Investigating effects of hydroalcoholic extract of saffron on sex hormones in female rats undergoing chemotherapy with cyclophosphamide

Cyclophosphamide is an antineoplastic medicine that causes disorder in functions of the body systems. Thus, the purpose of this study is to investigate the effect of hydroalcoholic extract of saffron on improving the complications of cyclophosphamide on sex hormones. Fifty-six adult female Wistar rats were randomly divided into seven groups; control, sham (received distilled water, solvent extract, and drug), experimental groups 1, 2, and 3 (received cyclophosphamide (5 mg/kg/bw) + hydroalcoholic extract of saffron (2, 1, and 0.5 g/kg/bw), experimental group 4 (saffron 2 g/kg/bw), and experimental group 5 (cyclophosphamide 5 mg/kg/bw). Cyclophosphamide was given intraperitoneally, and extract by gavage was prescribed for 21 days. At the end of the experiment, after blood and preparation of serum, ELISA method was used for measuring the estrogen, progesterone, FSH, and LH hormones. Data and LSD test were analyzed with SPSS software (version 18). Results show that the concurrent use of low-dose cyclophosphamide and saffron extract can reduce toxic effect of cyclophosphamide on pituitary-gonadal axis and cause estrogen to be produced.     

Vanillin confers antifungal drug synergism in Candida albicans by impeding CaCdr2p driven efflux

AimAmong the most common mechanisms of multidrug resistance (MDR) in prevalent human fungal pathogen, Candida albicans, overexpression of drug efflux pumps remains the predominant mechanism. Hence to inhibit efflux pumps and chemosensitize C. albicans against traditional antifungal drugs still represents an attractive approach. The present study aimed to analyze the effect of Vanillin (Van), a natural food flavoring agent, on drug efflux pump activity of Candida albicans.Methods and resultsWe observed that Van specifically inhibits Candida drug resistance protein 2 (CaCdr2p) activity belonging to ATP Binding Cassette (ABC) superfamily as revealed by abrogated rhodamine 6G efflux and nile red accumulation assay with CaCdr2p over expressing strain. Insight studies into the mechanisms suggested that abrogated efflux by CaCdr2p is due to competitive mode of inhibition by Van as depicted by Lineweaver-Burk plot. RT-PCR, western blot and confocal microscopy further unraveled that Van leads to reduced expression of CDR2 and CaCdr2p mislocalization respectively. Furthermore, Van sensitizes the azole sensitive and resistant clinical matched pair of isolates Gu4/Gu5 and led to abrogated rhodamine 6G efflux and depleted ergosterol. Furthermore, Van synergizes with membrane targeting drugs fluconazole and amphotericin B as their fractional inhibitory coefficient index was less than 0.5.ConclusionVan being a potent inhibitor of CaCdr2p and chemosensitizing of drug resistant C. albicans warrants further studies to be exploited as effective antifungal agent.     

Safe Sound Exposure in the Fetus and Preterm Infant

Exposure to sound can have beneficial and harmful effects on the developing fetus and preterm infant. Although recommendations for safe exposure to sound have existed for more than three decades, reports indicate that these recommendations are not being followed. Recommendations are made to promote attention to the problem of unsafe exposure to sound in early development, and a multidisciplinary team, including representatives from disciplines beyond medicine and nursing, must readdress safe exposure.     

Insights into the biochemical features and immunogenic epitopes of common bradyzoite markers of the ubiquitous Toxoplasma gondii

The widespread distribution of Toxoplasma gondii (T. gondii) infection and its harsh outcomes in pregnant women and immunocompromised patients lead researchers towards vaccination strategies. The present in silico investigation was done to reveal biophysical properties and immunogenic epitopes of six bradyzoite markers for rational vaccine design in future. For this purpose, different web servers were used to predict antigenicity, allergenicity, solubility, physicochemical properties, post-translational modification sites (PTMs), the presence of signal peptide and transmembrane domains. Moreover, the secondary and tertiary structures of the proteins were revealed followed by refinement and validation. Finally, NetCTL server was used to predict cytotoxic T-lymphocyte (CTL) epitopes, with subsequent immunogenicity analysis. Also, IEDB server was utilized to predict helper T-lymphocyte (HTL) epitopes, followed by IFN-γ and IL-4 induction, antigenicity and population coverage analysis. As well, several linear antigenic B-cell epitopes were found, with good water solubility and without allergenicity. Totally, these proteins showed appropriate antigenicity, abundant PTMs as well as many CTL, HTL and B-cell epitopes, which could be directed for future vaccination studies in the context of multi-epitope vaccine design.     

Ultrastructural changes in rat ovarian cells of fetuses and neonates from diabetic mothers

Maternal diabetes leads to increased blood glucose concentration in the mother and consequently in the fetus, causing various neonatal problems. This study was conducted to evaluate the effect of maternal diabetes on fetal ovarian structure. Forty adult female rats were divided into two equal groups. Diabetes was induced in one group by alloxan. Both groups became pregnant by natural mating. At days 14 to 20 of pregnancy and day 30, day 60, and day 90 after birth, the fetuses and neonates were collected from both groups and the female genital system was isolated from them. The numbers of germ cells were measured using routine histological techniques in fetuses. In the neonatal ovarian samples, various cellular parameters were determined using transmission electron microscopy (TEM) technique. Results revealed a significant decrease in the number of germ cells in the fetal female gonads in the gonads of fetuses from diabetic mothers compared to those of control. Results of TEM revealed some differences in the luteal cells and oocytes of primordial follicles in ovaries of neonates from diabetic mothers compared to that of control. Mitochondrial abnormalities were seen as mitochondrial cristae were destroyed and vacuolation occurred in the mitochondria and the nuclei of luteal cells were darken and condensed. It is generally concluded that maternal hyperglycemia affects fetal female gonads illustrated by a decrease in the oocytes and alteration in the mitochondria and nuclei of oocytes and luteal cells in neonatal ovaries.     

Efficacy and safety profile of a single dose of hydromorphone compared with morphine in older adults with acute,severe pain: A prospective,randomized, double-blind clinical trial

Background: Older adults (ie, those aged ≥65 years) are the fastest growing segment of the US population, with an estimated ~71 million expected by 2030. Over the past 10 years, there has been an 11% increase in the number of emergency department (ED) visits by older adults, and pain is their most common chief complaint.Objective: The goal of this study was to compare weight-based IV hydromorphone and IV morphine in adults aged ≥65 years presenting to the ED with acute, severe pain.Methods: This was a prospective, randomized, double-blind clinical trial of older adults with acute, severe pain at an adult, urban academic ED. Patients were randomly allocated to receive a single dose of 0.0075-mg/kg IV hydromorphone or 0.05-mg/kg IV morphine. The primary outcome was the between-group difference in decrease in pain from baseline to 30 minutes after the medications were infused. Patients' degree of pain was measured on a numerical rating scale (NRS) where “0” was defined as “no pain” and “10” was defined as “the worst pain possible.” Adverse effects, pain reduction at 10 minutes and 2 hours postbaseline, patient evaluations of satisfaction and pain relief at 30 minutes postbaseline, and use of additional analgesics and antiemetics were tracked as secondary outcomes.Results: A total of 194 patients were randomized to treatment; 183 patients (hydromorphone group, n = 93; morphine group, n = 90 [overall mean (SD) age, 75 (8) years]) had sufficient data for analysis at the primary end point of 30 minutes postbaseline. The mean decrease in pain from baseline to 30 minutes in patients allocated to IV hydromorphone was 3.8 versus 3.3 NRS units in patients allocated to IV morphine. This difference of 0.5 NRS unit (95% CI, ?0.2 to 1.3) was neither clinically nor statistically significant. A majority of patients in both groups (57.0% randomized to hydromorphone and 58.9% randomized to morphine) failed to achieve a ≥50% reduction in pain within 30 minutes of treatment. The incidence of adverse effects from baseline to 30 minutes was not statistically different in the 2 groups.Conclusions: A single dose of IV hydromorphone at 0.0075 mg/kg was neither clinically nor statistically different from IV morphine at 0.05 mg/kg for the treatment of acute, severe pain at 30 minutes postbaseline in these older adults in the ED. The incidence of adverse effects was not statistically different. Our data suggest that hydromorphone and morphine in the doses given had similar efficacy and safety profiles in these older adults. Neither regimen provided ≥50% pain relief for the majority of patients. Future investigations of acute pain management in older adults should examine the efficacy and safety of higher initial (loading) doses of opioids titrated at frequent intervals until adequate analgesia is achieved.     

Homocysteine level in Iranian patients with premature acute myocardial infarction

Homocysteine may impair vascular endothelial cell function. Besides, it may also induce cell damage,smooth muscle cell proliferation, thrombogenesis and oxidation of low-density lipoproteins.     

Mucormycosis after scorpion sting: case report

Mucor is a fungus, which give rise to opportunistic infection in immunocompromised patients. We described a 55‐year‐old immunocompetent woman with cutaneous mucormycosis after scorpion sting. Mucormycosis may happen in patients with intact immunity and is not allocated only to patients with immune deficiency.