Prolactin potentiates insulin-stimulated leptin expression and release from differentiated brown adipocytes

The pituitary hormone prolactin (PRL) exerts pleiotropic effects, which are mediated by a membrane receptor (PRLR) present in numerous cell types including adipocytes. Brown adipose tissue (BAT) expresses uncoupling proteins (UCPs), involved in thermogenesis, but also secretes leptin, a key hormone involved in the control of body weight. To investigate PRL effects on BAT, we used the T37i brown adipose cell line, and demonstrated that PRLRs are expressed as a function of cell differentiation. Addition of PRL leads to activation of the JAK/STAT and MAP kinase signaling pathways, demonstrating that PRLRs are functional in these cells. Basal and catecholamine-induced UCP1 expression were not affected by PRL. However, PRL combined with insulin significantly increases leptin expression and release, indicating that PRL potentiates the stimulatory effect of insulin as revealed by the recruitment of insulin receptor substrates and the activation of phosphatidylinositol 3-kinase. To explore the in vivo physiological relevance of PRL action in BAT, we showed that leptin content was significantly increased in BAT of PRLR-null mice compared with wild-type mice, highlighting the involvement of PRL in the leptin secretion process. This study provides the first evidence for a functional link between PRL and energy balance via a cross-talk between insulin and PRL signaling pathways in brown adipocytes.     

Uveitis associated with thyroïditis in HTLV-1 carriers

INTRODUCTION: The oncovirus HTLV-1 is aetiologically associated with uveitis and autoimmune thyroiditis in endemic areas. The association of uveitis with autoimmune thyroiditis in HTLV-1 carriers is less common moreover in non-endemic area. EXEGESE: We report two original cases of simultaneous uveitis and autoimmune thyroiditis in HTLV-1 carriers, without other disease due to HTLV-1. The visual outcome was favorable in both cases. CONCLUSION: A significant correlation exists between hyperthyroidism, uveitis and HTLV-1, but still needs to be confirmed. The autoimmune or immune mediated mecanism of HTLV-1 may be involved in the uveitis and the thyroidits.     

Relationship of serum TWEAK level to cytokine level, disease activity, and response to anti-TNF treatment in patients with rheumatoid arthritis

OBJECTIVES: To determine the serum concentration of tumour necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK) in patients with rheumatoid arthritis (RA) and to investigate the relationship between TWEAK level and disease activity, proinflammatory cytokine levels, and response to anti-TNF treatment. METHODS: Serum samples from 40 patients with RA, 40 patients with ankylosing spondylitis (AS), and 40 healthy subjects were collected. Serum samples from 26 patients with RA who received etanercept treatment were also collected in the 12th week of etanercept therapy. Serum TWEAK, TNFalpha, and interleukin (IL)-6 levels were determined by enzyme-linked immunosorbent assay (ELISA), and disease activity of RA was assessed according to the 28-joint count Disease Activity Score (DAS28). RESULTS: Patients with RA had significantly higher serum levels of TWEAK, TNFalpha, and IL-6 compared with controls (p<0.05). Patients with AS also had significantly higher serum levels of TNFalpha and IL-6 (p<0.05), but their serum TWEAK levels were not different from those of the controls. In patients with RA, serum TWEAK levels correlated with DAS28 (r(2) = 0.452, p = 0.012) and TNFalpha levels (r(2) = 0.653, p<0.001) but not with IL-6 levels. Among RA patients who were treated with etanercept, responders showed a significant decrease in serum TWEAK levels at the 12th week of treatment, whereas TWEAK levels in nonresponders were not different from their baseline levels. CONCLUSIONS: Serum levels of TWEAK were significantly elevated in patients with RA, and reflected disease activity and short-term response to etanercept treatment.     

Risk factors and clinical outcomes of ventilator-associated pneumonia in patients on the liver transplant waiting list

Background

Prolonged intubation results in ventilator-associated pneumonia (VAP), which contributes to significant mortality among patients on the waiting list. The aim of this study was to determine the risk factors for and clinical outcomes of VAP among patients into the intensive care unit (ICU).

Methods

We enrolled 50 consecutive critically ill patients with end-stage liver disease admitted to the ICU from January 2005 through December 2010. All patients were intubated for more than 4 days; no definite infection was found initially. We evaluated potential risks factors for VAP and clinical outcomes.

Results

Smoking, underlying liver disease, and lobar focal consolidations were significant factors for patients with versus without VAP. Fourteen-day mortality rates were 61.5% for VAP versus 40.5% for patients without VAP. Twenty-eight-day mortality rates for both groups were 92.3% and 86.5%, respectively. Multivariate analysis failed to identify independent predictors of early 14-day mortality.

Conclusions

Underlying liver disease and lobar focal consolidations were risks factors for VAP in patients with prolonged intubation. Patients with prolonged intubation have a dismal prognosis even without VAP. The clinical outcomes of patients with versus without VAP were similar. However, early liver transplantation (<14 days of intubation) improves the chance to rescue patients before development of VAP.     

Long-term outcomes of living kidney donors over the past 28 years in a single center in Taiwan

Background

The chronic shortage of kidneys for transplantation has increased the number of living donations, but demand remains high, which has created a long waiting list of end-stage kidney disease patients. Donors with decreased renal mass may suffer a higher risk of developing proteinuria, hypertension (HTN), and chronic renal disease (CKD) during long-term follow-up.

Methods

We retrospectively retrieved medical data of living kidney donors at our hospital over the past 28 years.

Results

There were 45 male and 60 female donors with a mean donation age of 46.34 ± 12.47 years (range = 20-70y). The mean follow-up duration was 4.67 ± 4.78 years. The serum creatinine (Cr) at donation was 0.93 ± 0.22 mg/dL, while the latest Cr was 1.26 ± 0.45 mg/dL (P < .001). The mean age at follow-up was 50.95 ± 14.57 years. At last follow-up, eight subjects (7.6%) displayed HTN requiring treatment, 10 (9.5%), proteinuria and 55.4%, an estimated glomerular filtration rate (eGFR) of less than 60 mL/min, including one with diabetic nephropathy at 10 years after donation who required long-term hemodialysis. Although gender did not correlate with occurrence of HTN, proteinuria, and CKD, the occurrence of CKD was associated with age at donation (P < .001, odds ratio [OR] = 1.076), and age at follow-up (P < .001, OR = 1.071). HTN donors were older (P = .036, OR = 1.057) with longer follow-up durations (P = .007, OR = 1.166) and had higher Cr values at donation (P = .044, OR = 94.4). Donors with proteinuria were not related to gender, follow-up duration, initial Cr, warm ischemic time, or duration of admission. eGFR was indeed worse after donation (P = .002).

Conclusions

Our results indicated a significant proportion of living donors may develop CKD upon long-term follow-up. The factors affecting donor risk of CKD were baseline renal function, older age, and duration after kidney donation.     

Platelet phenotyping in carriers for Glanzmann's thrombasthenia: a simple screening test for assessment of the molecular defect

SUMMARY. Glanzmann's thrombasthenia (GT) is a recessive autosomal bleeding disorder characterized by the abnormality of aggregation due to a platelet glycoprotein (GP) IIb-IIIa deficiency or a dysfunctional complex. Molecular abnormalities have been localized on the gene coding for GP IIb or IIIa. The aim of our work was an attempt to obtain indirectly information on the putative localization of the molecular defect in patients with GT type I or II by the determination of the HPA-1 (GP IIIa) and HPA-3 (GP IIb) alloantigenic systems' expression in GT carriers. If GT results from a defective GP IIb gene, a GT carrier would appear homozygous for HPA-3 by serology, because the normal gene will be expressed while the abnormal GP IIb gene product will not be present. Conversely, if the abnormality is in the GP IIIa gene, such an individual would appear homozygous for HPA-1. Therefore, the heterozygous status for HPA would result from the normal expression of the two genes for the considered alloantigenic system. Among the four families studied with informative members, our presumptions were strengthened by the preliminary genetic results in one family showing a mutation in the GP IIb gene. Thus, serology could be a simple screening test for the possible defective gene responsible for GT allowing molecular investigation focusing only on GP IIb or IIIa gene.