Nocturnal serum melatonin levels in sulfur mustard exposed patients with sleep disorders.

BACKGROUND: Sulfur mustard (SM) exposure causes respiratory disorders, progressive deterioration in lung function and mortality in injured victims and poor sleep quality is one of the most common problems among SM-exposed patients. Since melatonin has a critical role in regulation of sleep and awareness, this study aimed to evaluate the serum melatonin levels in SM-injured subjects. METHODS: A total of 30 SM-exposed male patients and 10 controls was evaluated. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI); daytime sleepiness was measured by the Epworth Sleepiness Scale (ESS), and the risk of obstructive sleep apnoea was determined by the STOP-Bang questionnaire. Polysomnography (PSG) and pulmonary function tests (PFTs) were also available. Nocturnal serum melatonin levels were measured using an ELISA kit. RESULTS: The mean of PSQI, ESS and STOP-Bang scores in patients (11.76±3.56, 12.6±3.03 and 5.03±1.09, respectively) were significantly (p<0.01) higher than those in the controls (2.78±0.83, 4.69±1.15 and 1.18±0.82, respectively). PFTs also showed declined respiratory quality in SM-patients. There was a significant difference regarding the PSG results between patients and controls (p<0.01). The mean of nocturnal serum melatonin levels in patients (29.78±19.31 pg/mL) was significantly (p=0.005) lower than that in the controls (78.53±34.41 pg/mL). CONCLUSIONS: Reduced nocturnal serum melatonin and respiratory disorders can be the reasons for poor sleep quality among these patients. TRIAL REGISTRATION NUMBER: IRCT2015092924267N1, Pre-results.

An Update on Biomedical Application of Nanotechnology for Alzheimer's Disease Diagnosis and Therapy.

Approximately 35 million people worldwide suffer from Alzheimer's disease (AD). The cellular uptake and specific transport of drugs and imaging agents to brain are common issues in the diagnosis and therapy of AD. New advances in nanotechnology have supplied favorable solutions to this issue. Various nanocarriers such as polymeric nanoparticles, liposomes, micelles, dendrimers and nanogels have been studied for the delivery of drugs and imaging agents to brain. This review presents a succinct discussion of the applications of nanotechnology for Alzheimer's disease diagnosis and therapy.

Adjunctive Therapy with Curcumin for Peptic Ulcer: a Randomized Controlled Trial.

BACKGROUND: Curcumin, the bioactive ingredient of turmeric, has been shown to improve the treatment of peptic ulcer (PU) in animal studies. However, clinical studies confirming this effect of curcumin have been scant. OBJECTIVE: To assess the efficacy of adjunctive therapy with curcumin on the eradication of Helicobacter pylori infection and severity of dyspepsia in patients with PU. METHODS: In this randomized double-blind placebo-controlled parallel-group trial, patients diagnosed with PU were assigned to standard H. pylori eradication triple therapy with clarithromycin (500 mg b.i.d.), amoxicillin (1 000 mg b.i.d.) and pantoprazole (40 mg b.i.d.), and randomized to receive either curcumin (500 mg/day) or placebo as adjunct to standard treatment. Severity of dyspepsia symptoms was evaluated using the Hong Kong dyspepsia index (HKDI). Eradication of H. pylori infection was assessed using the urea breath test (UBT) at 4 weeks following the end of treatment. RESULTS: Adjunctive therapy with curcumin was associated with a greater improvement of dyspepsia symptoms according to the HKDI score (change score: -12.90±2.81 vs. -9.60±3.39 in the curcumin and control group, respectively; p<0.001). The number of subjects whose dyspepsia was resolved during the course of treatment was significantly higher in the curcumin (27.6%) vs. placebo (6.7%) group (p=0.042). Nevertheless, the results of UBT test showed equal rate (73.3%) of H. pylori eradication in the study groups. Curcumin was safe during the course of trial. CONCLUSION: Addition of curcumin on top of the standard anti-helicobacter regimen in patients with PU is safe and improves dyspepsia symptoms but has no enhancing effect on the eradication of H. pylori infection.

SERUM LEVELS OF FIBROBLAST GROWTH FACTOR 21 IN TYPE 2 DIABETIC PATIENTS.

BACKGROUND AND PURPOSE: Fibroblast growth factor 21 (FGF21) has recently been identified as a metabolic regulator, but its physiological role is still not completely known. The aim of this study was to evaluate serum FGF21 levels in an Iranian population with type 2 diabetes. MATERIALS AND METHODS: This cross-sectional study was conducted in patients with type 2 diabetes. All patients were evaluated for fasting serum levels of glucose, glycated hemoglobin (HbA1c), lipids, urea and creatinine. Participants were divided into two groups with poorly-controlled and well-controlled diabetes based on their HbA1c levels. Healthy non-diabetic subjects (matched with patients in terms of age, sex and body mass index [BMI]) were also recruited as control group. Serum FGF21 concentrations were determined in all subjects using ELISA. RESULTS: Of the evaluated 141 subjects, 49 (34.8%) were categorized as having well-controlled diabetes, 66 (46.8%) had poorly-controlled diabetes, and there were 26 subjects in the normal control group. Mean serum FGF-21 concentration was 337.89±283.67 ng/L in the diabetic group and 237.25±43.22 ng/mL in the non-diabetic group (p<0.001). Mean serum FGF21 level was 237.25 ± 43.22 ng/mL in the control group, 309.81 ± 301.68 ng/mL in the well-controlled diabetic group, and 358.73 ± 269.98 ng/mL in the poorly controlled diabetic group. Serum FGF21 level in the poorly controlled diabetic group was significantly higher than that in the well-controlled diabetic and the healthy control groups (p=0.02) but there was no significant difference between the well-controlled and healthy groups. There was no significant association between serum FGF21 levels with lipid levels, presence of diabetic complications and BMI (p > 0.05). CONCLUSIONS: The present results suggested an association between elevated serum levels of FGF21 and poor control of diabetes. Future studies are warranted to elucidate the prognostic role of these elevated levels of FGF21 in diabetic subjects.

Comparative trial of Aloe vera/olive oil combination cream versus phenytoin cream in the treatment of chronic wounds.

OBJECTIVE: Aloe vera is a medicinal plant that has been traditionally used to accelerate wound healing. Olive oil is also a natural product that may contribute to wound healing owing to its antimicrobial and anti-inflammatory effects. The present study aimed to evaluate the effect of an Aloe vera-olive oil (AVO) combination cream on the healing process of chronic wounds. METHOD: In this randomised, double-blind, comparator-controlled, parallel-group trial, patients with chronic wounds were treated with either AVO cream or phenytoin cream as the standard treatment for a period of 30 days. Wound healing was evaluated using Bates-Jensen assessment tool and the severity of pain was assessed using a visual analogue scale (VAS). RESULTS: After initial assessment, 60 patients with chronic wounds (41 with pressure ulcer, 13 with diabetic wounds and 6 with venous ulcers), were recruited and randomised into 2 groups of 30. After 30 days of treatment, significant improvements in the wound size, depth, and edges; necrotic tissue type and amount; exudate type and amount; colour of wound surroundings; and peripheral tissue oedema score were observed in the AVO cream group (p<0.001). The total score of wound healing showed significant improvement with both AVO (p<0.001) and phenytoin (p<0.01) creams, although AVO was more efficacious (p<0.001). Likewise, although both treatments reduced the initial VAS score, the efficacy of AVO was significantly greater (p<0.001). CONCLUSION: AVO cream significantly accelerates biological healing of chronic wounds and helps to reduce pain severity with a higher efficacy compared with phenytoin cream.

Impact of Supplementation with Curcuminoids on Systemic Inflammation in Patients with Knee Osteoarthritis: Findings from a Randomized Double-Blind Placebo-Controlled Trial.

OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disease associated with inflammation. The present study aimed to determine changes in serum levels of inflammatory biomarkers in OA patients whose clinical symptoms were improved as a result of supplementation with curcuminoids. METHODS: This study was a randomized double-blind placebo-control parallel-group clinical trial in which 40 subjects with mild-to-moderate degree knee OA were randomly allocated to receive either pure curcuminoids (1,500 mg/day in 3 divided doses; n=19) or matched placebo (n=21) for 6 weeks. In order to enhance the bioavailability of curcuminoids, piperine (15 mg/day) was added to the treatment regimen. Serum levels of interleukins 4 (IL-4) and 6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß) and high-sensitivity C-reactive protein (hs-CRP), together with erythrocyte sedimentation rate (ESR) were determined at baseline as well as at the end of trial. RESULTS: Serum concentrations of IL-4 (p=0.001), IL-6 (p=0.006) and hs-CRP (p=0.004) were significantly reduced in the curcuminoid group whilst serum levels of TNF-α and TGF-ß and mean ESR remained unaltered by the end of trial (p>0.05). In the placebo group, serum concentrations of IL-4 (p=0.001), IL-6 (p=0.003), TNF-α (p=0.003) and TGF-ß (p=0.005) were significantly reduced but mean hs-CRP and ESR values remained statistically unchanged (p>0.05). Comparison of the magnitude of changes in the evaluated inflammatory biomarkers did not indicate any significant difference between the study groups (p>0.05). CONCLUSION: Significant improvement in clinical symptoms of OA in curcuminoid-treated subjects cannot be attributed to the systemic anti-inflammatory effects of these phytochemicals.

Short-term Curcuminoid Supplementation for Chronic Pulmonary Complications due to Sulfur Mustard Intoxication: Positive Results of a Randomized Double-blind Placebo-controlled Trial.

Pulmonary problems are among the most frequent chronic complications of sulfur mustard (SM) intoxication and are often accompanied by deregulated production of pro-inflammatory cytokines. Curcuminoids, comprising curcumin, demethoxycurcumin and bisdemethoxycurcumin, are phytochemicals with remarkable anti-inflammatory properties that are derived from dried rhizomes of the plant Curcuma longa L. (turmeric). The present pilot study aimed to investigate the clinical effects of supplementation with curcuminoids on markers of pulmonary function and systemic inflammation in SM-intoxicated subjects. In a randomized double-blind placebo-controlled trial, 89 male subjects who were suffering from chronic SM-induced pulmonary complications were recruited and assigned to either curcuminoids (500 mg TID per oral; n=45) or placebo (n=44) for a period of 4 weeks. Efficacy measures were changes in the spirometric parameters (FVC, FEV1, FEV1/FVC) and serum levels of inflammatory mediators including interleukins 6 (IL-6) and 8 (IL-8), tumor necrosis factor-α (TNFα), transforming growth factor-ß (TGFß), high-sensitivity C-reactive protein (hs-CRP), calcitonin gene related peptide (CGRP), substance P and monocyte chemotactic protein-1 (MCP-1). 78 subjects completed the trial. Although FEV1 and FVC remained comparable between the groups, there was a greater effect of curcuminoids vs. placebo in improving FEV1/FVC (p=0.002). Curcuminoids were also significantly more efficacious compared to placebo in modulating all assessed inflammatory mediators: IL-6 (p<0.001), IL-8 (p=0.035), TNFα (p<0.001), TGFß (p<0.001), substance P (p=0.016), hs-CRP (p<0.001), CGRP (p<0.001) and MCP-1 (p<0.001). Curcuminoids were safe and well-tolerated throughout the trial. Short-term adjunctive therapy with curcuminoids can suppress systemic inflammation in patients suffering from SM-induced chronic pulmonary complications.

A randomized, double-blind, placebo-controlled trial on the efficacy and tolerability of sertraline in Iranian veterans with post-traumatic stress disorder.

BACKGROUND: Unlike civilian post-traumatic stress disorder (PTSD), the efficacy of sertraline for the treatment of combat-related PTSD has not yet been proven. The present study aimed to evaluate the clinical efficacy of sertraline against combat-related PTSD in a randomized, double-blind, placebo-controlled trial. METHOD: Seventy Iranian veterans of the Iran-Iraq war who met the DSM-IV criteria for diagnosis of PTSD were randomized to receive either flexibly dosed sertraline (50-200 mg/day) (n=35, completers=32) or placebo (n=35, completers=30) for 10 weeks. Efficacy was evaluated by the Impact of Event Scale--Revised (IES-R) and the Clinical Global Impression scale--Severity (CGI-S) and Improvement (CGI-I) ratings. Responder criteria were defined as a ≥30% reduction in the IES-R total score plus a CGI-I rating of 'much' or 'very much' improved. RESULTS: On both intention-to-treat (ITT) and per protocol (completer) methods of analysis, the mean reductions in the IES-R total and subscale (re-experiencing/intrusion, avoidance/numbing and hyperarousal) scores (p<0.001) and also in the CGI-S score (p<0.01) were significantly greater in the sertraline group than in the placebo group. For the CGI-I, the mean endpoint score was significantly lower in the sertraline group than in the placebo group (p≤0.001). The number of responders in the sertraline group was significantly higher than in the placebo group (44% v. 3%, p≤0.001). Sertraline was well tolerated, with a 6% discontinuation rate as a result of adverse reactions. CONCLUSIONS: The results of this study suggest that sertraline can be an effective, safe and tolerable treatment for combat-related PTSD in Iranian veterans.

Allopurinol mouth rinse for prophylaxis of fluorouracil-induced mucositis.

To prepare and evaluate an allopurinol mouth rinse for prophylaxis of fluorouracil-induced mucositis, 33 patients with malignant disorders, who were going to receive 5-fluorouracil containing chemotherapy, were enrolled in a placebo-controlled double-blinded randomized clinical trial. Allopurinol mouthwash (1 mg/ml) or placebo was administered 1, 2 and 3 h after chemotherapy and three consecutive nights. A questionnaire consisting of demographic parameters, medical status, quality of life survey and mucosal injury scoring table (based on World Health Organization scales for mucositis) was completed for each patient at Day 1, 3 and 7 after chemotherapy. In allopurinol group nine participants (60.0%) were female and in placebo group, 10 (66.7%) (P = 0.705). Mean ages were 56.9 +/- 10.3 and 49.5 +/- 13.8 years in allopurinol and placebo groups respectively (P = 0.107). The analysis showed that the higher education level and the use of dentures significantly reduced the occurrence of mucositis, and allopurinol mouth rinse (1 mg/ml) was ineffective in the prophylaxis of fluorouracil-induced mucositis.

Specific PCR Assay for Rapid and Direct Detection of Neisseria meningitidis in Cerebrospinal Fluid Specimens.

BACKGROUND: Neisseria meninigitidis is one of the most frequently encountered microorganisms associated with central nervous system infections. The aim of this study was to evaluate a PCR-based assay for specific and rapid detection of N. meninigitidis in CSF specimens. METHODS: Since April 2002 to July 2006, 130 CSF specimens were collected from patients suspected of having bacterial meningitis. Bacterial isolation and identification was carried out according to the standard bacteriological methods. The PCR was used to amplify a 101bp fragment of capsular transport gene A (ctrA) of N. meningitidis. RESULTS: PCR yielded an amplified product with the expected size of 101 base pair fragment. Sensitivity test proved 500 ng of N. meningitidis DNA as the final detection limit and specificity test revealed no cross-reaction for a wide range of respiratory pathogenic organisms. CONCLUSION: The PCR assay was more sensitive than the bacterial culturing. It might be possible to apply this procedure for rapid diagnosis of meningococci in clinical samples.

Changing treatment protocol from azathioprine to mycophenolate mofetil: decrease in renal dysfunction, increase in infections.

INTRODUCTION: Immunosuppression for renal transplantation has shifted from azathioprine (AZA) regimens to those containing mycophenolate mofetil (MMF). This study investigated the impact of this change on the causes for rehospitalization as well as on graft and patient survival. METHODS: In this retrospective cohort study, we reviewed long-term patient and graft survivals as well as the causes of posttransplant admissions for 893 kidney recipients. Data on survival and readmissions were available for 811 subjects, who were divided to into the AZA cohort (n=289, transplantation between 1998 and 1999) and the MMF cohort (n=567, transplantation between 2000 and 2001). Survival, the cause for readmission, time interval between transplantation and readmission, intensive care unit (ICU) admission, mortality, and graft loss were compared between the two cohorts. RESULTS: Five-year patient and graft survival rates were 85% and 67% for the AZA cohort and 91% and 68% for the MMF cohort (P=.013). There were 202 (71%) and 371 (72%) readmissions registered for the AZA and MMF groups, respectively. In comparison with the AZA cohort, while readmissions secondary to graft rejection showed a significant decrease in the MMF cohort (62% vs 35%, P=.000), readmissions secondary to infections exhibited a significant increase (37% vs 50%, P=.002). A marginally significant increased mortality rate (2% vs 5%, P=.087) and ICU admission rate (3% vs 6%, P=.062) were also observed in the MMF cohort by comparison with the AZA cohort. CONCLUSION: The shift in the immunosuppression protocol from AZA to MMF, albeit advantageous in many instances, can sometimes undermine the outcome by giving rise to such complications as high infection rates.

Phenol and menthol in the treatment of chronic skin lesions following mustard gas exposure.

INTRODUCTION: Chronic skin lesions are common late complications of sulphur mustard exposure in veterans injured in chemical warfare. Pruritus is the most common complaint in the chronic phase, with significant effects on the patient's quality of life. The current study evaluated the efficacy of a combination of one percent phenol and one percent menthol in the control of pruritus in these affected patients. METHODS: This randomised, double-blinded clinical trial was performed in chemical warfare-injured veterans with mustard gas-induced pruritus. 80 subjects were selected randomly and divided into two equal groups. One group was treated with a combination of one percent phenol and one percent menthol twice a day, while the other group received a placebo. The therapeutic effects and side effects were evaluated during a six-week treatment course. Pruritus score with a range of 1-48 points was used to calculate the severity of pruritus before and after treatment in both groups. RESULTS: The final pruritus score in the drug group was significantly different, compared with the placebo group (p-value equals 0.03). There was also a statistically-significant difference between the pre-treatment (19 points) and post-treatment (15.5 points) pruritus scores in the drug group (p-value equals 0.001), but there was no significant difference in the response in the placebo group (p-value equals 0.66). Only a few patients had complaints about the drug, and these were generally minor. The most common complaints were of the greasy nature of the drug and its intolerable odour. CONCLUSION: A phenol one percent and menthol one percent combination has significant therapeutic effects for mustard gas-induced pruritus in chemical warfare-injured veterans, in comparison with the placebo.