Dermal Exposure to Vesicating Nettle Agent Phosgene Oxime: Clinically Relevant Biomarkers and Skin Injury Progression in Murine Models.

Phosgene oxime (CX), categorized as a vesicating chemical threat agent, causes effects that resemble an urticant or nettle agent. CX is an emerging potential threat agent that can be deployed alone or with other chemical threat agents to enhance their toxic effects. Studies on CX-induced skin toxicity, injury progression, and related biomarkers are largely unknown. To study the physiologic changes, skin clinical lesions and their progression, skin exposure of SKH-1 and C57BL/6 mice was carried out with vapor from 10 µl CX for 0.5-minute or 1.0-minute durations using a designed exposure system for consistent CX vapor exposure. One-minute exposure caused sharp (SKH-1) or sustained (C57BL/6) decrease in respiratory and heart rate, leading to mortality in both mouse strains. Both exposures caused immediate blanching, erythema with erythematous ring (wheel) and edema, and an increase in skin bifold thickness. Necrosis was also observed in the 0.5-minute CX exposure group. Both mouse strains showed comparative skin clinical lesions upon CX exposure; however, skin bifold thickness and erythema remained elevated up to 14 days postexposure in SKH-1 mice but not in C57BL/6 mice. Our data suggest that CX causes immediate changes in the physiologic parameters and gross skin lesions resembling urticaria, which could involve mast cell activation and intense systemic toxicity. This novel study recorded and compared the progression of skin injury to establish clinical biomarkers of CX dermal exposure in both the sexes of two murine strains relevant for skin and systemic injury studies and therapeutic target identification. SIGNIFICANCE STATEMENT: Phosgene oxime (CX), categorized as a vesicating agent, is considered as a potent chemical weapon and is of high military and terrorist threat interest since it produces rapid onset of severe injury as an urticant. However, biomarkers of clinical relevance related to its toxicity and injury progression are not studied. Data from this study provide useful clinical markers of CX skin toxicity in mouse models using a reliable CX exposure system for future mechanistic and efficacy studies.

Phosgene oxime: a highly toxic urticant and emerging chemical threat.

Highly toxic industrial chemicals that are widely accessible, and hazardous chemicals like phosgene oxime (CX) that can be easily synthesized, pose a serious threat as potential chemical weapons. In addition, their accidental release can lead to chemical emergencies and mass casualties. CX, an urticant, or nettle agent, grouped with vesicating agents, causes instant pain, injury and systemic effects, which can lead to mortality. With faster cutaneous penetration, corrosive properties, and more potent toxicity compared to other vesicating agents, CX causes instantaneous and severe tissue damage. CX, a potential chemical terrorism threat agent, could therefore be weaponized with other chemical warfare agents to enhance their harmful effects. CX is the least studied vesicant and its acute and long-term toxic effects as well as its mechanism of action are largely unknown. This has hampered the identification of therapeutic targets and the development of effective medical countermeasures. There are only protective measures, decontamination, and supportive treatments available for reducing the toxic effects from CX exposure. This review summarizes CX toxicity, its known mechanism of action, and our current studies exploring the role of mast cell activation and associated signaling pathways in CX cutaneous exposure under the National Institutes of Health Countermeasures Against Chemical Threats program. Potential treatment options and the development of effective targeted countermeasures against CX-induced morbidity and mortality is also discussed.

Adhesion molecules, chemokines and matrix metallo-proteinases response after albendazole and albendazole plus steroid therapy in swine neurocysticercosis.

The treatment of neurocysticercosis (NCC) varies with location, number and stage of the Taenia solium cysticerci (cysts). Albendazole (ABZ) effectively kills cysticerci, and subsequently induces neuro-inflammation facilitated by leukocyte infiltration. We hypothesize that immune response varies around drug responder (degenerating/dying) and non-responder (viable) cysts after ABZ and ABZ plus steroid (ABZS) therapy, which may determine the disease pathogenesis. Twenty cysticercotic swine were treated with ABZ (n = 10; group1) and ABZS (n = 10; group2). Expression of adhesion molecules, chemokines and matrix metallo-proteinases (MMPs) was measured by qRT-PCR (quantitative reverse transcriptase-polymerase chain reaction) and ELISA. Gelatin gel zymography was performed to detect the activity of MMP-2 and -9. In group1, ABZ therapy induced higher expressions of ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), E-selectin, MCP-1 (monocyte chemotactic protein-1), Eotaxin-1, MIP-1α (macrophage inflammatory protein-1α), RANTES (regulated on activation, normal T cell expressed and secreted), MMP-2 and MMP-9 around ABZ responder (AR) cysts. Three pigs with cyst burdens ≥10 died following ABZ therapy. However, in group2, moderate expressions of ICAM-1, VCAM-1, E-selectin, RANTES and MMP-9 were associated with ABZS responder (ASR), whereas low expressions of these molecules were associated with ABZS non-responder (ASNR) cysts. In conclusion, ABZ alone therapy is not safe since it causes death of pigs due to higher inflammatory immune response around dying cysts. However, combination therapy is an effective treatment regimen even with the high cyst burden.

Association of ICAM-1 K469E polymorphism with dengue infection in North Indian population.

Dengue infection is caused by flavivirus is one of the leading cause of mortality. There are certain factors which play role in the transformation of a mild form of the disease (DF) into a severe form (DHF) but the most important ones are: viral strain virulence, host genetics, and host immune status. In severe dengue infection, plasma leakage occurs due to vascular endothelial cell activation through expression of adhesion molecule like intercellular cell adhesion molecule-1 (ICAM-1). A total of 100 dengue patients (DF; n = 53 and DHF/DSS; n = 47) and 200 healthy controls were included in the study. ICAM-1 K469E genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP). Expression of ICAM-1 mRNA was done by Real time reverse transcription- PCR (rRT-PCR). Patients with homozygous genotype (EE) have 3.22 fold risk (P = 0.008) of developing severe form of disease (DHF/DSS) as compared to other genotypes. Patients with DHF/DSS exhibit higher expression of ICAM-1 mRNA as compared to dengue fever and controls (P = 0.001 and < 0.001). Patients (DHF/DSS) with homozygous (EE) genotype exhibit higher expression of ICAM-1 mRNA when compared with wild type (KK) genotype (P = 0.005). This study suggests a possible association between the ICAM-1 polymorphism and the disease severity.

Identification of species and genetic variation in Taenia isolates from human and swine of North India.

Taenia solium is the major cause of taeniasis and cysticercosis/neurocysticercosis (NCC) in the developing countries including India, but the existence of other Taenia species and genetic variation have not been studied in India. So, we studied the existence of different Taenia species, and sequence variation in Taenia isolates from human (proglottids and cysticerci) and swine (cysticerci) in North India. Amplification of cytochrome c oxidase subunit 1 gene (cox1) was done by polymerase chain reaction (PCR) followed by sequencing and phylogenetic analysis. We identified two species of Taenia i.e. T. solium and Taenia asiatica in our isolates. T. solium isolates showed similarity with Asian genotype and nucleotide variations from 0.25 to 1.01 %, whereas T. asiatica displayed nucleotide variations ranged from 0.25 to 0.5 %. These findings displayed the minimal genetic variations in North Indian isolates of T. solium and T. asiatica.

Antibiofilm and membrane-damaging potential of cuprous oxide nanoparticles against Staphylococcus aureus with reduced susceptibility to vancomycin.

The antimicrobial effects of copper ions and salts are well known, but the effects of cuprous oxide nanoparticles (Cu2O-NPs) on staphylococcal biofilms have not yet been clearly revealed. The present study evaluated Cu2O-NPs for their antibacterial and antibiofilm activities against heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and vancomycin-intermediate S. aureus (VISA). Nanoscaled Cu2O, generated by solution phase technology, contained Cu2O octahedral nanoparticles. Field emission electron microscopy demonstrated particles with sizes ranging from 100 to 150 nm. Cu2O-NPs inhibited the growth of S. aureus and showed antibiofilm activity. The MICs and minimum biofilm inhibitory concentrations ranged from 625 µg/ml to 5,000 µg/ml and from 2,500 µg/ml to 10,000 µg/ml, respectively. Exposure of S. aureus to Cu2O-NPs caused leakage of the cellular constituents and increased uptake of ethidium bromide and propidium iodide. Exposure also caused a significant reduction in the overall vancomycin-BODIPY (dipyrromethene boron difluoride [4,4-difluoro-4-bora-3a,4a-diaza-s-indacene] fluorescent dye) binding and a decrease in the viable cell count in the presence of 7.5% sodium chloride. Cu2O-NP toxicity assessment by hemolysis assay showed no cytotoxicity at 625 to 10,000 µg/ml concentrations. The results suggest that Cu2O-NPs exert their action by disruption of the bacterial cell membrane and can be used as effective antistaphylococcal and antibiofilm agents in diverse medical devices.

Segmental Abdominal Paresis Attributed to Herpes Zoster Infection Mimicking an Abdominal Hernia: An Interesting Case From a Surgical Unit of a Tertiary Healthcare Center.

The varicella-zoster virus reactivates to cause herpes zoster, commonly referred to as shingles. Shingles traditionally manifest as itchy vesicles in a dermatomal distribution, accompanied by related constitutional symptoms in immunocompetent patients. Usually, the rash resolves completely in seven to ten days. Herpetic neuralgia is the most typical herpes zoster consequence. Around 1% to 5% of individuals have motor impairments, with Ramsay-Hunt syndrome being the most prevalent ailment. Additional problems encompass abdominal pseudohernia, paralytic ileus/colonic pseudo-obstruction, hemidiaphragm paralysis, bladder dysfunction, localized paresis, constipation, and visceral neuropathy. Herpes zoster infection typically involves the posterior root ganglia, and most of the symptoms are sensory. Motor involvement can occur in the same distribution but is relatively uncommon. Segmental zoster paresis is a rare motor complication of herpes zoster, mimicking an abdominal hernia, which has an incidence of approximately 0.7%, but it needs no surgery different from the real abdominal wall hernia. In this case report, we describe a patient who, three weeks after developing a herpes zoster rash, acquired an abdominal protrusion, i.e., herpes-induced pseudohernia.

Post-irradiation chemical processing of DNA damage generates double-strand breaks in cells already engaged in repair.

In cells exposed to ionizing radiation (IR), double-strand breaks (DSBs) form within clustered-damage sites from lesions disrupting the DNA sugar-phosphate backbone. It is commonly assumed that these DSBs form promptly and are immediately detected and processed by the cellular DNA damage response (DDR) apparatus. This assumption is questioned by the observation that after irradiation of naked DNA, a fraction of DSBs forms minutes to hours after exposure as a result of temperature dependent, chemical processing of labile sugar lesions. Excess DSBs also form when IR-exposed cells are processed at 50°C, but have been hitherto considered method-related artifact. Thus, it remains unknown whether DSBs actually develop in cells after IR exposure from chemically labile damage. Here, we show that irradiation of 'naked' or chromatin-organized mammalian DNA produces lesions, which evolve to DSBs and add to those promptly induced, after 8-24 h in vitro incubation at 37°C or 50°C. The conversion is more efficient in chromatin-associated DNA, completed within 1 h in cells and delayed in a reducing environment. We conclude that IR generates sugar lesions within clustered-damage sites contributing to DSB formation only after chemical processing, which occurs efficiently at 37°C. This subset of delayed DSBs may challenge DDR, may affect the perceived repair kinetics and requires further characterization.

Effect of platelet counts and activator in platelet-rich plasma on the treatment of androgenetic alopecia, split-head comparison: A randomised, double-blind study.

Background Androgenetic alopecia is a common, chronic, non-scarring alopecia. It is characterised by stepwise miniaturisation of the hair follicles, due to alteration in the hair cycle dynamics, leading to the transformation of terminal hair follicles into a vellus ones. Oral finasteride and topical minoxidil are the only approved drugs for treating this condition. Due to a limited number of effective therapies for androgenetic alopecia, platelet-rich plasma may be an effective alternative treatment. Aims To study the effect of activator in platelet-rich plasma and baseline platelet count in platelet-rich plasma on the treatment of androgenetic alopecia. Methods A randomised, double-blind split-head comparative study. The sample size was calculated and randomisation was done. Patients with androgenetic alopecia were allocated into two groups; in the first group, autologous activated platelet-rich plasma was injected in the right half of the affected scalp and autologous non-activated platelet-rich plasma was injected in the left half of the affected scalp and vice versa in the second group. Patients were also categorised on the basis of platelet counts in their platelet-rich plasma in three groups; group A (6-8 lakh/mm3), group B (8.1-10 lakh/mm3) and group C (>10 lakh/mm3). Interventions were done monthly for three months and followed up for the next three months. Effects of interventions were assessed by hair density, hair thickness, patient self-assessment and clinical photography. Results A total of 80 patients were included in the study. Activated platelet-rich plasma produced significant improvement of hair density after four months and hair thickness at 6 months. An increase in platelet count led to a significant increase in hair density and hair thickness after three and four months respectively and a highly significant increase in both parameters at the end of the study. Limitations Long-term follow-up of cases was not done and no measurement of vellus hair count was done. Conclusion There is a significant effect of activator and platelet count of the platelet-rich plasma on hair density as well as hair thickness.

A Study on the Clinical Profiles of Patients With Cerebrovascular Accident (Stroke) in a Tertiary Care Hospital in Jharkhand.

Introduction Stroke is a devastating and disabling cerebrovascular disease with a significant amount of residual deficit. The prevalence of stroke is in a rising trend in India. Larger studies are needed for the evaluation of risk factors. Material and methods This cross-sectional study aimed to assess the clinical profile of patients with stroke. The demographic details of the patients were taken, comorbidities were noted, and laboratory tests were done. Observation The most common age group who presented with stroke was 61-80 years, followed by 41-60 years, comprising 47% and 46%, respectively. Ischemic stroke was more common (60%) than hemorrhagic stroke (40%). Male patients were more than female patients. Alcohol, smoking, hypertension, diabetes, anemia, and proteinuria were present in the study group. Conclusion Regular evaluation of blood pressure, blood sugar, lipid profile, and proteinuria should be routinely done in patients with diabetes and hypertension who are more than 40 years old.

Comparison of Autologous Platelet-Rich Fibrin Matrix and Transplantation of Autologous Noncultured Epidermal Cell Suspension in the Treatment of Chronic Non Healing Ulcer: Randomized Comparative Study.

Context: Chronic non-healing ulcer causes significant morbidity, high cost and reduced quality of life. Aims: To compare autologous platelet-rich fibrin matrix and transplantation of autologous non-cultured epidermal cell suspension in the treatment of chronic non-healing ulcers. Methods: The study was single-centre, prospective, randomised comparative study conducted in a tertiary care center in North India. Patients with chronic non-healing ulcer were included and randomly divided into two treatment groups- Group 1: Platelet-rich fibrin matrix (PRFM) procedure was done every 2 weeks with maximum three sittings and in Group 2: Transplantation of autologous noncultured epidermal cell suspension (NCES) procedure was done once. Follow-up was done every 2 weeks for 8 weeks then monthly for up to 5 months to evaluate the healing of the ulcer. The data were analysed by statistical package for social science (SPSS) trial version 22. To find out a significant difference in mean value between groups, the Chi-square test, student's t-test, and Mann-Whitney U test were used. Results: A total of 41 patients were included in the study. Complete healing of ulcers occurred in 89.5% of the patients in the PRFM group and 93.8% of the patients in the NCES group at the end of 5 months (P = 0.33). The mean duration of complete healing in PRFM was 1.7 months and in NCES was 2.13 months (P = 0.20). Conclusions: Both procedures were effective, and there was no significant difference between the two procedures.

A single ClpS monomer is sufficient to direct the activity of the ClpA hexamer.

ClpS is an adaptor protein that interacts with ClpA and promotes degradation of proteins with N-end rule degradation motifs (N-degrons) by ClpAP while blocking degradation of substrates with other motifs. Although monomeric ClpS forms a 1:1 complex with an isolated N-domain of ClpA, only one molecule of ClpS binds with high affinity to ClpA hexamers (ClpA(6)). One or two additional molecules per hexamer bind with lower affinity. Tightly bound ClpS dissociates slowly from ClpA(6) with a t((1/2)) of approximately 3 min at 37 degrees C. Maximum activation of degradation of the N-end rule substrate, LR-GFP(Venus), occurs with a single ClpS bound per ClpA(6); one ClpS is also sufficient to inhibit degradation of proteins without N-degrons. ClpS competitively inhibits degradation of unfolded substrates that interact with ClpA N-domains and is a non-competitive inhibitor with substrates that depend on internal binding sites in ClpA. ClpS inhibition of substrate binding is dependent on the order of addition. When added first, ClpS blocks binding of both high and low affinity substrates; however, when substrates first form committed complexes with ClpA(6), ClpS cannot displace them or block their degradation by ClpP. We propose that the first molecule of ClpS binds to the N-domain and to an additional functional binding site, sterically blocking binding of non-N-end rule substrates as well as additional ClpS molecules to ClpA(6). Limiting ClpS-mediated substrate delivery to one per ClpA(6) avoids congestion at the axial channel and allows facile transfer of proteins to the unfolding and translocation apparatus.

Association of MMP-2 and MMP-9 with clinical outcome of neurocysticercosis.

Matrix metalloproteinases (MMPs) are the major endopeptidases involved in proteolysis of blood brain barrier (BBB) during central nervous system (CNS) infections. The present study detected serum levels and activities of MMP-2 and MMP-9 in patients with neurocysticercosis (NCC) and their association with symptomatic disease. In total, 68 individuals with NCC (36 symptomatic patients with active seizures and 32 asymptomatic individuals) and 37 healthy controls were enrolled for the study. Serum MMP-2 and MMP-9 levels and their activities were measured by ELISA and gel zymography respectively. Mean serum MMP-2 levels (ng/ml) were higher both in asymptomatic and symptomatic NCC cases compared to healthy controls. However, significantly higher levels of serum MMP-9 (ng/ml) were detected only in symptomatic NCC patients compared to asymptomatic NCC cases and healthy controls. Levels of both MMPs positively correlated with symptomatic NCC. Serum MMP-2 activities were significantly higher in symptomatic and asymptomatic NCC compared to healthy controls whereas serum MMP-9 activity was significantly associated with symptomatic NCC compared to healthy controls and asymptomatic NCC. In conclusion, the elevated level of MMP-9 in serum appears to play an important role in the development of symptoms i.e. active seizures in patients with NCC. However, further studies are needed to elucidate its precise role in disease pathogenesis.

Global Surgery Fellowships-An Investigation of Opportunities, Outcomes, and Applicants.

Following the Lancet Commission on Global Surgery in 2015, the Global Surgery Fellowships have risen in popularity, advertised as formalized opportunities for surgical trainees who have an interest in international surgical care. There is currently no up-to-date review of all fellowships available and an urgently needed overview of these opportunities is presented, including critical appraisal of their accessibility, funding, and outcomes. Detailed searches were conducted on the web engine Google, using the term "global surgery fellowship" and iterations. From the 547 resulting links, after applying exclusion criteria, 69 relevant fellowships were included in analysis. The majority of fellowships based in the United States (55%) and arranged by non-governmental organizations (NGOs) or universities (>70%). Also, 60% of fellowships had a duration of 1 year or longer. Only a quarter of the fellowships was open solely to trainees from low- or middle-income countries (LMIC), with over 80% of these being full funded. But 40% of the fellowships were advertised as open to trainees from any country, though only one-third of these provided full funding. Key themes across the fellowships' outcomes included "Professional Development," "Research," and "LMIC Quality Improvement." Almost all of the fellowships (95%) stated international travel opportunities. Twelve of the fellowships offered higher degrees, with the most common being a Masters of Public Health. The global distribution of fellowships and reduced funding opportunities for trainees from LMIC limit accessibility of the Global Surgery Fellowships. It is, however, still promising that most of key themes and high rates of international work are in line with The Lancet Commission's recommendations. This overview of the Global Surgery Fellowships highlights the need for collaboration between institutions and has illustrated points for consideration when introducing new and the value of established fellowships.

Comparison of Sensitivities of Skin Prick and Intradermal Tests with Oral Rechallenge Test: A Prospective Interventional Hospital-Based Study.

BACKGROUND: Identification of culprit drug causing adverse cutaneous drug reactions may not be possible clinically due to the intake of more than one drug. AIM: To compare the sensitivity of skin tests with gold standard oral rechallenge test to detect adverse cutaneous drug reactions. MATERIALS AND METHODS: This is a prospective interventional hospital-based study of patients with adverse cutaneous drug reactions attending the outpatient department of dermatology and venereology at a tertiary care center over a 12-month period. Skin prick tests, intradermal tests, and oral rechallenge tests were performed in these patients and their sensitivities were compared. The data of quantitative nature is presented in mean and standard deviation, and categorical variables are presented in number and percentage. The sensitivity of skin tests is compared with the gold standard oral rechallenge test. RESULTS: A total of 49 patients with adverse cutaneous drug reactions were evaluated. Clinical spectrum of adverse cutaneous drug reactions ranged from mild to severe, with fixed drug eruption being the commonest (55.1%) followed by maculopapular exanthem (32.7%). The highest incidence was with fluoroquinolones (43.8%) followed by nonsteroidal anti-inflammatory drugs. Fluoroquinolones were the major cause of fixed drug eruption followed by nonsteroidal anti-inflammatory drugs. The sensitivity of skin prick test and intradermal tests were 49% and 73%, respectively and the difference was highly significant (P < 0.001). The difference in sensitivity in skin prick test versus oral rechallenge test and intradermal test versus oral rechallenge test was also highly significant (P < 0.001). LIMITATIONS: Small sample size was a major limitation. Histopathological examinations and human leukocyte antigen associations could not be done. CONCLUSION: Predominant causative drugs were fluoroquinolones followed by nonsteroidal anti-inflammatory drugs. Sensitivities of skin prick test and intradermal test were quite good and these skin tests should be performed before oral rechallenge test in cases of adverse cutaneous drug reactions.

CuO assisted borate 1393B3 glass scaffold with enhanced mechanical performance and cytocompatibility: An In vitro study.

Herein, three dimensional porous 1393B3 borate-based glass (BBG) scaffold along with their CuO derivatives (C1BBG, C2BBG, and C3BBG) tailored with trabecular bones' architecture were prepared by melt-quench route followed by foam replica technique. The properties of 'CuO incorporated' scaffolds, as compared to 'as prepared' scaffold were analyzed by a series of In vitro investigations for enhancement in biological compatibility, bioactivity, and physicomechanical performances. The in vitro study demonstrates superior mechanochemical stability of CBBGs (CuO derived 1393B3) than the pure BBG, while causing no or minimal effect on bioactivity and cytocompatibility post CuO incorporation to the BBG. In fact, the biological compatibility examined through MTT, Live/Dead, and cell adhesion study using the L929 cell lines was enhanced in the CBBGs up to 1% CuO incorporated scaffolds (C1BBG and C2BBG) in most cases. However, the enhanced biological compatibility was observed in C1BBG in comparison to other BBGs. Thus, the CuO incorporation into BBG enhanced mechanochemical and biological performance without affecting the bioactivity of the scaffold; henceforth, CBBGs could be considered neo bone tissue regenerative biomaterials.

Effect of supersaturated oxygen emulsion treatment on chloropicrin-induced chemical injury in ex vivo rabbit cornea.

With a possibility for the use of chemical weapons in battlefield or in terrorist activities, effective therapies against the devastating ocular injuries, from their exposure, are needed. Oxygen plays a vital role in ocular tissue preservation and wound repair. We tested the efficacy of supersaturated oxygen emulsion (SSOE) in reducing ex vivo corneal and keratocyte injury from chloropicrin (CP). CP, currently used as a pesticide, is a chemical threat agent like the vesicating mustard agents and causes severe corneal injury. Since our previous study in human corneal epithelial cells showed the treatment potential of SSOE (55 %), we further tested its efficacy in an ex vivo CP-induced rabbit corneal injury model. Corneas were exposed to CP (700 nmol) for 2 h, washed and cultured with or without SSOE for 24 h or 96 h. At 96 h post CP exposure, SSOE treatment presented a healing tendency of the corneal epithelial layer, and abrogated the CP-induced epithelial apoptotic cell death. SSOE treatment also reduced the CP induced DNA damage (H2A.X phosphorylation) and inflammatory markers (e.g. MMP9, IL-21, MIP-1ß, TNFα). Further examination of the treatment efficacy of SSOE alone or in combination with other therapies in in vivo cornea injury models for CP and vesicants, is warranted.

Efficacy of Terbinafine and Itraconazole in Different Doses and in Combination in the Treatment of Tinea Infection: A Randomized Controlled Parallel Group Open Labeled Trial with Clinico-Mycological Correlation.

BACKGROUND: There is a rising prevalence of dermatophyte infection especially in the tropics. It has been observed that the antifungals are not as effective as they used to be. AIMS: To determine the effectiveness of terbinafine and itraconazole in different doses and in combination in the treatment of tinea infection. MATERIALS AND METHODS: Study design was a randomized parallel group trial. Patients were randomly divided into five parallel arms in which two of the standard drugs in recommended doses were compared with their double doses and with combination of both the drugs. Patients were followed up every 2 weeks. Outcomes were assessed at 4 and 8 weeks. Cure was considered as complete clinical resolution of the lesions. Fungal culture and sensitivity were done by disk diffusion method for all patients. Parametric one-way analysis of variance (F test) and Chi-square test were used for the analysis. RESULTS: Two-hundred seventy-five patients were included in the study. Itraconazole containing groups showed significantly higher cure rates than terbinafine only groups both at 4 and 8 weeks (P < 0.001). Itraconazole containing groups, when compared against each other, were not found to be significantly different. The outcomes between terbinafine only groups were also not significantly different. Cure rates at 8 weeks were found to be greater than that at 4 weeks for all groups which were found to be highly significant (P < 0.001). CONCLUSIONS: Itraconazole seems to be more effective than terbinafine. There is no benefit in increasing the dose or using a combination regimen in the treatment of tinea. Prolonged duration of treatment is required for complete cure.

Association of Acanthosis Nigricans and Acrochordon with Insulin Resistance: A Cross-Sectional Hospital-Based Study from North India.

BACKGROUND: Insulin resistance (IR) is a pre-diabetic condition and has been reported in patients with acanthosis nigricans (AN) and acrochordon. AN and acrochordon are claimed to be cutaneous markers of IR. AIM: The purpose of this paper was to study the association of AN and acrochordon with IR. METHODS: It was a cross-sectional hospital-based study. Both groups were assessed for IR by using homeostatic model assessment of insulin resistance (HOMA-IR) formula. RESULTS: A total of 70 cases and an equal number of controls were studied. IR was observed more in cases (41.4%) compared to controls (17.1%) (P < 0.01). Mean HOMA-IR value was also significantly higher in cases (4.32 ± 4.44) compared to controls (2.27 ± 0.90) (P < 0.05). LIMITATIONS: Low number of cases and controls were taken in the study. Association with hyperlipidemia and metabolic syndrome was not elicited. CONCLUSIONS: AN and acrochordons were found to be associated with IR.

Id1 and Id3 Maintain Steady-State Hematopoiesis by Promoting Sinusoidal Endothelial Cell Survival and Regeneration.

Investigating mechanisms that regulate endothelial cell (EC) growth and survival is important for understanding EC homeostasis and how ECs maintain stem cell niches. We report here that targeted loss of Id genes in adult ECs results in dilated, leaky sinusoids and a pro-inflammatory state that increases in severity over time. Disruption in sinusoidal integrity leads to increased hematopoietic stem cell (HSC) proliferation, differentiation, migration, and exhaustion. Mechanistically, sinusoidal ECs (SECs) show increased apoptosis because of reduced Bcl2-family gene expression following Id gene ablation. Furthermore, Id1-/-Id3-/- SECs and upstream type H vessels show increased expression of cyclin-dependent kinase inhibitors p21 and p27 and impaired ability to proliferate, which is rescued by reducing E2-2 expression. Id1-/-Id3-/- mice do not survive sublethal irradiation because of impaired vessel regeneration and hematopoietic failure. Thus, Id genes are required for the survival and regeneration of BM SECs during homeostasis and stress to maintain HSC development.