Efficacy of simultaneous vaccination with Enterisol® Ileitis and Ingelvac® CircoFLEXTM in a Swiss breeding farm.

This study explores administration of two piglet vaccines as compared to the mono- and adjuvant-application. A vaccine against the Porcine Circovirus Type 2 (PCV2) cap protein subunit and a vaccine with attenuated live culture against Lawsonia (L.) intracellularis were applied to piglets aged 23.5 days on average. 1'405 animals were divided randomly into four groups. One piglet group was immunized with both vaccines while two other groups were immunized with a combination of one vaccine and adjuvants of alternate vaccination protocol and vice versa. These piglet groups were also compared to a control group supplemented with both adjuvants only. During fattening, pigs, which were simultaneously immunized with Enterisol(®) Ileitis and Ingelvac(®) CircoFLEX(TM) vaccine, gained significantly more weight (792 g/day) when compared to piglet groups mono-vaccinated with Ingelvac® CircoFLEXTM (772 g/day) or either with Enterisol® Ileitis (774 g/day). Moreover, immunized piglet groups showed significantly higher daily weight gain when compared to adjuvants only inoculated control group (751 g/day). Additionally, during fattening the control group displayed higher mortality (6,3 %) than the three vaccinated groups (Ingelvac(®) CircoFLEX(TM) 2,5 %, Enterisol(®) Ileitis 2,3 % and the combination of both vaccines 1,1 %). These data imply that simultaneous immunization with PCV2- and L. intracellularis specific vaccines positively benefit piglet growth observed by an additive effect on growth parameters in farms harboring both pathogens. Return of investment was calculated of 2.10 on the additional Enterisol(®) Ileitis vaccination.

[Personality changes in opioid-dependent subjects in a methadone maintenance treatment program]. / Changements psychologiques au cours d'un traitement de substitution de méthadone, mesurés par l'Inventaire de Personnalité d'Eysenck.

Personality disorders and particularly antisocial personality disorders (APD) are quite frequent in opioid-dependent subjects. They show various personality traits: high neuroticism, high impulsivity, higher extraversion than the general population. Previous studies have reported that some but not all personality traits improved with treatment. In a previous study, we found a low rate of APD in a French population of opioid-dependent subjects. For this reason, we evaluated personality traits at intake and during maintenance treatment with methadone. Methods - The form A of the Eysenck Personality Inventory (EPI) was given to opioid addicts at intake and after 6 and 12 months of methadone treatment. Results - 134 subjects (96 males and 38 females) took the test at intake, 60 completed 12 months of treatment. After 12 months, the EPI Neuroticism (N) and the Extraversion-introversion (E) scale scores decreased significantly. The N score improved in the first 6 months, while the E score improved only during the second 6 months of treatment. Compared to a reference group of French normal controls, male and female opioid addicts showed high N and E scores. Demographic data and EPI scores of patients who stayed in treatment for 12 months did not differ significantly from those of dropouts (n=23). Patients with a history of suicide attempts (SA) started to use heroin at an earlier age and they showed a higher E score and a tendency for a higher N score at intake. Discussion - The two personality dimensions of the EPI changed during MMT, and the N score converged towards the score of normal controls. Opioid addicts differ from normal controls mostly in their N score. The EPI did not help to differentiate 12-month completers from dropouts. Higher E scores in patients with an SA history might reflect a higher impulsivity, which has been linked to suicidality in other patient groups.

[The impact of substitution treatment by methadone among opiate-dependent subjects evaluated by Addiction Severity Index and by urine tests]. / Impact d'un traitement de substitution par méthadone sur des sujets dépendants aux opiacés évalué par l'Addiction Severity Index et des contrôles urinaires.

Methadone maintenance treatment (MMT) has been evaluated in the United States and in a few other countries. MMT has been developed in France since 1995, and over 5 000 patients receive this treatment. However no French study has yet been published on the efficacy of MMT as assessed by a validated scale. Retention in treatment for one year has been considered as a threshold to define maintenance of treatment benefits after discharge from a methadone program; determination of retention predictors is important. Over a three year period, we evaluated patients at admission and during treatment using the Addiction Severity Index (ASI), and urine drug screening was performed weekly; 95 patients (66 males and 29 females) were evaluated at intake. Their mean age was 30.2 5.5, and they had used opioids for a mean of 10.6 5.7 years. Their ASI severity scores for drugs were over 5, showing a clear need for treatment. Female patients differed from males only in the employment-finances ASI score; 43 patients completed at least one year of treatment, after which their drug and legal composite scores significantly improved. No significant changes in their consumption of cocaine, alcohol, benzodiazepines or cannabis were found, but they smoked fewer cigarettes at 12 months. Demographics, ASI severity scores, and history of suicide attempts did not differentiate one-year completers from dropouts (n=16). However, dropouts had used more buprenorphine and less methadone in the 30 days preceding their admission, and they received a lower dose of methadone during treatment. Our population is comparable to other French MMT populations; they enter treatment after a long history of opioid dependence. The improvement found on the ASI composite scores is also similar to the improvement described in other international studies. Dropouts in our study seem to be more treatment-resistant patients, in the sense that they had used more buprenorphine before intake and were not stabilized with it; and they may have had a more negative attitude towards methadone.

Do magnesium infusions protect the inner ear during middle ear surgery? A randomized double blind study.

Joachims et al. recently demonstrated that magnesium was able to protect the inner ear during exposure to noise and fire arms. During middle ear surgery, the inner ear is subjected to noise from fraising and drilling. We saw fit, therefore, to conduct a random double blind study to establish whether magnesium infusions would protect the inner ear during middle ear surgery. We examined 80 patients (38 verum, 42 placebo). The verum patients received 10 mg/kg body weight magnesium 12 hours and 1 hour prior to operation. Plasma and red cell magnesium levels were measured pre-operatively and intra-operatively; they rose as expected. Post-operative auditory tests showed that magnesium had no tendency to prevent inner ear damage. Advocates of magnesium criticize the limited number of patients in our study as well as the administration of the magnesium substitute. In our opinion, however, it should be borne in mind when evaluating these findings that noise from drilling and fraising is only one factor among many which can induce inner ear injury during middle ear surgery.

Macromolecular prodrugs. XX. Factors influencing model dextranase-mediated depolymerization of dextran derivatives in vitro.

Endo-dextranase-mediated depolymerization of dextran and dextran derivatives under various experimental conditions in vitro was determined. By a simultaneous determination of Mn and MW of dextrans treated with the enzyme in aqueous buffer, an initial increase of the polydispersity of the polysaccharide sample was observed, indicating that dextranase cleaved the dextran molecules into chains which differed significantly in length. A pH optimum of 5 for the enzyme action was found. However, in the pH range 5-8, which prevails in the colon, the initial depolymerization rates differed by a factor of less than 2. Dextranase treatment of a dextran sample resulted in a constant increase of the concentration of terminal reducing glucose residues per time unit suggesting, that the initial depolymerization reaction followed zero-order kinetics. For degrees of substitution below 12 the efficacy of dextranase fragmentation of dextran conjugates decreased almost linearly with increasing DS. The chemical nature of the attached drug did not significantly affect the depolymerization rates. Maximally depolymerized dextran derivatives were obtained by the combined action of dextranase and various alpha-glucosidases. Treatment of such solutions with: a) model esterases b) 80% plasma and c) 20% liver homogenate did not give rise to an acceleration of the initial drug regeneration, as compared to identical experiments carried out in pure buffer solution (pH 7.4 and 37 degrees C).

Macromolecular prodrugs. IXX. Kinetics of hydrolysis of benzyl dextran carbonate ester conjugates in aqueous buffer solutions and human plasma.

Benzyl carbonate esters of dextran with varying degrees of substitution have been synthesized. The kinetics of the hydrolytic cleavage of the carbonate ester bond in aqueous solution within the pH range 0.44-10.46 (37 degrees C) has been investigated. The degradation reactions followed pseudo-first-order kinetics and a rate expression encompassing hydrogen ion-, hydroxide ion- and water-catalyzed hydrolysis of the dextran conjugates was derived. No influence of the degree of substitution on the reaction rates was observed. In alkaline solution a slightly enhanced lability of trifluorethyl benzyl carbonate ester compared to the benzyl dextran carbonate esters was observed, indicating a lack of any significant intramolecular catalytic effect in the hydrolysis of the dextran esters. Almost identical rates of liberation of benzyl alcohol were found in 80% human plasma and aqueous buffer of pH 7.4, indicating the lack of enzyme-mediated cleavage of the dextran carbonate ester bond.

Interaction of cinnamaldehyde (a sensitizer in fragrance) with protein.

Formation of a cinnamaldehyde-protein conjugate in the skin by reaction of cinnamaldehyde with nucleophilic groups in proteins is considered to be responsible for the observed immunogenicity. The kinetics of the reaction of bovine serum albumin with cinnamaldehyde in aqueous solution at 30 degrees C have been investigated, and the rate of formation of conjugate over the pH range 6.4-10.5 showed a first-order dependence on cinnamaldehyde concentration. The cinnamaldehyde binding sites on the protein appeared mostly or exclusively to be the thiol groups of cysteine residues.

Penetration of the fragrance compounds, cinnamaldehyde and cinnamyl alcohol, through human skin in vitro.

The delivery of cinnamaldehyde and cinnamyl alcohol in fragrance through human skin has been investigated by in vitro penetration studies using full thickness human skin. Cinnamaldehyde was transformed to cinnamyl alcohol and cinnamic acid in the skin. The transformation took place in model protein solution, bovine serum albumin, as well as in skin homogenates. After conjugation of cinnamaldehyde with the protein, a lag time was observed after which cinnamyl alcohol and cinnamic acid were released. On the other hand, cinnamyl alcohol was not transformed in detectable amounts to either cinnamaldehyde or cinnamic acid during penetration of the skin.

Cross-sensitization patterns in guinea pigs between cinnamaldehyde, cinnamyl alcohol and cinnamic acid.

Guinea pig maximization tests (GPMT) were performed with cinnamon substances. There was a certain degree of cross-reactivity between cinnamaldehyde, cinnamyl alcohol and cinnamic acid as animals sensitized to cinnamaldehyde reacted to the challenge with the three substances. Animals sensitized to cinnamyl alcohol reacted to cinnamyl alcohol and cinnamaldehyde, but not to cinnamic acid. Cinnamic acid did not sensitize guinea pigs. Compared to the challenge concentration for cinnamaldehyde, approximately a 15 times higher concentration of cinnamyl alcohol and a 25 times higher concentration of cinnamic acid were required to give positive reactions in animals sensitized to cinnamaldehyde. This could not be explained by differences in permeability properties, as the penetration profiles of the three substances through guinea pig skin in vitro showed permeability coefficients of the same order of magnitude under the test conditions. The study suggests that cinnamaldehyde is the "true" allergen, while cinnamyl alcohol and cinnamic acid are transformed in the skin to cinnamaldehyde, before contact allergic reactions can occur.

[The effect of noise trauma on speech discrimination in silence and under influence of party noise (author's transl)]. / Die Auswirkungen von Knallschäden auf das Sprachgehör in Ruhe und bei Nebengeräuschen unter Berücksichtigung von Schweregrad der Schäden und Alter der Probanden.

Speech audiometry investigations were carried out in silence and under action of cocktail party noise in 44 soldiers. The testing subjects were grouped according to age and degree of noise lesion. The statistical evaluation of discrimination losses measured in silence and under acting party noise indicated that noise lesions induced considerable discrimination losses even in young subjects particularly under cocktail party noise conditions. Discrimination decreases significantly as the degree of noise trauma increases. In order to assess the real effect of the hearing loss caused by noise trauma upon speech discrimination, the tests of speech audiometry should be performed under noise conditions.