West Nile virus epidemic in horses,Tuscany region,Italy

During the late summer of 1998, veterinary authorities in Tuscany, Italy, received reports of cases of neurologic disease among horses residing in a large wetland area located in the provinces of Florence and Pistoia. West Nile virus was isolated from two of the six horses that died or were euthanized. A retrospective epidemiologic study identified 14 clinical neurologic cases that occurred from August 20 to October 6 (attack rate of 2.8%). A serologic survey conducted over a 700-km2 area in stables with and without apparent clinical cases confirmed a wider spread of the infection, with an overall seroprevalence rate of 38% in the affected area. No significant differences in age-specific prevalence were observed, suggesting that the horses residing in the area had not been exposed previously to West Nile virus and supporting the hypothesis of its introduction in the wetland area during the first half of 1998.     

International classification of functioning,disability and health (ICF) 2001

The approach which had been being employed to date for dealing with and classifying those aspects related to health and disability have been revised and updated thanks to the World Health Organization (WHO) having drafted the International Classification of Functioning, Disability and Health, which has now been accepted 191 countries after revamping the prior model and reaching a consensus regarding a new international model for describing and measuring health and disability. As background information, it must be recalled that the Classification of Impairments, Disabilities and Handicaps (CIDH) previously in effect was first published by the WHO in 1980. The process of revising this classification has resulted in some changes of far-reaching importance. The change in the name has been aimed at reflecting the wish to replace the negative perspective of impairments, disabilities and handicaps for a more neutral view of structure and function, considering the positive perspectives of activities and of participation. Another new aspect has been that of including a section related to environmental factors in recognition of their importance, given that by interacting with the health condition they may give rise to a disability, or, at the opposite end of the scale, may restore functioning. The data available has enabled the WHO make estimates including that of some 500 million years of life being lost annually due to disabilities related to health problems, which totals over one half of the years lost annually due to premature deaths. The main objective of this new classification is that of providing the conceptual framework by means of unified, standardized language with a view to of the underlying challenges, setting out a valuable instrument of practical use in public health.     

Risk factors of malignant skin melanoma in Italian population: review of results of a case-control study

Cutaneous melanoma incidence rates are rapidly increasing worldwide, including in the Mediterranean countries. Sunlight exposure has been associated with melanoma, but the mechanisms of UV radiation-induced carcinogenesis is still largely unknown. In mammalian cells, UV radiation induces DNA damage that can be repaired mostly by the nucleotide excision repair system. We summarize here the results of a case-control study conducted at the Bufalini Hospital in Cesena, Italy to assess host and environmental risk factors for melanoma. We recruited 183 incident cutaneous melanoma cases and 179 controls selected predominantly among partners or close friends of the cases. Presence of dysplasticlatypical nevi (OR: 4.2; 95% CI: 2.4-7.4), low propensity to tan (OR: 2.4; 95% CI 1.1-5.0), light skin (OR: 4.1; 95% CI: 1.4-12.1), and light eye color (OR: 2.4; 95% CI: 1.1-5.2) were the strongest risk factors for melanoma in this population. A chart identifying melanoma risk associated with multiple combinations of these factors is presented. We used the host-cell reactivation assay on subjects' lymphocytes to measure individual DNA repair capacity (DRC) after UV-induced DNA damage. Subjects with low tanning ability and low DRC had a higher melanoma risk (OR: 8.6; 95% CI: 2.7-27.5) than those with higher tanning ability and high DRC. Subjects with dysplastic nevi and low DRC had a higher risk (OR: 6.7; 95% CI: 2.4-18.6) than those lacking dysplastic nevi and with high DRC. These results may help identify high-risk subjects in the Mediterranean populations who would the benefit from preventive measures.     

Different mechanism of LPS-induced vasodilation in resistance and conductance arteries from SHR and normotensive rats

1. The direct and endothelium-dependent effects of lipopolysaccharide (LPS) were investigated on resistance and conductance arteries from normotensive Wistar (NWR) and spontaneously hypertensive (SHR) rats. 2. In both NWR and SHR, LPS induced dose-dependent relaxations of the mesenteric vascular bed, which were inhibited by L-NNA in SHR but not in NWR. Iberiotoxin (IBTX) inhibited the responses to LPS in both groups, indicating the participation of high conductance Ca(2+)-dependent K(+) channels. 3. In mesenteric artery rings, the resting membrane potentials and the hyperpolarizing responses of NWR to LPS did not differ in endothelized and denuded preparations but L-NNA inhibited the responses only in endothelized rings. These responses were reduced by bosentan, suggesting that endothelin release may mask a possible hyperpolarizing response to LPS. The hyperpolarizing responses to LPS were blocked by IBTX in both endothelized and de-endothelized NWR rings. In the SHR only intact rings showed hyperpolarization to LPS, which was inhibited by IBTX and byL-NNA. 4. In SHR aortic endothelized or denuded rings, LPS induced hyperpolarizing responses which, in endothelized rings, were partially blocked by L-NNA, by IBTX or by glibenclamide, but totally abolished by IBTX plus glibenclamide. No response to LPS was observed in NWR aortic rings. 5. Our results indicate that LPS activates large conductance Ca(2+)-sensitive K(+) channels located in the smooth muscle cell membrane both directly and indirectly, through NO release from the endothelium in NWR, whereas NO is the major mediator of the LPS responses in SHR resistance vessels.     

Effects of levobupivacaine,ropivacaine and bupivacaine on HERG channels: stereoselective bupivacaine block

1 Levobupivacaine and ropivacaine are the pure S(-) enantiomers of N-butyl- and N-propyl-2',6'-pipecoloxylidide, developed as less cardiotoxic alternatives to bupivacaine. In the present study, we have analysed the effects of levobupivacaine, ropivacaine and bupivacaine on HERG channels stably expressed in CHO cells. 2 The three drugs blocked HERG channels in a concentration-, time- and state-dependent manner. Block measured at the end of 5 s pulses to -10 mV induced by 20 microM bupivacaine (52.7+/-2.0%, n=15) and ropivacaine (55.5+/-2.7%, n=13) was similar (P>0.05) and both lower than that induced by levobupivacaine (67.5+/-4.2%, n=11) (P<0.05). 3 Dextrobupivacaine (20 microM) was less potent (47.2+/-5.2%, n=10) than levobupivacaine (P<0.05), indicating stereoselective HERG channel block. 4. Block induced by the three local anaesthetics exhibited a steep voltage dependence in the range of channel activation. In all cases, block measured at the maximum peak current at a test potential of 0 mV after promoting recovery from inactivation (I-->O) was lower than that observed at the end of 5-s pulses (I+O). 5. Levobupivacaine, ropivacaine and bupivacaine accelerated HERG inactivation kinetics, slowed the recovery from inactivation and shifted the inactivation curve towards more negative membrane potentials. The three local anaesthetics induced a rapid time-dependent decline after using a protocol that quickly activates HERG channels. 6. All these results suggest that: (1) these drugs bind to the open and the inactivated states of HERG channels, (2) they stabilize HERG channels in the inactivated state, and (3) block induced by bupivacaine enantiomers is stereoselective.     

Two angiotensin AT1 receptor antagonists,irbesartan and losartan,effects in cholesterol-fed rabbits

This study was performed to examine the long-term effects of irbesartan and losartan, two angiotensin (AT(1)) receptor antagonists, on lipoproteins and vascular responsiveness in vessels isolated from hypercholesterolemic rabbits. Four groups of rabbits (n=40) were used: Group 0 (control group), Group 1 [hypercholesterolemic group, 0.5% (wt./wt.) cholesterol-enriched diet], Group 2 (hypercholesterolemic+irbesartan 10 mg/kg/day) and Group 3 (hypercholesterolemic+losartan 10 mg/kg/day). After 17 weeks of treatment, total cholesterol and low-density lipoproteins levels in irbesartan- and losartan-treated groups were significantly lower than those of Group 1 (alpha=0.05). Furthermore, levels of high-density lipoproteins were higher in the treated groups than in the hypercholesterolemic (alpha=0.05) when we consider the same level of total cholesterol in the hypercholesterolemic and the treated groups. Despite the effect of the drugs on the abovementioned parameters, treatment with irbesartan or losartan did not improve endothelium-dependent and independent relaxation in aortic and mesenteric rings. Treatment with irbesartan and losartan decreased noradrenaline-induced contraction in aortic rings with respect to that in the hypercholesterolemic group (alpha=0.05). In addition, irbesartan treatment improved the increase in serotonin-induced contraction in proximal coronary arteries with respect to that in the hypercholesterolemic group (alpha=0.05). These results indicate that irbesartan and losartan restore noradrenaline-induced contraction in hypercholesterolemic rabbit-isolated arteries and improve lipoprotein profile in cholesterol-fed rabbits.     

The role of angiotensin II in hypertension due to adenosine receptors blockade

The renin-angiotensin system may be involved in hypertension induced by adenosine receptors blockade with 1,3-dipropyl-8-sulfophenylxanthine (DPSPX). Contractions of the mesenteric vasculature to angiotensin II, noradrenaline and potassium chloride were studied in DPSPX-induced hypertension. Male Wistar rats received infusions of saline or DPSPX (90 microg kg(-1) h(-1), i.p.) for 3 or 7 days. Blood pressure was determined by the tail-cuff method. On days 3 or 14, concentration-response curves were obtained on mesenteric arteries and veins. Plasma angiotensin II levels, measured by radioimmunoassay, were higher in DPSPX-hypertensive rats. The maximum contractile effect of angiotensin II was lower in vessels from DPSPX-hypertensive rats while that for noradrenaline was higher. Potassium chloride-induced contractions were larger in veins from DPSPX-hypertensive rats but similar in arteries, when compared with control rats. We conclude that raised angiotensin II levels and altered vascular reactivity are consistent with a renin-angiotensin-mediated hypertension.     

Characterization and solubility study of solid dispersions of flunarizine and polyvinylpyrrolidone

Flunarizine is a selective calcium entry blocker poorly water-soluble. In this report, the interactions of this drug with polyvinylpyrrolidone in solid dispersions, prepared according to the dissolution method using methanol as the solvent, have been investigated. For purposes of comparison physical mixtures were prepared by simple mixture and homogeneization of the two pulverized components. Combinations of flunarizine/polyvinylpyrrolidone of the following percentage proportions were prepared: 10/90, 20/80, 30/70, 40/60, 50/50, 60/40 and 80/20 (mean particle size of 0.175 mm). The physicochemical properties of solid dispersions were investigated with X-ray diffraction, infrared spectroscopy, differential scanning calorimetry and solubility in equilibrium. X-ray patterns and differential scanning calorimetry have shown that polyvinylpyrrolidone inhibits the crystallization of flunarizine when percentages drug/polymer are 10/90, 20/80 and 30/70. The infrared spectra suggest that there was no chemical interaction between flunarizine and polyvinylpyrrolidone. Equilibrium solubility studies showed that drug solubility was enhanced as the polymer content increased. In general, the solubility increase was greater in solid dispersions than in physical mixtures and the solubility in equilibrium for solid dispersions and physical mixtures at the same drug/polymer proportion showed significant differences (P < 0.05).     

Bioinformatics: the role and limitations of patents

The worldwide market for bioinformatics tools and services is estimated, by some, to exceed US$40 billion within the next five years. As with other biotech companies, patent protection will be key to survival in the marketplace. Although the total number of issued bioinformatics patents is still small, virtually all aspects of bioinformatics constitute patentable subject matter, and the opportunity to generate intellectual property value from investment in bioinformatics should not be neglected.