Soluble Urokinase Plasminogen Activator Receptor (suPAR) is Associated with Metabolic Changes in HIV-1-Infected Africans: A Prospective Study

Soluble urokinase plasminogen activator receptor (suPAR) is associated with inflammation and may predict lipodystrophy and dysmetabolism in human immunodeficiency virus (HIV)-infected individuals on antiretroviral therapy. We aimed to assess firstly, whether suPAR levels are elevated in treated and untreated HIV-1-infected Africans compared to uninfected controls at baseline and at a 3-year follow-up, and secondly whether suPAR levels are correlated with cardiovascular and/or metabolic changes. SuPAR, cardiovascular, and metabolic variables were assessed and the percentage change was determined. HIV-1-infected black South Africans had significantly higher suPAR levels than uninfected controls at baseline and at follow-up 3 years later. However, only the treated HIV-1-infected participants showed an increase in suPAR levels at follow-up. The treated group also showed signs of lipodystrophy and their baseline suPAR levels correlated positively with an increased waist circumference. This study indicates that suPAR levels increase and that baseline suPAR is associated with an increase in abdominal fat distribution in HIV-infected black Africans on antiretroviral therapy.     

Exploring soluble urokinase plasminogen activator receptor and its relationship with arterial stiffness in a bi-ethnic population: the SAfrEIC-study

Introduction

Elevated soluble urokinase-type plasminogen activator receptor (suPAR) indicates an inflammatory state caused by conditions such as HIV and cancer. Recently suPAR was identified as an indicator of cardiovascular disease (CVD). CVD is highly prevalent in black South Africans, but the potential role of suPAR is unknown. We investigated suPAR as a possible marker of arterial stiffness in Africans and Caucasians.

Methods

This study involved 207 Africans and 314 Caucasians (aged 20-70 yrs). C-reactive protein (CRP) and suPAR were determined in fasting blood samples. We measured blood pressure, pulse wave velocity (PWV) and Windkessel arterial compliance (Cwk).

Results

Africans displayed higher suPAR, CRP, PWV and lower Cwk (p < 0.001) compared to Caucasians. SuPAR was elevated in Africans irrespective of gender and smoking. We found strong relationships between PWV and suPAR (r = 0.27; p < 0.001) and Cwk and suPAR (r = − 0.39; p < 0.001) in the whole group, but found no independent relationship of any arterial stiffness measure and suPAR in Africans after adjustment for confounders. Caucasian men indicated a weak significant independent association between Cwk and suPAR (β = − 0.09; p = 0.028).

Conclusion

Africans had higher levels of suPAR and arterial stiffness than Caucasians (p < 0.001), but there was no independent relationship between arterial stiffness and suPAR in the Africans. It is speculated that due to the inflammatory role of suPAR, it will have stronger relationships with atherosclerosis, which has not yet manifested in this relatively young population group. SuPAR may therefore not be an ideal early marker of cardiovascular dysfunction, but may rather indicate established CVD.     

Help of third-year medical students decreases first-year medical students' negative psychological reactions on the first day of gross anatomy dissection

The assistance of third-year medical students (MS3) may be an easy, inexpensive, educational method to decrease physical and emotional stress among first-year medical students (MS1) on the first day of gross anatomy dissection. In the academic years 2000-2001 and 2001-2002, a questionnaire on the emotional and physical reactions on the first day of dissection was distributed to 84 MS1 at Mayo Medical School (Rochester, MN); 74 (88%) responded. Student perceptions were assessed on a 5-point Likert scale. The 42 second-year medical students (MS2) whose first academic year was 1999-2000 were used as a control group, because they had not had assistance from MS3. MS2 completed the same questionnaire (59% response rate). Data were collected from MS1 on the day of their first gross anatomy dissection. The most frequent reactions were headache, disgust, grief or sadness, and feeling light-headed. Significant differences (alpha < 0.05) were found with use of the chi(2) test to compare the emotional and physical reactions of MS1 and MS2. MS1 had significantly fewer physical reactions (64% vs. 88%), reporting lower levels of anxiety (23% vs. 48%), headache (14% vs. 36%), disgust (9% vs. 20%), feeling light-headed (11% vs. 24%), and reaction to the smell of the cadaver and laboratory (8% vs. 52%). MS1 commented that having MS3 at the dissection table was extremely helpful. They relied less on their peers and felt they learned more efficiently about the dissection techniques and anatomical structures. Using MS3 as assistants is one method to reduce fear and anxiety on the first day of gross anatomy dissection.     

Neuro-immune interactions in inflammatory bowel disease and irritable bowel syndrome: future therapeutic targets

The gastro-intestinal tract is well known for its largest neural network outside the central nervous system and for the most extensive immune system in the body. Research in neurogastroenterology implicates the involvement of both enteric nervous system and immune system in symptoms of inflammatory bowel disease and irritable bowel syndrome. Since both disorders are associated with increased immune cell numbers, nerve growth and activation of both immune cells and nerves, we focus in this review on the involvement of immune cell–nerve interactions in inflammatory bowel disease and irritable bowel syndrome. Firstly, the possible effects of enteric nerves, especially of the nonadrenergic and noncholinergic nerves, on the intestinal immune system and their possible role in the pathogenesis of chronic intestinal inflammatory diseases are described. Secondly, the possible effects of immunological factors, from the innate (chemokines and Toll-like receptors) as well as the adaptive (cytokines and immunoglobulins) immune system, on gastro-intestinal nerves and its potential role in the development of inflammatory bowel disease and irritable bowel syndrome are reviewed. Investigations of receptor-mediated and intracellular signal pathways in neuro-immune interactions might help to develop more effective therapeutic approaches for chronic inflammatory intestinal diseases.     

Subcutaneous Electrical Nerve Stimulation: A Feasible and New Method for the Treatment of Patients With Refractory Angina

Introduction: Patients suffering from chronic angina pectoris, insufficiently controllable with medication and revascularization, are an increasing medical and psychosocial problem. Although spinal cord stimulation (SCS) is proven to employ, safe, long‐term anti‐angina, and anti‐ischemic effects for these patients, the use of SCS in this group remains limited. The reason for this restricted use is largely unknown. However, among other reasons, it may be related to the difficulties in positioning an electrode in the epidural space. We studied the feasibility and efficacy of subcutaneous implantation of an entire system. Methods: Seven male patients, mean age 67 ± 3.6 years, received complete subcutaneously implanted electrical nerve stimulation (SENS) systems, with one or more leads fixed in parallel with the sternum, covering the angina area. At baseline and 2 months follow‐up patients performed exercise and quality of life tests (Seattle Angina Questionnaire and diaries number angina attacks and glyceryl trinitrate use). Results: All patients showed clinical relevant improvement (baseline vs. follow‐up), in exercise (63%) and quality of life (Seattle Angina Questionnaire 59%). The number of angina attacks dropped 82% and the number of glyceryl trinitrate use decreased by 90%. No major adverse events were observed. Conclusion: This small feasibility study demonstrates SENS to be an effective and safe method to treat patients suffering from refractory angina. Furthermore, SENS is less invasive and appears to have less lead migrations compared with SCS.     

A transition in health status from childhood to adulthood and associated lifestyle risk factors: a 13-year interval follow-up study in South Africa

South Africa is a developing country that also has developed aspects and as a result, has to cope with issues related to both worlds. There has been a definite change in the global patterns of diseases from a situation dominated by infectious diseases to a predominance of non-communicable diseases where the risk factors are largely associated with lifestyle. Results from a follow-up study were used to investigate a transition in health status of the study sample. Questionnaires were used in this historical cohort study, which reviews the health status and lifestyle aspects of young adults who participated as children in the Vaal Triangle Air Pollution Health Study (VAPS) during 1990. In general, the study sample had a higher prevalence of chronic diseases compared to the general South African population. Findings indicate that the transition in health status recorded elsewhere in the world can be demonstrated in this South African group.     

Human Milk Oligosaccharide 3′-GL Improves Influenza-Specific Vaccination Responsiveness and Immunity after Deoxynivalenol Exposure in Preclinical Models

Deoxynivalenol (DON), a highly prevalent mycotoxin food contaminant, is known to have immunotoxic effects. In the current study, the potential of dietary interventions with specific mixtures of trans-galactosyl-oligosaccharides (TOS) to alleviate these effects were assessed in a murine influenza vaccination model. Vaccine-specific immune responses were measured in C57Bl/6JOlaHsd mice fed diets containing DON, TOS or a combination, starting 2 weeks before the first vaccination. The direct effects of TOS and its main oligosaccharide, 3′-galactosyl-lactose (3′-GL), on DON-induced damage were studied in Caco-2 cells, as an in vitro model of the intestinal epithelial barrier. Exposure to DON significantly reduced vaccine-specific immune responses and the percentages of Tbet⁺ Th1 cells and B cells in the spleen. DON significantly altered epithelial structure and integrity in the ileum and reduced the SCFA levels in the cecum. Adding TOS into DON-containing diets significantly improved vaccine-specific immune responses, restored the immune cell balance in the spleen and increased SCFA concentrations in the cecum. Incubating Caco-2 cells with TOS and 3′-GL in vitro further confirmed their protective effects against DON-induced barrier disruption, supporting immune modulation. Overall, dietary intervention with TOS can attenuate the adverse effects of DON on Th1-mediated immune responses and gut homeostasis. These beneficial properties might be linked to the high levels of 3′-GL in TOS.