Long-Term Abstinent Alcoholics Have Normal Memory

It is generally believed that many non-Korsakoff alcoholics have subtle defects in memory. To determine whether such defects vary as a function of length of abstinence (LOA), we performed extensive memory testing with: (1) recently detoxified (n = 31; LOA-29 days); (2) intermediate-term abstinent (n = 28; LOA = 1.9 years); (3) long-term abstinent (n = 32; LOA-7.0 years) alcoholics; and (4) nonalcoholic controls (n = 37). All subjects were matched on age and education. Alcoholics were matched on years of alcoholic drinking. Memory measures were divided into the following domains: verbal learning, verbal recall, visual learning, visual recall, and paired associate learning. A series of MANOVAs were conducted that revealed a significant relationship between visual learning and length of abstinence, and a significant interaction between age and length of abstinence on visual recall. Long-term abstinent subjects were not significantly different from controls on any test. We conclude that memory disturbance demonstrable among recently detoxified alcoholics in the early weeks of their abstinence is not evident in demographically matched long-term abstinent alcoholics with similar drinking histories.     

Alteration in the Sensitivity of GABAA Receptors to Allosteric Modulatory Drugs in Rat Hippocampus After Chronic Intermittent Ethanol Treatment

Chronic intermittentethanol (CIE)-treated rats exhibited a kindlinglike persistent increase in withdrawal hyperexcitability. The alteration of GABA_A receptor (QABA_AR) function in the hippocampus was suggested as a possible mechanism underlying the hyperexcitability observed in CIE rats, because (1) GABA_AR agonist (muscimol)-evoked ³⁸Cl- efflux was decreased; (2) paired-pulse inhibition in the CA1 area, predominantly due to GABA_AR-mediated recurrent inhibition, was persistently decreased; and (3) GABA_AR subunit expression was altered in the hippocampus from CIE rats. To further characterize the functional alteration of GABA_AR after CIE treatment, their sensitivity to acute ethanol, a steroid anesthetic (alphaxalone), and a benzodiazepine inverse agonist (DMCM; methyl-6, 7-dimethoxy-4-ethyl-β-carboline-3-carboxylate) were studied using either synaptically evoked GABA_AR responses or exogenously applied muscimol-evoked responses in hippocampal slices. Bath application of ethanol (60 mM) enhanced the area of GABA_AR-mediated inhibitory postsynaptic potentials in the hippocampal CA1 region from control and CIE rats, and this potentiation was significantly (p = 0.027) greater in CIE rats (98%) than in control rats (53%). The positive modulatory effect of alphaxalone (1 μM) on GABAAR-inhibitory postsynaptic potentials was not significantly different between control and CIE rats (p = 0.375), whereas alphaxalone allosterically increased [³H]flunitrazepam binding in the CA1 area only in CIE rats (by 20 to 25%, p < 0.01), but not in controls. On the other hand, the negative modulatory effect of DMCM (1 μM) on muscimol-evoked responses was significantly larger in CIE rats (p = 0.002). These results suggest that the sensitization of GABA_AR to acute ethanol and benzodiazepine inverse agonists, and possibly neurosteroids, may underlie ethanol dependence after multiple ethanol withdrawal episodes. These altered pharmacological properties are most consistent with changes in the subunit composition in the CA1 area of this rat model of alcohol dependence.     

Predicting Vertical Jump Height from Bar Velocity

The objective of the study was to assess the use of maximum (V_max) and final propulsive phase (FPV) bar velocity to predict jump height in the weighted jump squat. FPV was defined as the velocity reached just before bar acceleration was lower than gravity (-9.81 m·s^-2). Vertical jump height was calculated from the take-off velocity (V_take-off) provided by a force platform. Thirty swimmers belonging to the National Slovenian swimming team performed a jump squat incremental loading test, lifting 25%, 50%, 75% and 100% of body weight in a Smith machine. Jump performance was simultaneously monitored using an AMTI portable force platform and a linear velocity transducer attached to the barbell. Simple linear regression was used to estimate jump height from the V_max and FPV recorded by the linear velocity transducer. V_max (y = 16.577x - 16.384) was able to explain 93% of jump height variance with a standard error of the estimate of 1.47 cm. FPV (y = 12.828x - 6.504) was able to explain 91% of jump height variance with a standard error of the estimate of 1.66 cm. Despite that both variables resulted to be good predictors, heteroscedasticity in the differences between FPV and V_take-off was observed (r² = 0.307), while the differences between V_max and V_take-off were homogenously distributed (r² = 0.071). These results suggest that V_max is a valid tool for estimating vertical jump height in a loaded jump squat test performed in a Smith machine.

Key points

• Vertical jump height in the loaded jump squat can be estimated with acceptable precision from the maximum bar velocity recorded by a linear velocity transducer.
• The relationship between the point at which bar acceleration is less than -9.81 m·s^-2 and the real take-off is affected by the velocity of movement.
• Mean propulsive velocity recorded by a linear velocity transducer does not appear to be optimal to monitor ballistic exercise performance.

Key words: Linear velocity transducer, force platform, jump performance, swimming     

Cloning and functional expression of venom prothrombin activator protease from Pseudonaja textilis with whole blood procoagulant activity

The snake venom group C prothrombin activators contain a number of components that enhance the rate of prothrombin activation. The cloning and expression of full-length cDNA for one of these components, an activated factor X (factor Xa)-like protease from Pseudonaja textilis as well as the generation of functional chimeric constructs with procoagulant activity were described. The complete cDNA codes for a propeptide, light chain, activation peptide (AP) and heavy chain related in sequence to mammalian factor X. Efficient expression of the protease was achieved with constructs where the AP was deleted and the cleavage sites between the heavy and light chains modified, or where the AP was replaced with a peptide involved in insulin receptor processing. In human kidney cells (H293F) transfected with these constructs, up to 80% of the pro-form was processed to heavy and light chains. Binding of the protease to barium citrate and use of specific antibodies demonstrated that gamma-carboxylation of glutamic acid residues had occurred on the light chain in both cases, as observed in human factor Xa and the native P. textilis protease. The recombinant protease caused efficient coagulation of whole citrated blood and citrated plasma that was enhanced by the presence of Ca2+. This study identified the complete cDNA sequence of a factor Xa-like protease from P. textilis and demonstrated for the first time the expression of a recombinant form of P. textilis protease capable of blood coagulation.     

ESC position paper on cardiovascular toxicity of cancer treatments: challenges and expectations

The recent position paper of the European Society of Cardiology (ESC) on cardiovascular toxicity of cancer treatments has attracted considerable interest by healthcare professionals, since it is the first concrete help in the difficult task of monitoring and approaching cardiovascular side effects of anticancer treatments. The ESC expert opinion was not intended as a clinical practice guideline; however, it reports major cardiovascular complications grouped into nine categories, addressing current clinical strategies for prevention and mitigation. In this point of view, we discuss key challenges emerging from critical appraisal of the ESC position paper: (1) the wide spectrum of cardiovascular toxicities associated with oncological drugs, focusing on targeted agents, (2) managing strategies in patients with cardiac implantable devices, (3) the underappreciated (but emerging) immune-related cardiovascular toxicities of checkpoint inhibitors, which may also result in severe heart failure and fulminant myocarditis, (4) the evolving role of anticoagulation in oncology, and the evidence supporting (or not) the use of direct-acting oral anticoagulants in cancer-associated thrombosis.