Safety of snake antivenom immunoglobulins: efficacy of viral inactivation in a complete downstream process.

Viral safety remains a challenge when processing a plasma-derived product. A variety of pathogens might be present in the starting material, which requires a downstream process capable of broad viral reduction. In this article, we used a wide panel of viruses to assess viral removal/inactivation of our downstream process for Snake Antivenom Immunoglobulin (SAI). First, we screened and excluded equine plasma that cross-reacted with any model virus, a procedure not published before for antivenoms. In addition, we evaluated for the first time the virucidal capacity of phenol applied to SAI products. Among the steps analyzed in the process, phenol addition was the most effective one, followed by heat, caprylic acid, and pepsin. All viruses were fully inactivated only by phenol treatment; heat, the second most effective step, did not inactivate the rotavirus and the adenovirus used. We therefore present a SAI downstream method that is cost-effective and eliminates viruses to the extent required by WHO for a safe product.

Bacillus atrophaeus inactivated spores as a potential adjuvant for veterinary rabies vaccine.

Rabies is a viral encephalitis, nearly always fatal, but preventable through vaccines. Rabid animal bite is the prime transmission act, while veterinary vaccination is one of the best strategies for rabies general prevention. Aluminum compounds and saponin are the commercial adjuvants used for this vaccine nowadays. Nevertheless, aluminum compounds can provoke undesired side effects and saponin has a narrow activity range without toxicity. B. atrophaeus inactivated spores (BAIS), with or without saponin, were then used as an alternative to boost the inactivated rabies virus response. BAIS was as effective as saponin in augmenting antibody titers, but combination of both adjuvants doubled the titers raised by them individually. The combined adjuvant formulation maintained viability for 21 months when stored at 4-8°C. Overall, BAIS was demonstrated as a viable alternative to commercial adjuvants, while its combination with saponin resulted in even higher vaccine potency with good stability.

Levobupivacaine 0.75% vs. lidocaine 4% for topical anaesthesia: a clinical comparison in cataract surgery.

BACKGROUND: The aim of this study was to compare the efficacy of topical levobupivacaine drops 0.75% vs. lidocaine drops 4% in cataract surgery. METHODS: We examined 203 patients undergoing cataract surgery by phacoemulsification. They were randomized into two groups: one received four drops of lidocaine 4% and the other received four drops of levobupivacaine 0.75%. The onset and offset times of sensory block were evaluated. Application, intraoperative and postoperative subjective pain was quantified by the patients using a verbal pain score. Complications, rates of supplemental anaesthesia, and the satisfaction of surgeon and patients were also recorded. RESULTS: The mean sensory onset and offset times were significantly higher for the levobupivacaine group (P < 0.01). Pain score was lower in the levobupivacaine group than in the lidocaine one and the difference was statistically significant at all stages (P < 0.01). The mean satisfaction scores of patients and surgeon were also statistically higher for levobupivacaine (P < 0.01). No significant differences for complications and rates of supplemental anaesthesia were found. CONCLUSIONS: Topical levobupivacaine 0.75% shows the same efficacy and safety as lidocaine 4% in cataract surgery by phacoemulsification. There was an adequate block with a good level of satisfaction of surgeon and patients. Levobupivacaine 0.75% offers a new and acceptable choice for topical anaesthesia in cataract surgery.

Artificial neural network assessment of substitutive pharmacological treatments in hospitalised intravenous drug users.

Artificial neural networks (ANNs) provide better solutions than linear discriminant analysis (LDA) to problems of classification and estimation involving a large number of non-homogeneous (categorical and metric) variables. In this study, we compared the ability of traditional LDA and a feed-forward back-propagation (FF-BP) ANN with self-momentum to predict pharmacological treatments received by intravenous drug users (IDUs) hospitalised for coexisting medical illness. When medical staff considered detoxification appropriate they usually suggested methadone (MET) and (or) benzodiazepines (BDZ). Given four different treatment options (MET, BDZ, MET+BDZ, no treatment) as dependent variables and 38 independent variables, the FF-BP ANN provided the best prediction of the consultant's decision (overall accuracy: 62.7%). It achieved the highest level of predictive accuracy for the BDZ option (90.5%), the lowest for no treatment (29.6), often misclassifying no treatment as BDZ. The LDA yielded a lower mean accuracy (50.3%). When the untreated group was excluded, ANN improved its absolute recognition rate by only 1.2% and the BDZ group remained the best predicted. In contrast, LDA improved its absolute recognition rate from 50.3 to 58.9%, maximum 65.7% for the BDZ group. In conclusion, the FF-BP ANN was more accurate than the statistical model (discriminant analysis) in predicting the pharmacological treatment of IDUs.

Quinpirole- and amphetamine-induced hyperdipsia: influence of fluid palatability and behavioral cost.

Daily administration of moderate doses of amphetamine or of the dopaminergic D2 agonist quinpirole is associated with the development of excessive, non-regulatory drinking. Here we compared the influence of manipulating fluid palatability and behavioral cost on the development of this drinking augmentation. Experiment 1 was based on the phenomenon of contrafreeloading (CFL): animals work for a resource even though the same resource is freely available. The effects of 15 daily injections of amphetamine (1.0 and 1.7 mg/kg i.p. ) or quinpirole (0.1 and 0.56 mg/kg i.p.) were evaluated in mildly water-deprived rats. For the first 6 days the rats obtained water by lever pressing (FR3) only; over the following 9 days water was also freely available (CFL). Initially, 0.56 mg/kg quinpirole reduced lever pressing for water. A complete recover of responding was then obtained, and was followed by a progressive increment in the amount water obtained by lever pressing during the CFL phase (from 10 to 50%). Amphetamine did not affect percent CFL, but at the highest dose (1.7 mg/kg) reduced total water intake during the last 3 days of treatment. In experiment 2 the rats had free access to two bottles, one of which contained tap water, and the other contained either an ethanol (6%) or a sucrose (5%) solution. After habituation to this regimen, the rats received 10 daily i.p. injections of vehicle, amphetamine (1.0 or 3 mg/kg), or quinpirole (0.1 or 0.56 mg/kg). Quinpirole 0.56 mg/kg enhanced daily fluid intake under both sucrose and ethanol conditions, but selectively reduced ethanol preference. The higher amphetamine dose reduced fluid intake and sucrose preference. In conclusion, chronic exposure to a dopaminergic D2 agonist, but not to amphetamine, produced an increment of drinking that was resistant to manipulation of either palatability or the behavioral cost of the fluid.