Evaluation of Two Simultaneous Metabolomic and Proteomic Extraction Protocols Assessed by Ultra-High-Performance Liquid Chromatography Tandem Mass Spectrometry.

Untargeted multi-omics analysis of plasma is an emerging tool for the identification of novel biomarkers for evaluating disease prognosis, and for developing a better understanding of molecular mechanisms underlying human disease. The successful application of metabolomic and proteomic approaches relies on reproducibly quantifying a wide range of metabolites and proteins. Herein, we report the results of untargeted metabolomic and proteomic analyses from blood plasma samples following analyte extraction by two frequently-used solvent systems: chloroform/methanol and methanol-only. Whole blood samples were collected from participants (n = 6) at University Hospital Sharjah (UHS) hospital, then plasma was separated and extracted by two methods: (i) methanol precipitation and (ii) 4:3 methanol:chloroform extraction. The coverage and reproducibility of the two methods were assessed by ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS). The study revealed that metabolite extraction by methanol-only showed greater reproducibility for both metabolomic and proteomic quantifications than did methanol/chloroform, while yielding similar peptide coverage. However, coverage of extracted metabolites was higher with the methanol/chloroform precipitation.

COVID-19 Vaccines, Effectiveness, and Immune Responses.

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has captivated the globe's attention since its emergence in 2019. This highly infectious, spreadable, and dangerous pathogen has caused health, social, and economic crises. Therefore, a worldwide collaborative effort was made to find an efficient strategy to overcome and develop vaccines. The new vaccines provide an effective immune response that safeguards the community from the virus' severity. WHO has approved nine vaccines for emergency use based on safety and efficacy data collected from various conducted clinical trials. Herein, we review the safety and effectiveness of the WHO-approved COVID-19 vaccines and associated immune responses, and their impact on improving the public's health. Several immunological studies have demonstrated that vaccination dramatically enhances the immune response and reduces the likelihood of future infections in previously infected individuals. However, the type of vaccination and individual health status can significantly affect immune responses. Exposure of healthy individuals to adenovirus vectors or mRNA vaccines causes the early production of antibodies from B and T cells. On the other hand, unhealthy individuals were more likely to experience harmful events due to relapses in their existing conditions. Taken together, aligning with the proper vaccination to a patient's case can result in better outcomes.

Metabolomics Analysis Revealed Significant Metabolic Changes in Brain Cancer Cells Treated with Paclitaxel and/or Etoposide.

Cancer of the central nervous system (CNS) is ranked as the 19th most prevalent form of the disease in 2020. This study aims to identify candidate biomarkers and metabolic pathways affected by paclitaxel and etoposide, which serve as potential treatments for glioblastoma, and are linked to the pathogenesis of glioblastoma. We utilized an untargeted metabolomics approach using the highly sensitive ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) for identification. In this study, 92 and 94 metabolites in U87 and U373 cell lines were profiled, respectively. The produced metabolites were then analyzed utilizing t-tests, volcano plots, and enrichment analysis modules. Our analysis revealed distinct metabolites to be significantly dysregulated (nutriacholic acid, L-phenylalanine, L-arginine, guanosine, ADP, hypoxanthine, and guanine), and to a lesser extent, mevalonic acid in paclitaxel and/or etoposide treated cells. Furthermore, both urea and citric acid cycles, and metabolism of polyamines and amino acids (aspartate, arginine, and proline) were significantly enriched. These findings can be used to create a map that can be utilized to assess the antitumor effect of paclitaxel and/or etoposide within the studied cancer cells.

Preclinical and Clinical Applications of Metabolomics and Proteomics in Glioblastoma Research.

Glioblastoma (GB) is a primary malignancy of the central nervous system that is classified by the WHO as a grade IV astrocytoma. Despite decades of research, several aspects about the biology of GB are still unclear. Its pathogenesis and resistance mechanisms are poorly understood, and methods to optimize patient diagnosis and prognosis remain a bottle neck owing to the heterogeneity of the malignancy. The field of omics has recently gained traction, as it can aid in understanding the dynamic spatiotemporal regulatory network of enzymes and metabolites that allows cancer cells to adjust to their surroundings to promote tumor development. In combination with other omics techniques, proteomic and metabolomic investigations, which are a potent means for examining a variety of metabolic enzymes as well as intermediate metabolites, might offer crucial information in this area. Therefore, this review intends to stress the major contribution these tools have made in GB clinical and preclinical research and highlights the crucial impacts made by the integrative "omics" approach in reducing some of the therapeutic challenges associated with GB research and treatment. Thus, our study can purvey the use of these powerful tools in research by serving as a hub that particularly summarizes studies employing metabolomics and proteomics in the realm of GB diagnosis, treatment, and prognosis.

p-Synephrine, ephedrine, p-octopamine and m-synephrine: Comparative mechanistic, physiological and pharmacological properties.

Confusion and misunderstanding exist regarding the lack of cardiovascular and other adverse health effects of p-synephrine and p-octopamine relative to ephedrine and m-synephrine (phenylephrine) which are known for their effects on the cardiovascular system. These four molecules have some structural similarities. However, the structural and stereochemical differences of p-synephrine and p-octopamine as related to ephedrine and m-synephrine result in markedly different adrenergic receptor binding characteristics as well as other mechanistic differences which are reviewed. p-Synephrine and p-octopamine exhibit little binding to α-1, α-2, ß-1 and ß-2 adrenergic receptors, nor are they known to exhibit indirect actions leading to an increase in available levels of endogenous norepinephrine and epinephrine at commonly used doses. The relative absence of these mechanistic actions provides an explanation for their lack of production of cardiovascular effects at commonly used oral doses as compared to ephedrine and m-synephrine. As a consequence, the effects of ephedrine and m-synephrine cannot be directly extrapolated to p-synephrine and p-octopamine which exhibit significantly different pharmacokinetic, and physiological/pharmacological properties. These conclusions are supported by human, animal and in vitro studies that are discussed.

Safety evaluation of p-synephrine following 15 days of oral administration to healthy subjects: A clinical study.

Extracts of bitter orange (BOE, Citrus aurantium L.) and its primary protoalkaloid p-synephrine are extensively consumed as dietary supplements. p-Synephrine is also present in foods and juices prepared from various Citrus species. The safety of p-synephrine has been questioned as a result of structural similarities with ephedrine. This study assessed the cardiovascular (stimulant) and hemodynamic effects of BOE (49 mg p-synephrine) daily given to 16 healthy subjects for 15 days in a placebo-controlled, cross-over, double-blinded study. A physical evaluation by a cardiologist, as well as heart rates, blood pressures, and electrocardiograms were determined, and blood samples were drawn at baseline, and Days 5, 10, and 15. Serum levels for caffeine and p-synephrine were measured at 1 and 2 weeks. Subjects completed a 10-item health and metabolic questionnaire at baseline and on Day 15. No significant changes occurred in heart rate, electrocardiograms, systolic blood or diastolic pressures, blood cell counts, or blood chemistries in either the control or p-synephrine treated groups at any time point. No adverse effects were reported in response to the bitter orange (p-synephrine). Caffeine consumed by the participants varied markedly. Under these experimental conditions, BOE and p-synephrine were without stimulant (cardiovascular) and adverse effects.

Cardiovascular Safety of Oral p-Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo-Controlled Cross-over Clinical Trial.

Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p-synephrine are widely consumed in combination with multiple herbal ingredients for weight management and sports performance. p-Synephrine is also present in juices and foods derived from a variety of Citrus species. Questions exist regarding the safety of p-synephrine because of structural similarities with other biogenic amines. This study assessed the cardiovascular (stimulatory) effects of bitter orange extract (49-mg p-synephrine) given to 18 healthy subjects (nine men and nine women) in a double-blinded, placebo-controlled cross-over study. Heart rates, blood pressures, and electrocardiograms were determined at baseline, 30, 60, 90 min, 2, 4 , 6, and 8 h. Blood samples were drawn at baseline, 2 h and 8 h for serum chemistries, blood cell counts, and p-synephrine and caffeine levels. No significant changes occurred in electrocardiograms, heart rates, systolic blood pressure, blood chemistries, or blood cell counts at any time point in either control or p-synephrine treated group. A small (4.5 mmHg) decrease in diastolic blood pressure occurred in the p-synephrine treated group at 60 min. No adverse effects were reported. Caffeine ingestion varied markedly among the participants. p-Synephrine does not act as a stimulant at the dose used. Copyright © 2016 John Wiley & Sons, Ltd.

Prevalence of non-adherence among psychiatric patients in Jordan, a cross sectional study.

BACKGROUND: It has been estimated that up to 50% of any patient population is at least partially non-adherent to their prescribed treatment. Identifying barriers to adherence is required to develop effective interventions for psychiatric patients. OBJECTIVE: To explore the prevalence and factors of non-adherence among psychiatric patients present at four psychiatric clinics. METHOD: A cross-sectional questionnaire-based study. A sample of psychiatric patients attending outpatient psychiatric clinics was enrolled between March and April 2011. RESULTS: A total of 243 psychiatric patients took part in this study with the majority of patients (92.5%) being prescribed more than one psychiatric disorder. The majority (64.2%) of the patients was classified as non-adherent according to the Morisky adherence questionnaire and forgetfulness was the most prevalent reason for that. CONCLUSIONS: Non-adherence is a common and important issue among psychiatric patients. Polypharmacy, safety concerns and lack of insight towards the prescribed treatment were reported as the main reasons of non-adherence.

Efficacy and Safety of White Willow Bark (Salix alba) Extracts.

Willow bark extract has been used for thousands of years as an anti-inflammatory, antipyretic, and analgesic. In spite of its long history of use, relatively few human and animal studies have been published that confirm anecdotal observations. A small number of clinical studies have been conducted that support the use of willow bark extracts in chronic lower back and joint pain and osteoarthritis. Willow bark extracts also are widely used in sports performance and weight loss products presumably because of anti-inflammatory and analgesic activities, although no human studies have been published that specifically and directly document beneficial effects. In recent years, various in vitro and animal studies have demonstrated that the anti-inflammatory activity of willow bark extract is associated with down regulation of the inflammatory mediators tumor necrosis factor-α and nuclear factor-kappa B. Although willow bark extracts are generally standardized to salicin, other ingredients in the extracts including other salicylates as well as polyphenols, and flavonoids may also play prominent roles in the therapeutic actions. Adverse effects appear to be minimal as compared to non-steroidal anti-inflammatory drugs including aspirin. The primary cause for concern may relate to allergic reactions in salicylate-sensitive individuals.

Sources of information used when prescribing for children, a survey of hospital based pediatricians.

BACKGROUND: Due to the lack of properly tested medicines for children, there is little available information with regards to indications and dosing of medications in children. AIM: To collect data on sources where hospital based pediatricians obtain prescribing information when treating children and the extent of collaboration with the hospital pharmacist. METHOD: Two hundred and fifty pediatricians in different hospitals within different cities in Jordan were asked to fill in a structured questionnaire regarding information sources used when prescribing for children. RESULTS: Questionnaires were collected from 162 (64.8%) hospital based pediatricians, who have completed the questionnaire by the designated date. Most (75.5%) reported that the Lexi Comp's Drug Information Handbook was the source that they most frequently used for drug information when prescribing for in children. The BNF and the BNFc (British National Formulary for children) were found to be the most sources that contain sufficient information that aids pediatricians when prescribing for children. A minority (22%) claimed to consult with the hospital pharmacist when they face difficulties when prescribing for children. CONCLUSIONS: Pediatricians rely on different information sources when they prescribe for children. Those sources vary in their reliability in aiding pediatrician when prescribing. Further work should be done in the provision of useful information on pediatric drug therapy to pediatricians. More steps should be taking place to activate collaboration and interaction between pediatricians and pharmacists as well.

Implementation of clinical pharmacy services at a university hospital in Jordan.

OBJECTIVE: Clinical pharmacy services are still in the early stages of implementation in the Middle East. This study assessed the implementation of clinical pharmacy services at a major university hospital. METHODS: All recommendations and services provided by clinical pharmacists were recorded for a period of 7 months. KEY FINDINGS: During the study period a total of 3026 patients were followed up and 10,783 recommendations and services were provided. The physicians' rate of acceptance of clinical pharmacists' recommendations was 69.4%. CONCLUSION: The implementation of clinical pharmacy services in this setting was successful and should positively impact patient care.

Public knowledge and awareness of cardiovascular disease and its risk factors: a cross-sectional study of 1000 Jordanians.

OBJECTIVE: To assess the level of the current knowledge and understanding of cardiovascular disease (CVD) among Jordan's general public, their behaviour towards CVD and the factors associated with different CVD knowledge levels. METHODS: The data in the present study were collected using an interview-administered questionnaire. One thousand members of the general public were interviewed face to face. CVD knowledge was computed as a continuous variable. KEY FINDINGS: The present study reports limited public knowledge and awareness of CVD. Participants were more likely to have better CVD knowledge scores if they were non-smokers, always or often paid attention to their diet, reported having an 'about right' weight, occupied a very high socioeconomic level, held a university degree and had positive family history of CVD. Participants indicated that the community pharmacists had to play a role in helping patients manage their prescribed medicines; however, they did not recognise the community pharmacists' role in other areas of CVD prevention and management. CONCLUSION: The present study reports that the general public in Jordan has limited knowledge and awareness of CVD. In planning to positively impact CVD prevention and management, community pharmacists must develop and promote effective and accessible services.

A review of the human clinical studies involving Citrus aurantium (bitter orange) extract and its primary protoalkaloid p-synephrine.

This review summarizes the published as well as unpublished human studies involving Citrus aurantium (bitter orange) extract and its primary protoalkaloid p-synephrine, providing information and an assessment of the safety and efficacy of these widely used products. The results of over 20 studies involving a total of approximately 360 subjects that consumed p-synephrine alone or in combination with other ingredients are reviewed and critiqued. Over 50 % of the subjects involved in these studies were overweight/obese, and approximately two-thirds of these overweight/obese subjects consumed caffeine (132-528 mg/day) in conjunction with p-synephrine (10-53 mg/day). Bitter orange/p-synephrine containing products were consumed for up to 12 weeks. Approximately 44 % of the subjects consumed a bitter orange/p-synephrine only product, while the remainder consumed a complex product that contained multiple ingredients in addition to p-synephrine. In general, bitter orange extract alone (p-synephrine) or in combination with other herbal ingredients did not produce significant adverse events as an increase in heart rate or blood pressure, or alter electrocardiographic data, serum chemistry, blood cell counts or urinalysis. p-Synephrine alone as well as in combination products were shown to increase resting metabolic rate and energy expenditure, and modest increases in weight loss were observed with bitter orange extract/p-synephrine-containing products when given for six to 12 weeks. Longer term studies are needed to further assess the efficacy of these products and affirm their safety under these conditions.

A review of the receptor-binding properties of p-synephrine as related to its pharmacological effects.

Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p-synephrine are used widely in weight loss/weight management and sports performance products. Because of structural similarities, the pharmacological effects of p-synephrine are widely assumed to be similar to those of ephedrine, m-synephrine (phenylephrine), and endogenous amine neurotransmitters as norepinephrine and epinephrine. However, small structural changes result in the receptor binding characteristics of these amines that are markedly different, providing a plausible explanation for the paucity of adverse effects associated with the wide-spread consumption of p-synephrine in the form of dietary supplements as well as in various Citrus foods and juices. This paper summarizes the adrenoreceptor binding characteristics of p-synephrine relative to m-synephrine, norepinephrine, and other amines as related to the observed pharmacological effects.

The safety of Citrus aurantium (bitter orange) and its primary protoalkaloid p-synephrine.

Citrus aurantium (bitter orange) extract and its principal protoalkaloidal constituent p-synephrine are widely used in weight loss and weight management as well as in sports performance products. However, questions are raised frequently regarding the safety of these ingredients. The potential inherent dangers associated with the use of products containing C. aurantium extract are frequently touted, while conversely, millions of doses of dietary supplements have been consumed by possibly millions of individuals in recent years. Furthermore, millions of people consume on a daily basis various juices and food products from Citrus species that contain p-synephrine. This review summarizes current information regarding the safety of C. aurantium (bitter orange) extract and p-synephrine based on human, animal and in vitro assessments as well as receptor binding and mechanistic studies. The data indicate that based on current knowledge, the use of bitter orange extract and p-synephrine appears to be exceedingly safe with no serious adverse effects being directly attributable to these ingredients.

Regulation of norepinephrine release from isolated bovine irides by histamine.

In the present study, we investigated the effect of histamine on sympathetic neurotransmission from isolated, superfused bovine irides. We also studied the pharmacology of prejunctional histamine receptors that regulate the release of norepinephrine (NE) from this tissue. The effect of exogenous histamine and various histamine receptor agonists was examined on the release of [(3)H]-norepinephrine ([(3)H]NE) triggered by electrical field stimulation using the Superfusion Method. Histamine receptor agonists caused a concentration-dependent inhibition of field-stimulated [(3)H]NE overflow with the following rank order of potency: imetit > histamine > R-alpha-methylhistamine. In all cases, the inhibitory action of histamine receptor agonists was attenuated at high concentrations of these compounds. The histamine receptor antagonists, clobenpropit (H(3)-antagonist/H(4)-agonist) and thioperamide (H(3)-antagonist) blocked the inhibitory response elicited by R-alpha-methylhistamine and imetit, respectively. Inhibitory effects of R-alpha-methylhistamine and clonidine were not additive suggesting that prejunctional H(3)- and alpha(2)-adrenoceptors coexist at neurotransmitter release sites. We conclude that histamine produces an inhibitory action on sympathetic neurotransmission in the bovine iris, an effect mimicked by selective H(3)-receptor agonists and blocked by H(3)-antagonists.