Drosophila: a model for understanding obesity and diabetic complications

The molecular mechanisms underlying development of obesity and diabetic complications are not well understood. Drosophila has become a popular model organism for studying a variety of human diseases. We discuss here emerging Drosophila models of obesity and diabetic complications.     

The effects of repeated delivery of angiotensin II AT(1) receptor antisense on distinct vasoactive systems in Ren-2 transgenic rats: young vs. adult animals

Although Ren-2 transgenic rat (TGR) is defined as a model of angiotensin II-dependent hypertension, we studied whether the renin-angiotensin system (RAS) is really the main contributor to blood pressure (BP) elevation in hetero- and homozygous TGRs. Moreover, we examined whether repeated antisense (AS) therapy against AT(1) receptors would have a similar effect on the BP and the contribution of the principle vasoconstrictor/vasodilator systems to BP regulation in young and adult TGRs. From the age of 30 (young) and 100 (adult) days, rats were injected with AS for 40 days in 10-day intervals. After 10 and 40 days of AS therapy, the basal BP and acute BP responses to the sequential blockade of the RAS, sympathetic nervous (SNS) and nitric oxide systems were determined in conscious rats. The RAS system was the major system maintaining elevated BP in young homozygous animals, whereas there was an increasing contribution of the SNS in heterozygous TGR with age. The AS therapy in the young TGR had a transient BP-lowering effect that was associated with reduced cardiac hypertrophy; the AS therapy was most effective in young homozygous TGR, causing a substantial reduction of angiotensin-dependent vasoconstriction. In heterozygous rats, AS therapy at earlier stages was related to an inhibition of sympathetic vasoconstriction, whereas to RAS inhibition in established hypertension. In conclusion, repeated AS therapy had transient antihypertensive effects exclusively in young TGR. The contribution of the RAS to BP maintenance is highly important only in homozygous TGRs, whereas it is surpassed by SNS in heterozygous TGR.     

Relation between indices of end-organ damage and mean platelet volume in hypertensive patients

Mean platelet volume (MPV) has been recognized as an independent risk factor of hypertension. Hypertensive end-organ damage worsens the prognosis in hypertensive patients. We aimed to investigate the relationship between MPV levels and subclinical end-organ damage in hypertensive patients. One hundred and sixteen hypertensive patients (81 women, 35 men, with a mean age of 53 ± 11) were included in the study. There was no correlation between MPV and left-ventricular mass index (LVMI) (r = 0.145; P = 0.14) or albuminuria (r = 0.009; P = 0.93). Among the individuals that had grade I and grade II retinopathy, MPV levels (8.3 ± 2 fL, 8.2 ± 1.3 fL; P = 0.28) were similar either. We concluded that there was no correlation between MPV and markers of end-organ damage in hypertensive patients.     

Factors associated with the presence of circulating active tissue factor and activated factor XI in stable angina patients

Circulating active tissue factor (TF) and activated factor XI (FXIa) have been detected in subgroups of acute coronary syndromes (ACSs) and stable angina patients. We sought to evaluate the determinants of active TF and FXIa in stable angina patients. We studied 124 consecutive stable angina patients. Recent ACS, atrial fibrillation, and anticoagulant therapy were the exclusion criteria. Plasma active TF and FXIa were determined by measuring the response to inhibitory antibodies. T helper 1 lymphocyte (Th1) and Th2 responses were assessed in plasma by interleukin (IL)-4, IL-6, IL-8, IL-10, IL-18, interferon-γ, and tumor necrosis factor-α, oxidative stress by 8-isoprostaglandin F(2α) (8-iso-PGF(2α)), and coagulation by prothrombin fragments F1+2 (F1+2) and free TF pathway inhibitor (f-TFPI). TF and FXIa activity were detected in 25 (20.2%) and 49 (39.5%) stable angina patients, respectively. Both factors were found in 23 (18.5%) patients. Patients with detectable TF or FXIa had higher F1+2, 8-iso-PGF(2α), IL-6, but not other cytokines, and lower f-TFPI (all P < 0.001) compared with the remainder. There were no intergroup differences with regard to cardiovascular risk factors or medication. Multivariate analysis showed that F1+2 and f-TFPI were the only independent predictors of the TF presence, whereas 8-iso-PGF(2α) and F1+2 predicted the presence of FXIa in stable angina patients. In stable angina patients, circulating active TF and FXIa are associated with enhanced thrombin formation, with a minor effect of inflammatory mediators. Moreover, FXIa is also related to oxidative stress, indicating additional links between coagulation and free radical generation in stable angina.     

Ischemic stroke in the setting of chronic immune thrombocytopenia in an elderly patient--a therapeutic dilemma

Chronic immune thrombocytopenia (ITP) carries a poor prognosis in the elderly patients. Increasing evidence proposes that a subgroup of patients with chronic ITP may be more susceptible to ischemic stroke. An 84-year-old Caucasian man with multiple ischemic stroke risk factors presented with acute onset of slurred speech, confusion, and unsteady gait. Physical examination and neurologic imaging were consistent with a new left thalamic infarct. Platelet counts ranged between 40 000 × 10(9)/L and 65 000 × 10(9) /L. Antiplatelet therapy for his newly acquired stroke was not initiated considering his low platelet counts and for mildly symptomatic thrombocytopenia, and the patient was discharged home. Both hematologic and neurologic guidelines for the management of chronic ITP and stroke have contradictory goals. Although anticoagulation is mandated in acute stroke, ITP causes low platelet counts that increase bleeding complications.