25 results on '"Zulu, S."'
Search Results
2. Macroseismic survey of the 6 February 2016 KwaZulu-Natal, South Africa earthquake.
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Mapuranga, V., Kijko, A., Saunders, I., Singh, A., Singh, M., and Zulu, S.
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GEOLOGICAL surveys ,EARTHQUAKE magnitude ,GEOLOGY ,SUBURBS ,EARTH sciences - Abstract
On the 6th of February 2016 at 11:00 hours local time (0900 UTC), KwaZulu-Natal was struck by an earthquake of local magnitude ML=3.8. The epicentre of the earthquake was located offshore in the Durban Basin. The earthquake shaking was widely felt within the province as well as in East London in the Eastern Cape province and was reported by various national media outlets. Minor structural damage was reported. A macroseismic survey using questionnaires was conducted by the Council for Geoscience (CGS) in collaboration with the University of KwaZulu-Natal (UKZN) which yielded 41 intensity data points. Additional intensity data points were obtained from the United States Geological Survey (USGS) Did You Feel It? programme. An attempt was made to define a local intensity attenuation model. Generally, the earthquake was more strongly felt in low-cost housing neighbourhoods than in more affluent suburbs. [ABSTRACT FROM AUTHOR]
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- 2022
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3. THE DEVELOPMENT OF A TECHNOLOGY ROADMAP FOR FERROCHROME PRODUCERS.
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Letaba, P. T. and Zulu, S.
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FERROCHROME , *RENEWABLE energy sources , *INDUSTRY 4.0 , *ALUMINUM smelting - Abstract
A 30-year technology roadmap for the South African ferrochrome industry is developed to address the increasing cost of electricity and competition from China. Research on possible technologies and their applicability in ferrochrome smelting is conducted, including Industry 4.0 technologies. The developed roadmap has three phases, with full-scale digitisation deferred to the second phase. The first phase addresses the stabilisation of the industry through the introduction of alternative energy sources. The last phase of the ferrochrome industry roadmap is sustainability, which builds on the successes of previous phases. This research contributes to methods the responsible introduction of Industry 4.0 technologies in industries with existing underlying challenges. The purpose of this article is to present a technology roadmap for ferrochrome producers in South Africa as chosen by the ferrochrome industry players. [ABSTRACT FROM AUTHOR]
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- 2021
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4. Seasonal variations in Schistosoma haematobium egg excretion in school-age girls in rural KwaZulu-Natal Province, South Africa.
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Christensen, E. E., Taylor, M., Zulu, S. G., Lillebo, K., Gundersen, S. G., Holmen, S., Kleppa, E., Vennervald, B. J., Ndhlovu, P. D., and Kjetland, E. F.
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- 2018
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5. Schistosoma PCR among high school girls in South Africa as a complimentary diagnostic tool for Female Genital Schistosomiasis (FGS)
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Pillay, P., Taylor, M., Zulu, S., Gundersen, S.G., Kleppa, E., Lillebo, K., Kjetland, E.F., Brienen, E., and van Lieshout, L.
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- 2014
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6. The influence of winter on the prevalence of urogenital schistosomiasis in rural southern KwaZulu-Natal
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Christensen, E.S., Taylor, M., Gagai, S., Zulu, S., Lillebø, K., Gundersen, S.G., Holmen, S.D., Kleppa, E., and Kjetland, E.F.
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- 2014
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7. Expression of the CCR5 HIV co-receptor in women with genital schistosomiasis
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Kleppa, E., Ramsuran, V., Zulu, S., Karlsen, G.H., Ndhlovu, P., Lillebø, K., Holmen, S.D., Onsrud, M., Gundersen, S.G., Taylor, M., Kjetland, E.F., and Ndung’u, T.
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- 2014
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8. Inflammatory pseudo-tumour of the colon mimicking acute appendicitis: A case report.
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Zulu, S., Kruger, C., Morare, N., Montwedi, D., and Ngwenya, S.
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Inflammatory pseudo-tumour (IPT) of the colon is a rare entity with an obscure pathophysiology and largely indeterminate aetiology. A young male patient presented with an Alvarado score of 9/10 and was admitted for appendectomy. An irregular hepatic flexure mass was discovered intraoperatively. The patient underwent an oncological right hemicolectomy with lymphadenectomy under the supposition that it was malignant and recovered with no short or long-term repercussions. Haemoxylin and eosin staining of the mass revealed features of a benign IPT. IPTs have clinical and radiological features that may be indistinguishable from those of malignancies, often resulting in extensive oncological resections despite recurrence and malignant transformation being negligibly rare. Benign pathologies such as IPT that mimic malignancy can sometimes result in extensive investigations or radical resections, the justification of which can only be a point of contention in retrospect. The following report explores our experience with one such patient and is accompanied by a review of the literature. • Inflammatory pseudotumours are often mistaken for malignant lesions • This error can result in unnecessary resection being performed • We investigated whether radiography can diagnose inflammatory pseudotumours • Our findings reveal that radiography may not be effective in this context • Further studies may be required to prevent unnecessarily extensive resection [ABSTRACT FROM AUTHOR]
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- 2022
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9. Cervical cytology as a diagnostic tool for genital schistosomiasis and cervical squamous cell atypia among young women from schistosoma and HIV endemic populations in South Africa.
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Pillay, P., Taylor, M., Galappathi-Arachchige, H. N., Zulu, S. G., Roald, B., and Kjetland, E. F.
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SCHISTOSOMIASIS diagnosis , *HIV-positive women , *CERVICAL cancer diagnosis , *CYTOLOGY , *SCHISTOSOMIASIS , *SQUAMOUS cell carcinoma , *DISEASE prevalence , *MEDICAL care , *DISEASE risk factors - Abstract
Background: Globally, Africa has the highest prevalence of HIV, schistosomiasis and another neglected entity: cervical cancer. Genital schistosomiasis manifests in lesions that are hypothesized to link with HIV and cervical atypia. Methods & Materials: This study was conducted among 833 young women aged 16-23 years from rural high schools in KwaZulu-Natal. Risk factors for schistosomiasis and cervical atypia and the association of genital schistosomiasis and squamous atypia of the cervix were investigated using diagnostic cytology, urine microscopy, and questionnaire data. Results: Participants were sexually active from a young age and 523 (63.0%) had at least one child and 742 (89.1%) relied on rivers as their primary water source. The Schistosoma prevalence detected cytologically and via urine microscopy was 12 (1.4%) and 178 (21.4%) respectively. Squamous cell atypia was detectedamong 567 (68%). There was a significant association between the participants who were positive for any squamous cell atypia and those whohad S. haematobium eggs in Pap smears (OR = 5.6, P = 0.005; 95% CI 1.6-21.0) and for S. haematobium eggs in urine OR= 2.9, 95% CI 1.72 - 4.99, P = 0.005). Conclusion: The specificity of cytology for Schistosoma detection was low using is seen previously, it is possible that an improved detection rate of genital schistosomiasis could be achieved using cervico-vaginal lavage Schistosoma DNA testing. While a significant association exists between urogenital schistosomiasis as detected by cytology and urine microscopy with squamous atypia in this young population, it must be noted that more than half of the young womenhave cervical atypia that could potentially regress. Cytology was useful in revealing the squamous atypiaamongthis young population who is not routinely screened, a limitation is that it was not feasible to confirm results using histology or other complementary tests. The relationship between schistosomiasis and cervical cancer is complex, while there may be association, it was not possible to prove causality or eliminate all confounders. In communities at risk, health promotion, screening and health care targeting not only HIV and schistosomiasis, but also cervical cancer should be made available in order to reduce the prevalence of these preventable diseases. [ABSTRACT FROM AUTHOR]
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- 2016
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10. "Killing two birds with one stone" - a qualitative study on women's perspectives on the dual prevention pill in Johannesburg, South Africa.
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Tenza S, Mampuru L, Moji M, Zulu S, Begg L, Bruce IV, Reddy K, Friedland BA, Palanee-Phillips T, and Mathur S
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- Humans, Female, South Africa, Adolescent, Adult, Young Adult, Pregnancy, Contraceptives, Oral, Combined therapeutic use, Contraceptives, Oral, Combined administration & dosage, Qualitative Research, HIV Infections prevention & control, Pre-Exposure Prophylaxis methods, Focus Groups
- Abstract
Background: HIV incidence remains high in South Africa, with ~ 60% of all new HIV infections among adolescent girls and women (Country factsheets HIV and AIDS Estimates, 2022). Oral pre-exposure prophylaxis (PrEP), approved for HIV prevention in South Africa since 2015, is hampered by low uptake and adherence, particularly among adolescent girls and young women (AGYW). Combining oral PrEP with oral contraceptives could increase PrEP uptake, persistence and address unmet needs for contraception. We investigated the acceptability of a dual prevention pill (DPP), combining oral PrEP and a combined oral contraceptive (COC) for HIV and pregnancy prevention among women in Johannesburg, South Africa., Methods: Between March-July 2021, we conducted 12 focus group discussions (FGDs) with adolescent girls and women (n = 74) aged 16-40 stratified by ages (16-17, 18-24, 25-40), half of whom were COC users. We explored adolescent girls and women's opinions about the DPP concept, existing HIV and pregnancy prevention options, and input on perceived facilitators and barriers to DPP use. FGDs were conducted in English or isiZulu, using a standardized interview guide. FGDs were audio-recorded, transcribed to English and analyzed using ethnographic content analysis., Results: The majority viewed the DPP favorably as a multipurpose option preventing unplanned pregnancy and HIV. Most saw it as a convenient "two-in-one" solution, requiring one clinic visit for both PrEP and COCs. AGYW were viewed as the most likely to benefit from the DPP due to the likelihood of multiple partners and unplanned sex, possibly preventing school dropout from unplanned pregnancy or HIV acquisition. The DPP was perceived to be more reliable than condoms, especially when condom negotiation is limited. Benefits were also seen by participants in rape cases, protecting against pregnancy and HIV. DPP use barriers included side effect concerns, unsupportive partners and judgmental healthcare providers., Conclusions/significance: The DPP was perceived as acceptable for HIV and pregnancy prevention to AGYW in Johannesburg and its dual indications helpful in supporting improved PrEP uptake and persistence. DPP implementation programs need to consider solutions to potential barriers, like education on DPP benefits, coupled with reliable side effect support and healthcare provider sensitization as part of routine sexual health services to encourage uptake and adherence., (© 2024. The Author(s).)
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- 2024
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11. Profile and outcomes of management of patients admitted to obstetric high care unit in a tertiary academic hospital in Gauteng Province, South Africa.
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Chauke L, Zulu S, and Mnyani C
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- Pregnancy, Humans, Female, South Africa epidemiology, Tertiary Care Centers, Family, Pre-Eclampsia epidemiology, Pre-Eclampsia therapy
- Abstract
The aim of this study was to describe maternal characteristics and pregnancy outcomes of women admitted in a dedicated obstetric high care unit (OHCU) in a tertiary hospital in Gauteng province, South Africa. The study involved review of clinical records of women admitted to OHCU between January and June 2016. Data collected included maternal demographic data, indication for admission, management and outcomes. A total of 4 637 of women gave birth and 114 (2.5%) were admitted to the OHCU during this period. Majority (90, 78.9%) were younger than 35 (mean 29.6) years with 32(28.1%), in their first pregnancy. Obstetric related indications for OHCU admission were mainly, pre-eclampsia and related complications (89, 78.1%), followed by obstetric haemorrhage (32, 28.1%). Cardiac disease, 14(12.3%) and pneumonia 6(5.3%) were the most common non-obstetrics indications for admission. Majority of patients stayed in OHCU for an average of 24-48 hours and were discharged alive (99.86.8%). Only 11(9.6%) were transferred to ICU and complications related to cardiac diseases were the most common reason for the transfer. Preeclampsia, obstetric hemorrhage and cardiac related complications are the most common reasons for OHCU and ICU admissions however most of these condition can be successfully managed in OHCU.
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- 2023
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12. The CYB5R3 c .350C>G and G6PD A alleles modify severity of anemia in malaria and sickle cell disease.
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Gordeuk VR, Shah BN, Zhang X, Thuma PE, Zulu S, Moono R, Reading NS, Song J, Zhang Y, Nouraie M, Campbell A, Minniti CP, Rana SR, Darbari DS, Kato GJ, Niu M, Castro OL, Machado R, Gladwin MT, and Prchal JT
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- Child, Preschool, Female, Glucosephosphate Dehydrogenase metabolism, Humans, Infant, Male, Severity of Illness Index, Zambia, Alleles, Anemia, Sickle Cell genetics, Anemia, Sickle Cell metabolism, Anemia, Sickle Cell parasitology, Cytochrome-B(5) Reductase genetics, Cytochrome-B(5) Reductase metabolism, Glucosephosphate Dehydrogenase genetics, Malaria, Falciparum genetics, Malaria, Falciparum metabolism, Plasmodium falciparum metabolism, Point Mutation
- Abstract
Genetic modifiers of anemia in Plasmodium falciparum infection and sickle cell disease (SCD) are not fully known. Both conditions are associated with oxidative stress, hemolysis and anemia. The CYB5R3 gene encodes cytochrome b5 reductase 3, which converts methemoglobin to hemoglobin through oxidation of NADH. CYB5R3
c.350C > G encoding CYB5R3T117S , the most frequent recognized African-specific polymorphism, does not have known functional significance, but its high allele frequency (23% in African Americans) suggests a selection advantage. Glucose-6-phosphate dehydrogenase (G6PD) is essential for protection from oxidants; its African-polymorphic X-linked A+ and A- alleles, and other variants with reduced activity, coincide with endemic malaria distribution, suggesting protection from lethal infection. We examined the association of CYB5R3c.350C > G with severe anemia (hemoglobin <5 g/dL) in the context of G6PD A+ and A- status among 165 Zambian children with malaria. CYB5R3c.350C > G offered protection against severe malarial anemia in children without G6PD deficiency (G6PD wild type or A+/A- heterozygotes) (odds ratio 0.29, P = .022) but not in G6PD A+ or A- hemizygotes/homozygotes. We also examined the relationship of CYB5R3c.350C > G with hemoglobin concentration among 267 children and 321 adults and adolescents with SCD in the US and UK and found higher hemoglobin in SCD patients without G6PD deficiency (β = 0.29, P = .022 children; β = 0.33, P = .004 adults). Functional studies in SCD erythrocytes revealed mildly lower activity of native CYB5R3T117S compared to wildtype CYB5R3 and higher NADH/NAD+ ratios. In conclusion, CYB5R3c.350C > G appears to ameliorate anemia severity in malaria and SCD patients without G6PD deficiency, possibly accounting for CYB5R3c.350C > G selection and its high prevalence., (© 2020 Wiley Periodicals LLC.)- Published
- 2020
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13. Anti-HIV drugs promote β-amyloid deposition and impair learning and memory in BALB/c mice.
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Zulu SS, Abboussi O, Simola N, Mabandla MV, and Daniels WMU
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- Administration, Oral, Amyloid Precursor Protein Secretases drug effects, Amyloid Precursor Protein Secretases metabolism, Amyloid beta-Peptides metabolism, Amyloid beta-Protein Precursor drug effects, Amyloid beta-Protein Precursor metabolism, Animals, Anti-HIV Agents adverse effects, Anti-HIV Agents toxicity, Aspartic Acid Endopeptidases drug effects, Aspartic Acid Endopeptidases metabolism, Brain drug effects, Brain metabolism, Brain virology, Cognitive Dysfunction chemically induced, Disease Models, Animal, Female, HIV Infections complications, HIV Infections virology, HIV-1 isolation & purification, Hippocampus metabolism, Lipid Peroxidation drug effects, Maze Learning drug effects, Mice, Mice, Inbred BALB C, Nevirapine adverse effects, Nevirapine pharmacology, Nevirapine toxicity, Tenofovir adverse effects, Tenofovir pharmacology, Tenofovir toxicity, AIDS Dementia Complex chemically induced, Amyloid beta-Peptides drug effects, Anti-HIV Agents pharmacology, HIV Infections drug therapy, Learning Disabilities chemically induced, Memory drug effects
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Objectives: Growing evidence suggested that antiretroviral (ARV) drugs may promote amyloid beta (Aβ) accumulation in HIV-1-infected brain and the persistence of HIV-associated neurocognitive disorders (HANDs). It has also been shown that lipid peroxidation upregulates β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) expression and subsequently promotes Aβ peptide production. In the present study, we examined whether chronic exposure to the anti-HIV drugs tenofovir disoproxil fumarate (TDF) and nevirapine induces lipid peroxidation thereby promoting BACE1 and Aβ generation and consequently impair cognitive function in mice., Methods: TDF or nevirapine was orally administered to female BALB/c mice once a day for 8 weeks. On the 7th week of treatment, spatial learning and memory were assessed using the Morris water maze test. The levels of lipid peroxidation, BACE1, amyloid β 1-42 (Aβ1-42) and Aβ deposits were measured in the hippocampal tissue upon completion of treatment., Results: Chronic administration of nevirapine induced spatial learning and memory impairment in the Morris water maze test, whereas TDF did not have an effect. TDF and nevirapine administration increased hippocampal lipid peroxidation and Aβ1-42 concentration. Nevirapine further upregulated BACE1 expression and Aβ deposits., Conclusion: Our results suggest that chronic exposure to TDF and nevirapine contributes to hippocampal lipid peroxidation and Aβ accumulation, respectively, as well as spatial learning and memory deficits in mice even in the absence of HIV infection. These findings further support a possible link between ARV drug toxicity, Aβ accumulation and the persistence of HANDs.
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- 2020
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14. Glutamatergic pathway in depressive-like behavior associated with pentylenetetrazole rat model of epilepsy with history of prolonged febrile seizures.
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Alese OO, Ngoupaye GT, Rakgantsho C, Mkhize NV, Zulu S, and Mabandla MV
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- Amygdala metabolism, Animals, Brain-Derived Neurotrophic Factor metabolism, Excitatory Amino Acid Transporter 1 metabolism, Glutamate Synthase metabolism, Hippocampus metabolism, Male, Pentylenetetrazole administration & dosage, Rats, Rats, Sprague-Dawley, Receptor, Metabotropic Glutamate 5 metabolism, Depression physiopathology, Epilepsy physiopathology, Glutamic Acid metabolism, Seizures, Febrile physiopathology
- Abstract
Background: Depression is the most significant cause of suicide among neuropsychiatric illnesses. Major depression further affects the quality of life in an individual with epilepsy. The treatment of depression in an epileptic patient could be very challenging because of drug selection or the fact that some antiepileptic drugs are known to cause depression. It has been shown that in addition to the known involvement of the serotonergic pathway in depression, the glutamatergic system is also involved in the evolution of the disease, but this knowledge is limited. This study assessed if induction of epilepsy in rats will cause depressive-like behavior, alters the concentrations of metabotropic receptor 5 (mGluR5), glutamate transport protein (GLAST), glutamate synthase (GS) and brain derived neurotrophic factor (BDNF)., Materials and Method: Epilepsy was induced in rats by injecting Pentylenetetrazole at 35 mg/kg every other day. At kindle, rats were subjected to sucrose preference test (SPT) and forced swim test (FST) and decapitated 4 h later. Hippocampal tissue was collected and the BDNF concentration was measured with ELISA; mGluR5 and GS protein expression was measured using western blot while amygdala tissue was used for GLAST expression with flow cytometry., Results: Our results showed that epilepsy leads to depressive-like behavior in rats and alters the glutamatergic system., Conclusion: Therefore, we conclude that targeting the glutamate pathway may be a good strategy to alleviate depressive-like behavior associated with epilepsy., Competing Interests: Declaration of competing interest The authors report no conflict of interest in this work., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2020
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15. Prolonged febrile seizure history exacerbates seizure severity in a pentylenetetrazole rat model of epilepsy.
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Alese OO, Rakgantsho C, Mkhize NV, Zulu S, and Mabandla MV
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- Animals, Disease Models, Animal, Epilepsy chemically induced, Glial Fibrillary Acidic Protein drug effects, Glial Fibrillary Acidic Protein metabolism, Hippocampus drug effects, Hippocampus metabolism, Male, Pentylenetetrazole administration & dosage, Rats, Sprague-Dawley, Receptors, Metabotropic Glutamate metabolism, Seizures, Febrile chemically induced, Severity of Illness Index, Synaptophysin metabolism, Epilepsy physiopathology, Seizures, Febrile physiopathology
- Abstract
Epilepsy is a debilitating neurological illness that affects all aspect of an individual life. Despite advancement in research there is little reduction in the incidence of this disease. Prolonged febrile seizure (PFS) has been linked to epilepsy however, the pathophysiology of this is still not clear. We therefore looked at the effect of PFS on the development of epilepsy in a pentylenetetrazole (PTZ) rat model of epilepsy. A total of 42 male Sprague-Dawley rats were used for the experiment. On post-natal day (PND) 14, PFS was induced in 14 rats. This was followed by the induction of epilepsy in the 14 PFS animal and 14 animals from the remaining 28 rats by an initial injection of PTZ at a dose of 60 mg/kg on day one followed by 35 mg/kg on alternate day until kindle. We looked at the effect of PFS on the onset and the stage of convulsion at kindle. We also observed it effect on the hippocampal glial fibrillary acidic protein (GFAP), synaptophysin and metabotropic glutamate receptor 3 (mGluR3) expression measured with immunofluorescence, LI Cor Tissue florescence and immunohistochemistry respectively. Our study showed that PFS reduced seizure threshold by decreasing the time it took animals to kindle and also increased the stage of convulsion. The hippocampal GFAP, synaptophysin and mGluR3 expressions where upregulated in PTZ rats with PFS history when compared to PTZ rats alone.These findings indicated that PFS may increase the severity of epilepsy and alter brain expression of GFAP, synaptophysin and mGluR3 proteins., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2020
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16. Seasonal variations in Schistosoma haematobium egg excretion in school-age girls in rural KwaZulu-Natal Province, South Africa.
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Christensen EE, Taylor M, Zulu SG, Lillebo K, Gundersen SG, Holmen S, Kleppa E, Vennervald BJ, Ndhlovu PD, and Kjetland EF
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Background: A predominant feature of Schistosoma haematobium infection is urinary egg excretion, and microscopic egg detection remains the accepted standard field diagnostic tool. Praziquantel is the drug of choice for schistosomiasis, and the World Health Organization recommends that it should be administered to all children >4 years of age living in schistosomiasis-endemic areas. The frequency of mass drug administration depends on the prevalence rate in the community. Urinary schistosome egg output has a day-to-day and hour-to-hour intrasubject variation. Therefore, it is important to assess possible seasonal variations in egg excretion to improve the planning of drug treatment., Objectives: To assess the influence of seasonality on urinary schistosome egg excretion in South Africa (SA)., Methods: We performed a prospective cohort study, exploring seasonal variations of S. haematobium egg excretion in 184 girls aged 10 - 12 years from randomly selected schools in a rural area of KwaZulu-Natal Province, SA. The area has a subtropical climate characterised by a cool dry season and a hot humid season. For children, water contact is higher in the latter season. At baseline, 108 girls were examined in the hot season, and 76 in the cold season. In the next year's cold season the untreated patients were re-investigated before treatment., Results: There was a decrease in infection in the group initially tested in the hot season compared with the group tested in the cold season at both time points when adjusted for age and water contact (adjusted odds ratio 3.61 (95% confidence interval 1.14 - 11.44); p=0.03)., Conclusions: This unique study shows that schistosomiasis prevalence determined by microscopy exhibits seasonal variation, with a higher prevalence in the hot rainy season. Precise community prevalence estimations are key in decisions to treat communities. There was significantly lower egg output in the cold season, and sampling in that season may therefore underestimate the prevalence of urinary schistosomiasis. The study indicates that sampling in SA should be done in the hot season.
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- 2018
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17. Principles of Conditioning Therapy and Cell Infusion
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Zulu S, Kenyon M, Kenyon M, and Babic A
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Prior to haematopoietic stem cell transplant (HSCT), conditioning therapy is used for disease eradication, creation of space for engraftment and immunosuppression. Conditioning therapy includes combinations of chemotherapy, radiotherapy and/or immunotherapy. Chemotherapy is delivered in different phases: induction, consolidation and maintenance. Total body irradiation (TBI) is widely used as part of conditioning regimens preceding allogeneic HSCT and is able to target sanctuary sites where some drugs cannot reach. Cancer immunotherapy treatment harnesses the body’s natural defences to fight the cancer, by involving components of the immune system. Conditioning therapy can have acute and chronic side effects due to the toxicity of the treatment. Nursing implications involve patient education and information, toxicity assessments, close monitoring and action plans. Stem cell infusion is usually a safe procedure but can cause adverse reactions ranging from flushing and nausea to life-threatening reactions. There should be written policies for the administration of cellular therapy products, and nurses must have training and competency in order to safely administer haematopoietic stem cells., (Copyright 2018, EBMT and the Author(s).)
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- 2018
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18. Effect of female genital schistosomiasis and anti-schistosomal treatment on monocytes, CD4+ T-cells and CCR5 expression in the female genital tract.
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Kleppa E, Ramsuran V, Zulu S, Karlsen GH, Bere A, Passmore JA, Ndhlovu P, Lillebø K, Holmen SD, Onsrud M, Gundersen SG, Taylor M, Kjetland EF, and Ndung'u T
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- Adolescent, Adult, Animals, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes immunology, Case-Control Studies, Coinfection, Female, Gene Expression, Genital Diseases, Female drug therapy, Genital Diseases, Female immunology, Genital Diseases, Female parasitology, Genitalia, Female immunology, Genitalia, Female metabolism, Genitalia, Female parasitology, Humans, Immunophenotyping, Monocytes drug effects, Monocytes immunology, Phenotype, Praziquantel pharmacology, Praziquantel therapeutic use, Receptors, CCR5 genetics, Schistosomiasis drug therapy, Schistosomiasis immunology, Schistosomiasis parasitology, Young Adult, CD4-Positive T-Lymphocytes metabolism, Genital Diseases, Female metabolism, Monocytes metabolism, Receptors, CCR5 metabolism, Schistosoma haematobium, Schistosomiasis metabolism
- Abstract
Background: Schistosoma haematobium is a waterborne parasite that may cause female genital schistosomiasis (FGS), characterized by genital mucosal lesions. There is clinical and epidemiological evidence for a relationship between FGS and HIV. We investigated the impact of FGS on HIV target cell density and expression of the HIV co-receptor CCR5 in blood and cervical cytobrush samples. Furthermore we evaluated the effect of anti-schistosomal treatment on these cell populations., Design: The study followed a case-control design with post treatment follow-up, nested in an on-going field study on FGS., Methods: Blood and cervical cytobrush samples were collected from FGS negative and positive women for flow cytometry analyses. Urine samples were investigated for schistosome ova by microscopy and polymerase chain reaction (PCR)., Results: FGS was associated with a higher frequency of CD14+ cells (monocytes) in blood (11.5% in FGS+ vs. 2.2% in FGS-, p = 0.042). Frequencies of CD4+ cells expressing CCR5 were higher in blood samples from FGS+ than from FGS- women (4.7% vs. 1.5%, p = 0.018). The CD14+ cell population decreased significantly in both compartments after anti-schistosomal treatment (p = 0.043). Although the frequency of CD4+ cells did not change after treatment, frequencies of CCR5 expression by CD4+ cells decreased significantly in both compartments (from 3.4% to 0.5% in blood, p = 0.036; and from 42.4% to 5.6% in genital samples, p = 0.025)., Conclusions: The results support the hypothesis that FGS may increase the risk of HIV acquisition, not only through damage of the mucosal epithelial barrier, but also by affecting HIV target cell populations, and that anti-schistosomal treatment can modify this.
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- 2014
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19. Assessment of the effect of the oral iron chelator deferiprone on asymptomatic Plasmodium falciparum parasitemia in humans.
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Thuma PE, Olivieri NF, Mabeza GF, Biemba G, Parry D, Zulu S, Fassos FF, McClelland RA, Koren G, Brittenham GM, and Gordeuk VR
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- Administration, Oral, Adult, Area Under Curve, Cross-Over Studies, Deferiprone, Dose-Response Relationship, Drug, Double-Blind Method, Humans, Iron Chelating Agents administration & dosage, Iron Chelating Agents pharmacokinetics, Malaria, Falciparum metabolism, Male, Parasitemia metabolism, Prospective Studies, Pyridones administration & dosage, Pyridones pharmacokinetics, Iron Chelating Agents therapeutic use, Malaria, Falciparum drug therapy, Parasitemia drug therapy, Pyridones therapeutic use
- Abstract
While the parenteral iron-chelating agent desferrioxamine B has anti-malarial activity in humans, the usefulness of an orally active chelator for this indication has not been investigated previously in vivo. We conducted a prospective, double-blind, placebo-controlled, cross-over trial of deferiprone (L1; CP20; 1,2-dimethyl-3-hydroxypyridin-4-one) in 25 adult Zambians with asymptomatic Plasmodium falciparum parasitemia. Deferiprone was administered daily for three or four days in divided doses of 75 or 100 mg/kg of body weight, dosages that are effective for treating iron overload. No reduction in asexual intra-erythrocytic parasites was observed during or after deferiprone treatment. The mean peak plasma concentration of deferiprone (108.9 +/- 24.9 micromol/L) achieved was within the range demonstrated to inhibit the growth of P. falciparum in vitro, but the systemic exposure as determined by the 24-hr plasma concentration-time curve would not be predicted inhibit growth in vivo. No evidence of deferiprone-associated hematological toxicity was noted in this short-term study of these subjects, all of whom had clinical evidence of normal body iron stores. Because of the risk of neutropenia and other adverse effects with higher doses or prolonged use of the chelator, additional trials of deferiprone as a sole anti-malarial agent would not seem to be justified. In contrast, further efforts are needed to develop other orally active iron-chelating agents specifically for their anti-malarial action.
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- 1998
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20. Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria.
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Thuma PE, Mabeza GF, Biemba G, Bhat GJ, McLaren CE, Moyo VM, Zulu S, Khumalo H, Mabeza P, M'Hango A, Parry D, Poltera AA, Brittenham GM, and Gordeuk VR
- Subjects
- Child, Child, Preschool, Coma drug therapy, Double-Blind Method, Drug Therapy, Combination, Female, Fever drug therapy, Humans, Infant, Male, Prospective Studies, Survival Rate, Treatment Outcome, Zambia epidemiology, Antidotes therapeutic use, Antimalarials therapeutic use, Deferoxamine therapeutic use, Iron Chelating Agents therapeutic use, Malaria, Cerebral drug therapy, Malaria, Cerebral mortality, Parasitemia drug therapy, Parasitemia mortality, Quinine therapeutic use
- Abstract
To examine the effect of iron chelation on mortality in cerebral malaria, we enrolled 352 children in a trial of deferoxamine in addition to standard quinine therapy at 2 centres in Zambia, one rural and one urban. Entrance criteria included age < 6 years, Plasmodium falciparum parasitaemia, normal cerebral spinal fluid, and unrousable coma. Deferoxamine (100 mg/kg/d infused for a total of 72 h) or placebo was added to a 7 d regimen of quinine that included a loading dose. Mortality overall was 18.3% (32/175) in the deferoxamine group and 10.7% (19/177) in the placebo group (adjusted odds ratio 1.8; 95% confidence interval 0.9-3.6; P = 0.074). At the rural study site, mortality was 15.4% (18/117) with deferoxamine compared to 12.7% (15/118) with placebo (P = 0.78, adjusted for covariates). At the urban site, mortality was 24.1% (14/58) with deferoxamine and 6.8% (4/59) with placebo (P = 0.061, adjusted for covariates). Among survivors, there was a non-significant trend to faster recovery from coma in the deferoxamine group (adjusted odds ratio 1.2; 95% confidence interval 0.97-1.6; P = 0.089). Hepatomegaly was significantly associated with higher mortality, while splenomegaly was associated with lower mortality. This study did not provide evidence for a beneficial effect on mortality in children with cerebral malaria when deferoxamine was added to quinine, given in a regimen that included a loading dose.
- Published
- 1998
- Full Text
- View/download PDF
21. Transferrin saturation and recovery from coma in cerebral malaria.
- Author
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Gordeuk VR, Thuma PE, McLaren CE, Biemba G, Zulu S, Poltera AA, Askin JE, and Brittenham GM
- Subjects
- Chelation Therapy, Child, Preschool, Cohort Studies, Coma etiology, Coma mortality, Deferoxamine therapeutic use, Double-Blind Method, Drug Therapy, Combination, Female, Free Radicals, Humans, Infant, Iron blood, Lipid Peroxidation, Malaria, Cerebral blood, Malaria, Cerebral drug therapy, Malaria, Cerebral mortality, Male, Prospective Studies, Pyrimethamine therapeutic use, Quinine therapeutic use, Retrospective Studies, Sulfadoxine therapeutic use, Treatment Outcome, Coma blood, Malaria, Cerebral complications, Transferrin analysis
- Abstract
To determine if the elevated transferrin saturations found in some patients with severe malaria are associated with an adverse outcome in cerebral malaria, we retrospectively measured baseline saturations in stored serum samples from 81 Zambian children with strictly defined cerebral malaria. The children had been treated with quinine, sulfadox-ine-pyrimethamine, and intravenous infusions of either placebo (n = 39) or the iron chelator, desferrioxamine B (n = 42), in a previously reported trial (Gordeuk et al, N Engl J Med 327:1473, 1992). More than one-third of children in both the placebo- and iron chelator-treated groups had transferrin saturations exceeding 43%, which is 3 standard deviations above the expected mean for age. Among children receiving quinine and placebo, those with elevated transferrin saturations had a delayed estimated median time to recover full consciousness (68.2 hours) compared with those with saturations < or = 43% (25.4 hours; P = .006). The addition of iron chelation to quinine therapy in children with high saturations appeared to hasten recovery (P = .046). We conclude that increased transferrin saturations may be associated with delayed recovery from coma during standard therapy for cerebral malaria and that serum iron and total iron binding capacity should be measured in future studies.
- Published
- 1995
22. Predictors of severity of illness on presentation in children with cerebral malaria.
- Author
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Mabeza GF, Moyo VM, Thuma PE, Biemba G, Parry D, Khumalo H, Nyarugwe P, Zulu S, and Gordeuk VR
- Subjects
- Age of Onset, Child, Preschool, Chloroquine therapeutic use, Double-Blind Method, Drug Resistance, Female, Fever etiology, Humans, Hypoglycemia etiology, Infant, Leukocytosis etiology, Malaria, Cerebral drug therapy, Malaria, Cerebral epidemiology, Male, Risk Factors, Severity of Illness Index, Splenomegaly complications, Zambia epidemiology, Anemia etiology, Coma etiology, Malaria, Cerebral complications
- Abstract
The presenting features of 195 children with cerebral malaria were analysed to determine which correlated with severity of coma and anaemia. The children, who came from a single community in southern Zambia, were enrolled in an ongoing blinded drug trial in 1992 and 1993. Children with deep coma (scoring 0-2) had significantly longer duration of coma before presentation (P = 0.019) and were more likely to have been treated with chloroquine (P = 0.022) than children with light coma (scoring 3 or 4 on the Blantyre coma scale). Children with severe anaemia (haematocrit < 18%) were younger (P = 0.005), had been febrile longer (P = 0.005), had splenomegaly (P < 0.005) and hypoglycaemia (P < 0.008) more often and were more likely to have been treated with chloroquine (P < 0.005) than those without severe anaemia. The counts of asexual parasites in the peripheral blood were not significantly correlated with depth of coma or severity of anaemia. The observed widespread and uncontrolled use of chloroquine has probably led to the development of resistant malaria and of many severe complications despite early consultation. While early treatment of febrile illnesses in young children and immediate medical attention for altered consciousness must be emphasized in the community approach to severe malaria, our data indicate that effective public health measures will be difficult to develop in the face of a high prevalence of chloroquine resistance.
- Published
- 1995
- Full Text
- View/download PDF
23. Iron chelation as a chemotherapeutic strategy for falciparum malaria.
- Author
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Gordeuk VR, Thuma PE, Brittenham GM, Biemba G, Zulu S, Simwanza G, Kalense P, M'Hango A, Parry D, and Poltera AA
- Subjects
- Adult, Animals, Deferoxamine administration & dosage, Deferoxamine pharmacology, Female, Humans, Infusion Pumps, Malaria, Falciparum blood, Male, Plasmodium falciparum drug effects, Deferoxamine therapeutic use, Malaria, Falciparum drug therapy
- Abstract
To examine the effect of iron chelation against human malaria, 37 Zambians with asymptomatic Plasmodium falciparum infections were randomly assigned to 72-hr infusions of desferrioxamine B or placebo. Mean concentrations of ring forms decreased significantly with desferrioxamine B (P < 0.001) but not with a placebo. Over seven days of observation, mean parasite concentrations remained at the initial levels in six individuals originally given placebo, but decreased promptly with administration of desferrioxamine B (P = 0.001). Mean parasitemia was significantly lower for up to four weeks in 16 subjects treated with desferrioxamine B when compared with the eight who had received placebo only (P = 0.027). We conclude that iron chelation has antiplasmodial activity and may offer a new therapeutic strategy for falciparum malaria.
- Published
- 1993
- Full Text
- View/download PDF
24. Iron chelation with desferrioxamine B in adults with asymptomatic Plasmodium falciparum parasitemia.
- Author
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Gordeuk VR, Thuma PE, Brittenham GM, Zulu S, Simwanza G, Mhangu A, Flesch G, and Parry D
- Subjects
- Adolescent, Adult, Animals, Deferoxamine adverse effects, Deferoxamine blood, Erythrocytes parasitology, Female, Humans, Malaria, Falciparum parasitology, Male, Middle Aged, Plasmodium falciparum isolation & purification, Zambia, Deferoxamine therapeutic use, Iron Chelating Agents therapeutic use, Malaria, Falciparum drug therapy
- Abstract
To determine if iron chelation therapy has activity against human malaria, we administered desferrioxamine B in amounts of 100 mg/kg per day by continuous 72-hour subcutaneous infusions to 28 volunteers with asymptomatic Plasmodium falciparum infection in a randomized, double-blind, placebo-controlled crossover trial. Peripheral blood concentrations of P falciparum ring forms were determined at 12-hour intervals in all subjects and serum concentrations of desferrioxamine B + ferrioxamine (the iron complex of desferrioxamine B) were measured in 26 subjects. Geometric mean concentrations of asexual intraerythrocytic parasites decreased with both chelator and placebo treatment, but the decrement with desferrioxamine B was significantly greater than that with placebo (P less than .006) during both the initial and crossover periods. Compared with placebo, desferrioxamine B treatment was associated with an almost 10-fold enhancement of the rate of parasite clearance during both phases of the trial (P less than .007). Mean +/- SEM steady state concentrations of desferrioxamine B + ferrioxamine were 6.90 +/- 0.60 mumol/L at 36 hours and 7.72 +/- 0.68 mumol/L at 72 hours; in vitro, the ID50 has been reported to be approximately 4 to 20 mumol/L. No drug toxicity was detected. Parasitemia recurred in 19 of 24 participants followed-up over 1 to 6 months. We conclude that desferrioxamine B enhances the clearance of P falciparum parasitemia and that iron chelation may provide a new strategy to be developed for the treatment of malaria.
- Published
- 1992
25. Oxygen saturation after bronchography under general anaesthesia.
- Author
-
Macgillivray RG and Zulu S
- Subjects
- Adult, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, Monitoring, Physiologic, Time Factors, Anesthesia, General, Bronchography, Oxygen blood
- Abstract
Thirty-six patients undergoing bronchography or bronchoscopy under general anaesthesia were continuously monitored by pulse oximetry for 5 hours after these procedures. Significant falls in oxygen saturation were observed in the first hour and were of most clinical relevance in patients with preexisting pulmonary dysfunction who underwent bronchography. These results support the recommendation that supplementary oxygen should be provided for all patients undergoing this investigation.
- Published
- 1989
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