Screening of Onion (Allium cepa L.) Genotypes for Drought Tolerance Using Physiological and Yield Based Indices Through Multivariate Analysis.

Drought is a leading abiotic constraints for onion production globally. Breeding by using unique genetic resources for drought tolerance is a vital mitigation strategy. With a total of 100 onion genotypes were screened for drought tolerance using multivariate analysis. The experiment was conducted in a controlled rainout shelter for 2 years 2017-2018 and 2018-2019 in a randomized block design with three replications and two treatments (control and drought stress). The plant was exposed to drought stress during the bulb development stage (i.e., 50-75 days after transplanting). The genotypes were screened on the basis of the drought tolerance efficiency (DTE), percent bulb yield reduction, and results of multivariate analysis viz. hierarchical cluster analysis by Ward's method, discriminate analysis and principal component analysis. The analysis of variance indicated significant differences among the tested genotypes and treatments for all the parameters studied, viz. phenotypic, physiological, biochemical, and yield attributes. Bulb yield was strongly positively correlated with membrane stability index (MSI), relative water content (RWC), total chlorophyll content, antioxidant enzyme activity, and leaf area under drought stress. The genotypes were categorized into five groups namely, highly tolerant, tolerant, intermediate, sensitive, and highly sensitive based on genetic distance. Under drought conditions, clusters II and IV contained highly tolerant and highly sensitive genotypes, respectively. Tolerant genotypes, viz. Acc. 1656, Acc. 1658, W-009, and W-085, had higher DTE (>90%), fewer yield losses (<20%), and performed superiorly for different traits under drought stress. Acc. 1627 and Acc. 1639 were found to be highly drought-sensitive genotypes, with more than 70% yield loss. In biplot, the tolerant genotypes (Acc. 1656, Acc. 1658, W-085, W-009, W-397, W-396, W-414, and W-448) were positively associated with bulb yield, DTE, RWC, MSI, leaf area, and antioxidant enzyme activity under drought stress. The study thus identified tolerant genotypes with favorable adaptive traits that may be useful in onion breeding program for drought tolerance.

Acute systemic inflammation impairs endothelium-dependent dilatation in humans.

BACKGROUND: We tested the hypothesis that endothelial dysfunction underlies the association between an acute inflammatory episode and the transiently increased risk of a cardiovascular event by examining the effects of an experimental inflammatory stimulus on endothelium-dependent vasodilation. METHODS AND RESULTS: Salmonella typhi vaccine was used to generate a systemic inflammatory response in healthy volunteers. In 12 subjects, dilatation of the brachial artery to flow and to sublingual nitroglycerin (NTG) was recorded (conduit vessel response), and in 6 subjects, venous occlusion plethysmography was used to measure forearm blood flow during intrabrachial infusion of the endothelium-dependent dilators acetylcholine (ACh) and bradykinin (BK) and the endothelium-independent dilators NTG and verapamil (resistance vessel response). Responses were assessed 16 hours before and 8 and 32 hours after vaccination. Vaccination resulted in elevations in white cell count and serum levels of interleukin-6 and interleukin-1 receptor antagonist. Eight hours after vaccination, resistance vessel responses to BK (P:=0.0099) and ACh (P:=0.0414) were markedly attenuated, and brachial artery flow-mediated dilatation was depressed. Resistance vessel responses to verapamil and NTG were unchanged, as was the conduit vessel response to NTG. Thirty-two hours after vaccination, resistance vessel responses to BK and ACh had returned to normal. CONCLUSIONS: S typhi vaccine generates a mild inflammatory reaction associated with temporary but profound dysfunction of the arterial endothelium in both resistance and conduit vessels to both physical and pharmacological dilator stimuli. This finding might explain the association between infection and inflammation and the enhanced risk of an acute cardiovascular event.

Endothelial "stunning" following a brief exposure to endotoxin: a mechanism to link infection and infarction?

BACKGROUND: There is an association between infection, inflammation and acute cardiovascular events. In an attempt to explore the mechanism of this association we have developed a model to examine the effects on endothelial function of a brief exposure to endotoxin. METHODS AND RESULTS: Endotoxin was instilled into isolated superficial hand veins of healthy volunteers. The vein was isolated by means of two wedges and endotoxin instilled into the isolated segment. After 1 h the contents of the vein were aspirated and the wedges removed. Dose-response curves to bradykinin (a stimulator of nitric oxide synthesis), arachidonic acid (the precursor of prostanoid production) and GTN (a nitric oxide donor) were constructed before and 1 h after endotoxin. Endotoxin caused a glucocorticoid-inhibitable attenuation in the dose-response curves to bradykinin and arachidonic acid (P < 0.05). This effect persisted for 48 h and took 7 days to recover. Exposure of saphenous vein to endotoxin in vitro also caused selective impairment of endothelium-dependent relaxation (P < 0.05) yet microscopy of the vessels exposed to endotoxin showed no endothelial denudation or structural damage. CONCLUSION: The results demonstrate that a brief local exposure to endotoxin caused endothelial dysfunction that persists for 48 h and takes up to 7 days to recover. The endothelial dysfunction is not due to expression of the inducible isoform of nitric oxide synthase and persists for far longer than the effects of endotoxin on vascular smooth muscle function. We have coined the term endothelial "stunning" to describe the transient endothelial dysfunction and suggest it might provide a mechanism underpinning the association between infection or inflammation and increased cardiovascular risk. Endothelial stunning appears to provide a novel, transient, variable and modifiable potential cardiovascular risk factor.

Cytokine-induced venodilatation in humans in vivo: eNOS masquerading as iNOS.

OBJECTIVE: Venodilatation is a feature of endotoxaemia and sepsis. We have tested directly the hypothesis that three cytokines (IL-1 beta, TNF alpha and IL-6) generated during endotoxaemia affect venous tone in humans in vivo by increasing NO generation and explored whether the NO comes from the iNOS or eNOS isoform. DESIGN AND INTERVENTION: Cytokines were given into a superficial vein in very low doses sufficient only to produce changes in the study vessel. The effects of cytokines on the response to noradrenaline were examined. RESULTS: IL-1 beta increased basal NO-induced dilatation in the study vein, and this was sufficient to attenuate the constrictor response to exogenous noradrenaline or sympathetic stimulation. The effects were maximal at 6 h and both NG-monomethyl-L-arginine and aminoguanidine caused significant reversal of the IL-1 beta effects. However, no induction of iNOS mRNA was detected in the tissue samples. Instead, mRNA encoding eNOS and GTP cyclohydrolase-1 was detected in all vessels. CONCLUSION: The simplest explanation of these results is that IL-1 beta induces expression of GTP cyclohydrolase-1 which leads to increased generation of BH4 and activation of eNOS. This study identifies IL-1 beta as a key cytokine causing physiologically significant venodilatation in humans by increasing NO generation and suggests that this can occur even in the absence of iNOS expression.

Flow associated or flow mediated dilatation? More than just semantics.

Dilatation of the brachial artery occurs after flow is increased, and an attenuation in this response is seen in subjects with cardiovascular risk factors, and in those with established coronary artery disease. The mechanisms linking ischaemia, flow changes, and brachial artery dilatation are unclear, and it is not known how these are affected by arterial disease. For the present it might be more appropriate to refer to flow associated rather than flow mediated dilatation, to describe the phenomenon in the brachial artery. Despite these caveats, the non-invasive measurement of brachial artery following ischaemic dilatation represents a significant advance, and its suitability as a surrogate marker for coronary artery dysfunction appears promising. The technique has potential as a tool for screening those at high risk of vascular disease, and as a surrogate endpoint in intervention studies. Further research should clarify the mechanisms involved, and lead to greater insights into the nature of endothelial dysfunction and cardiovascular disease.

Compliance with antihypertensive therapy after renal artery stenting.

Hypertension is an important clinical endpoint after renal artery revascularization for renal artery stenosis (RAS). Medication compliance is a critical determinant of blood pressure control. Although factors influencing compliance are known in essential hypertension, they have not been evaluated in studies investigating renal artery revascularization. The aim of this study was to assess the determinants of compliance to antihypertensive therapy in patients with RAS following renal artery stent placement (RASP). A cross-sectional study evaluating blood pressure, antihypertensive medications, quality of life, compliance, and determinants of compliance to antihypertensive therapy was undertaken in 112 patients undergoing RASP. Additionally, cardiovascular risk factors, antihypertensive medications, and cardiovascular history were reported. Self-reported compliance was 79% +/- 24% (scale of 0% [none] to 100% [complete] compliance) in patients after RASP. Determinants of compliance by multivariate analysis included physical symptoms, which correlated negatively to compliance and included loss of appetite (r2 = 0.26, P < 0.0001), dizziness (r2 = 0.06, P < 0.01), and cough (r2 = 0.03, P < 0.05). Systolic blood pressure correlated positively with compliance (r2 = 0.03, P < 0.05). The number or class of antihypertensive medications did not influence compliance. Patients' physical symptoms and level of systolic blood pressure, rather than the number or class of medications, influence compliance in patients with continued hypertension after RASP. Attention to physical symptoms may help to improve blood pressure control in this population.

White coat hypertension in Zimbabwean African women.

BACKGROUND: The prevalence of white coat hypertension in the Zimbabwean African female population has not been well defined. OBJECTIVE: To determine the prevalence of white coat hypertension and to compare the cardiovascular risk profiles of those with white coat hypertension to those with sustained hypertension. DESIGN: A cross-sectional study. SETTING: Out patient department of Parirenyatwa Medical School Teaching Hospital, Harare, Zimbabwe. SUBJECTS: Females with an average blood pressure of 140-160/90-105 mmHg. INTERVENTIONS: Females with an average blood pressure of 140-160/90-105 mmHg wore 24 hour ambulatory blood pressure monitors (ABPM). Subjects with >20 mmHg systolic or >10 mmHg diastolic difference between the average out-patient blood pressure and the average awake blood pressure from the ABPM were labelled as white coat hypertensives. RESULTS: The prevalence of white coat hypertension was 38% and the average number of risk factors per patient for the white coat group was 2.9. This result was similar to that for the sustained hypertensive group which had an average of 3.1 risk factors per patient. CONCLUSION: White coat hypertension may be a common finding in black hypertensive Zimbabwean females who have out patient blood pressure measurements of 140-160/90-105 mmHg. The cardiovascular risk profile of these white coat hypertensives was found to be very similar to that of sustained hypertensives.

Effects of non-steroidal anti-inflammatory drugs on hypertension control using angiotensin converting enzyme inhibitors and thiazide diuretics.

OBJECTIVES: To determine the impact of three non-steroidal anti-inflammatory drugs on the efficacy of two anti-hypertensive drugs. DESIGN: Fifteen women with arthritis and hypertension who were receiving lisinopril and HCT, and administered sequentially in random order ibuprofen, sulindac, and diclofenac for one month each, with an intervening two-week washout period between each treatment period. During the washout period, subjects received paracetamol. SETTING: Hypertension Clinic, Medical Centre, Harare, Zimbabwe. SUBJECTS: Fifteen female hypertensive women with documented arthritis. MAIN OUTCOME MEASURES: Blood pressure at the end of two weeks of paracetamol was compared with blood pressure after one month of treatment with each of the NSAID. RESULTS: Mean blood pressure was unchanged before and after all NSAIDs: 108 +/- 7 versus 107 +/- 9 for diclofenac, 108 +/- 9 versus 108 +/- 9 for sulindac, and 108 +/- 8 versus 107 +/- 9 for ibuprofen. The 24 hour urinary sodium excretion was not significantly different. CONCLUSION: The three NSAIDs investigated did not neutralise the antihypertensive effect of the combination of lisinopril and HCT, and hence the blood pressure lowering action of the combination may not be prostaglandin dependent.

HIV and vasculitis: case report.

Manifestation of vasculitis and HIV is now being increasingly being observed. However, clinicians need to be conscious of the possible direct association of this virus with vascular disease. It would appear that the nervous and musculoskeletal systems are most commonly affected. No systematic data exist on the benefit of pharmacological agents currently used and there is an axiomatic need to study these agents in terms of the risk/benefit.

General practitioners and clinical guidelines.

OBJECTIVE: To assess the attitudes of general practitioners in Harare, Zimbabwe, towards the use of clinical practice guidelines (CPG's). DESIGN: Cross sectional survey. SETTING: General practitioners in private practice within the urban Harare (Zimbabwe) environs. SUBJECTS: Two hundred and thirty two general practitioners in Harare, Zimbabwe. MAIN OUTCOME MEASURES: The response to a questionnaire enlisting attitudes to CPGs. RESULTS: Questionnaires were sent to 232 general practitioners. Of these, 137 (59.1%) returned a completed questionnaire. Among the respondents, 95.6% felt that general practitioners should be involved in the development of guidelines, 72.6% had read at least one guideline, 65.9% were prepared to use guidelines in their practice, 61.6% thought that guidelines would improve their treatment ability, and 59.7% thought that guidelines would improve their knowledge of disease. 76.5% felt that the government should not legislate, 66.2% felt that guidelines reduce practitioners' flexibility and 57.9% felt that guidelines would not improve their diagnostic ability. CONCLUSION: The respondents were, in general, favourably disposed towards CPGs. Most had already read some guidelines, and about two thirds were prepared to use them. Almost all respondents felt that general practitioners should be involved in the development of guidelines for use in general practice. These general practitioners felt that guidelines were likely to help them treat patients than to make a diagnosis. Despite these favourable attitudes, many practitioners felt that guidelines would limit their personal flexibility in caring for patients. Organisations developing or implementing CPGs in general practice should address these concerns.

Compliance with medication in patients with heart failure in Zimbabwe.

OBJECTIVES: To determine the extent of adherence to prescribed medication in patients with chronic heart failure and to determine to what extent patients recall information given regarding their medication. DESIGN: Compliance and knowledge of prescribed medication was studied in 22 heart failure patients [mean age 45 +/- 4 (range 40-67); 14 (64%) male], using in-depth interviews performed 30 days after having been prescribed medication. All patients received standardised verbal and written information regarding their medication. SETTING: Patients attending four general practices in the private sector (in Harare, Zimbabwe) for at least six months prior to enrolling were in included in the study. RESULTS: Only 12 (55%) patients could correctly name what medication had been prescribed, 11 (50%) were unable to state the prescribed doses and 14 (64%) could not account for when the medication was to be taken, that is to say, at what time of day and when in relation to meals the medication was to be taken. In the overall assessment six (27%) patients were found non-compliant and 16 (73%) patients were considered as possibly being compliant with their prescribed medication. CONCLUSIONS: Non-compliance was common in heart failure patients, as were shortcomings in patients' knowledge regarding prescribed medication, despite efforts to give adequate information. There exists a need for alternative strategies to improve compliance in these patients.

Use of a simple pain model to evaluate analgesic activity of ibuprofen versus paracetamol.

OBJECTIVE: To evaluate the analgesic activity of ibuprofen against paracetamol using a simple pain model. DESIGN: A double-blind study. SETTING: Twenty general practitioners in Harare, Zimbabwe. PATIENTS: Adults with acute sore throat of a maximum of two days' duration. INTERVENTIONS: One hundred and thirteen patients with acute pain associated with tonsillo-pharyngitis randomly received either 400 mg ibuprofen or 1000 mg paracetamol. The study design included repeated administration up to 48 hours to assess tolerability. MAIN OUTCOME MEASURES: At hourly intervals for six hours after the first dose of treatment, the patients evaluated pain intensity on swallowing, difficulty in swallowing and global pain relief according to visual analogue scales. RESULTS: Ibuprofen 400 mg was significantly more effective than paracetamol 1000 mg in all three ratings, at all time-points for pain intensity and difficulty in swallowing, and from two hours onwards for pain relief. There were no serious adverse effects and no statistically significant difference in the incidence of adverse effects in the two treatment groups. CONCLUSIONS: Sore throat pain provided a sensitive model to assess the analgesic efficacy of class I analgesics and discriminated between the analgesic efficacy of ibuprofen and paracetamol.

Non-pharmacological termination of a supraventricular tachycardia.

Patients with re-entrant supraventricular tachycardias frequently attend casualty departments for termination of their rhythm. With the advent of adenosine in the physician's pharmaceutical armoury, the ease and effectiveness of vagal stimulation is being forgotten.

Tachycardiomyopathy--a case report.

This case report describes a patient presenting with atrial tachyarrhythmia and severe left ventricular failure in which rate control was associated with restoration of normal contractile function.

Oh no, not nitric oxide!

Nitric oxide (NO) is a unique, endogenous regulatory molecule that is involved in a wide variety of physiological processes in multiple organ systems. This simple gas functions as a cellular messenger in a broad range of biological activities that include blood pressure regulation, immunomodulation and neurotransmission. It has also been implicated in a number of homeostatic functions in the cardiovascular system: it is a significant determinant of basal vascular tone and, in addition is thought to regulate myocardial contractility and platelet aggregation. Dysregulation of NO mediated effects have been implicated in the pathogenesis of essential hypertension, atherosclerosis, and the hypotension associated with septic shock. This review will focus on these multiple effects of NO in the cardiovascular system.

Current treatment and future prospects for the management of acute coronary syndromes.

The impact of ischaemic heart disease on the burden of cardiovascular disease continues to escalate worldwide, although international statistics suggest a levelling off in Western world, in the less industrialised parts of the world the effects of this disease are only beginning to be documented, nonetheless, rapid advances have been made in the diagnosis and management of the acute coronary syndromes (the term which encompasses the protean clinical manifestations of the ischaemic process). The therapeutic strategies discussed in this article cover two broad subjects that have been found to be critical in the evolution of the disease:- i. interfering with the haemostatic balance by retarding the thrombotic process; ii. modifying local and systemic vasoconstricting stimuli.

Pharmacological management of benign prostatic hyperplasia.

In men with mild to moderate BPH, pharmacotherapy is a safe and effective alternative to surgery. The primary care physician should be able to manage the treatment without referral to a urologist, provided he has undertaken appropriate steps to assure himself, and the patient, that there is no evidence of cancer of the prostate.

Prescribing patterns for the use of antithrombotics in the management of atrial fibrillation in Zimbabwe.

OBJECTIVES: To assess the prescribing patterns for the use of antithrombotics in the management of atrial fibrillation. DESIGN: A descriptive cross sectional study. SETTING: Parirenyatwa Hospital, Harare, Zimbabwe. SUBJECTS: The outpatient records of 200 outpatients attending the cardiac clinic (with a documented history of an irregular pulse) between January and August 1999 at Parirenyatwa Hospital, Harare, Zimbabwe were reviewed. MAIN OUTCOME MEASURES: In addition to antithrombotic therapy prescribed at the time of review, patient information (rural or urban), relative contra-indications to antithrombotic therapy, and risk factors for stroke were identified. RESULTS: Patients were similar in terms of age, sex, and risk factors for stroke. At least one stroke risk factor was noted in 79% of urban and 83% of rural patients. Two risk factors were noted in 26% of patients. It was noted that urban patients were more likely to have a relative contra-indication to antithrombotic therapy compared with rural patients (24% vs 10%, p = 0.028) but received antithrombotic therapy more often (38% vs 19%, p = 0.025). CONCLUSIONS: Patients with atrial fibrillation are being inappropriately managed in terms of their major prognostic risk factor. Rural patients with atrial fibrillation receive antithrombotic therapy less frequently than urban patients despite having a similar high risk profile and fewer relative contra-indications.

Clinical pharmacologist wanted--where?

Many people could define with ease the job of a cardiologist, a paediatrician or an obstetrician. However, only a few would have any clear idea of how a clinical pharmacologist might fill a day. Indeed, within the medical profession, and often within the scientific community, there has been a sneaking suspicion that clinical pharmacologists are themselves unsure of their remit. This article describes the possible role for clinical pharmacologists and different areas where they can make significant contributions to medical services.

Ethics and HIV research in Zimbabwe.

A plethora of articles are now being published in both local and international journals on research activities conducted on the human immunodeficiency virus (HIV) in Zimbabwe. Some of the bioethical issues they raise, however, are neither unique to HIV nor unique to developing countries. In this article we discuss several of these issues, including the failure to provide interventions of known efficacy, ethical relevance of study design, informed consent, and exploitation. A challenge raised by much of the research in HIV/AIDS is whether, or under what conditions, it is ethical in research to fail to provide an intervention of known efficacy. The further we diverge from this situation, in which an effective, easy to implement intervention is available, to situations that resemble the controversial international clinical trials to prevent perinatal transmission of HIV the less clear the ethical mandate becomes. In relation to clinical trials the debate has focused on whether the standard of care in the United States--an expensive and complex regimen of Zidovudine--must be provided to all HIV infected pregnant women who join a research study in developing countries. Different scientists and scholars in bioethics have drawn the line differently in terms of what interventions routinely available in the developed world must be provided to research participants in developing countries. At an extreme, no one suggests that the most expensive and complex of Western tertiary care, for example, renal dialysis or coronary bypass, must be provided in research conducted in Zimbabwe. Indeed, public debates about the HIV perinatal transmission trials have not even focused on whether the women in the trials should be provided with HIV combination therapy as they would be in the West or whether they should even have the Zidovudine continued post partum.