Characterization of chitosan/Persian gum nanoparticles for encapsulation of Nigella sativa extract as an antiviral agent against avian coronavirus.

The aim of this study was to investigate the physicochemical characteristics of nanoparticles formed by the ionic gelation method between chitosan and water-soluble fraction of Persian gum (WPG) for encapsulation of Nigella sativa extract (NSE) as an antiviral agent. Our findings revealed that the particle size, polydispersity index (PDI), and zeta potential of the particles were in the range of 316.7-476.6 nm, 0.259-0.466, and 37.0-58.1 mV, respectively. The amounts of chitosan and WPG as the wall material and the NSE as the core had a considerable impact on the nanoparticle properties. The proper samples were detected at 1:1 chitosan:WPG mixing ratio (MR) and NSE concentration of 6.25 mg/mL. Fourier-transformed infrared (FTIR) spectroscopy proved the interactions between the two biopolymers. The effect of NSE on infectious bronchitis virus (IBV) known as avian coronavirus, was performed by the in-ovo method determining remarkable antiviral activity of NSE (25 mg/mL) and its enhancement through encapsulation in the nanoparticles. These nanoparticles containing NSE could have a promising capability for application in both poultry industry and human medicine as an antiviral product.

Effect of Melatonin Administration on Sleep Quality in Sulfur Mustard Exposed Patients with Sleep Disorders.

Sulfur mustard (SM) is a toxic agent that targets several tissues. It is the leading cause of persistent lung disease, progressive deterioration in lung function, and mortality among injured patients. Disturbed sleep and poor quality of sleep are common in SM-exposed patients with chronic respiratory problems. Melatonin is an alternative medication that has been widely used to treat poor sleep quality caused by several specific conditions. This study aimed to evaluate the efficacy of melatonin administration in improvement of sleep quality in SM-injured patients. In this randomized, double-blind and placebo-controlled trial study a total of 30 SM-exposed male patients were recruited. Patients received 3 mg melatonin (N = 15) or placebo (N = 15), orally in a single dose, 1 h before bedtime for 56 consecutive days. Sleep quality was evaluated by Pittsburgh Sleep Quality Index (PSQI); daytime sleepiness was measured by Epworth Sleepiness Scale (ESS), and the risk of obstructive sleep apnea was determined by STOP-Bang questionnaire. Compared with placebo, melatonin administration significantly improved global PSQI score, particularly sleep latency (P = 0.03) and subjective sleep quality (P = 0.004). Mean of global PSQI score was declined significantly (P = 0.01) from 10.13 ± 3.44 to 6.66 ± 3.08 in melatonin group. No differences in ESS and STOP-Bang scores were observed between two groups. Melatonin was effective in improving global PSQI score and sleep latency, but not daytime sleepiness and obstructive sleep apnea in SM-exposed patients. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients.

Comparison of efficacy and safety of two available natural surfactants in Iran, Curosurf and Survanta in treatment of neonatal respiratory distress syndrome: A randomized clinical trial.

INTRODUCTION: The benefit of surfactant prescription for respiratory distress syndrome (RDS) has been approved. Curosurf and Survanta are two commonly used natural surfactants in Iran. Previous studies did not report priority for one of these two drugs. The present study aimed to compare the effectiveness and safety of Curosurf and Survanta in treatment of RDS. METHODS: In this randomized clinical trial, neonates were born with RDS diagnosis in two governmental and referral hospitals of Tehran (the capital of Iran) in 2014 were randomly selected. Neonates were randomly assigned into two groups receiving 100 mg/kg Curosurf or Survanta as soon as possible after randomization. Complications, mortality and needing the second dose were compared between the two groups. RESULTS: A total 112 patients with the mean gestational age of 32.59 ± 3.39 weeks were evaluated (56 patients in each group). There were no significant differences regarding birth weight, gestational age, delivery method, and parity between the two groups (P > 0.05). The complications were occurred in 18 neonates (32.1%) of Curosurf group and 20 neonates (35.7%) of Survanta group (RR = 0.922, 95% CI = 0.617-1.379). There were no significant differences regarding complications, mortality, and needing nasal CPAP and endotracheal tube between the two groups. In the neonates with gestational age of 29-32 weeks the IVH and NEC incidence were significantly more in Curosurf group compared to Survanta group (27.8% vs 0% and 22.3% vs 0%, P < 0.05). CONCLUSION: There was no significant difference in complications or mortality between those two groups; however Curosurf was associated with less need of ET tube (in >32 birth weeks subgroup) and NCPAP (in 29-32 birth weeks subgroup) (p = 0.008). Further evaluations with longer follow-up duration are needed for comparing these two surfactants.

Effect of Nasal Calcitonin on the Health-Related Quality of Life in Postmenopause Women Affected With Low Bone Density.

BACKGROUND: Physical activity and mental health could be affected by osteoporosis and various therapeutic options such as calcitonin may influence Quality Of Life (QOL) of these patients with Low Bone Density (LBD). OBJECTIVES: This study aimed to evaluate the effect of nasal calcitonin on QOL in post menopause women with LBD. PATIENTS AND METHODS: This clinical trial study was performed on one hundred and fifteen menopause women with LBD less than 1 SD in Bone Mineral Densitometry (BMD) referred to Baqiyatallah Hospital in Tehran, Iran, during 2009 - 2010. They were assigned to receive 200 IU calcitonin nasal spray along with calcium (1000 mg) and vitamin D (400 IU) for 6 months. Quality of life was assessed by Short-Form 36 (SF-36) questionnaire (Persian-validated version). RESULTS: The mean age (± SD) of the participants was 58.75 ± 8.15 years. Intranasal spray of calcitonin increased QOL scores significantly (88.05 ± 15.63 vs. 92.15 ± 13.22, P value = 0.000). Bone mineral density of spine was increased from 0.834 ± 0.11 to 0.12 ± 0.852 and this difference in BMD of lumbar spine was statistically significant (P value: 0.003) but not significant in femur's BMD (P value = 0.061). In comparison with BMD indexes, The QOL scores especially Mental Health domain changes had only a significant correlation with the changes of total T score in BMD (P = 0.031, Coefficient Correlation = 0.248). CONCLUSIONS: It seems that nasal spray of calcitonin can effectively improve QOL of women with LBD and QOL changes were not influenced by clinical or para-clinical alteration. Mental health domain must be more considered in further studies as a predicting domain for Health-Related Quality of Life (HR-QOL) changes.

Efficacy of Tiotropium Bromide and Rehabilitation Treatment on Pulmonary Function of Patients With Sulfur Mustard Lung Injury.

BACKGROUND: Chronic pulmonary complication is the most common delayed toxic effect of sulfur mustard (SM) and it has no treatment so far. OBJECTIVES: To evaluate short-term therapeutic effects of inhaled tiotropium bromide and pulmonary rehabilitation on pulmonary function of patients with SM induced lung injury. PATIENTS AND METHODS: In a randomized clinical trial, using convenient sampling method, 54 patients with chronic lung disease due to SM exposure were recruited in Baqiyatallah General Hospital, Tehran, Iran for a period of 2-month study. They were randomly divided into 3 groups of 18 participants each. Group 1 received routine drugs (Serevent, Flixotide), pulmonary rehabilitation 30 minutes/2 times a week, and tiotropium bromide 18 µg/day. Group 2 was treated with routine drugs and pulmonary rehabilitation and group 3 was only on the routine drugs. cardiopulmonary exercise test (CPET), plethysmographic measurements, and respiratory symptoms evaluation were performed before and after medical intervention. RESULTS: In group 1, compared to group 3, significant differences were found with regard to symptoms of cough ([difference between the first and last visit in group 1: Diff 1] = -1.6, Diff 3 = -0.3, P = 0.01) and nocturnal dyspnea (Diff 1 = -1.9, Diff 3 = 0.0, P = 0.01), likewise, compared to group 2, significant differences were found with regard to lung function parameters of forced vital capacity (Diff 1 = 3.0, Diff 2 = -3.5, P = 0.03), forced expiratory volume in one second (Diff 1 = 3.9, Diff 2 = -5.6, P = 0.009), maximal mid-expiratory flow rate 25% - 75% (Diff 1 = 1.5, Diff 2 = -3.2, P = 0.007) and peak expiratory flow (Diff 1 = -2.06, Diff 2 = -4.3, P = 0.04). Total lung capacity (Diff 2 = 9.28, Diff 3 = -12.07, P = 0.02) and residual volume (Diff2 = 32.1, Diff3 = -27.6, P = 0.04) were increased in group 2 compared to group 3. There were no significant differences with regard to CPET results among all groups (P > 0.05). CONCLUSIONS: Inhalation of tiotropium bromide in combination with pulmonary rehabilitation could improve some plethysmographic lung volumes and clinical outcomes in patients with chronic pulmonary disease due to SM. Short-term prescription of pulmonary rehabilitation has no effect on CPET of patients.

Serum level of substance P in patients with lung injuries due to sulfur mustard.

BACKGROUND: Chronic bronchiolitis is the most important problems of chemical victims of mustard gas. Diverse studies suggest that substance P (SP) as a member of tachykinin neuropeptides, has a significant role in the neurogenic inflammation processes of the airways and lungs. We aimed to determine the serum level of SP in chemical victims of mustard gas and compare it with normal subjects. MATERIALS AND METHODS: The chemical victims were divided into the 2 groups of 30:A group with mild to moderate pulmonary symptoms and other group with moderate to severe symptoms and compared with 3(rd) group as healthy controls. After preparing our samples and using the SP kit, final analysis was performed with enzyme-linked immunosorbent assay reader. RESULTS: The Concentration of circulatory SP levels in the chemical patients was 2.86 ± 1.47 ng/ml and had not a significant difference with the control group (3.15 ± 1.03 ng/ml) (P > 0.05). The circulatory SP levels were 2.48 ± 0.92 ng/ml and 3.28 ± 1.73 ng/ml in patients with moderate to severe symptoms and mild to moderates (P < 0.05) respectively. CONCLUSION: The SP may have a role in pulmonary complications of mustard gas. The lower level of SP in the moderate to severe patients may be due to corticosteroid consumption in such severe cases. However, further studies are needed to clarify the roles and mechanism of SP in this setting.

The role of N-acetylcysteine in the management of acute and chronic pulmonary complications of sulfur mustard: a literature review.

CONTEXT: Sulfur mustard exposure, as the most widely used chemical weapon, can lead to acute and long-term pulmonary complications via various pathways, such as triggering an imbalance between the oxidant and antioxidant system. Currently, there is no validated antidote, chemoprophylaxis and curative modality for pulmonary toxicities secondary to sulfur mustard exposure. OBJECTIVE: The aim of this literature review is to collect available experimental and clinical data on the efficacy of N-acetylcysteine (NAC), as a prominent antioxidant agent, in the prevention and/or treatment of sulfur mustard-induced acute and chronic pulmonary toxicities. METHODS: A literature search was performed by the relevant keywords like "N-acetyl cysteine", "Sulfur mustard" and "Lung injury" in databases such as Scopus, Medline, Embase and ISI Web of Knowledge. No time limitation was considered. Nineteen articles were selected for review. RESULTS: A number of in vitro and experimental studies concluded that oral, intravenous, intraperitoneal and intra-tracheal administration of NAC is effective in the management of sulfur mustard-induced acute lung injury, in a time-dependent manner, via direct scavenging, inhibition of oxidative stress, inflammatory responses and apoptosis. In addition, oral NAC alone (1200 or 1800 mg/day for 4 months) or at a dose 600 mg/day for 6 months in combination with clarithromycin (500 mg/day) have led to improvements of clinical and paraclinical pulmonary parameters of patients with bronchiolitis obliterans due to sulfur mustard, through undetermined mechanisms. CONCLUSION: Despite limitations of relevant experimental and clinical studies, NAC can be considered as a candidate agent for prevention and/or treatment of sulfur mustard-induced acute lung injuries, as well as its long-term pulmonary toxicities, especially bronchiolitis obliterans.

The role of serum level of interleukin-6 in severity of pulmonary complications of sulfur mustard injuries.

Diverse studies suggest that interleukin-6 (IL6), as a member of cytokines family, has a major role in inflammatory processes of airways and lungs. In this study, an attempt was made to determine the serum level of IL6 in sulfur mustard (SM) injured patients and its comparison with controls. The measured IL6 mean level in patients with chemical injuries (0.76±0.3 ng/ml) was significantly higher than the control group's mean level (0.34±0.12 ng/ml). Furthermore, patients with moderate to severe symptoms had a serum level of (0.95±0.92 ng/ml) which was significantly higher than mild (0.47±0.54) and control (0.34±0.12) groups. The outcome of this research program demonstrates that an increase in serum level of IL6 can have a role in pulmonary complications of SM, similar to other well defined pulmonary diseases.  However, further studies are required to clarify the role and mechanism of IL6 in such patients.

Early surfactant therapy with nasal continuous positive airway pressure or continued mechanical ventilation in very low birth weight neonates with respiratory distress syndrome.

BACKGROUND: Various strategies have been suggested for the treatment of respiratory distress syndrome (RDS). OBJECTIVES: The aim of this study was to compare the efficacies of two common methods of RDS management among neonates with low birth weight. PATIENTS AND METHODS: A cohort study was conducted on 98 neonates with definite diagnosis of RDS during 2008-2009. The neonates were divided into two groups by a blinded supervisor using simple randomization (odd and even numbers). Forty-five cases in the first group were treated with intubation, surfactant therapy, extubation (INSURE method) followed by nasal continuous positive airway pressure (N.CPAP) and 53 cases in the second group underwent intubation, surfactant therapy followed by mechanical ventilation (MV). RESULTS: Five (11.1%) cases in the first group and 23 (43%) cases in the second group expired during the study. The rates of MV dependency among cases with INSURE failure and cases in the MV group were 37% and 83%, respectively (P < 0.001). Birth weight (BW) (P = 0.017), presence of retinopathy of prematurity (P = 0.022), C/S delivery (P = 0.029) and presence of lung bleeding (P = 0.010) could significantly predict mortality in the second group, although only BW (P = 0.029) had a significant impact on the mortality rate in the first group. Moreover, BW was significantly related to the success rate in the first group (P = 0.001). CONCLUSIONS: Our findings demonstrated that INSURE plus NCPAP was more effective than the routine method (permanent intubation after surfactant prescription). In addition, the lower rates of mortality, MV dependency, duration of hospitalization, and complications were observed in cases treated with the INSURE method compared to the routine one.

Serum matrix metalloproteinase levels in patients exposed to sulfur mustard.

BACKGROUND: Matrix metalloproteinases (MMPs) are a group of endopeptidases which comprised of various types. These proteolytic enzymes are zinc-dependent and play role in degradation of extracellular matrix (ECM). Various types of cells such as macrophages, fibroblasts, neutrophils, synovial cells and some epithelial cells secrete MMPs. According to previous studies on bronchiolitis and respiratory tract lesions in these patients and unknown pathophysiology mechanism up to date, this cross-sectional study was performed. OBJECTIVES: The aim of this study was to compare the serum MMP level in patients with chemical injuries and normal people and also determine the role of these parameters in pulmonary disorders . MATERIALS AND METHODS: In this cross-sectional study, 25 Iranian patients exposed to the sulfur mustard and 25 unexposed participants as the control group were enrolled. Serum samples were collected from two groups and stored at -70˚C until the measurement of MMPs and TIMPs. ELISA kit was used for measurement of MMP and TIMP based on the kit's instruction. For validations in measurement, all samples were analyzed duplicate and in some cases triplicate. RESULTS: The mean level of MMP-9 in serum of chemically-injured group was 1592.42 and this amount in normal group was 679.72 .So there was a significant difference between two groups (P = 0.001) and the mean level of MMP-8 in serum of patients group was 49.10 and in normal group was 35.53. Then there was no significant difference between two groups (P = 0.197). The mean levels of MMP-1 and MMP-2 was not significantly different (P value > 0.05) in the patient and normal groups. And also the mean levels of TIMP-1 and TIMP-2 was not significantly different (P > 0.05) in the patients and normal groups. CONCLUSIONS: In summary, serum MMPs in chemically-injured has shown no significant difference with normal people except for the MMP-9.

Evaluation of Aggregometery Parameters and Efficacy of Plavix versus Clopidex in Patients Suffering from Ischemic Heart Disease: A Randomized Double Blind Clinical Trial.

BACKGROUND: Ischemic heart disease is the leading cause of death in most societies. In a pathophysiologic point of view, it chiefly results from the formation of thrombus in coronary arteries which could not be only prevented by aspirin. Many of clinical trials have shown the long-term benefits of antiplatelet drugs in reducing the risk of thrombotic accidents. OBJECTIVES: Clopidogrel is a thienopyridine derivative used to prevent platelets from adhering together by direct inhibition of Adenosine diphosphate (ADP), the major factor behind platelets aggregation. Sanofi-Aventis and Bristol-Myers are companies that produce Clopidogrel by the name of Clopidogrel bisulfate. Its trade name is Plavix, nonetheless in Iran it is distributed under the name of Clopidex by Exir Company. In this study we are to compare Plavix and Clopidex in terms of efficacy as well as aggregometry parameters like ADP and PRP (Platelet Rich Plasma). PATIENTS AND METHODS: This is a double blind clinical trial in which we had two groups of patients suffering from Ischemic heart disease who were selected by inclusion criteria. Group A (36 patients) took Plavix (75 mg/d) and group B (36 patients) used clopidex (75 mg/d) both for 30 days. The aggregometry parameters also consisted of PRP and ADP that were run on the patients before and after the study. Finally, a comparison of aforementioned tests, quality of life, lab parameters and compliance in both groups was provided. RESULTS: In groups A and B, the mean levels of PRP before the study were 348000 and 340000/µL respectively. The ADPs were also 73/76 and 68/07 µM that showed no significant difference (P > 0.05).The Means of ADP5 in group A before and after the study were 66.40 and 43.84 µM respectively that there was significant difference (P = 0.001). The Means of ADP5 in group B before and after the study were 58.04 and 40.16 µM respectively that there was significant difference (P < 0.001).The Means of ADP20 in group A before and after the study were 73.76 and 54.97 µM respectively which showed significant difference (P < 0.001). The Means of ADP20 in group B before and after the study were 68.07 and 52.49 µM respectively which showed significant difference (P = 0.001). Difference of ADP5 between group A and B was not significant (P = 0.495). Difference of ADP20 between group A and B was not significant (P = 0.721). The Means of PRP in group A before and after the study were 348000 and 335000/ µL respectively that there was no significant difference (P = 0.66). The Means of PRP in group B before and after the study were 340000 and 336000/ µL respectively that indicated no significant difference (P = 0.81). Difference of PRP between group A and B was not significant (P = 0.563). CONCLUSIONS: Our findings suggested that both drugs significantly lessen the ADP level; even so there was no significant difference between two groups in PRP and ADP factors.

Systemic complications of trinitrotoluene (TNT) in exposed workers.

INTRODUCTION: 2,4,6-trinitrotoluene (TNT) has been widely used as an explosive. TNT can induce some well-recognized toxic impacts comprising toxic hepatitis, aplastic anemia and cataract. The aim of study was evaluation of TNT exposed workers for systemic complication. METHODS: In a cross-sectional study, we carried out Liver Function Test (LFT), complete blood count (CBC) and slit lamp biomicroscopy to compare the prevalence and severity of these 3 complications between 47 male TNT exposed workers (with at least one year continuous experience of TNT exposure) and 43 unexposed male hospital worker who hadn't had any previous contacts with TNT. We also performed Pulmonary Function Test (PFT) to assess the probable obstructive/restrictive abnormalities, caused by TNT. RESULTS: Mean alkaline phosphatase (ALP) level of TNT exposed group was significantly higher than the unexposed group (p = 0.023) Forced Expiratory Volume in one second to Forced Vital Capacity (FEV1/FVC) ratios of both groups were in the range of restrictive pattern (82.03% and 81.42% for the exposed and unexposed group, respectively) with no meaningful difference. We didn't find out any specific TNT induced cataract and general cortical cataract (CC) and nuclear sclerotic cataract (NSC) prevalence was not significantly different. DISCUSSION: we haven't found TNT as a chemical, causing toxic hepatitis or aplastic anemia; neither did we find it as a compound, responsible for a meaningful increase in cataract prevalence. However, due to the increased ALP serum levels and FEV1/FVC ratios among TNT workers, safety precautions are advised.

Combination therapy for airflow limitation in COPD.

UNLABELLED: Background and the purpose of the study Existing evidence confirms that no pharmacologic agent ameliorates the decline in the lung function or changes the prognosis of chronic obstructive pulmonary disease (COPD). We tried a critical combination therapy for management of COPD. METHODS: Current or past smoker (passive or active) COPD patients with moderate to severe COPD who did not respond to primitive therapy (i.e., oral prednisolone (50 mg in the morning) for 5 days; with Beclomethasone Fort (3 puff q12h, totally 1500 micrograms/day), Salmeterol (2 puffs q12h, 50 micrograms/puff) and ipratropium bromide (4 puffs q8h) for two months, enrolled to study. Furthermore they were received N-Acetylcysteine (1200 mg/daily), Azithromycin (tablet 250 mg/every other day) and Theophylline (100 mg BD). RESULTS: The study group consisted of 44 men and 4 women, with a mean age and standard deviation of 63.6 ± 12.7 years (range 22-86 years). Thirteen of 48 patients (27.0%) was responder based on 15% increasing in FEV 1 (27.7 ± 7.9) after 6.7 ± 6.1 months (57.9 ± 12.9 year old). There were statistically significant differences in age and smoking between responders and non-responders (P value was 0.05 and 0.04 respectively). There was no difference in emphysema and air trapping between two groups (p = 0.13). CONCLUSION: Interestingly considerable proportion of patients with COPD can be reversible using combination drug therapy and patients will greatly benefit from different and synergic action of the drugs. The treatment was more effective in younger patients who smoke less.

Effect of nebulized morphine on dyspnea of mustard gas-exposed patients: a double-blind randomized clinical trial study.

Background. Dyspnea is one of the main complaints in a group of COPD patients due to exposure to sulfur mustard (SM) and is refractory to conventional therapies. We designed this study to evaluate effectiveness of nebulized morphine in such patients. Materials and Methods. In a double-blind clinical trial study, 40 patients with documented history of exposure to SM were allocated to two groups: group 1 who received 1 mg morphine sulfate diluted by 4 cc normal saline 0.5% using nebulizer once daily for 5 days and group 2 serving as control who received normal saline as placebo. They were visited by pulmonologist 7 times per day to check symptoms and signs and adverse events. Different parameters including patient-scored peak expiratory flow using pick flow meter, visual analogue scale (VAS) for dyspnea, global quality of life and cough, and number of respiratory rate, night time awaking for dyspnea and cough have been assessed. Results. The scores of VAS for dyspnea, cough and quality of life and also respiratory rate, heart rate, and night time awaking due to dyspnea and night time awaking due to cough improved significantly after morphine nebulization without any major adverse events. Also pick expiratory flow has been improved significantly after nebulization in each day. Conclusion. Our results showed the clinical benefit of nebulized morphine on respiratory complaints of patients due to exposure to SM without significant side effects.