The role of megalin in the transport of aminoglycosides across human placenta

Background: Intra-amniotic infections (IAIs) are common complications of labor and delivery. If inadequately treated, these infections can lead to significant morbidity and mortality in the mother and the fetus. Intrapartum aminoglycoside (AG) administration is recommended for the management of IAIs. AGs are known to cross the placenta and achieve bactericidal concentrations in fetal serum. However, the highest and most persistent fetal levels are achieved in renal tissue. So, the fetus may be vulnerable to the nephrotoxic effects of AGs. Megalin, a 600 kDaendocytic receptor, is responsible for the uptake of AGs into renal proximal tubular epithelial cells. This receptor is also expressed in human term placenta and it is reasonable to speculate that it is similarly involved in the placental transport of AGs. However, the mechanisms responsible for placental AG uptake and transport have not yet been characterized. Objective: To evaluate the role of megalin in the transport of AGs across human placenta. Specific aims: (1) To assess and compare megalin expression in term and preterm placental villous tissue, and (2) assess the functional activity of megalin in in vitro placental models. Methods: (1) Following IRB approval, placental tissue samples were collected from pregnant women undergoing term or preterm deliveries. Placental villous tissueswere used to quantify megalin expression by western blotting and q-PCR (2) The human choriocarcinoma cell line (BeWo cells) were grown on Transwell plates, and then megalin expression and function were assessed. Results: Megalin protein and mRNA expression were confirmed in samples of human placental villous tissues. Megalin mRNA expression declined steeply with gestational age till week 31 of gestation then it plateaued thereafter. Also, the expression in the early preterm (n=2) was six fold higher than that of both late preterm (n=3) and term placenta (n=10) (p\u3c0.05). The uptake of 3H-gentamicin by the BeWo cells was time-dependent, saturable (Vmax=42.9 ± 4.9 nmol/mg protein/min; Km=2.93±0.68mM) and partially inhibited by megalin inhibitors. Conclusion: Megalin is expressed in human placental villous tissues as well as the BeWo cells. When grown on Transwell® plates, the BeWo cells appear to be the most appropriate model to study the in vitro transport of AGs across the apical membrane. Time, temperature and concentration dependence of gentamicin uptake in the BeWo cells indicate protein-mediated transport. The inhibition data are consistent with megalin-mediated endocytosis of AGs

Awareness of combined oral contraceptives use among Jordanian women: A cross-sectional study

Purpose: To investigate Jordanian women’s knowledge, attitude, awareness and practice regarding combined oral contraceptives (COCs) benefits and risks.Methods: A cross-sectional study was conducted on 300 Jordanian women attending the Obstetrics and Gynecology clinics at Jordan University Hospital, Amman, Jordan. A closed- and open-ended questionnaire was used to explore Jordanian participants' knowledge, attitude and practice regarding COCs use, effect and side effects. Structured interviews were conducted by a trained research team. Thus, it was a pharmacist-assisted survey, and lay language was used to explain difficult medical terminologyResults: Most of participants were prescribed COCs by their physicians (77.1 %), half of them depend on others' experiences and media as sources of information rather than consulting their healthcare team. Half of participants have an idea of non-contraception uses of COCs (50.3 %). One fourth of women (26.0 %) believed that using COCs decreases fertility or even causes infertility, especially if used before their first pregnancy (43.3 %). Women in their middle age were more uncertain about the relation between COCs use and anemia (p = 0.014) or dysmenorrhea pain (p = 0.005). While women who used COCs believed more that the pills regulate menstruation (p < 0.001) and decrease dysmenorrhea pain (p < 0.001) compare with women who had never used COCs pills. Women in general are uncertain if COCs use has negative or positive relation with some types of cancer such as ovarian, cervical and breast. Women who are not affiliated to the healthcare professions were more uncertain about the relation between COCs use and atherosclerosis risk (p = 0.002), MI (p = 0.025) and stroke risk (p = 0.035).Conclusion: There is insufficient awareness and knowledge of the beneficial and non-contraceptive uses of COCs. Educational programs are needed to improve women’s awareness of the benefits and risks of COCs. Keywords: Combined oral contraceptives, COCs, Knowledge, Attitude, Practice, Beliefs, Benefits, Risk

Practice of pharmaceutical care in community pharmacies in Jordan

Purpose: To describe the current role played by pharmacists in delivering  pharmaceutical care (PC) in community pharmacies in Jordan (current activities and practices undertaken in the community and extent of provision of PC standards), pharmacists’ perspectives on PC implementation and barriers to implementing PC practices.Methods: This cross sectional study was conducted in 2014 in Amman, the capital of Jordan and Zarqa, the second biggest city in Jordan. The study involved a  validated questionnaire administered at random by trained pharmacy students to 180 community pharmacists. The questionnaire was designed to collect  demographic data, pharmacy practice features displayed by the pharmacists, dispensing activities undertaken, internationally proposed PC practice standards in community pharmacy settings, inter/intra-professional and public heath activities and barriers that may hinder the implementation of PC practice in Jordan.Results: 163 pharmacists agreed to participate in the study (response rate was 90.5 %). Most dispensing activities (98.1%) in the pharmacies were done under the supervision of pharmacists. All pharmacists were willing to implement PC, and nearly all of them (98.8 %) provided basic information about medication use. Nevertheless, only 31.0 % adapted standard procedures for patient’s data collection, 23.1 % formulated a therapeutic plan to be included within the patient’s permanent record in their pharmacy, 24.2 % documented over-the-counter  recommendations, and 29.7 % allocated time to discuss patient’s care plans.  Identified barriers preventing the provision of PC practice included lack of training on the concept (44.9 %) and lack of acceptability from the physicians (43.4 %).Conclusion: Although participating pharmacists showed willingness to implement PC practice, their actual application to the practice was found to be limited. Lack of adequate pharmaceutical training and acceptability by the physicians are the major barriers towards the provision of PC practice in the country.Keywords: Community pharmacists, Pharmaceutical care, Barriers, Jorda

Prevalence of Food Insecurity among Women in Northern Jordan

Food insecurity—not having sufficient quantities of good-quality foods—is inversely related to physical and mental health and directly related to poor dietary intake. The objectives of this research were to (a) measure the prevalence of food insecurity among women in northern Jordan, (b) study the socioeconomic factors associated with an increased risk of food insecurity, and (c) investigate the relationship between household food insecurity and women's reported body-weight. This cross-sectional study was conducted using an interview-based questionnaire. In total, 500 women were interviewed in the waiting rooms of the outpatient clinics of two major public hospitals in northern Jordan. Food insecurity was assessed using the short form of the U.S. food security survey module. The prevalence of food insecurity was 32.4%. Income below the poverty-line, illiteracy, unemployment, rented housing, and woman heading the household were among the socioeconomic factors that increased the probability of food insecurity. No evidence was found to support the relationship between obesity and food insecurity. Except grains, food-insecure women with hunger had lower intake of all food-groups. This study demonstrated that the problem of food insecurity is present in Jordan. Food-insecure women with hunger are at a risk of malnutrition. Interventions that target reduction of the factors associated with food insecurity are necessary

Investigation into the prophylactic and therapeutic activity of coenzyme Q10 against COVID-19

Purpose: To evaluate the anti-SARS CoV-2 effect of Coenzyme Q 10, Ubiquinol-10, and idebenone, which have beneficial therapeutic applications against diverse virus types, using molecular docking approach.Methods: The potential activity of Coenzyme Q10, Ubiquinol-10, and Idebenone against viral infections was explored through the collection of data from relevant literature, and by modelling these compounds virtually, using in silico investigation methods.Results: Coenzyme Q10 and ubiquinol-10 showed significant docking performance. They interacted with numerous amino acid residues of the main protease of SARS-CoV-2 ACE2 (7C8J), Alpha thrombin (1AE8), TYRO (4TS1) protein targets sides, SARS-coronavirus Orf7a accessory protein (1XAK), TNF (1RJ8), and Cytokine/receptor (1I1R).Conclusion: The findings of our study showed promising inhibitory activities of the selected compounds against the main proteases of SARS-CoV-2. Consequently, these compounds have theoretical effects on inhibiting the viral entry, reproduction, and ultimately the prevention and/or treatment of the SARSCoV2 infection

Prevalence of Food Insecurity among Women in Northern Jordan

Food insecurity\u2014not having sufficient quantities of good-quality foods\u2014is inversely related to physical and mental health and directly related to poor dietary intake. The objectives of this research were to (a) measure the prevalence of food insecurity among women in northern Jordan, (b) study the socioeconomic factors associated with an increased risk of food insecurity, and (c) investigate the relationship between household food insecurity and women\u2019s reported body-weight. This cross-sectional study was conducted using an interview-based questionnaire. In total, 500 women were interviewed in the waiting rooms of the outpatient clinics of two major public hospitals in northern Jordan. Food insecurity was assessed using the short form of the U.S. food security survey module. The prevalence of food insecurity was 32.4%. Income below the poverty-line, illiteracy, unemployment, rented housing, and woman heading the household were among the socioeconomic factors that increased the probability of food insecurity. No evidence was found to support the relationship between obesity and food insecurity. Except grains, food-insecure women with hunger had lower intake of all food-groups. This study demonstrated that the problem of food insecurity is present in Jordan. Food-insecure women with hunger are at a risk of malnutrition. Interventions that target reduction of the factors associated with food insecurity are necessary

Reproductive and fetal toxicity studies of histamine H3 receptor antagonist DL76 used in mice to prevent maximal electroshock-induced seizure

Introduction: Brain histamine is considered an endogenous anticonvulsant and histamine H1 receptor. H1R antagonists have, in earlier studies, been found to induce convulsions. Moreover, research during the last two decades has provided more information concerning the anticonvulsant activities of histamine H3R (H3R) antagonists investigated in a variety of animal epilepsy models.Methods: Therefore, the in vivo anticonvulsant effect of the H3R antagonist DL76, with proven high in vitro affinity, in vitro selectivity profile, and high in vivo antagonist potency in mice against maximal electroshock (MES)-induced seizures in mice, was assessed. Valproic acid (VPA) was used as a reference antiepileptic drug (AED). In addition, DL76 was tested for its reproductive and fetal toxicity in the same animal species.Results and discussion: Our observations showed that acute systemic administration (intraperitoneal; i.p.) of DL76 (7.5 mg/kg, 15 mg/kg, 30 mg/kg, and 60 mg/kg, i.p.) provided significant and dose-dependent protection against MES-induced seizures in female and male mice. Moreover, the DL76-provided protective effects were comparable to those offered by the VPA and were reversed when animals were co-administered the CNS-penetrant selective H3R agonist R-(α)-methylhistamine (RAM, 10 mg/kg, i.p.). Furthermore, the administration of single (7.5 mg/kg, 15 mg/kg, 30 mg/kg, or 60 mg/kg, i.p.) or multiple doses (3 × 15 mg/kg, i.p.) of H3R antagonist DL76 on gestation days (GD) 8 or 13 failed to affect the maternal body weight of mice when compared with the control mice group. No significant alterations were detected in the average number of implantations and resorptions between the control and DL76-treated groups at the early stages of gestation and the organogenesis period. In addition, no significant differences in the occurrence of skeletal abnormalities, urogenital abnormalities, exencephaly, exomphalos, facial clefts, and caudal malformations were observed. The only significant abnormalities witnessed in the treated groups of mice were in the length of long bones and body length. In conclusion, the novel H3R antagonist DL76 protected test animals against MES-induced seizures and had a low incidence of reproductive and fetal malformation with decreased long bone lengths in vivo, signifying the potential therapeutic value of H3R antagonist DL76 for future preclinical as well as clinical development for use in the management of epilepsy

Is It Just About Physical Health? : An Online Cross-Sectional Study Exploring the Psychological Distress Among University Students in Jordan in the Midst of COVID-19 Pandemic

Background: Since the spread of COVID-19 on a global scale, most of efforts at national and international levels were directed to mitigate the spread of the disease and its physical harm, paying less attention to the psychological impacts of COVID-19 on global mental health especially at early stages of the pandemic. Objectives: This study aimed to assess and explore (i) The levels of psychological distress and its correlates (ii) Motivation for distance learning (iii) Coping activities and pandemic related concerns, among university students in Jordan in the midst of COVID-19 pandemic. Methods: A cross-sectional study was conducted using an online self-administered questionnaire. The measure of psychological distress was obtained using the 10-item Kessler Psychological Distress Scale, while other questions have explored our study’s second and third aims. Results: A total of 381 completed questionnaires were included in the analysis. Female participants slightly predominated the sample (n = 199, 52.2%). The respondents aged 18–38 years (mean 22.6 years, SD: 3.16). Concerning distress severity, most of respondents were regarded as having severe psychological distress (n = 265, 69.5%). 209 students (54.9%) reported that they had no motivation for distance learning. Ordinal logistic regression revealed a significant correlation between distress severity and many predictors. Among the predictors that were found to act as protective factors against higher levels of distress included older age (aOR = 0.64, P = 0.022; 95% CI: 0.44–0.94), and having a strong motivation for distance learning (aOR = 0.10, P = 0.048; 95% CI: 0.01–0.96). In contrary, being a current smoker (aOR = 1.99, P = 0.049; 95% CI: 1.10–3.39), and having no motivation for distance learning (aOR = 2.49, P = 0.007; 95% CI: 1.29–4.80) acted as risk factors for having higher levels of psychological distress among the students. The most common coping activity reported was spending more time on social media platforms (n = 269, 70.6%), and 209 students (54.9%) reported distance learning as their most distressing concern. Conclusion: The COVID-19 pandemic and related control measures could impact the mental health of individuals, including students. We recommend a nationwide psychological support program to be incorporated into Jordan’s preparedness plan and response strategy in combating the COVID-19 pandemic