Left ventricular hypertrophy in daily dialysis

Cardiac hypertrophy, a well-known independent risk factor for cardiovascular death, is a very frequent complication in ESRD patients. Its frequency tends to be even higher in dialyzed patients due to the fact that the current dialytic treatments are unable to keep under a satisfactory control the various responsible factors and particularly the blood pressure, which is largely the most important. Daily hemodialysis, a more frequent schedule consisting of 6-7 sessions/week lasting 2 or more hours, has definitely proved its superiority in controlling blood pressure and in improving anemia, and thus has the requisites for positively influencing cardiac hypertrophy. In fact, a series of studies, both retrospective and prospective, performed during the last years by our group, have confirmed that this new, more frequent and thus more physiological schedule, is able not only to stop the progression of the cardiac hypertrophy in uremic patients but also to revert toward the normality, in a relatively short time. This appears to be essentially a consequence of the excellent blood pressure control, which in turn derives from the easier control of the true dry weight, achievable with this type of dialytic treatment.     

Environmental and occupational exposure to benzene by analysis of breath and blood.

Benzene exposure of chemical workers was studied, during the entire workshift, by continuous monitoring of workplace benzene concentration, and 16 hours after the end of the workshift by the measurement of alveolar and blood benzene concentrations and excretion of urinary phenol. Exposure of hospital staff was studied by measuring benzene concentrations in the alveolar and blood samples collected during the hospital workshift. Instantaneous environmental air samples were also collected, at the moment of the biological sampling, for all the subjects tested. A group of 34 chemical workers showed an eight hour exposure to benzene, as a geometric mean, of 1.12 micrograms/l which corresponded, 16 hours after the end of the workshift, to a geometric mean benzene concentration of 70 ng/l in the alveolar air and 597 ng/l in the blood. Another group of 27 chemical workers (group A) turned out to be exposed to an indeterminable eight hour exposure to benzene that corresponded, the morning after, to a geometric mean benzene concentration of 28 ng/l in the alveolar air and 256 ng/l in the blood. The group of hospital staff (group B) had a benzene concentration of 14 ng/l in the alveolar air and 269 ng/l in the blood. Instantaneous environmental samples showed that in the infirmaries the geometric mean benzene concentration was 58 ng/l during the examination of the 34 chemical workers, 36 ng/l during the examination of the 27 chemical workers (group A), and 5 ng/l during the examination of the 19 subjects of the hospital staff (group B). Statistical analysis showed that the alveolar and blood benzene concentrations in the 34 workers exposed to 1.12 microgram/l of benzene differed significantly from those in groups A and B. It was found, moreover, that the alveolar and blood benzene concentrations were higher in the smokers in groups A and B but not in the smokers in the group of 34 chemical workers. The slope of the linear correlation between the alveolar and the instantaneous environmental benzene concentrations suggested a benzene alveolar retention of about 55%. Blood and alveolar benzene concentrations showed a highly significant correlation and the blood/air partition coefficient, obtained from the slope of the regression line, was 7.4. In the group of the 34 chemical workers no correlation was found between the TWA benzene exposure and the urinary phenol excretion.     

Effect of nolomirole on monocrotaline-induced heart failure.

Neurohormonal activation has been shown to be a major factor in congestive heart failure progression and mortality. The beneficial effects obtained in clinical trials with angiotensin converting enzyme (ACE) inhibitors, beta-blockers and aldosterone antagonists have confirmed this hypothesis. 5,6-Diisobutirroyloxy-2-methyl-aminotetraline hydrochloride (nolomirole) is a selective agonist of prejunctional D(2)-dopaminergic and alpha(2)-adrenergic receptors. The stimulation of these receptors inhibits catecholamine release from sympathetic nerve endings. To confirm that this mechanism can be useful in congestive heart failure, we studied the effects of nolomirole on monocrotaline-induced congestive heart failure. The ACE inhibitor trandolapril was used as reference compound. Rats were given single intraperitoneal injection of either saline (control group; n=20) or monocrotaline (50 mg kg(-1)). Three days later, the monocrotaline-treated animals were randomly allocated (n=50 per group) to oral treatment with distilled water (vehicle group), nolomirole (0.25 mg kg(-1)) twice a day, or trandolapril (0.3 mg kg(-1)) once a day up to sacrifice. On the fourth week after monocrotaline injection, animals with signs of congestive heart failure were sacrificed for evaluation of heart hypertrophy and neuroendocrine alterations. Atrial natriuretic peptide (ANP) and alderosterone were determined by radioimmunoassay in plasma. Tissue norepinephrine concentration was quantified by high-pressure liquid chromatography. Nolomirole and trandolapril significantly reduced (a) hypertrophy of right atria and ventricles, (b) plasma levels of ANP and presence of pleural/peritoneal effusions and (c) norepinephrine depletion of right ventricle. These findings confirmed that nolomirole, like trandolapril, is able to attenuate the heart failure signs in the monocrotaline-induced congestive heart failure model.     

Solidarity and the Role of the State in Italian Health Care

The article deals with the issue of solidarity in health care,with particular reference to the Italian context. It presents thedifficulties of the Italian NHS and assesses the current proposalto counter the crisis of the Welfare State by giving upinstitutional arrangements, in order to favour the so-called`social private'. Moreover, it addresses the question ofprioritisation and targeting in the context of health care,arguing for the insufficiency of the standard approach of neutralliberalism, and showing how the concept of solidarity might helpto develop a different account. Lastly, it discusses the case oforgan transplantion in Italy, as an example ofsolidarity-inspired health care policy.     

Neuropsychopharmacological properties of neuroactive steroids in depression and anxiety disorders

Neuroactive steroids modulate neurotransmission through modulation of specific neurotransmitter receptors such as γ-aminobutyric acid type A (GABA_A) receptors. Preclinical studies suggested that neuroactive steroids may modulate anxiety- and depression-related behaviour and may contribute to the therapeutical effects of antidepressant drugs. Attenuations of 3α-reduced neuroactive steroids have been observed during major depression. This disequilibrium can be corrected by successful treatment with antidepressant drugs. However, non-pharmacological antidepressant treatment strategies did not affect neuroactive steroid composition independently from the clinical response. Further research is needed to clarify whether enhancement of neuroactive steroid levels might represent a new therapeutical approach in the treatment of affective disorders. Nevertheless, the first studies investigating the therapeutical effects of exogenously administered dehydroepiandosterone revealed promising results in the treatment of major depression. In addition, in various anxiety disorders alterations of neuroactive steroid levels have been observed. In panic disorder, in the absence of panic attacks, neuroactive steroid composition is opposite to that seen in depression, which may represent counter-regulatory mechanisms against the occurrence of spontaneous panic attacks. However, during experimentally induced panic attacks, there was a pronounced decline in GABAergic neuroactive steroids, which might contribute to the pathophysiology of panic attacks. In conclusion, neuroactive steroids contribute to the pathophysiology of affective disorders and the mechanisms of action of antidepressants. They are important endogenous modulators of depression and anxiety and may provide a basis for the development of novel therapeutic agents in the treatment of affective disorders.     

Influence of sleep deprivation on neuroactive steroids in major depression.

There is evidence from preclinical and clinical studies that concentrations of neuroactive steroids are altered in depression and normalize after antidepressant pharmacotherapy. However, no data are available concerning the impact of sleep deprivation on the concentrations of neuroactive steroids. A total of 29 drug-free patients (12 men, 17 women) suffering from major depression according to DSM-IV criteria were treated with partial sleep deprivation (PSD). Response to PSD was defined as a reduction of at least 30% according to the six-item version of the Hamilton depression scale (6-HAMD). Plasma samples were taken the day before and after PSD (days 0 and 1) and after one night of recovery sleep (day 2) at 8:00 am. The samples were quantified for neuroactive steroids by means of a highly sensitive and specific combined gas chromatography/mass spectrometry analysis. There was no influence of PSD on the concentrations of neuroactive steroids either in PSD responders (n=20) or in nonresponders (n=9). However, nonresponders showed significantly higher concentrations of 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP), 3alpha,5beta-tetrahydroprogesterone (3alpha,5beta-THP), and dehydroepiandrosterone (DHEA) before or after PSD compared to responders. In contrast to antidepressant drugs, which correct the dysequilibrium of neuroactive steroids in major depression within several weeks, PSD does not affect the concentrations of neuroactive steroids either in responders or in nonresponders.     

Structure-activity relationships in 4-aminoquinoline antiplasmodials. The role of the group at the 7-position

Antiplasmodial activities versus the chloroquine sensitive D10 strain of Plasmodium falciparum of a series of N(1),N(1)-diethyl-N(2)-(4-quinolinyl)-1,2-ethanediamines with 11 different substituents at the 7-position on the quinoline ring have been investigated in vitro. Electron-withdrawing groups at the 7-position have been shown to lower the pK(a) of both the quinoline ring nitrogen atom and the tertiary amino nitrogen in the alkyl side chain. The quinoline nitrogen pK(a) ranges from 6.28 in the nitro derivative to 8.36 in the amino derivative, while the tertiary amino nitrogen has a pK(a) ranging between 7.65 in the trifluoromethyl derivative and 10.02 in the amino derivative. Calculation suggests that the resulting pH trapping of these compounds in the parasite food vacuole ranges between about 7% of that observed in chloroquine for the NO(2) derivative and 97% in the amino derivative. A direct proportionality between antiplasmodial activity normalized for pH trapping and beta-hematin inhibitory activity was observed. Activity could not be correlated with any other observed physical parameter. The beta-hematin inhibitory activity of these derivatives appears to correlate with both the hematin-quinoline association constant and the electron-withdrawing capacity of the group at the 7-position (Hammett constant). For the compounds under investigation, the hematin association constant is in turn influenced by the lipophilicity of the group at the 7-position.