Prevalence of COVID-19 outcomes in patients referred to opioid agonist treatment centers.

Background: Coronavirus disease (COVID-19) is a mild to severe infectious respiratory illness caused by the SARS-CoV-2 virus. Based on the numerous pieces of evidence regarding the role of opioids in immune function, viral replication, and virus-mediated pathology, we decided to assess the incidence and severity of COVID-19 outcomes in people undergoing opioid maintenance treatment. Methods: This is a prospective, descriptive, multi-center study that included 452 patients undergoing maintenance treatment in opioid agonist treatment (OAT) clinics in different cities of Iran. Demographic information, underlying disease, history of maintenance treatment, type of drug used, history of addiction, smoking, and the kind of substance abused, were recorded. A physician evaluated the COVID-19 symptoms, and the severity of the disease was defined based on the number of observed symptoms. Results: The results have not shown any significant difference in the severity of COVID-19 symptoms in different nationalities, gender, and treatment groups. Furthermore, the history of drug abuse, including time and type of abuse and smoking, has not indicated any significant association with the occurrence of symptoms. Only the severity of COVID-19 in the mentioned cities (first and second follow-up: p < 0.001) and individuals with a history of underlying disease (first follow-up: p = 0.020; second follow-up: p = 0.043) were significantly different. Conclusion: Our results have demonstrated that the severity of symptoms in people with the underlying disease was significantly higher than in others. But there is no association between sex, race, treatment groups, and abuse history with the severity of COVID-19 symptoms in methadone maintenance treatment (MMT) patients.

Hypoglycemic, hypolipidemic and hepatoprotective effects of Alpinia officinarum on nicotinamide/streptozotocin induced type II diabetic rats.

OBJECTIVES: Alpinia officinarum Hance, commonly known as lesser galangal, is a member of the ginger family (Zingiberaceae) traditionally used for many decades to treat inflammation, pain, stomach ache and cold. In the present study, the antidiabetic and hypolipidemic potentials of the hydroalcoholic extract of A. officinarum (AO) were investigated in the nicotinamide/streptozotocin induced type II diabetic rats. METHODS: Male Wistar rats were divided into following six groups: Group I was normal control rats. Group II: normal diabetic control, Group III: Diabetic rats treated with glibenclamide (0.25 mg/kg), IV, V and VI: Diabetic rats treated with 100, 200 and 500 mg/kg AO hydroalcoholic extract by daily gavage for 28 days, respectively. At the end of treatment, biochemical analysis, histological study, phytochemical analysis and acute toxicity tests were carried out. RESULTS: The results show significant reduction in blood glucose, serum lipid profiles, and liver enzyme levels in diabetic rats compared with diabetic control in AO treated group. CONCLUSIONS: In conclusion, the present study demonstrated that AO extract had significant (p<0.05) antidiabetic and anti-hyperlipidemia effects in addition to hepatoprotective effect in type II diabetic rats.

Effect of Alpinia officinarum extract on reproductive damages in streptozotocin induced diabetic male rats.

PURPOSE: Infertility is one of the systemic problems in diabetic men. The purpose of the present study is investigation of the effects of the Alpinia officinarum (AO) hydro-alcoholic extract on the reproductive system damages in diabetic male rats. METHODS: Twenty four male rats were randomly assigned into 4 groups (n = 6); i.e., control, diabetic control, and diabetic rats treated orally with AO extract (200 and 500 mg kg-1). A single dose (60 mg kg-1) of streptozotocin (STZ) was injected intraperitoneally (IP) to induce diabetes. After 8 weeks of treatment, blood samples, testis, and cauda epididymis were excised to evaluate specific hormonal changes, sperm parameters, and testis morphology. RESULTS: Diabetic control rats showed remarkably lower body and testicular weights, testicular volumes, and sperm parameters compared with the control group (p <0.05). Diabetic control rats also exhibited significantly decreased serum testosterone and follicle stimulating hormone (FSH). Sperm parameters were considerably enhanced in diabetic animals gavaged with AO extract. Testosterone levels were significantly elevated by administrating 500 mg kg-1 AO extract to the diabetic control rats (p <0.05). The morphological assessment of testis of treatment group (500 mg kg-1) indicated remarkable differences (p <0.05) by increasing the seminiferous tubules diameter (STD) and thickness of the seminiferous epithelium (TSE) compared with diabetic control rats. CONCLUSION: As demonstrated by the results, AO extract ameliorated sperm damage and improved sperm morphology besides improving histological damage in the testis in diabetic rats. In addition, the dose of 500 mg kg-1 worked more efficiently than 200 mg kg-1.

Hypoglycemic, hepatoprotective, and hypolipidemic effects of hydroalcoholic extract of Eryngium billardieri root on nicotinamide/streptozotocin-induced type II diabetic rats.

BACKGROUND AND PURPOSE: Erynginum billardieri has been used to control diabetes in traditional medicine. This research was performed to study the antidiabetic, hepatoprotective, and hypolipidemic effects of E. billardieri root extract (EBRE) on streptozotocin/nicotinamide-induced type 2 diabetic male rats. EXPERIMENTAL APPROACH: Type two diabetic animals were treated by three different doses of EBRE (100, 200, and 400 mg/kg), orally administered for 4 weeks. Ultimately, after anesthesia, the glucose, insulin, lipid profiles, hepatic enzyme levels in the blood and liver, and pancreas tissues of the animals were analyzed. FINDINGS/RESULTS: Induction of diabetes caused a diminution in insulin level, high-density lipoprotein (HDL), and significantly enhanced the level of other lipid profiles, glucose, and liver enzymes (P < 0.05). Administration of the EBRE to diabetic-male rats significantly reduced glucose level, lipid profiles, and liver enzymes, and increased the level of HDL to near normal. CONCLUSION AND IMPLICATIONS: The results of the present study showed that E. billardieri had a positive effect on diminishing the lipid profiles, liver enzymes, and controlling diabetes. The most effective dose was found to be 100 mg/kg.

The effect of hydroalcoholic extract of Nigella Sativa seed on dehydroepiandrosterone-induced polycystic ovarian syndrome in rats: An experimental study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women. OBJECTIVE: The aim of this study was to investigate the therapeutic effect of hydroalcoholic extract of Nigella sativa (N. sativa) seed as a plant, the consumption of which has been recommended in Islam, on dehydroepiandrosterone (DHEA)-induced PCOS rats. MATERIALS AND METHODS: This experimental study was carried out on 36 Wistar female rats (3 wk, 60 ± 10 gr). Then rats were divided into 6 groups (n = 6/each): control; PCOS-induced (DHEA 60 mg/kg/sc); PCOS+ Metformine (30 mg/kg); and three experimental groups receiving DHEA + hydroalcoholic extract of N. sativa seeds in doses of 50, 100 and 200 mg/kg, respectively. Blood samples were taken for the evaluation of sexual hormones, oxidative stress, glucose, and insulin after 30 days of treatment. Ovarian tissue was used for histopathological study. RESULTS: The serum levels of luteinizing hormone, testosterone, glucose, insulin resistance, malondialdehyde, and insulin (p ≤ 0.001) and estrogen increased while the levels of progesterone (p = 0.01) and antioxidant enzymes in the PCOS group decreased (p ≤ 0.001). CONCLUSION: The administration of the N. sativa extract to the PCOS rats resulted in remarkable changes in the serumic factors relative to the PCOS group. In addition, the extract improved the structure of the ovarian tissue in the PCOS rat. The histopathological results which are in accordance with biochemical findings imply that N. sativa seed could be useful in the treatment of PCOS, the higher doses of the extract being more effective.

Comparative study of magnesium, sodium valproate, and concurrent magnesium-sodium valproate therapy in the prevention of migraine headaches: a randomized controlled double-blind trial.

OBJECTIVE: This study aimed to assess the efficacy of concurrent magnesium-sodium valproate therapy and compare it with either magnesium or sodium valproate alone in migraine prophylaxis. MATERIALS AND METHODS: This randomized single-center double-blind parallel-group controlled clinical trial study was conducted on migraine patients within the age range of 18-65 years. The subjects with at least four monthly attacks were randomly assigned to group A (n = 82) sodium valproate, group B (n = 70) magnesium with sodium valproate, and group C (n = 70) magnesium. The patients passed a one-month baseline without prophylactic therapy and then received a 3-month treatment. The characteristics of migraine, including frequency, severity, duration of the attacks, and the number of painkillers taken per month, were monthly recorded in each visit. The Migraine Disability Assessment (MIDAS) and Headache Impact Test-6 (HIT-6) scores were recorded at the baseline and after 3 months of treatment in each group. Within- and between-group analyses were performed in this study. RESULTS: The obtained results revealed a significant reduction in all migraine characteristics in all groups compared to those reported for the baseline (P <  0.001). Intragroup data analysis indicated that there was no statistically significant difference in headache frequency between groups A and B in the third month (P = 0.525); nevertheless, three other parameters showed a significant reduction in group B, compared to those reported for group A in the third month (P <  0.05). On the other hand, group C could not effectively reduce measured parameters in the patients, compared to groups A and B after 3 months (P <  0.001). Furthermore, the MIDAS and HIT-6 scores significantly diminished in groups A, B, and C compared to those reported at the baseline (P <  0.001), and these changes were more significant in groups A and B than in group C (P <  0.001). CONCLUSION: The obtained results of this study revealed that magnesium could enhance the antimigraine properties of sodium valproate in combination therapy and reduce the required valproate dose for migraine prophylaxis.

Effectiveness of Religious-Spiritual Group Therapy on Spiritual Health and Quality of Life in Methadone-treated Patients: A Randomized Clinical Trial.

BACKGROUND: Spirituality is one of the most important factors that can contribute to the recovery of substance use disorder (SUD). The objective of this study is to evaluate the efficacy of the religious-spiritual group therapy on the spiritual health and the quality of life in methadone-treated patients. METHODS: This study was carried out in Qom City, Iran, in 2018. 72 methadone-treated patients were randomly selected and assigned in two groups: the experimental group (which received religious-spiritual therapy) and control group (which received no treatment). At the beginning of the study (pre-test), eight weeks after the start of the study (post-test), and three months after the start of the study (follow-up test), all participants completed the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire and the Spiritual Well-Being Scale (SWBS). Participants in the experimental group received 8 sessions (90 minutes for each session) of spiritual and religious training, while the control group received no religious-spiritual intervention; it just was trained with general information on addiction. Data were analyzed using SPSS software and descriptive and inferential statistics methods. FINDINGS: The results of repeated measures analysis of variance (ANOVA) showed that there was no significant difference between the intervention and control groups in the pretest, but religious-spiritual training significantly increased spiritual health and the patients' quality of life (P < 0.001). CONCLUSION: Religious-spiritual education can improve the quality of life and spiritual well-being in methadone-treated patients. The findings suggest that religious -spiritual education can be considered as an inexpensive, accessible, useful, and effective treatment for SUD treatment.

Improvement of memory deficits in the rat model of Alzheimer's disease by erythropoietin-loaded solid lipid nanoparticles.

Erythropoietin (EPO), a hematopoietic factor, is one of the promising neuroprotective candidates in neurodegenerative disorders such as Alzheimer's disease (AD). Due to the high molecular weight, hydrophilicity and rapid clearance from circulation, EPO could not completely pass the blood-brain barrier in the case of systemic administration. To overcome this limitation, EPO-loaded Solid Lipid Nanoparticle (EPO-SLN) was developed in this study using a double emulsion solvent evaporation method (W1/O/W2). Glycerin monostearate (GMS), span®80/span®60, Dichloromethane (DCM) and tween®80 were chosen as lipid, internal phase surfactants, solvent, and external aqueous phase surfactant, respectively. After physicochemical evaluations, the effect of EPO-SLN on the beta-amyloid-induced AD-like animal model was investigated. In vivo evaluations, it was demonstrated that the memory was significantly restored in cognitive deficit rats treated with EPO-SLN compared to the rats treated with native drug using the Morris water maze test. In addition, EPO-SLN reduced the oxidative stress, ADP/ATP ratio, and beta-amyloid plaque deposition in the hippocampus more effectively than the free EPO. Hence, the designed SLN can be regarded as a promising system for safe and effective delivery of EPO in the AD.

"Evaluation of the effect of roasted lentil flour (lentil savigh) as a functional food in menstrual bleeding reduction".

BACKGROUND: Menorrhagia is a regular menstrual cycle lasting more than seven days and/or blood loss over 80 mL per cycle. One of the herbs recommended in Iranian traditional medicine for menorrhagia treatment is lentil savigh, which is the flour made from roasted lentil (Lens culinaris medic). METHODS: The current randomized clinical trial was conducted on 54 patients within the age range of 18 to 50 years randomly divided into two groups. The treatment group took three 10-gram lentil savigh sachets in the morning. The control group was treated with 500 mg tranexamic acid capsule every eight hours, both from the first day of menstruation for seven days. Patient's bleeding was evaluated by the pictorial blood loss assessment chart (PBAC), before and in each of the three treatment cycles. Quality of life was evaluated by the menorrhagia questionnaire (MQ) at the beginning and the end of the study for each patient. RESULTS: The mean (SD) of PBAC scores significantly decreased before and after three cycles from 383.5(163) to 222.1(128.6) in the lentil savigh group (P < 0.0001), and from 333.8(141.3) to 239.1(132.6) in the tranexamic acid group (P < 0.0001). There was no significant difference between the two groups (P < 0.6). Quality of life significantly improved in the lentil savigh group from 61.5(12.3) to 34.4(14.6) in comparison with that of the tranexamic acid group changing from 56.3(11.1) to 46.8(12.7) (P < 0.004). CONCLUSION: Both products were effective in menstrual bleeding reduction, but lentil savigh improved the quality of life more effectively. Therefore, lentil savigh, as a functional food, could be introduced as a good initial choice for menorrhagia treatment.

Use of artificial neural networks for analysis of the factors affecting particle size in mebudipine nanoemulsion.

In this study, a nanoemulsion containing mebudipine [composed of ethyl oleate (oil phase), Tween 80 (T80), Span 80 (S80) (surfactants), polyethylene glycol 400, ethanol (cosurfactants), and deionized water] was prepared with the aim of improving its bioavailability for an effective antihypertensive therapy. Particle size of the formulation was measured by dynamic light scattering. Then, artificial neural networks were used in identifying factors that influence the particle size of the nanoemulsion. Three variables, namely, amount of surfactant system (T80 + S80), amount of polyethylene glycol, and amount of ethanol as cosurfactants, were considered as input values and the particle size was used as output. The developed model showed that all the three inputs had some degrees of effect on particles size: increasing the value of each input decreased the size. Furthermore, amount of surfactant was found to be the dominant factor in controlling the final particle size of nanoemulsion. Communicated by Ramaswamy H. Sarma.

Design and evaluation of oral nanoemulsion drug delivery system of mebudipine.

A nanoemulsion drug delivery system was developed to increase the oral bioavailability of mebudipine as a calcium channel blocker with very low bioavailability profile. The impact of nano-formulation on the pharmacokinetic parameters of mebudipine in rats was investigated. Nanoemulsion formulations containing ethyl oleate, Tween 80, Span 80, polyethylene glycol 400, ethanol and deionized water were prepared using probe sonicator. The optimum formulation was evaluated for physicochemical properties, such as particle size, morphology and stability. The particle size of optimum formulation was 22.8 ± 4.0 nm. Based on the results of this study, the relative bioavailability of mebudipine nanoemulsion was enhanced by about 2.6-, 2.0- and 1.9-fold, respectively, compared with suspension, ethyl oleate solution and micellar solution. In conclusion, nanoemulsion is an interesting option for the delivery of poorly water soluble molecules, such as mebudipine.

Improved oral bioavalability of mebudipine upon administration in PhytoSolve and Phosal-based formulation (PBF).

The aim of this investigation was to examine the efficacy of PhytoSolve and Phosal-based formulation (PBF) to enhance the oral bioavailability of mebudipine, which is a poorly water-soluble calcium channel blocker. The solubility of mebudipine in various oils was determined. PhytoSolve was prepared with a medium-chain triglyceride (MCT) oil (20%), soybean phospholipids (5%), and a 70% fructose solution (75%). The influence of the weight ratio of Phosal 50PG to glycerol in PBF on the mean globule size was studied with dynamic light scattering. The optimized formulation was evaluated for robustness toward dilution, transparency, droplet size, and zeta potential. The in vivo oral absorption of different mebudipine formulations (PhytoSolve, PBF, oily solution, and suspension) were evaluated in rats. The optimized PBF contained Phosal 50PG/glycerol in a 6:4 ratio (w/w). The PBF and PhytoSolve formulations were miscible with water in any ratio and did not demonstrate any phase separation or drug precipitation over 1 month of storage. The mean particle size of PhytoSolve and PBF were 138.5 ± 9.0 and 74.4 ± 2.5 nm, respectively. The in vivo study demonstrated that the oral bioavailability of PhytoSolve and PBF in rats was significantly higher than that of the other formulations. The PhytoSolve and PBF formulations of mebudipine are found to be more bioavailable compared with suspension and oily solutions during an in vivo study in rats. These formulations might be new alternative carriers that increase the oral bioavailability of poorly water-soluble molecules, such as mebudipine.

Evaluation of Lipid-based Drug Delivery System (Phytosolve) on Oral Bioavailability of Dibudipine.

The objective of present study was to evaluate pharmacokinetic parameters of dibudipine Phytosolve after oral administration in rats. The solubility test was carried out to select suitable oily solvent for dibudipine. Phytosolve formulation was prepared with a medium chain triglyceride (MCT) oil (20%), soybean phospholipids (5%) and a 70% fructose solution (75%). The effect of polyol content on the mean globule size of Phytosolve formulation was studied. The optimized formulation was evaluated for robustness toward dilution, transparency, droplet size, zeta potential and transmission electron microscopic analysis. The Phytosolve of dibudipine with an average droplet size of 142.3 ± 4.3 nm and surface charge -18.36 ± 0.37 mv was administered orally to rats. The average relative bioavalabilities of dibudipine in the plasma with Phytosolve were 170.4% and 211.2% as compared to the oily solution and aqueous suspension respectively. So this formulation could be offered as a useful technique to improve the oral delivery of the poorly water soluble drugs such as dibudipine.