Value of albumin dialysis therapy in severe liver insufficiency

Abstract A blood purification system, molecular adsorbents re-circulating system (MARS), is based on the removal of both protein-bound and water-soluble substances and toxins in the liver. We treated a total of 88 patients within 2 years. Of these patients, 45 had acute liver failure (ALF), 31 had acute decompensation of chronic liver disease, eight had graft failure and four had miscellaneous conditions. Of the patients with ALF, 80% survived; in 23 patients their own liver recovered and 13 patients underwent successful transplantation. Only 23% of patients with acute-on-chronic liver failure survived. Most of them were not considered for transplantation due to their having liver failure from alcoholism and from not abstaining from drinking. MARS is a promising therapy for ALF, allowing the patient's own liver to recover or allowing enough time to find a liver graft. Best results were achieved in patients who had been intoxicated with a lethal dose of toxin. On the other hand, we did not observe much benefit in patients with severe acute-on-chronic liver failure (AcoChr) who did not undergo liver transplantation.     

Effect of linoleic acid, linoleic acid anilide, and arachidonic acid on the expression of adhesion molecules on human neutrophils

The effects of linoleic acid, linoleic acid anilide, and arachidonic acid on the expression of CD11b/CD18, CD11c/CD18 integrins and l-selectin on human neutrophils were studied by flow cytometry in a whole blood assay. None of these compounds had any effect on the basal expression of CD11b, CD11c, or l-selectin in the concentration range of 20–100 μM. However, linoleic acid at a concentration of 1000 μM slightly up-regulated CD11b and CD11c by a factor of 2.1 and 1.7, respectively. Linoleic acid, linoleic acid anilide, and arachidonic acid did not affect the formyl-methionyl-leucyl-phenylalanine induced up-regulation of CD11b or CD11c. However, linoleic acid and linoleic acid anilide slightly inhibited the phorbol myristate acetate (PMA)-induced expression of CD11b, which was decreased by 27 and 21% at concentrations of 100 and 1000 μM, respectively. Likewise, arachidonic acid at 40 μM inhibited the PMA-induced expression of CD11b by 19%. Our results suggest that linoleic acid, linoleic acid anilide, and arachidonic acid do not dramatically affect the expression of leukocyte adhesion molecules in a whole blood assay. Received: 17 February 1997  / Accepted: 5 May 1997     

Biological divergence and equality during the first millennium BC in human populations of central Italy.

The frequencies of nine discrete cranial traits are contrasted among 10 skeletal series of central Italy to assess the patterning of biological affinity or divergence. In this study various statistical applications were used: Mean Measure of Divergence (MMD), which was elaborated using the WPGMA cluster analysis, neighbor-joining method and principal coordinate analysis. The results show two main groups divided by the Apennines, which probably were a geographic barrier to biological exchange during the Italian Iron Age. This fact induced endogamous phenomena in the populations on the two sides of Italy (Adriatic and Tyrrenian) and probably increased the familial segregation of traits. The group on the western side has a further division between samples of the central coast and those of the southern coast. The latter samples seem to be more closely connected to Sardinian peoples, and this indicates gene flow and cultural contacts, which were not hindered by the sea. This segregation appears to have receded by Roman times.     

Antisense knockdown of the Shaker-like Kv1.1 gene abolishes the central stimulatory effects of amphetamines in mice and rats.

Amphetamine (AMPH) is an indirect sympathomimetic compound classified as a substrate-type releaser that distinguishes it from other stimulants that act as uptake 1 blockers, such as cocaine (COC). In mammals, AMPH elicits central stimulation, hypermotility, anorexia, analgesia and analeptic activity, mainly through the increase of extracellular brain dopamine (DA). The inversion of vesicular transporters and/or intravesicular alkalinization is assumed to have a role in AMPH-induced exocytosis. However, the action mechanism of this compound has not yet been completely clarified. Recent evidence on the action of AMPHs indicates potassium channel-blocking properties in peripheral tissues. We investigated the possible involvement of a Shaker-like Kv1.1 channel subtype in the central effects of AMPH, using an antisense oligodeoxyribonucleotide (aODN) that specifically and reversibly inhibits the expression of these channels in the brain. The effect of aODN pretreatments was studied by evaluating the modification of behavioral effects induced in mice through the intracerebroventricular administration of AMPH, COC, or other compounds. The aODN in mice almost completely blocked the stimulatory effects of AMPH and other releasers but was ineffective in reducing the central activity of COC. In aODN-pretreated rats a strong reduction of the AMPH, but not of the COC-stimulated DA efflux from nucleus accumbens was observed. Our results suggest that the stimulant effects of AMPH and chemically related compounds, but not COC, require the presence of functionally active Kv1.1 channels in the brain.     

Effects of long-term acetyl-L-carnitine administration in rats--II: Protection against the disrupting effect of stress on the acquisition of appetitive behavior.

Long-term acetyl-L-carnitine (ALCAR) administration prevents the development of escape deficit produced by acute exposure to unavoidable stress. However, it does not revert the escape deficit sustained by chronic stress exposure. Rats exposed to chronic stress show a low dopamine (DA) output in the nucleus accumbens shell (NAcS) and do not acquire an appetitive behavior sustained by the earning of vanilla sugar (VS) made contingent on the choice of one of the two divergent arms of a Y-maze (VS-sustained appetitive behavior, VAB), while control rats consistently do. The present study shows that ALCAR treatment in rats exposed to a 7-day stress protocol prevented a decrease in DA output in the NAcS and medial prefrontal cortex (mPFC) of rats, and that it strengthened the DA response to VS consummation in the same two areas. Moreover, rats treated with long-term ALCAR or exposed to chronic stress while treated with ALCAR acquired VAB as efficiently as control rats. Moreover, VAB acquisition in stressed rats treated with ALCAR coincided with the reversal of the deficits in escape and in dopaminergic transmission in the NAcS. Thus, repeated ALCAR treatment preserved the DA response to VS in chronically stressed rats and this effect appeared to be predictive of the rat's competence to acquire VAB.     

Therapy of refractory/relapsed acute myeloid leukemia and blast crisis of chronic myeloid leukemia with the combination of cytosine arabinoside,tetrahydrouridine, and carboplatin

Summary Eight patients, of whom four had acute myeloid leukemia (AML) and four had chronic myeloid leukemia (CML) blast crisis, were treated with a combination of cytosine arabinoside (ARA-C: 1,600 mg/m² in three patients, 1,200 mg/m² in five patients), tetrahydrouridine (THU: 2,800 mg/m² in two patients, 2,646 mg/m² in one patient, 2,100 mg/m² in five patients), and carboplatin (900 mg/m² in four patients, 720 mg/m² in one patient, 450 mg/m² in three patients). As a result of this treatment, five of the eight patients became aplastic. Two of the four patients with CML blast crisis reverted to the chronic phase and two of the four patients with acute nonlymphocytic leukemia (ANLL) attained a remission (one partial remission and one complete remission). The major toxicities included myelosuppression, unacceptable hepatotoxicity, and diarrhea. Pharmacokinetics studies revealed that the addition of carboplatin did not significantly change the disposition of ARA-C. ARA-C levels were not significantly changed in comparison with those obtained in a prior study of ARA-C with THU (ARA-C plasma levels at 3 h, 2630±1170 ng/ml).Supported by the Don Monti Memorial Research Foundation