Combined X-ray radiotherapy and laser photothermal therapy of melanoma cancer cells using dual-sensitization of platinum nanoparticles.

Metal nanostructures are promising agents sensitizing by laser light and X-ray in photothermal therapy (PTT) and radiotherapy (RT) of cancer that improve treatment strategies of cancer. Nanoscale platinum materials are favorable in nanomedicine applications. In this study, platinum nanoparticles (PtNPs) were synthesized and applied for cancer therapy upon 808-nm laser light and X-ray radiation, or their combination. Two power densities of laser (1.0 and 1.5 W cm-2) and three X-ray doses (2, 4 and 6 Gy) were selected for irradiation of B16/F10 cell line at 24 and 72 h-post treatment. The synthesized PtNPs had a spherical shape with a diameter of 12.2 ± 0.7 nm, and were cytocompatible up to 250 µg mL-1. A photothermal conversion activity in a concentration-dependent manner at 72 h-post treatment was observed. Also, PtNPs represented cytotoxicity upon X-ray radiation doses of 2, 4, and 6 Gy after 24 h, while, 72-h time passing led to deeper outcomes. Dual radiation of laser light and X-ray into PtNPs considerably improved the treatment via reactive oxygen species (ROS) production. PtNPs can act as a novel dual absorber of laser light and X-ray, a common sensitizer, for treatment of cancer. The results of this study can be considered after further clinical investigations for treatment of tumor models.

Enhanced melanoma cell-killing by combined phototherapy/radiotherapy using a mesoporous platinum nanostructure.

BACKGROUND: Metal nanomaterials have a significant potential as photosensitizer and radiosensitizer. The purpose of this study was to evaluate the cytotoxicity of a platinum mesoporous nanostructure (Pt MN) toward a melanoma cancer cell line upon combined laser radiation (808 nm, 1 and 1.5 W cm-2) and X-ray irradiation (6 MV, 2, 4, and 6 Gy). METHODS: Pt MN was synthesized by a simple procedure and characterized by field emission scanning and transmission electron microscopy. A mouse malignant melanoma cell line C540 (B16/F10) was treated with Pt MN, laser light and/or X-ray. RESULTS: Pt MN had a mesoporous structure with a sponge-resemble shape comprised of ensembles of very small adhered particles of <11 nm and about 5-nm pores. While Pt MN represented a low toxicity toward and considerable uptake into the cell line in a concentration range of 10-100 µg mL-1, laser light radiation alone was also not toxic, and X-ray irradiation alone induced a limited toxicity, Pt MN was toxic against the cells in a dose dependent manner upon laser light radiation, X-ray irradiation, or their combined exposure. The killing efficacy of Pt MN upon X-ray irradiation was more obvious at 72 h post-treatment. The combined exposure (laser radiation followed by X-ray irradiation) led to a deep cell killing and a very low melanoma cell viability (∼1%). Significant melanoma cancer cell killing of Pt MN was due to reactive oxygen species (ROS) production upon combined exposure of laser and X-ray, while cell killing upon laser light radiation was due to heat generation. CONCLUSION: Pt MN was introduced as a supreme laser/X-ray sensitizer for treatment of cancer with a high ability to produce ROS and a potent impact on decreasing cell viability.

Prevalence of endocrine disorders and their associated factors in transfusion-dependent thalassemia patients: a historical cohort study in Southern Iran.

PURPOSE: Transfusion-dependent beta-thalassemia (TDT) patients suffer from various endocrinopathies. The main contributing factor associated with these complications is iron overload, secondary to frequent blood transfusions. To improve patients' quality of life, we evaluated the prevalence of endocrine disorders while considering the associated factors for further assessment. METHODS: Seven hundred thirteen transfusion-dependent thalassemia patients with age range 10-62 years were enrolled in this study. Serum calcium, phosphorous, fast blood sugar, ferritin, 25-OH vitamin D, free thyroxin, thyroid-stimulating hormone and parathyroid hormone were assessed. Bone mineral density was measured by dual-energy X-ray absorptiometry. RESULTS: In total, 86.8% of the TDT patients suffered from at least one endocrinopathy. The prevalence of endocrinopathies in descending order of frequency was low bone mass (72.6%), hypogonadism (44.5%), diabetes mellitus (15.9%), hypoparathyroidism (13.2%), and hypothyroidism (10.7%). Age, body mass index and splenectomy were significantly associated with most of the endocrine disorders. CONCLUSION: Endocrine complications are frequently observed in TDT patients. Splenectomy is a major risk factor and should be generally avoided unless it is highly indicated. Periodic surveillance of endocrine function and proper management of iron overload are advised.

Evaluation of a self-nanoemulsifying docetaxel delivery system.

A self-nanoemulsifying drug delivery system (SNEDDS) was developed as a novel route to enhance the efficacy of docetaxel lipophilic drug. SNEDDS comprised ethyl oleate, Tween 80 and poly(ethylene glycol) 600, as oil, surfactant and co-surfactant, and formed stabilized monodispersed oil nanodroplets upon dilution in water. SNEDDS represented encapsulation efficiency and loading capacity of 21.4 and 52.7%, respectively. The docetaxel release profile from the drug-loaded SNEDDS was recorded, its effectiveness against MCF-7 cell line was investigated, and an IC50 value of 0.98 ± 0.05 µg mL-1 was attained. The drug-loaded SNEDDS was administrated in rats, and the pharmacokinetic parameters of maximum concentration of 22.2 ± 0.8 µg mL-1, time to attain this maximum concentration of 230 min, and area under the curve of 1.71 ± 0.18 µg min mL-1 were obtained. The developed SNEDDS formulation can be represented as an alternative to docetaxel administration.

An evidence-based approach to medicinal plants for the treatment of sperm abnormalities in traditional Persian medicine.

Infertility is defined as inability of a sexually active couple to conceive after 1 year of regular intercourse without contraception. Male factors account for 20%-50% of cases of infertility. The aim of this study was to review medicinal plants that proposed to improve sperm abnormalities in traditional Persian medicine. For this purpose, PubMed, Scopus, GoogleScholar and Cochrane library were explored for medicinal plants used in traditional Persian medicine for sperm abnormalities to obtain studies giving any evidence for their efficacy and pharmacological mechanisms related to male infertility. Data were collected for the years 1966 to March 2015. For some of them, including Chlorophytum borivilianum, Crocus sativus, Nigella sativa, Sesamum indicum, Tribulus terrestris, Mucuna pruriens and Withania somnifera, more reliable evidence was found. The mechanisms involved in the beneficial effects of medicinal plants in sperm abnormalities are antioxidant, anti-inflammatory, anti-oedematous and venotonic activity as well as containing precursors for sperm production and increasing blood testosterone level. Various phytochemical categories including saponins, phytosterols, carotenoids, oxygenated volatile compounds, phenolic compounds and alkaloids seem to be responsible for these beneficial effects. Further studies are recommended for obtaining more conclusive results about the efficacy and safety of the mentioned medicinal plants.

Combination therapy - deferasirox and deferoxamine - in thalassemia major patients in emerging countries with limited resources.

BACKGROUND: The problem of iron-overload observed in thalassemia patients can be overcome using chelating agents such as deferiprone (Ferroprox(®) ), deferasirox (Exjade(®) ) and deferoxamine (Desferal(®) ). Although these drugs can be used as monotherapy, combined therapy, especially deferiprone with deferoxamine, has led to promising outcomes in various studies. METHODS AND MATERIALS: In this quasi-experimental study, serum ferritin levels were evaluated in 32 ß-thalassemia major patients with severe iron overload before and after receiving combined deferasirox (30-40 mg kg(-1) day(-1) ) and deferoxamine (40-50 mg kg(-1) day(-1) ) 2 days a week. This study was conducted from September 2012 to September 2013 in Southern Iran. RESULTS: The mean of serum ferritin levels significantly reduced from 4031 ± 1955 to 2416 ± 1653 ng mL(-1) after 12 months of therapy (P < 0·001). Echocardiograph findings showed significant improvement 1year after end of the study (P < 0·001). No drug toxicity was observed by monitoring serum creatinine, liver enzymes and blood urea nitrogen (BUN) during the study period. We observed no correlation between mean serum ferritin change and age (P = 0·87). In addition, the mean serum ferritin change did not differ between male and female thalassemia patients (P = 0·454). No difference in mean serum ferritin change was observed between patients who had undergone splenectomy compared to those who had not done so (P = 0·307). CONCLUSION: The study suggests that combination chelating therapy with deferasirox and deferoxamine can effectively reduce iron burden in ß-thalassemia major patients with heavy iron overload without any significant complications.

Effect of L-carnitine supplementation in comparison with moderate aerobic training on serum inflammatory parameters in healthy obese women.

AIM: Obesity is an important worldwide public health problem and considered a disease of chronic low-grade inflammation. The aim of this study was to evaluate the effect of L-carnitine supplementation in comparison with moderate aerobic exercise training on serum inflammatory parameters in healthy obese women. METHODS: In this double-blind randomized controlled clinical trial, 44 obese women were randomly assigned to 4 groups (N.=11) as follows: 1: L-carnitine supplementation (2 g/day) (CAR), 2: aerobic training + placebo (EXR+PLA), 3: L-carnitine supplementation + aerobic training (CAR+EXR) and 4: placebo (PLA). All intervention periods were eight weeks and subjects of aerobic training groups underwent 8-week aerobic training protocol (3 sessions a week [24 sessions]). Body Mass Index, daily dietary intake and serum free L-carnitine, IL-6, high-sensitivity C-reactive protein (Hs-CRP) and IL-10 levels of subjects were measured before and after interventions. RESULTS: Interventions had no significant effects on body weight, BMI, daily dietary intake and serum IL-10 levels of subjects in all groups. Serum free L-carnitine concentration increased significantly after interventions in CAR and CAR+EXR groups. Significant decreases of IL-6 were observed in EXR+PLA and CAR+EXR groups compared with placebo group. L-carnitine supplementation plus aerobic training led to significant decrease of serum Hs-CRP levels in CAR+EXR group compared with baseline values. CONCLUSION: L-carnitine supplementation did not affect serum IL-6, Hs-CRP and IL-10 levels in obese women. Aerobic training alone or in combination with L-carnitine had favorable effect on serum Il-6 and Hs-CRP levels as markers of inflammation in studied subjects.

International network on endocrine complications in thalassaemia (I-CET): an opportunity to grow.

Most of the endocrine complications in thalassaemia are attributable to iron overload which may be the result of economic circumstances (expense of the chelation therapy), late onset of chelation therapy or poor compliance with the iron chelation therapy. The major difficulties reported by hematologists or pediatric endocrinologists experienced in thalassaemias or thalassaemia syndromes in following growth disorders and endocrine complications were: lack of familiarity with medical treatment of endocrine complications (40%), interpretation of endocrine tests (30%), costs (65%), absence of paediatric endocrinologist for consultation on growth disorders and endocrine complications (27%), facilities (27%), other (e.g. lack of collaboration and on-time consultation between thalassaemic Centers supervised by hematologists and endocrinologists) (17%). Because any progress we make in research into growth disorders and endocrine complications in thalassaemia should be passed on to all those suffering from it, guaranteeing them the same therapeutic benefits and the same quality of life, on the 8th of May, 2009 in Ferrara (Italy), the International Network on Endocrine Complications in Thalassemia (I-CET) was founded. The I-CET group is planning to conduct, in Ferrara in May 2012, a workshop, "MRI and Endocrine Complications in Thalassaemia", and in Doha (Qatar) in September 2012, a 3-day intensive course entitled, "Growth disorders and Endocrine Complications in Thalassaemia", to provide interested pediatricians, physicians and hematologists from all over the world with an in-depth approach to the diagnosis and management of growth and endocrine disorders in thalassaemic patients.

Compliance of deferoxamine injection in beta-thalassaemia major patients in Iran.

AIM/OBJECTIVE: Iran is located on the Mediterranean belt and has high prevalence of thalassaemia. Deferoxamine therapy requires burdensome hours of daily infusion several times a week. METHODS: We studied 510 thalassaemia major patients referring to thalassaemia tertiary care centre for compliance of deferoxamine and also assessed various reasons for non-compliance. A questionnaire was developed. RESULTS: Our study showed that 418 (82%) subjects were adherent to deferoxamine therapy. Females were more adherent to the chelation therapy. Among patients whose age was ≤ 12 years, 90.4% showed drug compliance compared with 80.3% in patients aged >12 years (P = 0.03). The most frequently reported reason for poor compliance was pain (38%). CONCLUSION: High percentage of patients had adherence to iron chelation, which is in contrast to previous studies. This may be attributed to the vigorous efforts of governmental and non-governmental organisations in educating patients and provision of free drug and equipment in the past few years. The results were satisfying but still more is to be done to increase drug adherence and to minimise reasons causing poor compliance.

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.

Renal tubular function in patients with beta-thalassaemia major in Zahedan, southeast Iran.

INTRODUCTION: In patients with beta-thalassaemia major, impaired biosynthesis of the beta-globin leads to accumulation of unpaired alpha-globin chain. Shortened red cell lifespan and iron overload cause functional and physiological abnormalities in various organ systems. Thus, in patients with beta-thalassaemia major, the most important cause of mortality and morbidity is organ failure due to deposits of iron. The aim of this study is to investigate renal tubular and glomerular functions in patients with beta-thalassaemia major. METHODS: 166 subjects with beta-thalassaemia major (96 male, 70 female) were enrolled in the study. Fasting blood and 24-hour urine samples were obtained for haematological and biochemical analyses. RESULTS: Patients with beta-thalassaemia major showed significant signs of renal tubulopathy, such as hypercalciuria (12.9 percent), proteinuria (8.6 percent), phosphaturia (9.2 percent), magnesiumuria (8.6 percent), hyperuricosuria (38 percent) and excretion of beta-2 microglobin (13.5 percent). We found that 95.1 percent of patients had iron overload (ferritin more than 1,000 ng/ml). CONCLUSION: The determination of biochemical indices of renal function might help prevention of serious kidney damage before any clinical symptom is observed. Beta-thalassaemia patients present multiple renal abnormalities which may be due to iron overload. We suggest the appropriate chelation therapy and regular monitoring of the status of iron overload.

The CD30 gene promoter microsatellite binds transcription factor Yin Yang 1 (YY1) and shows genetic instability in anaplastic large cell lymphoma.

CD30 is a member of the TNF receptor family. Our interest lies in understanding the control of CD30 expression, particularly as its over-expression provides a diagnostic marker for a subset of non-Hodgkin's lymphomas, particularly anaplastic large cell lymphoma (ALCL), and because anti-CD30 treatment has been shown to be efficacious. We have identified a number of regulatory regions, including an Sp1 element in the minimal promoter, and a downstream promoter element that is required for start site selection. The discovery of both an activating AP1 site and an upstream microsatellite that represses transcriptional activity of CD30 suggests that this region is involved in dysregulation of CD30 expression. We have now identified the major microsatellite binding activity as transcription factor Yin Yang 1 by both one-hybrid cDNA library screening and peptide mass fingerprinting. Due to the strong repressive effect of the microsatellite, we also investigated whether microsatellite instability may induce changes in CD30 expression and hence explain the over-expression of CD30 in ALCL. Laser capture microdissection of ALCL biopsies and CD30 microsatellite typing indicated that the neoplastic cells show a high degree of variation, but this does not correlate with high CD30 expression seen in ALCL.

Assessment of annual effective dose from 238U and 226Ra due to consumption of foodstuffs by inhabitants of Tehran city, Iran.

The concentrations of (238)U and (226)Ra were determined in different foodstuffs purchased from markets in Tehran. Determinations of the radionuclides have been carried out using alpha spectrometry technique, on samples of egg, lentil, potato, rice, soya, spinach, tea and wheat. Average concentrations of natural radionuclides and foodstuff consumption rate were used to assess annual intake and based on intake values, the annual effective ingestion dose has been estimated for Tehran city residents. The measurement results show that soya has the maximum concentration of (238)U equal to 15.6 +/- 2.6 mBq kg(-1) and tea has the maximum concentration of (226)Ra equal to 1153.3 +/- 265.3 mBq kg(-1). Besides, the maximum annual effective dose from (238)U and (226)Ra were assessed to be 2.88 x 10(-2) +/- 7.20 x 10(-3) and 2.15 +/- 0.54 muSv, respectively, from wheat samples.

Evaluation of the immunomodulatory effects of five herbal plants.

A group of medicinal plants including, Silybum marianum, Matricaria chamomilla, Calendula officinalis, Cichorium intybus and Dracocephalum kotschyi which grow in Iran, were extracted with ethanol 70% and the mitogenic activity was examined both on human peripheral blood lymphocytes and thymocytes. Effect of these extracts on proliferative responsiveness of human lymphocytes to phytohemagglutinin (PHA) and on the mixed lymphocyte reaction (MLR) was also investigated. The results obtained indicated that none of the extracts had a direct mitogenic effect on human lymphocytes or thymocytes (stimulation index, SI<0.07). Among the plants studied, C. intybus and C. officinalis showed a complete inhibitory effect on the proliferation of lymphocytes in the presence of PHA (SI range 0.01-0.49). A dose dependent inhibitory effect was obtained in the case of D. kotschyi. Extract of M. chamomilla showed almost no stimulatory effect. A significant decrease in proliferation assay due to 0.1-10 microg/ml of S. marianum was observed (SI<0.46, P<0.05). In MLR, a markedly stimulatory effect with some lower concentrations of all the extracts except Dracocephalum was detected. The highest stimulatory effect was due to 100 microg/ml of S. marianum (SI 2.82). Treatment of mixed lymphocytes with 0.1-10 microg/ml of C. officinalis (SI range 1.34-1.80) and 10 microg/ml of M. chamomilla and C. intybus (SI 2.18 and 1.70, respectively) strongly increased the cell proliferation. In conclusion, this in vitro study revealed the capacity of all the extracts except Dracocephalum to enhance the proliferation of lymphocytes after stimulation with the allogenic cells.