Hemanta Kumar Kar

IFN-γ signaling maintains skin pigmentation homeostasis through regulation of melanosome maturation

Significance Skin tanning is a protective response of epidermal cells involving increased melanin formation. Overexposure to sun can cause sunburn and even skin cancer, and such conditions are partly attributable to the accumulation of toxic side products of melanin and its intermediates. In this study, we reveal the importance of key immune cytokine IFN-γ in pigmentation biology by studying cultured human melanocyte cells as well as mice and human disease models. We show that IFN-γ signaling regulates enzymes involved in melanin biosynthesis through a transcription factor IFN regulatory factor-1. Our study identifies a new mechanism of skin pigmentation homeostasis and proposes that strength and durability of local skin immune response may be decisive factors to delineate outcome between skin tanning and cancer. Cellular homeostasis is an outcome of complex interacting processes with nonlinear feedbacks that can span distinct spatial and temporal dimensions. Skin tanning is one such dynamic response that maintains genome integrity of epidermal cells. Although pathways underlying hyperpigmentation cascade are recognized, negative feedback regulatory loops that can dampen the activated melanogenesis process are not completely understood. In this study, we delineate a regulatory role of IFN-γ in skin pigmentation biology. We show that IFN-γ signaling impedes maturation of the key organelle melanosome by concerted regulation of several pigmentation genes. Withdrawal of IFN-γ signal spontaneously restores normal cellular programming. This effect in melanocytes is mediated by IFN regulatory factor-1 and is not dependent on the central regulator microphthalmia-associated transcription factor. Chronic IFN-γ signaling shows a clear hypopigmentation phenotype in both mouse and human skin. Interestingly, IFN-γ KO mice display a delayed recovery response to restore basal state of epidermal pigmentation after UV-induced tanning. Together, our studies delineate a new spatiotemporal role of the IFN-γ signaling network in skin pigmentation homeostasis, which could have implications in various cutaneous depigmentary and malignant disorders.

Treatment of leprosy

Leprosy is a curable disease, having been eliminated from many countries, including India. This has been possible due to the wide availability of effective and safe drugs. Treatment of leprosy has undergone considerable changes over decades, from chaulmoogra oil in 1915 to dapsone monotherapy in 1946, then eventually to multidrug therapy (MDT) in 1982. In the last two decades, reports of resistance to all first-line drugs have appeared in the literature, with the need to conduct clinical trials using newer but highly bactericidal drugs and their combinations against Mycobacterium leprae.

A comparative study on efficacy of high and low fluence Q-switched Nd:YAG laser and glycolic acid peel in melasma

BACKGROUND Melasma is acquired symmetric hypermelanosis characterized by light-to-deep brown pigmentation over cheeks, forehead, upper lip, and nose. Treatment of this condition is difficult and associated with high recurrence rates. With the advent of newer therapies, there is interest in the use of glycolic acid peels and Q-switched Nd:YAG laser (QSNYL) in high and low fluence for this disorder. AIMS To compare the therapeutic efficacy of low fluence QSNYL, high fluence QSNYL, and glycolic acid peel in melasma in three study groups of 25 patients each. METHODS Seventy-five Indian patients diagnosed as melasma were included. These patients were randomly divided in three groups (Group A = 25 patients of melasma treated with low-fluence QSNYL at weekly intervals, Group B = 25 patients of melasma treated with glycolic acid peel at 2 weeks intervals, Group C = 25 patients of melasma treated with high-fluence QSNYL at 2 weeks intervals). Study period and follow-up period was of 12 weeks each. Out of the 75 patients included, 21 patients in Group A, 19 patients in Group B, and 20 patients in Group C completed the study. Response to treatment was assessed using melasma area and severity index score. RESULTS Significant improvement was recorded in all the three groups. The improvement was statistically highly significant in Group A as compared to Group C (P<0.005), significant in Group A as compared to Group B (P<0.05), and also in Group B when compared to Group C (P<0.05). Low-fluence QSNYL was associated with least side effects. CONCLUSIONS This study shows the efficacy of low-fluence QSNYL and glycolic acid peel in melasma. These could be an effective treatment options compared to conventional methods for the treatment of melasma.

1064 nm Q switched Nd: YAG laser treatment of nevus of Ota: An Indian open label prospective study of 50 patients.

BACKGROUND Nevus of Ota is very common in Asians. Estimated male to female ratio is 1:4.8. Patients seek treatment early in life due to psychological trauma and cosmetic disfigurement. The creation of high power, short pulse Q switched lasers has recently provided tools for considerable therapeutic advances in the treatment of dermal pigmented lesions. AIMS To determine the efficacy and side-effect profile of Q switched Nd:YAG Laser (QSNYL) in fifty Indian patients. METHODS Fifty patients of nevus of Ota underwent multiple treatments (average 5 sessions) at monthly intervals carried out over a period of 2 years with QSNYL (Med-lite C6). Of the 50 patients, 2 were males; and the rest were females. Skin types treated included phototype IV and V. The response after subsequent treatments was documented through serial photographs that were taken before and after every treatment session. Response to the treatment was graded based on quartile grading scale. RESULTS Near total improvement was seen in 8%, marked improvement in 22%, moderate improvement in 38% and 32% patients reported less than 25% clearing of the lesion. All patients reported some improvement. Transient postinflammatory hyperpigmentation was observed in 4 (8%) patients, which cleared with use of sunscreens and bleaching agents within 2 months. No textural change or scarring was observed in any patient. CONCLUSIONS QSNYL is an easy-to-perform and effective treatment in cases of nevus of Ota in Indian patients with few side effects.

Mycobacterium w vaccine, a useful adjuvant to multidrug therapy in multibacillary leprosy: a report on hospital based immunotherapeutic clinical trials with a follow-up of 1-7 years after treatment.

A vaccine based on autoclaved Mycobacterium w was administered, in addition to standard multidrug therapy (MDT), to 156 bacteriologically positive, lepromin negative multibacillary leprosy patients compared to a well matched control group of 145 patients with a similar type of disease who received a placebo injection in addition to MDT. The MDT was given for a minimum period of 2 years and continued until skin smear negativity, while the vaccine was given at 3-month intervals up to a maximum of eight doses. The fall in clinical scores and bacteriological indices was significantly more rapid in vaccinated patients, from 6 months onward until years 2 or 3 of therapy. However, no difference was observed in the fall in bacteriological index in the two groups from year 4 onwards. The number of LL and BL patients released from therapy (RFT) following attainment of skin smear negativity, after 24-29 months of treatment was 84/133 (63.1%) in vaccinated and 30/120 (25.0%) in the placebo group; the difference was highly statistically significant (P < 0.0001). In all, 90.2% patients (146/162) converted from lepromin negativity to positivity in the vaccine group, as against 37.9% (56/148) in the placebo group. The average duration of lepromin positivity maintained following eight doses of vaccine administered over 2 years was 3.016 years in the vaccine and 0.920 years in the placebo group. Histological upgrading after 2 years of treatment in the LL type was observed in 34/84 (40.5%) cases in the vaccine and 5/85 (5.9%) cases in the placebo group, the difference being statistically significant (P < 0.001). The incidence of type 1 reactions was significantly higher (30.5%) in the vaccine group than (19.7%) in the placebo group (P = 0.0413); the difference was mainly observed in LL type (P = 0.009). The incidence of type 2 reactions was similar (31.8 and 34.6%) in vaccine and placebo groups. The vaccine did not precipitate neuritis or impairments over and above that encountered with MDT alone. After 5 years of follow-up following RFT, no incidence of bacteriological or clinical relapses was observed in both groups.

Reactional states and neuritis in multibacillary leprosy patients following MDT with/without immunotherapy with Mycobacterium w antileprosy vaccine

A vaccine based on autoclaved Mycobacterium w was administered, in addition to standard multidrug therapy (MDT), to 157 untreated, bacteriologically positive, lepromin negative multibacillary leprosy patients, supported by a well matched control group of 147 patients with similar type of disease, who received a placebo injection in addition to MDT. The MDT was given for a minimum period of 2 years and continued until skin smear negativity, while the vaccine/placebo was given at 3-monthly intervals up to a maximum of eight doses. The incidence of type 2 reaction and neuritis during treatment and follow-up showed no statistically significant difference in the vaccine and placebo groups. The incidence of type 1 reaction (mild in most cases), however, was higher in the vaccine group (P = 0.041, relative risk ratio 1.79), considering LL, BL and BB leprosy types together, and considerably higher (P = 0.009) in LL type, probably because of confounding due to higher number of patients with previous history of reaction in this group. The occurrence of reactions and neuritis in terms of single or multiple episodes was similar in the vaccine and placebo groups. The association of neuritis and reactions, as well as their timing of occurrence (during MDT or follow-up), was also similar in the two groups, with more than 90% of occurrences taking place during MDT. The incidence of reversal reaction was significantly higher among the males in the vaccine group (34.5% versus 8.3%, P = 0.019). Patients with high initial BI (4.1-6.0) showed higher incidence of reactions (70.3%) as compared to those with medium (2.1-4.0) and low (0.3-2.0) BI where the reactions were observed with a frequency of 56.1% and 38.8%, respectively. However, unlike reactions, neuritis incidence did not seem to be affected by initial BI to the same extent in the vaccine group, with frequencies of 35.3%, 36.3% and 25.9% in the three mentioned BI ranges. Overall, the vaccine did not precipitate reactional states and neuritis over and above that observed with MDT alone.

A case of angiokeratoma circumscriptum of the tongue: response with carbon dioxide and pulsed dye laser.

Solitary angiokeratoma circumscriptum (AC) of the tongue is a rare entity. We present a case of solitary AC over the ventral surface of the tongue present for 3 years. The patient was treated with a combination of carbon dioxide (CO2) and pulsed dye laser (PDL). There was more than 75% improvement in the lesion after treating with alternate sessions of CO2 and PDL.

Evaluation of Repigmentation with Cultured Melanocyte Transplantation (CMT) Compared with Non-Cultured Epidermal Cell Transplantation in Vitiligo at 12th Week Reveals Better Repigmentation with CMT

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Granuloma faciale with extrafacial involvement and response to tacrolimus.

Granuloma faciale (GF) is a chronic condition characterized by red-brown plaques with follicular accentuation present usually on the face. We present a case of 35-year-old female with 5 year history of plaques over cheek and extra facial sites consistent with GF and its response to topical tacrolimus. This case supports previous reports of successful treatment of GF with topical tacrolimus.

Antidermatophytic activity of miconazole nanoformulation against Trichophyton rubrum

Abstract Objective To formulate and evaluate the antifungal activity of miconazole nitrate proniosomes against Trichophyton rubrum. Methods Miconazole loaded proniosomal vesicles were prepared by coacervation phase separation method using surfactants, cholesterol and phosphatidylcholine as excipients. The in vitro antifungal activity of prepared vesicles was performed using agar disc diffusion technique. Results The miconazole nitrate lipid vesicle preparation F5A and F5B showed good antifungal activity with high zones of inhibition i.e . (12.96 ± 0.63) mm and (14.06 ± 0.58) mm than nonvesicular plain drug gel i.e . (10.48 ± 0.79) mm after 3 days at 250 µg/mL concentration (For all comparisons P 0.05 was considered as significant). Conclusions Proniosomal preparation resulted in better permeation of the miconazole nitrate and there was a constant increase in zone of inhibition with increase in drug concentration. This study proves antifungal potential of novel proniosomal preparation of miconazole nitrate against Trichophyton rubrum in the treatment of tinea infections.