Tazarotene gel with narrow-band UVB phototherapy: a synergistic combination in psoriasis

Abstract: BACKGROUND: Narrow-band UVB (NB-UVB) has been shown to be one of the most effective treatment modalities for psoriasis. Tazarotene, a known effective anti-psoriatic modality, when combined with NB-UVB may enhance the therapeutic success. OBJECTIVE: To study clinical efficacy and safety of combination of NB-UVB with topical tazarotene 0.05% gel in psoriasis. METHOD: Thirty patients with plaque psoriasis having symmetrical lesions were enrolled for 12 weeks. All patients were instructed to apply tazarotene gel on target plaque on left side of body once daily. In addition, the whole body was irradiated with NB-UVB twice weekly. Efficacy was assessed by target plaque scoring and number of treatment sessions for clearance. RESULT: Our study resulted in 3 key findings: Firstly, therapeutic efficacy of NB-UVB was enhanced by addition of tazarotene. This enhanced efficacy was more apparent in decreasing scaling and thickness as compared to decrease in erythema. Secondly, combination therapy showed faster clearance of target plaques, with reduction in mean number of treatment sessions. Thirdly, mean cumulative NB-UVB dose needed to achieve clearance of target plaques was significantly reduced with combination therapy. STUDY LIMITATIONS: The study was not randomized or controlled, but an open-label trial. The study period was relatively short, i.e., 12 weeks, without any follow-up period. CONCLUSION: Tazarotene gel significantly enhances the therapeutic efficacy of NB-UVB irradiation with faster clearance and without serious side effects.

Discovery of potential nicotinic acid receptor agonists from Chinese herbal medicines based on molecular simulation / 中国中药杂志

Nicotinic acid could increase high density lipoprotein and reduce serum total cholesterol, low density lipoprotein cholesterol and triglycerides in human bodies, thus is frequently applied in treating low high-density lipoprotein cholesterol and hypertriglyceridemia in clinic. However, according to the findings, nicotinic acid could also cause adverse effects, such as skin flush, beside its curative effects. In this study, bioisosterism, fragment-based search and Lipinski's Rule of Five were used to preliminarily screen out potential TCM ingredients that may have similar pharmacological effects with nicotinic acid from Traditional Chinese medicine database (TCMD). Afterwards, homology modeling and flexible docking were used to further screen out potential nicotinic acid receptor agonists. As a result, eleven candidate compounds were derived from eight commonly used traditional Chinese medicines. Specifically, all of the candidate compounds' interaction with nicotinic acid receptor was similar to nicotinic acid, and their docking scores were all higher than that of nicotinic acid, but their druggability remained to be further studied. Some of the eight source traditional Chinese medicines were used to lower lipid according to literature studies, implying that they may show effect through above means. In summary, this study provides basis and reference for extracting new nicotinic acid receptor agonists from traditional Chinese medicines and improving the medication status of hyperlipidemia.

Stabilized thiomer PAA-Cys-6MNA / 药学学报

The aimed of this study was to prepare stabilized thiomers to overcome the poor stability character of traditional thiomers. Poly(acrylic acid)-cysteine (PAA-Cys) was synthesized by conjugating cysteine with poly(acrylic acid) and poly(acrylic acid)-cysteine-6-mercaptonicotinic acid (PAA-Cys-6MNA, stabilized thiomers) was synthesized by grafting a protecting group 6-mercaptonicotinic acid (6MNA) with PAA-Cys. The free thiol of PAA-Cys was determined by Ellmann's reagent method and the ratio of 6MNA coupled was determined by glutathione reduction method. The study of permeation enhancement and stabilized function was conducted by using Franz diffusion cell method, with fluorescein isothiocyanate dextran (FD4) used as model drug. The influence of polymers on tight junctions of Caco-2 cell monolayer was detected with laser scanning confocal fluorescence microscope. The results indicated that both PAA-Cys and PAA-Cys-6MNA could promote the permeation of FD4 across excised rat intestine, and the permeation function of PAA-Cys-6MNA was not influence by the pH of the storage environment and the oxidation of air after the protecting group 6MNA was grafted. The distribution of tight junction protein of Caco-2 cell monolayer F-actin was influenced after incubation with PAA-Cys and PAA-Cys-6MNA. In conclusion, stabilized thiomers (PAA-Cys-6MNA) maintained the permeation function compared with the traditional thiomers (PAA-Cys) and its stability was improved. The mechanism of the permeation enhancement function of the polymers might be related to their influence on tight junction relating proteins of cells.

Pre-clinical evaluation of a new indirectly labeled ⁹⁹mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide with HYNIC as bifunctional chelator / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Technetium-99m or (99m)Tc is widely used for labeling peptide in nuclear medicine. Somatostatin and its analog can inhibit tumor cell growth after binding with its receptor. This research was to study the preclinical effect of a new (99m)Tc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide, indirect (99m)Tc labeling of depreotide using HYNIC as a bifunctional chelator.</p><p><b>METHODS</b>The cyclopeptide, cyclo-[(N-Me) Phe-Tyr-D-Trp-Lys-Val-Hcy], the linear peptide, and [ClCH(2)-CO×b-Dap-Lys- Cys-Lys×amide] were synthesized by Fmoc solid-phase synthesis. The cyclopeptide and the linear peptide were linked by liquid-phase synthesis. The product depreotide was isolated and purified by high performance liquid chromatography and was confirmed by mass spectrography. Depreotide was labeled with (99m)Tc through a direct labeling method, using HYNIC as a bifunctional chelator. Paper chromatography method was used to calculate the labeling rate, and through the comparative analysis selected the best mark conditions. The new (99m)Tc-HYNIC-depreotide was tested by high-performance liquid chromatography (HPLC). The internalization and externalization rates of the new (99m)Tc-HYNIC-depreotide were studied in A549 cells. Furthermore, biodistribution of the radiopeptide was studied in nude mice, bearing tumors from human lung carcinoma cells SPC-A1.</p><p><b>RESULTS</b>The molecular of synthesize depreotide was 1358, and the purity of it was 95.29%. The labeling efficiency of (99m)Tc-HYNIC-depreotide was highest at pH 6.0 and 15°C, about (70.95 ± 0.84)%. The labeling rate of the new (99m)Tc-HYNIC-depreotide rose to a peak of (20.75 ± 0.48)% at 60 minutes in A549 cells at 37°C and decreased slightly later, while it elevated gradually during the time course at 4°C and 25°C. The internalization rate of the new (99m)Tc-HYNIC-depreotide at 37°C increased gradually and reached the peak of 84.4% in 120 minutes, while the externalization rate of the new (99m)Tc-HYNIC-depreotide was always less than 20%. In mice bearing the experimental SPC-A1 tumor, the new (99m)Tc-HYNIC-depreotide demonstrated a high tumor uptake of (4.05 ± 0.04)% ID/g at 1.5 hpi and remained high ((2.51 ± 0.06)% ID/g) at 4 hpi. The tumor-to-lung activity concentration ratio (T/Lu) was very high for the new (99m)Tc-HYNIC-depreotide at all time points. So did the tumor-to-muscle activity (T/Mu) and tumor-to-blood activity concentration ratios (T/Bl).</p><p><b>CONCLUSION</b>The findings suggested that the new (99m)Tc-HYNIC-depreotide might be a promising candidate radiopharmaceutical for imaging somatostatin receptor positive lung cancer.</p>

Synthesis and evaluation of a new radiolabeled bombesin analogue for diagnosis of GRP receptor expressing tumors

Bombesin [BN], a 14-amino acid neuropeptide, shows high affinity for the human GRP [gastrin releasing peptide] receptors, which are overexpressed by a variety of cancers, including prostate, breast, pancreas, gastrointestinal, and small cell lung cancer. Aim was to prepare [6-hydrazinopyridine-3-carboxylic acid [HYNIC[0], D-Tyr[6], D-Trp[8]] - BN [6-14] NH[2] that could be easily labeled with[99m]Tc and evaluation of its potential as an imaging agent. Synthesis of the peptide amide was carried out onto Rink Amide MB HA [4-Methylbenzhydrylamine] resin. A bifunctional chelating agent [BFCA] was attached to the N terminal peptide in solid-phase. [99m]Tc labeling was performed by addition of sodium pertechnetate to solution that include [HYNIC[0], D-Tyr[6], D-Trp[8]] Bombesin [6-14] NH[2], tricine, ethylenediamine-N,N'-diaeetic acid [EDDA] and SnCl[2]. Radiochemical evaluation was carried out by reverse phase high-performance liquid chromatography [HPLC] and instant thin layer chromatography [ITLC]. In- vitro internalization was tested using human prostate cancer cells [PC-3] with blocked and non-blocked receptors. Biodistribution was determined in rats. [99m]Tc/tricine/EDDA-HYNIC[0], D-Tyr[6], D-Trp[8]] bombesin [6-14] NH[2] was obtained with radiochemical purities >98%. Results of in-vitro studies demonstrated a high stability in serum and suitable internalization. Biodistribution data showed a rapid blood clearance, with renal excretion and specific binding towards GRP receptor-positive tissues such as pancreas. In this study, labeling of this novel conjugate with [99m] Tc easily was performed using coligand. The prepared [99m]Tc-HYNIC-BN conjugate has promising characteristics for the diagnosis of malignant tumors

Effects of all-trans retinioic acid and tazarotene on MMP-1 and TIMP-1 expression in cultured human fibroblasts after heat shock / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the molecular mechanism of dermal damage in heat shock-induced skin aging by observing the expressions of metalloproteinase-1 (MMP-1) and tissue inhibitor of MMP-1 (TIMP-1) in retinoic acid-treated cultured human fibroblasts with heat shock.</p><p><b>METHODS</b>Cultured human fibroblasts were treated with tazarotene or all-trans-retinioic acid (at-RA) after heat shock for 30 min in 43 degrees celsius; water bath. Twenty-four hours later, MMP-1 and TIMP-1 contents in the supernatant of the cell culture medium were measured using enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Both tazarotene and at-RA dose-dependently reduced the expression of MMP-1 and increased the expression of TIMP-1 in cultured human fibroblasts exposed to heat shock, and tazarotene produced stronger effect than at-RA.</p><p><b>CONCLUSION</b>Retinoic acid can reduce the expression of MMP-1 and increase the expression of TIMP-1 in cultured human fibroblasts, suggesting its therapeutic potential for heat shock-induced skin aging.</p>

Comparison of clinical efficacy of topical tazarotene 0.1% cream with topical clobetasol propionate 0.05% cream in chronic plaque psoriasis: a double-blind, randomized, right-left comparison study.

BACKGROUND: No controlled data is available till date comparing topical tazarotene and clobetasol in Indian psoriatic patients. OBJECTIVE: The aim was to compare the clinical efficacy of 12 weeks of once-daily tazarotene 0.1% cream with that of once-daily clobetasol propionate 0.05% cream in the treatment of patients with chronic plaque psoriasis. METHODS: About 36 patients with bilaterally symmetrical lesions were enrolled in this double-blind randomized controlled study. A left-right randomized study was conducted. RESULTS: Clobetasol cream was better than tazarotene cream in reducing the erythema throughout the treatment period with statistically significant differences favoring clobetasol at weeks 2, 4, 6 and 8 ( P <0.05). Tazarotene was better in reducing the induration at weeks 2 ( P <0.05), 4, 10 and 12. Clobetasol cream was better in reducing the scaling throughout the treatment period with statistically significant differences favoring clobetasol over the entire treatment period. Treatment success rate was 100% with clobetasol and 88% with tazarotene at the end of week 12 with clobetasol achieving 100% success rate at the end of week 6. Treatment with tazarotene resulted in uniform reduction of plaque elevation and was not associated with the development of hot spots. CONCLUSION: Topical tazarotene 0.1% cream is less effective than topical clobetasol propionate 0.05% cream in the treatment of plaque psoriasis. It has more effect on induration than on erythema and scaling of psoriatic lesions.

Recent progress in the study of HIV-1 transcription factor NF-kappaB and its inhibitors / 药学学报

Human immunodeficiency virus type 1 (HIV-1) transcription is a crucial step in the viral replication cycle, which is considered to be a potential target for inhibition of HIV-1 replication. Among the factors involved in this step, the cellular protein nuclear factor NF-kappaB is the most powerful inducer of HIV-1 transcription. HIV-1 transcription is initiated by the binding of NF-kappaB to the enhancer region in the long terminal repeat (LTR) of HIV-1. Several compounds suppress HIV-1 transcription through the inhibition of NF-kappaB activation. The mechanisms of NF-kappaB in the transcription of HIV-1 and progress of the current inhibitors of NF-kappaB are reviewed.

Ichthyosis bullosa of Siemens: response to topical tazarotene.

In 1937, Siemens described a Dutch family with superficial blistering, flexural hyperkeratosis, and characteristic mauserung appearance. Since then, less than 20 kindreds with this condition have been described in the English dermatologic literature. A 14-year-old boy presented with history of recurrent blistering and peeling of skin since the age of 1 month, predominantly seen over limbs and trunk, often associated with secondary infection. His mother also had similar symptoms from childhood. On examination, the child had typical mauserung peeling of the skin and dirty gray hyperkeratosis in a rippled pattern over flexures. Skin biopsy from the boy showed intracorneal blistering with epidermolytic hyperkeratosis in the upper spinous layers. The typical history and clinical features along with characteristic histological findings confirmed our diagnosis of ichthyosis bullosa of Siemens. It must be differentiated from other conditions with epidermolytic hyperkeratosis and skin peeling, such as bullous ichthyosiform erythroderma of Brocq and peeling skin syndrome. Our patient responded well to 0.05% topical tazarotene gel over four weeks.

Inhibition of promyelocytic leukemia gene by tazarotene in hyperproliferative epidermis of psoriasis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism of tazarotene against active psoriasis vulgaris.</p><p><b>METHODS</b>A randomized, controlled trial was conducted in 43 patients with active psoriasis vulgaris, who were divided into tazarotene and control groups. Promyelocytic leukemia (PML) mRNA in active psoriatic lesions before and 14 days after tazarotene treatment was detected by in situ hybridization.</p><p><b>RESULTS</b>PML mRNA expression was detected not only in the basal layer (86.96%), but also in the suprabasal layers of the epidermis in the manner of focal expression (78.26%). After tazarotene treatment, virtually no PML mRNA expression could be detected in the psoriatic lesions (8.69% in the basal layer and 4.35% in the suprabasal layers). PML mRNA expression in the control group underwent no obvious changes during the observation.</p><p><b>CONCLUSIONS</b>Tazarotene may inhibit abnormal proliferation of keratinocytes through down-regulating PML gene expression in active psoriatic epidermis.</p>

Effects of dengue virus infection on peripheral blood cells of mice exposed to hexavalent chromium with drinking water.

BACKGROUND & OBJECTIVE: The occupational and non-occupational exposure to hexavalent chromium Cr (VI) is common. The effect of chromium compromises the immune response of the host. Dengue virus (DV) infection causes various changes in the peripheral blood cells. It is, therefore, possible that the chromium toxicity may affect the disease process during DV infection. The present study aims to study the effects of dengue virus infection on peripheral blood cells of mice fed Cr (VI) with drinking water. METHODS: One group of mice was given ad libitum drinking water containing Cr (VI) and the other group used as the normal control mice was given plain water to drink. At the 3, 6 and 9 wk of Cr (VI) drinking, a set of mice from each group was inoculated intracerebrally (ic) with DV and studied at the 4th and 8th day post inoculation. RESULTS: It was observed that Cr (VI) drinking led to reduction in lymphocytes, haemoglobin and the haematocrit values while the granulocyte, monocyte and platelet counts were increased. On the other hand, most of the parameters were decreased following inoculation of normal mice with DV. In Cr (VI)-fed mice the effects of DV infection were minimal. The most significant finding of these experiments was that the reduction in platelet counts following inoculation with DV was markedly less in Cr (VI)-fed mice than that in DV-inoculated normal control mice. INTERPRETATION & CONCLUSION: Cr(VI) compounds have been declared as a potent occupational carcinogen. On the contrary, Cr(III) salts such as chromium polynicotinate, chromium chloride and chromium picolinate, are used as micronutrients and nutritional supplements, and have been shown to exhibit health benefits in animals and humans. Whether therapeutic doses of chromium (III) compounds may be able to prevent the DV-induced fall in platelet counts, needs to be investigated.

Influence of megadoses of nicotinic acid [Niacin] on lipids turnover and atherosclerosis in mice

The effect of megadoses of nicotinic acid [niacin, vitamin B3] on lipids turnover and atherosclerosis was evaluated in male adult mice fed diets containing different levels of nicotinic acid Six groups each of eight mice, mean weight varied between 17.1 to 19.6 g were fed on either basal control diet containing 30 mg nicotinic acid/kg diet or experimental diets containing 300,1500,3000,4500 and 6000 mg nicotinic acid/kg diet. Production performance and serum biochemical parameters were evaluated. Relative weights of liver and brain were significantly different while relative weights of heart showed no significant variations between different groups. The values of serum total lipids, cholesterol, LDL-cholesterol and glucose were significantly decreased in mice fed on diets containing 300mg [G2], 1500mg [G3] and 3000mg [G4] of nicotinic acid/kg diet and increased in groups containing 4500mg [G5] and 6000mg [G6] when compared with control group. Whereas, serum triacylglycerols and VLDL-cholesterol concentrations were significantly decreased in all groups except G6 as compared with control group. Significant increase in serum HDL-cholesterol values and HDL-c/LDL-c ratio were observed in G2,G3 and G4 and decreased in G5 and G6.Serum levels of creatine kinase activity [CK] enzyme were not affected by different treatments. While levels of lactate dehydrogenase [LDH] enzyme were significantly increased in all groups as compared with the control group, It was concluded that high doses of niacin rang between 300 to 3000 mg/kg diet had hypolipidemic action and reduced the hazards of atherosclerosis in mice

effects of Rheum Ribes on serum lipids in hyperlipidemic rabbits

Coronary heart disease [CHD] is the major cause of morbidity and mortality both in industrial and developing countries. Hypercholesterolemia is the main primary contributory factor for CHD, and also there are reports that triglycerid rich lipoproleins directly or indirectly are atherogenic. In all subjects with one or more CHD risk factors in whom risk reduction is recommended non- drug therapy is a valid treatment regimen. The present study investigates the effects of ethanolic and aqueous extracts of rheum ribes [RR] of the family polygonacea on lipid concentrations in hypothyroid rabbits. To induce hypothyroidism and hyperlipidemia, 0.05% [w/w] methimazol powder was given in drinking water to rabbits with 2 +/- 0.3 kg weight, throughout the experiment. Hypothyroid animals were divided into 5 groups and treated with different regimens for 18 days as following: group A was received daily 10-15 ml of distilled water [D.W] orally; group B as positive control was received 570 mg of nicotinic acid powder in D.W orally/ day; groups C and D were received daily 4 g/kg B.W orally of aqueous and ethanolic extracts respectively and finally group E was received 6 g/kg.B.W ethanolic extract in D.W/day [this group was not concidered in results]. Blood samples were taken by the end of day 10 and 18 and serum cholesterol and triglycerid were determined by enzymatic routin laboratory methods. Aqueous extract of RR vs D.W decreased serum cholesterol by the end of day 10 and 18 by 56.34% and 84.87% [P<0.01] respectively. Triglycerid concentration was decreased by aqueous extract by day 10 and 18 by 11.29% [NS] and 66.8% [P<0.05] respectively. Ethanolic extract when compared with D.W decreased cholesterol level by 40.56% [P<0.05] and 72.27% [P<0.01] by day 10 and 18 respectively. This extract also decreased triglycerid at day 10 by 34.39% [NS] and at day 18 by 79.14% [P<0.01]. Nicotinic acid vs. D.W decreased serum cholesterol by day 10 and 18 by 54.7% [P<0.001] and 62.8% [P<0.05] respectively. Triglycerid reduction by nicotinic acid was 62.11% and 62.68% [P<0.05] by day 10 and 18 respectively. These results demonstrate that both aqueous and ethanolic extracts of RR can decrease plasma lipids in hyperlipidemic rabbits and the reductions are at the rank of or greater than that of nicotinic acid. Therefore, it may suggest that rheum ribes is potentially hypolipidemic and might be used in such status for treatment of hypercholesterolemia and hypertriglyceridemia to reduce CHD risk factors

Chromium uptake by Saccharomyces cerevisiae and isolation of glucose tolerance factor from yeast biomass.

Fermentations with yeast Saccharomyces cerevisiae in semiaerobic and in static conditions with the addition of chromic chloride into the used molasses medium were analysed. It was proved that the addition of optimal amounts of CrCl3 into the basal medium enhanced the kinetics of alcohol fermentations. The addition of 200 mg/l CrCl3 into the medium stimulated both the yeast growth and the ethanol production in all experimental conditions. On the other hand, the results showed that Cr3+ ions were incorporated into yeast cells during fermentation. Under these conditions the accumulation of Cr3+ ions was performed by yeast cells during the exponential growth phase, and with enriched amounts of 30-45 microg/g(d.m) of cells. Yeast biomass enriched with chromium ions was extracted with 0.1 mol/l NH4OH assuming that the extracts had the glucose tolerance factor (GTF). Then the extracts were passed through a gel-filtration column in order to isolate and purify the GTF. The presence of GTF in the purified fractions was determined by measuring the absorbance at 260 nm. It is evident from the obtained results that the added purified fractions enhanced the rates of CO2 production as well as the glucose utilization during alcoholic fermentation. As expected, the enhancement of both rates depended on the amounts of extracts added to the fermentation substrate. Thus, it is evident that purified extracts contained the GTF compound, and that Cr3+ ions were bonded to the protein molecule.

Synthesis of new pyrazoline derivatives II reaction of Erythro-2,3-dibromoketones with nicotinic and isonicotinic acid hydrazides

The reaction of a series of erythro-2, 3-dibromo-1, 3-diaryl-1-propanones 1 a-g with 2 molar equivalents of nicotinic and isonicotinic acid hydrazides afforded 4-bromo-1-nicotinoyl and 1-isonicotinoyl-3, 5-diaryl-2-pyrazolines 2 a-g and 3 a-g, respectively. The structure of the products was confirmed by chemical and spectral tools. The mechanism of the reaction was discussed

Heterocyclic synthesis with nitriles: synthesis of some novel furo [2,3-b] nicotinic acid derivatives of anticipated biological activity

2-Amino-5-phenylfuran-3-carbonitrile 2 reacts with malonic acid derivatives 3a-d and 6 to afford the furo [2, 3-b] pyridine derivatives 5a-c. Compounds 2 reacts with urea and thiourea to afford the pyrrole derivative 10 which was also obtained from 2 and ammonium acetate. The reaction of 2 with the arylidene derivatives 11a-f yield the furo [2, 3-b] nicotinonitrile derivatives 13a, c, e; which were hydrolyzed to the nicotinic acid derivatives 14a, c, e, respectively. Compound 2 reacts also with the acrylic acid derivatively 15a-c to afford the furo [2, 3-b] nicotinic acid derivatives 17a-c, which were hydrolyzed to give the furo [2, 3-b] nicotinic acid 18. Compounds 5b, c undergo S-or N-alkylation on reaction with phenacyl bromide 19a and ethyl bromoacetate 19b to yield compounds 20a-d, respectively. Compound 5b reacts with hydrazine hydrate to afford the hydrazino derivative 22 which could be cyclized into the furopyridopyrazole derivative 23. Compound 5b reacts also with I2/Kl in DMF to afford the disulphide 24

Mejoría de la insulinosensibilidad asociada al uso prolongado de acipimox en un obeso mórbido / Improvement of insulin sensitivity associated to the large use of acipimox in a morbidly obese patient

Insulin sensitivity was estimated in a morbidity obese, insulin-resistant, glucose-intolerant patient before and after 4 weeks of treatment with acipimox (250 mg t.i.d), an orally-administred, long-acting antilypolitic drug. The ensuing fall in circulating levels of fasting free fatty acids was associated with a clear amelioration of insulin resistance, as assessed by a minimal model analysis of a frequently sampled intravenous glucose tolerance test as well as by an oral glucose tolerance test. Similarly, this treatment brought about a reappearence of GH response to oral stimulation with clonidine. The evidence showing acipimox-induced amelioration of insulin resistance in this patient without diet, exercise or weight loss should encourage exploring the potential utility of this drug in this type of patient