Effects of epigallocatechin gallate on total antioxidant capacity,biomarkers of systemic low-grade inflammation and metabolic risk factors in patients with type 2 diabetes mellitus: the role of FTO-rs9939609 polymorphism

IntroductionType 2 diabetes mellitus (T2DM) is known as one of the most common metabolic diseases and FTO polymorphism has been implicated in the susceptibility to this disease. Epigallocatechin-3-gallate (EGCG) has shown favorable effects on risk factors related to T2DM. The present study aimed to investigate the effects of EGCG on total antioxidant capacity, biomarkers of systemic low-grade inflammation and metabolic risk factors in patients with T2DM considering the role of FTO polymorphism.Material and methodsIn this double-blind randomized clinical trial, 60 patients with T2DM (20–60 years) were randomly allocated to three groups. Group 1 received 300 mg of EGCG (TT genotype). Group 2 received 300 mg of EGCG (AA + AT genotypes) and Group 3 received placebo. We genotyped FTO (rs9939609) and measured body mass index (BMI), blood pressure, profile lipid, interleukin-6, high sensitivity C-reactive protein and total antioxidant capacity, before and after the intervention, at 2 months.ResultsIn carriers of A allele, EGCG intervention caused a significant decrease in BMI, diastolic blood pressure (DBP), mean arterial pressure and serum cholesterol level compared with placebo (p < 0.05). Also, we found a significant gene-treatment interaction effect between FTO-rs9939609 and EGCG on BMI and DBP (P > 0.05).ConclusionsThese findings suggest that carriers of the risk alleles (A) of FTO-rs9939609 have a better response to EGCG in improving BMI and DBP in patients with T2DM.     

Herbal formulation “turmeric extract,black pepper,and ginger” versus Naproxen for chronic knee osteoarthritis: A randomized,double‐blind,controlled clinical trial

Osteoarthritis is the most common articular disease that can lead to chronic pain and severe disability. Curcumin—an effective ingredient in turmeric with anti inflammatory property—plays an important role in protecting the joints against destructive factors. Gingerols and piperine, are the effective ingredients of ginger and black pepper, which may potentially enhance and sustain the effect of curcumin in this direction. To determine the effect of cosupplementation with turmeric extract, black pepper, and ginger on prostaglandin E₂ (PGE₂) in patients with chronic knee osteoarthritis, compared with Naproxen. Sixty patients with two different levels of knee osteoarthritis (Grade 2 and 3) were studied. Individuals were randomly assigned to receive daily turmeric extract, ginger, and black pepper together or Naproxen capsule for 4 weeks. PGE₂ was evaluated by ELISA method. 24‐hr recall was also assessed. All of participants completed the study. PGE₂ decreased significantly in both groups (p < .001), but there was no significant differences between groups. The results of this study indicated that intake of the selected herbs twice a day for 4 weeks may improve the PGE₂ levels in patients with chronic knee osteoarthritis similar to Naproxen drug.     

Facilitators and Barriers to Implementation of Long-Acting Reversible Contraceptive Services for Adolescent Girls and Young Women in Gaborone,Botswana

Study ObjectiveBotswana has a high pregnancy rate among adolescent girls and young women (AGYW). Long-acting reversible contraceptive (LARC) use among AGYW in Botswana is low, despite its high effectiveness for preventing pregnancy. Using an implementation science framework, we assessed barriers and facilitators to LARC implementation among AGYW in Botswana.DesignCross-sectional mixed methods.SettingGaborone, Botswana.ParticipantsTwenty sexually active AGYW ages 18-24 years; 20 health system stakeholders.InterventionsSurveys and semistructured interviews grounded in the Consolidated Framework for Implementation Research.Main Outcome MeasuresThemes reflecting barriers and facilitators of LARC implementation.ResultsThe median age for AGYW was 22 (interquartile range, 21-23) years. Twenty percent were using an implant and none had ever used an intrauterine device. Barriers and facilitators of LARC implementation spanned factors at each Consolidated Framework for Implementation Research domain: (1) LARC characteristics like side effects; (2) the clinics’ inner settings, including availability of youth-friendly services; (3) characteristics of health system stakeholders, such as LARC skills, and AGYW experiences, attitudes, and beliefs about LARCs; (4) the outer setting external to clinics and Botswana's health system including reproductive health law and policy for minor adolescents; and (5) the implementation process level such as the availability of free or low-cost LARCs.ConclusionWe identified multilevel, context-specific factors that affect LARC implementation. Our findings can inform the development of interventions to increase LARC implementation in Botswana by addressing intersecting factors across patient, clinic, health system, and sociopolitical levels, such as providing confidential services to minors and improving LARC training and supply chain pipelines.     

Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells

The cytokines controlling the development of human interleukin (IL) 17--producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17--producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) beta, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17--producing T cells. These data suggest that IL-12Rbeta1- and STAT-3--dependent signals play a key role in the differentiation and/or expansion of human IL-17-producing T cell populations in vivo.     

Lacosamide treatment of juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy is the most common form of idiopathic generalized epilepsy with onset at puberty or late teenage years. About 80-90% of patients with juvenile myoclonic epilepsy respond to appropriate antiepileptic treatment and achieve seizure freedom, and about 15% of patients become intractable. Valproic acid, levetiracetam, lamotrigine, topiramate and zonisamide are used as first line or adjunctive therapy of this disorder. Lacosamide is approved for adjunctive treatment of partial onset epilepsies. The role of lacosamide in treatment of idiopathic generalized epilepsy including juvenile myoclonic epilepsy is unknown. We present three patients with classic clinical and electrographic features of juvenile myoclonic epilepsy that were maintained on lacosamide (one on monotherapy and two as adjuvant therapy). There were no special pharmacodynamic actions causing exacerbation or worsening of myoclonic jerks or generalized seizures in these three patients. In conclusion, although, the data from our three patients' suggest that lacosamide may be effective in the treatment of juvenile myoclonic epilepsy, larger studies are needed to explore efficacy and role of lacosamide in the treatment of this disorder.     

Inhibition of JNK phosphorylation reverses memory deficit induced by β-amyloid (1-42) associated with decrease of apoptotic factors

Alzheimer's disease (AD) is the most common form of dementia that is degenerative and terminal disease. The main reason of the disease is still unknown. β-amyloid (Aβ) plaques are the important hallmarks of memory impairment in patients suffering from AD. Aggregation of these plaques in the hippocampus appears during the development of the disease. One of the prominent factors having crucial impact in this process is MAPK. JNK, as a member of MAPK family has a pivotal role, especially in cell survival. We hypothesized that JNK may have beneficial effect on the process of memory improvement. Hence, we performed Morris water maze to investigate the possible impact of JNK inhibitor on spatial memory in Aβ-injected rats. Our data indicated that intracerebroventricular administration of SP600125, a JNK inhibitor, could significantly decrease escape latency and increase time spent in target quadrant, in treatment group. Furthermore, we evaluated some of the apoptotic factors in the hippocampus of the treated rats. Based on our data, the inhibitor led to the significant decrease in the amount of caspase-3, TUNEL positive cells, cyclooxygenase-2 and increase in Bcl-2/Bax ratio. Given the possible neuroprotective effects of SP600125 on Aβ-induced memory impairment and apoptosis, our results may open a new avenue for the treatment of AD.