Downregulation of involucrin in psoriatic lesions following therapy with propylthiouracil, an anti-thyroid thioureylene: immunohistochemistry and gene expression analysis.

BACKGROUND: Propylthiouracil (PTU), an anti-thyroid thioureylene, has been shown to be effective in chronic plaque psoriasis. Involucrin is a precursor protein that is upregulated in psoriasis. OBJECTIVES: This study evaluated the expression of involucrin in the epidermis of skin in psoriatic plaques before and after treatment with PTU. METHODS: This was an open-label, prospective study in which 25 psoriasis patients underwent skin biopsies prior to treatment with oral PTU 100 mg three times per day for 12 weeks. Patients were assessed at 2, 6, and 12 weeks. Skin biopsies were repeated at the same sites at 12 weeks. Pre- and post-treatment specimens were subjected to immunohistochemical staining and real-time polymerase chain reaction for involucrin. RESULTS: Mean ± standard deviation (SD) scores on the Psoriasis Area and Severity Index reduced significantly from 17.86 ± 9.9 at baseline to 4.63 ± 4.1 at week 12 (P < 0.001). Histomorphometric analysis revealed marked decreases in numbers of positively stained cells and intensity of staining. Staining became localized to the upper granular layers after therapy. Immunohistochemical scoring for involucrin reduced from a mean ± SD of 9.00 ± 0.67 at baseline to 3.90 ± 0.88 at week 12 (P < 0.0001). CONCLUSIONS: In psoriasis, there is increased expression of involucrin, which leads to abnormal keratinocyte differentiation and hence to the formation of psoriatic plaques. The therapeutic effect of PTU in psoriasis may be attributable to the downregulation of involucrin. Larger trials should further elucidate the mechanism and therapeutic potential of PTU in psoriasis.

Impact of methotrexate on oxidative stress and apoptosis markers in psoriatic patients.

Methotrexate (MTX), a cytotoxic chemotherapeutic agent, is considered an effective drug in the treatment of psoriasis. The aim of this study was to find out whether the effect of MTX treatment in psoriasis is due to oxidative stress-induced apoptosis. Psoriasis vulgaris patients (58 in number) were recruited for this study. Healthy volunteers (45 in number) served as control. Samples of psoriatic patients were collected and analyzed for total reactive oxygen species (ROS), malondialdehyde (MDA) levels, nitrite, nitrate levels and the activities of antioxidants like superoxide dismutase (SOD), catalase (CAT) and total antioxidant status (TAS) and also the protein expression of caspase-3, before (Day 0) and after (at the end of 6 and 12 weeks) MTX treatment. Our results show a significant increase in tissue ROS and plasma MDA after MTX treatment when compared with before MTX treatment in psoriasis patients (p < 0.001). The levels of serum nitrite and nitrate were decreased significantly after MTX treatment (p < 0.001). The activities of plasma SOD, TAS and serum CAT levels were decreased, but not significantly after 12 weeks of treatment. The expression of caspase-3 was increased after MTX treatment. In conclusion, MTX induce apoptosis through oxidative stress by reducing NO and increasing caspase-3 levels. MTX-induced apoptosis may account for the beneficial effect of MTX treatment in psoriasis patients, which is characterized by acanthosis.

Serum interleukin-6 levels in response to methotrexate treatment in psoriatic patients.

BACKGROUND: Psoriasis is a chronic autoimmune hyperproliferative skin disease. In psoriasis, the cutaneous and systemic overexpression of various proinflammatory cytokines, such as interleukin-6 (IL-6) has been demonstrated. Methotrexate (MTX) has been used in the treatment of psoriasis. The aim of this study is to assess the effect of MTX on serum IL-6 levels and also to find the association between PASI score and IL-6 levels in psoriatic patients during MTX therapy. METHODS: We recruited 20 control subjects and 22 Psoriasis vulgaris patients for this study. The patients were treated with 7.5mg of methotrexate per week for 12 weeks. Folic acid was given at 5mg once daily except on the day of MTX for 12 weeks. There were 2 dropouts, because of increased liver enzyme levels. Blood samples were collected at three intervals (i.e., Day 0, 6 weeks, 12 weeks) from psoriatic patients and only once from control subjects. PASI score, biochemical and hematological parameters were assessed. Serum IL-6 level was analyzed by using ELISA. RESULTS: Biochemical and hematological parameters showed no significant changes. Serum IL-6 level and PASI score declined significantly (p<0.001) from Day 0 to 12 weeks of MTX treatment and also showed positive correlation before (r=0.992; p<0.000) and after (r=0.987; p<0.000) treatment with MTX. Out of 4 clinical indices of PASI, only 2 indices namely Infiltration (I) and Desquamation (D) showed positive correlation with IL-6 before and after MTX treatment. CONCLUSION: The treatment response with MTX in psoriatic patients can be seen both at clinical and molecular levels.

Role of sudarshan kriya and pranayam on lipid profile and blood cell parameters during exam stress: A randomized controlled trial.

BACKGROUND: Yoga is a science practiced in India over thousands of years. It produces constituent physiological changes and has sound scientific basis. AIM: Since exam stress modifies lipid profile and hematological parameters, we conducted an investigation on the effect of sudarshan kriya (SK and P) program on these parameters. MATERIALS AND METHODS: Blood samples of 43 engineering students were collected at four intervals namely baseline (BL), exam stress (ES), three and six weeks practice of SK and P during exam stress. Lipid profile and hematological parameters were measured at all four intervals. RESULTS: ES elevated total cholesterol (TC), triglycerides (TGL) and very low density lipoprotein (VLDL) levels. Hematological parameters affected by ES included neutrophil, lymphocytes, platelet count, packed cell volume (PCV) and mean cell volume (MCV). Three and six weeks practice of SK and P reduced the elevated lipid profile, hematological parameters and improved lymphocyte levels. CONCLUSION: Our study indicates that SK and P practice has the potential to overcome ES by improving lipid profile and hematological parameters.

Therapeutic efficacy and safety of propylthiouracil in psoriasis: an open-label study.

BACKGROUND: Psoriasis is a common hyperproliferative disorder of the skin associated with significant morbidity. Most of the drugs used in psoriasis provide only a temporary relief, whereas they are riddled with potential toxicities and cost concerns. Hence, there is a constant need to explore newer, effective, orally administered, and cost-effective drugs with minimal adverse effects. In this scenario, propylthiouracil (PTU), an antithyroid thioureylene has been shown to be effective in psoriasis which satisfies the above criteria. AIM: The objective of our study is to assess the clinical efficacy of PTU in psoriasis. METHODS: A total of 25 patients with plaque psoriasis were treated with oral PTU for 12 weeks. Clinical response was assessed using the "Psoriasis Area and Severity Index" (PASI) score. Routine blood analyses and thyroid function tests were carried out periodically during the study. RESULTS: Oral PTU produced significant clearing of lesions at 6 weeks and 12 weeks of the study period in all patients, as demonstrated by the reduction in PASI scores (33.9% in 6 weeks and 74.1% reduction in 12 weeks). Four patients experienced near complete clearing of the lesions. One patient developed mild elevation of liver enzymes which reversed on withdrawal of PTU. None of the patients had hypothyroidism or cytopenias. CONCLUSION: PTU significantly clears the lesions in psoriasis with minimal adverse effects. Hence, it can be considered as a therapeutic option in psoriasis, especially when the standard drugs cannot be used due to their toxicities or forbidding cost.

Clinical efficacy of propylthiouracil and its influence on prolactin in psoriatic patients.

OBJECTIVE: Propylthiouracil (PTU) is an effective drug for psoriasis treatment. Prolactin (PRL) is increased during psoriasis which has hyperproliferative effect on keratinocytes. Hence, the objective is to find the effect of PTU on PRL level in psoriatic patients. DESIGN AND METHODS: 25 psoriatic patients and 10 control subjects were involved in the study. Serum PRL, hematological and biochemical parameters, thyroid profile and histopathological examination were performed. RESULTS: PTU treatment for 6 weeks and 12 weeks cleared psoriatic lesions indicated by decreased PASI score (p<0.001). Patients before treatment showed significantly increased PRL levels (male p<0.01, female p<0.001) when compared to controls, which was found to decrease significantly (male p<0.01, female p<0.001) after 12 weeks. Hematological and biochemical parameters showed no significant change. Histopathology showed reduced thickening of the epidermis and acanthosis after PTU treatment. CONCLUSION: Since PRL is a growth hormone involved in hyperproliferation of keratinocytes, this study reveals the antiproliferative effect of PTU. Furthermore, no major side effects were observed following PTU treatment.

Impact of propylthiouracil on quality of life in psoriasis patients.

BACKGROUND: Psoriasis greatly impacts the quality of life (QOL) of patients including several dermatological conditions that are listed in the Dermatology Life Quality Index (DLQI). Decrease in psoriatic lesion as measured by Psoriasis Area Severity Index (PASI) score is associated with improvement in QOL. Propylthiouracil (PTU) was found to be clinically efficient in clearing psoriatic lesions. Our objective is to find the extent of improvement in QOL in psoriatic patients treated with PTU. MATERIALS AND METHODS: Twenty-three psoriatic patients who were taking 300 mg PTU/day were involved in the study. Clinical improvement was assessed by PASI score and QOL was assessed by DLQI questionnaire at baseline, 6 th and 12 th week of PTU treatment. RESULTS: Psoriatic patients before treatment showed significantly increased DLQI score when compared with 6 and 12 weeks of PTU treatment which was found to be decreased significantly (P < 0.001) after PTU treatment. There was a positive correlation between DLQI and PASI score at all three intervals of treatment period at P < 0.001 (r = 0.793, r = 0.834, r = 0.801), respectively. CONCLUSION: Since PTU was found to improve the QOL of psoriasis patients, this study adds an advantage of using it as treatment option in psoriasis.