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PurposeDevelopment and validation of a selective analytical method to accurately and precisely quantify nicotine and cotinine levels in rat's plasma after exposure to tobacco cigarettes and tobacco water-pipe.MethodsAn easy HPLC-Photodiode-Array Detection (PDA) method was developed and validated for simultaneous determination of nicotine and cotinine levels in plasma of 15 rats (10 rats after tobacco products exposure and 5 control rats). Nicotine and cotinine were extracted in one step from plasma using acetonitrile and concentrated to lowest volume using nitrogen stream.ResultsThe developed method offered a rapid analysis time of 14 min with single step of analytes extraction from rat's plasma with recovery percentage range between 93 and 95% and excellent linearity with correlation factor more than 0.994 with analytical range between 50 and 1000 ng mL−1 and LOD of 25 ng mL−1 and 23 ng mL−1 for nicotine and cotinine, respectively. The analysis of rat's plasma after 28 days of exposure to tobacco cigarettes and tobacco water-pipe revealed that the average concentrations of 376 ng mL−1 for cotinine and 223 ng mL−1 for nicotine were obtained after tobacco cigarettes exposure, and 220 ng mL−1 for cotinine and 192 ng mL−1 for nicotine after tobacco water-pipe exposure.ConclusionHigher nicotine and cotinine levels were found in plasma after tobacco cigarettes exposure than water-pipe exposure which may have potential undesirable effects on passive smokers in both cases.

Grape seed of Obeidi, a white Lebanese autochthonous variety, was previously tested in different studies as a valuable source of bioactive molecules such as polyphenols, oils, and proteins by means of extraction procedures for the development of cosmetic and therapeutic products. However, an un-valorized, exhausted grape seed residue remains as “secondary waste” after the extraction processes. In this study, the exhausted seeds have been further exploited to produce cosmetic scrubs capable of releasing antioxidant molecules during the exfoliation process, in accordance with the principles of the circular economy and going toward a zero-waste process. The deep characterization of the exhausted seeds confirmed the presence of antioxidant phenolic molecules including gallic acid, catechins and protocatechuic acid (0.13, 0.126, and 0.089 mg/g of dry matter DM), and a high phenolic content (11.85 mg gallic acid equivalents (GAE)/g of dry matter (DM)). Moreover, these residues were shown to possess a sandy texture (Hausner ratio (HR): 1.154, Carr index (CI): 0.133, and angle of repose: 31.62 (°) degrees), similar to commercial natural exfoliants. In this respect, exhausted Obeidi grape seed residues were incorporated at increasing concentrations (0.5, 1, 1.5, and 2% w/w) in a cosmetic scrub, and stored for 5 weeks at 4, 25, and 50 °C for stability testing. All tested scrub formulations exhibited good spreadability with a spread diameter of 3.6–4.7 cm and excellent physical stability, as no phase separation or color change were observed after four cycles of heat shock at 4 and 50 °C. Finally, an in vivo skin irritation test showed that the scrub enriched with 1.5% of exhausted Obeidi grape seed residues was the most promising formulation, as it possessed a high amount of phenolic molecules (0.042 ± 0.001 mg GAE/mL of scrub) and good stability and could be safely applied to the skin with no irritation phenomena. Overall results underlined that exhausted grape seed residues can be transformed into promising systems for both physical and chemical exfoliation, thus confirming the importance of the effective exploitation of agro-industrial by-products for the development of high value cosmeceutics towards a more sustainable and zero-waste approach.

Chronic tobacco exposure can alter the endocannabinoid (eCB) system, consequently leading to an anxiety state. In this study, we investigated the effects of waterpipe tobacco smoke (WTS) on cannabinoid receptor 1 and 2 (CBR1 and CBR2) gene and protein expression in mesocorticolimbic brain regions. Using elevated plus maze (EPM) and open field (OF) tests, the effects of WTS exposure on withdrawal-induced anxiety-like behavior were examined. The effect of ceftriaxone (CEF), a β-lactam known to upregulate glutamate transporter 1 (GLT-1), on anxiety and the expression of cannabinoid receptors was also determined. Male Sprague-Dawley rats were randomly assigned to four groups: 1) the Control group was exposed only to standard room air; 2) the WTS group was exposed to tobacco smoke and treated with saline vehicle; 3) the WTS-CEF group was exposed to WTS and treated with ceftriaxone; and 4) the CEF group was exposed only to standard room air and treated with ceftriaxone. Rats were exposed to WTS (or room air) for two hours per day, five days per week for a period of four weeks. Behavioral tests (EPM and OF) were conducted weekly during acute withdrawal, 24 h following WTS exposure. Rats were given either saline or ceftriaxone (200 mg/kg i.p.) for five days during Week 4, 30 min prior to WTS exposure. Withdrawal-induced anxiety was induced by WTS exposure but was reduced by ceftriaxone treatment. WTS exposure decreased CBR1 mRNA and protein expression in the NAc and VTA, but not PFC, and ceftriaxone treatment attenuated these effects. WTS exposure did not change CBR2 mRNA expression in the NAc, VTA, or PFC. These findings demonstrate that WTS exposure dysregulated the endocannabinoid system and increased anxiety-like behavior, and these effects were reversed by ceftriaxone treatment, which suggest the involvement of glutamate transporter 1 in these effects.

Background: The use of health-related applications (apps) on smartphones has become widespread. This is especially of value during the ongoing SAR-COV-2 pandemic, where accessibility to health care services has been greatly limited. Patients with free access to apps can obtain information to improve their understanding and management of health issues. Currently, there are cancer-related apps available on iPhones and androids. However, there are no guidelines to control these apps and ensure their quality. Furthermore, these apps may significantly modify the patients’ perception and knowledge about drug-related health services. Objective: The aim of this study was to assess the convenience, quality, safety and efficacy of apps for cancer patient care. Methods: The study was conducted by searching all apps related to cancer care on both Google Play Store and Apple iTunes Store. A detailed assessment was then performed using the mobile application rating scale (MARS) and risk assessment tools. Results: The results indicated that on a scale from 1-5, 47% of the apps were rated ≥ 4. The MARS assessment of the apps yielded an overall quality rating of 3.38 ± 0.9 (mean ± SD). The visual appeal of the app was found to have a significant effect on app functionality and user engagement. The potential benefits of these apps come with challenges and limitations. Patents related to smartphone applications targeting patients were also discussed. Conclusion: We recommend a greater emphasis toward producing evidence-based apps. These apps should be rigorously tested, evaluated and updated by experts, particularly clinical pharmacists. Also, these apps may alter patient attitudes toward services provided by physicians and pharmacists. Finally, these apps should not replace in-person interactive health services.

Tobacco smoking is a preventable main cause of fatal diseases. Accurate measurements of the effects it has on neurotransmitters are essential in developing new strategies for smoking cessation. Moreover, measurements of neurotransmitter levels can aid in developing drugs that counteract the effects of smoking. The aim of this study is to develop and validate a fast, simultaneous and sensitive method for measuring the levels of neurotransmitters in rat brain after the exposure of tobacco cigarettes. The selected neurotransmitters include dopamine, GABA, serotonin, glutamine and glutamate. The method is based on high-performance liquid chromatography-tandem mass spectrometry. Chromatographic separation was achieved within 3 min using a Zorbax SB C

Purpose: To examine the quality of pharmaceutical experiential training by developing an experiential training survey. Methods: An online survey was placed on E-learning platforms in Jordan and UK to develop a validated instrument that can assess pharmacy students' perceptions of the experiential program implemented in their curricula. Results: A total of 377 students from Jordan (250 students) and the UK (127 students) completed the survey. Principal component analysis was used to conduct exploratory factor analysis and to assess the factor structure for the data. A two-factor model was applied to the data obtained from the students. These factors included students’ feelings toward experiential training (Perceiver Feelings; PF) and their ability to conduct a full Pharmaceutical Care Plan (PCP). Students from both Jordan and the UK showed a higher satisfaction PF score toward the experiential training program compared to PCP. Being female and not having prior practice experience led to significantly lower PCP scores compared to males and having a prior practice experience, respectively. Conclusion: The availability of a validated questionnaire will help in investigating the effectiveness of experiential training courses. Keywords: Experiential training; Factor Analysis; Survey development; Pharmacy

Rhoifolin (ROF) is a bioactive plant flavonoid with potent antioxidant and anti-inflammatory activity. However, no delivery system has yet been developed for ROF to overcome its biopharmaceutical limitations. The purpose of this study was to design a ROF-loaded polymeric nanocarrier as a potential anti-inflammatory nanomedicine. ROF was isolated from Jordanian

Substance abuse is a worldwide problem with serious repercussions for patients and the communities where they live. Pregabalin (Lyrica), is a medication commonly used to treat neuropathic pain. Like other analgesic medications there has been concern about pregabalin abuse and misuse. Although it was initially suggested that pregabalin, like other gabapentinoids, has limited abuse liability, questions still remain concerning this inquiry. Changes in glutamate system homeostasis are a hallmark of adaptations underlying drug dependence, including down-regulation of the glutamate transporter 1 (GLT-1; SLC1A2) and the cystine/glutamate antiporter (xCT; SLC7A11). In this study, it was found that pregabalin (90mg/kg) produces a conditioned place preference (CPP), indicative of reinforcing effects that suggest a potential for abuse liability. Moreover, like other drugs of abuse, pregabalin also produced alterations in glutamate homeostasis, reducing the mRNA expression of Slc1a2 and Slc7a11 in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). Amoxicillin clavulanic acid, a β-lactam antibiotic, blocked the reinforcing effects of pregabalin and normalized glutamate homeostasis. These results suggest that pregabalin has abuse potential that should be examined more critically, and that, moreover, the mechanisms underlying these effects are similar to those of other drugs of abuse, such as heroin and cocaine. Additionally, these results support previous findings showing normalization of glutamate homeostasis by β-lactam drugs that provides a novel potential therapeutic approach for the treatment of drug abuse and dependence.

Objective: This study assesses misconceptions about coronavirus disease 2019 (COVID-19) vaccine and the factors associated with misconception among Jordanians. Methods: A cross-sectional online survey was conducted. The survey was formulated on Google Forms, and was hosted on an online platform. These questions were created based on extensive review of online information about the vaccines. Frequencies and percentages (%) were used for categorical variables, while means and standard deviations (SDs) were used for continuous variables. Stepwise binary logistic regression was conducted to evaluate variables associated with participant’s misconception questions. Results: Of 1195 survey respondents who participated in the study, 41.3% had received the COVID-19 vaccine. The mean misconception score was (60.0 ± 19.1). The statement with the highest mean was “The vaccine hasn’t been tested on enough people” (3.6 ± 1.0). The statement with the lowest mean was “The COVID-19 vaccine includes a microchip to control us” (2.2 ± 1.1) in the conspiracy theory portion. Females, 18- to 29-age group, higher educational level, living in a city, the participants who took lectures about the COVID-19 vaccine and vaccinated participants had higher odds of being in the low misconception level group. Conclusion: Targeted campaigns and vaccine safety information should be part of a broader health education campaign to alleviate vaccination safety concerns.

The outbreak of the novel SARS-CoV-2 virus has an enormous impact on health. People’s views about the virus impact public health efforts to mitigate the pandemic. In this study, we measured misconceptions toward coronavirus in the Jordanian population; 2,544 participants from the Jordanian population completed an online survey. Questions in the survey addressed misconceptions divided into four categories: optimism bias, pessimism bias, magical beliefs, and conspiracy theory beliefs. Questions were evaluated on a Likert scale, and average/median scores for each category were evaluated (“one” high misconception to “five” low misconception). Overall, the most common misconceptions involved conspiracy theory beliefs (2.68 ± 0.83), whereas the least common involved magical beliefs (2.25 ± 0.75). Females had more misconceptions than males (2.52 versus 2.47, P = 0.04). Participants who had attended a lecture on coronavirus, had a higher level of education, worked in a medical field, lived in urban area, or resided in Amman or northern Jordan had fewer misconceptions about SARS-CoV-2/COVID-19 (2.64, 2.34, 2.33, 2.50 and 2.50 versus 2.53, 2.73, 2.72, 2.64, and 2.66, respectively, P < 0.001). The use of social media appeared to be an important factor influencing the likelihood of false beliefs (2.61 versus 2.38, P < 0.001). Understanding of the factors influencing public perceptions surrounding the SARS-CoV-2/COVID-19 pandemic will help public health authorities improve public understanding and compliance with public health recommendations directed at combatting the virus, including the use of surgical masks, thorough handwashing, and avoiding close contact. These messages will be better received by the public through correcting misconceptions surrounding COVID-19.

Alcohol dependence results in long-lasting neuroadaptive changes in meso-corticolimbic system, especially in the nucleus accumbens (NAc), which drives relapse-like ethanol drinking upon abstinence or withdrawal. Within NAc, altered glutamate homeostasis is one of the neuroadaptive changes caused by alcohol dependence. Accumbal glutamate homeostasis is tightly maintained through glutamate transporter 1 (GLT-1) and cystine-glutamate antiporter (xCT). But the role of GLT-1 and xCT in relapse-like ethanol drinking is poorly understood. Here, we used alcohol-preferring (P) rats in relapse-like ethanol drinking paradigm to (a) determine the effect of relapse-like ethanol drinking on gene and protein expression of GLT-1 and xCT in NAc, measured by quantitative polymerase chain reaction (qPCR) and Western blot, respectively; (b) examine if glutamate uptake is affected by relapse-like ethanol drinking in NAc, measured by radioactive glutamate uptake assay; (c) elucidate if upregulation of either/both GLT-1 or/and xCT through ceftriaxone is/are required to attenuate relapse-like ethanol drinking. The GLT-1 or xCT protein expression was suppressed during ceftriaxone treatments through microinjection of GLT-1/xCT anti-sense vivo-morpholinos. We found that relapse-like ethanol drinking did not affect the gene and protein expression of GLT-1 and xCT in NAc. The glutamate uptake was also unaltered. Ceftriaxone (200 mg/kg body weight, i.p.) treatments during the last 5 days of abstinence attenuated relapse-like ethanol drinking. The suppression of GLT-1 or xCT expression prevented the ceftriaxone-induced attenuation of relapse-like ethanol drinking. These findings confirm that upregulation of both GLT-1 and xCT within NAc is crucial for ceftriaxone-mediated attenuation of relapse-like ethanol drinking.

Aim Glutamate has been considered as neurotransmitter that is critical in triggering relapse to drugs of abuse, including ethanol and cocaine. Extracellular glutamate concentrations are tightly regulated by several mechanisms, including reuptake through glutamate transporters. Glutamate transporter type 1 (GLT-1) is responsible for clearing the majority of extracellular glutamate. The astrocytic cystine/glutamate antiporter (xCT) regulates also glutamate homeostasis. In this study, we investigated the effects of cocaine exposure and ampicillin/sulbactam (AMP/SUL), a β-lactam antibiotic known to upregulate GLT-1 and xCT, on relapse-like ethanol intake and the expression of astrocytic glutamate transporters in mesocorticolimbic brain regions. Methods Male alcohol-preferring (P) rats had free access to ethanol for 5 weeks. On Week 6, rats were exposed to either cocaine (20 mg/kg, i.p.) or saline for 12 consecutive days. Ethanol bottles were then removed for 7 days; during the last 5 days, either AMP/SUL (100 or 200 mg/kg, i.p.) or saline was administered to the P rats. Ethanol bottles were reintroduced, and ethanol intake was measured for 4 days. Results Cocaine exposure induced an alcohol deprivation effect (ADE), which was associated in part by a decrease in the expression of GLT-1 and xCT in the nucleus accumbens (NAc) core. AMP/SUL (100 mg/kg, i.p.) attenuated the ADE, while AMP/SUL (200 mg/kg, i.p.) reduced ethanol intake during 4 days of ethanol re-exposure and upregulated GLT-1 and xCT expression in the NAc core, NAc shell and dorsomedial prefrontal cortex (dmPFC). Conclusion This study suggests that these astrocytic glutamate transporters might be considered as potential targets for the treatment of polysubstance abuse.

Introduction\ud The Global Lung Function Initiative (GLI) 2012 introduced new multi-ethnic spirometry reference values for numerous ethnicities. \ud \ud Objectives\ud The aim of this study was to investigate the suitability of the GLI reference values for the adult Jordanian population. Methods: 1875 (1029 females and 846 males) healthy non-smoking adults were enrolled from several locations in Jordan. Spirometry tests were performed. Z scores and predicted normal values were calculated for each participant using GLI 2012 equations in addition to other local equations from the Middle East.\ud \ud Results\ud Our results indicated that none of the GLI 2012 or other regional equations studied produced an acceptable fit to our data. \ud \ud Conclusion\ud A need to formulate a specific equation for the Jordanian population is urgently required to better evaluate their respiratory conditions.\ud Keywords

Oxandrolone (OXA) is an androgen and anabolic steroid (AAS) that is used to reverse weight loss associated with some medical conditions. One of the side effects of OXA is its potential to induce depressive symptoms. Growing evidence suggested that neuroinflammation and cytokines play crucial roles in sickness behavioral and associated mood disturbances. Previous studies showed that metformin attenuated neuroinflammation. This study investigated the potential protective role of metformin against OXA-induced depression-like behavior and neuroinflammation. Twenty- four Wistar male rats were randomly grouped into four groups: the control group (Control) received only vehicle; the oxandrolone group (OXA) received oxandrolone (0.28 mg/kg, i.p); the metformin group (MET) received metformin (100 mg/kg, i.p); and the oxandrolone / metformin group (OXA + MET) received both oxandrolone (0.28 mg/kg, i.p) and metformin (100 mg/kg, i.p). These treatments were administered for fourteen consecutive days. Behavioral tests to measure depression-like behavior were conducted before and after treatments. qRT-PCR was used to measure the relative expression of proinflammatory and anti-inflammatory cytokines in the hippocampus and hypothalamus. The results showed that oxandrolone induced depression-like behavior and dysregulated pro-/anti-inflammatory cytokines, while metformin attenuated these effects. These findings suggest that metformin is a potential treatment to reverse the depressive effects induced by oxandrolone that involve neuroinflammatory effects.

Preventive and control measures implemented by many countries to mitigate the spread of COVID-19 may negatively impact medication and chronic disease management, which can interfere with achieving patients' therapeutic goals. This study aims to evaluate the effect of the COVID-19 lockdown on these aspects, while exploring the role of community pharmacists. A cross-sectional study was conducted via a web-based questionnaire that targeted individuals who suffer from chronic diseases in Jordan. Participants were recruited by convenience sampling and were asked to self-report their ability to access medication, and the perceived role of community pharmacists. Among the 431 participants, the mean age ± SD (years) was 53.8 ± 13.7 and 60.1% (n= 259) were females. Participants mainly reported difficulties in accessing medication (n=198, 45.9%), reduced supplies or unavailability of medications (n=213, 49.4%), nonadherence to medications due to lack of access (n=98, 22.7%) and high costs (n=85, 19.7%). Participants avoided follow-ups due to a fear of infection (n=367, 82.5%) or prolonged waiting time in clinics (n=322, 74.7%). An increased reliance on the community pharmacy for medical advice was reported by 39.9% (n=172) of the participants, with half of them (n=217, 50.3%) depending on the pharmacists for advice regarding over-the-counter medications and COVID-19-related information (n=119, 27.6%). There is an urgent need to involve community pharmacists in medication and chronic disease management with a focus on patient adherence to ensure the optimal management of such vulnerable patient groups. Future studies to assess the effect of pharmacists' contributions towards enhancing medication/disease management are warranted.

Tobacco exposure has been linked to neuroinflammation and adaptive/maladaptive changes in neurotransmitter systems, including in glutamatergic systems. We examined the effects of waterpipe tobacco smoke (WTS) on inflammatory mediators and astroglial glutamate transporters in mesocorticolimbic brain regions including the prefrontal cortex (PFC), nucleus accumbens (NAc) and ventral tegmental area (VTA). The behavioral consequences of WTS exposure on withdrawal-induced anxiety-like behavior were assessed using elevated plus maze (EPM) and open field (OF) tests. Male Sprague-Dawley rats were randomly assigned to 3 experimental groups: a control group exposed only to standard room air, a WTS exposed group treated with saline vehicle, and a WTS exposed group treated with ceftriaxone. WTS exposure was performed for 2 h/day, 5 days/week, for 4 weeks. Behavioral tests (EPM and OF) were conducted weekly 24 h after WTS exposure, during acute withdrawal. During week 4, rats were given either saline or ceftriaxone (200 mg/kg i.p.) 30 min before WTS exposure. WTS increased withdrawal-induced anxiety, and ceftriaxone attenuated this effect. WTS exposure increased the relative mRNA levels for nuclear factor ĸB (NFĸB), tumor necrosis factor-α (TNF-α), and brain-derived neurotrophic factor (BDNF) in the PFC, NAc and VTA, and ceftriaxone treatment reversed these effects. In addition, WTS decreased the relative mRNA of nuclear factor erythroid 2 related factor 2 (Nrf2), glutamate transporter 1 (GLT-1) and cystine-glutamate transporter (xCT) in PFC, NAc and VTA, and ceftriaxone treatment normalized their expression. WTS caused neuroinflammation, alteration in relative mRNA glutamate transport expression, and increased anxiety-like behavior, and these effects were attenuated by ceftriaxone treatment.

The coronavirus disease-2019 (COVID-19) pandemic is a public health emergency of international concern. This pandemic poses a challenge to research and scientific community. In this study, we developed and tested content reliability and content validity of a questionnaire designed for evaluating the readiness and willingness of researchers to participate in virology research in Jordan. The survey was hosted on an online platform, and the link was emailed. A total of 332 participants from universities across Jordan completed the survey. For factor analysis, Kaiser-Meyer-Olkin value (KMO) and Bartlett’s Test of Sphericity were conducted. Furthermore, exploratory factor analysis (EFA) with parallel analysis and scree plots were conducted to evaluate the most suitable model for the data. The result of the EFA suggested a 5-factor model would fit the survey. Data showed that the lowest means were for researchers’ readiness to conduct virology research and readiness for virology research with means of 2.07 and 2.95, respectively. Moreover, years of experience and speciality had a significant effect on the readiness and willingness of virology research in Jordan. In conclusion, readiness for research and researchers should be addressed and authorities should pay attention to these shortcomings in virology research.

Nicotine exposure increases the release of glutamate in part through stimulatory effects on pre-synaptic nicotinic acetylcholine receptors (nAChRs). To assess the impact of chronic electronic (e)-cigarette use on these drug dependence pathways, we exposed C57BL/6 mice to three types of inhalant exposures for 3 months; 1) e-cigarette aerosol generated from liquids containing nicotine (ECN), 2) e-cigarette aerosol generated from liquids containing vehicle chemicals without nicotine (Veh), and 3) air only (AC). We investigated the effects of daily e-cigarette exposure on protein levels of α7 nAChR and α4/β2 nAChR, gene expression and protein levels of astroglial glutamate transporters, including glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT), in the frontal cortex (FC), striatum (STR) and hippocampus (HIP). We found that chronic inhalation of ECN increased α4/β2 nAChR in all brain regions, and increased α7 nAChR expression in the FC and STR. The total GLT-1 relative mRNA and protein expression were decreased in the STR. Moreover, GLT-1 isoforms (GLT-1a and GLT-1b) were downregulated in the STR in ECN group. However, inhalation of e-cigarette aerosol downregulated xCT expression in STR and HIP compared to AC and Veh groups. ECN group had increased brain-derived neurotrophic factor in the STR compared to control groups. Finally, mass spectrometry detected high concentrations of the nicotine metabolite, cotinine, in the FC and STR in ECN group. This work demonstrates that chronic inhalation of nicotine within e-cigarette aerosols significantly alters the expression of nAChRs and astroglial glutamate transporters in specific mesocorticolimbic brain regions.

Thymoquinone (TQ) is a water-insoluble natural compound isolated from Nigella sativa that has demonstrated promising chemotherapeutic activity. The purpose of this study was to develop a polymeric nanoscale formulation for TQ to circumvent its delivery challenges. TQ-encapsulated nanoparticles (NPs) were fabricated using methoxy poly(ethylene glycol)-b-poly(&epsilon, caprolactone) (mPEG-PCL) copolymers by the nanoprecipitation technique. Formulation variables included PCL chain length and NP architecture (matrix-type nanospheres or reservoir-type nanocapsules). The formulations were characterized in terms of their particle size, polydispersity index (PDI), drug loading efficiency, and drug release. An optimized TQ NP formulation in the form of oil-filled nanocapsules (F2-NC) was obtained with a mean hydrodynamic diameter of 117 nm, PDI of 0.16, about 60% loading efficiency, and sustained in vitro drug release. The formulation was then tested in cultured human cancer cell lines to verify its antiproliferative efficacy as a potential anticancer nanomedicine. A pilot pharmacokinetic study was also carried out in healthy mice to evaluate the oral bioavailability of the optimized formulation, which revealed a significant increase in the maximum plasma concentration (Cmax) and a 1.3-fold increase in bioavailability compared to free TQ. Our findings demonstrate that the versatility of polymeric NPs can be effectively applied to design a nanoscale delivery platform for TQ that can overcome its biopharmaceutical limitations.

Aim Reinforcing properties of ethanol and cocaine are mediated in part through the glutamatergic system. Extracellular glutamate concentration is strictly maintained through several glutamate transporters, such as glutamate transporter 1 (GLT-1), cystine/glutamate transporter (xCT) and glutamate aspartate transporter (GLAST). Previous findings revealed that cocaine and ethanol exposure downregulated GLT-1 and xCT, and that β-lactam antibiotics restored their expression. Methods In this study, we investigated the effect of ampicillin/sulbactam (AMP/SUL) (200 mg/kg, i.p.), a β-lactam antibiotic, on cocaine-induced reinstatement and locomotor activity in male alcohol preferring (P) rats using free choice ethanol (15 and 30%, v/v) and water. We also investigated the effect of co-exposure to ethanol and cocaine (20 mg/kg, i.p.) on GLT-1, xCT and GLAST expression in the nucleus accumbens (NAc) core, NAc shell and dorsomedial prefrontal cortex (dmPFC). Results Cocaine exposure decreased ethanol intake and preference. Cocaine and ethanol co-exposure acquired place preference and increased locomotor activity compared to ethanol-exposed rats. GLT-1 and xCT expression were downregulated after cocaine and ethanol co-exposure in the NAc core and shell, but not in dmPFC. AMP/SUL attenuated reinstatement to cocaine as well attenuated the decrease in locomotor activity and ethanol intake and preference. These effects were associated with upregulation of GLT-1 and xCT expression in the NAc core/shell and dmPFC. GLAST expression was not affected after ethanol and cocaine co-exposure or AMP/SUL treatment. Conclusion Our findings demonstrate that astrocytic glutamate transporters within the mesocorticolimbic area are critical targets in modulating cocaine-seeking behavior while being consuming ethanol.

Two efflux transporters, ATP-binding cassettes B1 (ABCB1) and G2 (ABCG2), are highly expressed in the endothelial cells of the brain, where they regulate the bioavailability and distribution of several endogenous and xenobiotic compounds. However, whether ABCB1 or ABCG2 has any link with drug dependence, drug withdrawal effects, or the incidence of adverse effects in drug abuser is not known. In this study, we determined the effects of voluntary ethanol consumption following repeated exposure to cocaine or vehicle on the relative mRNA and protein expression of Abcg2/ABCG2 and Abcb1/ABCB1 in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) of male alcohol-preferring (P) rats. Male P rats were allowed free choice access to ethanol (15 and 30% v/v) and water for 5 weeks to establish baseline drinking behavior. The following week, rats were either injected with 20 mg/kg i.p. of cocaine or saline, once a day, for 7 days. The relative mRNA and protein expression of Abcb1/ABCB1 and Abcg2/ABCG2 in the NAc and mPFC were significantly decreased in ethanol-saline- and ethanol-cocaine-exposed rats compared to control rats that received neither ethanol nor cocaine. Thus, prolonged exposure to commonly abused drugs, ethanol and cocaine, alters the expression of Abcb1/ABCB1 and Abcg2/ABCG2 mRNA and protein levels in brain areas that play a role in drug dependence.

Spirometric reference values are crucial in screening, diagnosis and monitoring the therapeutic course of respiratory diseases. These values from a representative population are key to making a precise interpretation of respiratory diseases. The objective of this study is to determine the spirometric reference values of a healthy Jordanian population.Participants were recruited from Al-Zaytoonah University of Jordan and from several pharmacies, polyclinics and hospitals in different cities in Jordan. To formulate Jordanian-specific spirometric reference values, generalised additive models for location scale and shape (GAMLSS) were used.Spirometric reference values were derived from 1,949 healthy nonsmoking adults (1,061 females) and validated in 300 healthy nonsmoking subjects (150 females).Spirometric reference values were developed for a Middle Eastern adult population.

Impairment in glutamate neurotransmission mediates the development of dependence upon nicotine (NIC) and ethanol (EtOH). Previous work indicates that continuous access to EtOH or phasic exposure to NIC reduces expression of the glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT) but not the glutamate/aspartate transporter (GLAST). Additionally, metabotropic glutamate receptors (mGluRs) expression was affected following exposure to EtOH or NIC. However, little is known about the effects of EtOH and NIC co-consumption on GLT-1, xCT, GLAST, and mGluR1 expression. In this study, peri-adolescent female alcohol preferring (P) rats were given binge-like access to water, sucrose (SUC), SUC-NIC, EtOH, or EtOH-NIC for four weeks. The present study determined the effects of these reinforcers on GLT-1, xCT, GLAST, and mGluR1 expression in the nucleus accumbens (NAc), hippocampus (HIP) and prefrontal cortex (PFC). GLT-1 and xCT expression were decreased in the NAc following both SUC-NIC and EtOH-NIC. In addition, only xCT expression was downregulated in the HIP in both of these latter groups. Also, glutathione peroxidase (GPx) activity in the HIP was reduced following SUC, SUC-NIC, EtOH, and EtOH-NIC consumption. Similar to previous work, GLAST expression was not altered in any brain region by any of the reinforcers. However, mGluR1 expression was increased in the NAc in the SUC-NIC, EtOH, and EtOH-NIC groups. These results indicate that peri-adolescent binge-like drinking of EtOH or SUC with or without NIC may exert differential effects on astroglial glutamate transporters and receptors. Our data further parallel some of the previous findings observed in adult rats.

Glutamatergic neurotransmission within the brain’s reward circuits plays a major role in the reinforcing properties of both ethanol and cocaine. Glutamate homeostasis is regulated by several glutamate transporters, including glutamate transporter type 1 (GLT-1), cystine/glutamate transporter (xCT), and glutamate aspartate transporter (GLAST). Cocaine exposure has been shown to induce a dysregulation in glutamate homeostasis and a decrease in the expression of GLT-1 and xCT in the nucleus accumbens (NAc). In this study, alcohol preferring (P) rats were exposed to free-choice of ethanol (15% and 30%) and/ or water for five weeks. On Week 6, rats were administered (i.p.) cocaine (10 and 20 mg/kg) or saline for 12 consecutive days. This study tested two groups of rats: the first group was euthanized after seven days of repeated cocaine i.p. injection, and the second group was deprived from cocaine for five days and euthanized at Day 5 after cocaine withdrawal. Only repeated cocaine (20 mg/kg, i.p.) exposure decreased ethanol intake from Day 3 through Day 8. Co-exposure of cocaine and ethanol decreased the relative mRNA expression and the expression of GLT-1 in the NAc but not in the medial prefrontal cortex (mPFC). Importantly, co-exposure of cocaine and ethanol decreased relative expression of xCT in the NAc but not in the mPFC. Our findings demonstrated that chronic cocaine exposure affects ethanol intake; and ethanol and cocaine co-abuse alters the expression of glial glutamate transporters.

The glutamatergic system has an important role in cocaine-seeking behavior. Studies have reported that chronic exposure to cocaine induces downregulation of glutamate transporter-1 (GLT-1) and cystine/glutamate exchanger (xCT) in the central reward brain regions. Ceftriaxone, a β-lactam antibiotic, restored GLT-1 expression and consequently reduced cue-induced reinstatement of cocaine-seeking behavior. In this study, we investigated the reinstatement to cocaine (20 mg/kg, i.p.) seeking behavior using a conditioned place preference (CPP) paradigm in male alcohol-preferring (P) rats. In addition, we investigated the effects of Ampicillin/Sulbactam (AMP/SUL) (200 mg/kg, i.p.), a β-lactam antibiotic, on cocaine-induced reinstatement. We also investigated the effects of AMP/SUL on the expression of glial glutamate transporters and metabotropic glutamate receptor 1 (mGluR1) in the nucleus accumbens (NAc) core and shell and the dorsomedial prefrontal cortex (dmPFC). We found that AMP/SUL treatment reduced cocaine-triggered reinstatement. This effect was associated with a decrease in locomotor activity. Moreover, GLT-1 and xCT were downregulated in the NAc core and shell, but not in the dmPFC, following cocaine-primed reinstatement. However, cocaine exposure increased the expression of mGluR1 in the NAc core, but not in the NAc shell or dmPFC. Importantly, AMP/SUL treatment normalized GLT-1 and xCT expression in the NAc core and shell; however, the drug normalized mGluR1 expression in the NAc core only. Additionally, AMP/SUL increased the expression of GLT-1 and xCT in the dmPFC as compared to the water naïve group. These findings demonstrated that glial glutamate transporters and mGluR1 in the mesocorticolimbic area could be potential therapeutic targets for the attenuation of reinstatement to cocaine-seeking behavior.

Alcohol dependence is associated with alteration of glutamate transport and glutamate neurotransmission. Glutamate transporter 1 (GLT-1) is a major transporter that regulates the majority of extracellular glutamate concentration, which is also regulated by cystine-glutamate exchanger (xCT). Importantly, we recently reported that amoxicillin and Augmentin (amoxicillin/clavulanate) upreglulated GLT-1 expression in nucleus accumbens (NAc) and prefrontal cortex (PFC) as well as reduced ethanol consumption in male P rats. In this study, we examined the effects of amoxicillin and Augmentin on GLT-1 isoforms (GLT-1a and GLT-1b), xCT and glutamate/aspartate transporter (GLAST) expression in NAc and PFC as well as ethanol intake in male P rats. We found that both compounds significantly reduced ethanol intake, and increased GLT-1a, GLT-1b and xCT expression in NAc. However, only Augmentin increased GLT-1a, GLT-1b and xCT expression in PFC. There were no effects of these compounds on GLAST expression in NAc and PFC. These findings demonstrated that Augmentin and amoxicillin have the potential to upregulate GLT-1 isoforms and xCT expression, and consequently attenuate ethanol dependence.