Assessment of In Vitro Airway Smooth Muscle Relaxant Activity of Rhus coriaria L. Fruit Ethanolic Extract and Its Possible Mechanisms.

Rhus coriaria L. (Anacardiaceae), also known as Sumac, is commonly used as a spice, flavoring agent, and as a traditional medicinal herb. This includes also the traditional use for treating asthma, catarrh, and common colds. The accumulating evidence supports its cardioprotective, antidiabetic, neuroprotective, anticancer, gastroprotective, antibacterial, anti-inflammatory, antiviral, antioxidant, and respiratory effects. However, there are no previous studies that have shown its effects and mechanism in the airway smooth muscle tone, and therefore, the aim of our study was to investigate the in vitro pharmacological action of R. coriaria L. extract (RCE) on the rat isolated tracheal and bronchial preparations by exploring its relaxant activity and mechanism of action. The direct relaxant effect of RCE (0.1-0.7 mg/mL) was tested in the rat bronchi and trachea rings precontracted by carbachol (CCh). In addition, the pretreatment with RCE (1 mg/mL) was tested on the bronchial and tracheal reactivity induced by CCh, potassium chloride (KCl), or CaCl2. In addition, the cyclooxygenase inhibitor indomethacin and the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME), respectively, were used for exploring the mechanisms of RCE-induced relaxation and reduction of reactivity. Our findings demonstrated that RCE induced a concentration-dependent relaxation and a significant reduction of reactivity, significantly reduced with either indomethacin or L-NAME. In addition, RCE decreased the responsiveness to KCl and affected the extracellular Ca2+-induced contraction in the tissues with added CCh or KCl in Ca2+-free Krebs-Henseleit solution. In summary, we have shown that RCE displayed relaxant activities in the in vitro airway smooth muscles, and the possible mechanisms seems to involve the prostaglandin, nitric oxide, and Ca2+ pathways. Taken together, our findings indicate the potential role of RCE in the treatment of respiratory diseases with limited airflow, or obstructive respiratory diseases, and could justify its traditional use in the respiratory diseases.

Role of omega-3 polyunsaturated fatty acids in gestational diabetes, maternal and fetal insights: current use and future directions.

ω-3-Polyunsaturated fatty acids (ω-3 PUFAs) are widely used during pregnancy and gestational diabetes mellitus (GDM). ω-3 PUFAs are beneficial in the regulation of maternal and fetal metabolic function, inflammation, immunity, macrosomia (MAC), oxidative stress, preeclampsia, intrauterine growth, preterm birth, offspring metabolic function, and neurodevelopment. Dietary counseling is vital for improving therapeutic outcomes in patients with GDM. In maternal circulation, ω-3 PUFAs are transported via transporters, synthesis enzymes, and intracellular proteins, which activate nuclear receptors and play central roles in the cellular metabolic processes of placental trophoblasts. In patients with GDM, this process is compromised due to abnormal functioning of the placenta, which disrupts the normal mother to fetus transport. This results in reduced fetal levels of ω-3 PUFAs, which contributes negatively to fetal growth, metabolic function, and development. Dietary counseling and nutritional assessment remain challenging in the prevention and alleviation of GDM. Therefore, personalized approaches, including measurement of the ω-3 index, pharmacogenetic implementation strategies, and appropriate supplementation with ω-3 PUFAs are used to achieve sufficient distribution in the maternal and fetal fluids during the entire pregnancy period. Developing new dosing guidelines and personalized approaches, determining the mechanisms of ω-3 PUFAs in the placenta, and examining the pharmacodynamic and pharmacokinetics interactions involving ω-3 PUFAs will lead to better management and increase the quality of life of patients with GDM and their offspring. Moreover, different strategies for supplementing with ω-3 PUFAs, improving their placental transport, and pharmacological exploration of the maternal-fetal interactions will help to further elucidate the role of ω-3 PUFAs in women with GDM. In this review, we summarize the current information on the potential therapeutic benefits and clinical applicability of ω-3 PUFAs in patients with GDM and their offspring, highlighting recent progress and future perspectives in this field. Studies investigating the mechanisms of ω-3 PUFA transport to targeted tissues have spurred an interest in personalized treatment strategies for patients with GDM and their offspring. To implement such therapies, we need to clarify the index/ratio of ω-3 PUFAs in maternal and fetal fluids, delineate the ω-3 PUFA transport pathways, and establish the guidelines for FA profiling prepregnancy and during pregnancy-associated weight gain. Such therapies also need to take into account the gender of the fetus, and whether the patient is obese.

Effect of omega-3 polyunsaturated fatty acids in modulation of vascular tone under physiological and pathological conditions.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are mainly found in marine fish oils and commercially available fish oil supplements. Several studies have documented that n-3 PUFAs can reduce the risk of cardiovascular diseases through anti-inflammatory, anti-thrombotic, and anti-atherosclerotic properties. Notably, regulation of vascular tone is one of the most important bases of cardiovascular health and especially for maintaining blood pressure within optimal physiological ranges. Recent clinical and animal studies indicate an association between n-3 PUFAs and vascular functions. In this regard, many clinical trials and basic experimental studies have been conducted so far to investigate the influence of n-3 PUFAs on vascular tone. In this review, we have summarized the results obtained from both clinical and basic studies that evaluated the effect of n-3 PUFAs under physiological and pathological conditions. Moreover, we also focus on verifying the underlying basic molecular mechanism of n-3 PUFAs on the vascular system.

Tuberculosis drug safety and pharmacovigilance in health system of Kosova: A cross-sectional analysis.

BACKGROUND: Tuberculosis (TB) remains a significant worldwide social and life-threatening epidemiological problem. Because this disease requires multiple drug treatment and prolonged therapy for several months, followed by a high probability of adverse effects (AEs), we assessed AE monitoring for anti-TB drugs in the Health Care System of Kosova. METHODS: This survey was a cross-sectional analysis performed at the primary, secondary and tertiary health care levels in Kosova. We included 930 registered tuberculosis patients within three levels of this health system in our study. Furthermore, we interviewed 62 physicians and 71 nurses at TB health facilities. Data were collected from official TB registers and personal contact with patients for 12 months. RESULTS: The representative age group was 19 to 29 years (30.49%), followed by a group of patients aged >60 years (23.23%). Among 930 patients treated with TB drugs, the total incidence of adverse AEs was 29.03%. Female TB patients had a higher rate of AEs than did male patients (33.56% vs 28.84%, respectively). The highest incidence of registered AEs was recorded in the gastrointestinal system (270, 80.83%), followed by the central nervous system (CNS, 7.50%) and was lower in other organ systems. The reporting of anti-TB drug effects by medical staff (TB medical doctor and TB medical nurse) at different levels of TB medical settings occurred among 62.90% of medical doctors and 81.69% of nurses. Only 53.23% of medical doctors and 46.48% of nurses completed pharmacovigilance training. CONCLUSION: The pharmacovigilance approach in Health System of Kosova is not comprehensible and not systematic. The relatively low incidence of AEs among TB patients is due under reporting of these by medical staff. The knowledge, attitudes, and adherence of medical staff reveal low awareness for pharmacovigilance activities, and this concern should be addressed to reinforce this important issue for the safe treatment of TB patients.

Standardization of solvent extracts from Onopordum acanthium fruits by GC-MS, HPLC-UV/DAD, HPLC-TQMS and 1H-NMR and evaluation of their inhibitory effects on the expression of IL-8 and E-selectin in immortalized endothelial cells (HUVECtert).

In this work we have characterized and standardized the solvent extracts of the fruits of Onopordum acanthium, a plant widely distributed from Europe to Asia and used in different traditional medicines. Fruits were extracted with methanol (ME) and n-hexane (HE) and the extract compositions determined by GC-MS, HPLC-UV/DAD, HPLC-TQMS and 1H NMR spectroscopy. Anti-inflammatory activity (IL-8 and E-selectin, qPCR and ELISA) was investigated in HUVECtert cells stimulated with TNF-alpha and LPS. Arctiin and isochlorogenic acid were found in ME (87 +/- 2%, w/w, and 10.2 +/- 0.2%, w/w; 38.0 +/- 3.2 mg/gFRUITS and 3.5 +/- 0.4 mg/gFRUITS) and (ii) paraffins in the HE (195.6 +/- 5.6 mg/g). A dose dependent (from 15 to 40 microgME/mL corresponding to 20-75 microM arctiin) inhibition of E-selectin and of the induction of IL-8 was induced by LPS. The results of this study support the use of O. acanthium fruits in traditional medicine as an anti-inflammatory agent and for cancer prevention and treatment.

Gestational diabetes mellitus (GDM) in the Republic of Kosovo: a retrospective pilot study.

BACKGROUND: GDM is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy. Pregnancy causes some insulin resistance in all women, but only a few develop GDM. OBJECTIVE: To test the hypothesis that women with GDM have impaired regulation of blood iron storage and transport, decreased renal function due to decreased glomerular filtration rate and occurrence of urinary tract infection (UTI). STUDY DESIGN AND METHODS: Incidence of blood iron storage was investigated in n=30 pregnant kosovar women with GDM after mild of pregnancy and in n=30 pregnant women without GDM (years 2010-2012). RESULTS AND DISCUSSION: Baby weights, both systolic and diastolic BP, creatinine, albumin, lymphocytes, monocytes, WBC and granulocytes in both groups were within their normal ranges in both groups. Compared to control group, glucose was higher in women with GDM (mean +/- SD: 7.43 +/- 2.23 mg/dL vs. 4.33 +/- 0.63 mg/dL; P < 0.001). Women with GDM had also higher RBC (mean +/- SD: 4.4 +/- 0.8% vs. 3.8 +/- 0.3%; P < 0.005) and HGB (mean +/- SD: 13.0 +/- 3.2 g/dL vs. 11.2 +/- 1.4 mg/dL; P < 0.05), and decreased renal functionality (MDRD-GFR: 92.8 +/- 25.8 g/dL vs. 108.2 +/- 38.2 g/dL; P < .05). CONCLUSION: There is a potential association between iron status and GDM. The role of iron from diet and/or from supplementation in GDM pathogenesis needs still to be examined. In addition we have observed a decrease of glomerular filtration rate in women with GDM. Due to the lack of studies on the relationships between GDM and UTI, and to the retrospective design of the present investigation, it is difficult to establish whether UTI may be a GDM causal factor or a consequence of GDM symptoms, signs and/or of its correlated pathologies.