ABSTRACT
FGF2 is a potent stimulator of vascular growth; however, even with a deficiency of FGF2 (Fgf2-/-), developmental vessel growth or ischaemia-induced revascularization still transpires. It remains to be elucidated as to what function, if any, FGF2 has during ischaemic injury. Wildtype (WT) or Fgf2-/- mice were subjected to hindlimb ischaemia for up to 42 days. Limb function, vascular growth, inflammatory- and angiogenesis-related proteins, and inflammatory cell infiltration were assessed in sham and ischaemic limbs at various timepoints. Recovery of ischaemic limb function was delayed in Fgf2-/- mice. Yet, vascular growth response to ischaemia was similar between WT and Fgf2-/- hindlimbs. Several angiogenesis- and inflammatory-related proteins (MCP-1, CXCL16, MMPs and PAI-1) were increased in Fgf2-/- ischaemic muscle. Neutrophil or monocyte recruitment/infiltration was elevated in Fgf2-/- ischaemic muscle. In summary, our study indicates that loss of FGF2 induces a pro-inflammatory microenvironment in skeletal muscle which exacerbates ischaemic injury and delays functional limb use.
Subject(s)
Fibroblast Growth Factor 2/metabolism , Muscle, Skeletal/metabolism , Neovascularization, Physiologic , Reperfusion Injury/metabolism , Animals , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Chemokine CXCL16/genetics , Chemokine CXCL16/metabolism , Fibroblast Growth Factor 2/genetics , Hindlimb/blood supply , Matrix Metalloproteinases/genetics , Matrix Metalloproteinases/metabolism , Mice , Muscle, Skeletal/blood supply , Muscle, Skeletal/physiology , Plasminogen Activator Inhibitor 1/genetics , Plasminogen Activator Inhibitor 1/metabolism , RegenerationABSTRACT
BACKGROUND: As part of global efforts to contain the spread of the 2009 pandemic influenza A (H1N1), the Federal Ministry of Health of Nigeria is embarking on the vaccination of health care workers employed in health facilities nationwide. This study was designed to assess the willingness of doctors and nurses working in public health facilities in Ibadan, Nigeria to receive the influenza A (H1N1) vaccine. METHODS: A descriptive cross-sectional study design was employed. Stratified simple random sampling was used to select a total of 304 doctors and nurses who worked at the public primary (70), secondary (51) and tertiary (183) levels of health care facilities in Ibadan. A self-administered, structured questionnaire that contained items on socio-demographics, sources of information, knowledge about the infection and the vaccine, risk perception, willingness to receive the vaccine and suggestions to improve vaccination acceptance by health-care workers was used to collect the data. MAIN FINDINGS: A total of 255 providers responded for an overall response rate of 84%. The mean age of the respondents was 35.0 ± 9.7 years. A high proportion (88.2%) of the participants, including 94.9% of the doctors and 87.0% of the nurses, reported a willingness to receive the vaccine. Perceptions regarding the risk of contracting influenza, the availability of effective vaccinations for prevention and beliefs that the disease is fatal were reasons given by respondents who reported willingness to receive the vaccination. Those participants who reported ever hearing about the pandemic (AOR 2.0, 95% CI 1.2-3.2) and those who had a high-risk perception of contracting the disease (AOR 2.0, 95% CI 1.2-3.7) were likely to receive the vaccine. CONCLUSION: Doctors and nurses at the three levels of health care facilities in Ibadan were willing to receive the pandemic influenza A (H1N1) vaccine. Efforts should be made to deliver the vaccines via adequate planning.
Subject(s)
Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Nurses/psychology , Patient Acceptance of Health Care/psychology , Physicians/psychology , Vaccination/psychology , Adult , Cross-Sectional Studies , Female , Health Facilities , Hospitals, Public , Humans , Influenza Vaccines/immunology , Influenza, Human/epidemiology , Male , Middle Aged , Nigeria , Surveys and Questionnaires , Young AdultABSTRACT
The occurrence of cardiovascular dysfunction in sepsis is associated with a significantly increased mortality rate of 70% to 90% compared with 20% in septic patients without cardiovascular impairment. Thus, rectification or blockade of myocardial depressant factors should partly ameliorate sepsis progression. Heat shock protein 20 (Hsp20) has been shown to enhance myocardial contractile function and protect against doxorubicin-induced cardiotoxicity. To investigate the possible role of Hsp20 in sepsis-mediated cardiac injury, we first examined the expression profiles of five major Hsps in response to lipopolysaccharide (LPS) challenge, and observed that only the expression of Hsp20 was downregulated in LPS-treated myocardium, suggesting that this decrease might be one of the mechanisms contributing to LPS-induced cardiovascular defects. Further studies using loss-of-function and gain-of-function approaches in adult rat cardiomyocytes verified that reduced Hsp20 levels were indeed correlated with the impaired contractile function. In fact, overexpression of Hsp20 significantly enhanced cardiomyocyte contractility upon LPS treatment. Moreover, after administration of LPS (25 microg/g) in vivo, Hsp20 transgenic mice (10-fold overexpression) displayed: 1) an improvement in myocardial function; 2) reduced the degree of cardiac apoptosis; and 3) decreased NF-kappaB activity, accompanied with reduced myocardial cytokines IL-1beta and TNF-alpha production, compared to the LPS-treated non-transgenic littermate controls. Thus, the increases in Hsp20 levels can protect against LPS-induced cardiac apoptosis and dysfunction, associated with inhibition of NF-kappaB activity, suggesting that Hsp20 may be a new therapeutic agent for the treatment of sepsis.
