Towards the management of hypertension: Modulation of the renin-angiotensin system by food protein hydrolysates and peptides

In response to the side effects of antihypertensive drugs, dietary and lifestyle modification approaches have become alternative strategies for prevention and modulation of mild hypertension. Moreover, the use of low molecular size bioactive peptides (BAPs) as antihypertensive agents has gained particular attention as a result of the safety, low cost, and consumer preference for natural health products compared to drugs. BAPs are produced by enzymatic hydrolysis of food proteins followed by post-hydrolysis processing to fractionate the active peptides. Antihypertensive BAPs exert their effect mostly by modulating the renin-angiotensin system pathway leading to decrease in vasoactive peptides with concomitant reduction of elevated blood pressure associated with hypertension in animal models and humans. This review revisits the prevalence of hypertension and the molecular basis of activity, bioavailability and safety of BAPS as well as contradictions and controversies on the use of peptides as antihypertensive agents

Spectroscopic characterization, DFT calculations, in vitro pharmacological potentials, and molecular docking studies of N, N, O-Schiff base and its trivalent metal complexes

In this study, trivalent metal complexes of the category: [M(L)(H2O)nCly] obtained from the interaction of metal3+ ion salts with organic N, N, O-Schiff base (HL) (where: HL = 4-{(Z)-((2-{(E)-((2-hydroxyphenyl)methylidene)amino}ethyl)imino)methyl}-2-methoxyphenol; n, y = 1 or 2 and M = Ti(III), Fe(III), Ru(III), Cr(III) and Al(III)) were synthesized and characterized viz molar conductance, FT-IR, and UV–Vis spectroscopies, elemental analyses, thermal analyses (TGA and DTA), and UV–Vis spectroscopy, theoretical calculations. A distorted octahedral structure around the metal ions was proposed based on the obtained experimental and calculated data. Thermal examination of the complexes signposts the step-by-step disintegration to give the final decomposition product as metal oxides. Moreover, DFT calculations were executed utilizing the B3LYP/LANL2DZ theory level, which revealed that the synthesized metal (III) complexes were more stable than the free ligand (HL). The value of ΔE for HL is 4.60 eV while the related values for the complexes of Cr(III) (C1), Ru(III) (C2), Fe(III) (C3), Al(III) (C4), and Ti(III) (C5) are respectively 2.59, 3.68, 3.15, 1.64, and 2.75 eV. Scavenging abilities of DPPH and ABTS radicals by the test compounds revealed promising antioxidant behavior. It was observed that the compounds are proficient DPPH radical scavengers in a dose-dependent configuration. Ru(III); IC50 = 1.69 ± 2.68 µM for DPPH and Ti(III); IC50 = 8.70 ± 2.78 µM for ABTS performed best. Similarly, the complexes demonstrated higher antimicrobial activities compared to HL against the designated strains, while ciprofloxacin acted as a standard antibiotic. Furthermore, the ligand and its most effective complexes C2 and C5 were docked against the targets S. aureus DNA gyrase (2XCT), S. pneumoniae DNA gyrase (5BOD), and E. coli DNA gyrase (5L3J). The binding sites were evaluated and the docking results showed that the studied molecules bind to the targets through classical O—H…O and/or N—H…O hydrogen bonds, as well as via hydrophobic contacts

Sphingomyelinase inhibitory and free radical scavenging potential of selected Nigerian medicinal plant extracts

Ceramides from sphingolipid breakdown, and other sphingolipid metabolites, mediate cellular signalling in infectious and other diseases. Therefore, inhibitors of sphingomyelinases (SMases), hold promise as prospective therapeutic agents. Considering the potential therapeutic utility, this in vitro study explored the sphingomyelinase inhibitory, and free radical scavenging potential of five Nigerian medicinal plant leaf extracts, purported to have efficacy against diseases, including HIV/AIDS. The extracts\u2019 sphingomyelinase inhibitory potencies were assessed colorimetrically and theirfree radical scavenging capabilities were assayed by the ability to quench 2,2\u2010diphenyl\u20101\u2010picrylhydrazyl (DPPH) radical and superoxide anion (O2.\u2010) radical. Considering their IC50 (\u3bcg/ml) values, the extracts inhibited the biochemical activity of sphingomyelinase in a dose-dependent manner, relative to imipramine the standard inhibitor (IC50 38.5 \ub1 2.4 \u3bcg/ml). With Aloe vera as least inhibitory, inhibition increased as follows: Aloe vera (Asphodelaceae) (1132 \ub1 10.8) < Senna siamea (Fabaceae) (992.2 \ub1 11.2) < Azadirachta indica (Meliaceae) (984 \ub1 7.4) < Landolphia owariensis (Apocynaceae) (146.3 \ub1 9.4) < Stachytarpheta angustifolia (Verbenacae) (100.3 \ub1 8.7). DPPH radical scavenging relative to ascorbic acid standard increased as: A. indica < A. vera < S. siamea < S. angustifolia < L. owariensis; and superoxide anion quenching, relative to standard rutin increased as: A. vera < S. angustifolia < L. owariensis < S. siamea < A. indica.These results showed thatthe most potent SMase inhibitor was S. angustifolia; whereas, for DPPH radical scavenging and superoxide inhibition, the most potent of the five extracts were L. owariensis and A. indica respectively.These extracts deserve further investigation into their biological effects

Musculoskeletal imaging authority, levels of training, attitude, competence, and utilisation among clinical physiotherapists in Nigeria: a cross-sectional survey

BACKGROUND: Direct-access physiotherapy practice has led to a global review of the use of differential-diagnostic modalities such as musculoskeletal imaging (MI) in physiotherapy. OBJECTIVE: To explore the MI authority, levels of training, attitude, utilisation, and competence among clinical physiotherapists in Nigeria. METHODS: This national cross-sectional study analysed a voluntary response sample of 400 Nigerian physiotherapists that completed the online version of the Physiotherapist’s Musculoskeletal Imaging Profiling Questionnaire (PMIPQ), using descriptive statistics, Spearman’s correlation, Mann-Whitney U, Kruskal-Wallis, and Friedman’s ANOVA tests. RESULTS: Of the 400 participants, 93.2% believed that physiotherapists should use MI in clinical practice. However, only 79.8% reported having MI authority in their practice settings. The participants’ median (interquartile range) levels of training =10 (24) and competence =16 (24) were moderate. Nonetheless, levels of training (χ2 [15] = 1285.899, p = 0.001), and competence (χ2 [15] = 1310.769, p < 0.001) differed across MI procedures. The level of training and competence in x-ray referral and utilisation was significantly higher than magnetic resonance imaging, computed tomography scan, ultrasonography, scintigraphy, and dual-energy x-ray absorptiometry, in that order (p < 0.05). There was a significant positive correlation between the levels of training and competence (rho =0.61, p < 0.001). The participants had a positive attitude =32 (32) and occasionally used MI in clinical practice =21 (28). CONCLUSION: Majority of the respondents believed they had MI authority although there was no explicit affirmation of MI authority in the Nigerian Physiotherapy Practice Act. Participants had a positive attitude towards MI. However, levels of MI training, competence, and utilisation were moderate. Our findings have legislative and curriculum implications

A standardised Phase III clinical trial framework to assess therapeutic interventions for Lassa fever

BACKGROUND: Only one recommendation currently exists for the treatment of Lassa fever (LF), which is ribavirin administered in conjunction with supportive care. This recommendation is primarily based on evidence generated from a single clinical trial that was conducted more than 30 years ago-the methodology and results of which have recently come under scrutiny. The requirement for novel therapeutics and reassessment of ribavirin is therefore urgent. However, a significant amount of work now needs to be undertaken to ensure that future trials for LF can be conducted consistently and reliably to facilitate the efficient generation of evidence. METHODOLOGY: We convened a consultation group to establish the position of clinicians and researchers on the core components of future trials. A Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV) were developed through the process of a multi-stakeholder consultation that took place using a modified-Delphi methodology. RESULTS: A consensus position was achieved for each aspect of the framework, which accounts for the inclusion of pregnant women and children in future LF clinical trials. The framework consists of 8 core criteria, as well as additional considerations for trial protocols. CONCLUSIONS: This project represents the first step towards delineating the clinical development pathway for new Lassa fever therapeutics, following a period of 40 years without advancement. Future planned projects will bolster the work initiated here to continue the advancement of LF clinical research through a regionally-centred, collaborative methodology, with the aim of delineating a clear pathway through which LF clinical trials can progress efficiently and ensure sustainable investments are made in research capacity at a regional level

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Metagenome Analysis of a Hydrocarbon-Degrading Bacterial Consortium Reveals the Specific Roles of BTEX Biodegraders

Environmental contamination by petroleum hydrocarbons is of concern due to the carcinogenicity and neurotoxicity of these compounds. Successful bioremediation of organic contaminants requires bacterial populations with degradative capacity for these contaminants. Through successive enrichment of microorganisms from a petroleum-contaminated soil using diesel fuel as the sole carbon and energy source, we successfully isolated a bacterial consortium that can degrade diesel fuel hydrocarbons. Metagenome analysis revealed the specific roles of different microbial populations involved in the degradation of benzene, toluene, ethylbenzene and xylene (BTEX), and the metabolic pathways involved in these reactions. One hundred and five putative coding DNA sequences were identified as responsible for both the activation of BTEX and central metabolism (ring-cleavage) of catechol and alkylcatechols during BTEX degradation. The majority of the Coding DNA sequences (CDSs) were affiliated to Acidocella, which was also the dominant bacterial genus in the consortium. The inoculation of diesel fuel contaminated soils with the consortium resulted in approximately 70% hydrocarbon biodegradation, indicating the potential of the consortium for environmental remediation of petroleum hydrocarbons