Role of immune-derived diffusible mediators in AIDS-associated neurological disorders

Neurologic abnormalities are common in HIV-1 infected patients and often represent the dominant clinical manifestation of pediatric AIDS. Although the neurological dysfunction has been directly related to CNS invasion by HIV-1, the pathogenesis of neurologic disorders remains unclear. This review will first discuss the spectrum of potential interactions between HIV-1 and neural (neuronal and glial) cells, in the face of experimental data. Next, we will focus on the role of immune-derived cytokines and other soluble compounds which have been proposed to act as neurotoxic mediators and appear to play a role in the pathogenesis of AIDS-associated neurodegeneration.     

Effects of erdosteine on sputum biochemical and rheologic properties: Pharmacokinetics in chronic obstructive lung disease

Erdosteine is a new thioderivative endowed with mucokinetic, mucolytic, and free-radical-scavenging properties. This study evaluated (in a double-blind design vs. placebo) its efficacy on biochemical and rheologic properties of sputum and on some indices of respiratory function in chronic patients with chronic bronchitis (10 per group), while receiving basic treatment with a controlled-release theophylline preparation. The pharmacokinetics of erdosteine and theophylline were also studied. We found that a 2 week treatment with erdosteine (300 mg 3 times daily) was able to reduce significantly (p<0.05) the sputum apparent viscosity, fucose content, and macromolecular dry weight (MDW) with no statistically significant influence on sputum elasticity, DNA, albumin, total proteins, total IgA, lactoferrin, and lysozyme content. The treatment caused a significant increase in the following ratios: total IgA/albumin, lactoferrin/albumin, and lysozyme/albumin. The pharmacokinetics of erdosteine, its metabolites, and theophylline were the same after 1 or 14 days of treatment, evidence both of absence of en enzymatic induction and of an accumulation process. Further confirmation that there was no interference between erdosteine and theophylline was obtained from the data available on the group of patients receiving only theophylline, since its plasma levels and related pharmacokinetic parameters were identical to those obtained in patients receiving both drugs. In conclusion, 2 weeks of therapy with erdosteine reduced the marker for mucus glycoproteins (fucose) in patients with chronic bronchitis but did not interfere with the pharmacokinetics of xanthine derivatives. We also suggest that the significant increment in the IgA/albumin ratio might be related to a sum of other local effects such as reduction of the inflammatory process and enhancement of the humoral defense mechanism.     

Isotopy and multicorticality: two fundamental principles

Starting out from Oral Implantology pioneers, the Author comes down to the present situation, in an effort to show which values should be considered as the true ones. "Nothing new under the skies" is the Author's comment, when he examines all the techniques and materials presented as "new" for commercial purposes, whereas they are not new at all. To prove his statements he goes back to the work of some implantology pioneers, such as Formiggini, Perron Andrès, Cherchève, Strock, Pasqualini, Muratori, Tramonte, Linkow and others. In going over their most remarkable techniques, he maintains that what is being proposed nowadays as brand new was actually done long ago. Only names are now different: the process now called fibrous osseointegration used to be named osteofibrosis, and what is now called osseointegration was known as complete ossification. In order to remove the great confusion now prevailing in the dozens of implant systems, as well as in implant philosophy itself, the Author maintains that good implantologists should follow two fundamental principles: 1) implants should be built in a great variety of sizes, in order to take full advantage of cortical bones. They should be multicortical, generally quadricortical, since they should rest on the sinus floor cortical bone, on the alveolar ridge, the palatal and the buccal cortical bones (this is true for the elements implanted in the upper arch and in the front-mesial arch).(ABSTRACT TRUNCATED AT 250 WORDS)     

Propofol and thiopentone for caesarean section revisited: maternal effects and neonatal outcome

In 56 women undergoing elective caesarean section, general anaesthesia was induced with either propofol 1% or thiopentone 2.5% followed by 50% nitrous oxide in oxygen and isoflurane 0.75% until delivery. In the thiopentone group the arterial pressure rose following tracheal intubation and skin incision, while in the propofol group there was a significant tendency to hypotension immediately following induction of anaesthesia. There were differences in electroencephalogram (EEG) between the groups, while laryngoscopy, intubation and surgical stimulation had no effect on EEG pattern. Recovery after anaesthesia did not differ between groups. None of the patients had recall of the intraoperative period, but 53% of patients induced with propofol showed signs of light anaesthesia between induction and delivery. Neonates in the propofol group had lower Apgar scores 1 min after birth than those in the thiopentone group, but these differences were no longer significant at 5 min. No differences were noted in neurobehavioural status at 1, 4 and 24 h.     

Uteroglobin and transglutaminase modulate human sperm functions

During the process of capacitation, spermatozoa undergo significant changes in membrane composition, including removal of decapacitating factors (DFs), which are present in seminal plasma, that lead to increased sensitivity to physiological stimuli of the acrosome reaction. In the present study we investigated the presence, localization, and effects on human spermatozoa of 2 proteins of seminal plasma origin, uteroglobin (UG) and transglutaminase (TG). These 2 proteins interact with one another because TG promotes covalent links of UG to sperm surface proteins. We found that UG is localized around the entire surface of ejaculated human sperm, whereas TG is predominantly localized in the neck. FACScan analysis confirmed the surface localization of both antigens and demonstrated that swim-up selection of spermatozoa was associated with a significant reduction in the contents of the 2 substances when compared with unselected samples. Western blot analysis of UG in total sperm lysates confirmed the lower content of the protein in swim-up-selected sperm. Swim-up-selected sperm were characterized by their ability to undergo a spontaneous, time-dependent increase of capacitation-characteristic chlortetracycline pattern of fluorescence and increase in responsiveness to progesterone. Such changes were not observed in unselected sperm. Exogenous addition of TG, together with recombinant rabbit UG, prevented the spontaneous increase in responsiveness to progesterone (acrosome reaction and intracellular calcium) at 24 hours in swim-up-selected sperm, suggesting the occurrence of a capacitation-inhibiting activity of the 2 substances. In addition, we found that endogenous UG and TG contents, as determined by FACScan analysis, were negatively correlated (P < .0001) with sperm motility and that exogenous addition of the 2 substances resulted in a substantial reduction of progressive motility (P < .01). Collectively, these data indicate that TG and UG represent 2 DFs, and contribute to understanding the biochemical mechanisms that characterize the process of capacitation.     

Very Low Alcohol Consumption Is Associated with Lower Prevalence of Cirrhosis and Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease

The role of moderate alcohol consumption in the evolution of NAFLD is still debated. The aim of this study is to evaluate the impact of current and lifelong alcohol consumption in patients with NAFLD. From 2015 to 2020, we enrolled 276 consecutive patients fulfilling criteria of NAFLD (alcohol consumption up to 140 g/week for women and 210 g/week for men). According to their current alcohol intake per week, patients were divided in: abstainers, very low consumers (C1: <70 g/week) and moderate consumers (C2). We created a new tool, called LACU (Lifetime Alcohol Consuming Unit) to estimate the alcohol exposure across lifetime: 1 LACU was defined as 7 alcohol units per week for 1 drinking year. Patients were divided into lifelong abstainers and consumers and the latter furtherly divided into quartiles: Q1-Q4. Stratification according to alcohol intake, both current and cumulative as estimated by LACU, showed that very low consumers (C1 and Q1-Q3) displayed lower frequency of cirrhosis and hepatocellular carcinoma compared to abstainers and moderate consumers (C2 and Q4). We can speculate that up to one glass of wine daily in the context of a Mediterranean diet may be a long-term useful approach in selected NAFLD patients.     

Effects of acute angiotensin-converting enzyme inhibition on diastolic ventricular interaction in the dilated heart

BACKGROUND: The normal and dilated heart behaves as a single functional unit during preload reduction: volume unloading in the setting of diastolic ventricular interaction allows for increased left ventricular (LV) filling. HYPOTHESIS: We hypothesized that reduction of venous return induced by a physiologic stimulus (tilting) or by acute angiotensin-converting enzyme (ACE) inhibitors in dilated heart is likely to have a marked and similar effect on ventricular chamber geometry and filling. This study was designed to assess how the normal and dilated heart adapts to preload reduction. METHODS: Twenty normal subjects and 20 patients with moderate heart failure due to dilated cardiomyopathy were studied with two-dimensional and Doppler echocardiography in supine position (B) and after 40 degrees of head-up tilting (T). The following day, patients repeated supine (C) and tilting test (TC) after administration of captopril (25 mg s.l.). Right ventricular (RV) and LV dimensions, LV geometry, and tricuspid, mitral, and pulmonary venous flow patterns were recorded at each step of the study. RESULTS: In the two groups, T was associated with reduction of RV area and LV volumes; C and TC produced a similar effect on RV and LV. Changes in LV septal-lateral diameter and anterior-posterior diameter were different at each step of the study: during T (both groups) and after C and TC, the septallateral diameter increased slightly while the anterior-posterior diameter decreased. During T, mitral and tricuspid peak flow velocities decreased, peak late velocities were unchanged, and the deceleration time of mitral flow increased; the systolic forward flow of pulmonary venous flow decreased, the diastolic forward flow did not change, and the difference in duration between reverse pulmonary flow and mitral peak late flow decreased: C and CT induced similar changes. CONCLUSION: Preload reduction induced by tilting or by ACE inhibitors induces profound and similar effects on LV and RV dimensions, LV geometry, and biventricular filling. Reduction of RV dimension is associated with adaptation of LV geometry and decrease of LV diastolic pressure, which facilitates LV filling and pulmonary venous drainage: ACE inhibition associated with tilting exerts an additional effect on these changes. These data confirm the role of ventricular interaction in modulating LV filling in heart failure.     

Cabergoline: long-acting oral treatment of hyperprolactinemic disorders

Cabergoline, a new orally active dopaminergic drug with an extremely long-lasting PRL-lowering effect, was given to 48 hyperprolactinemic women for 3-18 months (median, 8 months) at doses varying between 0.2-3 mg/week administered one to three times weekly. Serum PRL levels declined to normal in 41 women, 30 of whom received 0.2-1 mg cabergoline once weekly, 8 received 0.2-0.5 mg twice weekly, and 3 received 0.4-0.6 mg 3 times weekly. Five women had slightly supranormal serum PRL levels while receiving 0.3-0.6 mg once weekly, but the dose was not increased because the lower dose had produced the desired clinical benefit. Two women had 50% reductions in their serum PRL levels, but remained hyperprolactinemic while receiving 2-3 mg cabergoline weekly. Among 30 amenorrheic women, 28 had resumption of menses, the exceptions being 2 hypopituitary women, presumptive evidence of ovulation was available in 21. Marked tumor shrinkage occurred after 3-month treatment in 5 of the 6 women who had macroprolactinomas. Only 4 women had side-effects during the first weeks of treatment, and these vanished despite continued cabergoline administration at the same or reduced, but still effective, doses. In a short term, double blind study, cabergoline at 3 different schedules (0.4 mg twice weekly, 0.2 mg 4 times weekly, and 0.4 mg 3 times weekly for 3 weeks, followed by 0.4 mg twice weekly) or placebo was given to a total of 24 hyperprolactinemic women (6 in each subgroup) for 8 weeks, with weekly evaluation of serum PRL levels and side-effects. All 3 cabergoline schedules, but not placebo, induced significant reductions in serum PRL concentrations during the 8-week treatment period. Mild transient side-effects occurred in 7 drug-treated patients (nausea in 5; dizziness in 3). We conclude that cabergoline is effective treatment for hyperprolactinemia. Its efficacy, tolerability, and long duration of action may make it the drug of choice for patients with hyperprolactinemia.