Search

A solid state potentiometric biosensor for urea determination was assembled coupling a nonactin-based ISE without an internal solution with immobilized urease. The system proved to be useful for continuous monitoring of urea during dialysis treatment using the ultrafiltrate of blood as sample. A noticeable shift of potential occurred during the dialysis (probably due to continuous extraction of ionophore by the ultrafiltrate). Therefore a flow injection analysis assembly was necessary to control the shift of electrode potential.

Ciliary neurotrophic factor (CNTF) and interleukin-6 (IL-6) potentiate the elevation of serum corticosterone induced by suboptimal doses of interleukin-1 (IL-1). CNTF also potentiates IL-1-induced serum IL-6. Here, we report that four other cytokines (leukemia inhibitory factor [LIF], oncostatin M [OSM], interleukin-11 and cardiotrophin-1) also potentiated the elevation of serum corticosterone and IL-6 levels induced by IL-1. Furthermore, all the six cytokines studied induced the acute-phase protein serum amyloid A when administered alone. Because these cytokines differ both in structure and in function, but share gp130 as a subunit of their receptors, these results indicate that signaling through gp130 mediates potentiation of IL-1 activities. The potentiation of IL-1-induced serum corticosterone levels is not a consequence of the increased serum IL-6 observed after IL-1 administration. In fact, in IL-6 deficient mice, IL-1 increased serum corticosterone to a level comparable to that observed in wild-type mice. Thus, either endogenous IL-6 does not mediate IL-1-induced corticosterone increase, or its role may be fulfilled by other cytokines. To the extent that gp130-dependent cytokines may serve this role, they may be important feedback regulators of inflammation through the activation of the hypothalamus-pituitary-adrenal axis and the potentiation of acute-phase protein synthesis.

Glucocorticoids (GC) are known inhibitors of TNF production and are increased by endotoxin (LPS) through a stimulation of the hypothalamus-pituitary-adrenal axis (HPAA), suggesting a feedback mechanism. We tried different approaches to study the role of the HPAA and endogenous GC in the regulation of TNF production. Cyanoketone, a GC synthesis inhibitor, inhibited corticosterone (CS) induction by LPS and increased LPS-induced serum TNF levels. Similar results were obtained by pretreating mice with anticorticotropin-releasing hormone Abs. Administration of adrenocorticotropic hormone increased blood CS and inhibited LPS-induced serum TNF. TNF production by mouse blood stimulated in vitro with LPS was inhibited by addition of CS. Blood from stressed or adrenocorticotropic-releasing hormone-treated mice (in which CS levels are elevated) stimulated ex vivo with LPS produced significantly less TNF than blood from control mice. Normal TNF production was restored by the addition of the GC receptor antagonist RU 38486, indicating a role for the elevated endogenous CS levels in the inhibition of TNF production. These data indicate that the HPAA is a major regulator of TNF production.

Chronic administration of cocaine produces sensitization to its behavioral effects in humans and experimental animals. In the present study, rats treated with cocaine (10 mg/kg, i.p.) once daily for 10 days showed an enhancement in the acute drug stimulation of locomotor activity and stereotypy. Biochemical analysis in the nucleus accumbens of chronic cocaine-treated animals indicated that sensitization of D1 dopamine (DA) receptors had also developed. In fact, stimulation of adenylyl cyclase activity by DA was increased in nucleus accumbens membranes from sensitized rats. Our findings suggest that a novel postsynaptic mechanism, i.e., an increased DA-D1 receptor function, may play a role in the sensitization. A causal relationship between the two events is supported by the observation that neither motor behavioral sensitization nor DA-dependent adenylyl cyclase hyperactivity developed when the opiate antagonist naltrexone (2 mg/kg, s.c.) was given daily for 10 days before cocaine. When given alone, naltrexone was inactive in all respects, which rules out any unspecific action and suggests that its effects may be due to competition at receptors with endogenous opioids mobilized by cocaine. This was indirectly supported by the finding that desensitization of opioid inhibition of adenylyl cyclase developed in nucleus accumbens membranes of cocaine-sensitized rats. Chronic blockade of opioid receptors by naltrexone also counteracted the reinforcing properties of cocaine; conditioned place preference, clearly displayed by cocaine-treated animals, was antagonized in a dose-related manner. Overall, these results confirm that endogenous opioid peptides play an important role in cocaine addiction.

Background: The receptor of ciliary neurotrophic factor (CNTF) contains the signal transduction protein gp130, which is also a component of the receptors of cytokines such as interleukin (IL)-6, leukemia-inhibitory factor (LIF), IL-11, and oncostatin M. This suggests that these cytokines might share common signaling pathways. We previously reported that CNTF augments the levels of corticosterone (CS) and of IL-6 induced by IL-1 and induces the production of the acute-phase protein serum amyloid A (SAA). Since the elevation of serum CS is an important feedback mechanism to limit the synthesis of proinflammatory cytokines, particularly tumor necrosis factor (TNF), we have investigated the effect of CNTF on both TNF production and lipopolysaccharide (LPS) toxicity., Materials and Methods: To induce serum TNF levels, LPS was administered to mice at 30 mg/kg i.p. and CNTF was administered as a single dose of 10 micrograms/mouse i.v., either alone or in combination with its soluble receptor sCNTFR alpha at 20 micrograms/mouse. Serum TNF levels were the measured by cytotoxicity on L929 cells. In order to measure the effects of CNTF on LPS-induced TNF production in the brain, mice were injected intracerebroventricularly (i.c.v.) with 2.5 micrograms/kg LPS. Mouse spleen cells cultured for 4 hr with 1 microgram LPS/ml, with or without 10 micrograms CNTF/ml, were also analyzed for TNF production., Results: CNTF, administered either alone or in combination with its soluble receptor, inhibited the induction of serum TNF levels by LPS. This inhibition was also observed in the brain when CNTF and LPS were administered centrally. In vitro, CNTF only marginally affected TNF production by LPS-stimulated mouse splenocytes, but it acted synergistically with dexamethasone (DEX) in inhibiting TNF production. Most importantly, CNTF administered together with sCNTFR alpha protected mice against LPS-induced mortality., Conclusions: These data suggest that CNTF might act as a protective cytokine against TNF-mediated pathologies both in the brain and in the periphery.

During rat liver regeneration, at the onset of S-phase of the first cell cycle, an enhanced mevalonate incorporation into prenylated proteins is observed. The analysis of the lipid moieties of such proteins shows a 20-fold increased content of geraniol and farnesol. The expected increase of farnesylated and geranylgeranylated proteins in pre-S phase is confirmed by an increased level of lamin A, B, C and of several GTP-binding proteins. These results suggest a relevance of both farnesylation and geranylgeranylation in this phase of the cell cycle.

Our purpose was to retrospectively evaluate major risk of non cardiac surgery in patients with valvular heart disease. We studied retrospectively 136 patients, 44 affected by aortic, 81 by mitral and 11 by mitroaortic valve disease. NYHA class was I-II in 130 and III in 6 patients. Sixty four patients underwent orthopedic surgery, 57 patients occulistic surgery and 5 patients urological surgery. There were no hospital deaths. Fifteen patients developed major perioperative complication: 7 serious ventricular arrhythmias, 6 hypotension, 2 "hypertensive attacks". We conclude that non cardiac surgery is safe in patients with valvular heart disease.

Between 1972 and 1985, 107 patients with chronic Idiopathic Thrombocytopenic Purpura underwent splenectomy. Platelet life span and sites of sequestration were studied with labelled platelets and external scanning. Medical treatment was always of scarce and transient effectiveness and had considerable side effects. Splenectomy had minimal complications and mortality and caused no hazard of overwhelming sepsis in adults. The results of splenectomy were very satisfying, especially when platelet sequestration was mainly splenic (remission in about 90% of patients). Surgical treatment is at present the most effective in patients with chronic ITP.