Antibacterial, Anti-HIV-1 Protease and Cytotoxic Activities of Aqueous Ethanolic Extracts from Combretum Adenogonium Steud. Ex A. Rich (Combretaceae).

\ud \ud Records have shown that Combretum adenogonium Steud. Ex A. Rich (Combretaceae) is used in traditional medicine systems of several tribes in Tanzania. This study focused on the investigation of antibacterial activity, anti-HIV-1 protease activity, toxicity properties and classes of phytochemicals in extracts from C. adenogonium Steud. Ex A. Rich (Combretaceae) to evaluate potential of these extracts for development as herbal remedies. Dried plant material were ground to fine powder and extracted using 80% aqueous ethanol to afford root, leaf and stem bark extracts. The extracts were assayed for anti-HIV-1 protease activities, antibacterial activities using microdilution methods and cytotoxicity using brine shrimps lethality assay. Screening for major phytochemical classes was carried out using standard chemical tests. All extracts exhibited antibacterial activity to at least one of the test bacteria with MIC-values ranging from 0.31-5.0 mg/ml. Two extracts, namely, root and stem bark exhibited anti-HIV-1 PR activity with IC50 values of 24.7 and 26.5 μg/ml, respectively. Stem bark and leaf extracts showed mild toxicity with LC50 values of 65.768 μg/ml and 76.965 μg/ml, respectively, whereas roots were relatively non-toxic (LC50 = 110.042 μg/ml). Phytochemical screening of the extracts indicated presence of flavonoids, terpenoids, alkaloids, tannins, glycosides and saponins. These results provide promising baseline information for the potential development of C. adenogonium extracts in treatment of bacterial and HIV/AIDS-related opportunistic infections

Effect of hydrochlorothiazide on serum uric acid concentration : a genome-wide association study

Aim: To recognize genetic associations of hydrochlorothiazide-induced change in serum uric acid (SUA) concentration. Patients & methods: We conducted a genome-wide association study on hydrochlorothiazide-induced change in SUA in 214 Finnish men from the GENRES study. Replication analyses were performed in 465 Finns from the LIFE study. Results: In GENRES, we identified 31 loci associated with hydrochlorothiazide-induced change in SUA at p <5 x 10(-5). rs1002976 near VEGFC associated with the change in GENRES and in LIFE. rs950569 near BRINP3 associated with the change in SUA in GENRES and LIFE. The analysis of previously reported SNPs and candidate genes provided some proof for PADI4 and ABCC4. Conclusion: We report genetic markers that may predict the increase in SUA concentration during thiazide treatment.Peer reviewe

Pharmacoepigenetics of hypertension : genome-wide methylation analysis of responsiveness to four classes of antihypertensive drugs using a double-blind crossover study design

Essential hypertension remains the leading risk factor of global disease burden, but its treatment goals are often not met. We investigated whether DNA methylation is associated with antihypertensive responses to a diuretic, a beta-blocker, a calcium channel blocker or an angiotensin receptor antagonist. In addition, since we previously showed an SNP at the transcription start site (TSS) of the catecholamine biosynthesis-related ACY3 gene to associate with blood pressure (BP) response to beta-blockers, we specifically analysed the association of methylation sites close to the ACY3 TSS with BP responses to beta-blockers. We conducted an epigenome-wide association study between leukocyte DNA methylation and BP responses to antihypertensive monotherapies in two hypertensive Finnish cohorts: the GENRES (; amlodipine 5 mg, bisoprolol 5 mg, hydrochlorothiazide 25 mg, or losartan 50 mg daily) and the LIFE-Fin studies (; atenolol 50 mg or losartan 50 mg daily). The monotherapy groups consisted of approximately 200 individuals each. We identified 64 methylation sites to suggestively associate (P < 1E-5) with either systolic or diastolic BP responses to a particular study drug in GENRES. These associations did not replicate in LIFE-Fin . Three methylation sites close to the ACY3 TSS were associated with systolic BP responses to bisoprolol in GENRES but not genome-wide significantly (P < 0.05). No robust associations between DNA methylation and BP responses to four different antihypertensive drugs were identified. However, the findings on the methylation sites close to the ACY3 TSS may support the role of ACY3 genetic and epigenetic variation in BP response to bisoprolol.Peer reviewe

Replicated evidence for aminoacylase 3 and nephrin gene variations to predict antihypertensive drug responses

Peer reviewe

Human essential hypertension : no significant association of polygenic risk scores with antihypertensive drug responses

Polygenic risk scores (PRSs) for essential hypertension, calculated from>900 genomic loci, were recently found to explain a significant fraction of hypertension heritability and complications. To investigate whether variation of hypertension PRS also captures variation of antihypertensive drug responsiveness, we calculated two different PRSs for both systolic and diastolic blood pressure: one based on the top 793 independent hypertension-associated single nucleotide polymorphisms and another based on over 1 million genome-wide variants. Using our pharmacogenomic GENRES study comprising four different antihypertensive monotherapies (n similar to 200 for all drugs), we identified a weak, but (after Bonferroni correction) statistically nonsignificant association of higher genome-wide PRSs with weaker response to a diuretic. In addition, we noticed a correlation between high genome-wide PRS and electrocardiographic left ventricular hypertrophy. Finally, using data of the Finnish arm of the LIFE study (n=346), we found that PRSs for systolic blood pressure were slightly higher in patients with drug-resistant hypertension than in those with drug-controlled hypertension (p=0.03, not significant after Bonferroni correction). In conclusion, our results indicate that patients with elevated hypertension PRSs may be predisposed to difficult-to-control hypertension and complications thereof. No general association between a high PRS and less efficient drug responsiveness was noticed.Peer reviewe

Green areas around homes reduce atopic sensitization in children

Peer reviewe

Effects of Randomized Controlled Infancy-Onset Dietary Intervention on Leukocyte Telomere Length—The Special Turku Coronary Risk Factor Intervention Project (STRIP)

Reduced telomere length (TL) is a biological marker of aging. A high inter-individual variation in TL exists already in childhood, which is partly explained by genetics, but also by lifestyle factors. We examined the influence of a 20-year dietary/lifestyle intervention on TL attrition from childhood to early adulthood. The study comprised participants of the longitudinal randomized Special Turku Coronary Risk Factor Intervention Project (STRIP) conducted between 1990 and 2011. Healthy 7-month-old children were randomized to the intervention group (n = 540) receiving dietary counseling mainly focused on dietary fat quality and to the control group (n = 522). Leukocyte TL was measured using the Southern blot method from whole blood samples collected twice: at a mean age of 7.5 and 19.8 years (n = 232; intervention n = 108, control n = 124). Yearly TL attrition rate was calculated. The participants of the intervention group had slower yearly TL attrition rate compared to the controls (intervention: mean = −7.5 bp/year, SD = 24.4 vs. control: mean = −15.0 bp/year, SD = 30.3; age, sex and baseline TL adjusted β = 0.007, SE = 0.004, p = 0.040). The result became stronger after additional adjustments for dietary fat quality and fiber intake, serum lipid and insulin concentrations, systolic blood pressure, physical activity and smoking (β = 0.013, SE = 0.005, p = 0.009). A long-term intervention focused mainly on dietary fat quality may affect the yearly TL attrition rate in healthy children/adolescents

Effects of Randomized Controlled Infancy-Onset Dietary Intervention on Leukocyte Telomere Length—The Special Turku Coronary Risk Factor Intervention Project (STRIP)

Reduced telomere length (TL) is a biological marker of aging. A high inter-individual variation in TL exists already in childhood, which is partly explained by genetics, but also by lifestyle factors. We examined the influence of a 20-year dietary/lifestyle intervention on TL attrition from childhood to early adulthood. The study comprised participants of the longitudinal randomized Special Turku Coronary Risk Factor Intervention Project (STRIP) conducted between 1990 and 2011. Healthy 7-month-old children were randomized to the intervention group (n = 540) receiving dietary counseling mainly focused on dietary fat quality and to the control group (n = 522). Leukocyte TL was measured using the Southern blot method from whole blood samples collected twice: at a mean age of 7.5 and 19.8 years (n = 232; intervention n = 108, control n = 124). Yearly TL attrition rate was calculated. The participants of the intervention group had slower yearly TL attrition rate compared to the controls (intervention: mean = −7.5 bp/year, SD = 24.4 vs. control: mean = −15.0 bp/year, SD = 30.3; age, sex and baseline TL adjusted β = 0.007, SE = 0.004, p = 0.040). The result became stronger after additional adjustments for dietary fat quality and fiber intake, serum lipid and insulin concentrations, systolic blood pressure, physical activity and smoking (β = 0.013, SE = 0.005, p = 0.009). A long-term intervention focused mainly on dietary fat quality may affect the yearly TL attrition rate in healthy children/adolescents