Agents' beliefs and economic regimes polarization in interacting markets.

In the present paper, a model of a market consisting of real and financial interacting sectors is studied. Agents populating the stock market are assumed to be not able to observe the true underlying fundamental, and their beliefs are biased by either optimism or pessimism. Depending on the relevance they give to beliefs, they select the best performing strategy in an evolutionary perspective. The real side of the economy is described within a multiplier-accelerator framework with a nonlinear, bounded investment function. We study the effect of market integration, in particular, of the financialization of the real market. We show that strongly polarized beliefs in an evolutionary framework can introduce multiplicity of steady states, which, consisting in enhanced or depressed levels of income, reflect and reproduce the optimistic or pessimistic nature of the agents' beliefs. The polarization of these steady states, which coexist with an unbiased steady state, positively depends on that of the beliefs and on their relevance. Moreover, with a mixture of analytical and numerical tools, we show that such static characterization is inherited also at the dynamical level, with possibly complex attractors that are characterized by endogenously fluctuating pessimistic and optimistic prices and levels of national income, with the effect of having several coexisting business cycles. This framework, when stochastic perturbations are included, is able to account for stylized facts commonly observed in real financial markets, such as fat tails and excess volatility in the returns distributions, as well as bubbles and crashes for stock prices.

Real and financial market interactions in a multiplier-accelerator model: Nonlinear dynamics, multistability and stylized facts.

In the present paper, we investigate the dynamics of a model in which the real part of the economy, described within a multiplier-accelerator framework, interacts with a financial market with heterogeneous speculators, in order to study the channels through which the two sectors influence each other. Employing analytical and numerical tools, we investigate stability conditions as well as bifurcations and possible periodic, quasi-periodic, and chaotic dynamics, enlightening how the degree of market interaction, together with the accelerator parameter and the intervention of the fiscal authority, may affect the business cycle and the course of the financial market. In particular, we show that even if the steady state is locally stable, multistability phenomena can occur, with several and complex dynamic structures coexisting with the steady state. Finally, simulations reveal that the proposed model is able to explain several statistical properties and stylized facts observed in real financial markets, including persistent high volatility, fat-tailed return distributions, volatility clustering, and positive autocorrelation of absolute returns.

16-year follow-up study of Vena Cava Filters Group.

AIM: The prevalence of venous thromboembolic disease (VTED) is between 0.05% and 0.1% whereas its incidence is approximately 0.1%. Out of 100 patients with deep vein thrombosis (DVT), 5 will develop clinically serious pulmonary embolism (PE), one of which will be fatal. It is well known from the literature that surgical interventions carried out without antithrombotic prophylaxis have a 30% incidence of DVT, which can be halved with adequate prophylaxis. The aim of this study is to evaluate the immediate, middle- and long-term complications of caval filters by identifying any of the problems connected with or independent of the presence of the filter, also in relation to international literature data. METHODS: In view of the evolution of VTED surgical prevention methods, we have analyzed our case record composed of 821 patients (October 1984-October 2002), treated with different surgical solutions for VTED, with indications for the placement of 634 caval filters. RESULTS: The 30-day follow-up of all the 634 filters placed (100%) shows no mortality from the procedure and any of its immediate complications. The middle-term follow-up (from 1 month to 5 years) of 361 filters (57%) shows 0.55% mortality from PE while the long-term follow-up (5-16 years) of 105 filters (17%) shows a percentage decrease in all complications and no mortality from PE. The results also show a progressive annual decrease in the number of filters placed. CONCLUSIONS: The lower incidence of complications, compared to that reported in the literature, can be attributed to both improved operator dexterity in the placement of the filter and correct management of the complications. The lower number of filters used can be explained by improved therapeutic possibilities with new low molecular weight heparins (LMWH) and by current diagnostic as well as instrumental and biochemical monitoring methodologies.

CD5 expression by B lymphocytes and its regulation upon Epstein-Barr virus transformation.

Dim expression of CD5 on human B lymphocytes has been used to delineate B1 and B2 subsets. Nevertheless, others have suggested that the molecule is an activation marker and does not predicate a subset distinction. We have used enzymatic amplification staining, a technology that enhances the resolution of flow cytometric analysis of cell surface molecules by as much as 100-fold, to determine that essentially all human B cells express CD5. Furthermore, we show that this expression is regulated during Epstein-Barr virus transformation.

Reduced platelet glutamate uptake in Parkinson's disease.

Defects in mitochondrial enzymes have been found not only in substantia nigra, but also in platelets from Parkinson's Disease (PD) patients, suggesting a systemic impairment of energy metabolism. Since platelets present an energy-dependent glutamate uptake similar to that described in central nervous system, glutamate uptake was determined in platelets from 34PD patients and 21 age-related normal controls, as Na+-dependent [3H]glutamate influx; glutamate level was also analyzed by reverse-phase HPLC. A 50% reduction of glutamate uptake (p < 0.001) was observed in idiopathic PD patients, respect to controls and secondary parkinsonian syndromes. The decrease correlated with the severity of PD, measured by the UPDRS (r = -0.54; P < 0.05). Glutamate level was increased in platelets of PD patients, but was not correlated to the uptake decrease. Both phoenomena may be explained by the modifications of mitochondrial enzymes described in platelets, which could be used as a peripheral model of glutamatergic function in PD.

Up-regulation of peripheral benzodiazepine receptor system in hepatocellular carcinoma.

Increased number of peripheral benzodiazepine receptors (PBRs) have been found in some tumors outside the liver. The present study was to verify whether the PBR system is altered in hepatocellular carcinoma (HCC). The levels of endogenous benzodiazepine-like compounds (BZDs), measured by radioreceptor binding technique after HPLC purification and the endogenous ligand for PBRs, termed diazepam binding inhibitor (DBI), measured by radioimmunoassay utilizing a specific antibody for human DBI, were studied in the blood of 15 normal subjects, 12 liver cirrhosis and 10 patients with HCC. The levels of BZDs in serum were increased hundred fold in liver cirrhosis patients and slightly elevated in HCC patients. DBI was found to be increased in HCC patients. The binding recognition sites for PBRs (Bmax) were increased 4 to 7 fold in HCC tissue in comparison with that found in non-tumoral liver tissue (NTLT). On the contrary the concentrations of DBI were found to be significantly decreased in HCC tissue in comparison with the respective NTLT. These results seem to suggest an implication of PBRs and of their putative endogenous ligands in the metabolism of these neoplastic cells and possibly in their proliferation. The up-regulation of PBRs found in HCC tissue seems to indicate an increased functional activity of these receptors and opens up the possibility of new pharmacological and diagnostic approaches while the changes in the circulating endogenous ligands for the above receptors might be envisaged as early markers of tumorigenesis in liver cirrhosis.

Endogenous benzodiazepine-like compounds and diazepam binding inhibitor in serum of patients with liver cirrhosis with and without overt encephalopathy.

BACKGROUND/AIM: Despite some controversy, it has been suggested that endogenous benzodiazepine plays a role in the pathogenesis of hepatic encephalopathy. The aim of the present study was to evaluate the concentrations of endogenous benzodiazepines and the peptide, diazepam binding inhibitor, in the blood of patients with liver cirrhosis with and without overt encephalopathy, and to compare these levels with those of consumers of commercial benzodiazepines. SUBJECTS: Normal subjects (90), benzodiazepine consumers (14), and cirrhotic patients (113) were studied. METHODS: Endogenous benzodiazepines were measured by the radioligand binding technique after high performance liquid chromatography (HPLC) purification. The presence of diazepam and N-desmethyldiazepam was assayed by HPLC-electrospray tandem mass spectrometry. Diazepam binding inhibitor was studied in serum by radioimmunoassay. RESULTS: Endogenous benzodiazepines were below the limit of detection in 7% of patients with encephalopathy. When detectable, their levels were at least comparable with those of benzodiazepine consumers and correlated with the liver dysfunction but not the stage of encephalopathy. Serum levels of diazepam binding inhibitor tended to decrease when endogenous benzodiazepines levels increased. CONCLUSIONS: Endogenous benzodiazepines may accumulate in patients with liver cirrhosis during the course of the disease, and the phenomenon appears to be independent of the presence or absence of encephalopathy.

Diazepam binding inhibitor and total cholesterol plasma levels in cirrhosis and hepatocellular carcinoma.

Cholesterol is used by cells for biosynthetic processes and for steroid synthesis. Although the role of cholesterol in tumorigenesis is not clear it is known that steroids are important factors in human carcinogenesis. A polypeptide, diazepam binding inhibitor (DBI), which is an endogenous ligand for peripheral benzodiazepine receptors enhances steroidigenesis by promoting cholesterol delivery to the inner mitochondrial membrane which represents the rate-limiting step of steroid biosynthesis. We have assayed the total cholesterol (TC) and the DBI plasma concentrations in patients with liver cirrhosis complicated by hepatocellular carcinoma (HCC) in comparison with those of uncomplicated liver cirrhosis. TC and DBI levels have been studied in 73 cirrhotic patients and in 23 patients with HCC. Both TC and DBI levels were higher in HCC patients when compared with age, sex and Child-Pugh class matched cirrhotic controls. The values (mean+/-S.D.) in patients in Child-Pugh class B and C with and without HCC were respectively 128+/-30 mg/dl vs. 106+/-27 mg/dl (P < 0.01) and 2.05+/-0.78 pmol/ml vs. 0.78+/-0.84 pmol/ml (P < 0.0001). The data may be the result of the metabolic influence of tumors that enhances steroid biosynthesis during tumor proliferation.

Modifications of diazepam binding inhibitor and peripheral benzodiazepine receptors in the lymphocytes of epileptic patients.

Recent experimental evidence has suggested that peripheral benzodiazepine receptors (PBR) may play a role in epilepsy and antiepileptic drug action. Since PBR are also present in circulating lymphocytes, and may interact with anticonvulsant drugs, this study was designed to look for possible modifications of these receptors and their endogenous ligand diazepam binding inhibitor (DBI) in the lymphocytes of epileptic patients treated with various drugs. PBR levels were 50% to 80% higher in patients treated with carbamazepine, phenobarbital and valproic acid than in controls and untreated epileptics. DBI levels were significantly increased in the lymphocytes of untreated patients, and showed only a slight further increase after anticonvulsant therapy. The possibility that PBR and DBI modifications in the lymphocytes of epileptic patients may be linked to the immunological alterations reported in these patients and/or may represent possible markers of neurochemical modifications in the central nervous system is discussed.

Assessment of reliability and biological significance of glutamate levels in cerebrospinal fluid.

The published information on glutamate levels in cerebrospinal fluid (CSF) and modifications in neurological disorders is controversial. In the present study, we demonstrated a metabolic instability of glutamate in untreated CSF and a spurious elevation of its levels by the current methods of CSF acidification. These findings may explain the discrepancies observed with different methods of CSF processing and analysis. We suggest a method of inactivating CSF enzymes that yields stable glutamate levels under different storage conditions. Use of such a method may be necessary for clinical studies.

Benzodiazepine receptors and diazepam binding inhibitor: a possible link between stress, anxiety and the immune system.

This review summarizes the evidence available on the involvement in stress of different classes of benzodiazepine receptors and their putative endogenous ligand, diazepam binding inhibitor (DBI), with particular reference to their role in modifications of the immune response. The presented data from in vitro, experimental, and clinical studies suggest that benzodiazepine receptors and DBI play a major role in regulating steroid production in both the adrenals and central nervous system, and may be involved in the activation of the hypothalamic-pituitary-adrenal axis in stress response.

Hepatic protoporphyria is associated with a decrease in ligand binding for the mitochondrial benzodiazepine receptors in the liver.

Protoporphyrin IX (PP) and N-methylprotoporphyrin IX (N-MePP) added in vitro to liver membranes reduced dose-dependently the affinity of [3H]PK 11195 for the mitochondrial benzodiazepine receptors (MBRs), the latter being about 20 times more potent (Ki 4.5 and 0.25 microM). Preincubation of these two porphyrins with liver homogenates for 120 min at 4 degrees resulted in significant inhibition of [3H]PK 11195 binding even after repeated washings of the membranes due to the residual presence in the membranes of about 35 and 5% of PP and N-MePP, respectively. Thus, the hypothesis that an in vivo increase in the hepatic porphyrin content modifies the binding of the isoquinoline PK 11195 to the MBRs was investigated in an experimental model of protoporphyria. PP and N-MePP were allowed to accumulate in vivo through treatment with 3,5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) (100 mg/kg i.p., once), and rats were killed 5 h after treatment when hepatic porphyrin accumulation was marked (10-fold increase), PP predominating. In the liver, treatment reduced the affinity (Kd) of [3H]PK 11195 for MBRs (from 3.56 to 15.37 nM, P < 0.01) and the maximum number of binding sites (Bmax) (55% decrease, P < 0.05); the affinity (Ki) of RO 5-4864 for [3H]PK 11195 binding sites was also reduced (from 23.9 to 72.99 nM, P < 0.05). No significant differences were found in the brain cortex. Liver and brain diazepam binding inhibitor levels and plasma corticosterone levels were unchanged. The reduction in [3H]PK 11195 binding to MBRs in the liver of DDC-treated rats thus appears to be attributable to a specific effect of the DDC-induced formation of the two protoporphyrins; this conclusion suggests that in hepatic protoporphyria processes modulated by MBRs may be altered.

Diazepam binding inhibitor (DBI) increases after acute stress in rat.

Diazepam binding inhibitor (DBI) acts in brain by binding to GABAA/benzodiazepine receptors (GBR) and to mitochondrial benzodiazepine receptors (MBR). Because DBI acting at MBR, has been shown to be an effector of ACTH-induced steroidogenesis and stress is known to change the level of GBR and MBR, the model of acute noise stress in rats was used to study modifications of DBI and GRB or the content of MBR in various areas of the brain and adrenal gland. It was found that, in the brain of stressed rats, DBI and its processing products (ODN-like immunoreactivity), increased selectively in the hippocampus. This increase in the content of DBI was preceded and followed by a net decrease of GBR and an increase of MBR. Similarly, in adrenal cortex, the content of DBI and MBR increased during the first hour, following acute stress and this increase paralleled the increase in plasma corticosterone. These data suggest that DBI, acting on MBR may regulate steroidogenic function in stress.

Acute noise stress in rats increases the levels of diazepam binding inhibitor (DBI) in hippocampus and adrenal gland.

We investigated the effect of acute noise-induced stress on the concentrations of diazepam binding inhibitor (DBI) and its processing products in brain regions and adrenal glands of rats. DBI levels in hippocampus began to increase at 15 and 30 min and became significantly higher (+100%) at 90 and 120 min after stress; they returned to normal values at 360 min. While basal DBI levels were similar in the left and right hippocampus, the stress-induced increase of DBI levels was significantly higher in the left compared to the right side. A significant increase was also detected in the adrenals; here, the time course of DBI increase paralleled that of previously reported plasma corticosterone in stressed rats, being significantly higher 30 min after stress, and recovering to normal values at 60 and 90 min. After acute noise-induced stress, no significant change of DBI levels was detectable in cerebral cortex, striatum, hypothalamus and cerebellum. The present study reports for the first time the occurrence of a modification of DBI and its processing products (ODN-like immunoreactivity) in an experimental model of stress, and suggests a role for these neuropeptides in emotional responses.

Central catheter-related infections: comparison of pulmonary artery catheters and triple lumen catheters for the delivery of hyperalimentation in a critical care setting.

We prospectively studied the risk of catheter-related sepsis (CRS) in 75 critically ill patients who received total parenteral nutrition (TPN) through 158 pulmonary artery catheters (PACs) and 214 triple-lumen catheters (TLCs). We relied on semiquantitative cultures of the catheter tips, peripheral blood cultures in febrile patients and clinical response to catheter removal to diagnose catheter-related sepsis. The infection rate was 2.5% (4/158) of PACs and 6.5% (14/214) of TLCs (p = 0.124). Colonization rates were 29.1% for PACs and 32% for TLCs. PACs were left in place a significantly shorter length of time than TLCs, 3.1 vs 5.1 days (p less than 0.005). Guidewire exchanges and subclavian vein insertions were associated with a decreased rate of CRS when compared to new insertions and internal jugular vein insertions, respectively. We conclude that pulmonary artery catheters can be used safely for the delivery of hyperalimentation in critically ill patients with no increased risk for catheter-related sepsis compared to triple-lumen catheters. The use of the PAC in this manner allows for the use of a single central venous catheter for the delivery of hyperalimentation and hemodynamic monitoring.

Cerebral extract from morphine-tolerant rats shows antiopiate properties in guinea pig ileum bioassay.

The existence of an endogenous antiopiate system which counteracts endogenous opiate effects has been proposed. The present study set out to seek substance/s with morphine-antagonist activity in the brain and serum of morphine-tolerant rats. Cerebral extracts were partly purified on Sephadex G 25 and serum was ultrafiltered through membranes with pore diameter smaller than 0.005 micron. On the guinea pig ileum myenteric plexus longitudinal muscle a fraction of the cerebral extract and the serum ultrafiltrate in toto did increase electrically induced contractions, and antagonized the depressant effect of morphine. The serum ultrafiltrate also enhanced longitudinal smooth muscle tone. Preliminary findings suggest that levels of endogenous morphine-antagonist substance/s are higher in morphine-tolerant rats than in controls. Only cerebral extract, not serum ultrafiltrate, inhibited [3H]-naloxone binding to cerebral opiate receptors. In the guinea pig bioassay both the cerebral extract and serum ultrafiltrate antagonized, to some extent, the inhibition elicited by morphine, norepinephrine and adenosine. These observations support the existence of endogenous compound/s which may be functional antagonist/s of opiates and play a role in the development of tolerance and dependence.

Binding studies of dermorphin and its L-form on rat brain opioid receptors.

It is well known dermorphin is a potent and long-acting opioid peptide while its synthetic L-form is almost completely devoid of biological activity. We investigated whether the L-Ala2 residue might affect the affinity of the compound for opioid receptors or make [L-Ala2] dermorphin more sensitive to metabolic degradation. Dermorphin and [L-Ala2] dermorphin were assayed in [3H]naloxone binding to opioid receptors in rat brain preparations in the absence and presence of peptidase inhibitors bestatin, captopril and thiorphan. The synthetic [L-Ala2] dermorphin showed very low affinity for the opioid receptors. This was only slightly increased in the presence of the peptidase inhibitor bestatin, alone and in combination with captopril and thiorphan. The low affinity of [L-Ala2] dermorphin was not improved even when the binding assay was carried out at 0 degrees C. We suggest that the D-Ala2 residue is essential for the binding of dermorphin to the opioid receptors as well as for its pharmacological activity.

Further investigations on neurotensin as central modulator of intestinal motility in rats.

Previous studies have shown that neurotensin (NT) administered intracerebroventricularly (i.c.v.) to rats provokes an inhibition of intestinal propulsion linearly related to the log of administered doses. In the present study it is demonstrated that, in contrast to morphine, repeated i.c.v. administrations of NT (2.5 nmol/rat/day) did not result in tolerance to the intestinal effect. Naloxone (Nx) administered i.c.v. fully antagonized the intestinal inhibition of i.c.v. morphine, but did not significantly alter the NT effect. However, centrally administered thyrotropin-releasing hormone (TRH) inhibited NT-induced (but not morphine-induced) intestinal inhibition. Direct microinjections of NT into the periaqueductal gray matter (PAG) produced complete inhibition of intestinal propulsion when the microinjections were localized in the dorsal portion. Finally, subdiaphragmatic vagotomy totally abolished the inhibition induced by NT into the PAG, while morphine was not affected. Some considerations are put forward concerning the existence in the central nervous system of a peptidergic pathway modulating intestinal function.

Pertussis toxin inhibits the antinociceptive action of morphine in the rat.

The influence of pertussis toxin (PTX) injected intracerebroventricularly (i.c.v., 0.5 micrograms) on the analgesic effect induced in the rat by i.c.v. injection of morphine (5 micrograms) was studied. Morphine analgesia was unaffected 24 h after toxin administration, but there was a significant decrease after 6 days. Therefore a PTX-sensitive substrate, probably a guanine nucleotide regulatory protein could be involved in the coupling of opiate receptors to cellular effectors responsible for the expression of the antinociceptive action of morphine.

Further investigations on serum ultrafiltrate as medium for tissue respiration in vitro.

Serum ultrafiltrate was shown to be able to sustain in vitro the oxygen consumption of various tissue slices, attaining values very close to those reached in vivo. Serum ultrafiltrate also exerted its stimulating effect on homogenate, and maintained this activity for some time, after dilution, after lyophilization and after boiling; finally it was not species-specific. Serum ultrafiltrate was also more efficient than Eagle's Minimum Essential Medium in supporting tissue respiration. Preliminary data, obtained from gel fractionating serum ultrafiltrate, suggested that the metabolic activity should be ascribed to a sum of small single effects due to the single fractions of serum ultrafiltrate.