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1.
PLoS One ; 18(11): e0286906, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37922301

RESUMEN

BACKGROUND: Despite the overall reduction in the HIV mother-to-child transmission (MTCT) rate in South Africa, poor adherence and retention in care during breastfeeding contribute to this period being a major driver of MTCT in South Africa. To improve this retention, postnatal clubs were created as an integrated, differentiated model of care providing psychosocial support and comprehensive care for the mother-infant pairs (MIP), including HIV and under-5-child services. We describe the implementation of these facility-based clubs and examine its health outcomes in a peri-urban primary health care setting in Cape Town, South Africa. METHODS: In this prospective cohort study, conducted between June 2016 and December 2019, MIPs were recruited into postnatal clubs between 6 weeks and 6 months of age and followed-up until 18 months of age. Outcomes including maternal Viral Load (VL), and children's HIV testing were compared to a historical control group. Children's immunizations and maternal sexual and reproductive health outcomes are also described. RESULTS: During the implementation of the postnatal club study period, 484 MIP were recruited with 84% overall attendance, 95% overall viral load suppression, and 98% overall uptake of HIV infant testing. Compared to historical controls, the club infant rapid test uptake was 1.6 times higher (95% CI: 1.4-1.9) at 9 months and 2.0 times higher at 18 months (95% CI: 1.6-2.6). Through 12 months and between 12-18 months, maternal VL monitoring was higher in the club group compared to the historical control by 1.5 times (95% CI: 1.3-1.6) and 2.6 times (95% CI: 2.1-3.2), respectively, with similar maternal VL suppression. Of 105 infants attending the 12 months visit, 99% were fully vaccinated by one year. CONCLUSION: MIP in the postnatal clubs showed better PMTCT outcomes than historical controls with high levels of retention in care. Other outcomes such as immunisation results suggest that integration of services, such as in the postnatal club, is feasible and beneficial for MIPs.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Lactante , Humanos , Femenino , Embarazo , Madres , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Estudios Prospectivos , Sudáfrica/epidemiología , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico
2.
JMIR Pediatr Parent ; 6: e40561, 2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37213174

RESUMEN

BACKGROUND: Signing Deaf South Africans have limited access to health information and, consequently, limited knowledge about health. Maternal and neonatal mortality rates are high. Cell phone use is high, making it a potentially effective way of communicating about maternal and child health. OBJECTIVE: The primary aim of this study was to assess whether an SMS text messaging-based health information campaign could improve knowledge about pregnancy, antenatal care, and healthy living during pregnancy for signing Deaf South African women of reproductive age. The secondary aim was to evaluate the acceptability of such an intervention. METHODS: This study was designed as a pretest-posttest study. A baseline questionnaire assessed participants' knowledge about pregnancy, antenatal care, and healthy living during pregnancy before an SMS text messaging-based information campaign was conducted. After the campaign, an exit questionnaire was administered containing the same questions as the baseline questionnaire with additional questions on general acceptability and communication preferences. The results were compared between baseline and exit using the McNemar and Wilcoxon signed rank tests. A focus group aimed to obtain further information on the impact and acceptability of SMS text messages. The focus group was analyzed inductively. RESULTS: The study showed a statistically significant improvement in overall health knowledge among participants. Despite this, some participants found the medical terminology challenging to understand. Several ways of improving SMS text messaging campaigns for the Deaf were identified, including using Multimedia Messaging Services with a person signing messages and linking information campaigns to a communication service that would enable Deaf people to pose questions. The focus group also suggested that SMS text messages might play a role in motivating healthy behaviors during pregnancy. CONCLUSIONS: The SMS text messaging campaign effectively improved Deaf women's knowledge about pregnancy, antenatal care, and healthy living during pregnancy and has the potential to affect health behavior. This contrasts with a similar study on hearing pregnant women. This suggests that SMS text messages may be particularly effective in improving Deaf people's health knowledge. However, attention should be paid to Deaf participants' specific needs and communication preferences to optimize impact. The potential of using SMS text messaging campaigns to affect behavior should be studied. TRIAL REGISTRATION: Pan-African Clinical Trials Registry (PACTR) PACTR201512001352180; https://tinyurl.com/3rxvsrbe.

3.
AIDS Behav ; 26(9): 2891-2896, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35235106

RESUMEN

In South Africa, where an estimated 34% of nearly 7-million HIV-positive people were not on antiretroviral therapy (ART) in 2019, innovative strategies to diagnose and link people to care are needed. HIV self-testing (HIVST) is one such strategy. However, there is concern that access to HIVST might result in re-testing among people on ART, with a risk of false negative results and disengagement from care. Between November 2017 and December 2018, HIVST kits were distributed at a private pharmacy and at HIV testing outreach events. Each participant was instructed to report their result via SMS and those who did not were followed-up telephonically 10 days later. Electronic medical records of participants were searched for evidence of HIV services 6 months before and after enrollment. Of 1482 participants, 163 (11%) were previously diagnosed HIV-positive prior to taking the test. Of these, 123 reported a result, however 87% reported a negative result. Of the 163 previously diagnosed, 84 were not in ART care prior to the test, with 15 (18%) linking to care post-test. Of 79 who were in ART care prior to the test, 76 (96%) remained in care, even though 51 (67%) had reported a negative result. Overall, 29% of participants reported their result via SMS, and 48% when telephoned. Despite efforts to dissuade them, some previously diagnosed HIV-positive utilised HIVST. For those disengaged from care this may facilitate re-engagement. Self-testing among those already in care, regardless of the reported result, did not disrupt their treatment, and their reasons for doing the test remain unclear.


Asunto(s)
Infecciones por VIH , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Prueba de VIH , Humanos , Tamizaje Masivo/métodos , Autoevaluación , Sudáfrica/epidemiología
4.
J Med Internet Res ; 21(12): e14012, 2019 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-31821150

RESUMEN

BACKGROUND: Youths in South Africa are poor utilizers of HIV health services. Medecins Sans Frontieres has been piloting youth-adapted services at a youth clinic in Khayelitsha, including a peer virtual mentorship program over mobile phones, piloted from March 2015 to May 2016. OBJECTIVE: The objective of this study was to evaluate the effect of the peer mentorship program on youth engagement with HIV services and explore the acceptability of the program to both mentors and mentees. METHODS: Antiretroviral initiation, retention in care (RIC), and viral load suppression were compared between youths engaged in the virtual mentorship program and two matched controls. In-depth interviews were also conducted for 5 mentors and 5 mentees to explore acceptability and impact of the program. RESULTS: A total of 40 youths were recruited into the virtual mentorship program over the study period. Of these, data were obtained for 35 and 2 matched controls were randomly sampled for each. There was no difference in baseline demographics (eg, age, gender, and CD4 count). Mentees had increased antiretroviral initiation (28/35, 80% vs 30/70, 42% in matched controls) and viral load completion (28/35, 80% vs 32/70, 45%); however, no differences were found in viral load suppression or RIC at 6 or 12 months. Mentors reported being motivated to participate in the program because of previous personal struggles with HIV and a desire to help their peers. Mentees reported fears of disclosure and lack of acceptance of their status as barrier to accessing services, but they felt free to talk to their mentors, valued the mentorship program, and indicated a preference for phone calls. CONCLUSIONS: Peer mentorship in youths is acceptable to both mentors and mentees and appears to increase linkage to care and viral load completion rates.


Asunto(s)
Teléfono Celular/instrumentación , Infecciones por VIH/terapia , Mentores/psicología , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Grupo Paritario , Sudáfrica , Adulto Joven
5.
PLoS One ; 14(5): e0215454, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31048859

RESUMEN

INTRODUCTION: HIV self-testing (HIVST) offers a useful addition to HIV testing services and enables individuals to test privately. Despite recommendations to the contrary, repeat HIV testing is frequent among people already on anti-retroviral treatment (ART) and there are concerns that oral self-testing might lead to false negative results. A study was conducted in Khayelitsha, South Africa, to assess feasibility and uptake of HIVST and linkage-to-care following HIVST. METHODS: Participants were recruited at two health facilities from 1 March 2016 to 31 March 2017. People under 18 years, or with self-reported previously-diagnosed HIV infection, were excluded. Participants received an OraQuick Rapid HIV-1/2 Antibody kit, and reported their HIVST results by pre-paid text message (SMS) or by returning to the facility. Those not reporting within 7 days were contacted by phone. Electronic and paper-based clinical and laboratory records were retrospectively examined for all participants to identify known HIV outcomes, after matching for name, date of birth, and sex. These findings were compared with self-reported HIVST results where available. RESULTS: Of 639 participants, 401 (62.8%) self-reported a negative HIVST result, 27 (4.2%) a positive result, and 211 (33.0%) did not report. The record search identified that of the 401 participants self-reporting a negative HIVST result, 19 (4.7%) were already known to be HIV positive; of the 27 self-reporting positive, 12 (44%) were known HIV positive. Overall, records showed 57/639 (8.9%) were HIV positive of whom 39/57 (68.4%) had previously-diagnosed infection and 18/57 (31.6%) newly-diagnosed infection. Of the 428 participants who self-reported a result, 366 (85.5%) reported by SMS. CONCLUSIONS: HIVST can improve HIV testing uptake and linkage to care. SMS is acceptable for reporting HIVST results but negative self-reports by participants may be unreliable. Use of HIVST by individuals on ART is frequent despite recommendations to the contrary and its implications need further consideration.


Asunto(s)
Infecciones por VIH/diagnóstico , Tamizaje Masivo/métodos , Adolescente , Adulto , Antirretrovirales/uso terapéutico , Femenino , Anticuerpos Anti-VIH/análisis , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/inmunología , VIH-1/fisiología , VIH-2/inmunología , VIH-2/fisiología , Humanos , Masculino , Juego de Reactivos para Diagnóstico , Estudios Retrospectivos , Autoinforme , Sudáfrica , Carga Viral , Adulto Joven
6.
BMC Public Health ; 17(1): 663, 2017 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-28821288

RESUMEN

BACKGROUND: Signing Deaf South Africans have limited access to health information. As a result, their knowledge about health is limited. Cell phone usage in South Africa is high. This study aimed to assess whether a short message service (SMS)-based health promotion campaign could improve Deaf people's knowledge of hypertension and healthy living. Additionally, the study aimed to assess the acceptability of using SMSs for health promotion targeting Deaf people. METHODS: A baseline questionnaire assessed participants' knowledge about hypertension before an SMS-based information campaign was conducted. After the campaign, an exit questionnaire was conducted, containing the same questions as the baseline questionnaire with additional questions about general acceptability and communication preferences. Results were compared between baseline and exit, using McNemar's test, paired t-test and Wilcoxon signed-rank test. Focus groups aimed to get further information on the impact and acceptability of SMSs. The focus groups were analysed using inductive thematic analysis. RESULTS: The campaign recruited 82 participants for the baseline survey, but due to significant loss-to-follow-up and exclusions only 41 participants were included in the analysis of the survey. The majority (60%) were men. Eighty percent were employed, while 98% had not finished high school. The campaign showed a statistically significant improvement in overall knowledge about hypertension and healthy living amongst participants. Six individual questions out of 19 also showed a statistically significant improvement. Despite this, participants in focus groups found the medical terminology difficult to understand. Several ways of improving SMS campaigns for the Deaf were identified. These included using using pictures, using 'signed' SMSs, combining SMSs with signed drama and linking SMS-campaigns to an interactive communication service that would enable the Deaf to pose questions for clarification. Focus groups suggested that participants who were hypertensive during the campaign adopted a healthier lifestyle. CONCLUSION: SMSs were effective in improving Deaf people's knowledge of hypertension and healthy living. However, SMS-campaigns should be cognizant of Deaf people's unique needs and communication preference and explore how to accommodate these. TRIAL REGISTRATION: The research was registered with the Pan African Clinical Trial Registry on December 1, 2015. Identification number: PACTR201512001353476 .


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Promoción de la Salud/métodos , Hipertensión/prevención & control , Personas con Deficiencia Auditiva/psicología , Envío de Mensajes de Texto , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Personas con Deficiencia Auditiva/estadística & datos numéricos , Evaluación de Programas y Proyectos de Salud , Sudáfrica , Encuestas y Cuestionarios
7.
AIDS Care ; 28(7): 898-903, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27098208

RESUMEN

INTRODUCTION: Médecins Sans Frontières supports human immunodeficiency virus (HIV)-infected youth, aged 12-25 years, at a clinic in Khayelitsha, South Africa. Patients are enrolled in youth clubs, and provided with a virtual chat room, using the cell-phone-based social networking platform, MXit, to support members between monthly/bimonthly club meetings. The acceptability and uptake of MXit was assessed. METHODS: MXit was facilitated by lay counsellors, was password protected, and participants could enter and leave at will. Club members were asked to complete self-administered questionnaires and participate in two focus-group discussions. RESULTS AND DISCUSSION: In total, 60 club members completed the questionnaire, and 12 participated in the focus groups. Fifty-eight percentage were aged 23-25 years, 63% were female and 83% had a cell phone. Sixty percentage had used MXit before, with 38% having used it in the past month. Sixty-five percentage were aware of the chat-room and 39% knew how to access it. Thirty-four percentage used the chat-room at least once, 20% had visited the chat-room in the past month, and 29% had used MXit to have private conversations with other club members. Fifty-seven percentage used the chat-room to get advice, and 84% of all respondents felt that offering a service outside the youth club meetings was important and would like to see one to continue. The cost of using social media platforms was an issue with some, as well as the need for anonymity. Preference for other platforms, logistical obstacles, or loss of interest contributed to non-use. CONCLUSIONS: Reported usage of the MXit chat-room was low, but participants indicated acceptance of the programme and their desire to interact with their peers through social media. Suggestions to improve the platform included accessible chat histories, using more popular platforms such as Facebook or WhatsApp, and to have topical discussions where pertinent information for youth is provided.


Asunto(s)
Infecciones por VIH , Grupos de Autoayuda/organización & administración , Red Social , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Infecciones por VIH/rehabilitación , Accesibilidad a los Servicios de Salud , Humanos , Difusión de la Información/métodos , Relaciones Interpersonales , Masculino , Motivación , Grupo Paritario , Apoyo Social , Sudáfrica/epidemiología , Encuestas y Cuestionarios , Interfaz Usuario-Computador , Adulto Joven
8.
JMIR Mhealth Uhealth ; 4(1): e22, 2016 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-26964505

RESUMEN

BACKGROUND: The use of mobile phones to deliver health care (mHealth) is increasing in popularity due to the high prevalence of mobile phone penetration. This is seen in developing countries, where mHealth may be particularly useful in overcoming traditional access barriers. Non-communicable diseases may be particularly amenable to mHealth interventions, and hypertension is one with an escalating burden in the developing world. OBJECTIVE: The objective of this study was to test whether the dissemination of health information via a short message service (SMS) led to improvements in health knowledge and self-reported health-related behaviors. METHODS: A mixed methods study was carried out among a cohort of 223 hypertension clinic patients, in a resource-poor setting in Cape Town, South Africa, in 2012. Hypertensive outpatients were recruited at the clinic and administered a baseline questionnaire to establish existing knowledge of hypertension. Participants were then randomly assigned to intervention or control groups. The intervention group received 90 SMSes over a period of 17 weeks. Thereafter, the baseline questionnaire was readministered to both groups to gauge if any improvements in health knowledge had occurred. Those who received SMSes were asked additional questions about health-related behavior changes. A focus group was then conducted to obtain in-depth feedback about participants' experience with, and response to, the SMS campaign. RESULTS: No statistically significant changes in overall health knowledge were observed between the control and intervention groups. The intervention group had positive increases in self-reported behavior changes. These were reaffirmed by the focus groups, which also revealed a strong preference for the SMS campaign and the belief that the SMSes acted as a reminder to change, as opposed to providing new information. CONCLUSIONS: Although the content of the SMSes was not new, and did not improve health knowledge, SMSes were effective in motivating positive self-reported behavior change among hypertensive patients. TRIAL REGISTRATION: Pan African Clinical Trials Registry Number: PACTR201412000968462. Registered 18 December 2014 (Archived by WebCite at http://www.webcitation.org/6fhtyLRcO).

9.
Health Res Policy Syst ; 14: 10, 2016 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-26861120

RESUMEN

BACKGROUND: Setting priorities is important in health research given the limited resources available for research. Various guidelines exist to assist in the priority setting process; however, priority setting still faces significant challenges such as the clear ranking of identified priorities. The World Health Organization (WHO) proposed a Disability Adjusted Life Year (DALY)-based model to rank priorities by research area (basic, health systems and biomedical) by dividing the DALYs into 'unavertable with existing interventions', 'avertable with improved efficiency' and 'avertable with existing but non-cost-effective interventions', respectively. However, the model has conceptual flaws and no clear methodology for its construction. Therefore, the aim of this paper was to amend the model to address these flaws, and develop a clear methodology by using tuberculosis in South Africa as a worked example. METHODS: An amended model was constructed to represent total DALYs as the product of DALYs per person and absolute burden of disease. These figures were calculated for all countries from WHO datasets. The lowest figures achieved by any country were assumed to represent 'unavertable with existing interventions' if extrapolated to South Africa. The ratio of 'cost per patient treated' (adjusted for purchasing power and outcome weighted) between South Africa and the best country was used to calculate the 'avertable with improved efficiency section'. Finally, 'avertable with existing but non-cost-effective interventions' was calculated using Disease Control Priorities Project efficacy data, and the ratio between the best intervention and South Africa's current intervention, irrespective of cost. RESULTS: The amended model shows that South Africa has a tuberculosis burden of 1,009,837.3 DALYs; 0.009% of DALYs are unavertable with existing interventions and 96.3% of DALYs could be averted with improvements in efficiency. Of the remaining DALYs, a further 56.9% could be averted with existing but non-cost-effective interventions. CONCLUSIONS: The amended model was successfully constructed using limited data sources. The generalizability of the data used is the main limitation of the model. More complex formulas are required to deal with such potential confounding variables; however, the results act as starting point for development of a more robust model.


Asunto(s)
Investigación Biomédica/organización & administración , Modelos Teóricos , Tuberculosis/epidemiología , Organización Mundial de la Salud , Antituberculosos/economía , Antituberculosos/uso terapéutico , Análisis Costo-Beneficio , Humanos , Incidencia , Prevalencia , Años de Vida Ajustados por Calidad de Vida , Sudáfrica , Tuberculosis/tratamiento farmacológico , Tuberculosis/economía
10.
S Afr Med J ; 106(1): 47-9, 2015 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-26792304

RESUMEN

Cell phone-based health information (mobile health or mHealth) campaigns are an emerging technology. This evaluation focused on the aspect of cost of two health information campaigns, one on hypertension and one on pregnancy. Researchers could either contract out the technical components of the campaigns or attempt to run the campaigns themselves, in-house. The in-house campaigns cost an estimated ZAR13 548.72 v. the private provider quotes which ranged from ZAR27 542.97 to ZAR34 227.59. Running the campaigns in-house was more labour intensive and required more technical expertise, but had a reduced delivery failure rate (9.2% in-house v. 30.0% private provider). Running small to medium SMS (text message) campaigns for evaluative purposes proved advantageous over contracting out to private providers. Larger-scale evaluations and full-scale roll-out will require the services of private providers, but it is still essential that researchers actively engage with and monitor the technical aspects of these campaigns.


Asunto(s)
Citas y Horarios , Teléfono Celular , Sordera/rehabilitación , Sistemas Recordatorios/instrumentación , Envío de Mensajes de Texto , Humanos
11.
BMC Pregnancy Childbirth ; 14: 284, 2014 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-25145970

RESUMEN

BACKGROUND: Adequate antenatal care is important to both the health of a pregnant woman and her unborn baby. Given South Africa's high rate of cellphone penetration, mobile health interventions have been touted as a potentially powerful means to disseminate health information. This study aimed to increase antenatal health knowledge and awareness by disseminating text messages about clinic procedures at antenatal visits, and how to be healthy during pregnancy. METHODS: Participants recruited were pregnant women attending a primary health care facility in Cape Town. A controlled clinical trial was carried out where the intervention group (n = 102) received text messages staggered according to the week of pregnancy at the time of recruitment. The control group (n = 104) received no text messages. These text messages contained antenatal health information, and were delivered in English, Xhosa or Afrikaans, according to the preference of each participant. A baseline knowledge questionnaire with nine questions was administered prior to the intervention. The same questionnaire was used with added health-related behaviour questions for the intervention group at exit. A modified intention-to-treat analysis was done. To compare the control and intervention group's knowledge, Fisher's exact tests and two-sample t-tests tests were carried out for binary and continuous outcomes, respectively. A focus group of seven participants from the intervention group was then conducted to gain more insight into how the text messages were perceived. RESULTS: There was substantial loss to follow-up during the study with only 57% of the participants retained at exit. No statistically significant difference was detected between the control and intervention group in any of the nine knowledge questions at exit (all p > 0.05). Responses from the focus group indicated that the text messages acted as a welcome reminder and a source of positive motivation, and were perceived as extended care from the health care provider. CONCLUSIONS: While the intervention failed to improve antenatal health knowledge, evidence from self-reported behaviour and the focus group suggests that text messages have the potential to motivate change in health-seeking behaviour. One should be mindful of loss to follow-up when rolling out mobile health interventions in developing country settings. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201406000841188. Registered 3 June 2014.


Asunto(s)
Promoción de la Salud/métodos , Partería/métodos , Educación del Paciente como Asunto/métodos , Atención Prenatal , Envío de Mensajes de Texto , Adulto , Femenino , Grupos Focales , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Embarazo , Sudáfrica , Encuestas y Cuestionarios , Adulto Joven
12.
Cardiovasc J Afr ; 25(3): 118-23, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25000441

RESUMEN

AIM: Sphingosine-1-phosphate (S1P) is a cardioprotective agent. Signal transducer and activator of transcription 3 (STAT-3) is a key mediator of many cardioprotective agents. We aimed to explore whether STAT-3 is a key mediator in S1P-induced preconditioning. METHODS: Langendorff-perfused hearts from Wistar rats and wild-type or cardiomyocyte-specific STAT-3 knockout mice were pre-treated with S1P (10 nmol/l), with or without the STAT-3 pathway inhibitor AG490, before an ischaemia-reperfusion insult. Triphenyltetrazolium chloride and Evans blue staining were used for the determination of infarct size. Western blot analysis was carried out on the S1P pre-treated hearts for detection of cytosolic, nuclear and mitochondrial phosphorylated and total STAT-3 proteins. RESULTS: Pre-treatment with S1P decreased the infarct size in isolated rat (5 ± 3% vs control 26 ± 8%, p < 0.01) and wild-type mouse hearts (13 ± 1% vs control 33 ± 3%, p < 0.05). This protective effect was abolished in the rat hearts pre-treated with AG490 (30 ± 10%, p = ns vs control) and in the hearts from STAT-3 knockout mice (35 ± 4% vs control 30 ± 3%, p = ns). Levels of phosphorylated STAT-3 were significantly increased in both the nuclear (p < 0.05 vs control) and mitochondrial (p < 0.05 vs control) fractions in the S1P pre-treated hearts, but remained unchanged in the cytosolic fraction (p = ns vs control). CONCLUSION: These novel results demonstrate that pharmacological preconditioning with S1P in the isolated heart is mediated by activation of mitochondrial and nuclear STAT-3, therefore suggesting that S1P may be a novel therapeutic target to modulate mitochondrial and nuclear function in cardiovascular disease in order to protect the heart against ischaemia-reperfusion.


Asunto(s)
Cardiotónicos/uso terapéutico , Lisofosfolípidos/farmacología , Infarto del Miocardio/tratamiento farmacológico , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Esfingosina/análogos & derivados , Tirfostinos/uso terapéutico , Animales , Modelos Animales de Enfermedad , Precondicionamiento Isquémico Miocárdico , Masculino , Ratones , Ratones Noqueados , Miocardio/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Ratas Wistar , Esfingosina/farmacología
13.
Atherosclerosis ; 228(1): 110-6, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23497785

RESUMEN

OBJECTIVE: High density lipoproteins (HDL) protect against ischemia reperfusion injury (IRI). However the precise mechanisms are not clearly understood. The novel intrinsic prosurvival signaling pathway named survivor activating factor enhancement (SAFE) path involves the activation of tumor necrosis factor (TNF) alpha and signal transducer and activator of transcription 3 (STAT3). SAFE plays a crucial role in cardioprotection against IRI. We propose that HDL protect against IRI via activation of the SAFE pathway and modulation of the mitochondrial permeability transition pore (mPTP) opening. METHODS AND RESULTS: Isolated mouse hearts were subjected to global ischemia (35 min) followed by reperfusion (45 min). HDL were given during the first 7 min of reperfusion. In control hearts, the post-reperfusion infarct size was 41.3 ± 2.3%. Addition of HDL during reperfusion reduced the infarct size in a dose-dependent manner (HDL 200 µg protein/ml: 25.5 ± 1.6%, p < 0.001 vs. control). This protective effect was absent in TNF deficient mice (TNF-KO) or cardiomyocyte-STAT3 deficient mice (STAT3-KO). Similarly, HDL, given as a preconditioning stimulus, improved cell survival and inhibited mPTP opening in isolated cardiomyocytes subjected to simulated ischemia. These protective responses were inhibited in cardiomyocytes from TNF-KO and STAT3-KO mice. CONCLUSION: Our data demonstrate that HDL protect against IRI by inhibition of mPTP opening, an effect mediated via activation of the SAFE pathway.


Asunto(s)
HDL-Colesterol/metabolismo , Mitocondrias/metabolismo , Membranas Mitocondriales/metabolismo , Infarto del Miocardio/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Animales , Supervivencia Celular/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Fosforilación/fisiología , Factor de Transcripción STAT3/genética , Transducción de Señal/fisiología , Factor de Necrosis Tumoral alfa/genética
14.
Basic Res Cardiol ; 105(6): 763-70, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20938668

RESUMEN

Ethanolamine is a biogenic amine found naturally in the body as part of membrane lipids and as a metabolite of the cardioprotective substances, sphingosine-1-phosphate (S1P) and anandamide. In the brain, ethanolamine, formed from the breakdown of anandamide protects against ischaemic apoptosis. However, the effects of ethanolamine in the heart are unknown. Signal transducer and activator of transcription 3 (STAT-3) is a critical prosurvival factor in ischaemia/reperfusion (I/R) injury. Therefore, we investigated whether ethanolamine protects the heart via activation of STAT-3. Isolated hearts from wildtype or cardiomyocyte specific STAT-3 knockout (K/O) mice were pre-treated with ethanolamine (Etn) (0.3 mmol/L) before I/R insult. In vivo rat hearts were subjected to 30 min ischaemia/2 h reperfusion in the presence or absence of 5 mg/kg S1P and/or the FAAH inhibitor, URB597. Infarct size was measured at the end of each protocol by triphenyltetrazolium chloride staining. Pre-treatment with ethanolamine decreased infarct size in isolated mouse or rat hearts subjected to I/R but this infarct sparing effect was lost in cardiomyocyte specific STAT-3 deficient mice. Pre-treatment with ethanolamine increased nuclear phosphorylated STAT-3 [control 0.75 ± 0.08 vs. Etn 1.50 ± 0.09 arbitrary units; P < 0.05]. Our findings suggest a novel cardioprotective role for ethanolamine against I/R injury via activation of STAT-3.


Asunto(s)
Fármacos Cardiovasculares/farmacología , Etanolamina/farmacología , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Miocardio/metabolismo , Factor de Transcripción STAT3/metabolismo , Amidohidrolasas/antagonistas & inhibidores , Amidohidrolasas/metabolismo , Animales , Benzamidas/farmacología , Carbamatos/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Quinasas Janus/antagonistas & inhibidores , Quinasas Janus/metabolismo , Lisofosfolípidos/metabolismo , Masculino , Ratones , Ratones Noqueados , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocardio/patología , Fosforilación , Ratas , Ratas Wistar , Factor de Transcripción STAT3/deficiencia , Factor de Transcripción STAT3/genética , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Tirfostinos/farmacología
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