Improved long-term bone-implant integration Experiments in transgenic mice overexpressing bovine growth hormone

Several recent studies have investigated the effects of growth hormone (GH) on the healing of fractures and bone ingrowth, but with conflicting results. The negative results may be due to antibody formation against injected GH or because some experimental models are able to prove only positive GH effects. In this study, we wanted to investigate the effect of GH on implant integration in bone. To avoid potential formation of antibodies against injected GH, we used a model with transgenic mice overexpressing bovine GH (bGH).

Titanium implants were inserted in the forehead of the mice. 4 months after insertion, the implants were cut out en bloc with the surrounding bone. The calcified specimens were cut and ground to a thickness of approximately 10m. Histomorphometry demonstrated significantly more direct bone-to-metal contact in the transgenic mice than in the nontransgenic littermates. Our findings indicate that systemic administration of GH in humans may improve implant integration in bone.     

Sex-specific effects for body mass index in the new Norwegian twin panel

Sex-specific effects for body mass index (BMI) were explored in a newly established, population-based Norwegian twin panel. The sample includes 5,864 individuals, aged 18–25 years, who responded to a questionnaire containing items for zygosity classification, height, weight, health, health-related behaviors, well-being, and demographic information. Among the 2,570 intact pairs who returned the questionnaire there were 416 identical (MZ) male pairs, 387 fraternal (DZ) male pairs, 528 MZ female pairs, 443 DZ female pairs, and 796 unlike-sexed pairs. Alternate sets of models testing for either sex-specific genetic or environmental parameters were evaluated using structural equation analysis. Results from the most parsimonious model indicated that the genes contributing to variation in BMI are not identical for men and women; rather, some genetic effects were shared by the sexes and some were unique to each sex. Total variation in BMI could be explained by sex-specific additive genetic effects, as well as genetic and non-shared environmental effects common to men and women. Estimates of heritability were .708 for men and .789 for women, and the male-female genetic correlation was 0.622. The series of models specifying sex-specific shared environment also fit the data and suggests that shared environmental factors may be important for males but not for females. The findings raise questions concerning the relationship between sex-specific effects for BMI and sex differences in health outcomes. ©1995 Wiley-Liss, Inc.     

Receptor binding of N-(methyl-11C) clozapine in the brain of rhesus monkey studied by positron emission tomography (PET)

By means of positron emission tomography the uptake and kinetics of N-(methyl-¹¹C)clozapine in different brain regions have been studied in Rhesus monkeys. ¹¹C-clozapine rapidly entered the brain and maximum radioactive uptake was seen 5–12 min after administration. Highest uptake was measured in the striatum. Other regions with an uptake higher than in the cerebellum were thalamus and mesencephalon. The radioactivity from different brain regions decreased with an elimination half-life of about 5 h and parallelled the plasma kinetics of unlabelled clozapine. The striatum/cerebellum ratio of ¹¹C-clozapine-derived radioactivity remained constant during the period studied and did not change after pretreatment with atropine. In contrast, the striatum/cerebellum ratio was somewhat lower after pretreatment with N-methylspiperone (NMSP), indicating competition for the same binding sites in the striatum. After pretreatment with increasing doses of clozapine, a dose-dependent protection of binding sites in the striatum for ¹¹C-NMSP was seen. It is concluded that clozapine is more loosely bound to dopamine receptors in the striatum than N-methylspiperone and that the kinetics of clozapine in the brain parallel that in the plasma. The binding properties of clozapine within the brain may explain some of the clinical properties of the drug.     

Interactions between serotonin and substance P in the spinal regulation of nociception

Interactions between 5-hydroxytryptamine (5-HT) and substance P (SP) in the mouse spinal cord were investigated using the tail-flick test and the behavioral response evoked by intrathecal (i.th.) SP or i.th. 5-HT. I.th. injection of 5-HT (20 μg) or the 5-HT₁ receptor agonists(+)-8-hydroxy-2-(di-n-propylamino)tetralin ((+)-8-OH-DPAT) (20 μg) or 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole (RU 24969) (20 μg) markedly inhibited the tail-flick reflex. The effect of these compounds was reduced when SP (5 μg) was given i.th. 55 min, or 55 and 45 min before the agonists. The tail-flick latencies recorded 5 min before injection of a 5-HT agonist were similar in animals treated with SP or vehicle. The changes in the tail-flick test were not due to changes in tail skin temperature since only minimal differences in the skin temperature were recorded between the groups injected with SP or vehicle. I.th. injection of SP (10 ng) or 5-HT (2 μg) produced a similar behavioral response consisting of biting, licking and scratching of the caudal part of the body, indicative of nociceptive stimulation. The responses both to i.th. SP and 5-HT were reduced after i.th. application of SP receptor antagonist [d-Arg¹,d-Trp^7,9,Leu¹¹]-SP (Spantide) (5 μg), as well as 5 min after i.th. injection of the 5-HT receptor antagonist metergoline (4 μg). The data may indicate functional interactions between SP and 5-HT in the mouse spinal cord, which may take place in neurons involved in the processing of nociception.     

Contractile properties of in situ perfused skeletal muscles from rats with congestive heart failure

We hypothesized that in congestive heart failure (CHF) slow-twitch but not fast-twitch muscles exhibit decreased fatigue resistance in the sense of accelerated reduction of muscle force during activity. Experiments were carried out on anaesthetized rats 6 weeks after induction of myocardial infarction or a sham operation (Sham). Animals with left ventricular end-diastolic pressure (LVEDP) > 15 mmHg under anaesthesia were selected for the CHF group. There was no muscle atrophy in CHF. Force generation by in situ perfused soleus (Sol) or extensor digitorum longus (EDL) muscles was recorded during stimulation (trains at 5 Hz for 6 s (Sol) or 10 Hz for 1.5 s (EDL) at 10 or 2.5 s intervals, respectively) for 1 h in Sol and 10 min in EDL at 37 °C. Initial force was almost the same in Sol from CHF and Sham rats, but relaxation was slower in CHF. Relaxation times (95–5 % of peak force) were 177 ± 55 and 131 ± 44 ms in CHF and Sham, respectively, following the first stimulation train. After 2 min of stimulation the muscles transiently became slower and maximum relaxation times were 264 ± 71 and 220 ± 45 ms in CHF and Sham, respectively (   P < 0.05  ). After 60 min they recovered to 204 ± 60 and 122 ± 55 ms in CHF and Sham, respectively (   P < 0.05  ). In CHF but not in Sham rats the force of contraction of Sol declined from the second to the sixtieth minute to 70 % of peak force. The EDL of both CHF and Sham fatigued to 24–28 % of initial force, but no differences in contractility pattern were detected. Thus, slow-twitch muscle is severely affected in CHF by slower than normal relaxation and significantly reduced fatigue resistance, which may explain the sensation of both muscle stiffness and fatigue in CHF patients.     

Prevention of Secondary Insults in Neurointensive Care of Traumatic Brain Injury

Background: Secondary insults/complications have a major impact on the prognosis after traumatic brain injury (TBI). The aim was to study the occurrence and prognostic value of secondary insults occurring in TBI patients, during standardized neurointensive care (NIC) dedicated to avoiding secondary insults. Material and Methods: 154 patients, 17-79 years, with acute head trauma and pathologic CT, treated during a 2-year period at the NIC unit were studied. The occurrence of defined secondary insults (standard and severe) was recorded during the 1st week of NIC from bedside surveillance charts containing one value per hour and parameter (intracranial pressure, cerebral perfusion pressure, systolic blood pressure, PaO₂, temperature, and blood glucose). The data set was analyzed using univariate and multivariate logistic regression with favorable outcome as the response variable. Both admission variables (Glasgow Coma Scale Motor Score [GCS M], CT class, Injury Severity Score [ISS], age, and gender) and secondary insult variables were included as explanatory variables. Results: In total, 1,570 insults were identified (320 severe). In the univariate analysis, the sum of all insults, blood glucose, GCS M, CT class, and ISS showed significant effects on outcome (p < 0.05). In the multiple regression analysis, GCS M was the only significant explanatory variable. Conclusions: The occurrence of secondary insults in the NIC unit was not negligible, despite the fact that major efforts were made to avoid them. The sum score of all insult categories and high blood glucose had a statistically significant effect on favorable outcome in the univariate analysis, but secondary insults did not add any prognostic information to the neurologic grade in the multivariate analysis. This finding indicates that the insults that occurred were related to the degree of primary injury/neurologic grade.