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The article examines Jews living on the Greek island of Crete during the 16th century, when the island was under Venetian rule, with focus given to the Capsali family. Cretan Jewish relations with the Venetian Duke of Candia, Crete, are outlined along with Jews' economic relations in the community, financial transactions, and lawsuits. The author emphasizes her use of documents housed in the Venetian State Archives (Archivio di Stato di Venezia) and the "Taqqanot Qandiah," a collection of regulations that impact Cretan Jewish life.

An abstract of the article "The CRPO Score: Quality of Life in the ICU," by Stefania Paudice and Stefano Emanuele Pirrone is presented.

Background & Aims: The phenotypic and functional characteristics of natural killer (NK) cells in chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are incompletely defined and largely controversial. Methods: We studied NK cell receptor expression, cytotoxic activity, and cytokine production in peripheral blood mononuclear cells from 35 patients with chronic hepatitis C, 22 with chronic hepatitis B, and 30 healthy controls. Results: Patients with chronic HBV infection had an increased proportion of NKG2C+ NK cells with normal inhibitory receptor expression and a lower proportion of activated NK cells compared with HCV+ patients, which was associated with normal or reduced cytolytic activity and markedly dysfunctional tumor necrosis factor-α and interferon-γ production. Patients with chronic HCV infection showed a predominantly activating phenotype, featuring a decreased percentage of cells expressing the inhibitory receptor KIR3DL1 and a concomitant increase in the proportion of NKG2D+ NK cells. Expression of the CD69 early activation antigen on NK cells positively correlated with serum alanine aminotransferase and HCV RNA values, suggesting participation of virus-induced effector NK cells in liver necroinflammation. Phenotypic changes in HCV+ patients were associated with enhanced cytokine-induced cytolytic activity and increased usage of natural cytotoxicity and NKG2D receptor pathways, accompanied by defective cytokine production, although to a lesser extent than patients with chronic HBV infection. Conclusions: These findings provide evidence for a functional dichotomy in patients with chronic HBV and HCV infections, featuring conserved or enhanced cytolytic activity and dysfunctional cytokine production, which may contribute to virus persistence. [Copyright &y& Elsevier]

The effects of bergamot essential oil (BEO) on the release of amino acid neurotransmitters in rat hippocampus have been studied by in vivo microdialysis and by in vitro superfusion of isolated nerve terminals. Intraperitoneal administration of BEO (100microl/kg) significantly elevated the extracellular concentration of aspartate, glycine and taurine in a Ca(2+)-dependent manner. A dose-relation study generated a bell-shaped curve. When perfused into the hippocampus via the dialysis probe (20microl/20min), BEO produced a significant increase of extracellular aspartate, glycine, taurine as well as of GABA and glutamate. The augmentation of all amino acids was Ca(2+)-independent. Focally injected 1:1 diluted BEO preferentially caused extracellular increase of glutamate. Interestingly, this release appeared to be strictly Ca(2+)-dependent. BEO concentration-dependently enhanced the release of [(3)H]D-aspartate from superfused hippocampal synaptosomes. Similar results were obtained by monitoring the BEO-evoked release of endogenous glutamate. At relatively high concentrations, the BEO-induced [(3)H]d-aspartate release was almost entirely prevented by the glutamate transporter blocker dl-threo-beta-benzyloxyaspartic acid (DL-TBOA) and was Ca(2+)-independent. At relatively low concentrations the release of [(3)H]D-aspartate was only in part ( approximately 50%) DL-TBOA-sensitive and Ca(2+)-independent; the remaining portion of release was dependent on extracellular Ca(2+). Interestingly, the monoterpene hydrocarbon-free fraction of the essential oil appeared to be inactive while the bergapten-free fraction superimposed the releasing effect of BEO supporting the deduction that psoralens may not be implicated. To conclude, BEO contains into its volatile fraction still unidentified monoterpene hydrocarbons able to stimulate glutamate release by transporter reversal and/or by exocytosis, depending on the dose administered.

It was previously reported that the K+-evoked release of somatostatin-like immunoreactivity (SRIF-LI) and of cholecystokinin-like immunoreactivity (CCK-LI) from superfused rat cerebrocortical synaptosomes can be enhanced by NMDA or D-serine alone. We here studied the effects of extraterminal pH changes on SRIF-LI and CCK-LI release. Lowering pH from 7.4 to 6.9 or 6.4 abolished the effects of NMDA or D-serine on the K+-evoked peptide release. Identical results were obtained when external pH was raised to 8 or 8.7. Sudden alkalinization of the superfusion medium, in absence of K+-depolarization, induced SRIF-LI or CCK-LI release which was insensitive to NMDA. Based on experiments in Ca2+-free medium and with voltage-sensitive Ca2+ channel (VSCC) blockers, the pH 8.7-induced release of SRIF-LI and CCK-LI was only in part (30-50%) dependent on external Ca2+ and Ca2+ channel activation. In contrast, the alkalinization-evoked release of [3H]noradrenaline was highly sensitive to external Ca2+ removal and to blockade of Ca2+ channels with omega-conotoxins. The pH 8.7-evoked SRIF-LI and CCK-LI was about halved in synaptosomes intoxicated with botulinum toxin C1. The results suggest that the pH-sensitive NMDA receptors mediating somatostatin and cholecystokinin release contain NR1 subunits lacking the exon-5 cassette. Alkalinization represents a novel releasing stimulus which elicits neuropeptide release in part by conventional exocytosis and largely by an external Ca2+-independent mechanism. Differently, the release of noradrenaline provoked by alkalinization occurs entirely by conventional exocytosis.

The objective of this study was to investigate the effects of the HIV-1 envelope protein gp120 and its peptide fragments on the function of N-methyl-D-aspartate (NMDA) receptors mediating release of cholecystokinin (CCK) and somatostatin (SRIF). These are nonconventional NMDA receptors recently found to be activated by glycine or D-serine 'only'. The release of cholecystokinin-like immunoreactivity (CCK-LI) and of somatostatin-like immunoreactivity (SRIF-LI) elicited by 12 mM K+ from superfused rat neocortex synaptosomes was potently increased by gp120, its cyclic V3 loop and the linear V3 sequence BRU-C-34-A, but not by RP-135 (a central portion of BRU-C-34-A). The EC50 values of gp120 were 0.02 nM (CCK-LI release) and 0.01 nM (SRIF-LI release). The releasing effect of gp120 was prevented by blocking the glycine site or the ion channel of NMDA receptors, but not the glutamate recognition site; in addition, the gp120 effect was strongly inhibited by nanomolar concentrations of Zn2+ ions and by low micromolar concentrations of ifenprodil. It is concluded that gp120 acts as a very potent agonist at the glycine site of NMDA receptors sited on CCK- and SRIF-releasing nerve endings; the protein is able to activate the receptor channel in the absence of glutamate. Gp120 activates the receptors through its V3 loop as peptide fragments related to V3 retain near-maximal activity. The sensitivity of the gp120 effect to both Zn2+ and ifenprodil would not be incompatible with the idea that these NMDA receptors contain the triple subunit combination NR1/NR2A/NR2B.

In this study we have examined the effects of N-methyl-D-aspartate (NMDA) receptor activation on the release of cholecystokinin and somatostatin from rat neocortical nerve endings. The release of cholecystokinin-like immunoreactivity (CCK-LI) and of somatostatin-like immunoreactivity (SRIF-LI) elicited by 12 mM K+ from superfused synaptosomes, but not the spontaneous release, was increased by NMDA in a concentration-dependent manner. The effects of NMDA could be prevented by antagonists selective for the glutamate recognition site, the receptor channel and the glycine site of the NMDA receptor. In the absence of NMDA, glycine increased on its own and in a concentration-dependent manner the depolarization-evoked release of both CCK-LI and SRIF-LI. This effect of glycine was strychnine-insensitive and could be mimicked by D-serine, a stereoselective agonist at the NMDA receptor glycine site. Antagonists selective for the glycine site or for the NMDA receptor channel prevented the effects of glycine/D-serine; these effects were, however, insensitive to blockade of the glutamate recognition site of the NMDA receptor, suggesting that glutamate released from synaptosomes or present as contaminant was not involved. The neuropeptide release elicited by D-serine was strongly inhibited by ifenprodil (0.3 microM) and by Zn2+ ions (50 nM), selective ligands at the NR2B and NR2A subunits of NMDA receptors, respectively. It is concluded that nerve terminals of CCK- and SRIF-releasing neurons possess non-conventional NMDA receptors whose channels can be operated by glycine or D-serine without apparent activation of the glutamatergic coagonist site. These receptors may display the triple subunit combination NR1/NR2A/NR2B.

1. The effects of 5-hydroxytryptamine (5-HT) on the release of cholexystokinin-like immunoreactivity (CCK-LI) were examined in synaptosomes prepared from rat cerebral cortex and nucleus accumbens and depolarized by superfusion with 15 mM KCl. 2. In both areas 5-HT, tested between 0.1 and 100 nM, increased the calcium-dependent, depolarization-evoked CCK-LI release in a concentration-related manner. The concentration-response curves did not differ significantly between the two brain areas (EC50: 0.4 +/- 0.045 nM and 0.48 +/- 0.053 nM, respectively, in cortical and n. accumbens synaptosomes; maximal effect: about 60% at 10 nM 5-HT). 3. The 5-HT1/5-HT2 receptor antagonist methiothepin (300 nM) did not affect the CCK-LI release elicited by 10 nM 5-HT. However, the effects of 10 nM 5-HT were antagonized in a concentration-dependent manner by the 5-HT3 receptor antagonists (3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205-930; 0.1-100 nM; IC50: 3.56 +/- 0.42 nM in the cortex and 3.90 +/- 0.50 nM in the n. accumbens) and ondasetron (IC50: 8.15 +/- 0.73 nM in the cerebral cortex). 5-HT (10 nM) was also strongly antagonized by 100 nM 1 alpha H, 3 alpha 5 alpha H-tropan-3-yl-3,5-dichlorobenzoate (MDL 72222) another blocker of the 5-HT3 receptor. Moreover, the 5-HT3 receptor agonist 1-phenylbiguanide (tested in the cerebral cortex between 0.1 and 100 nM) enhanced CCK-LI release in a manner almost identical to that of 5-HT (EC50 = 0.64 +/- 0.071 nM). 4. It is concluded that 5-HT can act as a potent releaser of CCK-LI in rat cerebrocortex and nucleus accumbens through the activation of receptors of the 5-HT3 type situated on the CCK-releasing terminals. This interaction may provide a rationale for the clinical development of both 5-HT3 and CCK receptor antagonists as novel anxiolytic drugs.

The existence of presynaptic autoreceptors modulating acetylcholine release from central cholinergic nerve endings was investigated by using rat hippocampal synaptosomes in a superfusion system. The presence of exogenous acetylcholine, carbachol or oxotremorine in the superfusion fluid produced a dose-dependent inhibition of the release of [3H]acetylcholine elicited by 15 mM KCl in synaptosomes prelabeled with tritiated choline. The inhibition was counteracted by atropine. Another well known muscarinic agonist, bethanechol, had no effect on [3H]acetylcholine release. Our results indicate that central cholinergic nerve terminals possess autoreceptors of the muscarinic type for the control of acetylcholine release. Moreover, differences seem to exist between pre-and postsynaptic muscarinic receptors in the central nervous system.

The effects of acetylcholine (ACh) on the release of [3H]5-hydroxytryptamine ([3H]5-HT) were investigated in synaptosomes prepared from rat cerebral cortex, hypothalamus and hippocampus and depolarized with 15 mM KCl under superfusion conditions. ACh inhibited the release of [3H]5-HT in all three brain areas. This effect was not modified by hexamethonium but was antagonized by atropine and by the non-classical antagonists pirenzepine and dicyclomine.

The presence in cholinergic nerve endings of muscarinic autoreceptors regulating the release of acetylcholine elicited by depolarizing stimuli was investigated in different areas of the rat brain. Synaptosomes prepared from cerebral cortex, hippocampus or corpus striatum were prelabeled with [3H]choline and the inhibitory effect of exogenous acetylcholine on the Ca2+-dependent release of [3H]acetylcholine evoked by 15 mM KCl was analyzed by superfusion. While acetylcholine was equally active in reducing its own release in hippocampus and cortex, it was much less effective in striatal synaptosomes. In contrast the values of several presynaptic cholinergic parameters ([3H]choline uptake, [3H]acetylcholine synthesis and release) were the highest in the striatum. Since experiments with slices showed that autoregulation of acetylcholine release through muscarinic receptors appeared to occur as efficiently in the striatum as in the two other areas, the present results suggest that in the striatum the autoregulation of acetylcholine release may not necessarily require the activation of autoreceptors located on cholinergic nerve terminals.