b> Bangladesh is a densely populated country with intermediate endemicity for chronic hepatitis B (CHB). The aim of the present study was to evaluate the biochemical, virological and histological character of CHB patients and to examine the relationship between these indices. <b> Materials and Methods:</b> One thousand and twenty-two patients of CHB fulfilled our inclusion criteria. Inclusion criteria were (1) HBsAg positive for at least 6 months, (2) HBeAg-positive or negative and (3) hepatitis B virus (HBV) DNA positive. Patients with detectable antibodies to human immunodeficiency virus (HIV), hepatitis Delta virus (HDV) or hepatitis C virus (HCV), with previous antiviral treatment, overt cirrhosis and hepatocellular carcinoma, were excluded. Of these, 191 patients were randomly selected for liver biopsy and were evaluated for analysis. <b> Results:</b> In the 191 patients, male to female ratio was 4.6:1; age distribution was 26.5 &#x00B1; 8.5 (mean &#x00B1; standard deviation) years. One hundred and seventy-eight (93.2&#x0025;) patients were under 40 years. Sixty-eight (35.6&#x0025;) patients were HBeAg-negative, had less DNA load, and were significantly older, more fibrotic and cirrhotic (<i> P</i> &lt; 0.001). Correlation was not found between DNA level and histological activity. Histological activity was not correlated with ALT level in HBeAg-positive patients (<i> P</i> &lt; 0.001). <b> Conclusion:</b> CHB affects the younger population in Bangladesh. HBeAg-positive CHB was associated with more fibrosis and cirrhosis. Serum HBV DNA levels do not correlate with the severity of histological lesions in all patients. Evaluation by liver biopsy remains gold standard for taking decision of treatment

Modelling and Optimization of Syngas Production by Methane Dry Reforming Over Samarium Oxide Supported Cobalt Catalyst: Response Surface Methodology and Artificial Neural Networks Approach

The reforming of methane by carbon dioxide for the production of syngas is a potential technological route for the mitigation of greenhouse gases. However, the process is highly endothermic and often accompanied by catalyst deactivation from sintering and carbon deposition. Besides, the applications of dissimilar catalytic systems in methane dry reforming have made it difficult to obtain generalized optimum conditions for the desired products. Hence, optimization studies of any catalytic system often resulted in a unique optimum condition. The present study aimed to investigate optimum conditions of variables such as methane (CH4) partial pressure, carbon dioxide (CO2) partial pressure and reaction temperature that will maximize syngas yields from methane dry reforming over samarium oxide supported cobalt (Co/Sm2O3) catalyst. The Co/Sm2O3 catalyst was synthesized using wet-impregnation method and characterized by thermogravimetric analysis), field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray powder diffraction and nitrogen (N2) physisorption. Syngas production by methane dry reforming over the synthesized Co/Sm2O3 catalyst was investigated in a stainless steel fixed-bed reactor. The process variables (CH4 partial pressure, CO2 partial pressure and reaction temperature) for the syngas production were optimized using response surface methodology (RSM). The RSM and artificial neural networks (ANNs) were used to predict the syngas production from the experimental data. The comparative analysis between the two models showed that the ANN model has better prediction of the syngas yields compared to the RSM model as evident from the good agreement between the observed and the predicted values. At maximum desirability value of 0.97, optimum CH4 and CO2 partial pressures of 47.9 and 48.9 kPa were obtained at reaction temperature of 735 °C resulting in syngas yield of ~79.4 and 79.0% for hydrogen (H2) and carbon monoxide (CO), respectively

A One-Stop Protocol to Assess Myocardial Fibrosis in Frozen and Paraffin Sections

Masson&rsquo;s Trichrome Staining (MTS) is a useful tool for analyzing fibrosis in a plethora of disease pathologies by differential staining of tissue components. It is used to identify collagen fibers in different tissues like heart, lung, skin, and muscles. Especially in cardiac fibrosis, MTS stains the collagen fibers (blue color), which helps in the distinction of scar area versus the healthy area (red color). However, there are several challenges to stain both paraffin-embedded sections and frozen (cryosections) using a single protocol. Therefore, the goal of this study was to develop a simple short protocol to assess cardiac fibrosis in both paraffin-embedded and cryo heart sections. MTS uses three different stains, i.e., Weigert&rsquo;s Iron Hematoxylin, Biebrich scarlet-acid fuchsin, and aniline blue to detect nuclei, cytoplasm, and collagen, respectively. In this study, we developed a simple short protocol that can be adapted by any lab to easily assess cardiac fibrosis in paraffin and frozen heart sections. Furthermore, we have addressed the challenges that are commonly faced during the immunostaining process and troubleshooting techniques. Overall, we have successfully developed a simple one-step protocol to assess myocardial fibrosis in paraffin-embedded and frozen cryosections

Association of Strong Immune Responses to PPE Protein Rv1168c with Active Tuberculosis ▿

Accurate diagnosis of tuberculosis (TB) infection is critical for the treatment, prevention, and control of TB. Conventional diagnostic tests based on purified protein derivative (PPD) do not achieve the required diagnostic sensitivity. Therefore, in this study, we have evaluated the immunogenic properties of Rv1168c, a member of the PPE family, in comparison with PPD, which is routinely used in the tuberculin test, and Hsp60 and ESAT-6, well-known immunodominant antigens of Mycobacterium tuberculosis. In a conventional enzyme immunoassay, the recombinant Rv1168c protein displayed stronger immunoreactivity against the sera obtained from patients with clinically active TB than did PPD, Hsp60, or ESAT-6 and could distinguish TB patients from Mycobacterium bovis BCG-vaccinated controls. Interestingly, Rv1168c antigen permits diagnosis of smear-negative pulmonary TB as well as extrapulmonary TB cases, which are often difficult to diagnose by conventional tests. The immunodominant nature of Rv1168c makes it a promising candidate to use in serodiagnosis of TB. In addition, our studies also show that Rv1168c is a potent T-cell antigen which elicits a strong gamma interferon response in sensitized peripheral blood mononuclear cells obtained from TB patients