Phase I Study in Healthy Women of a Novel Antimycotic Vaginal Ovule Combining Econazole and Benzydamine.

Purpose: A novel fixed-dose combination of 150 mg of econazole with 6 mg of benzydamine formulated in vaginal ovules was investigated in a randomised, double-blind, four-parallel group, tolerability, and pharmacokinetic Phase I study in healthy women. Methods: The fixed-dose combination was compared to econazole and benzydamine single-drug formulations and with placebo after daily applications for 3 consecutive days. Safety and tolerability were evaluated recording the adverse drug reactions, local and general tolerability scores, clinical laboratory assays, and vital signs. Econazole, benzydamine, and its metabolite benzydamine N-oxide pharmacokinetics were investigated after single and multiple applications. Results: Local reactions were generally absent. Pruritus and pain at the application site were infrequently reported. According to the subjects' evaluations, the overall tolerability of the ovules was rated as excellent or good. No significant effect of any treatment on laboratory parameters, vital signs, body weight, vaginal pH, or ECG was observed. Very low econazole, benzydamine, and benzydamine-N-oxide concentrations were measured in plasma, though quantifiable in almost all samples. Conclusion: The tested fixed-dose combination showed a good safety profile consistently with the known tolerability of both active substances. In addition, the confirmed low bioavailability of the drugs excludes the possibility of any accumulation effects and limits the risk of undesired systemic effects. This trial is registered at ClinicalTrials.gov with the identifier NCT02720783 last updated on 07 February 2017.

Effects of high Zn and Pb concentrations on Phragmites australis (Cav.) Trin. Ex. Steudel: Photosynthetic performance and metal accumulation capacity under controlled conditions.

The response of Phragmites australis (Cav.) Trin. Ex. Steudel to zinc (Zn) and lead (Pb) was studied separately in two hydroponic tests, during a three weeks experiment. The effects on ecophysiology and biomass partitioning were evaluated during the metal treatments and at the recovery, and total metal content and accumulation capacity in different plant organs were assessed. Zn and Pb had different effects on the overall measured parameters, highlighting different mechanism of action. In particular, Zn concentration was higher in roots and, being a micronutrient, it was translocated into leaves, producing a reduction of assimilation rate, stomatal conductance (-71.9 and -81.3% respect to the control plant respectively), and a strong down regulation of photosystems functionality both at PSII and PSI level. Otherwise, Pb was accumulated mainly in the more lignified tissue such as rhizomes, with slightly effect on gas exchange. Chlorophyll a fluorescence highlighted that Pb inhibits the electron transfer process at the PSI donor side, without recovery after the removal of the metal stress. Despite these physiological limitations, P. australis showed a high capacity to accumulate both metals, and only slight reduction of biomass, being therefore a suitable species for phytoremediation interventions.

Acute stroke treatment using the Penumbra endovascular mechanical thrombolysis device: a single-centre experience.

PURPOSE: Ischaemic stroke due to occlusion of large cerebral vessels has a poor prognosis. The clinical outcome is related to efficacy and timing of recanalisation of the occluded arteries. We report our experience with a thrombus aspiration device (Penumbra), and focus on pre- and postprocedural management. MATERIALS AND METHODS: We retrospectively reviewed 18 consecutive patients with acute ischaemic stroke due to the occlusion of large cerebral vessels who were treated with mechanical thrombolysis at our centre between September 2009 and July 2010. Preprocedural symptoms were quantified using the National Institutes of Health Stroke Scale (NIHSS). Mechanical thrombolysis was performed with the Penumbra system. Intravenous thrombolysis was done only if <3 h had elapsed since symptom onset. Associated vessel stenoses were treated with stenting. All patients underwent neurological examination and postprocedural magnetic resonance angiography (MRA) at 3 and 6 months. RESULTS: Mechanical thrombolysis using the Penumbra system was performed in all cases. A total of 83% of treated vessels had a value of 2/3 according to the Thrombolysis in Cerebral Infarction (TICI) scale. In seven patients (39%) intravenous thrombolysis was unsuccessful, and salvage mechanical thrombolysis followed. Three patients died after the procedure (16.7%). Five patients (27.8%) required a stenting procedure. All patients reported a significant improvement in symptoms (mean baseline NIHSS 19.6±5.6; mean postprocedural NIHSS, 7.8±5.5 p<0.0001) CONCLUSIONS: Our preliminary experience with the Penumbra mechanical thrombolysis system confirms previously reported results showing the efficacy and safety of the device in treating acute stroke caused by the occlusion of large intracranial vessels.

The -A2518G polymorphism of monocyte chemoattractant protein-1 is associated with Crohn's disease.

OBJECTIVES: The -A2518G variation in monocyte chemoattractant protein (MCP)-1 gene promoter has been associated with autoimmune diseases. Our aim was to investigate the gene polymorphism and MCP-1 plasma levels in patients with inflammatory bowel disease (IBD). METHODS: Family-based and case-control association analyses of the -A2518G polymorphism (rs1024611) were performed in 1,936 subjects (770 patients with Crohn's disease (CD), 316 patients with ulcerative colitis (UC), 302 healthy relatives (151 CD trios), and 548 healthy controls (HCs)). Extensive gene sequencing was also undertaken, and a further six single-nucleotide polymorphisms (SNPs) were genotyped in 435 CD patients and 189 HCs. MCP-1 protein plasma levels in 234 CD patients, 117 UC patients, and 108 HCs were assessed by an immunosorbent assay. RESULTS: Five SNPs in strong linkage disequilibrium (D'>0.85) were associated with CD, with the strongest signal found at the -A2518G SNP. The frequency of the G allele was significantly lower in CD patients (22.1%), compared with HCs (29.8%), both at case-control (P=6 x 10(-6)) and at transmission disequilibrium test analyses (T/U 41/88; P=4 x 10(-4)). No difference in alleles (26.1%) and genotype frequencies were found in UC patients. MCP-1 plasma levels in CD and UC patients were similar to those in HCs (P=0.38), irrespective of disease activity, or MCP-1 genotypes. However, 30 CD (13%) and 20 UC patients (17%) with extensive colonic involvement had plasma levels significantly higher than HCs (P=0.02). CONCLUSIONS: The -A2518G polymorphism seems to be associated with CD but does not influence MCP-1 plasma levels, which in contrast are increased in UC and CD with extensive colonic involvement.

Peripheral obstructive arterial disease and carotid artery stenosis in end stage renal disease: a case-control study.

AIM: Cardiovascular diseases are an important cause of morbidity and mortality in end stage renal disease (ESRD) patients. The purpose of this study was to evaluate the predominance of carotid stenosis and peripheral obstructive arterial disease (POAD) in a group of patients subject to dialysis compared with a control group. METHODS: It is a control-case study performed on patients at different hemodialysis facilities; the exams were carried out in ambulatory care. Two groups of patients were examined, the first group was made up of 40 dialysis patients (46.6% men, average age 58.8), the second was the control group made up of 58 subjects matched by age, sex, arterial pressure, presence of diabetes and smoking habits. All patients underwent an Eco-Color Doppler exam on the over aortal trunks and lower extremities and had their Ankle-Brakial-Index (ABI) measured. Carotid stenosis was considered only if equal or over 50%. RESULTS: Twenty percent of dialysis patients showed carotid stenosis (CS) versus 12% in the control group, with an OR of 7.9 (CI 95% 1.3-47.7) adjusted to sex, age and hypertension. The ultrasound picture of the lesions showed large amounts of calcium deposits. Predominance of POAD in dialysis patients was 20% versus 9% in the control group. In dialysis patients the OR adjusted to age, sex and arterial pressure was 6.3 (CI 95%, 1.2-32.6). CONCLUSION: The ultrasound picture of the lesions showed mainly underpopliteal lesions with ''rosary bead'' calcifications. In diabetic dialysis patients the OR was 7.6 (CI 95% 1.4-46.3).

Chronic daily headache and medication overuse headache: clinical read-outs and rehabilitation procedures.

The impact of headache on the person and society represents a public health issue. Recently a study evaluated 51% of headache's prevalence in Europe, of which 14% is affected by migraine. Besides, 4% of adult population is affected by chronic forms, which constitute therefore an even more relevant problem in terms of health and social policies. The International Classification of Headache Disorders, II version (ICHD-II) recognises 24 types of chronic headache and states primary episodic headaches as chronic when attacks appear for more than 15 days per month, for at least three months. Headache given by drugs overuse, defined by ICDH-II in 2004 (and revised in 2005) as Medication Overuse Headache (MOH), is associated with overuse of a combination of analgesics, barbiturates, opioids, ergot alkaloids, aspirin, AINS, caffeine and triptans. Patients affected by MOH present a reduced work performance and a significant alteration in the quality of life. Furthermore, some psychological and behavioural states seem particularly important in promoting and sustaining drug abuse. The management and rehabilitation of patients affected by CDH, abusing symptomatic drugs, consists in the withdrawal and/or gradual reduction of their assumption, because of tolerance and addiction possibilities.

[Chronic daily headache: management and rehabilitation]. / Cefalea cronica quotidiana: gestione e riabilitazione.

In 2001, WHO evidenced headache among the first twenty disability agents in the world. The International Classification of Headache Disorders, II version (ICHD-II) recognises 24 types of chronic headache and states primary headaches as chronic when attacks appear for more than 15 days per month, for at least three months. Migraine given by drugs overuse, defined by ICDH-II in 2004 (and revised in 2005) as MOH, represents a common and debilitating disorder, which can be defined as generation, perpetuation and persistence of intense chronic migraine caused by the frequent and excessive use of (symptomatic) drugs, giving an immediate relief. MOH is associated with overuse of a combination of analgesics, barbiturates, opiods, Ergot alkaloids, aspirin, FANS, caffeine and triptans. Furthermore, some psychological and behavioural states seem particularly important in promoting and sustaining drugs abuse. The management and rehabilitation of patients affected by CDH, over-using symptomatic drugs, consists in the suspension and gradual reduction of their assumption, because of tolerance and addiction possibilities. Therapeutic success, defined as total absence of headache or frequency reduction over 50% in a period of time from 1 to 6 months, stands around 72-74%.

Early and late adjustments of the photosynthetic traits and stomatal density in Quercus ilex L. grown in an ozone-enriched environment.

Quercus ilex L. seedlings were exposed in open-top chambers for one growing season to three levels of ozone (O3 ): charcoal filtered air, non-filtered air supplemented with +30% or +74% ambient air O3 . Key functional parameters related to photosynthetic performance and stomatal density were measured to evaluate the response mechanisms of Q. ilex to chronic O3 exposure, clarifying how ecophysiological traits are modulated during the season in an ozone-enriched environment. Dark respiration showed an early response to O3 exposure, increasing approximately 45% relative to charcoal-filtered air in both O3 enriched treatments. However, at the end of the growing season, maximum rate of assimilation (Amax ) and stomatal conductance (gs ) showed a decline (-13% and -36%, for Amax and gs , respectively) only in plants under higher O3 levels. Photosystem I functionality supported the capacity of Q. ilex to cope with oxidative stress by adjusting the energy flow partitioning inside the photosystems. The response to O3 was also characterised by increased stomatal density in both O3 enriched treatments relative to controls. Our results suggest that in order to improve the reliability of metrics for O3 risk assessment, the seasonal changes in the response of gs and photosynthetic machinery to O3 stress should be considered.

Prulifloxacin versus ciprofloxacin in the treatment of adults with complicated urinary tract infections.

INTRODUCTION: The present study was performed to evaluate the efficacy and safety of a 10-day regimen of prulifloxacin 600 mg once daily as compared to ciprofloxacin 500 mg twice daily in the treatment of patients with complicated urinary tract infections (UTIs). MATERIALS AND METHODS: 257 patients (mean age +/- SD 62.3 +/- 16.5) were enrolled and orally treated with prulifloxacin (127 patients) or ciprofloxacin (130 patients). The study was designed as a randomized, double-blind, double-dummy, controlled clinical trial. The primary efficacy parameter was the eradication of infecting strains (<10(3) cfu/ml). The clinical outcome and tolerability were also assessed. RESULTS: At baseline, the most common infecting strains were Escherichia coli (62.8%), Proteus mirabilis (7.1%) and Klebsiella pneumoniae (4.1%). At the early follow-up, the rate of patients showing successful treatment was 90.8% in the prulifloxacin group, and 77.8% in the ciprofloxacin group (p = 0.008). A positive clinical outcome was observed in 94.8 and 93.3% of prulifloxacin- and ciprofloxacin-treated patients. Both drugs were well tolerated. Two patients dropped out for treatment-related adverse events. CONCLUSIONS: The high urinary concentrations of prulifloxacin, combined with a broad-spectrum antimicrobial activity, allow its use in the empiric therapy of UTIs.

Four-year study of rotavirus electropherotypes from cases of infantile diarrhea in Rome.

Rotavirus infections were detected in 210 of 675 children with acute diarrhea admitted to a major pediatric hospital in Rome from January 1982 through December 1985. Most of the patients with rotavirus infections were admitted during the winter season in both 1982 and 1985, whereas during the two intermediate years, cases occurred in all months. Among 84 rotavirus samples examined, 14 different electropherotypes were recognized, 2 of which largely predominated over the others. The two electropherotypes were particularly frequent in the 2 epidemic years, altogether accounting for 70.2% of the samples typed, and circulated in distinct periods. None of the viruses showed a short pattern of electrophoretic migration of the genome, indicating a minor involvement of subgroup I rotaviruses in hospitalization-requiring diarrheas occurring in the area surveyed.

Laboratory diagnosis of rotavirus infection in diarrhoeal patients by immunoenzymatic and latex-agglutination assays.

One hundred stool samples from children with acute diarrhoea were examined by six commercial latex and immunoenzymatic assays for the diagnosis of rotavirus infection in four different laboratories. Samples were also analyzed by solid-phase immune electron microscopy using a rabbit anti-group A rotavirus antiserum. With electron microscopy as a basis for comparison, sensitivity and specificity for the latex and ELISA assays varied from 91.1 to 92.9% and from 94.2 to 99.4%, respectively. Statistically significant differences were revealed in the confirmation rate of electron microscopy-negative samples between different commercial assays. Significant variability was also found between results obtained by the laboratories taking part in the study.