Protective effect of apocynin, a NADPH-oxidase inhibitor, against contrast-induced nephropathy in the diabetic rats: a comparison with n-acetylcysteine.

The aim of this study was to investigate the effects of apocynin, a NADPH (nicotinamide adenine dinucleotide phosphate)-oxidase inhibitor, in diabetic rats with nephropathy induced by contrast medium (CIN). Diabetes was induced in male Wistar rats by a single dose of streptozotocin (60 mg/kg i.v.). Animals were then divided into the following groups: 1) control group (diabetic rats treated i.v. with saline solution); 2) iomeprol group (iomeprol at 10 ml/kg was injected i.v. 30 min after saline administration); 3) apocynin group (identical to the iomeprol group, except for pre-treatment with apocynin 5mg/kg i.v., 30 min before iomeprol injection) and 4) N-acetylcysteine group (NAC) (same as iomeprol group, except for the treatment with NAC 20 mg/kg i.v. 30 min before iomeprol injection). CIN in animals were assessed 24h after administration of iomeprol. Apocynin significantly attenuates the impaired glomerular function, concentration of Na(+), K(+), alpha glutathione S-transferase levels in urine and neutrophil gelatinase-associated lipocalin levels in plasma caused by iomeprol. In kidney, immunohistochemical analysis of some inflammatory mediators, such as nitrotyrosine, poly-ADP-ribosyl polymerase, tumor necrosis factor-α, interleukin-1ß as well as apoptosis (evaluated as terminal deoxynucleotidyltransferase-mediated UTP end labeling assay) revealed positive staining in tissue obtained from iomeprol group. These parameters were markedly reduced in animals treated with apocynin. Similarly, these parameters were also markedly modified by NAC pre-treatment. Here, we have shown that apocynin attenuates the degree of iomeprol-induced nephropathy in diabetic rats.

Pharmacological and clinical overview of cloperastine in treatment of cough.

Cough constitutes an impressive expression of the normal defense mechanisms of the respiratory system. Productive cough associated with catarrh is an important protective system for the lung because it favors the upward movement of secretions and foreign bodies to the larynx and mouth. Cough may also appear without bronchial secretions, as dry cough, which may be persistent when inflammatory disease is chronic or when, in the early stages of respiratory disease, bronchial secretions are not yet fluid. Sometimes bronchitis-induced cough does not significantly affect quality of life, whilst in other cases cough may become so intense as to impair daily activities severely, resulting in permanent disability. This type of cough is one of the most frequent reasons for seeking medical advice. The use of cough suppressants may be appropriate for reaching a precise diagnosis and when dry cough is persistent. Cloperastine has been investigated in various types of cough and, unlike codeine, has been shown to possess dual activity. It also acts as a mild bronchorelaxant and has antihistaminic activity, without acting on the central nervous system or the respiratory center. Here we review the preclinical and clinical evidence of the efficacy and tolerability of cloperastine.

Design and evaluation of a semantic approach for the homogeneous identification of events in eight patient databases: a contribution to the European EU-ADR project.

The overall objective of the EU-ADR project is the design, development, and validation of a computerised system that exploits data from electronic health records and biomedical databases for the early detection of adverse drug reactions. Eight different databases, containing health records of more than 30 million European citizens, are involved in the project. Unique queries cannot be performed across different databases because of their heterogeneity: Medical record and Claims databases, four different terminologies for coding diagnoses, and two languages for the information described in free text. The aim of our study was to provide database owners with a common basis for the construction of their queries. Using the UMLS, we provided a list of medical concepts, with their corresponding terms and codes in the four terminologies, which should be considered to retrieve the relevant information for the events of interest from the databases.

Hemorrhagic cystitis induced by an herbal mixture.

A healthy 33-year-old woman consumed a slimming product containing a mixture of herbal remedies without seeking medical advice. Two months later, the patient had hemorrhagic cystitis and discontinued the herbal product. Symptoms spontaneously remitted in a few days. Four months later, she took the same herbal remedy and the hemorrhagic cystitis reappeared. She then consulted her general practitioner. A urine culture test was negative, and the patient was advised to discontinue the herb intake. Again, the cystitis resolved within a week. The product involved contains a mixture of herbs, some of which have been associated with adverse effects that might account for the symptoms reported in this case.

Data mining on electronic health record databases for signal detection in pharmacovigilance: which events to monitor?

PURPOSE: Data mining on electronic health records (EHRs) has emerged as a promising complementary method for post-marketing drug safety surveillance. The EU-ADR project, funded by the European Commission, is developing techniques that allow mining of EHRs for adverse drug events across different countries in Europe. Since mining on all possible events was considered to unduly increase the number of spurious signals, we wanted to create a ranked list of high-priority events. METHODS: Scientific literature, medical textbooks, and websites of regulatory agencies were reviewed to create a preliminary list of events that are deemed important in pharmacovigilance. Two teams of pharmacovigilance experts independently rated each event on five criteria: 'trigger for drug withdrawal', 'trigger for black box warning', 'leading to emergency department visit or hospital admission', 'probability of event to be drug-related', and 'likelihood of death'. In case of disagreement, a consensus score was obtained. Ordinal scales between 0 and 3 were used for rating the criteria, and an overall score was computed to rank the events. RESULTS: An initial list comprising 23 adverse events was identified. After rating all the events and calculation of overall scores, a ranked list was established. The top-ranking events were: cutaneous bullous eruptions, acute renal failure, anaphylactic shock, acute myocardial infarction, and rhabdomyolysis. CONCLUSIONS: A ranked list of 23 adverse drug events judged as important in pharmacovigilance was created to permit focused data mining. The list will need to be updated periodically as knowledge on drug safety evolves and new issues in drug safety arise.

A semantic approach for the homogeneous identification of events in eight patient databases: a contribution to the European eu-ADR project.

The overall objective of the eu-ADR project is the design, development, and validation of a computerised system that exploits data from electronic health records and biomedical databases for the early detection of adverse drug reactions. Eight different databases, containing health records of more than 30 million European citizens, are involved in the project. Unique queries cannot be performed across different databases because of their heterogeneity: Medical record and Claims databases, four different terminologies for coding diagnoses, and two languages for the information described in free text. The aim of our study was to provide database owners with a common basis for the construction of their queries. Using the UMLS, we provided a list of medical concepts, with their corresponding terms and codes in the four terminologies, which should be considered to retrieve the relevant information for the events of interest from the databases.

Drug safety information through the internet: the experience of an Italian website.

BACKGROUND: The Internet may play a crucial role in the prompt provision of updated drug safety information. Nevertheless, limited knowledge of the English language among healthcare professionals or suboptimal search skills constitute barriers to widespread and appropriate use of the Internet for this purpose in Italy. In order to provide accurate information on drug safety and to promote the reporting of adverse drug reactions, in 1999 the clinical section of the Italian Society of Pharmacology created the website www.farmacovigilanza.org, financially supported by a non-profit foundation. The website promptly and independently provides news published in the international literature on drug safety, translated into Italian. The site also contains specific sections dedicated to adverse reactions to herbal products and cosmetic preparations. OBJECTIVES: The aim of this paper was to describe the number and characteristics of users and the most intensively visited sections of the website. Furthermore, in September 2006, 300 registered users who had accessed a registered users area aimed specifically at health professionals more than 20 times in the preceding 12 months received a ten-item multiple choice questionnaire via e-mail, to assess satisfaction with the accuracy and promptness of information provided, text comprehension and other information sources for drug-related issues. We hereby describe the results of the survey, after careful analysis of the questionnaires. RESULTS: Up until July 2007, the site had over 600 000 direct accesses and 9760 healthcare professionals registered to use the site. A total of 108 responses to the e-mailed questionnaire were received (response rate = 36%), of which 103 were analysed; five were excluded due to missing information. Overall, the majority of responders judged the information on the site as objective and understandable. More than 85% of participants declared that the site has influenced their opinion and attitudes toward the safety of medicines. In particular, responders said that they pay more attention to drug interactions and to the safety profile of newly marketed drugs, and spend more time on communicating the risks of drugs used by their patients. Specifically, responders stated that they pay more attention to drug interactions (87.7%), newly marketed drugs (68.5%), herbal remedies (56.2%), drugs in patients at increased risk (42.5%), drugs in pregnant women (42.5%) and cosmetics (13.7%). CONCLUSIONS: The website www.farmacovigilanza.org appears to be an effective tool that provides users of the site with independent, relevant and reliable safety information. It was found to influence (and possibly improve) the quality of prescribing of a large proportion of the general practitioners who responded to our questionnaire, and our results indicate a high appreciation of the information found on the website. Moreover, the survey disclosed that there is a substantial need for such information in the national language by healthcare professionals. We think that our approach can serve as a model for similar initiatives in countries elsewhere in the world.

Gynecomastia possibly induced by rosuvastatin.

Gynecomastia is characterized by benign progressive enlargement of the male breast. A pharmacologic origin is identified in 10-20% of cases. Several case reports have associated this condition to the use of statins. However, to our knowledge, no case of rosuvastatin-induced gynecomastia has been reported in the literature. We describe a 57-year-old man who developed bilateral gynecomastia after 2 months of rosuvastatin therapy. After switching to a different statin, atorvastatin, his symptoms resolved within 1 month. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship between the patient's development of gynecomastia and rosuvastatin therapy. The relatively strong effect of rosuvastatin on inhibiting steroidogenesis might have explained why our patient's gynecomastia occurred only with this agent. Clinicians should be aware of the possibility of adverse endocrine reactions when statins are prescribed, including newer agents such as rosuvastatin.

Enhancement of expression of vascular endothelial growth factor after adeno-associated virus gene transfer is associated with improvement of brain ischemia injury in the gerbil.

Angiogenesis induced by growth factors may represent a rational therapy for patients with stroke. Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis and VEGF expression is enhanced in the post-ischemic brain. VEGF induced by brain hypoxia can lead to the growth of new vessels and may represent a natural protective mechanism improving survival after stroke. In the light of these findings we investigated changes of VEGF expression in different brain regions after intracerebroventricular injection of adeno-associated virus transferring gene for VEGF (rAAV-VEGF) in the gerbil, and after transient brain ischemic injury, we studied the effects of rAAV-VEGF injection on survival, brain edema, delayed neuronal death in the CA1 area and learning ability. Treatment with rAAV-VEGF 6 days or 12 days before ischemia significantly improves survival, brain edema and CA1 delayed neuronal death and post-ischemic learning evaluated by passive avoidance test. Animals treated with rAAV-VEGF showed in the thalamus and the cortex, a significant positive immunostaining for VEGF similar to those subjected to brain ischemia and not treated with rAAV-VEGF. These data represent a further contribution to a possible employment of gene therapy by using rAAV-VEGF in brain ischemia and indicate that thalamus and cortex may be targets for neuroprotective effects of VEGF.

Oral administration of a soy extract improves endothelial dysfunction in ovariectomized rats.

Effects of oral administration for 4 weeks of a soy fraction with mainly isoflavones (Glycine max, Leguminosae) (SOYPH; 5 mg/kg) on vascular dysfunction induced by bilateral ovariectomy (OVX) in rats were studied. We evaluated vascular reactivity of aortic rings after acetylcholine (ACh 10 nM-10 microM), sodium nitroprussiate (SN 15 - 30 nM) and NG-L-arginine (L-NMA; 10 - 100 microM). Uterine weight and nitric oxide synthase (NOS) activity were also investigated. The same parameters were observed after 4 weeks treatment with 17beta-estradiol. In OVX rats endothelial-dependent vascular responses were changed: reduction of induced contraction ( L-NMA 100 mM: sham OVX 2.1 +/- 0.2 g/mg tissue; OVX 1.7 +/- 0.4 g/mg tissue). Ovariectomy produced a reduction of constitutive NOS activity. Uterine weight was increased in animals treated with 17beta-estradiol but not with SOYPH. Either SOYPH or 17beta-estradiol produced a similar improvement of endothelial dysfunction and increased NOS activity. Our data suggest that soy isoflavones produce an improvement of endothelial dysfunction induced by ovariectomy so as 17beta-estradiol, but probably without changes in reproductive system.