CCK receptors in release of pancreatic polypeptide (PP) in dogs

Pancreatic polypeptide (PP) is released after ingestion of protein-fat meals and following administration of some gut hormones (CCK and bombesin), but the hormonal contribution to the physiological release of PP has not been elucidated. We used specific and potent CCK-receptor antagonist, L-364,718, administered intravenously in a dose of 0.5 mumol/kg or intraduodenally in a dose of 2 mumol/kg to assess the role of CCK in the release of PP. Exogenous CCK-8 infused intravenously in gradually increasing doses (12.5-400 pmol/kg/hr) caused a dose-dependent increase in plasma PP from basal 28 +/- 4 pM to 136 +/- 18 pM, and this PP increase was completely suppressed by both intravenous and intraduodenal administration of L-364,718. Meat feeding caused a dramatic increase in plasma PP from a basal level of 26 +/- 4 pM to a peak of about 190 +/- 32 pM, and the pretreatment with intravenous or intraduodenal L-364,718 reduced this PP increase by about 60%. Duodenal perfusion with oleate (0.12-4.0 mmol/hr) or L-Trp (0.12-4.0 mmol/hr) also increased plasma PP, reaching, respectively, 180 +/- 28 pM and 76 +/- 6 pM. Pretreatment with intravenous or intraduodenal L-364,718 completely abolished the plasma PP responses to oleate and L-Trp. Bombesin (100 pmol/kg/hr) raised plasma PP to the level similar to that achieved by meat feeding and L-364,718 given intravenously or intraduodenally blocked completely these plasma PP increments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lymphocyte function in patients with chronic glomerulonephritis

Lymphocyte suppressive activity after stimulation with Con A and lymphocyte function as the effectors in the ADCC test had been examined in 68 patients with chronic glomerulonephritis (GN) and in 20 healthy controls. Lymphocyte suppressive activity was lower in patients with chronic GN than in the healthy individuals. In regard to chronic proliferative GN and mesangial GN the difference was statistically significant. The lymphocyte efficiency in the ADCC test was generally adequate in patients with chronic GN and none of the morphological types showed significant deviation from the control group. In the general analysis of patients with chronic proliferative, mesangial, membrano-proliferative and membranous GN a decrease of lymphocyte suppressive activity below the lower standard limit has been detected (45% of cases). A similar defect in lymphocyte function in the ADCC test has been found in 18.6%. A statistically significant relationship between the lymphocyte function disorders and the high clinical dynamism of GN has been noticed, although in some cases there was a deviation from this tendency. It is supposed that circulating immune complexes, detected in some patients with chronic GN are not the only decisive factors responsible for defects in lymphocyte function.     

Mast cells as a source of nitric oxide in the human placenta--morphometric analysis in preeclampsia complicated pregnancy

The aim of the study was to test hypothesis, that in placenta mast cells are significant source of iNOS. Material: Placentas were collected after term delivery from healthy (control, n=13) and preeclamptic (n=11) women. Mast cells and iNOS expression were detected in obtained samples with monoclonal anti-iNOS and anti-tryptase antibodies. Next, morphometric analysis were performed. There were no significant difference between iNOS expression and number of iNOS-positive cells in normal and preeclamptic placentas. There was a significant increase in mast cells number in preeclamptic placentas (8.32 +/- 1.3 SD vs 5.14 +/- 1.2 SD in control) and decrease in percentage of iNOS positive cells among them (68.1% vs 23.6%). We conclude, that in uncomplicated pregnancies, mast cells are the main source of iNOS in placenta while in preeclampsia they loss their potential to synthetase iNOS.     

Systemic management of autoimmune anterior uveitis

Autoimmune uveitis is an acute, recurrent, sight-threatening disease that can lead to severe visual loss and blindness. It requires systemic immunosuppressive therapy and continuous monitoring by ophthalmologist and rheumatologist. There are no universally accepted referral patterns for the treatment of endogenous uveitis. Most specialists indicate corticosteroids, methotrexate and cyclosporine A as the first use drugs. Anti-cytokine drugs are a new opportunity for the patients unresponsive to the conventional anti-inflammatory and immunosuppressive therapy.     

Zinc and depression. An update

Unsatisfactory clinical efficacy and a variety of adverse effects of current antidepressant drugs have incited search for better therapy. Zinc, an antagonist of the glutamate/N-methyl-D-aspartate (NMDA) receptor, exhibits antidepressant-like activity in rodent tests/models of depression. Similarly to antidepressants, zinc induces brain derived neurotrophic factor (BDNF) gene expression and increases level of synaptic pool of zinc in the hippocampus. Clinical observations demonstrated serum hypozincemia in depression, which was normalized by effective antidepressant treatment. Moreover, our preliminary clinical study demonstrated the benefit of zinc supplementation in antidepressant therapy. All the data indicate the important role of zinc homeostasis in psychopathology and therapy of depression and potential clinical antidepressant activity of this ion.     

Increased plasma fibrinogen predicts one-year mortality in patients with acute ischemic stroke

BACKGROUND AND PURPOSE: Increased plasma fibrinogen is a risk factor for vascular diseases related to atherosclerosis. Its long-term predictive value in stroke survivors is not established. We conducted this study to establish the significance of hyperfibrinogenemia as the possible predictor of 30-day and one-year mortality in patients with acute ischemic stroke. METHODS: We studied 900 unselected patients with ischemic stroke admitted to the hospital within 24 h after onset of symptoms. We noted demographic data, risk factors for stroke, neurological deficit and disturbances of consciousness on admission. We measured plasma concentration of fibrinogen and the body temperature on day 1 and registered vital status at 1, 3, 6 and 12 months after stroke. RESULTS: Mean concentration of plasma fibrinogen was 2.9 g/L and 25.2% of patients had increased plasma concentration of fibrinogen (i.e. > or = 3.5 g/L) on day 1. Patients with hyperfibrinogenemia were more likely to die after 1, 3, 6 and 12 months than those with normal plasma fibrinogen (21.1% vs. 15.6%, 36.4% vs. 24.6%, 42.6% vs. 27.3%, 45.7% vs. 31.2%, respectively; P < 0.001 for the last three differences). Hyperfibrinogenemia did not predict short-term case-fatality, but increased concentration of plasma fibrinogen was an independent predictor of one-year case-fatality (P = 0.013; OR: 1.69 (95% CI 1.12-2.55)). Other independent predictors of one-year case-fatality were: neurological deficit on admission, age, white blood cell count, and body temperature on day 1. CONCLUSIONS: Increased concentration of plasma fibrinogen shortly after ischemic stroke independently increases risk of death within one year after stroke.