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1.
BMJ Open ; 13(8): e068551, 2023 08 22.
Article in English | MEDLINE | ID: mdl-37607792

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has wide-reaching health and non-health consequences, especially on mental health and psychosocial well-being. Healthcare workers involved in COVID-19 patient care are particularly vulnerable to psychosocial distress due to increased pressure on healthcare systems. We explored the psychosocial experiences of front-line healthcare workers during the COVID-19 pandemic in Sierra Leone. METHODS: This qualitative study used purposive sampling to recruit 13 healthcare workers from different cadres across 5 designated COVID-19 treatment centres in Freetown, Sierra Leone. In-depth interviews were conducted remotely in July and August 2020, transcribed verbatim and analysed using the framework approach. RESULTS: This study identified three overarching themes: vulnerability, resilience and support structures. Participants expressed vulnerability relating to the challenging work environment and lack of medications as key stressors resulting in anxiety, stress, anger, isolation and stigmatisation. Signs of resilience with experiences drawn from the 2014 Ebola outbreak, teamwork and a sense of duty were also seen. Peer support was the main support structure with no professional psychosocial support services available to healthcare workers. CONCLUSIONS: This is the first study to provide evidence of the psychosocial impacts of COVID-19 among front-line healthcare workers in Sierra Leone. Despite signs of resilience and coping mechanisms displayed, they also experienced adverse psychosocial outcomes. There is a need to focus on enhancing strategies such as psychosocial support for healthcare workers and those that overall strengthen the health system to protect healthcare workers, promote resilience and guide recommendations for interventions during future outbreaks.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Sierra Leone/epidemiology , COVID-19 Drug Treatment , Pandemics , Health Personnel
2.
Foodborne Pathog Dis ; 19(6): 408-416, 2022 06.
Article in English | MEDLINE | ID: mdl-35451874

ABSTRACT

Antimicrobials have been widely used in dairy farms to prevent and control dairy cattle diseases since 1960s. This led to the emergence of antimicrobial resistant bacteria (ARB) that, along with their antimicrobial resistance genes (ARGs), can spread from dairy farms to humans. Therefore, regular antimicrobial resistance (AMR) monitoring is important to implement proper mitigation measures. The objective of this study was to determine the prevalence of AMR and extended-spectrum beta-lactamases (ESBLs)-producing Escherichia coli in dairy cattle. A cross-sectional study was conducted in four dairy cattle farms (A-D) in East Tennessee. A total of 80 samples consisting of 20 samples each of bulk tank milk, feces, dairy cattle manure-amended soil, and prairie soil adjacent to the farms were collected and cultured for the isolation of E. coli. Tetracycline (TETr)-, third-generation cephalosporin (TGCr)- and nalidixic acid (NALr)-resistant E. coli (n = 88) were isolated and identified on agar media supplemented with TET, cefotaxime, and NAL, respectively. TGCr E. coli were tested for ESBLs and other coselected ARGs. TETr (74%, n = 88) was the most common, followed by TGCr (20%) and NALr (8%). Farms had significant (p < 0.001) differences: the highest prevalence of TGCr (55%) and TETr (100%) were observed in farm D, while all NALr isolates were from farm C. Over 83% of TGCr isolates (n = 18) harbored ESBL gene blaCTX-M. Majority (78%) of the E. coli isolates were multidrug-resistant (MDR), being positive for beta-lactams (blaCTX-M), TETs tet(A), tet(B), tet(M)), sulfonamides (sul2), aminoglycosides (strA), and phenicols (floR). This study indicated the widespread occurrence of MDR ESBLs-E. coli in dairy cattle farms. AMR surveillance of more dairy farms and identification of farm-level risk factors are important to mitigate the occurrence and spread of ARB of significant public health importance, such as ESBLs-E. coli.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Bacterial , Escherichia coli Infections , Escherichia coli , Animals , Anti-Bacterial Agents/pharmacology , Cattle/microbiology , Cross-Sectional Studies , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Escherichia coli Infections/veterinary , Farms , Prevalence , Soil , Tennessee/epidemiology , beta-Lactamases/genetics
3.
ScientificWorldJournal ; 2019: 7357048, 2019.
Article in English | MEDLINE | ID: mdl-31427902

ABSTRACT

Mushrooms produce a variety of bioactive compounds that are known to have a potential source of antioxidant and antimicrobial properties. Natural antioxidants can protect against free radicals without any side effects. The purpose of this study was to evaluate the antioxidant and antimicrobial activities of Auricularia and Termitomyces extracts. Specimens of Auricularia and Termitomyces spp. were collected from Kakamega National Reserve Forest in Kenya. Specimens were identified, extracted, and screened for their antioxidant and antimicrobial activities using stable free radical DPPH and colorimetric bioassay methods, respectively. The antimicrobial activity of the extracts was tested against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, MRSA, Candida albicans, and Candida parapsilosis. The maximum scavenging activity of hot water extract of Auricularia spp. was observed at 70.4% with the IC50 value of 40 µg/mL. Of the three extracts of Termitomyces spp., 70% ethanol extract has shown the highest scavenging activity (63%) with the IC50 value of 50 µg/mL. Chloroform and hot water extracts of Auricularia have shown statistically significantly different antifungal activities against C. parapsilosis (df = 2, F = 22.49, p ≤ 0.05). Of all the organisms, S. aureus was highly susceptible to 70% ethanol and hot water extracts of Termitomyces spp. with minimum inhibitory concentration values of 0.67±0.29 mg/mL. S. aureus and E. coli were the most susceptible and resistant bacteria to the hot water extract, respectively. In conclusion, the extracts of Auricularia spp. and Termitomyces spp. have shown promising antimicrobial and antioxidant activities.


Subject(s)
Agaricales/chemistry , Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Plant Extracts/pharmacology , Termitomyces/chemistry , Free Radical Scavengers/pharmacology , Geography , Kenya , Microbial Sensitivity Tests
4.
Am J Hum Biol ; 31(6): e23296, 2019 11.
Article in English | MEDLINE | ID: mdl-31332861

ABSTRACT

OBJECTIVE: Police officers have higher rates of cardiovascular disease (CVD) morbidity and mortality than the U.S. general population. Officers are exposed to conventional and unexpected workplace stressors. The hypothalamic-pituitary-adrenal (HPA) axis plays a major role responding to stressor exposure by releasing cortisol. Prolonged release or excessive levels may result in disease. Our study investigated cross-sectional associations between self-reported work stress and various salivary cortisol parameters. METHODS: A total of 285 police officers (76.5% male) from the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) Study (2004-2009) completed the Spielberger Police Stress Survey, reporting frequency and severity of work events during the past month and year to calculate stress indices. Officers provided saliva samples to measure levels of cortisol secretion. Linear regression assessed associations between stress indices and various cortisol parameters, adjusted for age, gender, race/ethnicity, abdominal height, and smoking status. RESULTS: Significant positive associations were observed between stress indices (overall stress, physical danger stress, and past-month lack of support) and diurnal cortisol (AUCg: total area under the curve). Administrative, overall, and physical danger stress in the past year were significantly associated with the diurnal slope. Overall, administrative, and physical danger stress were significantly associated with bedtime levels. There were no significant associations between the stress indices and the awakening cortisol parameters. CONCLUSIONS: Higher stress ratings were related to blunted diurnal decline in cortisol, suggesting conventional and unexpected police stressors may result in HPA axis dysfunction. Future studies investigating possible associations between elevated cortisol and subclinical CVD are needed.


Subject(s)
Hydrocortisone/metabolism , Occupational Stress/epidemiology , Police/statistics & numerical data , Adult , Circadian Rhythm , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , New York/epidemiology , Occupational Stress/psychology , Saliva/chemistry , Self Report
5.
Epilepsy Behav ; 37: 236-40, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25108115

ABSTRACT

Epilepsy is associated with a significant burden of false beliefs and social stigma in the setting of Sub-Saharan Africa. To assess the impacts of epilepsy on child education in Sierra Leone (SL), we carried out a cross-sectional descriptive study examining its effects on school attendance, participation in physical activities, and social acceptance among classmates. We also assessed the knowledge, beliefs, and attitudes regarding epilepsy of both the children's caregivers and teachers. The data were collected at various epilepsy clinics and schools in Freetown, SL. A total of 50 patients were interviewed and questionnaires administered to their caregivers and teachers, making a total of 150 respondents. Fifty-one percent of the children were absent from school for >5 days per month. Ninety percent did not participate in games and sports, with the commonest reason being fear of occurrence of seizures. Thirty-six percent claimed having experienced negative attitude from their classmates. Regarding the caregivers, 48% believed that epilepsy was a medical illness, while 34% considered it a demonic manifestation. Forty-eight percent were apprehensive about sending their children to school, with 83% of these caregivers stating fear of seizures and potential injuries. Only 8% of the caregivers did not prevent their children from taking part in any physical activity at school. Regarding the teachers, 16% believed that epilepsy was a demonic manifestation, and 10% thought that it was contagious. Fourteen percent did not think that children with epilepsy should go to school, and 80% would prevent children with epilepsy from participating in games and sports. When faced with a child having a seizure, 48% would hold the child down, 12% would place a hard object in the child's mouth, and 12% would avoid any physical contact. In total, 20% of the children ceased attending school permanently; daily occurrence of seizures (p<0.05), negative attitude of classmates (p<0.001), and having an illiterate caregiver (p<0.02) all showed a significant association with permanent cessation of schooling. The study demonstrates significant negative impacts of epilepsy on child education. Notably, the reasons for permanent exclusion from school appear to be as much related to attitudes as to the medical aspects of the disease itself. The data thus highlight the need for educational programs to address the widely prevalent misconceptions among both caregivers and teachers.


Subject(s)
Epilepsy/complications , Epilepsy/psychology , Schools , Seizures/psychology , Adolescent , Child , Cross-Sectional Studies , Fear , Health Knowledge, Attitudes, Practice , Health Services Needs and Demand , Humans , Interviews as Topic , Psychological Distance , Seizures/etiology , Sickness Impact Profile , Sierra Leone , Social Stigma , Surveys and Questionnaires
6.
J Toxicol Environ Health A ; 77(12): 705-15, 2014.
Article in English | MEDLINE | ID: mdl-24786677

ABSTRACT

Welding fume is composed of a complex of different metal particulates. Pulmonary exposure to different welding fumes may exert a negative impact on cardiac function, although the underlying mechanisms remain unclear. To explore the effect of welding fumes on cardiac function, Sprague-Dawley rats were exposed by intratracheal instillation to 2 mg/rat of manual metal arc hard surfacing welding fume (MMA-HS) once per week for 7 wk. Control rats received saline. Cardiomyocytes were isolated enzymatically at d 1 and 7 postexposure. Intracellular calcium ([Ca(2+)]i) transients (fluorescence ratio) were measured on the stage of an inverted phase-contrast microscope using a myocyte calcium imaging/cell length system. Phosphorylation levels of cardiac troponin I (cTnI) were determined by Western blot. The levels of nonspecific inflammatory marker C-reactive protein (CRP) and proinflammatory cytokine interleukin-6 (IL-6) in serum were measured by enzyme-linked immunosorbent assay (ELISA). Contraction of isolated cardiomyocytes was significantly reduced at d 1 and d 7 postexposure. Intracellular calcium levels were decreased in response to extracellular calcium stimulation at d 7 postexposure. Changes of intracellular calcium levels after isoprenaline hydrochloride (ISO) stimulation were not markedly different between groups at either time point. Phosphorylation levels of cTnI in the left ventricle were significantly lower at d 1 postexposure. The serum levels of CRP were not markedly different between groups at either time point. Serum levels of IL-6 were not detectable in both groups. Cardiomyocyte alterations observed after welding fume treatment were mainly due to alterations in intracellular calcium handling and phosphorylation levels of cTnI.


Subject(s)
Gases/toxicity , Lung/drug effects , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Stainless Steel , Welding , Animals , C-Reactive Protein/metabolism , Calcium/metabolism , Endpoint Determination , Enzyme-Linked Immunosorbent Assay , Interleukin-6/blood , Isoproterenol/metabolism , Lung/metabolism , Male , Models, Animal , Phosphorylation , Rats , Rats, Sprague-Dawley , Troponin I/metabolism
8.
Am J Hum Biol ; 25(4): 499-507, 2013.
Article in English | MEDLINE | ID: mdl-23606277

ABSTRACT

OBJECTIVES: Chronic stress, characteristic of police work, affects the hypothalamic-pituitary-adrenal axis' control of cortisol production. Capacity to vary cortisol may be the appropriate measurement to interpret associations with chronic diseases, including obesity, best measured by variability within a person, not central tendency. METHODS: On each of 217 policemen, 18 saliva specimens were obtained for cortisol. Statistical models examined the associations of within-subjects (W-S) cortisol standard deviation (SD) and W-S cortisol mean with waist circumference and four body composition indexes: BMI, and three derived from DEXA: fat-mass, and trunk and extremities lean-mass. Explained variance and the functional nature of associations are reported. RESULTS: Associations of anthropometrics with W-S cortisol mean were not statistically significant at P < 0.05; all associations with W-S cortisol SD were significant. The association of trunk lean mass index (LMIt ) with W-S cortisol SD dominated all models. Associations of W-S cortisol SD with other indexes vanished when models contained LMIt ; when any other index was included in models predicting LMIt , associations with W-S cortisol SD remained significant. The functional association between LMIt and W-S cortisol SD is progressively "hockey stick," monotonic increasing, and flattens at joint high values. CONCLUSIONS: Results support inferences that LMIt measures visceral adiposity and W-S cortisol variability appears to be an appropriate construct to measure in association with visceral adiposity. The "hockey stick" character of the association is consistent with other investigations suggesting obesity is associated with less W-S cortisol variation; however, the monotonic increase and flattening of association at increasing W-ScortisolSD values suggests a more complex association, potentially interpretable by allostasis models of causation.


Subject(s)
Hydrocortisone/analysis , Obesity/metabolism , Police , Saliva/chemistry , Stress, Psychological/metabolism , Adult , Black or African American , Body Fat Distribution , Body Mass Index , Body Weights and Measures , Cross-Sectional Studies , Humans , Male , Middle Aged , Obesity/ethnology , Stress, Psychological/ethnology , White People
9.
Psychosom Med ; 69(7): 651-9, 2007.
Article in English | MEDLINE | ID: mdl-17766693

ABSTRACT

OBJECTIVE: To derive the area under the curve and related summary measures of stress from saliva samples collected over time and to provide insight into the interpretation of the derived parameters. In research designed to assess the health consequences of stress these samples are often used as a physiologic indicator of the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis. To make these repeated measurements of salivary cortisol more useful in defining the relationships between stress and health there is a need to derive two forms of area under the curve that summarize the measurements: area under the curve with respect to ground (AUC(G)) and area under the curve with respect to increase (AUC(I)). The latter parameters, AUC(I), however, is seldom used by research scientists. METHODS: In this study, interpretation and generic definition of the area under the curve was provided through graphical analyses and examination of its association with other summary measures using data from the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) Pilot Study. In generic form, AUC(I) is derived as the area under the curve above the baseline value minus the area above the curve below the baseline value. RESULTS: The sign and magnitude of AUC(I) are related to the profile and the rate of change of the measurements over time. The parameter showed significant associations with other summary indicators that measure pattern or rate of change of the measurements over time. CONCLUSION: Principal components analyses revealed that summary parameters derived from repeated cortisol measurements can be grouped into two meaningful general categories: measures of the magnitude of response and measures of the pattern of response over time.


Subject(s)
Hydrocortisone/analysis , Saliva/chemistry , Area Under Curve , Humans , Hydrocortisone/pharmacokinetics , Principal Component Analysis , Reference Values , Reproducibility of Results , Wakefulness
10.
Gen Pharmacol ; 30(3): 403-10, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9510094

ABSTRACT

1. Studies were designed to investigate the responses of isolated pulmonary arteries from control pigs or pigs chronically treated with dexfenfluramine (7.2 mg/kg per day orally for 4 weeks). 2. Rings with and without endothelium were suspended in organ chambers for recording of isometric tension. 3. Dexfenfluramine (10[-9] to 10[-6] M) did not affect vascular tone, but at higher concentrations caused contractions that were not affected by indomethacin, methiothepin, the presence of endothelium or by the chronic treatment. 4. Chronic treatment augmented the endothelium-dependent relaxations to serotonin and aggregating platelets but not those to adenosine diphosphate. It did not affect the contraction or rings without endothelium evoked by platelets, nor the relaxation to SIN-1, a nitric oxide donor. The maximal contraction to endothelin-1 (but not that of norepinephrine) was impaired in treated pigs. 5. These results show that dexfenfluramine causes contraction of isolated porcine pulmonary arteries only at concentrations higher than 3 x 10(-6) M, and that chronic treatment with dexfenfluramine potentiates the endothelium-dependent relaxations to serotonin and aggregating platelets in the porcine pulmonary artery without affecting their direct effect on the smooth muscle.


Subject(s)
Fenfluramine/pharmacology , Muscle, Smooth, Vascular/drug effects , Pulmonary Artery/drug effects , Selective Serotonin Reuptake Inhibitors/pharmacology , Animals , In Vitro Techniques , Male , Muscle, Smooth, Vascular/physiology , Pulmonary Artery/physiology , Serotonin/pharmacology , Swine , Vasoconstriction
11.
Funct Neurol ; 12(1): 3-9, 1997.
Article in English | MEDLINE | ID: mdl-9127118

ABSTRACT

Rizatriptan (MK-462) is a novel 5-HT1D-receptor agonist and is effective in the treatment of migraine headache. As angiographic studies have shown that the prototypic 5-HT1D/1B-receptor agonist sumatriptan can cause coronary artery constriction in patients with mild coronary artery disease, we have compared the contractile effects of rizatriptan on human isolated coronary artery with those of sumatriptan and 5-HT. Two different experimental protocols were used. In Study 1 (to avoid agonist desensitisation and interaction effects), arterial segments were exposed to a single agonist (either 5-HT, sumatriptan or rizatriptan) and in Study 2 each arterial segment was exposed to all three agonists with randomised first exposure to sumatriptan or rizatriptan. In both these studies the maximum contractions evoked by sumatriptan and rizatriptan were found to be smaller than those evoked by 5-HT, and the maximum contraction evoked by rizatriptan was significantly smaller than that for sumatriptan.


Subject(s)
Coronary Vessels/drug effects , Serotonin Receptor Agonists/pharmacology , Sumatriptan/pharmacology , Triazoles/pharmacology , Adult , Aged , Arteries/drug effects , Dose-Response Relationship, Drug , Female , Humans , In Vitro Techniques , Male , Middle Aged , Osmolar Concentration , Serotonin/pharmacology , Tryptamines , Vasoconstrictor Agents/pharmacology
12.
J Pharmacol Exp Ther ; 279(3): 1077-85, 1996 Dec.
Article in English | MEDLINE | ID: mdl-8968327

ABSTRACT

Experiments were designed to verify whether or not acute or chronic exposure to dexfenfluramine favors the occurrence of coronary vasospasm in vivo or in vitro. Rings of left anterior and left circumflex porcine coronary artery, with and without endothelium, were studied in conventional organ chambers for the measurement of isometric force. The donor pigs were divided into two groups: controls and animals fed for 4 weeks with dexfenfluramine. In each group, one-half of the animals underwent balloon denudation of the left anterior descending coronary artery at the beginning of the study. Coronary angiography was performed at the time of denudation and, in all animals, during the 3rd week of the study. Acutely, dexfenfluramine at concentrations higher than 10(-5) M caused contractions which were blunted by the presence of the endothelium and inhibited by indomethacin (an inhibitor of cyclooxygenase). Chronic treatment with dexfenfluramine did not affect coronary diameter and did not alter the response to intracoronary infusion of serotonin. Chronic treatment with dexfenfluramine reduced the contractions of rings without endothelium to serotonin, but not those to norepinephrine or endothelin. It did not affect endothelium-dependent relaxations in the absence or presence of pertussis toxin to serotonin, UK14304 (alpha-2 adrenergic agonist), adenosine diphosphate or aggregating platelets. Chronic treatment with dexfenfluramine did not modify relaxations of rings without endothelium to SIN-1 (nitric oxide donor; the active metabolite of molsidomine) or adenosine diphosphate. These findings do not support the hypothesis that acute or chronic exposure to dexfenfluramine favors the occurrence of coronary vasospasm.


Subject(s)
Coronary Vessels/drug effects , Fenfluramine/pharmacology , Vasoconstrictor Agents/pharmacology , Animals , Body Weight , In Vitro Techniques , Male , Platelet Aggregation/drug effects , Serotonin/pharmacology , Swine , Vasodilator Agents/pharmacology
13.
Br J Clin Pharmacol ; 42(4): 431-41, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8904614

ABSTRACT

1. Rizatriptan (MK-462, (N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl] ethylamine)) and its structurally related analogue L-741,519 (N-methyl-4-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]piperidine) are novel 5-HT1D-receptor agonists. Rizatriptan has shown efficacy as an anti-migraine agent in clinical trials. Since angiographic studies in patients have shown that sumatriptan (an established 5-HT1D-receptor agonist) can cause coronary artery vasoconstriction, we compared the effects of rizatriptan and L-741,519 with those of 5-HT and sumatriptan on endothelium-denuded segments of human coronary artery in vitro. 2. Coronary arteries were obtained from explanted hearts from patients undergoing cardiac transplantation (n = 16 viable arteries from 13 males, 3 females, aged 38-68 years) and arterial segments (5-6 mm in length) were mounted in organ baths for isometric tension recording. Each segment was first exposed to 45mM KCl and then to 5-HT (1 nM-100 microM). Concentration-effect curves to rizatriptan and sumatriptan (Study 1, n = 6 or 7 arteries) or sumatriptan and L-741,519 (Study 2, n = 8 arteries) were then performed in a consecutive and random manner. The response to repeated application of 5-HT was obtained in separate segments. 3. One artery showed severe atheroma and was not included in the analysis. ANOVA showed that 5-HT responsiveness varied significantly between arteries from different patients; but not between arterial segments from the same patient. Desensitization was seen consistently across all agonists but did not significantly affect inter-agonist comparisons. 4. There was graded effectiveness in the ability of the agonists to cause contraction with the rank order of Emax values being 5-HT >> sumatriptan > L-741,519 > rizatriptan. In terms of EC50 values, L-741,519 was significantly more potent than sumatriptan. 5. The present study (using a 'cross-over' experimental protocol) confirms our previous observation that rizatriptan is less effective than sumatriptan in causing contraction of human isolated coronary artery. Furthermore, it shows that the lower maximum contractile response to rizatriptan, compared with that of sumatriptan, is not merely the consequence of variability in response to 5-HT1D-receptor agonists between patients or between segments from the same artery.


Subject(s)
Arteries/drug effects , Coronary Vessels/drug effects , Receptors, Serotonin/drug effects , Serotonin Receptor Agonists/pharmacology , Adult , Aged , Arteries/physiology , Coronary Vessels/physiology , Female , Humans , In Vitro Techniques , Male , Middle Aged , Muscle Contraction/drug effects , Receptor, Serotonin, 5-HT1D , Serotonin/pharmacology , Sumatriptan/pharmacology , Triazoles/pharmacology , Tryptamines
14.
Am J Hypertens ; 8(5 Pt 2): 1S-6S, 1995 May.
Article in English | MEDLINE | ID: mdl-7544135

ABSTRACT

Experiments were designed to investigate the mechanism underlying the endothelium-dependent relaxations to perindoprilat, a converting enzyme inhibitor, in canine coronary arteries previously exposed to bradykinin. Rings suspended in organ chambers were exposed to bradykinin for 3 min and washed extensively for 150 min. In rings previously exposed to the peptide, bradykinin induced relaxations which were augmented in the presence of perindoprilat; this response was not affected by indomethacin, but nitro-L-arginine induced a rightward shift of the relaxation to the peptide without affecting its maximal effect. In canine coronary arteries previously exposed to the peptide, perindoprilat caused endothelium-dependent relaxations (IC50 = 7.83), which had been observed previously at concentrations where the converting enzyme inhibitor did not augment the response to bradykinin. Carboxypeptidase B, but not aprotinin, impaired the relaxation to perindoprilat, suggesting a contribution of bradykinin. The relaxation to perindoprilat was not affected by the B1 antagonist Leu8-des-Arg9-bradykinin. However, the bradykinin B2 antagonist HOE-140 displayed a noncompetitive antagonism against the response to perindoprilat. The response to the converting enzyme inhibitor was not affected by indomethacin but was impaired significantly by nitro-L-arginine. The present findings suggest that in canine coronary arteries previously exposed to bradykinin, the relaxation to perindoprilat is mediated mainly by endothelium-derived nitric oxide. In addition, the response to perindoprilat may be due to factors other than just protection of bound bradykinin from degradation.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Coronary Vessels/drug effects , Endothelium, Vascular/drug effects , Indoles/pharmacology , Nitric Oxide/metabolism , Vasodilation/drug effects , Animals , Aprotinin/pharmacology , Bradykinin/antagonists & inhibitors , Bradykinin/pharmacology , Carboxypeptidase B , Carboxypeptidases/pharmacology , Coronary Vessels/metabolism , Dogs , Endothelium, Vascular/metabolism , Female , In Vitro Techniques , Male , Vasodilation/physiology
15.
J Pharmacol Exp Ther ; 272(2): 885-91, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7531766

ABSTRACT

Experiments were designed to investigate the mechanism underlying the endothelium-dependent relaxation to trandolaprilat, a converting enzyme inhibitor, in canine coronary arteries previously exposed to bradykinin. Rings suspended in organ chambers were exposed to bradykinin for 3 min and washed repeatedly for 150 min. Trandolaprilat caused relaxations [IC50(-log M)8.59] in rings with endothelium previously exposed to bradykinin. This response was observed already at concentrations where trandolaprilat did not augment relaxations to bradykinin. When the rings were exposed to acetylcholine or to Des-Arg9-bradykinin (B1 agonist) trandolaprilat caused only a minimal response. Carboxypeptidase B but not aprotinin impaired the relaxation to trandolaprilat, suggesting a contribution of bradykinin. After exposure to [3H]-bradykinin, no detectable amounts of the peptide were released by trandolaprilat or found in the preparations. The relaxation to trandolaprilat was not affected by the B1 antagonist Leu8-des-Arg9-bradykinin. HOE-140, a B2 antagonist impaired the maximal response to trandolaprilat, while exhibiting competitive antagonism against bradykinin (pA2 9.00). The maximal relaxation to trandolaprilat was impaired in the presence of nitro-L-arginine and methylene blue. The potency, but not the maximal effect of bradykinin was reduced by these inhibitors. Exogenous bradykinin, but not trandolaprilat, caused an endothelium-dependent hyperpolarization. At equipotent submaximal concentrations, bradykinin released both nitric oxide and endothelium-derived hyperpolarizing factor although trandolaprilat stimulated the production of nitric oxide only. These findings suggest that acute endothelium-dependent relaxations to trandolaprilat in preparations previously exposed to bradykinin are mediated by nitric oxide and may be due partially to protection of bound bradykinin but also to some other unresolved mechanism(s) as well.


Subject(s)
Bradykinin/pharmacology , Coronary Vessels/drug effects , Endothelium, Vascular/physiology , Indoles/pharmacology , Vasodilation/drug effects , Animals , Aprotinin/pharmacology , Bradykinin/analogs & derivatives , Bradykinin/metabolism , Carboxypeptidase B , Carboxypeptidases/pharmacology , Coronary Vessels/physiology , Dogs , Female , In Vitro Techniques , Male , Membrane Potentials/drug effects , Methylene Blue/pharmacology
16.
J Ethnopharmacol ; 45(1): 27-33, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7739224

ABSTRACT

The quantitative toxicities of 33 taenicidal herbal drugs are presented, expressed as their intraperitoneal LD50 values in mice and their respective median effective oral dose and worm expulsion time in humans. Rank orders of toxicity, taenicidal potency and worm expulsion time of the herbal medications are indicated along with a discussion of their respective therapeutic merits and untoward effects. On the basis of considerations of lower toxicity, higher potency and shorter worm expulsion time, the taenicidal herbal medications are arranged in decreasing rank order of preference. Other therapeutic uses of the herbs are also presented and discussed.


Subject(s)
Anthelmintics/toxicity , Anthelmintics/therapeutic use , Medicine, African Traditional , Plants, Medicinal/chemistry , Taeniasis/drug therapy , Animals , Ethiopia , Feces/parasitology , Female , Humans , Lethal Dose 50 , Male , Mice , Plant Extracts/therapeutic use , Plant Extracts/toxicity , Taeniasis/parasitology
17.
J Cardiovasc Pharmacol ; 26 Suppl 4: S53-8, 1995.
Article in English | MEDLINE | ID: mdl-8839227

ABSTRACT

Experiments were designed to compare the relaxant activity of the new nitrate ester ITF 296 in isolated arteries and veins of the dog and to determine the extent of modulation by the endothelium of the response to the compound. Rings (with and without endothelium) of coronary, basilar, mesenteric, and femoral arteries and of mesenteric, femoral, and saphenous veins were suspended in organ chambers for measurement of changes in isometric tension. In all blood vessels without endothelium, ITF 296 caused concentration-dependent relaxation. The order of potency (from measurements of ED50) was: basilar artery > or = coronary artery > femoral artery > mesenteric vein > femoral vein > saphenous vein > mesenteric artery. The maximal relaxation to ITF 296 was greater in the arteries (with the exception of the mesenteric) than in veins. In all blood vessels except for the basilar artery, nitroglycerin caused larger relaxations than ITF 296: The ED50 for nitroglycerin was comparable in all blood vessels studied except for the mesenteric artery, where it was less. ITF 296 did not cause hyperpolarization of vascular smooth muscle in coronary arteries either with or without endothelium. The presence of endothelial cells blunted the relaxation to ITF 296 in basilar and coronary arteries, but not in the other blood vessels studied. These results demonstrate that ITF 296 has a direct inhibitory effect on vascular smooth muscle, which is most pronounced in coronary and cerebral arteries. These findings are in line with the vascular selectivity profile reported for the compound in vivo.


Subject(s)
Muscle, Smooth, Vascular/drug effects , Nitrates/pharmacology , Oxazines/pharmacology , Vasodilator Agents/pharmacology , Animals , Arteries/drug effects , Benzoxazines , Dogs , Electrophysiology , Endothelium, Vascular/physiology , Female , In Vitro Techniques , Male , Molsidomine/analogs & derivatives , Molsidomine/pharmacology , Muscle Relaxation/drug effects , Nitroglycerin/pharmacology , Veins/drug effects
18.
J Ethnopharmacol ; 44(3): 199-209, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7898127

ABSTRACT

A total of 210 extracts/fractions from 70 traditionally used Ethiopian plants were subjected to uterotonic and anti-implantation bioassays. A total of 24% of the samples had uterotonic activity and 33% exhibited anti-implantation activity, while 13% had both uterotonic and anti-implantation activity. The percentage cumulative activity for aqueous, 95% ethanolic and n-butanolic extracts/fractions was 10%, 31% and 25%, respectively. The number of plants whose aqueous extracts, 95% ethanolic extracts and n-butanolic fractions had both uterotonic and anti-implantation activity were 2, 15 and 11, respectively. These findings tend to support traditional claims of antifertility activity for some of the herbs.


Subject(s)
Contraceptive Agents, Female/pharmacology , Plants, Medicinal , Uterus/drug effects , Animals , Embryo Implantation , Ethiopia , Female , Phytotherapy , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Rats , Rats, Sprague-Dawley
19.
Blood Press ; 3(3): 193-6, 1994 May.
Article in English | MEDLINE | ID: mdl-8069408

ABSTRACT

Experiments were designed to determine whether or not chronic treatment with the Ca2+ channel antagonist RO 40-5967 affects endothelium-dependent relaxations in the aorta of hypertensive, salt-sensitive Dahl rats. Salt-resistant and salt-sensitive Dahl rats were fed a diet containing 8% NaCl (for 8 weeks); in each group, half of the animals were given RO 40-5967 chronically (0.4 mg/l; in the drinking water). RO 40-5967 lowered arterial blood pressure in the salt-sensitive, hypertensive, but not in the salt-resistant, normotensive rats. Rings, with and without endothelium, of thoracic aortas were suspended for isometric tension recording in conventional organ chambers. The chronic treatment with RO 40-5967 potentiated endothelium-dependent relaxations to acetylcholine, adenosine-diphosphate and thrombin in preparations from salt-sensitive, but not in those of salt-resistant Dahl rats. The treatment also augmented, in aortas from salt-sensitive animals, the relaxations of rings without endothelium to the donor of nitric oxide, SIN-1. These experiments demonstrate that chronic administration of RO 40-5967 potentiates endothelium-dependent relaxations in arteries from animals with salt-induced hypertension. This potentiation can be explained in part by an augmented sensitivity of the vascular smooth muscle to endothelium-derived nitric oxide.


Subject(s)
Aorta/drug effects , Benzimidazoles/pharmacology , Calcium Channel Blockers/pharmacology , Endothelium, Vascular/physiopathology , Hypertension/physiopathology , Tetrahydronaphthalenes/pharmacology , Vasodilation/drug effects , Animals , Blood Pressure/drug effects , Hypertension/chemically induced , Hypertension/genetics , Male , Mibefradil , Rats , Rats, Mutant Strains , Reference Values , Sodium Chloride , Time Factors , Vasodilator Agents/pharmacology
20.
J Ethnopharmacol ; 39(2): 129-39, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8412246

ABSTRACT

A total of 315 extracts/fractions from 63 traditionally used Ethiopian plants were subjected to antimicrobial screening using known strains of Staphylococcus aureus, Salmonella gallinarum, Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans. The agar plate well-diffusion method was used at a sample concentration of 1000 micrograms/ml; it was found that all of the plants showed activity against one or more of the microorganism(s). Direct aqueous extracts from six plants were found to be active against all of the test organisms. These findings confirm traditional therapeutic claims for aqueous dosage forms of these herbs. The relative susceptibility of the test organisms to the five types of extracts/fractions indicated a decreasing rank order of: S. aureus, P. aeruginosa, C. albicans, S. gallinarum, E. coli, K. pneumoniae and P. vulgaris.


Subject(s)
Anti-Infective Agents/pharmacology , Medicine, African Traditional , Plant Extracts/pharmacology , Plants, Medicinal , Anti-Bacterial Agents , Candida albicans/drug effects , Escherichia coli/drug effects , Ethiopia , Klebsiella pneumoniae/drug effects , Microbial Sensitivity Tests , Proteus vulgaris/drug effects , Salmonella/drug effects , Staphylococcus aureus/drug effects
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