College of Health Sciences

Permanent URI for this communityhttps://hdl.handle.net/10413/6698

Browse

Now showing 1 - 20 of 1799

1,4,7,10,13,16-Hexaazacyclooctadecane (Hexacyclen) Induced Nitrosative Stress and Downregulated NF-κB Cell Survival Pathway in Human Embryonic Kidney (Hek293) and Colorectal Adenocarcinoma (Caco2) Cells.
(2022) Nxumalo, Mthokozisi Bongani.; Khan, Rene Bernadette.; Khumalo, H.
Colorectal cancer (CRC) is the third most common malignancy detected and the second leading cause of cancer-related mortality. Mammalian cells require metals for the physiological process as they are part of the structure or co-factor of many proteins. However, excessive accumulation may manifest in toxicity. In addition, the promotion of oncogenesis and tumour growth has been associated with an increased presence of metals. Promising anticancer compounds that disrupt the onset and progression of carcinogenesis are currently being intensely investigated by the scientific community. Hexacyclen, a nitrogen electron donor and a potent metal ion chelator that binds various metal and transition metal cations, is one such anticancer drug. The cytotoxic effects of Hexacyclen on human colorectal adenocarcinoma cells (Caco2) and normal embryonic kidney cells (Hek293) were investigated in this work after acute exposure (48 hours). The toxicity of Hexacyclen was studied in Hek293 and Caco2 cells at different concentration ranges [(0-500 μM) and (0-50 μM), respectively]. The MTT (to determine IC20 and IC50), ATP and mitochondrial membrane potential (ΔΨM) assays were used to assess metabolic activity, while TBARS, NOS and GSH assays were used to assess oxidative activity. Caspase activity (-8, -9, -3/7), phosphatidylserine externalisation and LDH leakage were used to assess cell death by apoptosis. In addition, western blotting was used to examine the expression of antioxidant (SOD2, GPx, catalase), pro-and anti-apoptotic (p-p53, Bcl-2, HSP70, PARP, cPARP) and inflammatory (NF-κB, STAT3 and p-STAT3) proteins. From the dose-dependent MTT curve, an IC20 and IC50 of 6μM and 38μM (Hek293) and 1.2μM and 5μM (Caco2 cells) were determined. The decreased ATP concentration in Hek293 (p<0.05) and Caco2 (p>0.05) cells for both treatments was consistent with altered ΔΨM in both cell lines, indicating reduced metabolic activity. Elevated RNS was implied by increased iNOS particularly at the Caco2 IC50 (p<0.05) that promoted nitric oxide production at the IC20 (p>0.05) and IC50 (p<0.05) for Hek293 and Caco2 cells respectively. The decreased MDA in Hek293 cells (p>0.05) was associated with increased SOD2 (p<0.05) and GPx (p<0.05), while slightly increased MDA in Caco2 cells (p>0.05) accompanied increased SOD2 (p>0.05) and GPx (p<0.05 at the IC50 only). Furthermore, GSH levels were increased significantly in IC50-treated Hek293 and Caco2 cells (p<0.05), but downregulation of catalase in Hek293 and Caco2 cells was not significant. In this study, apoptosis was initiated by an increase in caspase-9 (IC50, p<0.05) but not caspase 8, which was decreased for both treatments in Hek293 cells (p<0.05). In Caco2 cells, caspase-8 (p<0.05) and caspase 9 (p>0.05) were increased. Anti-apoptotic Bcl-2 (p<0.05) and HSP70 (p<0.05 for Caco2 cells) were downregulated in both cell lines. The activity of p-p53 was not affected in IC20, whereas it was significantly reduced in IC50-treated (p<0.05) in Hek293 and Caco2 cells. Apoptosis was executed as caspase 3/7 was increased in all treatments (p<0.05), albeit non-significantly for IC20-treated Hek293 cells. Moreover, phosphatidylserine externalisation, an early apoptosis marker, was increased in both cell lines (p<0.05 for IC50-treated Hek293 cells), while LDH (a late marker) was increased for Hek293 cells (p<0.05) but not Caco2 cells (p>0.05). Interestingly, decreased cPARP/PARP activity was observed for IC50-treated cells (p<0.05) in both cell lines. Finally, the inflammatory markers NF-κB (p>0.05 for IC20-treated Hek293 cells) and p-STAT3/STAT3 (p>0.05 for IC20-treated Caco2 cells) were downregulated in this study. Hexacyclen induced apoptosis in Hek293 and Caco2 cells via an RNS-mediated mechanism. Intrinsic apoptosis was noted in Hek293 cells, while both pathways facilitated apoptosis in Caco2 cells. Interestingly, apoptosis proceeded concurrently with a reduction in the NF-κB cell survival pathway.
A 10-year institutional review of surgery for structural valve dysfunction in the developing world.
(2017) Chih-Yuan, Chen.
Background Prosthetic heart valves do not fulfil the requirements for an ideal valve, resulting in the development of prosthetic dysfunction or complications over time. Structural valve dysfunction may be influenced by multiple components which include patient’s factors, valve related factors and intraoperative factors. The inter-relation of these factors has a significant impact on morbidity and mortality associated with reoperative surgery for prosthetic valve dysfunction, particularly in a developing world where a large burden of communicable diseases together with lack of health care resources affect surgical outcome. In this study we examined the clinical records of the patients who underwent reoperative valve surgery to evaluate the clinical profile and factors that affect the surgical outcome after reoperation at a large tertiary referral center in a developing country. Objectives 1) To describe the demographic profile of patients with malfunctioning prosthetic heart valves and define their clinical presentation 2) To describe the clinical presentation of valve dysfunction 3) To determine the possible mechanisms of mechanical and bioprosthetic valve failure 4) To determine the factors affecting the immediate surgical outcomes in subjects undergoing redo cardiac prosthetic valve surgery. Materials and methods A retrospective analysis of the clinical, perioperative and follow-up data of patients who underwent redo cardiac valve surgery for structural valve dysfunction between January 2005 and December 2014 at Inkosi Albert Luthuli Central Hospital, Durban, South Africa was undertaken. Patients were identified using the Speedminer software program which is a Data Warehouse software package used to store data collected on the hospital Medicom database. The file of each of patient who underwent redo cardiac prosthetic valve replacement for structural valve dysfunction was accessed and data were extracted on age, gender, potential risk factors for valve thrombosis, symptomatology, investigations including International normalized Ratio (INR) status and follow up. All patients were evaluated preoperatively by the cardiologist and the cardiothoracic surgical team and submitted for either an elective or emergency valve replacement. Excluded from the study were those patients who underwent cardiothoracic surgery for nonvalvular reasons, i.e. coronary artery bypass surgery and congenital heart disease. Results During the ten year period (2005 to 2014) 2618 valve replacement operations were performed. During the same period 128 reoperations (4.9%) were performed in 113 patients (mean age 35.59 (SD±16.66) years). The majority of the patients were Black (72.6%) and female (75%). Fifteen patients (13.3%) were HIV infected and nine were pregnant. Acute dyspnoea (NYHA class III 34.37% and class IV 21.88%) was the presenting feature in 72 patients (56.25%). Clinical presenting features of an obstructed valve (flash pulmonary oedema with or without clinically audible prosthetic valve clicks) were documented in the clinical records of 44 of the 128 (34.4%) reoperations. In seventeen instances subjects presented with acute onset of cardiac failure (13.3%) and in eleven the presentation was characterised by signs of low cardiac output state (5.3%). There were no clinical indicators of an obstructed valve in the remaining 56 (43.8%). Of these 56 patients: 38 presented with change in effort tolerance and 18 where asymptomatic. Valve dysfunction was detected by echocardiography and confirmed fluoroscopically in 71/128 cases (55.47%). In the remaining patients the diagnosis was made either at fluoroscopy (11.72%) or on echocardiography (32.81%). The ejection fraction (EF) was severely impaired (EF<40%) in 7.08% of patients. The mean left atrial size was 52.28mm and mean pulmonary systolic pressure 45mmHg (range 26-104). Mechanical valve dysfunction was documented in 110/128 reoperations (obstructed valve (100) and prosthetic infective endocarditis (10). In almost two thirds of instances with obstructed mechanical prostheses levels of anticoagulation achieved were poor (INR<2.0); 30/110 (27.27%) were within therapeutic ranges of 2-4 and 9/110 (8.18%) was >4.0. HIV status did not influence the outcome of surgery and did not appear to be the main mechanism of valve obstruction. The bioprosthetic valve group comprised the remaining 18 of 128 reoperations. In this group 13/18 patients had structural valve deterioration with periprosthetic leaks, and remaining 5 had prosthetic infective endocarditis (aortic root abscess (1) and annular dehiscence (4).Emergency surgery was performed in 54.7% of the study population, of which 60.2% were in the mitral position. There was a total of 13 early in-hospital deaths (11.5%) of which one “on table” death was due to a low cardiac output state (LCOS). Postoperative mortality was related to prosthetic endocarditis (5/13) and high grade dyspnoea at presentation (7/13). Multivariate analysis revealed that bypass time >3.5 hours (HR 5.58, 95%CI 1.24-24.95), cross clamp time >120 minutes (HR 4.48, 95%CI 1.25-18.73), and third time redo operations (HR 4.26, 95%CI 1.23-14.75) were the independent predictors for early in-hospital mortality. Conclusion Our study shows a 4.9% reoperation rate after the previous valve replacement surgery with 11.5% perioperative mortality. Our results confirm that reoperative surgery is associated with significant morbidity and mortality. More than half the patients presented acutely for mechanical valve obstruction which was due to inadequate levels of anticoagulation and required emergency surgery. Early mortality was related to poor NYHA class at presentation and to the presence of infective endocarditis. An important finding of this study was the high rate of valve obstruction associated with poor anticoagulation in patients who received the Cryolife On–X valve. They had a shorter interval to valve obstruction requiring redo valve replacement compared to the other mechanical prostheses.
A prospective study of the value of the oesophageal electrocardiogram in the differentiation of wide complex tachycardias.
(1990) Moodley, Rajendran.; Sewdarsen, Mohan.
The accurate differentiation of a ventricular from a supraventricular origin of a wide QRS tachycardia (QRS > 120 milliseconds) is an important clinical problem. Misdiagnosis of this arrhythmia can lead to institution of inappropriate drug therapy acutely with potentially catastrophic consequences. Various diagnostic aids have been used to obtain electrocardiographic potentials to aid in the differentiation. This report assesses the clinical usefulness of oesophageal electrocardiography in the differentiation of wide complex tachycardias and describes a simple, safe technique to obtain oesophageal electrocardiograms. Eighteen consecutive patients between the ages of 27 and 71 years who were haemodynamically stable were selected for this study. The technique was performed in the following manner: A temporary pacing catheter was lubricated and passed nasally and advanced with the patient being instructed to swallow. Adjustments in catheter depth were made as necessary to obtain an optimal recording on a standard electrocardiograph recorder. Satisfactory placement with minimal patient discomfort was achieved within 6.5 minutes (average 4.5 minutes) in all cases. High quality tracings were obtained in every instance. In the 18 patients with tachyarrhythmia, AV dissociation consistent with ventricular tachycardia was demonstrated in 11 instances; in the remainder the diagnosis was supraventricular tachycardia. Of the 11 patients diagnosed as ventricular tachycardia, 9 were initially misdiagnosed as supraventricular tachycardia, whilst only 1 of 7 patients with supraventricular tachycardia was misdiagnosed. This study has demonstrated that oesophageal electrocardiography is useful in the differentiation of wide complex tachycardias. The technique outlined in this report is simple and offers the following advantages: the temporary pacing catheter is associated with minimal discomfort; the catheter allows easy manoeuverability within the oesophagus which allows proper depth to be easily obtained; the equipment used is routinely available. Therefore the technique offers a rapid, safe and simple method of obtaining an oesophageal electrocardiogram which is invaluable in the electrocardiographic differentiation of a wide complex tachycardia.
A social constructionist analysis of talk in episodes of psychiatric student nurse-psychiatric client community clinic based interaction.
(2007) Middleton, Lyn Elizabeth.; Uys, Leana Ria.
The study seeks to explore and to offer a critical account for the 'discursive doings' of student psychiatric nmsing practice as they are jointly constructed in the episodes of conversation between the nmse and client-speakers within the context of the communitybased psychiatric clinic. The study is built around a social constructionist framework and is concerned with the analysis of the discursive activities present within seven (7) transttibed, audio-recordings of student nurse-psychiatric client interactions. A thick and sometimes critical description of three of the contextual forces back grounding/foregrounding the discursive processes of psychiatric nursing is given. These include the public health psychiatric care context, the problem-solving approach of the undergraduate psychiatric nursing curriculum and the assumption and effects of modem psychiatric nursing theory. The first level of analysis is an aspect of the methodology and offers a descriptive and interpretive analysis of the talk in the texts. Various conversational discourse analytic tools were used here to transform talk into text and to develop the starting point for the subsequent positioning theory analysis. The second level of analysis is a positioning theory analysis of happenings within these texts. Some of the textual descriptions generated in the first level of analysis are used to illuminate and to add substance to the accounts of these positioning theory happenings. The analysis has shown that from a social constructionist positioning perspective, the unfolding nurse-client dialogue in these texts operates in four potentially distinct ways - highlighting, herding, hectoring and heeding - with specific effects for their going on together in conditions of relationship. These ways of talking are shown to be contrary to the person-eentered rhetoric of modem psychiatric nursing and more aligned with the bio-medical format of talk in helping contexts. Can these activities be dismissed as non-nursing activities? The implications for a modem psychiatric nursing theory that holds the person-centred approach to be its quintessential essence are considered and a number of ideas for how client-authorised expressions may be jointly manifest in conversations situated in this practice context are offered.
Abnormal IgA1 O-glycosylation in a multi-ethnic population of IgA nephropathy patients in KwaZulu-Natal, South Africa.
(2013) Nansook, Prishani.; Assounga, Alain Guy Honore.
Background: The pathogenesis of IgA Nephropathy (IgAN) is poorly understood globally and curative therapy currently does not exist. Variable presentation among IgAN patients globally may be indicative of various underlying pathogenic mechanisms. Pathogenetic data on IgAN in Africa is scarce to nil. The current study provides the first O-glycosylation data for IgAN in South Africa or Africa. Methods: An enzyme-linked immunosorbent assay-type lectin binding assay was used to compare the serum IgA1 O-galactosylation in 19 IgAN patients and 20 controls. During 2007, 2009, and 2011, blood was extracted from consenting biopsy-diagnosed South African IgAN patients of African, Caucasian, Indian (predominantly) and mixed-race descent in KwaZulu Natal. The mean absorbance value corresponding to the degree of degalactosylation for the IgAN group was compared to that of the normal control group for each test. A non-parametric Wilcoxon matched-pairs test was used accordingly. The two-tailed p-value was used to assess for statistical significance between the groups. The low number of attending and consenting IgAN patients precluded IgA1 O-galactosylation analyses between race, gender, and disease stage. Results: The average means of the experiments for the IgAN group is 0.3678 ± 0.0790 (SEM) and is statistically significantly greater than the normal control group which is 0.2969 ± 0.0586 (SEM); (p = 0.0076). Conclusion: Thus, IgAN patients exhibited abnormal IgA1 O-glycosylation with a greater level of terminal degalactosylation of IgA1 in comparison to controls. Such a finding is consistent with other studies in Caucasian and Asian populations globally. Future specific therapeutic strategies that target the formation of abnormal glycosylation in IgA1 may be potentially beneficial in the study population.
Acceptability and effectiveness of rapid ART initiation: patients’ and healthcare workers’ perspectives.
(2022) Govere, Sabina May.; Chimbari, Moses John.
The Joint United Nations Programme on HIV/AIDS is leading the global effort to end AIDS as a public health threat by 2030. In achieving these goals, emphasis has been on the 95–95–95 targets that by 2030, 95% of people living with HIV know their HIV status. However, the focus is on achieving the second 95 and third 95; having 95% of people diagnosed with HIV initiating on treatment within the expected timeframe and 95% of those on treatment obtaining a suppressed viral load. Commendable efforts have been made in increasing HIV testing numbers however, same day initiation on treatment and achieving viral load suppression remains a challenge. According to the WHO recommendations; same day (ART) initiation should be offered to all people living with HIV following a confirmed diagnosis. This study determined the factors influencing the acceptability and implementation of Universal Test and Treat by both patients and healthcare workers. Universal Test and Treat is a prevention strategy encourages that if a person tests HIV positive, irrespective of the persons CD4 count and clinical staging at the time of testing they will have to begin treatment immediately. Furthermore, patient’s clinical outcomes following test and treat in eThekwini municipality in KwaZulu-Natal were determined. This study was cross-sectional and used prospective - mixed methodology to collect data from 403 patients who either accepted or deferred same day ART initiation from June 2020 to May 2021. A structured questionnaire was used to collect demographic information, sexual behaviour, acceptance of same day ART initiation and knowledge of Universal Test and Treat on the day of HIV diagnosis. Key informant in-depth interviews were conducted with healthcare workers and patients were followed up at 6 months after HIV diagnosis to determine clinical outcomes for both groups, rapid and deferred ART initiators using medical charts and electronic databases. Two different analysis univariate and multivariate logistic regression were performed to examine associations between same day ART initiation and several explanatory factors. Logistic regression was performed to examine associations between same day ART initiation and several explanatory factors, retention in care, clinical outcomes and facility related factors. Thematic analysis was used to assess experiences, knowledge and observations of healthcare workers in implementing the Universal Test and Treat policy. Among the 403 participants same-day initiation was 69.2% (n=279). In an adjusted analysis (age, gender, level of education were adjusted at 0.5 significance level in univariate level) number of sexual partners (aOR: 0.35; 95% CI: 0.15-0.81), HIV status of the partner (aOR: 5.03; 95% CI: 2.74-9.26), knowledge of universal test and treat (aOR: 1.97; 95% CI: 1.34-2.90), support from non-governmental organizations (chi-square = 10.18; p-value= 0.015 and provision of clinic staff (chi-square = 7.51; p value = 0.006) were identified as major factors influencing uptake of same-day ART initiation. In the bivariate analysis; gender (OR: 1.672; 95% CI: 1.002–2.791), number of sexual partners (OR: 2.092; 95% CI: 1.07–4.061), age (OR: 0.941; 95% CI: 0.734–2.791), ART start date (OR: 0.078; 95% CI: 0.042–0.141) and partner HIV status (OR: 0.621; 95% CI: 0.387–0.995) were significantly associated with viral load detection and retention in care. (All variables that were significant at e.g. 0.5 level in univariate). Our results suggest a steady increase in uptake of same day ART initiation with poor retention in care. The results also emphasise a vital need to not only streamline processes to increase immediate ART uptake further but also ensure retention in care in order to meet the 95-95-95 targets. The findings of the study contribute to knowledge useful for strengthening rapid ART initiation implementation by considering individual patient factors, healthcare workers’ perspectives and facility level factors. The qualitative findings revealed variations in UTT knowledge, experiences and observations among diverse healthcare workers from the four clinics in different geographical settings. While training on UTT and SDI of ART initiation was conducted at the inception of the implementation phase, the understanding and interpretation varied especially between clinicians and non-clinical healthcare providers. Denial, feeling healthy, fear of disclosure, limited knowledge about ART, fear of ART side effects, fear of stigma and discrimination were some of the factors HCW observed as hindering uptake of SDI. These findings relate to some of the reasons given by patients with fear of disclosure frequently mentioned by those who deferred SDI of ART.
The acceptability and efficiency of routine "opt-out" HIV testing in a South African antenatal clinic setting.
(2008) Van Wyk, Erika.; Giddy, Janet.; Roberts, C. B.; Naidoo, S. S.
Background and Objectives The improved uptake of antenatal Opt-out testing has been documented internationally. In South Africa little is known about the efficiency and die acceptability of Opt-out testing. This study compared VCT with Opt-out testing by measuring the efficiency (defined as uptake of testing, number of women identified as HIV positive and consultation duration of the testing approach) and the acceptability to patients and staff. Methodology We conducted a prospective, quasi-experimental equivalent time-samples clinical trial in which we enrolled a consecutive sample of women who presented at die McCord Hospital antenatal clinic from June to August 2006. The study consisted of 2 phases. During the 6 week intervention period women were offered HIV testing with the Opt-out mediod. During die 6 week control period women were offered midwife-provided VCT. Efficiency was measured in each phase, with 150 participants in the VCT arm and 150 in die Opt-out arm. Participants also completed a survey questionnaire. In depth interviews were conducted with 9 purposefully selected participants from each arm. Two focus group discussions were held with staff. The staff focus group findings were followed-up and validated by conducting in-depdi interviews with die staff members who participated in die focus groups 18 mondis later. Results The uptake of HIV testing during the VCT period was 134/150(89.3%) compared to 147/150(98.0%) in die Opt-out period (p<0.001). The percentage of women identified as being HIV positive during the VCT period was 7.33% (11/150) vs. 12.6% (19/150) during the Opt-out period (p=0.133). Time was saved as a decrease in the duration of midwife consultations from 34 min (VCT) to 26 min (Opt-out) was found with p<0.001. Qualitative analysis revealed Opt-out testing to be an acceptable way of testing. Patients found Opt-out emotionally less distressing than VCT (p<0.05). Staff reported that Opt-out decreased the burden on human resources (only one person needed to facilitate the group and shorter consultations) while it identified more women infected with HIV. Conclusion Opt-out testing is significantly more efficient and acceptable than VCT. Opt-out testing should include a group pre-test information session, adequate and ongoing post-test counselling, to be effective and acceptable.
Acceptability, knowledge and perceptions of pregnant women towards HIV testing in pregnancy at Ilembe district.
(2005) Dube, Faith Nana.; Nkosi, Zerish Zethu.
This research study aimed at investigating the acceptability, knowledge and perceptions ofpregnant women towards IDV testing in pregnancy in Ilembe District. An exploratory research design guided the study. A systematic random sampling was used to select fourty pregnant women who were attending clinic for the first time in their current pregnancy. Self-administered questionnaires with close-ended questions were used in the collection ofdata. The questions included the women's demographic details, their views towards IDV testing, knowledge and acceptability ofIDV testing. Forty questionnaires were distributed and they were all returned. Quantitative method was used to analyse data. The fmdings ofthe study revealed that women in the sample were relatively young (18-25) with the percentage of45% and most ofthem were unmarried (90%). The majority ofwomen (92.5%) said testing was a good idea and 85% said it is necessary. However only 52.5% said they will opt for HIV testing. Uptake ofHIV testing was found to be low. Eighty-seven and a half percent (87.5%) women were ofthe opinion that IDV testing in pregnancy was ofbenefit to the mother and her baby. Women in the study were found to have good understanding and good perceptions towards IDV testing in pregnancy, but thus was not consistent with their behaviour. Meaning that in spite of their good understanding and good perceptions towards IDV testing in pregnancy, only a small percentage (52%) of respondents said they will opt for the IDV test. The researcher's expectations were one hundred percent response.
The acceptance of males in midwifery practice in the Seychelles.
(2001) Agricole, Winifred Jeanneton.; Gwele, Nomthandazo S.; Cassimjee, Rabia.
The aim of the study was to discover, describe and analyze factors related to the perceived acceptance of male nurses in the practice of midwifery in the Seychelles as perceived by nurses, pregnant women and their partners. A descriptive study using the qualitative approach was used. Theoretical sampling was employed and thirty-four participants comprising nurses, pregnant women and their partners were interviewed using an interview guide. Probing was done throughout. The nurses, the pregnant women and their partners were interviewed both in focus groups and individually. Participants taking part in individual interview were different from those taking part in focus group interview. The focus groups were homogeneous comprising professional nurses and consumers of service (pregnant women and their husbands) respectively. The findings revealed multitude of factors associated with the perceived acceptance of males in the practice of midwifery. These were classified as positive, negative and ambivalent. The major positive themes were unconditional acceptance, conditional acceptance, and equitable treatment, by all three groups of informants while traditional belief was the major negative theme. Other positive themes by the nurses were change of attitudes over time, and males as caring professionals, while for pregnant women; it was viewed as prior acceptance of male obstetrician. Both the nurses and partners saw the intimate nature of midwifery as a negative factor while only the nurses identified fear of competition and religious belief. Lack of trust was another negative factor identified by the partners/husbands. Professionals and the husbands identified societal versus individual readiness as an ambivalent factor while the pregnant women and professionals saw conditional acceptance as an ambivalent factor. Recommendations made from this study have implications for nursing research, nursing practice, and nursing education. The study could also be helpful for decision makers at different levels in the health care system.
Access to healthcare : investigating the barriers to accessing antiretroviral treatment at a public sector antiretroviral clinic in Durban, South Africa.
(2013) Kriel, Yolandie.; De la Porte, Susan.; Magula, Nombulelo Princess.
South Africa has the largest HIV/AIDS epidemic in the world and due to the rapid scale up of access to antiretroviral drugs now has the largest antiretroviral program in the world. However access to antiretroviral treatment remains a challenge and the scale up of the drug programs has caused an additional burden on an already stretched and stressed public healthcare sector. At present there are only two lines of drug regimens available to the general public that rely on the public healthcare sector for the supply of their antiretroviral drugs. Resistance to the current regimens is a major concern that is not effectively being addressed. One of the major aspects that can contribute to a rise in resistance is barriers to continually accessing antiretroviral treatment. This ethnographic investigation into the barriers to accessing antiretroviral treatment was conducted in a public health sector clinic based at a large hospital in Durban. The specific objectives of the study were to elucidate the major barriers to accessing the treatment as perceived by the patients of the clinic, to understand the structural drivers behind the barriers and to capture the patients’ reactions to these obstacles that they face on a continuous basis. Unlike most studies that focuses only on adherence this study’s focus was rather on the concept of access to healthcare and how barriers perceived by the patients influence their ability to effectively access their treatment. Thus the concept of access to healthcare is explored in detail and an argument is made for the importance of understanding and applying the holistic concept of access to healthcare within the ART setting. An ethnographic approach was adopted to conduct this study, and the study utilized a triangulation of data collection techniques including participant observation, in-depth interviews, focus groups and a questionnaire. The research was done over a period of seven months and focused on adults who were already part of a regimen for a period of at least one year. Antiretroviral treatment regimens are for life and once people start with these regimens they cannot stop. However this study found that a range of barriers exist that present obstacles for patients to continually access ART drugs. Structural violence theory provided the framework for contextualizing the specific barriers that were reported and is important in terms of situating the barriers within the larger structures that create them. What is evident is that poor healthcare related policies, stigma, discrimination, economic inequality, gender and poverty are the structural drivers behind barriers to accessing ART. By incorporating a broader understanding of access to healthcare a deeper understanding of the barriers is gained and better interventions can be created to prevent disengagement from life-long ART services.
Access to higher education in the health sciences : a policy implementation analysis.
(2014) Orton, Penelope M.; Brysiewicz, Petra.; Essack, Sabiha Yusuf.
Access to health sciences education in South Africa is a challenging and contested area of higher education seeped in politics and history within a context of transformation. There are a large number of students wanting to study health science courses but there are limited places. The first democratically elected government in South Africa issued White Paper 3: A Programme for the Transformation of Higher Education with a vision of transforming the higher education system to one that was more representative of the country`s demographic profile. However in the absence of any guidelines for the implementation of this White Paper 3, higher education in many instances has not been transformed as the government envisaged. The aim of this study was to identify the factors affecting access to health sciences education at universities in South Africa and to develop guidelines to broaden access for social redress. This study was conducted within a pragmatic paradigm using a mixed methods sequential exploratory design in the complementarity genre. Universities offering traditional health science courses` including medicine were included in the study. The research consisted of 3 Phases – Phase 1 reviewed existing policies and practices through the review of relevant documents; Phase 2 assessed existing practices through one-on-one interviews and Policy Delphi and Phase 3 developed policy implementation guidelines and two policy briefs to broaden access using the information gathered from the literature reviewed and data collected from stakeholders. The Policy Delphi questionnaire was developed following the analysis of qualitative data collected in Phase 2 and the instrument was subjected to 2 cycles of item content validity index (I-CVI). The results indicated that achieving equity of access is multi-factorial and has diverse and complex challenges. Some of these challenges are ingrained in South Africa`s apartheid history, some are rooted in the process of access and some in the mind-set of the actors involved in access. The research identified eight categories, promotion of health science disciplines; challenges to transformation; competitiveness; health sciences sets the “bar”; alternative access; reason for choosing a health sciences profession; innovation in teaching and learning and retention and throughput rates which were related to access to health sciences education in universities. The data indicated that the student demographic has changed substantially in Health Science programmes but more could be done. Faculties of Health Sciences need to implement some strategies to reach out to the eligible students in rural and remote areas. Student success in Health science courses is relatively good as would be expected as the selection and admission criteria, is generally higher. Health Sciences at many of the universities are committed to the imperative of transformation for social redress but there are others who are caught between facilitating transformation and overwhelming demand for their programmes. Guidelines for the Implementation of the Access Policy in Health Sciences Education and the Access for Success in Health Sciences Education in Universities Policy briefs were informed by the results. Universities have implemented a number of initiatives to address the past injustice in higher education access however the issue of enabling access for those who are socio-economically disadvantaged is very much more complex and challenging to address. Transformation of health sciences education in universities is essential to the transformation of the health service to reflect a health service that is accessible, available, affordable and agreeable, something that every South African citizen.
Accessing antiretroviral treatment in the rural Eastern Cape : patients' perceptions of a decentralised pre-packing model of care and the impact on direct out-of-pocket spending.
Lines, Monique.; Suleman, Fatima.
Background: With an estimated 5.51 million HIV infected South Africans, HIV/AIDS contributes significantly to the burden of disease in the country, with far-reaching socio-economic implications particularly for poor and vulnerable groups. High out-of-pocket health expenditure associated with HIV/AIDS care has a serious impact on vulnerable individuals and is likely to severely affect the wellbeing of the affected household. Geographic inaccessibility of centralised, hospital-based antiretroviral treatment (ART) services and excessive transportation costs may contribute to patient attrition and these barriers are exacerbated in rural populations. Aim: The objectives of this study are to ascertain the out-of-pocket expenses that are incurred by patients travelling to their ART down-referral site, and compare this with the out-of-pocket expenses of those patients from the same catchment area still receiving their ART from the central hospital. The study also aims to determine whether or not the down-referral programme has impacted the patients’ economic status and improved their treatment experience. Methods: A semi-quantitative cross sectional study design was employed. Zithulele Hospital ARV Clinic and five different PHC collection points within the hospital’s catchment area were selected as the study sites. Included in the study were 44 hospital-based patients and 73 clinic-based patients registered on the Zithulele Hospital HIV Programme. Using a standard questionnaire, all socio-economic data and information related to mode of transportation and associated costs, as well as other out-of-pocket spending associated with accessing ART, was collected. Clinical data was recorded from patient medical records during the interview. Results: The average monthly household income was R1653 (R301.05 per capita) for hospital-based patients and R1617 (R392.66 per capita) for clinic-based patients. Income was predominantly sourced from either child support or pension grants. Study participants had an overall unemployment rate of 94% and, subsequently, 75% of hospital-based patients and 68.5% of clinic-based patients were living below the food poverty line of R400 per month. A higher proportion of hospital-based patients used taxis (80.5% versus 28.8%) while more clinic-based patients walked to the facility for their treatment (71.2% versus 14.6%). In terms of monthly transport costs, hospital-based patients spent on average R71.92, significantly more than the R25.81 spent by clinic-based patients. With a point estimate of 1.169, regression analysis indicated that for every one Rand increase on transport, the odds of the patient being hospital-based rather than clinic-based are 16.9% higher. There were higher levels of satisfaction recorded amongst the hospital-based group (95.5% compared to 89%) but despite this, 100% of the clinic-based patients listed their respective clinic as their preferred ART collection point. Conclusion: Decentralisation and down-referral of patients to their nearest primary healthcare clinic minimises out-of-pocket spending in rural communities while maintaining good levels of satisfaction with the healthcare service provided. It is important to consider the social, geographical and cultural context of the individuals seeking and utilizing healthcare before interventions are implemented.
The accuracy, sensitivity and specificity of rapid point-of-care testing for CD4+ T cell count enumeration and TB diagnosis.
(2014) Skhosana, Mandisa.; Kiepiela, Photini.; Coutsoudis, Anna.
Objectives: The PIMA CD4+ T cell count analyser has been favourably evaluated for use in point-of-care (POC) situations in Mozambique and Zimbabwe, has also been recommended by the World Health Organisation (WHO), however, there is limited information on its use in Primary Healthcare (PHC) settings in KwaZulu Natal (KZN) South Africa. The main aim of this study therefore assessed the accuracy, sensitivity and specificity of the Alere PIMA Point of Care (POC) analyser CD4+ T cell count enumeration compared to the South African National Health Laboratory Services (SA-NHLS) methodology, which uses Beckman Coulter with Panleucogating (PLG/CD4). The potential role of using the PIMA CD4 analyser as a predictor of antiretroviral therapy (ART) eligibility was also assessed. Material and Methods: The study took place at Lancers Road clinic, a busy primary health clinic (PHC) facility under the eThekwini Health Unit. An extra two millilitres of venous blood was drawn from the same blood draw as for the routine CD4 NHLS test (Beckman Coulter) into another EDTA tube for the comparison of the enumeration of CD4+ T cells using the PIMA analyser during January – July 2013. Results: A total of 268 patients were recruited for the PIMA analyser comparison with NHLS PLG/CD4 while a sub-set of 100 blood samples were also analysed on the FACS calibur. In the 100 samples the PIMA analyser results correlated better with the FACS calibur results (mean bias of 7.52, Bland Altman limits of agreement -111 to 126 and correlation of 0.970) than with the NHLS PLG/CD4 results (mean bias of -12.78, Bland Altman limits of agreement -226.041 to 200.481 and correlation of 0.90). In the 268 samples the overall mean difference between the PIMA analyser – NHLS PLG/CD4 was 17.5 cells/μl (95% CI 6.2 to 28.8). The percentage similarity (SIM) between the two (Mean ± SD) was 106 ± 15.5; indicative of acceptable agreement between the two tests. When categorised by the following CD4+ T cell counts of: ≤350 cells/μl; 351-500 cells/μl; ≤500 cells/μl and > 500 cells/μl , the mean difference of PIMA analysers – NHLS PLG/CD4 was 33 cells/μl (95% CI 23 to 42); 22 cells/μl (95% CI -3.5 to 47); 30 cells/μl (95%CI 21 to 39); and cells/μl (95% CI -78 to 6.1) respectively. Under the current South African guidelines of ≤350 cells/μl CD4+ T cells, the sensitivity of the PIMA analyser was 83.5% and specificity 92%. At this threshold of ≤ 350 cells/μl there were 35 (13%) misclassifications, of which 27 were false negatives. This implies that 27 patients would have been falsely deemed ineligible for ART according to the PIMA analyser. The mean difference between the PIMA analyser and NHLS PLG/CD4 in this group of 27 patients was 112 cells/μl. The positive predictive value was high at 95% such that 95% of the patients eligible for treatment according to PIMA analysers would have also been deemed eligible for treatment on the NHLS PLG/CD4 test. Using future South African treatment guidelines threshold of CD4+ T cell counts ≤500 cells/μl , a high sensitivity of 94% was observed at the sacrifice of lower specificity of 78%. According to the NHLS PLG/ CD4 test result, 164/268 (61%) of patients were eligible for ART (CD4+ T cell count ≤350 cells/μl) compared to 145/268 (54%) with the PIMA analyser POC CD4+ T cell test. Of those eligible for ART according to the ART register at Lancers Road PHC, 110/164 (only 67%) of these patients were initiated on ART. Of those who did not return for their results 35/268 (13%), twenty of 35 (57%) were eligible for ART according to the NHLS PLG/CD4 laboratory CD4 test result, all of whom were not initiated on ART. Conclusion: The overall agreement between the PIMA analyser POC and NHLS PLG/ CD4+ T cell count enumeration in adult HIV positive individuals was acceptable with clinically insignificant mean bias. Together with high positive predictive value, and sensitivity and acceptable specificity the PIMA analyser POC lends itself to an excellent facilitator of improved healthcare.
Acquired and transmitted drug resistance in HIV-1 subtype C : implications of novel mutations on replication capacity, cleavage and drug susceptibility.
(2015) Singh, Urisha.; Gordon, Michelle Lucille.
Introduction Large scale roll-out of combination antiretroviral therapy (cART) has been successful in improving the quality of life of HIV-1 infected individuals in South Africa (SA). However the development and transmission of drug resistance threatens the future success and longevity of cART in the country. Studies have shown that resistance to Protease inhibitors (PI’s), in the absence of mutations in Protease (PR), is increasing in SA. Whilst some studies attribute this to poor treatment adherence, others have shown that mutations in Gag contribute to PI resistance. The majority of these studies however have been conducted on HIV-1 subtype B, despite HIV-1 subtype C being the most prevalent subtype globally. Given that Gag is highly polymorphic between subtypes, studies focusing on HIV-1 subtype C are required. Despite the high rate of virologic failure of patients on PI inclusive treatment regimens, no transmitted drug resistance (TDR) studies have identified PI associated TDR mutations. This could be due to the high fitness cost associated with PR mutations which would result in rapid reversion or low frequency of mutations within the viral quasispecies. Most TDR studies in SA, as in other resource limited settings, have used recently infected cohorts to measure TDR. It is however unlikely that rapidly reverting mutations would be detected in recent infection. Furthermore, these studies have all used Sanger sequencing which only detects mutations at frequencies >15-20%. With recent studies showing that low frequency mutations present at frequencies as low as 1% impact treatment outcomes, the elucidation of these mutations using deep-sequencing techniques is necessary. For a true measure of TDR, studies employing acute infection cohorts and deep-sequencing techniques are required. The current study aimed to identify mutations in Gag-Protease associated with PI resistance/exposure, and to determine their impact on replication capacity and drug susceptibility. The prevalence of low frequency TDR mutations in an HIV-1 subtype C acute infection cohort was also investigated. Methods A cohort of 80 HIV-1 subtype C infected participants failing a PI inclusive treatment regimen (i.e. PCS cohort) from 2009–2013 in Durban, South Africa was used to assess the role of Gag in PI resistance. Gag mutations were divided into three groups: PI exposure associated Gag mutations; resistance associated Gag mutations (rGag) and novel Gag mutations (nGag). Frequencies of each of these mutations were compared amongst: 80 PCS cohort sequences, 2,481 HIV-1 subtype B treatment naïve sequences, 954 HIV-1 subtype C treatment naïve sequences and 54 HIV-1 subtype C sequences from acutely infected individuals, in order to identify PI associated mutations and natural polymorphisms. Next, recombinant viruses for all 80 participants were generated by co-transfection of a CEM derived T-cell line (i.e. GXR cells) with an NL43-deleted-gag-protease (NL43Δgag-protease) backbone and patient derived Gag-Protease amplicons. Thereafter, the replication capacity of each virus was assessed using a replication assay that employed a green fluorescent protein reporter cell line and flow cytometry. Associations between replication capacity and Gag-Protease mutations were established. Eighteen viruses with mutations of interest were then selected for use in drug susceptibility assays, where the impact of mutations on susceptibility to lopinavir (LPV) and darunavir (DRV) was assessed in a luciferase based assay. Lastly, the impact of novel Gag mutations on replication capacity and drug susceptibility was validated by generating site-directed mutant viruses with mutations of interest and using these mutant viruses in replication capacity and drug susceptibility assays. Furthermore the cleavage profile of each site-directed mutant virus was established by western blotting. Samples available from 47 HIV-1 subtype C acutely infected individuals collected from 2007-2014 in Durban, South Africa, was used to assess low frequency TDR mutations in HIV-1 subtype C acute infection. Firstly the RT and PR region of each virus was genotyped using the Viroseq HIV-1 genotyping system in order to identify the prevalence of TDR in the cohort. Thereafter 14 participant samples were selected, based on the availability of plasma at one week after onset of plasma viremia (OPV), for sequencing by ultra-deep pyrosequencing (UDPS). This served to identify low frequency mutations. Comparisons in TDR prevalence was made between Sanger sequencing and UDPS. Thereafter, the impact of low frequency TDR mutations on treatment outcomes was assessed by comparing time to virologic suppression for two participants with low frequency mutations to that of four participants without low frequency mutations. Results Protease resistance associated mutations (RAMs) occurred in 34/80 (42.5%) participants, whilst Gag mutations associated with PI resistance in subtype B were detected in 67/80 (84%) participants. Overall, 12 Gag mutations associated with PI exposure (i.e. E12K, V35I, G62R, V370A/M, S373P/Q/T, A374P, T375N, I376V, G381S, I389T, I401T and H219Q), eight rGag mutations (i.e. R76K, Y79F, V128I, A431V, K436R, L449F, R452K and P453L) and four nGag mutations (i.e. Q69K, S111C/I, T239A/S and I256V) were identified in the PCS cohort. The E12K, V370A/M, T375N, G381S, R76K and Y79F mutations all occurred as natural polymorphism in HIV-1 subtype C. The A431V, K436R, L449F, R452K, P453L, Q69K, S111C/I, T239A/S and I256V mutations were all associated with PI resistance/exposure. Interestingly all viruses with PR RAMs harboured rGag and nGag mutations, however rGag and nGag mutations were also found to occur without PR RAMs. Protease RAMs were associated with significantly reduced replication capacity. The K335R and A431V mutations were the only Gag mutations associated with significantly reduced replication capacity. Viruses with PR RAMs were associated with significantly reduced susceptibility to LPV (>15 FC in IC50) and DRV (>6 FC in IC50). Furthermore, the following combinations of rGag and nGag mutations were found to confer reduced susceptibility to LPV and DRV in the absence of PR RAMs: R76K+Y79F+K436R+L449P+I256V (5.2 fold increase in IC50 for DRV), R76K+R453L (23.88 fold increase in IC50 for LPV and a 6.73 fold increase in IC50 for DRV) and R76K+K436R+Q69K+S111C (7.40 fold increase in IC50 for LPV). Analysis of recombinant viruses showed that the Q69K nGag mutation rescued replication capacity of all viruses harbouring A431V+PR RAMs. This was validated by SDM, where Q69K rescued the replication capacity of site-directed mutant viruses harbouring A431V+V82A. The Q69K mutation was also associated with increasing polyprotein cleavage when found in conjunction with A431V+V82A. With regards to TDR, we demonstrated a prevalence of 57% of TDR mutations with UDPS and 2.2% with Sanger sequencing. Sanger sequencing identified the K103N non-nucleoside reverse transcriptase inhibitor (NNRTI)-associated TDR mutation. In addition to K103N (frequency: >99%), the following low frequency mutations were detected by UDPS: the K65R (1-1.5%) and D67N (3.88%) nucleotide reverse transcriptase inhibitor (NRTI)-associated TDR mutations, the F53L (17.6%) and M46L (6.3%) Protease inhibitor (PI)-associated TDR mutations, and the T97A (2.90%) integrase strand transfer inhibitor (InSTI)-associated TDR mutations. Participants with low frequency TDR mutations took 40 days longer to achieve viral suppression than participants without low frequency TDR mutations, when placed on fixed dose combination antiretroviral therapy.
Activation of silent biosynthetic gene clusters and profiling of secondary metabolites secreted by Endophytic Fungi for use as potential anti-HIV agents.
(2022) Makhwitine, John Phuti.; Ndlovu, Sizwe Innocent.; Mkhwanazi, Nompumelelo Prudence.
The continuous burden of Human Immunodeficiency Virus-1 in Sub-Saharan Africa, coupled with the inability of antiretroviral agents to eradicate HIV-1 from viral reservoirs, the potential risks of drug resistance development, and the development of adverse effects, emphasizes the need to develop a new class of HIV-1 inhibitors. Here, we cultivated five endophytic fungi isolated from Albizia adianthifolia with the addition of small epigenetic modifiers, sodium butyrate and valproic acid, to induce the expression of biosynthetic gene clusters encoding active secondary metabolites with probable anti-HIV activities. We identified a non-toxic crude extract of the endophytic fungus Penicillium chrysogenum treated with sodium butyrate to possess significantly greater anti-HIV activity than the untreated extracts. Single-round fractionated extracts of treated P.chrysogenum showed potent anti-HIV activity with an IC₅₀ of 5.90 μg/mL and a 5-fold increase compared to the untreated fraction. The active fractionated extracts were subjected to gas chromatography-mass spectrometry (GCMS), and more bioactive compounds were detected in treated P.chrysogenum fractions than in untreated fractions. These results indicate that treatment of endophytic fungi with small epigenetic modifiers enhances the secretion of secondary metabolites with anti-HIV-1 properties, acknowledging the feasibility of epigenetic modification as an innovative approach for the discovery of cryptic fungal metabolites as therapeutic compounds
The activity of nybomycin against mycobacterium tuberculosis.
(2018) Niehaus, Abraham Johannes.; Moodley, Prashini.; Sturm, Adriaan Willem.
Nybomycin was discovered in 1955, but was never developed for clinical use. The compound was noticed again in recent years when it displayed bactericidal activity against certain fluoroquinolone-resistant bacterial species. The work presented here aims chiefly at describing the effect of nybomycin on Mycobacterium tuberculosis. The study is made up of three parts. In the first part, in vitro nybomycin susceptibility testing was conducted with various fluoroquinolone-susceptible and fluoroquinolone-resistant bacterialspecies. All M. tuberculosis isolates displayed low nybomycin inhibitory concentrations regardless of fluoroquinolone resistance. Similar susceptibility results were obtained for N. gonorrhoeae isolates, but results obtained with other bacterial species were less promising. In the second part, in silico investigations were conducted to elucidate the mechanism of action of nybomycin in M. tuberculosis. Results show that nybomycin binds to M. tuberculosis gyrase enzyme with an affinity at least similar to that of fluoroquinolones. No clear differences in binding affinity were observed when gyrA mutations, commonly associated with fluoroquinolone resistance, were considered. The results suggest that the mechanism of action of nybomycin against M. tuberculosis involves inhibition of gyrase enzyme. In the third part, M. tuberculosis mutants with increased nybomycin minimum inhibitory concentrations were selected and compared with the wild type organism through whole genome sequencing. None of the isolates harbored any mutations commonly linked to known drug resistance mechanisms. This indicates that M. tuberculosis likely employs a novel mechanism of resistance against nybomycin. This may further signify that nybomycin has an additional mechanism of action against M. tuberculosis, besides the action on gyrase enzyme, as suggested by the in silico results from this study. Twenty-two genes were identified through whole genome sequencing that may potentially be linked to the mechanism of resistance and possibly an additional mechanism of action.
Acute care in occupational therapy a package of care and the essential therapeutic equipment needed.
(2017) Chetty, Angela.; Tsoka.Gwegwen, Joyce.
ABSTRACT Introduction: Occupational therapy, together other clinical services are required by government to describe and outline their services so that minimum standards can be set, to ensure that quality care is delivered to all who use the public health service in South Africa. In KZN, where this study is focused, the vast majority of health institutions deliver acute care services at either a district, regional or tertiary level. Aligning therapeutic services to appropriate clinical service at each level will have an impact on optimal health care. Aim: This study focused on developing a package of services for occupational therapy in acute care and outlining an essential therapeutic equipment list. Methodology: A mixed methods explorative sequential study with three phases was implemented. The first phase focused on a documentation audit to determine the context, background and any relevant information on the topic. Approximately 13 documents were selected to conduct a thematic analysis and extract pertinent information to answer the research question. The second phase consisted of implementing a survey in KZN with all eligible occupational therapists to determine their opinions on existing information and generate new ideas. This survey was constructed utilizing information from the document analysis. The final phase ensured that consensus was drawn on a package of occupational therapy services and equipment list by conducting a focus group utilizing the nominal group technique. Senior experienced occupational therapists that worked in acute care constituted the expert group. Results: The documentation audit yielded a rich description of information which set the background on the survey questionnaire. A 78 % response from the survey ensured that the senior experts on the nominal focus group were well informed xii when drawing consensus on a final package of occupational therapy in acute care and the essential therapeutic equipment and assessments needed. Conclusion: This study will provide therapists with a baseline standard of care for acute care hospitals and assist them with motivating for appropriate cost effective resources to deliver effective services in KZN.
The acute effects of dioxidovanadium on blood glucose concentration and oxidative stress in the hippocampus of non-diabetic male Sprague Dawley rats and the chronic effects of dioxidovanadium on selected markers associated with hippocampal dysfunction in male streptozotocin-induced diabetic rats.
(2022) Dayanand, Yalka.; Ngubane, Phikelelani Siphosethu.; Khathi, Andile.; Sibiya, Ntethelelo Hopewell.
Diabetes mellitus is a disease associated with derangements in glucose metabolism and chronic hyperglycaemia. Chronic hyperglycaemia induces oxidative stress and inflammation that affect glucose sensitive hippocampal neurons resulting in generation of amyloid plaques and tau tangles. These are the primary markers used in the detection of neurodegenerative diseases such as Alzheimer’s and dementia. Hence, there is a strong correlation between diabetes and memory impairment. Current therapeutic options such as bolus insulin have been successful in the management of the disease. Despite the efficacy of these therapies, they however have been shown to possess undesirable effects that exacerbate the secondary pathological effects of diabetes on the hippocampus thereby contributing to the detriment of cognitive tasks such as learning and memory. Therefore, there is a need to explore alternative treatments. Transition metals have been shown to possess therapeutic effects with vanadium possessing the greatest potency in lowering blood glucose concentrations. However, studies have demonstrated toxic accumulation of vanadium in the hippocampus which result in the generation of oxidative stress and neurodegeneration. In our laboratory, we have synthesised dioxidovanadium (V) complex by attaching organic ligands to reduce the toxicity and improve potency of the metal. This complex has been shown to efficiently reduce blood glucose and elicit cardio and reno-protective properties. Despite these advancements the effects of this complex on the hippocampus and learning and memory are yet to be established. Therefore, in this study the aim was to evaluate the effect of dioxidovanadium complex on selected learning and memory parameters. Methodology The effect of vanadium on the brain was studied acutely and chronically. In the acute study, animals were separated into 2 groups, non-diabetic control group and a non-diabetic animal group which was were treated with vanadium complex (40 mg.kg-1 p.o). The treatment was administered at time 0. Subsequently an n=3 from each group was sacrificed at regular time intervals (1 hour, 2 hours, 6 hours, 24 hours, 5 days, 10 days) in each group. Blood glucose concentration was monitored before sacrificing and hippocampal tissue was harvested for malonaldehyde (MDA) analysis and glutathione peroxidase (GPx1) and tumour necrosis alpha (TNF-α). The second study was conducted over 5 weeks and consisted of an untreated non-diabetic control, a diabetic control, a positive insulin treated group (0.175 mg.kg-1 s.c) and two dioxidovanadium (V) treated groups (40 mg.kg-1 p.o), a non-diabetic and a diabetic group. Blood glucose was monitored weekly and the Morris water maze was conducted on the last week of the study. After 5 weeks the animals were sacrificed and hippocampal tissue was harvested for malonaldehyde (MDA) analysis, glutathione peroxidase (GPx1) tumour necrosis alpha (TNF-α), amyloid beta (Aβ) and hyperphosphorylated tau (pTau) ELISA’s. Results Acutely, dioxidovandium (V) did not lower blood glucose significantly in comparison to the control group. Interestingly, MDA, GPx1 and (TNF-α) were also not significantly different from the control group over all time periods in the study. Chronically, the glucose concentration of the dioxidovandium (V) treated diabetic group was significantly lowered when compared to the untreated group which displayed significantly increased glucose concentration in comparison to the non-diabetic control. The non-diabetic dioxidovanadium (V) treated group did not show a significant difference in glycaemic level. Increased MDA concentration in the diabetic group was significantly lowered by dioxidovanadium(V) treatment. GPx1 concentration in the dioxidovanadium (V) treated group significantly improved in comparison to the diabetic untreated control. The non-diabetic dioxidovandium (V) treated group showed no significant change in MDA and Gpx1 after the 5-week period. There was no significant difference in TNF-α in dioxidovanadium (V) treated groups, diabetic and non-diabetic. The concentration of Amyloid β was significantly lower in the diabetic control when compared to the non-diabetic control. The dioxidovanadium (V) treated groups, both diabetic and non-diabetic did not have a significant difference in comparison to the diabetic control. pTau concentrations in all groups did not significantly differ. Latency times for the last day of training the Morris water maze followed the same trend. The probe test results, which measured spatial memory, for the diabetic untreated and dioxidovanadium (V) treated groups were significantly reduced in comparison to the non-diabetic control group. The non-diabetic untreated and non-diabetic dioxodivanadium (V) treated were not significantly different. Conclusion Dioxidovanadium (V) treatment in non-diabetic animals did not induce hypoglycaemia acutely however reduced blood glucose concentration in diabetic animals when administered chronically. Dioxidovanadium (V) did not induce oxidative stress and may protect against neurodegeneration by enhancing antioxidant status and therefore was considered as a pro-oxidant in the hippocampus.
Acute pancreatitis in a high HIV prevalence environment: analysis of prevalence, demographics, prognosticators and outcomes.
(2019) Anderson, Frank.; Thomson, Sandie Rutherford.
Background It is unclear what is the true prevalence of HIV related acute pancreatitis and whether diagnostic and prognostic markers used in patients without HIV infection are as effective in HIV related pancreatitis and if morbidity is worse in HIV infected patients. Methods Using a prospective, descriptive design, HIV prevalence was compared in trauma and acute pancreatitis patients. Serum amylase was used to diagnose acute pancreatitis. Prognostication was by CRP, BISAP, Glasgow and APACHE II scores at 24 hours. Sensitivity, specificity and AUC were compared in predicting a severe outcome in acute pancreatitis. Complications and mortality were compared in 238 HIV+ve and HIV-ve patients admitted to 2 regional hospitals in Durban between August 2013 and October 2015. One hundred and eighty one patients were admitted with trauma. Results Between August 2013 and October 2015, 238 patients were admitted with acute pancreatitis and 181 with trauma. HIV infection was higher in patients with acute pancreatitis (38% vs 16%) (p=0.001) and they were also older (40 vs 33 years) (p=0.001). Fifty three percent of HIV +ve patients were female and 65% of the HIV-ve patients were male in the pancreatitis cohort and 59% of the trauma and pancreatitis patients were on Highly Active Antiretroviral Therapy. The prevalence of gallstone (27% vs 30%), alcohol (41% vs 52%), dyslipidaemia (0% vs 3%) and idiopathic (6% vs 14%) aetiologies were similar in HIV+ve and HIV-ve patients and a drug related aetiology (24% vs 0%) (p<0.001) was more prevalent in HIV related acute pancreatitis. CRP was more effective in predicting severe disease in HIV-ve patients (AUC= 0.75) and patients with CD4 counts of ≥ 200 cells/mm3 (AUC=0.73) and not HIV+ve patients (AUC= 0.59) or patients with counts below 200 cells/mm3 (AUC= 0.46). The BISAP system had similar efficacy with AUC of 0,71 and 0.74 in HIV-ve and HIV+ve patients respectively, was poor in CD4 count < 200 cells/mm3 (AUC=0.68) and good in CD4 count> 200 cells/mm3 (AUC=0.9). The Glasgow score was of similar efficacy in HIV-ve (AUC = 0.72) and HIV+ve patients (AUC=0.78) and better in patients with CD4 count < 200 cells/mm3 (AUC=0.83) and CD4 count ≥ 200 cells/mm3 (AUC=0.81). The APACHE II had uniform efficacy in both HIV-ve and HIV+ve patients (AUC >0.8) and both CD4 count ranges (AUC > 0.80). Septic complications occurred in 10(8%) of HIV-ve patients and 4(4%) HIV+ve patients. There was no difference in morbidity (25% vs 33%) and mortality (6% vs 6%). Conclusions HIV infections is more prevalent in acute pancreatitis than in a hospital trauma cohort which represented the general population. The APACHE II system was the most accurate in predicting morbidity and CRP least accurate. The outcomes were similar in HIV+ve and HIV-ve patients but the statistical assumptions in calculating the sample size, given the low frequency of morbidity and mortality observed in this study may have resulted in an alpha error.
Acute stress and strain due to backpack loading among primary school pupils.
(2011) Abrahams, Sumaya.; Ellapen, Terry Jeremy.; Van Heerden, H. J.
Schoolbag carriage represents a considerable daily occupational load for children (Negrini et al., 1999). Whittfield et al., (2001) and Puckree et al., (2004) have reported that the carriage of heavy schoolbags is a suspected aetiological factor of the daily physical stress of school pupils. Methods: One hundred and eighty-seven pupils voluntarily participated in a controlled, descriptive, epidemiological retrospective study. Subjects’ biographical, epidemiological, exercise history and lifestyle information was gathered by a self-report questionnaire (adapted from Puckree et al., 2004). Subjects’ body mass, stature and mass of their schoolbags were measured using a Detecto stadiometer scale. Digital images, electromyographical muscular activity and a posture profile assessments were captured in the frontal and sagittal planes whilst the pupils were in the loaded (carrying a schoolbag) and the unloaded phases (not carrying schoolbags). These images were analyzed using biomechanical software, Dartfish. The study being retrospective in nature recorded the prevalence of schoolbag carriage musculoskeletal pain over the last 12 months. Descriptive statistical tests such as mean, mode, frequency, percentages and inferential chi-square statistical test (set at a probability of 0.05) were employed to analyze the data. Results: The result indicated that 78.99% of the cohort experience musculoskeletal pain due to schoolbag carriage (p<0.0001). The most prevalent anatomical sites of pain were the shoulders (37.04%), neck (20.37%), lumbar (11.73%) and thorax (10.49%) (p<0.0001). The mean mass of the schoolbag carried by the cohort was 5.45kg which was approximately 11.5% of their body mass. The predisposing factors of the musculoskeletal pain were the methods employed to carry the schoolbag (single strap (20.21%) versus double straps (76.6%), altered posture due to excessive schoolbag mass together with a reduced craniovertebral angle (p<0.05). Discussion & Conclusion: The excessive schoolbag mass carried by the pupils placed strain on the immature vertebral column of these pupils thus causing postural deviations which induced musculoskeletal pain and discomfort.

Browse

Browsing College of Health Sciences by Title