Histopathological Correlation in Different Types of Leprosy in a Tertiary Health Care Centre

Hansen’s disease or Leprosy, is a chronic infectious disease that is contagious and has a slow evolution. It affects mainly skin and schwann cells in the peripheral nerves and causes peripheral neuropathy which contributes to the permanent functional impairments [1]. It is caused by a rod shaped,acid fast staining bacteria known as Mycobacterium Leprae which has parallel sides, round ends and a characteristic bundle of cigar appearance due to the presence of a glial substance which is a surface lipid that makes the bacilli to be arranged side by side in parallel arrays [2]. It has a distinctive empathy towards the peripheral nerves where it establishes originally therefore it is the site where the pathological processes start mainly with the principal target being Schwann cell [3,4]. Amidst the communicable diseases, Leprosy is the most common cause of physical disabilities which is permanent. When the bacterium enters a person with good cell-mediated immunity against it, it gets destroyed. If there is a slight impairment in the cell-mediated immunity against it, some bacilli will multiply and a lesion develops. Depending upon the immune status of a host, it expresses itself in different clinico-histopathological forms [5]. Ridley and Jopling suggested a five-group classification of leprosy known as immunological classification based upon the immunological status of the patient as (a) tuberculoid (TT), (b) borderline tuberculoid (BT), (c) mid-borderline (BB), (d) borderline lepromatous (BL) and (e) lepromatous (LL) [6]. Bacteriological, immunological, clinical and histopathological features exhibit continuous but slow changes from one pole to another pole. The main disadvantage of this classification is that there is no specific position for pure neuritic as well as indeterminate leprosy in the spectrum [7].

Nanotherapeutic approaches to overcome distinct drug resistance barriers in models of breast cancer

Targeted delivery of drugs to tumor cells, which circumvent resistance mechanisms and induce cell killing, is a lingering challenge that requires innovative solutions. Here, we provide two bioengineered strategies in which nanotechnology is blended with cancer medicine to preferentially target distinct mechanisms of drug resistance. In the first ‘case study’, we demonstrate the use of lipid–drug conjugates that target molecular signaling pathways, which result from taxane-induced drug tolerance via cell surface lipid raft accumulations. Through a small molecule drug screen, we identify a kinase inhibitor that optimally destroys drug tolerant cancer cells and conjugate it to a rationally-chosen lipid scaffold, which enhances anticancer efficacy in vitro and in vivo. In the second ‘case study’, we address resistance mechanisms that can occur through exocytosis of nanomedicines. Using adenocarcinoma HeLa and MCF-7 cells, we describe the use of gold nanorod and nanoporous vehicles integrated with an optical antenna for on-demand, photoactivation at ∼650 nm enabling release of payloads into cells including cytotoxic anthracyclines. Together, these provide two approaches, which exploit engineering strategies capable of circumventing distinct resistance barriers and induce killing by multimodal, including nanophotonic mechanisms.

Efficacy of Calcipotriol 0.005% Ointment for Uremic Xerosis with Pruritus in Chronic Kidney Diseases Undergoing Hemodialysis Patients: Randomized Double Blind Clinical Trial

Introduction: Uremic xerosis with pruritus (UXP) is a chronic cutaneous complication among patients undergoing maintenance renal dialysis. Uremic xerosis level is directly related with pruritus severity or vice versa. Uremic xerosis with pruritus may lead to discomfort and negative psychological effect. The ethiopathogenesis still unknown, Most of treatments are empirical, and there is no effective and safe therapy. Emollient has not been effective enough to improve quality of life. There is some report about efficacy of topical vitamin D in xerosis and chronic pruritus. Objective: We evaluate the efficacy of calcipotriol 0.005% ointment for uremic xerosis and uremic pruritus in chronic kidney disease patients undergoing hemodialysis. Material & methode: Sixty two patients with UXP were enrolled, randomized double blind study. Patients were divided to two group, calcipotriol 0.005% ointment group or placebo. In baseline, patients were instructed to apply twice daily for four weeks. We assesesment the efficacy and safety of calcipotriol 0.005% ointment and placebo after 2nd and 4th weeks treatment using overall dry skin score (ODSS), visual analog scale (VAS), corneometer and sebumeter. We also assessed adverse effect and tolerance this drugs using visual assessment scale. Results: Overall dry skin score (ODSS) and visual analog scale (VAS) significantly decreased in calcipotriol 0.005% ointment group than in placebo group (p <0.05). Skin hydration level based on Corneometer score and skin surface lipid based on Sebumeter score was significantly increased in calcipotriol 0.005% ointment group than in placebo group (p <0.05). Cure rate and clinical improvement for calcipotriol 0.005% ointment group was significantly higher than placebo group. There was no adverse effect between two groups after treatment. Conclusion: calcipotriol 0.005% ointment is effective than placebo and can be used as alternative or adjuctive treatment and safe and tolerance for UXP.

Efficacy of Calcipotriol 0.005% Ointment for Uremic Xerosis with Pruritus in Chronic Kidney Diseases Undergoing Hemodialysis Patients: Randomized Double Blind Clinical Trial

Introduction: Uremic xerosis with pruritus (UXP) is a chronic cutaneous complication among patients undergoing maintenance renal dialysis. Uremic xerosis level is directly related with pruritus severity or vice versa. Uremic xerosis with pruritus may lead to discomfort and negative psychological effect. The ethiopathogenesis still unknown, Most of treatments are empirical, and there is no effective and safe therapy. Emollient has not been effective enough to improve quality of life. There is some report about efficacy of topical vitamin D in xerosis and chronic pruritus. Objective: We evaluate the efficacy of calcipotriol 0.005% ointment for uremic xerosis and uremic pruritus in chronic kidney disease patients undergoing hemodialysis. Material & methode: Sixty two patients with UXP were enrolled, randomized double blind study. Patients were divided to two group, calcipotriol 0.005% ointment group or placebo. In baseline, patients were instructed to apply twice daily for four weeks. We assesesment the efficacy and safety of calcipotriol 0.005% ointment and placebo after 2nd and 4th weeks treatment using overall dry skin score (ODSS), visual analog scale (VAS), corneometer and sebumeter. We also assessed adverse effect and tolerance this drugs using visual assessment scale. Results: Overall dry skin score (ODSS) and visual analog scale (VAS) significantly decreased in calcipotriol 0.005% ointment group than in placebo group (p <0.05). Skin hydration level based on Corneometer score and skin surface lipid based on Sebumeter score was significantly increased in calcipotriol 0.005% ointment group than in placebo group (p <0.05). Cure rate and clinical improvement for calcipotriol 0.005% ointment group was significantly higher than placebo group. There was no adverse effect between two groups after treatment. Conclusion: calcipotriol 0.005% ointment is effective than placebo and can be used as alternative or adjuctive treatment and safe and tolerance for UXP.

Lipid presentation by the protein C receptor links coagulation with autoimmunity

Antiphospholipid antibodies (aPLs) cause severe autoimmune disease characterized by vascular pathologies and pregnancy complications. Here, we identify endosomal lysobisphosphatidic acid (LBPA) presented by the CD1d-like endothelial protein C receptor (EPCR) as a pathogenic cell surface antigen recognized by aPLs for induction of thrombosis and endosomal inflammatory signaling. The engagement of aPLs with EPCR-LBPA expressed on innate immune cells sustains interferon- and toll-like receptor 7–dependent B1a cell expansion and autoantibody production. Specific pharmacological interruption of EPCR-LBPA signaling attenuates major aPL-elicited pathologies and the development of autoimmunity in a mouse model of systemic lupus erythematosus. Thus, aPLs recognize a single cell surface lipid–protein receptor complex to perpetuate a self-amplifying autoimmune signaling loop dependent on the cooperation with the innate immune complement and coagulation pathways.

Lipidomic analysis of facial skin surface lipid reveals the causes of pregnancy-related skin barrier weakness

Self-reported skin discomfort is a common problem during pregnancy, but it is not clear whether skin barrier function is altered in the process. Few studies have described the skin barrier function during pregnancy. In this work, we used highly sensitive and high-resolution ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to distinguish skin surface lipid (SSL) combined with multivariate analysis of lipids and metabolic changes to determine the relationship between SSL changes and skin physiology during pregnancy in order to better understand the skin condition of pregnant women. The results showed a significant reduction in the total lipid content in pregnant women. A total of 2270 lipids were detected, and the relative abundances of fatty acyls and glycerolipids were significantly reduced, while glycerophospholipids (GPs), sphingolipids, and saccharolipids was significantly increased in the pregnancy group. Multivariate data analysis indicated that 23 entities constituted the most important individual species responsible for the discrimination and phosphatidylcholine was the most abundant lipid in pregnancy group. In addition, compared to SSL profile of control group, it was observed that the average chain length of ceramides and fatty acids both decreased in SSL profile of pregnancy group. The main and most commonly affected pathway was that of GP pathways. These findings indicate that skin lipids are significantly altered in mid-pregnancy compared to the control group. Changes in ostrogen during pregnancy also make the skin more susceptible to inflammatory factors and lead to more fragile and susceptible skin, weakening the skin barrier along with the lipid alterations.

Spreading of a mycobacterial cell-surface lipid into host epithelial membranes promotes infectivity

Several virulence lipids populate the outer cell wall of pathogenic mycobacteria. Phthiocerol dimycocerosate (PDIM), one of the most abundant outer membrane lipids, plays important roles in both defending against host antimicrobial programs and in evading these programs altogether. Immediately following infection, mycobacteria rely on PDIM to evade Myd88-dependent recruitment of microbicidal monocytes which can clear infection. To circumvent the limitations in using genetics to understand virulence lipids, we developed a chemical approach to track PDIM during Mycobacterium marinum infection of zebrafish. We found that PDIM's methyl-branched lipid tails enabled it to spread into host epithelial membranes to prevent immune activation. Additionally, PDIM’s affinity for cholesterol promoted this phenotype; treatment of zebrafish with statins, cholesterol synthesis inhibitors, decreased spreading and provided protection from infection. This work establishes that interactions between host and pathogen lipids influence mycobacterial infectivity and suggests the use of statins as tuberculosis preventive therapy by inhibiting PDIM spread.

A Role of Newly Found Auxiliary Site in Phospholipase A1 from Thai Banded Tiger Wasp (Vespa affinis) in Its Enzymatic Enhancement: In Silico Homology Modeling and Molecular Dynamics Insights

Phospholipase A1 from Thai banded tiger wasp (Vespa affinis) venom also known as Ves a 1 plays an essential role in fatal vespid allergy. Ves a 1 becomes an important therapeutic target for toxin remedy. However, established Ves a 1 structure or a mechanism of Ves a 1 function were not well documented. This circumstance has prevented efficient design of a potential phospholipase A1 inhibitor. In our study, we successfully recruited homology modeling and molecular dynamic (MD) simulation to model Ves a 1 three-dimensional structure. The Ves a 1 structure along with dynamic behaviors were visualized and explained. In addition, we performed molecular docking of Ves a 1 with 1,2-Dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) lipid to assess a possible lipid binding site. Interestingly, molecular docking predicted another lipid binding region apart from its corresponding catalytic site, suggesting an auxiliary role of the alternative site at the Ves a 1 surface. The new molecular mechanism related to the surface lipid binding site (auxiliary site) provided better understanding of how phospholipase A1 structure facilitates its enzymatic function. This auxiliary site, conserved among Hymenoptera species as well as some mammalian lipases, could be a guide for interaction-based design of a novel phospholipase A1 inhibitor.