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1.
Article in English | MEDLINE | ID: mdl-38989810

ABSTRACT

INTRODUCTION: Degeneration in choroideraemia, unlike typical centripetal photoreceptor degenerations, is centred temporal to the fovea. Once the fovea is affected, the nasal visual field (temporal retina) is relatively spared, and the preferred retinal locus shifts temporally. Therefore, when reading left to right, only the right eye reads into a scotoma. We investigate how this unique property affects the ability to read an eye chart. METHODS: Standard- and low-luminance visual acuity (VA) for right and left eyes were measured with the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. Letters in each line were labelled by column position. The numbers of letter errors for each position across the whole chart were summed to produce total column error scores for each participant. Macular sensitivity was assessed using microperimetry. Central sensitivity asymmetry was determined by the temporal-versus-nasal central macular difference and subsequently correlated to a weighted ETDRS column error score. Healthy volunteers and participants with X-linked retinitis pigmentosa GTPase regulator associated retinitis pigmentosa (RPGR-RP) were used as controls. RESULTS: Thirty-nine choroideraemia participants (median age 44.9 years [IQR 35.7-53.5]), 23 RPGR-RP participants (median age 30.8 years [IQR 26.5-40.5]) and 35 healthy controls (median age 23.8 years [IQR 20.3-29.0]) were examined. In choroideraemia, standard VA in the right eye showed significantly greater ETDRS column errors on the temporal side compared with the nasal side (p = 0.002). This significantly correlated with greater asymmetry in temporal-versus-nasal central macular sensitivity (p = 0.04). No significant patterns in ETDRS column errors or central macular sensitivity were seen in the choroideraemia left eyes, nor in RPGR-RP and control eyes. CONCLUSION: Difficulty in tracking across lines during ETDRS VA testing may cause excess errors independent of true VA. VA assessment with single-letter optotype systems may be more suitable, particularly for patients with choroideraemia, and potentially other retinal diseases with asymmetric central macular sensitivity or large central scotomas including geographic atrophy.

2.
Sci Rep ; 14(1): 15110, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38956303

ABSTRACT

Recent studies show declining trends in hysterectomy rates in several countries. The objective of this study was to analyse hysterectomy time trends in Germany over a fifteen-year period using an age-period-cohort approach. Using an ecological study design, inpatient data from Diagnoses Related Group on hysterectomies by subtype performed in Germany from 2005 to 2019 were retrieved from the German Statistical Office. Descriptive time trends and age-period-cohort analyses were then performed. A total of 1,974,836 hysterectomies were performed over the study period. The absolute number of hysterectomies reduced progressively from 155,680 (365 procedures/100,000 women) in 2005 to 101,046 (257 procedures/100,000 women) in 2019. Total and radical hysterectomy decreased by 49.7% and 44.2%, respectively, whilst subtotal hysterectomy increased five-fold. The age-period-cohort analysis revealed highest hysterectomy rates in women aged 45-49 for total and subtotal hysterectomy with 608.63 procedures/100,000 women (95% CI 565.70, 654.82) and 151.30 procedures/100,000 women (95% CI 138.38, 165.44) respectively. Radical hysterectomy peaked later at 65-69 years with a rate of 40.63 procedures/100,000 women (95% CI 38.84, 42.52). The risk of undergoing total or radical hysterectomy decreased over the study period but increased for subtotal hysterectomy. Although, overall hysterectomy rates have declined, subtotal hysterectomy rates have increased; reflecting changes in clinical practice largely influenced by the availability of uterus-sparing options, evolving guidelines and introduction of newer surgical approaches.


Subject(s)
Hysterectomy , Humans , Hysterectomy/trends , Hysterectomy/statistics & numerical data , Female , Germany/epidemiology , Middle Aged , Aged , Adult , Cohort Studies , Incidence , Age Factors , Aged, 80 and over , Young Adult
3.
GM Crops Food ; 15(1): 16-27, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38859562

ABSTRACT

Ghana's parliament in 2011 passed the Biosafety Act to allow for the application of genetically modified organism (GMO) technology in the country's agriculture. In a vibrant democracy, there have been extensive media discussions on whether GM crops will benefit or harm citizens. In June 2022, the state GMO regulator, the National Biosafety Authority (NBA), approved the country's first GM crop (Bt cowpea) for environmental release, declaring the crop does not present an altered environmental risk or a food/feed safety concern. This study identified 3 of the country's most vibrant digital news outlets and did a content analysis of all GMO stories reported 18 months pre- and post-approval to assess whether the approval changed the focus of GMO issues the media reports on. 91 articles were identified. The results show media reports on the likely impact of GMOs on the country's food security shot up after the approval. However, media reports on the possible health, sociocultural, and environmental impact of GMOs declined. We observe the media and the public appear interested in deliberations on how the technology could address or worsen food insecurity and urge agricultural biotechnology actors in Ghana to focus on that in their sensitization activities.


Subject(s)
Crops, Agricultural , Plants, Genetically Modified , Ghana , Crops, Agricultural/growth & development , Crops, Agricultural/genetics , Food, Genetically Modified , Humans , Mass Media , Agriculture/methods , Agriculture/legislation & jurisprudence , Food Safety , Food Security
4.
J Hum Hypertens ; 38(2): 89-101, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38017087

ABSTRACT

Blood pressure (BP) management reduces the risk of cardiovascular disease (CVD). The renin-angiotensin-aldosterone system (RAAS) plays an important role in regulating and maintaining blood volume and pressure. This analysis aimed to investigate the effect of exercise training on plasma renin, angiotensin-II and aldosterone, epinephrine, norepinephrine, urinary sodium and potassium, BP and heart rate (HR). We systematically searched PubMed, Web of Science, and the Cochrane Library of Controlled Trials until 30 November 2022. The search strategy included RAAS key words in combination with exercise training terms and medical subject headings. Manual searching of reference lists from systematic reviews and eligible studies completed the search. A random effects meta-analysis model was used. Eighteen trials with a total of 803 participants were included. After exercise training, plasma angiotensin-II (SMD -0.71; 95% CI -1.24, -0.19; p = 0.008; n = 9 trials), aldosterone (SMD -0.37; 95% CI -0.65, -0.09; p = 0.009; n = 8 trials) and norepinephrine (SMD -0.82; 95% CI -1.18, -0.46; p < 0.001; n = 8 trials) were reduced. However, plasma renin activity, epinephrine, and 24-h urinary sodium and potassium excretion remained unchanged with exercise training. Systolic BP was reduced (MD -6.2 mmHg; 95% CI -9.9, -2.6; p = 0.001) as was diastolic BP (MD -4.5 mmHg; 95% CI -6.9, -2.1; p < 0.001) but not HR (MD -3.0 bpm; 95% CI -6.0, 0.4; p = 0.053). Exercise training may reduce some aspects of RAAS and sympathetic nervous system activity, and this explains some of the anti-hypertensive response.


Subject(s)
Renin-Angiotensin System , Renin , Humans , Renin-Angiotensin System/physiology , Aldosterone , Blood Pressure , Norepinephrine/pharmacology , Epinephrine/pharmacology , Angiotensin II , Potassium , Sodium , Exercise
5.
RSC Adv ; 13(13): 8779-8793, 2023 Mar 14.
Article in English | MEDLINE | ID: mdl-36950081

ABSTRACT

Membrane fusion is a critical and indispensable step in the replication cycles of viruses such as SARS-CoV-2 and human immunodeficiency virus type-1 (HIV-1). In this step, a trimer of the heptad repeat 1 (HR1) region interacts with the three HR2 regions and forms a 6-helix bundle (6-HB) structure to proceed with membrane fusion of the virus envelope and host cells. Recently, several researchers have developed potent peptidic SARS-CoV-2 fusion inhibitors based on the HR2 sequence and including some modifications. We have developed highly potent HIV-1 fusion inhibitors by dimerization of its HR2 peptides. Here, we report the development of dimerized HR2 peptides of SARS-CoV-2, which showed significantly higher antiviral activity than the corresponding monomers, suggesting that the dimerization strategy can facilitate the design of potent inhibitors of SARS-CoV-2.

6.
Clin Hypertens ; 29(1): 9, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36918919

ABSTRACT

More than 30 randomized controlled trials, supported by individual patient-level and group-level meta-analyses and a Delphi analysis of expert opinion, unequivocally show isometric resistance training (IRT) elicits antihypertensive benefits in healthy people and those with chronic illness. We aim to provide efficacy and safety evidence, and a guide for IRT prescription and delivery. Recommendations are made for the use of IRT in specific patient populations and appropriate methods for IRT delivery. Published data suggest IRT consistently elicits mean blood pressure reductions of 7.4/3.3 mmHg systolic blood pressure/diastolic blood pressure, equivalent to antihypertensive medication monotherapy. Blood pressure reductions of this size are associated with an approximate 13% to 22% reduction in major cardiovascular events. Moreover, IRT is safe in a range of patient populations. We suggest that IRT has the greatest potential benefit when used as an antihypertensive therapy in individuals unwilling and/or unable to complete aerobic exercise, or who have had limited adherence or success with it; individuals with resistant or uncontrolled hypertension, already taking at least two pharmacological antihypertensive agents; and healthy or clinical populations, as an adjunct to aerobic exercise and dietary intervention in those who have not yet attained control of their hypertension. IRT is efficacious and produces clinically meaningful blood pressure reductions (systolic blood pressure, 7 mmHg; diastolic blood pressure, 3 mmHg). IRT is safe and typical program delivery requires only about 17 min weekly. IRT should be used as an adjunct to other exercise modalities, in people unable to complete other types of exercise, or in resistant hypertension.

7.
Curr Hypertens Rep ; 25(4): 35-49, 2023 04.
Article in English | MEDLINE | ID: mdl-36853479

ABSTRACT

PURPOSE OF REVIEW: Hypertension is the primary risk factor for cardiovascular disease and adequate blood pressure control is often elusive. The objective of this work was to conduct a meta-analysis of trial data of isometric resistance training (IRT) studies in people with hypertension, to establish if IRT produced an anti-hypertensive effect. A database search (PubMed, CINAHL, Cochrane Central Register of Controlled Trials, and MEDLINE) identified randomised controlled and crossover trials of IRT versus a sedentary or sham control group in adults with hypertension. RECENT FINDINGS: We included 12 studies (14 intervention groups) in the meta-analyses, with an aggregate of 415 participants. IRT reduced systolic blood pressure (SBP), mean difference (MD) - 7.47 mmHg (95%CI - 10.10, - 4.84), P < 0.01; diastolic blood pressure (DBP) MD - 3.17 mmHg (95%CI - 5.29, - 1.04), P < 0.01; and mean arterial blood pressure (MAP) MD - 7.19 mmHg (95%CI - 9.06, - 5.32), P < 0.0001. Office pulse pressure and resting heart rate was not significantly reduced, neither were 24-h or day-time ambulatory blood pressures (SBP, DBP). Night-time blood pressures, however, were significantly reduced with SBP MD - 4.28 mmHg (95%CI - 7.88, - 0.67), P = 0.02, and DBP MD - 2.22 mmHg (95%CI - 3.55, - 0.88), P < 0.01. IRT does lower SBP, DBP and MAP office and night-time ambulatory SBP and DBP, but not 24-h mean ambulatory blood pressures in people with hypertension.


Subject(s)
Cardiovascular Diseases , Hypertension , Hypotension , Resistance Training , Adult , Humans , Hypertension/therapy , Blood Pressure/physiology
8.
BMJ Open ; 12(10): e064499, 2022 10 25.
Article in English | MEDLINE | ID: mdl-36283753

ABSTRACT

OBJECTIVE: The strict implementation of occupational health and safety policy curbs exposure to occupational hazards. However, empirical evidence is lacking in the Ghanaian context. This review primarily aimed to explore exposure to occupational hazards among healthcare providers and ancillary staff in Ghana. DESIGN: A scoping review was conducted based on Arksey and O'Malley's methodological framework and Levac et al's methodological enhancement. DATA SOURCES: Searches were conducted of the PubMed, MEDLINE, CINAHL, Embase, PsycINFO and Scopus databases, as well as Google Scholar and websites of tertiary institutions in Ghana, for publications from 1 January 2010 to 30 November 2021. ELIGIBILITY CRITERIA: Quantitative studies that were published in the English language and focused on occupational exposure to biological and/or non-biological hazards among healthcare professionals in Ghana were included. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted the data based on the type of occupational exposure and descriptive characteristics of the studies. The data are presented in tables and graphs. A narrative summary of review findings was prepared based on the review research questions. RESULTS: Our systematic search strategy retrieved 507 publications; however, only 43 met the inclusion criteria. A little over one-quarter were unpublished theses/dissertations. The included studies were related to biological, psychosocial, ergonomic and other non-biological hazards. 55.8% of the studies were related to exposure to biological hazards and related preventive measures. In general, health workers were reported to use and comply with control and preventive measures; however, knowledge of control and preventive measures was suboptimal. CONCLUSION: Work is needed to address the issue of occupational health hazard exposure in Ghana's health system. More research is needed to understand the extent of these exposures and their effects on the health system.


Subject(s)
Occupational Exposure , Occupational Health , Humans , Ghana , Health Personnel , Ergonomics , Occupational Exposure/adverse effects , Occupational Exposure/prevention & control
9.
Hypertens Res ; 45(3): 483-495, 2022 03.
Article in English | MEDLINE | ID: mdl-35017680

ABSTRACT

Uncontrolled hypertension remains the major risk factor for cardiovascular disease. Isometric resistance training (IRT) has been shown to be a useful nonpharmacological therapy for reducing blood pressure (BP); however, some exercise physiologists and other health professionals are uncertain of the efficacy and safety of IRT. Experts' consensus was sought in light of the current variability of IRT use as an adjunct treatment for hypertension. An expert consensus-building analysis (Delphi study) was conducted on items relevant to the safety, efficacy and delivery of IRT. The study consisted of 3 phases: (1) identification of items and expert participants for inclusion; (2) a two-round modified Delphi exercise involving expert panelists to build consensus; and (3) a study team consensus meeting for a final item review. A list of 50 items was generated, and 42 international experts were invited to join the Delphi panel. Thirteen and 10 experts completed Delphi Rounds 1 and 2, respectively, reaching consensus on 26 items in Round 1 and 10 items in Round 2. The study team consensus meeting conducted a final item review and considered the remaining 14 items for the content list. A final list of 43 items regarding IRT reached expert consensus: 7/10 items on safety, 11/11 items on efficacy, 10/12 items on programming, 8/10 items on delivery, and 7/7 on the mechanism of action. This study highlights that while experts reached a consensus that IRT is efficacious as an antihypertensive therapy, some still have safety concerns, and there is also ongoing conjecture regarding optimal delivery.


Subject(s)
Resistance Training , Blood Pressure , Consensus , Delphi Technique , Humans
10.
J Evid Based Integr Med ; 27: 2515690X211073709, 2022.
Article in English | MEDLINE | ID: mdl-35037519

ABSTRACT

Malaria affects about half of the world's population. The sub-Saharan African region is the most affected. Plant natural products have been a major source of antimalarial drugs; the first (quinine) and present (artemisinin) antimalarials are of natural product origin. Some secondary metabolites demonstrate adjuvant antioxidant effects and selective activity. The focus of this study was to investigate the anti-plasmodial activity, cytotoxicities and antioxidant properties of eight (8) Ghanaian medicinal plants. The anti-plasmodial activity was determined using the SYBR green assay and the tetrazolium-based colorimetric assay (MTT) was employed to assess cytotoxicity of extracts to human RBCs and HL-60 cells. Antioxidant potential of plant extracts was evaluated using Folin-Ciocalteu and superoxide dismutase assays. Phytochemical contstituents of the plant extracts were also assessed. All the extracts demonstrated anti-plasmodial activities at concentrations <50 µg/ml. Parkia clappertoniana and Terminalia ivorensis elicited the strongest anti-plasmodial activities with 50% inhibitory concentrations (IC50) of 1.13 µg/ml and 0.95 µg/ml, respectively. This is the first report on anti-plasmodial activities of Baphia nitida, Tabernaemontana crassa and Treculia Africana. T. Africana showed moderate anti-plasmodial activity with IC50 value of 6.62 µg/mL. Extracts of P. clappertoniana, T. Africana and T. ivorensis (0.4 mg/mL) showed >50% antioxidant effect (SOD). The extracts were not cytotoxicity towards RBCs at the concentration tested (200 µg/ml) but were weakly cytotoxic to HL-60 cell. Selectivity indices of most of the extracts were greater than 10. Our results suggest that most of the plant extracts have strong anti-plasmodial activity and antioxidant activity which warrants further investigations.


Subject(s)
Plants, Medicinal , Antioxidants/pharmacology , Ghana , Humans , Plants, Medicinal/chemistry , Plasmodium berghei , Plasmodium falciparum
11.
BMJ Open ; 12(1): e058048, 2022 Jan 04.
Article in English | MEDLINE | ID: mdl-34983774

ABSTRACT

INTRODUCTION: The formation, modification and implementation of occupational health and safety policy for the Ghana healthcare industry hinge on data and reviews on occupational exposures. However, there is no synthesised review to speak to the issues of these occupational exposures. A scoping review on occupational exposures among the health workforce in Ghana will provide a broad overview of exposures, and can guide and assist in making decisions on occupational health issues relating to healthcare workers. METHODS AND ANALYSIS: Arksey and O'Malley's scoping review methodology framework will guide the conduct of this scoping review. Primary research studies, government documents and other information on occupational exposures among healthcare workers published in the English language will be retrieved from databases including PubMed, CINAHL, Embase, MEDLINE, Scopus, PsycINFO and Google scholar. A systematic search strategy will be employed to identify articles from 1 January 2010 until 30 November 2021. Also, grey literature sources in Ghana including government and tertiary institutions websites will be searched. A reference list of key studies and other available non-electronic materials will also be screened to identify relevant studies for inclusion. The review will consider studies that address prevalence, knowledge and predisposing factors of occupational exposures along with the use of occupational hazards control/preventive measures. After removal of duplicates, and title and abstract screening, relevant articles will be subjected to full-text analysis. The screening processes will be conducted independently by two reviewers. Data will then be extracted and presented in tabular form with a narrative to aid easy comprehension. ETHICS AND DISSEMINATION: This scoping review does not require ethical approval. The findings will be disseminated through publications, conference presentations and stakeholder meetings.


Subject(s)
Occupational Health , Delivery of Health Care/methods , Ghana , Health Personnel , Health Workforce , Humans , Research Design , Review Literature as Topic
12.
Int J Cardiol Hypertens ; 8: 100081, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33748739

ABSTRACT

BACKGROUND: Previous work has evaluated the effect of remote ischaemic conditioning (RIC) in a number of clinical conditions (e.g. cardiac surgery and acute kidney injury), but only one analysis has examined blood pressure (BP) changes. While individual studies have reported the effects of acute bouts and repeated RIC exposure on resting BP, efficacy is equivocal. We conducted a systematic review and meta-analysis to evaluate the effects of acute and repeat RIC on BP. METHODS: A systematic search was performed using PubMed, Web of Science, EMBASE, and Cochrane Library of Controlled Trials up until October 31, 2020. Additionally, manual searches of reference lists were performed. Studies that compared BP responses after exposing participants to either an acute bout or repeated cycles of RIC with a minimum one-week intervention period were considered. RESULTS: Eighteen studies were included in this systematic review, ten examined acute effects while eight investigated repeat effects of RIC. Mean differences (MD) for outcome measures from acute RIC studies were: systolic BP 0.18 mmHg (95%CI -0.95, 1.31; p = 0.76), diastolic BP -0.43 mmHg (95%CI -2.36, 1.50; p = 0.66), MAP -1.73 mmHg (95%CI -3.11, -0.34; p = 0.01) and HR -1.15 bpm (95%CI -2.92, 0.62; p = 0.20). Only MAP was significantly reduced. Repeat RIC exposure showed non-significant change in systolic BP -3.23 mmHg (95%CI -6.57, 0.11; p = 0.06) and HR -0.16 bpm (95%CI -7.08, 6.77; p = 0.96) while diastolic BP -2.94 mmHg (95%CI -4.08, -1.79; p < 0.00001) and MAP -3.21 mmHg (95%CI -4.82, -1.61; p < 0.0001) were significantly reduced. CONCLUSIONS: Our data suggests repeated, but not acute, RIC produced clinically meaningful reductions in diastolic BP and MAP.

13.
J Exp Pharmacol ; 13: 223-234, 2021.
Article in English | MEDLINE | ID: mdl-33707973

ABSTRACT

PURPOSE: Male sexual dysfunction negatively affects an individual's quality of life and thus its of prime public concern, hence the need to boost reproductive abilities in such individuals. This study assessed the effect of hydroethanolic root extracts of Caesalpinia benthamiana (CBRE), Sphenocentrum jollyanum (SJRE), and Paullinia pinnata (PPRE), commonly used as aphrodisiacs in Ghana, using male Sprague-Dawley rats. METHODS: Plasma testosterone, follicle-stimulating hormone, and luteinizing hormone were assayed in grouped rats treated orally with 1 mL/kg normal saline, 50 mg/kg monosodium glutamate (MSG), and 100, 300, or 1000 mg/kg CBRE, SJRE, and PPRE, respectively, for 60 days. Epididymis and testis weights were determined. Semen was assessed on spermatozoa count, motility, and morphology. Malonyladehyde formation in lipid-peroxidation assay and histological examinations were performed to assess pathological changes in testes. Testicular testosterone was also assayed. RESULTS: While MSG, CBRE, SJRE, and PPRE treatments did not result in significant reduction (p>0.05) in plasma testosterone, there was significant reduction (p≤0.05 -0.0001) in plasma luteinizing hormone, and follicle-stimulating hormone. The combined mean wet weights of epididymides and testes of all treated groups did not vary significantly (p>0.05) from the control. There was significant reduction (p≤0.0001) in sperm motility and count, with significant morphological changes (p≤0.05-0.001), ie, bent necks, tails, and midpieces, and multiple anomalies in the spermatozoa in extract and MSG-treated groups. There was also significant (p≤0.0001) reduction in testicular testosterone among all treatment groups. CONCLUSION: Hydroethanolic CBRE, SJRE, and PPRE were found to have detrimental effects on reproductive function with prolonged usage and thus may not be safe to use in healthy males who intend to reproduce.

14.
Breast Cancer Res Treat ; 186(2): 391-401, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33576900

ABSTRACT

PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive subtype most prevalent among women of Western Sub-Saharan African ancestry. It accounts for 15-25% of African American (AA) breast cancers (BC) and up to 80% of Ghanaian breast cancers, thus contributing to outcome disparities in BC for black women. The aggressive biology of TNBC has been shown to be regulated partially by breast cancer stem cells (BCSC) which mediate tumor recurrence and metastasis and are more abundant in African breast tumors. METHODS: We studied the biological differences between TNBC in women with African ancestry and those of Caucasian women by comparing the gene expression of the BCSC. From low-passage patient derived xenografts (PDX) from Ghanaian (GH), AA, and Caucasian American (CA) TNBCs, we sorted for and sequenced the stem cell populations and analyzed for differential gene enrichment. RESULTS: In our cohort of TNBC tumors, we observed that the ALDH expressing stem cells display distinct ethnic specific gene expression patterns, with the largest difference existing between the GH and AA ALDH+ cells. Furthermore, the tumors from the women of African ancestry [GH/AA] had ALDH stem cell (SC) enrichment for expression of immune related genes and processes. Among the significantly upregulated genes were CD274 (PD-L1), CXCR9, CXCR10 and IFI27, which could serve as potential drug targets. CONCLUSIONS: Further exploration of the role of immune regulated genes and biological processes in BCSC may offer insight into developing novel approaches to treating TNBC to help ameliorate survival disparities in women with African ancestry.


Subject(s)
Triple Negative Breast Neoplasms , Black or African American/genetics , Female , Ghana/epidemiology , Humans , Neoplasm Recurrence, Local , Triple Negative Breast Neoplasms/genetics , White People
15.
Toxicon ; 193: 28-37, 2021 Apr 15.
Article in English | MEDLINE | ID: mdl-33493498

ABSTRACT

Dichapetalum madagascariense Poir (Dichapetalaceae) is traditionally used to treat bacterial infections, jaundice, urethritis and viral hepatitis in Africa. Its root contains a broad spectrum of biologically active dichapetalins. To evaluate the plant's effect on human MCF-7 cells and its' antibacterial and antiparasitic potentials, we isolated and identified the known dichapetalins A and M from the roots. Both dichapetalins were tested on six bacterial strains (Shigella flexneri, Bacillus cereus, Salmonella paratyphi B, Listeria monocytogenes, Escherichia coli, Staphylococcus aureus) and two parasite strains; Trypanosoma brucei brucei, and Leishmania donovani using the Alamar Blue assay system. Dichapetalins A and M were more potent against B. cereus with IC50 values of 11.15 and 3.15 µg/ml, respectively, compared to the positive control ampicillin (IC50 = 19.50 µg/ml). Dichapetalins A (IC50 = 74.22 µg/ml) and M (IC50 = 72.34 µg/ml) were less active against T. b. brucei, compared to the standard Suramin (IC50 = 4.96 µg/ml). Dichapetalin M showed moderate activity against L. donovani (Amphotericin B: IC50 = 0.21 µg/ml) with an IC50 of 16.80 µg/ml. In human MCF-7 cells expressing the NR1I2 receptor, the activity of dichapetalin M was higher (IC50 = 4.71 µM and 3.95 µM) for 48 and 72 h of treatment, respectively compared to Curcumin with IC50 of 17.49 µM and 12.53 µM for 48 and 72 h of treatment, respectively. Results from in vitro expression studies with qPCR confirmed an antagonistic effect of dichapetalin M on PXR (NR1I2) signaling; supporting the PXR signaling pathway as a possible mode of action of dichapetalin M as predicted by in silico results. These findings confirm previous studies that D. madagascariense can be a source of potential lead compounds for development of novel antibiotic, antiparasitic and anticancer medicines, and provide further insights into the mechanism of action of the dichapetalins.


Subject(s)
Anti-Bacterial Agents , Plant Extracts/pharmacology , Africa , Anti-Bacterial Agents/pharmacology , Computer Simulation , Humans , Microbial Sensitivity Tests , Staphylococcus aureus
16.
Bioorg Med Chem ; 30: 115923, 2021 01 15.
Article in English | MEDLINE | ID: mdl-33316719

ABSTRACT

Several anti-HIV-1 peptides have previously been found among overlapping fragment peptide libraries that contain an octa-arginyl moiety and cover the whole sequence of an HIV-1 capsid (CA) protein. Several derivatives based on a potent CA fragment peptide CA-19L have been synthesized. CA-19L overlaps with the Helix 9 region of the CA protein, which could be important for oligomerization of the CA proteins. Derivatives of CA-19L in which several amino acid residues were added to the N- and C-termini according to the natural CA sequence, were synthesized and their anti-HIV activity was evaluated. Some potent compounds were found, and these potential new anti-HIV agents are expected to be useful as new tools for elucidation of CA functions.


Subject(s)
Anti-HIV Agents/pharmacology , Capsid Proteins/antagonists & inhibitors , HIV-1/drug effects , Anti-HIV Agents/chemistry , Capsid Proteins/metabolism , Dose-Response Relationship, Drug , Humans , Microbial Sensitivity Tests , Protein Conformation , Structure-Activity Relationship
17.
Article in English | WPRIM (Western Pacific) | ID: wpr-916028

ABSTRACT

Objectives@#The mandible and other parts of the maxillofacial region suffer significant morbid injuries following road traffic accidents. Our studygives epidemiological description of mandibular fractures in Ghana and also evaluates the relevance of closed reduction and indirect fixation for managing mandibular fractures in low-resource health facilities in low-income countries like Ghana. @*Patients and Methods@#This is a retrospective study involving 268 patients who reported to the Department of Oral and Maxillofacial Surgery of the Sunyani Regional Hospital with mandibular fractures from January 2010 to December 2019. Patient medical records were assessed for information on age, sex, fracture etiology, anatomic location of fracture, time of day of road traffic accident, and other associated injuries. @*Results@#A total of 268 patients were included in this study (males, 216 [80.6%]; females, 52 [19.4%]). Motor vehicular accident (MVA) was the lead-ing cause of mandibular fractures (202 injuries, 75.4%). Other etiologies included assault (39, 14.6%), gunshot (13, 4.9%), falls (12, 4.5%), and indus-trial accidents (2, 0.7%). Of the 161 male cases caused by MVA, 121 (75.2%) occurred at night and in the evening while the remaining 40 (24.8%) oc-curred in the morning and afternoon. Among all managed 222 patients, 212 (79.1%) were treated with closed reduction and indirect fixation technique while 10 (3.7%) were treated with open reduction and direct fixation. @*Conclusion@#Closed reduction with indirect fixation could successfully be used to manage mandibular fractures in low resourced health facilities, es-pecially in low-income countries. The poor lightening system on roads in Ghana is a major contributory factor to motor vehicular accidents.

18.
BMC Infect Dis ; 20(1): 323, 2020 May 06.
Article in English | MEDLINE | ID: mdl-32375658

ABSTRACT

BACKGROUND: Praziquantel (PZQ) is the standard treatment for Schistosomiasis in sub-Saharan Africa. However, there is evidence suggesting praziquantel treatment failure in Schistosome infections with associated potential renal impairment. The objective of this study was to determine the effect of three monthly doses of 60 mg/kg/day PZQ on schistosome egg count, liver and renal function during the treatment of urinary schistosomiasis in Ghana. METHODS: A nested case-control study was designed from a cohort screened for schistosomiasis; 28 schistosomiasis positive cases by microscopy matched with 53 healthy controls by age and gender. The study population was urban dwellers from the Asokwa sub-metropolitan area, Kumasi in Ghana. Participants were within the age range of 6 to 30 years. We assessed Schistosoma haematobium egg counts in urine and its associated impact on liver and renal function at baseline, treatment and post-treatment phases using serum. RESULTS: Of the 28 cases and 53 controls, 78.6% and 81.1% were males respectively. Globulin levels before treatment was higher in cases [36.7 (32.8, 40.1) vrs 30.5 (22.4, 33.8), p = 0.005] at pre-treatment but not at post-treatment [35.8 (31.2, 39.1) vrs 37.4 (29.7, 43.0), p = 0.767]. Estimated cure rate was 42.9, 46.4 and 96.4% after first, second and third dose respectively. Schistosome egg counts dropped significantly (p = 0.001) from before second dose to post-treatment. Similarly, levels of alanine aminotransferase (p = 0.001), aspartate aminotransferase (p = 0.028) and gamma glutamyl transferase (p = 0.001) significantly declined towards post-treatment. Estimated glomerular filtration rate significantly improved from before second dose to post-treatment using both the Chronic Kidney Disease Epidemiology Program (p = 0.001) and 4-variable Modification of Diet in Renal Disease (p = 0.002) equations. CONCLUSION: Treatment of urinary Schistosoma hematobium infections with a repeated high monthly dose of 60 mg/kg of praziquantel for 3 months is safe and effective.


Subject(s)
Anthelmintics/administration & dosage , Praziquantel/administration & dosage , Schistosoma haematobium/drug effects , Schistosomiasis haematobia/drug therapy , Adolescent , Adult , Alanine Transaminase/blood , Animals , Anthelmintics/therapeutic use , Aspartate Aminotransferases/blood , Case-Control Studies , Child , Cohort Studies , Drug Administration Schedule , Female , Ghana , Glomerular Filtration Rate , Humans , Kidney Function Tests , Liver/drug effects , Liver/physiology , Male , Parasite Egg Count , Praziquantel/therapeutic use , Treatment Failure , Treatment Outcome , Young Adult
19.
J Fam Pract ; 69(3): 135-144, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32289127

ABSTRACT

It's an exciting era of asthma management, with the introduction of several novel modalities, including biological therapy and bronchial thermoplasty.


Subject(s)
Asthma/therapy , Azithromycin/therapeutic use , Bronchial Thermoplasty/standards , Corticosterone/therapeutic use , Muscarinic Agonists/therapeutic use , Practice Guidelines as Topic , Adult , Aged , Aged, 80 and over , Asthma/epidemiology , Asthma/physiopathology , Female , Humans , Male , Middle Aged , United States/epidemiology
20.
Bioorg Med Chem ; 28(11): 115488, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32305183

ABSTRACT

Utilizing overlapping fragment peptide libraries covering the whole sequence of an HIV-1 capsid (CA) protein with the addition of an octa-arginyl moiety, we had previously found several peptides with anti-HIV-1 activity. Herein, among these potent CA fragment peptides, CA-15L was examined because this peptide sequence overlaps with Helix 7, a helix region of the CA protein, which may be important for oligomerization of the CA proteins. A CA-15L surrogate with hydrophilic residues, and its derivatives, in which amino acid sequences are shifted toward the C-terminus by one or more residues, were synthesized and their anti-HIV activity was evaluated. In addition, its derivatives with substitution for the Ser149 residue were synthesized and their anti-HIV activity was evaluated because Ser149 might be phosphorylated in the step of degradation of CA protein oligomers. Several active compounds were found and might become new anti-HIV agents and new tools for elucidation of CA functions.


Subject(s)
Anti-HIV Agents/pharmacology , Capsid Proteins/antagonists & inhibitors , HIV/drug effects , Peptide Fragments/pharmacology , Anti-HIV Agents/chemistry , Capsid Proteins/metabolism , Dose-Response Relationship, Drug , Humans , Microbial Sensitivity Tests , Molecular Structure , Peptide Fragments/chemistry , Structure-Activity Relationship
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