Differential effects of specific opioid receptor agonists on rat pup isolation calls.

The possibility was investigated that specific opioid receptor types might selectively alter the production of isolation-induced ultrasonic vocalizations. Intracisternal injections of mu, delta and kappa opioid receptor agonists were administered to isolated 10-day-old rat pups. The mu receptor agonist [D-Ala2-NMe-Phe4-Gly-ol]-enkephalin (DAMGO) and delta receptor agonist [D-Pen2, D-Pen5]-enkephalin (DPDPE) both reduced the rate of isolation-induced ultrasonic calling in the absence of sedation. The kappa receptor agonist U50,488 had the opposite effect, significantly raising the rate of vocalization. Fourteen-day-old pups, with a larger delta receptor population, showed a greater sensitivity to DPDPE than was seen in the younger animals.     

Adrenergic Receptor Genotype but Not Perioperative Bisoprolol Therapy May Determine Cardiovascular Outcome in At-risk Patients Undergoing Surgery with Spinal Block: The Swiss Beta Blocker in Spinal Anesthesia (BBSA) Study: A Double-blinded, Placebo-controlled, Multicenter Trial with 1-Year Follow-up

Background: Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block.

Methods: The authors performed a double-blinded, placebo-controlled, multicenter trial to compare the effect of bisoprolol with that of placebo on 1-yr composite outcome including cardiovascular mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and cerebrovascular insult. Bisoprolol was given orally before and after surgery for a maximum of 10 days. Adrenergic receptor polymorphisms and safety outcome measures of bisoprolol therapy were also determined.

Results: A total of 224 patients were enrolled. Spinal block could not be established in 5 patients. One hundred ten patients were assigned to the bisoprolol group, and 109 patients were assigned to the placebo group. The mean duration of treatment was 4.9 days in the bisoprolol group and 5.1 days in the placebo group. Bisoprolol therapy reduced mean heart rate by 10 beats/min. The primary outcome was identical between treatment groups and occurred in 25 patients (22.7%) in the bisoprolol group and 24 patients (22.0%) in the placebo group during the 1-yr follow-up (hazard ratio, 0.97; 95% confidence interval, 0.55-1.69; P = 0.90). However, carriers of at least one Gly allele of the [beta]1-adrenergic receptor polymorphism Arg389Gly showed a higher number of adverse events than Arg homozygous (32.4% vs. 18.7%; hazard ratio, 1.87; 95% confidence interval, 1.04-3.35; P = 0.04).     

Down's syndrome and the acquisition of phonology by Cantonese-speaking children

ABSTRACT. The phonological abilities of two groups of 4–9-year-old intellectually impaired Cantonese-speaking children are described. Children with Down's syndrome did not differ from matched non-Down's syndrome controls in terms of a lexical comprehension measure, the size of their phoneme repertoires, the range of sounds affected by articulatory imprecision, or the number of consonants, vowels or tones produced in error. However, the types of errors made by the Down's syndrome children were different from those made by the control subjects. Cantonese-speaking children with Downs syndrome, as compared with controls, made a greater number of inconsistent errors, were more likely to produce non-developmental errors and were better in imitation than in spontaneous production. Despite extensive differences between the phonological structures of Cantonese and English, children with Downs syndrome acquiring these languages show the same characteristic pattern of speech errors. One unexpected finding was that the control group of non-Down's syndrome children failed to present with delayed phonological development typically reported for their English-speaking counterparts. The argument made is that cross-linguistic studies of intellectually impaired children's language acquisition provide evidence concerning language-specific characteristics of impairment, as opposed to those characteristics that, remaining constant across languages, are an integral part of the disorder. The results reported here support the hypothesis that the speech disorder typically associated with Down's syndrome arises from impaired phonological planning, i.e. a cognitive linguistic deficit.     

Unstable fractures of the upper thoracic spine

Unstable fractures of the upper thoracic spine are a therapeutic challenge because of the high rate of associated injuries and frequent occurrence of spinal cord lesions. This study focuses on the operative treatment of these injuries. We present nine patients with unstable injuries of the upper thoracic spine. According to the classification of Magerl et al., there are seven type C and two type B fractures. Eight patients had complete transverse lesions of the cord and one had no evidence of spinal cord injury. All patients presented associated injuries: nine patients had fractured ribs, three a fractured sternum and three a severe haemothorax. All underwent operative treatment: six posterior fusions only, two anterior interbody fusions only after thoractotomy owing to severe bleeding from ruptured intercostal arteries, and one a combined fusion after failure of posterior fusion. The treatment of these patients should be individualized, depending on the associated injuries, loss of blood owing to fractured spine and ruptured vessels and depending on the back pain resulting from an unstable thorax. In general, we prefer the posterior approach to unstable fractures of the upper thoracic spine.     

Maternal effects in infant and adult phenotypes of 5HT1A and 5HT1B receptor knockout mice

The influence of the pre- and postweaning maternal environment on the offspring's phenotype was examined in 5-HT1A and 5-HT1B receptor knockout mice (KO1A and KO1B, respectively). We have previously shown that, when born to and raised by homozygous dams of the same genotype, adult KO1A are more anxious than wild-type (WT) mice, and adult KO1B are hyperactive and slightly less anxious than WT mice. We extend our studies here to the behavioral results of the offspring's own genotype, when the dam's genotype is constant, and the effects of the dam's genotype when the offspring's genotype is constant. In Experiments 1 and 2, KO1A-/- pups produced less ultrasonic vocalizations (USV) than controls in an isolation test on postnatal Day 7 when born to and reared by KO1A dams, either -/- or +/-. Heterozygous F1 pups reared by KO1A-/- dams produced more USV and were less anxious in the plus-maze at 2 to 3 months of age than F1 pups born to and reared by WT dams (Experiment 3). F1 pups reared by KO1B-/- dams produced less USV and were more anxious in the plus-maze than F1 pups reared by WT dams (Experiment 4). The results support a role for maternal effects that may comprise direct effects such as the dam's behavior and nutritional care of the pup, and possibly more complex indirect effects through the establishment of idiosyncratic dam-pup dyadic interactions. We recommend that breeding techniques that rely on same genotype (mutant-mutant or WT-WT) breeding pairs not be used to generate offspring when the focus of research is the study of gene function, but rather when familial effects need to be studied.     

Electroretinography in rats

Basic mechanisms of the rat ERG were reinvestigated with contemporary methods of recording and photic stimulation via an optic fiber system connected with a contact lens. Flash stimulation and background illuminance were performed with photometrically defined light stimuli. ERGs recorded in darkness, from dark adapted rats, were similar with those observed in earlier work in which light flashes of much longer duration had been used. Flash stimulation carried out under stepwise increased background illuminance gave new information on the characteristics of oscillatory potentials of the ERG. In general the present observations agreed with the notion that the rods of the rat retina are as sensitive as in man, whereas the cones are functionally less efficient with respect to light sensitivity and temporal resolution. Differences in function of the cones from rat to man have to be kept in mind when using the rat ERG as a model for risk assessment in safety studies.     

Prevention of collagen-induced arthritis (CIA) by treatment with polyethylene glycol-conjugated type II collagen; distinct tolerogenic property of the conjugated collagen from the native one

Administration of a soluble protein into animals prior to challenge immunization induces immunological tolerance which is specific for the protein. In addition, chemical modification of proteins with polyethylene glycol (PEG) has been reported to convert the immunogenic proteins to become tolerogenic. However, differences in tolerogenic properties between PEG-modified proteins and the native counterparts have never been analysed. The ability of PEG-conjugated type II collagen (PEG-CII) to attenuate CIA, an animal model for rheumatoid arthritis, was compared with the native unconjugated CII. Groups of DBA/1 J mice were treated weekly with i.p. injections with PEG-CII, native CII, or vehicle alone for 3 weeks, before they were challenged with CII in adjuvants. The induction of tolerance was confirmed in both PEG-CII- and CII-pretreated mice when suppression of lymph node T cell proliferation in response to CII was noted. The degrees of suppression of T cell proliferation were comparable between the two pretreated groups. However, induction of arthritis and production of IgG anti-CII antibody were more markedly suppressed in PEG-CII-pretreated mice than in native CII-pretreated mice, although the severity of arthritis and antibody levels in the latter group were also lower than in control mice. IgG2a and IgG2b antibody levels were equally suppressed in the two pretreated groups, whereas the IgG1 level was significantly lower in the PEG-CII-pretreated group than in the native CII-pretreated group. The results provide the first evidence that attachment of PEG to CII renders the protein more tolerogenic.     

Survival and recovery of physiologic functions after early maternal separation in rats.

Fourteen-day-old rats separated from their mothers have greatly increased survival rates, if provided with a local heat source. Body weight, temperature, cardiac and respiratory rates declined for 3 days in all separated animals, and eye opening was delayed most in those separated at room temperature. In survivors, a second phase followed in which all measures rebounded to levels characteristic of normally mothered infants. Cardiac rate, having fallen 40 percent in the first days after separation, rose to levels higher than normally mothered infants at 21 and 30 days of age. Recovery was not clearly initiated by any singly system studied, although non-survivors showed greater weight and temperature loss and evidence of gross motor deficit during the separation response phase.