The effect of alpha-lipoic acid on temporary threshold shift in humans: a preliminary study.

Noise-induced hearing loss (NHIL) is a significant source of hearing loss in industrialized countries. Recent research on the cellular bases of NIHL has led to new avenues for protection through prophylactic drugs. Although in experimental animal models several compounds have shown a protective effect in NIHL, limited data are available in humans. Many authors are focusing their attention on the role of antioxidant on hearing protection. Alpha-lipoic acid (ALA), an essential cofactor in mitochondrial enzymes, is a novel biological antioxidant and a potent free radical scavenger and, in animal models, it has been shown to protect from age-induced and cisplatin-induced hearing loss. The aim of our study was to evaluate the effect of alpha-lipoic acid on temporary threshold shift measured 2 minutes after the end of exposure (TTS(2)) induced by a 3 kHz tone in young normally hearing subjects. Thirty young normal hearing volunteers served as control subjects. Individuals were randomly assigned to three groups. Group A (10 subjects) subjects were exposed to a 90 dB HL 3 kHz pure tone for 10 min. Group B (10 subjects) subjects were exposed to a 90 dB HL 3 kHz pure tone one hour after oral ingestion of 600 mg of ALA. Group C (10 subjects) were exposed to a 90 dB HL 3 kHz pure tone after 10 days of oral ingestion of 600 mg of ALA. Statistical analysis showed that prior to the exposure the hearing thresholds did not differ significantly among the three groups. TTS(2) of group C was significantly lower that TTS2 of Groups A and B at 6 kHz (p 0.03), and TEOAEs amplitude change after noise exposure was lower for group C compared to Groups A (p = 0.089) and B (p = 0.03). ALA is a powerful lipophilic antioxidant and free radical scavenger currently used in clinical practice. A single dose of 600 mg of dose ALA did not induce any protection on the TTS(2) induced by a 90 dB HL 3 kHz tone, while 10 days of therapeutic dosage assumption of ALA was associated with significant protection at 6 kHz. The results of this study show that a short course of ALA protects from TTS(2) in humans, and therefore further studies are needed to better define the role of ALA in the prevention of noise induced hearing loss.

A methodological approach for the identification of arsenic bearing phases in polluted soils.

A methodological approach is used to characterize arsenic pollution in three soils and to determine arsenic speciation and association with solid phases in three polluted soils. HPLC-ICP-MS was used for arsenic speciation analysis, SEM-EDS and XRD for physical characterization of arsenic pollution, and sequential chemical extractions to identify arsenic distribution. Arsenic was concentrated in the finest size fractions also enriched in iron and aluminium. Total arsenic concentrations in soils are close to 1%. Arsenic was mainly present as arsenate, representing more than 90% of total arsenic. No crystallised arsenic minerals were detected by XRD analysis. SEM-EDS observations indicated arsenic/iron associations. Modified Tessier's procedure showed that arsenic was mainly extracted from amorphous iron oxide phase. The results of this methodological approach lead to predict the formation of iron arsenates in the case of one of the studied soils while arsenic sorption on iron amorphous (hydr)oxides seemed to be the determinant in the two other soils.

Renal tubular function in patients receiving anticonvulsant therapy: a long-term study.

PURPOSE: The goal of the study was to evaluate the tubular renal function in children and adolescents who are undergoing monotherapy with sodium valproate (VPA), carbamazepine (CBZ), and phenobarbital (PB). METHODS: The urinary excretion of N-acetyl-beta-glucosaminidase (NAG), beta-galactosidase (beta-Gal), alanine-amino-peptidase (AAP), and alpha1-microglobulin (alpha1M) was measured in 58 epileptic patients (29 girls and 29 boys), aged 12.6 +/- 3.9 years, who were subdivided into three groups according to their therapy. Fifty healthy sex-and age-matched children served as controls. The measurements were taken before the beginning of therapy and after 6 months, 1 year, and 2 years of therapy. RESULTS: Before the beginning of therapy, there were no significant differences in NAG, beta-Gal, AAP, and alpha1M values between the control group and the three groups of epileptic children. After 6 months of therapy, patients treated with VPA and CBZ showed a significant increase in the urinary excretion of NAG and beta-Gal compared with baseline data and control values. After 1 and 2 years, these patients showed a persistence of the changes found after 6 months of therapy. In patients treated with PB, we did not find any significant variation in NAG, beta-Gal, AAP, and alpha1M urinary excretion. CONCLUSIONS: Our study demonstrates that in patients treated with VPA and CBZ, an impairment of tubular function can be present, whereas PB does not cause any significant change.

Platelet count and function in children receiving sodium valproate.

To evaluate whether valproic acid (VPA) can cause thrombocytopenia and impaired platelet function, the authors prospectively studied 20 children (12 female and eight male; age range 4.9-9.2 years) before and after 6 months of VPA monotherapy. Fifteen healthy sex- and age-matched children served as control subjects. VPA was prescribed at normal dosages (19.7 +/- 9.9 mg/kg), and plasma levels were within the therapeutic range (60.1 +/- 16.5 microg/mL). At the first evaluation, no significant difference between patients and control subjects was observed for platelet count and function. At the second evaluation the platelet counts were significantly lower in the patients (194,200 +/- 37,800/microL; range 157,700-222,400) than in the control subjects (291,100 +/- 41,300/microL; range 261,000-332,500; P < 0.01). Significant differences occurred between patients and control subjects in the release of adenosine triphosphate (ATP) after collagen and adenosine diphosphate (ADP) stimuli and in aggregation after stimulation with collagen, ADP, and arachidonic acid. Significant correlations between platelet count, aggregation, and ATP release and VPA dosage and plasma concentration were also observed. VPA can cause a decreased platelet count and aggregation and ATP release impairment. These side effects can appear after a few months of therapy and with plasma valproate levels within the normal range. They do not seem to be associated with clinical symptoms, and drug discontinuation is not necessary.

Comparative study of pentoxifylline vs antiaggregants in patients with transient ischaemic attacks.

Out of 235 patients with recent cerebral transient ischaemic attacks, 208 subjects were available for final evaluation after 6 months' randomised treatment with either pentoxifylline (PTX 1200 mg/day) or a combination (ASAD) of acetylsalicylic acid (ASA, 1050 mg/day) and dipyridamole (D, 150 mg/day). Prevention of TIA, stroke or death attributable to previous events were endpoint criteria. The pentoxifylline group (n = 100) exhibited no recurrent episodes in 86 patients (86%). TIA occurred in 9 patients, stroke in 5 patients and there was 1 death. In the ASAD group (n = 108) no recurrence of ischaemic episodes was recorded in 82 cases (75.9%). TIA occurred in 20 patients, stroke in 6 patients and there were 3 deaths of vascular origin. Side effects were recorded in 4 ASAD and 1 PTX patients. The total rate of recurrence was 14% with PTX as compared to 24.1% with ASAD treatment.

Randomised trial of pentoxifylline versus acetylsalicylic acid plus dipyridamole in preventing transient ischaemic attacks.

In a multicentre trial to compare the ability of a combination of acetylsalicylic acid and dipyridamole (1050 mg + 150 mg/day, group A) to prevent recurrence of transient ischaemic attacks (TIA) with that of pentoxifylline (1200 mg/day, group B), 36 patients received the combination and 30 pentoxifylline. There was no statistically significant difference between the groups as regards age, sex, blood pressure, site of origin of TIA, and incidence of other risk factors. The incidence of recurrent TIAs during 1 year of follow-up was 28% in group A and 10% in group B; this difference was significant (p less than 0.05). The incidence of permanent strokes was similar in the two groups but distinctly lower (4.5%) than that usually reported after untreated TIA.

A randomized clinical trial of pentoxifylline and antiaggregants in recent transient ischemic attacks (TIA). A one year follow-up.

A multicenter comparative trial was conducted in patients with transient ischemic attacks (TIA) to study the preventive capacity of a combination of acetylsalicylic acid and dipyridamol (1,050 mg + 150 mg/day - group A) and of pentoxifylline (1,200 mg/day - group P) in the reduction of morbidity rates. Sixty-six patients, 36 on A and 30 on P, were evaluated. There was no statistically significant difference between both groups as regards age, sex, blood pressure, localisation of TIA and incidence of risk factors. Incidence of new ischemic events during a one year follow up period in the A-group was 28% compared to 10% in the P-group, this difference being statistically significant in favour of P (p less than 0.05). Stroke incidence was similar in both groups but distinctly lower (4.5%) than the natural frequency in TIA.