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.     

Erenumab for the preventive treatment of chronic migraine complicated with medication overuse headache: an observational,retrospective, 12-month real-life study

Background

Erenumab is a monoclonal antibody blocking the calcitonin gene–related peptide receptor, which has been approved for the preventive treatment of chronic migraine (CM). The aim of this study was to explore the safety and effectiveness of erenumab in patients suffering from CM and medication overuse headache (MOH) in a real-life setting, up to 1 year.

Methods

Data regarding 81 patients treated with erenumab were retrospectively analyzed. Every 3 months, the following variables were collected: the mean number of headache days per month (headache index (HI)), the average number of painkillers taken per month (analgesic consumption (AC)), the mean number of days with painkiller consumption (number of days on medication (NDM)), the headache intensity (numeric rating scale (NRS) score), the 6-item Headache Impact Test (HIT-6), and the Self-Reported Instrument to Assess Work-Related Difficulties in Patients With Migraine (HEADWORK) scores.

Results

The HI, AC, and NDM and the NRS, HIT-6, and HEADWORK scores were significantly lower at every time point from the 3rd month onward compared to baseline (all P < 0.0001). No significant differences were found between patients who underwent painkiller detoxification before starting erenumab and those who did not (all P > 0.05). No significant differences were found between patients taking erenumab in combination with other preventive treatments and the ones taking it alone (all P ≥ 0.05). Five patients dropped out because of adverse events, which resolved after stopping erenumab.

Conclusion

Erenumab was safe and effective for CM complicated with MOH. Painkiller withdrawal and the association with other preventive treatment(s) seem useless.

     

Comparison between titanium and anatase miRNAs regulation

Titanium is the gold standard among materials used for prosthetic devices because of its good mechanical and chemical properties. There are three allotropic forms of titanium dioxide: brookite, rutile, and anatase. Anatase can be prepared as a colloidal suspension and used to coat surfaces. Anatase coating (AC) can potentially have biological effects and specifically can induce bone formation. To obtain more information about the osteogenic effect of AC in comparison to to titanium we used microRNA (miRNA) microarray techniques to investigate the translation regulation in osteoblasts exposed to both titanium and AC. There were three upregulated miRNAs (mir-1, mir-34c, mir-210) and eight downregulated miRNAs (mir-23b, mir-377, mir-22, mir-93, mir-422b, mir-17-5p, mir-24, mir-130b) for false discovery rate = 0 and score >3. The data reported are relevant to understand the molecular mechanism of bone regeneration and as a model for comparing other materials with similar clinical effects.     

Basal cutaneous pain threshold in headache patients

The aim of this study was to analyze cutaneous pain threshold (CPT) during the interictal phase in headache patients, and the relationships between headache frequency and analgesic use. A consecutive series of 98 headache patients and 26 sex- and age-balanced controls were evaluated. Acute allodynia (AA) was assessed by Jakubowski questionnaire, and interictal allodynia (IA) by a skin test with calibrated monofilaments. AA is widely known as a symptom more present in migraine than in TTH spectrum: in our study this was confirmed only in cases of episodic attacks. When headache index rises towards chronicization, the prevalence of AA increases in both headache spectrums (χ ² 13.55; p < 0.01). AA was associated with IA only in cases of chronic headache. When headache becomes chronic, mostly in presence of medication overuse, interictal CPT decreases and IA prevalence increases (χ ² 20.44; p < 0.01), with closer association than AA. In MOH patients there were no significant differences depending on the diagnosis of starting headache (migraine or tension type headache) and, in both groups, we found the overuse of analgesics plays an important role: intake of more than one daily drug dramatically reduces the CPT (p < 0.05). Thus, when acute allodynia increases frequency, worsens or appears for the first time in patients with a long-standing history of chronic headache, it could reasonably suggest that the reduction of CPT had started, without using a specific practical skin test but simply by questioning clinical headache history. In conclusion, these results indicate that the role of medication overuse is more important than chronicization in lowering CPT, and suggest that prolonged periods of medication overuse can interfere with pain perception by a reduction of the pain threshold that facilitates the onset of every new attack leading to chronicization.     

Inferences and metaphoric comprehension in unilaterally implanted children with adequate formal oral language performance

Objectives

To assess skills in inferences during conversations and in metaphors comprehension of unilaterally cochlear implanted children with adequate abilities at the formal language tests, comparing them with well-matched hearing peers; to verify the influence of age of implantation on overall skills.

Methods

The study was designed as a matched case–control study. 31 deaf children, unilateral cochlear implant users, with normal linguistic competence at formal language tests were compared with 31 normal hearing matched peers. Inferences and metaphor comprehension skills were assessed through the Implicit Meaning Comprehension, Situations and Metaphors subtests of the Italian Standardized Battery of “Pragmatic Language Skills MEDEA”. Differences between patient and control groups were tested by the Mann–Whitney U test. Correlations between age at implantation and time of implant use with each subtest were investigated by the Spearman rank correlation coefficient.

Results

No significant differences between the two groups were found in inferencing skills (p = 0.24 and p = 0.011 respectively for Situations and Implicit Meaning Comprehension). Regarding figurative language, unilaterally cochlear implanted children performed significantly below their normal hearing peers in Verbal Metaphor comprehension (p = 0.001). Performances were related to age at implantation, but not with time of implant use.

Conclusions

Unilaterally cochlear implanted children with normal language level showed responses similar to NH children in discourse inferences, but not in figurative language comprehension. Metaphors still remains a challenge for unilateral implant users and above all when they have not any reference, as demonstrated by the significant difference in verbal rather than figurative metaphors comprehension. Older age at implantation was related to worse performance for all items. These aspects, until now less investigated, had to receive more attention to deeply understand specific mechanisms involved and possible effects of different levels of figurative language complexity (presence or absence of contextual input, degree of transparency and syntactic frozenness). New insight is needed to orient programs in early intervention settings in considering and adequately responding to all these complex communicative need of children with hearing loss.     

Seminal estrone, estrone sulfate, and estradiol-17 beta levels in fertile and infertile males

The seminal levels of estrone (E1), estrone sulphate (E1S), and estradiol-17 beta (E2) were measured simultaneously after a chromatographic step in the semen samples of 79 men, including fertile volunteers, vasectomized subjects, and patients with oligozoospermia and secretory azoospermia. E1S concentrations in seminal plasma were higher than in serum (with a semen/serum ratio of approximately 2). Seminal E1 and E1S levels in oligozoospermic subjects were significantly decreased compared to controls (p less than 0.02 and p less than 0.03, respectively). The seminal E1S concentration was significantly reduced in azoospermic patients (p less than 0.02) and to a greater extent in vasectomized subjects (p less than 0.001). As seminal E1S is likely to be mainly of testicular origin, the decreased seminal E1S levels in oligoazoospermia are an index of impaired testicular function.