Apremilast in chronic recalcitrant erythema nodosum leprosum: a report of two cases.

Erythema nodosum leprosum (ENL) is a severe immune reaction commonly encountered as a complication in patients with multibacillary leprosy. Management of chronic ENL in leprosy is challenging and necessitates the use of systemic immunosuppressants, including corticosteroids and thalidomide. No single drug is universally effective and most current therapeutic agents carry a significant risk of systemic toxicity. Apremilast is an orally effective phosphodiesterase-4 inhibitor with a potent immunomodulatory action and is clinically effective in inflammatory conditions like chronic plaque psoriasis. We report two patients with poorly controlled chronic ENL, despite the use of multiple therapeutic agents. Both patients demonstrated significant clinical improvement with apremilast, without any adverse effects, thereby suggesting its potential as a novel therapeutic option in chronic ENL. What's already known about this topic? Erythema nodosum leprosum (ENL) is an immune-mediated reaction in patients with multibacillary leprosy, with chronicity and recurrences frequently reported. Management of chronic ENL requires systemic immunosuppressants like corticosteroids, which may not be universally effective and carry a risk of serious toxicity. Apremilast is an oral immunomodulator with good efficacy in inflammatory conditions like chronic plaque psoriasis. What does this study? Apremilast may be an effective therapeutic agent in patients with chronic ENL.

Paediatric morphoea: a holistic review. Part 2: diagnosis, measures of disease activity, management and natural history.

Paediatric morphoea is a debilitating fibrosing disorder of uncertain aetiology, affecting the skin and subcutaneous tissues. Defining optimum management strategies in paediatric morphoea remains an ongoing challenge, owing to the varied presentations and a relative paucity of paediatric-specific studies. We performed a literature search on PubMed, MEDLINE and Google Scholar, using keywords such as 'pediatric morphea', 'juvenile localised scleroderma' and 'juvenile systemic sclerosis'. Relevant studies, including randomized trials, reviews of standard current guidelines and original research articles, were selected and results analysed before summarizing them. In Part 1 of this review, we described the epidemiology, aetiopathogenesis and clinical classification; in this part, we discuss the diagnosis, markers of disease activity, management and natural history in paediatric morphoea.

Paediatric morphoea: a holistic review. Part 1: epidemiology, aetiopathogenesis and clinical classification.

Morphoea, also known as localized scleroderma, is a debilitating fibrosing disorder of uncertain aetiology, affecting the skin and subcutaneous tissues. Paediatric-onset disease is not uncommon and is associated with frequent relapses. The disease has complex pathogenetic mechanisms and multiple clinical subtypes, and affects children of all ages. Recent research has focused on elucidating the disease pathophysiology and identifying measures of disease activity. We performed a literature search on PubMed, MEDLINE and Google Scholar, using keywords such as 'pediatric morphea', 'juvenile localised scleroderma' and 'juvenile systemic sclerosis'. Relevant studies, including randomized trials, reviews of standard current guidelines and original research articles, were selected, and results were analysed before being summarized. In the first of this two-part review, we provide a bird's-eye view of the current literature concerning the epidemiology, aetiopathogenesis and clinical classification of paediatric morphoea; in Part 2, we review the diagnosis, markers of disease activity, management and natural history.

Metal removal and recovery using bioelectrochemical technology: The major determinants and opportunities for synchronic wastewater treatment and energy production.

Microbial fuel cell (MFC) technology has emerged as a new and attractive bioelectrochemical approach in the last one and a half decade that offers an alternative to conventional treatment methods to remove and recover heavy metals and organics from wastewaters with simultaneous energy production. This technique has advantage over the conventional wastewater treatment techniques, which are energy intensive, sludge producing and with little effectivity at high concentrations. Significant work has been done in the recent years on MFC principle, electrode configuration, biofilm composition, application of MFC in wastewater treatment, metal removal or recovery and energy production. Basically, metal in the cathode chamber acts as acceptor of the electrons released from the oxidation of organic matter in the anode chamber by electrogenic microbes. Literature shows that efficacy of MFCs in removal and recovery of metals and power production is significantly influenced by redox potential of the metal, initial concentration, mix metal systems, carbon source in substrate, pH, biocathode, biofilm composition, gaseous environment in cathode, electrode modification and external resistance, which have been critically reviewed for the first time in the present paper to understand the role of the determinant factors that may be explored for improvement of the MFC performance. The paper provides further insights into the techno-economic aspects of MFC technology and suggests research needs for enhanced performance and reduced costs to increase its feasibility for application at commercial level.

Activated carbon from sugarcane bagasse ash for melanoidins recovery.

This work investigates the value added utilization of two sugar-distillery wastes: (i) melanoidins, which are complex Maillard reaction products in molasses distillery wastewater, and (ii) unburnt carbon in sugarcane bagasse ash. Activated unburnt carbon (AUC), prepared by deashing and steam activation, had properties comparable to commercial activated carbon (CAC). Both carbons are suitable for melanoidins adsorption followed by desorption using 25% pyridine solution. For AUC, the equilibrium adsorption data is well described by Langmuir isotherm up to 35 °C while Freundlich model fits better at higher temperature. Adsorption using CAC followed Freundlich isotherm at all temperatures. Both carbons followed pseudo second order kinetics and displayed endothermic physisorption. Recovery of melanoidins from AUC (78%) was close to that observed with CAC (80%).

Microglia-derived HIV Nef+ exosome impairment of the blood-brain barrier is treatable by nanomedicine-based delivery of Nef peptides.

The negative factor (Nef) of human immunodeficiency virus (HIV) is an accessory protein that is thought to be integral to HIV-associated immune- and neuroimmune pathogenesis. Here, we show that nef-transfected microglia-released Nef+ exosome (exNef) disrupts the apical blood-brain barrier (BBB) and that only nef-transfected microglia release Nef in exosomes. nef-gfp-transduced neurons and astrocytes release exosomes but did not release exNef in the extracellular space. Apical administration of exNef derived from nef-transfected 293T cells reduced transendothelial electrical resistance (TEER) and increased permeability of the BBB. Microglia-derived exNef applied to either the apical/basal BBB significantly reduced expression of the tight junction protein, ZO-1, suggesting a mechanism of exNef-mediated neuropathogenesis. Microglia exposed to exNef release elevated levels of Toll-like receptor-induced cytokines and chemokines IL-12, IL-8, IL-6, RANTES, and IL-17A. Magnetic nanoparticle delivery of Nef peptides containing the Nef myrisolation site across an in vitro BBB ultimately reduced nef-transfected microglia release of Nef exosomes and prevented the loss of BBB integrity and permeability as measured by TEER and dextran-FITC transport studies, respectively. Overall, we show that exNef is released from nef-gfp-transfected microglia; exNef disrupts integrity and permeability, and tight junctions of the BBB, and induces microglial cytokine/chemokine secretion. These exNef-mediated effects were significantly restricted by Nef peptides. Taken together, this study provides preliminary evidence of the role of exNef in HIV neuroimmune pathogenesis and the feasibility of a nanomedicine-based therapeutics targeting exNef to treat HIV-associated neuropathogenesis.

VH and VL Domains of Polyspecific IgM and Monospecific IgG Antibodies Contribute Differentially to Antigen Recognition and Virus Neutralization Functions.

We analysed contributions of variable heavy (FdVH ) and variable light (FdVL ) domains in comparison to scFv (FdVH +FdVL ) of naturally occurring polyspecific bovine IgM with an exceptionally long CDR3H and an induced monospecific bovine herpes virus-1 (BoHV-1) neutralizing IgG1 antibody in the context of to antigen-binding site and antibody function. Various recombinant FdVH , FdVL and scFv were constructed and expressed in Pichia pastoris from the bovine IgM and IgG1 antibody encoding cDNA. The scFv1H12 showed polyspecific antigen binding similar to parent IgM antibody, though subtle differences, for example, higher thyroglobulin recognition. Such differences reflect influence of the constant region on the antigen-binding site configuration. Unlike, variable light domain FdVL 1H12, the variable heavy domain FdVH 1H12 alone recognized multiple antigens that differed from the recognition pattern of scFv1H12 (FdVH +FdVL ) and the parent IgM antibody. Nonetheless, role of FdVL 1H12 in providing structural support to FdVH in antigen recognition is noted, apart from its intrinsic antigen recognition ability. Surface plasmon resonance analysis revealed low to moderate affinity of scFv1H12 to IgG antigen. By contrast, the individual FdVH 073 and FdVL 074, originating from induced BoHV-1 neutralizing IgG1 antibody, recognized target epitope on BoHV-1 weakly when compared to FdVH +FdVL (scFv3-18L). Interestingly, both the FdVH and FdVL domains of induced IgG antibody are required to achieve BoHV-1 neutralization. To conclude, there exist subtle functional differences in the contribution of FdVH and FdVL to antigen-binding site generation of polyspecific IgM and monospecific IgG antibodies relevant to antigen recognition and virus neutralization functions.

Dentigerous Cysts of Maxillofacial Region- Clinical, Radiographic and Biochemical Analysis.

BACKGROUND: Dentigerous cyst is the second most common type of odontogenic cysts that encloses the crown of an unerupted tooth by expansion of its follicle due to the collection of cystic fluid. In view of the capability of these lesions attaining a marked size if not diagnosed early and treated properly, the present study was done based on the clinical and radiographic presentation of the dentigerous cyst in addition to the analysis of the cystic contents. OBJECTIVE: The present study reported 14 cases of dentigerous cysts (DC) with their incidence and relative distribution of the maxillofacial region along with the clinical and radiographic features and biochemical analysis of cystic fluid. METHOD: The study was conducted at Sri Govind Tricentenary Dental College, Hospital and Research Institute, Gurgaon, Haryana for a period of one year and six months. A detailed case history and thorough clinical examination was done for the patients who were provisionally found to have odontogenic cysts. Necessary radiographs, aspiration of the cystic fluid and incisional biopsy were performed to the 14 patients who were provisionally diagnosed with dentigerous cysts (DC) after obtaining the informed consent and the cystic fluid was subjected to biochemical analysis. RESULTS: Majority of the affected patients with DC were in their second decade and showed more predilection for mandible with a male predominance. The area of predilection was third molar region in the mandible and it is the canine region in maxilla. All the cases were associated with impacted teeth and majority showed expansion of the buccal/labial cortical plate. The various biochemical variables (total protein content, albumin, globulin and albumin: globulin ratio) were also assessed in the present study. CONCLUSION: The awareness of protean features of DC evident through this study is essential for the general as well as specialty practitioners for the accurate diagnosis and proper treatment planning of these non cancerous but potentially destructive lesions and also opens new avenues for further research.

Seasonal trends in organochlorine pesticide residues in raw bovine milk from rural areas of Haryana, India.

Seasonal trends in organochlorine pesticides residues namely, 1,2,3,4,5,6-hexachlorocyclohexane (HCH) isomers, 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane (DDT) and its metabolites and endosulfan stereo isomers were investigated in raw bovine milk samples from rural areas of Ambala, Gurgaon and Hisar districts of the state of Haryana for winter, summer, and post-monsoon seasons. Highest concentration of HCH and DDT was found in 43 % and 53 % milk samples, respectively in post-monsoon season whereas highest values of endosulfan was reported in 36 % samples during winter season. During the study period only 2 % milk samples exceeded the maximum residue limit recommended by WHO for ΣHCH, 1 % samples each for α-HCH and γ-HCH, 9 % samples for ß-HCH as recommended by PFAA and 30 % samples for ΣDDT as prescribed by FAO. No statistical difference in the mean concentration of ∑HCH and ∑Endosulfan could be observed in any of the three districts. However, ∑DDT concentration showed marked difference [F(2, 25) = 12.42, p = 0.00018)] among the three districts.

Monte Carlo simulation and experimental validation of plant microtubules cathode in biodegradable battery.

For the first time, electrochemical methods are utilized to study the response of tubulin monomers (extracted from plant source such as Green Peas: Arachis Hypogea) towards charge perturbations in the form of conductivity, conformational changes via self-assembly and adsorption on Au surface. The obtained dimerization and surface adsorption energetics of the tubulins from Cyclic Voltammetry agree well with the literature value of 6.9 and 14.9 kCal/mol for lateral and longitudinal bond formation energy respectively. In addition to the effects of charge perturbations on change in structure, ionic and electronic conductivity of tubulin with increasing load are investigated and found to be 1.25 Sm-1 and 2.89 mSm-1 respectively. The electronic conductivity is 1.93 times higher than the literature value of 1.5 mSm-1, demonstrating the fact that the microtubules (dimer of tubulins, MTs) from plant source can be used as a semiconductor electrode material in energy conversion and storage applications. Thus, motivated by the Monte Carlo simulation and electrochemical results the MTs extracted from plant source are used as cathode material for energy storage device such as Bio-battery and the Galvanostatic Charge/Discharge studies are carried out in coin cell configuration. The configuration of the bio-battery cell is as follows: Al/CB//PP-1M KCl//MTs/SS; where SS and Al are used as current collectors for cathode and anode respectively, Polypropylene (PP) membrane soaked in 1M KCl as electrolyte and Carbon Black (CB) is the anode material. Another configuration of the cell would be replacement of CB by biopolymer such as ethyl cellulose anode (Al/EC/PP-1M KCl/MTs/SS).

Organochlorine pesticide residues in drinking water in the rural areas of Haryana, India.

Drinking water samples collected from rural areas of three districts of Haryana during pre-monsoon and post-monsoon periods were analysed for the presence of organochlorine pesticide residues. The main source of drinking water in rural areas, i.e. groundwater in Ambala and Gurgaon districts and surface water supply in Hisar district, was found to be contaminated with isomers of HCH and endosulfan and metabolites of DDT, whereas dieldrin remained below detection limits. During the study period, the mean values observed for total HCH, DDT and endosulfan were 87.6, 848.2, and 27.4 ng/L and 99.8, 275.3 and 164.2 ng/L, respectively, for Ambala and Gurgaon districts. In the case of Hisar district, the values were 78.5, 115.9, and 53.0 ng/L, respectively. During the study period, 37% of the samples exceeded the total pesticide level of 500 ng/L indicated in the EECD directive for drinking water. Seasonal variations of pesticide residues were also observed during the study period.

Organochlorine pesticide residues in human blood samples collected from Haryana, India and the changing pattern.

Blood samples were collected during August 1992 and August 2002 from various hospitals of Haryana state and analyzed for the presence of HCH and DDT residues and the change in concentration of pesticide residues was calculated in terms of % reduction. The study revealed that the mean residue levels of total HCH in human blood samples have declined by 87.6% while those of total DDT have decreased by 98.9% during a gap of 10 years. The obtained results reveal that during 1992 p,p'-DDT was the major component with the mean value of 6.125 mg/L followed by p,p'-DDE, γ-HCH, α-HCH and ß-HCH while in 2002, ß-HCH and p,p'-DDE were comparable with mean value of 0.053 and 0.052 mg/L, respectively followed by p,p'-DDT, α-HCH and p,p'-DDD.