Skin permeation studies of chromium species - Evaluation of a reconstructed human epidermis model.

A reconstructed human epidermis (RHE) model, the EpiDerm, was investigated and compared to human skin ex vivo regarding tissue penetration and distribution of two chromium species, relevant in both occupational and general exposure in the population. Imaging mass spectrometry was used in analysis of the sectioned tissue. The RHE model gave similar results compared to human skin ex vivo for skin penetration of CrVI. However, the penetration of CrIII into the tissue of the RHE model compared to human skin ex vivo differed markedly, such that in the RHE model the CrIII species accumulated in the tissue layer corresponding to stratum corneum whereas in human skin ex vivo, the CrIII species penetrated evenly through the skin tissue. Further, skin lipids such as cholesterol were less abundant in the RHE model compared to the human skin tissue. Results presented here indicate that the RHE models do not possess the same fundamental properties as human skin tissue. As the RHE models appear to be able to give false negative results, experiments using RHE models for the study of skin penetration should be evaluated with caution.

Anhedonia symptoms: The assessment of brain functional mechanism following music stimuli using functional magnetic resonance imaging.

PURPOSE: This study aimed to investigate the effect of music stimulation on the brain functional mechanism of depressed patients with anhedonia symptoms using functional magnetic resonance imaging (fMRI). METHODS: Participants in this study included 20 healthy subjects as the control group, 25 subjects with depression and no anhedonia as the intervention group A, and 24 subjects with depression and anhedonia as the intervention group B. The safely emotional stimulation was done by Iranian music. To investigate the effect of music therapy on the brain, a task including 50 tracks of 12 s Iranian music (traditional and pop) was used. Finally, the data were analyzed using SPM Toolbox in MATLAB software. RESULTS: The results showed that brain patterns in depressed patients with and without anhedonia could be distinguished based on positive and negative musical stimuli (p < 0.05). Important fMRI biomarker such as effective connectivity strength related to the fronto-limbic network, including the supragenual ACC, subgenual ACC, AMYG, and FFG were evaluated in depressed patients with anhedonia. CONCLUSION: This was the first study to investigate the neural circuits involved in music-related emotional processing in patients with anhedonia symptoms. These findings could help advance neurological understandings of anhedonia and suggest new treatments.

The barriers against initiating insulin therapy among patients with diabetes living in Yazd, Iran.

INTRODUCTION: The decision to start insulin therapy is often difficult. Determining the barriers against insulin therapy initiation can facilitate care and treatment strategies. The aim of this study was to evaluate the barriers against initiating insulin therapy among patients with diabetes living in Yazd, Iran. METHODS: This descriptive study was conducted on 214 patients referred to the Diabetes Center of Yazd University of Medical Sciences in 2015. Participants were randomly selected, and then they completed the insulin noncompliance questionnaire (20 questions). The percentage of adherence and the factors contributing to nonadherence to insulin therapy were analyzed using descriptive statistics, the Kruskal-Wallis test, and the Mann-Whitney test. RESULTS: The most prevalent reason for insulin therapy refusal was expecting a new method of diabetes treatment (54.7%), followed by requiring someone else to administer the injection (19.2%), fear of needles, cost, traveling (18.7%), and stress/emotional problems (18.2%). Lack of trust in the physician was the least restrictive reason for nonadherence to insulin therapy. CONCLUSION: The most common reason given for insulin therapy refusal was the lack of adequate education. Therefore, specialized educational interventions can help minimize barriers and improve patients' outcomes.

Nontoxic combretafuranone analogues with high in vitro antibacterial activity.

A library of thirty two 3,4-diphenylfuranones related to both combretastatin A-4 and antifungal 5-(acyloxymethyl)-3-(halophenyl)-2,5-dihydrofuran-2-ones was prepared. Cytotoxic effects on a panel of cancer and normal cell lines and antiinfective activity were evaluated, and the data were complemented with tests for the activation of caspase 3 and 7. High cytotoxicity was observed in some of the halogenated analogues, eg. 3-(3,4-dichlorophenyl)-4-(4-methylphenyl)-2,5-dihydrofuran-2-one with IC50 0.12-0.23 µM, but the compounds were also highly toxic against non-malignant control cells. More importantly, notable antibacterial activity indicating G+ selectivity has been found in the 3,4-diarylfuranone class of compounds for the first time. Hydroxymethylation of furanone C5 knocked out cytotoxic effects (up to 40 µM) while maintaining significant activity against Staphylococcus strains in some derivatives. MIC95 of the most promising compound, 3-(4-bromophenyl)-5,5-bis(hydroxymethyl)-4-(4-methylphenyl)-2,5-dihydrofuran-2-one against S. aureus strain ATCC 6538 was 0.98 µM (0.38 µg/mL) and 3.9 µM (1.52 µg/mL) after 24 and 48 h, respectively.

Age at adiposity rebound and body mass index trajectory from early childhood to adolescence; differences by breastfeeding and maternal immigration background.

OBJECTIVE: This paper aims to assess association between breastfeeding and maternal immigration background and body mass index development trajectories from age 2 to 16 years. METHODS: A cohort of children born in Stockholm during 1994 to 1996 was followed from age 2 to 16 years with repeated measurement of height and weight at eight time points (n = 2278). Children were categorized into groups by breastfeeding status during the first 6 months of life and maternal immigration background. Body mass index (BMI) trajectories and age at adiposity rebound were estimated using mixed-effects linear models. RESULTS: Body mass index trajectories were different by breastfeeding and maternal immigration status (P-value < 0.0001). Compared with exclusively breastfed counterparts, never/short breastfed children of Swedish mothers had a higher BMI trajectory, whereas never/short breastfed children of immigrant mothers followed a lower BMI trajectory. Ages at adiposity rebound were earlier for higher BMI trajectories regardless of maternal immigration background. CONCLUSION: Differences in BMI trajectories between offspring of immigrant and of Swedish mothers suggest a lack of beneficial association between breastfeeding and long-term BMI development among children of immigrant mothers. Given the relation between long-term BMI development and risk of overweight/obesity, these differences challenge the notion that exclusive breastfeeding is always beneficial for children's BMI development and subsequent risk of overweight/obesity.

[Binge eating disorder: Links with personality and emotionality]. / Hyperphagie boulimique : liens avec la personnalité et l'émotionnalité.

OBJECTIVES: Our two objectives were: (1) to investigate the relationship between binge eating disorder, dimensions of personality (according to the Big Five model of Costa and McCrae) and those of emotionality in the "tripartite" model of emotions of Watson and Clark; (2) to evaluate the correspondence between the Binge Eating Scale (BES) and the Eating Disorder Inventory (EDI-2) scores. METHOD: Four self-administered questionnaires were completed on a shared doc website: the EDI-2, the BES, the BFI-Fr (Big Five Inventory-French version) and the EPN-31 (Positive and Negative Emotionality Scale). The analyses were conducted in a sample of 101 participants (36 men and 65 women), aged 20-59 years (mean age=35.28±9.76) from the general population. RESULTS: We found that 11% of the participants had moderate to severe binge eating disorder. Among them, nearly 4% were overweight and 4% were obese. The correlations analyses indicated that binge eating disorder was associated with two dimensions of personality, the neuroticism (P=0.001) and the consciousness (P=0.010), and with the emotions of joy (P=0.008), tenderness (P=0.036), fear (P=0.011), shame (P<0.001) and sadness (P=0.009). From a comparative perspective, participants with binge eating disorder get higher scores on EDI-2 subscales: search for thinness (P=0.001), bulimia (P<0.001), dissatisfaction with the body (P<0.001) and interceptive awareness (P<0.001). CONCLUSION: These results suggest that binge eating disorder is associated with negative affectivity both as a personality dimension and as an emotional feeling. The patterns of associations, observed with the EDI scale, seem to confirm the good convergent validity of the Binge Eating Scale. Thus, like other eating disorders, emotional functioning should be a prime target for prevention and treatment.

Construction of recombinant fusion protein of influenza, a virus neuraminidase and heat shock protein 70 gene: expression in baculovirus and bioactivity.

Background: Two structural antigens, hemagglutinin and neuraminidase, are a major component for the development of influenza vaccine candidates. Recombinant vaccines are produced by a simple method, although expected to induce an immune response to a specific antigen, remaining to be further improved for their high effectiveness. In general, heat shock protein 70 of Mycobacterium tuberculosis, as a potent adjuvant, is commonly used to improve antigen-presenting cell (APC) function and thereby elicit T lymphocytes. Objective: The purpose of this research was to evaluate the efficacy of the NA antigen fused to the C-terminus of HSP70, as a vaccine candidate, in the induction of potent, protective immune answers specific to the vaccine antigen. Material and Method: The NA gene was strengthened via a polymerase chain reaction and then cloned to a eukaryotic expressing vector pFastBac HTA. Subsequently, a recombinant NA protein fusing to HSP70 was expressed in Baculovirus. The purity of the expressed NA-HSP70 fusion protein was investigated on the SDS-PAGE electrophoresis. Western blot was carried out to investigate the expression of NA-HSP70. Additionally, an immunofluorescence assay was used qualitatively to assess the biological and antigenicity activity profiles of the protein of recombinant, NA-HSP70, on the infected Sf9 cell surface by using immunized rabbit antiserum. Result and conclusion: Interestingly, the findings in the present studies suggested that HSP proteins have the ability to both stimulate and increase potent humoral- and cell-mediated immune responses, and play an adjuvant role when combined with other proteins. Therefore, a recombinant protein fusing to HSP raised hope regarding the development of an HSP-based vaccine.

Red/blue spectral shifts of laser-induced fluorescence emission due to different nanoparticle suspensions in various dye solutions.

Red/blue shifts of laser-induced fluorescence (LIF) are investigated using several guest dielectric nanoscatterers, such as TiO2, ZnO, Al2O3, and SiO2, in the host Rd6G, RdB, Coumarin 4, and Coumarin 7 ethanolic solutions. A couple of inflection points are identified varying nanoparticle (NP) density into dye solutions based on LIF spectroscopy. The inflection of the spectral shift exhibits that the suspension of NPs in dye solutions significantly involves a couple of competitive chemical and optical mechanisms during photon traveling in scattering media regarding ballistic and diffusive transport. It is shown that the low, medium, and high NP additives in fluorescent suspension induce blue, red, and blue spectral shifts, respectively.

Nanomaterial containing wall paints can increase radon concentration in houses located in radon prone areas.

BACKGROUND: Nowadays, extensive technological advancements have made it possible to use nanopaints which show exciting properties. In IR Iran excessive radon levels (up to 3700 Bq m-3) have been reported in homes located in radon prone areas. Over the past decades, concerns have been raised about the risk posed by residential radon exposure. OBJECTIVE: This study aims at investigating the effect of using nanomaterial containing wall paints on radon concentration in homes. METHODS: Two wooden model houses were used in this study. Soil samples from Ramsar high background radiation areas were used for simulating the situation of a typical house in radon-prone areas. Conventional water-soluble wall paint was used for painting the walls of the 1st house model; while the 2nd house model was painted with the same wall paint with montmorillonitenanoclay. RESULTS: Three days after sealing the house models, radon level was measured by using a portable radon survey meter. The mean radon level inside the 1st house model (conventional paint) was 515.3 ± 17.8 Bq/m(3) while the mean radon concentration in the 2nd house model (nano-painted house model) was 570.8 ± 18.5 Bq/m(3). The difference between these means was statistically significant (P<0.001). CONCLUSION: To the best of our knowledge, this study is the first investigation on the effect of nano-material containing wall paints on indoor radon concentrations.  It can be concluded that nano-material-containing wall paints should not be used in houses with wooden walls located in radon prone areas. Although the mechanism of this effect is not clearly known, decreased porosity in nano-paints might be a key factor in increasing the radon concentration in homes.

Safety and Efficacy of MLC601 in Iranian Patients after Stroke: A Double-Blind, Placebo-Controlled Clinical Trial.

Objective. To investigate the safety and efficacy of MLC601 (NeuroAid) as a traditional Chinese medicine on motor recovery after ischemic stroke. Methods. This study was a double-blind, placebo-controlled clinical trial on 150 patients with a recent (less than 3 month) ischemic stroke. All patients were given either MLC601 (100 patients) or placebo (50 patients), 4 capsules 3 times a day, as an add-on to standard stroke treatment for 3 months. Results. Sex, age, elapsed time from stroke onset, and risk factors in the treatment group were not significantly different from placebo group at baseline (P > .05). Repeated measures analysis showed that Fugl-Meyer assessment was significantly higher in the treatment group during 12 weeks after stroke (P < .001). Good tolerability to treatment was shown, and adverse events were mild and transient. Conclusion. MLC601 showed better motor recovery than placebo and was safe on top of standard ischemic stroke medications especially in the severe and moderate cases.

Occupational dose assessment and National Dose Registry System in Iran.

This report presents status of external and internal dose assessment of workers and introducing the structure of National Dose Registry System of Iran (NDRSI). As well as types of individual dosemeters in use, techniques for internal dose assessment are presented. Results obtained from the International Atomic Energy Agency intercomparison programme on measurement of personal dose equivalent H(p) (10) and consistency of the measured doses with the delivered doses are shown. Also, implementation of dosimetry standards, establishment of quality management system, authorisation and approval procedure of dosimetry service providers are discussed.

The Effect of Vitamin D3 Alone and Mixed With IFN-γ on Tachyzoites of Toxoplasma gondii (RH Strain) Proliferation and Nitric Oxide (NO) Production in Infected Macrophages of BALB/C Mice.

INTRODUCTION: Toxoplasma gondii is an obligatory interacelullar parasite that infects nucleated cells in its intermediate hosts. The aim of the present study was to determine the effect of vitamin D3 on the multiplication of T. gondii in peritoneal macrophage of Balb/c mice and nitric oxide production by macrophages. METHODS: According to usage of vitamin D3 (one dose or seven doses) and INFγ in vitro and in vivo, this study was divided into four experiments. In all experiments, the macrophages were collected from peritoneum and cultured in RPMI-1640. Then the supernatants were collected after 24 h and their nitric oxide was measure. After 96 h, the macrophages were collected and stained and the number of tachyzoites was measured. RESULTS: The first experiment (the mice were infected with tachyzoites and after 2 h, got one dose vitamin D3 intraperitonealy) showed the best results. The mean of tachyzoites per macrophages was 2.37, and mean±SD of nitric oxide was 187.8±9. DISCUSSION: High-level production of nitric oxide may be related to the only one injection of vitamin D3. The injection in long time might suppress the immune system.

Reactive oxygen and nitrogen species in normal physiological processes.

Abstract Reactive oxygen species (ROS) and reactive nitrogen species have generally been considered as being highly reactive and cytotoxic molecules. Besides their noxious effects, ROS participate in physiological processes in a carefully regulated manner. By way of example, microbicidal ROS are produced in professional phagocytes, ROS function as short-lived messengers having a role in signal transduction and, among other processes, participate in the synthesis of the iodothyronine hormones, reproduction, apoptosis and necrosis. Because of their ability to mediate a crosstalk between key molecules, their role might be dual (at least in some cases). The levels of ROS increase from a certain age, being associated with various diseases typical of senescence. The aim of this review is to summarize the recent findings on the physiological role of ROS. Other issues addressed are an increase in ROS levels during ageing, and the possibility of the physiological nature of this process.

Malignant melanoma of the oral cavity: a review of literature.

UNLABELLED: Oral malignant melanoma is a rare aggressive neoplasm of the middle age. This malignancy commonly affects male subjects and is more frequently seen at the level of the hard palate and gingiva. At present, the clinicopathological classification of oral melanoma is not yet clearly outlined; consequently, the skin form is often taken as a reference. In many cases (up to 30%), the diagnosis of melanoma is made on lesions, which have evolved from the pre-existing pigmented lesions. The poor prognosis of oral melanomas requires that pigmented lesions of undetermined origin be routinely biopsied. The surgical approach, combined with the chemotherapeutic one, is the first choice treatment. The purpose of this study is to review literature that has been published about malignant melanoma of the oral cavity. MATERIALS AND METHODS: Thirty-eight published articles and 8 textbooks related to oral malignant melanoma and been published in the last two decades are reviewed. CONCLUSION: The review of literature in the field of malignant melanoma of the oral cavity show that this malignancy might be different from cutaneous malignant melanomas, and new criteria for diagnosis and therapy should be considered for this disease. Physicians and dentists who treat problems of the oral cavity should be aware of the need for early diagnosis of oral melanomas and performing biopsies of doubtful pigmented lesions.

Spontaneous osteonecrosis of the knee: biochemical markers of bone turnover and pathohistology.

OBJECTIVE: The aim of this study was to evaluate bone metabolism in patients with spontaneous osteonecrosis (ON) of the medial femoral condyle. METHOD: In 22 consecutive patients, undergoing total knee arthroplasty, biochemical markers of bone metabolism were measured in aspirates from cancellous bone and in samples obtained simultaneously from peripheral blood. Specimens of the medial femoral condyle were available for histologic examination and the lesion size, assessed on radiographs, was compared with the results from bone turnover measurements. Twenty patients with osteoarthritis (OA) of the knee served as a control. Bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), and C-terminal cross-linking telopeptide (ICTP) were studied. RESULTS: Mean serum levels of analytes were not different in patients with ON and OA. The serum concentrations averaged 16.2 vs 13.3 ng/mL (OC), 10.2 vs 12.1 ng/mL (bone ALP), 4.6 vs 4.1 ng/mL (ICTP), and 33.2 vs 40.4 ng/mL (PINP) in patients with ON and OA, respectively. In samples obtained from cancellous bone, mean concentrations of all markers were elevated significantly when compared to serum levels. The mean marker concentrations in samples obtained from cancellous bone were 33.8 vs 43.3 ng/mL (OC), 34.6 vs 37.3 ng/mL (bone ALP), 64.8 vs 36.1 ng/mL (ICTP, P=0.02), and 208.0 vs 176.2 ng/mL (PINP) in patients with ON and OA, respectively. The lesion size was at mean 440.5+/-275.8mm(2) in knees with ON and did not correlate with either serum or bone concentrations of all markers tested (P>0.1). CONCLUSION: The marked elevation of markers in samples obtained from cancellous bone pointed at increased turnover in both diseases when compared to healthy individuals. In line with histologic findings of necrosis of subchondral bone, focal degradation of collagen type I was more pronounced in knees with ON. Mean serum concentrations of all markers, however, were not different from healthy individuals and thus did not provide any useful clue in the diagnosis spontaneous ON.

Disposition study of a new potential antineoplastic agent dimefluron in rats using high-performance liquid chromatography with ultraviolet and mass spectrometric detection.

The disposition of a new potential antineoplastic drug dimefluron after an oral administration to rats was investigated. Dimefluron, 3,9-dimethoxy-5-(2-dimethylaminoethoxy)-7H-benzo[c]fluoren-7-one hydrochloride, was administered in a single oral dose (250 mg kg(-1) of body weight) in the form of an aqueous solution via a gastric probe. Dimefluron metabolites were being searched for in rat faeces. Synthetic standards of the expected phase I metabolites (the products of O- and N-desmethylation, N-oxidation and carbonyl reduction of dimefluron) were prepared and used together with dimefluron and internal standard in the development of two HPLC bioanalytical methods based on different separation principles. The first separation of dimefluron and the phase I metabolites was tested on a 250 mm x 4 mm chromatographic column with LiChrospher 60 RP-selectB 5 microm (Merck) using an isocratic mobile phase containing 0.01 M nonylamine buffer (pH 7.4) and acetonitrile in the 1:2 ratio (v/v). The second separation was performed on a 250 mm x 4 mm chromatographic column Discovery HS F5, 5 microm (Supelco) using a linear gradient mode with the mobile phase containing acetonitrile and phosphate buffer (0.05 M KH2PO4, pH 3). The flow rate was 1 ml min(-1) in both cases. UV detection was performed in the dual wavelength mode, with 317 nm having been used for dimefluron and all 7H-benzo[c]fluoren-7-one metabolites, 367 nm for 7H-benzo[c]fluoren-7-ol metabolites. A higher homologue of dimefluron served as an internal standard. The identity of the dimefluron metabolites in biological samples was confirmed using HPLC-MS experiments. The elimination study showed that the concentration maximum for dimefluron and its metabolites in rat faeces was reached 48 h after the administration of the parent drug. O-Desmethylated derivatives of dimefluron prevailed among the phase I metabolites.

A new flavonoid: tinctosid from Anthemis tinctoria L.

Patuletin 7-O-beta-D-(6"-caffeoylglucoside) was isolated from the methanolic extract of the flowers of Anthemis tinctoria L. (Asteraceae). The isolated compound was identified by spectroscopic means and by comparison with authentic samples after enzymatic hydrolysis. A new flavonoid glycoside, tinctosid, from Anthemis tinctoria L. was isolated from a plant source for the first time.

The effect of sildenafil on gastric emptying in patients with end-stage renal failure and symptoms of gastroparesis.

BACKGROUND: Delayed gastric emptying is a common disorder among patients with end-stage renal failure (ESRF). Pyloric relaxation, a major determinant of gastric emptying, is a nitric oxide (NO)-mediated process. NO-induced smooth muscle relaxation is mediated through its second messenger cyclic guanosine monophosphate, which is broken by tissue phosphodiesterases (PDEs). Thus the inhibition of cyclic guanosine monophosphate breakdown by PDE inhibitors can potentiate NO-mediated responses and facilitate pyloric relaxation. In an animal model of diabetes mellitus, treatment with sildenafil (a PDE-5 inhibitor) restored NO-mediated pyloric relaxation and improved gastric emptying. The aim of our study was to examine the hypothesis that sildenafil may improve gastric emptying in patients with ESRF and symptoms of gastric paresis. METHODS: We studied 12 patients with ESRF (6 men; age range, 54-80 years; 5 with diabetic nephropathy; 4 +/- 1 years receiving long-term renal replacement therapy) after either placebo or a 25-mg tablet of sildenafil (Viagra; Pfizer Inc). Gastric emptying of a solid meal (one medium-sized fried egg mixed with 37 MBq [1 mCi] technetium Tc 99m phytate plus 1 slice of bread and 150 mL of water at the end of the meal) was assessed 1 hour after dosing by use of a single-headed camera. Images were acquired every 30 seconds for 90 minutes immediately after patients ate. RESULTS: The gastric emptying rate was decreased at baseline (after placebo), to 33% +/- 6% (normal, > or =50%). Treatment with sildenafil had no effect on gastric emptying rates after 90 minutes (from 33% +/- 6% after placebo to 30% +/- 6% after sildenafil, P =.9). CONCLUSIONS: Sildenafil did not improve gastric emptying in patients with ESRF and gastric paresis. Sildenafil may have opposing effects on gastric peristalsis (causing gastric relaxation) compared with its effects on pyloric relaxation. Studies combining sildenafil with prokinetic drugs are of interest.