Significance of serum VIP and PACAP in multiple sclerosis: an exploratory case-control study.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system. Vasoactive and intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are neuropeptides that play roles in anti-inflammation and neuroprotection in MS. In this study, we aimed to determine the serum levels of VIP and PACAP in MS patients versus healthy controls and to correlate them with demographics and clinical characteristics. METHODS: Serum samples were collected from MS patients (n = 145) and healthy controls (n = 73) to measure serum levels VIP and PACAP. RESULTS: VIP serum levels were lower in MS patients than healthy controls (p < 0.001). Serum PACAP levels were the same among the two groups. Gender-based analysis showed that VIP levels were lower in healthy females (1238.840 pg/ml) than healthy males (3300.105 pg/ml; p < 0.001), and PACAP serum levels were significantly lower in male MS patients (48,516.214 fg/ml) than female MS patients (62,466.400 fg/ml; p = 0.029). ROC curve suggested that serum VIP level can discriminate patients with MS from healthy controls. Relapsing-remitting MS, progressive-MS, and clinically isolated syndrome groups were different in age, MS disease duration, EDSS score, and VIP levels (p < 0.05). MS disease type and history of previous relapses in the preceding 24 months predicted serum VIP levels, while gender predicted PACAP levels. CONCLUSION: VIP serum levels are decreased in MS patients and can be used to differentiate between MS patients and healthy controls. Further studies with larger sample sizes are required to investigate VIP as a marker to reflect MS disease progression.

A Prospective Non-Randomized Open-Label Comparative Study of The Effects of Matcha Tea on Overweight and Obese Individuals: A Pilot Observational Study.

Matcha tea has been used as an adjunct in weight loss programs. The weight loss effects of matcha tea were evaluated in a prospective non-randomized open-label comparative study of overweight and obese individuals who followed a specified low-calorie diet (LCD) plan. A total of 40 participants were enrolled and assigned to either matcha tea or control groups. The matcha tea group followed a LCD plan and received matcha tea once daily, whereas the control group followed only the LCD diet plan. The study lasted 12 weeks. The main outcome measures included anthropometric measurements, fasting blood glucose, hemoglobin A1c (HbA1c), lipid profile, obesity-related hormone peptides, pro-inflammatory and anti-inflammatory cytokines, and oxidative stress biomarkers. Thirty-four participants had completed the study. The matcha tea and control groups showed significant reductions in body weight, body mass index, waist circumference, water content, minerals, and fat mass at week 12. The post-treatment body composition and anthropometric measurements were not significantly different between the two groups. The matcha tea group showed a potential increase in HDL-C, a potential decrease in blood glucose, and a potential increase in HbA1c. Furthermore, the study indicated a potential decrease in insulin and leptin levels, a potential increase in the activity of superoxide dismutase, and a potential decreased activity of glutathione peroxidase. IL-10 was increased by matcha tea consumption. The data suggest that matcha tea may have some potential effect on weight loss, along with anti-inflammatory properties. The findings of this study will be used to design a multicenter randomized clinical trial to examine the potential weight loss benefits of matcha tea.

The effect of electronic cigarettes exposure on learning and memory functions: behavioral and molecular analysis.

Objective: Electronic cigarettes (ECIGs) are battery-powered devices that emit vaporized solutions for the user to inhale. ECIGs are marketed as a less harmful alternative to combustible cigarettes. The current study examined the effects of ECIG aerosol exposure on learning and memory, expression of brain derived neurotrophic factor (BDNF), and the activity of antioxidant enzymes in the hippocampus.Methods: Male Wistar rats were exposed to ECIG aerosol, by a whole-body exposure system, 1 h/day for 1 week, 4 weeks, and 12 weeks. Spatial learning and memory were tested using the Radial Arm Water Maze (RAWM). Hippocampal BDNF protein level, and oxidative stress biomarkers (GPx, SOD, GSH, GSSG, GSH/GSSG ratio) were also assessed.Results: ECIG aerosol exposure for 4 and 12 weeks impaired both short- and long- term memory and induced reductions in the hippocampus BDNF, SOD and GPx activities, and GSH/GSSG ratio (p < 0.05). No changes in any examined biomarkers were observed after 1-week exposure to ECIG aerosol (p > 0.05).Conclusions: ECIG aerosol exposure impaired functional memory and elicited changes in brain chemistry that are consistent with reduced function and oxidative stress.

The knowledge of community pharmacists about appropriate dosing of antibiotics among paediatrics: A national study from Jordan.

OBJECTIVE: Paediatric patients are highly exposed to medication errors especially dosing errors. This study assessed the community pharmacists' knowledge about appropriate dosing of antibiotics among paediatric patients, factors affecting community pharmacists' knowledge and barriers that lead to inappropriate dosing of antibiotics. METHODS: A self-administered questionnaire was distributed to 1283 Jordanian pharmacists who worked in community pharmacies. Descriptive statistics and multivariate regression were conducted. RESULTS: The response rate was 87.1%. The majority of pharmacists (86.4%) were non-knowledgeable about appropriate dosing of antibiotics among paediatrics. The monthly income of the pharmacist was positively associated with pharmacists' knowledge. The case of azithromycin dosing in acute bacterial pharyngitis was answered correctly by the highest percentage of community pharmacists (55.8%) while the case of trimethoprim-sulfamethoxazole dosing in lower urinary tract infection was answered correctly by the lowest percentage (15.7%). Poor scientific knowledge about dose calculation was the most reported barrier by the participants (54.7%). CONCLUSION: Most community pharmacists were non-knowledgeable about appropriate dosing of antibiotics in paediatrics and the level of knowledge was affected by monthly income. Implementing adequate and appropriate educational programmes, constructing specific guidelines that regulate antibiotics practice among community pharmacists are highly recommended.

Remdesivir: A Closer Look at Its Effect in COVID-19 Pandemic.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiology of COVID-19 pandemic, resulted in significant harm to the affected countries in every aspect of life. The virus infected over 139 million patients and resulted in over 2.9 million deaths until April 16, 2021. New variants of this virus were identified that spread rapidly worldwide. SUMMARY: Remdesivir, a prodrug of adenosine nucleotide analog, is an antiviral with a broad spectrum of activity that was tested on SARS and Middle East respiratory syndrome infections. In vitro studies conducted on SARS-CoV-2 revealed that remdesivir inhibited viral replication with high selectivity index in cell cultures. In vivo studies showed that remdesivir reduced viral load in bronchoalveolar lavage fluid and attenuated pulmonary infiltrates in infected animals. Further, remdesivir showed promising results in terms of clinical improvement, shortening the recovery time, mortality rate, and the duration of oxygen need, despite that some clinical trials did not reveal significant effect on remdesivir use. Several studies showed positive results of remdesivir against the new variants. Key Messages: Remdesivir showed a promising beneficial effect against new variants of SARS-CoV-2, but more clinical evidence is needed to confirm this effect.

Effect of E-Cigarette aerosol exposure on airway inflammation in a murine model of asthma.

OBJECTIVE: The popularity of electronic cigarettes (E-Cigs) smoking is increasing worldwide including patients with asthma. In this study, the effects of E-Cigs aerosol exposure on airway inflammation in an allergen-driven murine model of asthma were investigated. MATERIALS AND METHODS: Balb/c mice were randomly assigned to; control group (received fresh air, Ovalbumin (Ova) sensitization and saline challenge), E-Cig group (received E-Cig aerosol, Ova sensitization, and saline challenge), Ova S/C group (received fresh air, Ova sensitization and Ova challenge) and E-Cig + Ova S/C group. Bronchoalveolar lavage fluid (BALF) and lung tissue were evaluated for inflammatory cells and inflammatory mediators, respectively. RESULTS: Exposure to E-Cig aerosol significantly increased the number of all types of inflammatory cells in BALF (p < 0.05). Further, E-Cig aerosol reduced levels of transforming growth factor (TGF)-ß1 and matrix metalloproteinase (MMP)-2 in lung tissue homogenate (p < 0.05). Combined E-Cig aerosol and Ova S/C increased the airway recruitment of inflammatory cells, especially neutrophils, eosinophils, and lymphocytes (p < 0.05), increased the level of interleukin (IL)-13, and reduced the level of TGF-ß1 (p < 0.05). CONCLUSIONS: E-Cig aerosol exposure induced airway inflammation in both control mice and allergen-driven murine model of asthma. The inflammatory response induced by E-Cig was slightly higher in allergen-driven murine model of asthma than in healthy animals.

ß2-Adrenoceptor signaling in airway epithelial cells promotes eosinophilic inflammation, mucous metaplasia, and airway contractility.

The mostly widely used bronchodilators in asthma therapy are ß2-adrenoreceptor (ß2AR) agonists, but their chronic use causes paradoxical adverse effects. We have previously determined that ß2AR activation is required for expression of the asthma phenotype in mice, but the cell types involved are unknown. We now demonstrate that ß2AR signaling in the airway epithelium is sufficient to mediate key features of the asthmatic responses to IL-13 in murine models. Our data show that inhibition of ß2AR signaling with an aerosolized antagonist attenuates airway hyperresponsiveness (AHR), eosinophilic inflammation, and mucus-production responses to IL-13, whereas treatment with an aerosolized agonist worsens these phenotypes, suggesting that ß2AR signaling on resident lung cells modulates the asthma phenotype. Labeling with a fluorescent ß2AR ligand shows the receptors are highly expressed in airway epithelium. In ß2AR-/- mice, transgenic expression of ß2ARs only in airway epithelium is sufficient to rescue IL-13-induced AHR, inflammation, and mucus production, and transgenic overexpression in WT mice exacerbates these phenotypes. Knockout of ß-arrestin-2 (ßarr-2-/-) attenuates the asthma phenotype as in ß2AR-/- mice. In contrast to eosinophilic inflammation, neutrophilic inflammation was not promoted by ß2AR signaling. Together, these results suggest ß2ARs on airway epithelial cells promote the asthma phenotype and that the proinflammatory pathway downstream of the ß2AR involves ßarr-2. These results identify ß2AR signaling in the airway epithelium as capable of controlling integrated responses to IL-13 and affecting the function of other cell types such as airway smooth muscle cells.

Influence of prenatal waterpipe tobacco smoke exposure on renal biomarkers in adult offspring rats.

Background: Waterpipe tobacco smoke (WTS) is a popular form of tobacco consumption. Prenatal exposure to cigarette smoke altered kidney function and oxidative stress balance in offspring. However, the effect of prenatal WTS exposure on kidney function parameters, blood pressure and oxidative stress in adult offspring rats were unknown. Methods: Pregnant Wister rats were exposed to either WTS for 2 hours per day utilizing a whole body exposure system or fresh air from day 0 of gestation to day 21. Systolic blood pressure, histological analysis of kidney, kidney function biomarkers [angiotensin converting enzyme (ACE), angiotensin I, angiotensin II, urea nitrogen, creatinine and albumin], and oxidative stress biomarkers (glutathione peroxidase (GPx), catalase and thiobarbituric acid reactive substances (TBARS)) were measured in male- and female- offspring rats on week 20. Results: Prenatal exposure to WTS significantly decreased kidneys' weight and glomeruli area (p < 0.05) in offspring rats. Prenatal WTS exposure increased blood pressure in offspring rats (p < 0.05). Further, prenatal WTS exposure increased the level of urine albumin (p < 0.05) in offspring rats. Prenatal WTS exposure increased the level of ACE and angiotensin I (p < 0.05) in female offspring rats. Prenatal WTS exposure increased the level of TBARS (p < 0.05) in female offspring rats and there was a trend of decreased activity of GPx in male and female offspring rats, but was not significant (p > 0.05). Conclusions: Maternal WTS exposure during pregnancy resulted in detrimental effects on the renal system as indicated by altered kidney parameters and function, increased systolic blood pressure and oxidative stress in adult offspring rats.

Influence of prenatal waterpipe tobacco smoke exposure on reproductive hormones and oxidative stress of adult male offspring rats.

Male infertility is adversely affected by tobacco cigarette smoking. Herein, the effects of prenatal waterpipe tobacco smoke (WTS) exposure on reproductive hormones and oxidative stress of adult offspring rats were evaluated. Pregnant rats received either fresh air or mainstream WTS (2 hr daily). Pregnancy outcomes, circulatory levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin, testicular levels of oestrogen, testosterone and oxidative stress biomarkers [catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS)] were assessed in their adult male offspring rats. Prenatal WTS exposure reduced the number of born offspring, female to pups ratio and birthweight (p < 0.05). Prenatal WTS exposure increased the circulatory levels of FSH and the testicular levels of oestrogen, testosterone and TBARS and catalase activity compared with control group (p < 0.05). However, GPx activity was reduced by WTS exposure (p < 0.05). There appeared to be a trend of increased LH and prolactin levels with prenatal WTS exposure; however, it was not statistically significant compared with control group (p > 0.05). The activity of SOD was not affected by prenatal WTS exposure (p > 0.05). In conclusion, prenatal WTS exposure altered reproductive hormones as well as oxidative stress biomarkers in adult male offspring rats.

Effect of Prenatal Exposure to Waterpipe Tobacco Smoke on Learning and Memory of Adult Offspring Rats.

Introduction: Waterpipe tobacco smoking has increased in prevalence worldwide, including among pregnant women. In this study, we investigated the effect of prenatal maternal waterpipe tobacco smoke (WTS) exposure during different stages of pregnancy on learning and memory of adult offspring rats. Methods: Pregnant rats received either fresh air or mainstream WTS (2 hours daily) during early, mid, late, or whole gestational period. Male offspring rats were followed through 20 weeks. Outcomes included (1) spatial learning and memory using the radial arm water maze (RAWM), (2) levels of brain derived neurotrophic factor (BDNF) in the hippocampus, and (3) oxidative stress biomarkers (superoxide dismutase, catalase, glutathione peroxidase and thiobarbituric acid reactive substances). Results: Relative to offspring whose mothers were exposed to fresh air, prenatal exposure to WTS at any stage of pregnancy resulted in short- and long-term memory impairment in adult offspring rats (p < .05). This impairment was associated with reduced levels of BDNF in hippocampus (p < .05). However, prenatal WTS did not affect the level of oxidative stress biomarkers in hippocampus. Prenatal WTS during late gestation increased the activity of catalase as compared to control. Conclusion: Prenatal maternal WTS exposure can impair the memory of adult male offspring. These results support development of interventions that target pregnant women who smoke waterpipe during pregnancy. Implications: We examined for the first time the effect of prenatal waterpipe tobacco smoke exposure on learning and memory of offspring. The results showed that in utero exposure to waterpipe tobacco smoke was associated with impaired memory and decreased brain derived neurotrophic factor in hippocampus of adult male offspring rats.

Healthcare providers' attitude and knowledge regarding medication use in breastfeeding women: a Jordanian national questionnaire study.

Medication use among women who have recently given birth is unavoidable in some situations. The aim of this study was to assess the attitude and knowledge of healthcare providers (HCPs) in Jordan about the safe use of medications during breastfeeding. The data were collected from HCPs in maternal and children care centres and hospitals from April 2015 to January 2016, using a self-administered questionnaire. A total of 904 HCPs (79.3%) were enrolled in the study. Half of the participants followed the World Health Organisation's and American Academy of Pediatrics' recommendations. The awareness of HCPs regarding these recommendations was lower among nurses (OR 0.212, 95%CI 0.132-0.338, p < .001) and pharmacists (OR 0.476, 95%CI 0.297-0.763, p = .002) than physicians. The majority of participants (80%) had low level of knowledge and nurses were more likely to have low knowledge than physicians (OR 0.099, 95%CI 0.050-0.197, p < .001). Professional continuous education programmes were highly encouraged. Impact statement What is already known on this subject: Use of medications among women who have recently given birth is unavoidable in some situations and most of them are safe to be given during breastfeeding. What the results of this study add: Healthcare providers in Jordan have variable attitudes regarding the safety of medication use during breastfeeding. The majority of healthcare providers have a low level of knowledge regarding the safe use of medication during breastfeeding. Nurses are more likely to have low knowledge as compared to physicians. IMPLICATIONS FOR CLINICAL PRACTICE: Healthcare providers should be encouraged to seek information regarding compatibility of medication use during breastfeeding from reliable sources. Professional continuing education programmes concerning the safety of medication use during breastfeeding period are needed to target all involved HCPs. More attention should be directed toward medical schools' curricula to widen the knowledge of medication use and focus on practice-based clinical experience.

Potential of Phenylbutyrate as Adjuvant Chemotherapy: An Overview of Cellular and Molecular Anticancer Mechanisms.

Despite the advancement in cancer therapy, a high number of patients fail treatment because of drug resistance. Several preclinical in vitro data suggest that phenylbutyrate has antiproliferative, antiangiogenic, antimetastatic, immunomodulatory, and differentiating properties. Moreover, phenylbutyrate administration in vivo provided an oncoprotective effect. However, the results of clinical trials indicate that the antineoplastic potential of phenylbutyrate is hindered by its pharmacokinetic and pharmacodynamic properties. Thus, understanding the exact mechanisms of the anticancer effect of phenylbutyrate could assist in the selection of patients who will best benefit from this drug. The present review discusses the proposed mechanisms of antineoplastic effect of phenylbutyrate and the preclinical and clinical evidence suggesting its potential role as anticancer in different types of cancer.

Effect of prenatal waterpipe tobacco smoke on airway inflammation in murine model of asthma of adult offspring mice.

OBJECTIVE: Worldwide popularity of waterpipe tobacco smoking has increased, including in pregnant women. This study investigates the effect of prenatal waterpipe tobacco smoke (WTS) exposure on airway inflammation in a murine model of asthma of adult offspring mice. MATERIALS AND METHODS: Pregnant BALB/c mice were exposed to fresh air or WTS, using a whole-body exposure system that mimics human use during WTS. Adult male offspring mice were divided into; (1) control (prenatal fresh air, postnatal ovalbumin sensitization and saline challenge), (2) postnatal Ova S/C (prenatal fresh air, postnatal ovalbumin sensitization and challenge (Ova S/C)), (3) prenatal WTS (prenatal WTS, postnatal ovalbumin sensitization and saline challenge) and (4) prenatal WTS + postnatal Ova S/C. Cells from the bronchoalveolar lavage fluid, cytokines, and oxidative stress markers (superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS)) from lung homogenates were evaluated. RESULTS: Prenatal WTS increased recruitment of cells in lungs and levels of SOD and catalase when compared to unexposed offspring's. The levels of cytokines, GPx and TBARS were not affected by prenatal WTS. Prenatal WTS exposure and postnatal Ova S/C increased airway inflammation and activity of SOD compared to control and Ova S/C mice and reduced IL-18 levels compared to Ova S/C mice. DISCUSSION AND CONCLUSIONS: Prenatal exposure to WTS induced airway inflammation, further enhanced by a murine model of asthma in adult offspring. Prenatal exposure to WTS adversely affects the lung function of the offspring and careful strategies for increasing public awareness regarding the harmful effects of WTS during pregnancy is important.

Effect of waterpipe tobacco smoking on airway inflammation in murine model of asthma.

OBJECTIVE: There has been an increase in the popularity of waterpipe tobacco smoking (WTS) worldwide, especially in the younger population, including asthma patients. In this study, we investigated the effects of waterpipe smoking on airway inflammation, cytokine levels and oxidative stress markers in an antigen-driven murine model of asthma. MATERIALS AND METHODS: Balb/c mice were divided into four groups; (1) control (received fresh air, ovalbumin sensitization and saline challenge), (2) WTS (received WTS, ovalbumin sensitization and saline challenge), (3) Ova S/C (received fresh air, ovalbumin sensitization and ovalbumin challenge) and (4) simultaneous WTS and Ova S/C (received WTS, ovalbumin sensitization and ovalbumin challenge). Airway inflammatory cells were evaluated in the broncho-alveolar lavage fluid. Cytokines [interleukin (IL)-13, 10 and 18] and oxidative stress markers [superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx)] were evaluated in the lung homogenates. RESULTS: Chronic exposure to WTS significantly increased the number of airway inflammatory cells in mice, specifically: eosinophils, neutrophils, macrophages and lymphocytes. The level of IL-13 in the lungs was increased and the level of IL-10 was reduced (p < 0.05) by WTS. Chronic WTS potentiated the increase in inflammatory cells induced by Ova S/C (p < 0.05). The level of IL-13 in the lungs was increased by simultaneous WTS and Ova S/C (p < 0.05) while, levels of IL-10, IL-18, SOD, catalase and GPx in the lungs were not affected. CONCLUSIONS: Chronic WTS exposure induced airway inflammation in control mice and enhanced airway inflammation in murine model of asthma.

Phosphodiesterase 4 Inhibitors Attenuate the Asthma Phenotype Produced by ß2-Adrenoceptor Agonists in Phenylethanolamine N-Methyltransferase-Knockout Mice.

Mice lacking the endogenous ß2-adrenoceptor (ß2AR) agonist epinephrine (phenylethanolamine N-methyltransferase [PNMT]-knockout mice) are resistant to developing an "asthma-like" phenotype in an ovalbumin sensitization and challenge (Ova S/C) model, and chronic administration of ß2AR agonists to PNMT-KO mice restores the phenotype. Based on these and other studies showing differential effects of various ß2AR ligands on the asthma phenotype, we have speculated that the permissive effect of endogenous epinephrine and exogenous ß2AR agonists on allergic lung inflammation can be explained by qualitative ß2AR signaling. The ß2AR can signal through at least two pathways: the canonical Gαs-cAMP pathway and a ß-arrestin-dependent pathway. Previous studies suggest that ß-arrestin-2 is required for allergic lung inflammation. On the other hand, cell-based assays suggest antiinflammatory effects of Gαs-cAMP signaling. This study was designed to test whether the in vitro antiinflammatory effects of phosphodiesterase 4 inhibitors, known to increase intracellular cAMP in multiple airway cell types, attenuate the asthma-like phenotype produced by the ß2AR agonists formoterol and salmeterol in vivo in PNMT-KO mice, based on the hypothesis that skewing ß2AR signaling toward Gαs-cAMP pathway is beneficial. Airway inflammatory cells, epithelial mucus production, and airway hyperresponsiveness were quantified. In Ova S/C PNMT-KO mice, formoterol and salmeterol restored the asthma-like phenotype comparable to Ova S/C wild-type mice. However, coadministration of either roflumilast or rolipram attenuated this formoterol- or salmeterol-driven phenotype in Ova S/C PNMT-KO. These findings suggest that amplification of ß2AR-mediated cAMP by phosphodiesterase 4 inhibitors attenuates the asthma-like phenotype promoted by ß-agonists.

Asthma insights from Jordan: cross-sectional observational study.

OBJECTIVE: The burden of uncontrolled asthma on patients in Jordan is largely unknown. This study assessed different aspects of asthma clinical features: the level of asthma control, its correlation with quality of life, and possible predictors of asthma control. METHODS: Face-to-face interviews with asthmatic patients (≥16 years old) in north Jordan from 2013 to 2014 were conducted. Outcomes measures were assessed using the asthma control test (ACT), the mini asthma quality of life questionnaire (mini-AQLQ), and the Generic health-related quality of life (EQ-5D). The relationship between asthma control and quality of life was examined using Spearman's correlation coefficient. Predictors of asthma control were determined using multivariable logistic regression adjusted for confounders. RESULTS: A total of 255 patients were recruited (mean age 45.16 years, 74.5% female). Approximately one-third of subjects (30.6%; n = 78) had controlled asthma (ACT ≥ 20). A strong correlation between asthma control and both mini-AQLQ and EQ-5D scores was identified (p < 0.001). Subjects who required to step-up treatment (OR = 0.12, 95% CI: 0.02-0.63, p = 0.01) and with acute asthma exacerbation (OR = 0.32, 95% CI: 0.18-0.58, p < 0.001) were independently associated with poor asthma control. CONCLUSIONS: Most of the recruited patients have not achieved optimal asthma control and was associated with low quality of life. The study highlights that even in low-income countries, a simple assessment tool such as the ACT can be utilized to screen and categorize asthma control. This approach would facilitate a better treatment plan and eventually improve asthma control and quality of life in asthma patients.

Statins in Asthma: A Closer Look into the Pharmacological Mechanism of Action.

The effect of stains in asthma is mediated through targeting several signaling molecules that are involved in the development of asthma phenotype. In vitro and in vivo studies revealed that statins reduce airway smooth muscle cells proliferation and inflammatory mediators' release. Statins reduce chemokine release and mucus production from airway epithelial cells besides attenuating subepithelial fibrosis and eosinophils recruitment. In acute and chronic allergen driven animal models of asthma, statins reduce airway hyper-responsiveness, inflammation and remodeling. However, the effectiveness of statins in clinical trials results in contradictory conclusions based on study design and treatment protocol. Therefore, more clinical trials are needed to evaluate their role in asthma patients.

Alpha Calcitonin Gene-related Peptide, Neuropeptide Y, and Substance P as Biomarkers for Diagnosis and Disease Activity and Severity in Multiple Sclerosis.

BACKGROUND: Alpha calcitonin gene-related peptide (aCGRP), neuropeptide Y (NPY), and substance P (SP) are neuropeptides that have emerged recently as potent immunomodulatory factors with potential as novel biomarkers and therapeutic targets in multiple sclerosis (MS). OBJECTIVE: The study aimed to detect serum levels of aCGRP, NPY, and SP in MS patients versus healthy controls and their association with disease activity and severity. METHODS: Serum levels were measured in MS patients and age and sex-matched healthy controls using ELISA. RESULTS: We included 67 MS patients: 61 relapsing-remitting MS (RR-MS) and 6 progressive MS (PR-MS), and 67 healthy controls. Serum NPY level was found to be lower in MS patients than in healthy controls (p < 0.001). Serum aCGRP level was higher in PR-MS compared to RR-MS (p = 0.007) and healthy controls (p = 0.001), and it positively correlated with EDSS (r = 0.270, p = 0.028). Serum NPY level was significantly higher in RR-MS and PR-MS than in healthy controls (p < 0.001 and p = 0.001, respectively), and it was lower in patients with mild or moderate/severe disease than in healthy controls (p < 0.001). Significant inverse correlations were found between SP level and MS disease duration (r = -0.279, p = 0.022) and duration of current DMT (r = -0.315, p = 0.042). CONCLUSION: Lower serum levels of NPY were revealed in MS patients compared to healthy controls. Since serum levels of aCGRP are significantly associated with disease activity and severity, it is a potential disease progression marker.

Effects of empagliflozin on gonadal functions of hyperglycemic male wistar rats.

Empagliflozin (EMPA) showed antiapoptotic, oxidative and anti-inflammatory potential effect. EMPA attenuates the inflammation and oxidative stress biomarkers in patients with heart failure while significantly decreases the malondialdehyde (a lipid peroxidation marker) levels in the plasma of diabetic patients. The present study examined the effects of moderate hyperglycemia on reproductive function. Sixty male Wister rats were divided and randomly allocated into four groups of 15 animals each . Diabetes was induced by a single intraperitoneal injection of a prepared solution containing STZ diluted in 0.1 M sodium citrate buffer (pH 4.5) at a dosage of 40 mg/kg body weight in selected in groups II and III for seven days before starting the treatment with EMPA. The current study revealed that EMPA for eight weeks prevented testicular high glucose-induced oxidative stress markers such as penile nitric oxide (NO), glutathione peroxidase (GPX) and total anti-oxidant capacity (TAC) in STZ-induced hyperglycemia in a rat model. In addition, EMPA ameliorated the high levels of endogenous Interleukin-6 (IL-6) present in gonads in response to an acute inflammatory found in the hyperglycemic STZ-induced rats. The present study further suggested the protective effects of EMPA and how it has a beneficial role and can effectively attenuate hyperglycemia-induced testicular oxidative damage and inflammatory markers as well as androgen dependent testicular enzymes activity as a protective role against the consequences of hyperglycemia and male sub-infertility.

ß2-Adrenoceptor agonists are required for development of the asthma phenotype in a murine model.

ß(2)-Adrenoceptor (ß2AR) agonists are the most effective class of bronchodilators and a mainstay of asthma management. The first potent ß2AR agonist discovered and widely used in reversing the airway constriction associated with asthma exacerbation was the endogenous activator of the ß2AR, epinephrine. In this study, we demonstrate that activation of the ß2AR by epinephrine is paradoxically required for development of the asthma phenotype. In an antigen-driven model, mice sensitized and challenged with ovalbumin showed marked elevations in three cardinal features of the asthma phenotype: inflammatory cells in their bronchoalveolar lavage fluid, mucin over production, and airway hyperresponsiveness. However, genetic depletion of epinephrine using mice lacking the enzyme to synthesize epinephrine, phenylethanolamine N-methyltransferase, or mice that had undergone pharmacological sympathectomy with reserpine to deplete epinephrine, had complete attenuation of these three cardinal features of the asthma phenotype. Furthermore, administration of the long-acting ß2AR agonist, formoterol, a drug currently used in asthma treatment, to phenylethanolamine N-methyltransferase-null mice restored the asthma phenotype. We conclude that ß2AR agonist-induced activation is needed for pathogenesis of the asthma phenotype. These findings also rule out constitutive signaling by the ß2AR as sufficient to drive the asthma phenotype, and may help explain why chronic administration of ß2AR agonists, such as formoterol, have been associated with adverse outcomes in asthma. These data further support the hypothesis that chronic asthma management may be better served by treatment with certain "ß-blockers."