Alterations in dopamine release but not dopamine autoreceptor function in dopamine D3 receptor mutant mice

Dopamine (DA) autoreceptors expressed along the somatodendritic extent of midbrain DA neurons modulate impulse activity, whereas those expressed at DA nerve terminals regulate both DA synthesis and release. Considerable evidence has indicated that these DA autoreceptors are of the D2 subtype of DA receptors. However, many pharmacological studies have suggested an autoreceptor role for the DA D3 receptor. This possibility was tested with mice lacking the D3 receptor as a result of gene targeting. The basal firing rates of DA neurons within both the substantia nigra and ventral tegmental area were not different in D3 receptor mutant and wild-type mice. The putative D3 receptor-selective agonist R(+)-trans-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin+ ++-9-ol (PD 128907) was equipotent at inhibiting the activity of both populations of midbrain DA neurons in the two groups of mice. In the gamma-butyrolactone (GBL) model of DA autoreceptor function, mutant and wild-type mice were identical with respect to striatal DA synthesis and its suppression by PD 128907. In vivo microdialysis studies of DA release in ventral striatum revealed higher basal levels of extracellular DA in mutant mice but similar inhibitory effects of PD 128907 in mutant and wild-type mice. These results suggest that the effects of PD 128907 on dopamine cell function reflect stimulation of D2 as opposed to D3 receptors. Although D3 receptors do not seem to be significantly involved in DA autoreceptor function, they may participate in postsynaptically activated short-loop feedback modulation of DA release.     

The compartments of the hand: an anatomic study

To determine the nature and number of enclosed myofascial spaces in the hand, an anatomic study that included 21 cadaver hands was conducted using a gelatin injection method. Data were collected from the prepared cross-sections of each specimen. The results showed the thenar space to comprise 2 or more discrete compartments in 52% of the hands. In 76% of the specimens, the hypothenar space demonstrated at least 2 compartments. The adductor pollicis and first dorsal interosseous muscles were discrete compartments in 71% of the hands. The interosseous compartments demonstrated significant variability. The dorsal and palmar interosseous muscles were discrete compartments within the second interosseous compartment in 48% of the hands, within the third interosseous compartment in 67%, and within the fourth interosseous compartment in 33%. Subcompartmentalization of the enclosed myofascial spaces of the hand should be anticipated in cases requiring fasciotomy. Thorough inspection within anatomic areas or generous release of the muscular origin along the metacarpal at the time of fasciotomy is suggested to ensure complete inspection.     

Effects of immobilization restraint on Syrian golden hamsters

A 2 x 2 x 4 factorial design was used to study variation of protein and fat contents in beef broths as affected by cut type (flank, shank), salt treatments (addition of salt to the medium, no salt), and initial temperatures of simmering (25, 70, 75, and 100 degrees C). Flank portions yielded slightly more protein (0.29 g/100 mL) and had three-fold less fat (0.39 g/mL) than those of shank (0.25 and 1.12 g/mL, respectively) (P < 0.05). No linear relationship of temperature and amount of extractable components was observed, but it was clear that the greatest protein extraction was accomplished when meat was immersed in cooking water at boiling point (P < 0.05). In general, salting of water reduced fat content of beef broths. However, a significant Salting x Cut type interaction showed this effect was only present in shanks (P < 0.05). Conversely, the reducing effect (P < 0.05) of salting on amount of protein extracted from flank was not observed in shanks. Based on these data, we conclude that larger amounts of protein and less fat could be transferred from meat pieces to the medium by immersing beef in salted water at the boiling point.     

Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil

Increasing resistance of Plasmodium falciparum malaria parasites to chloroquine and the dihydrofolate reductase (DHFR) inhibitors pyrimethamine and cycloguanil have sparked renewed interest in the antimalarial drugs WR99210 and proguanil, the cycloguanil precursor. To investigate suggestions that WR99210 and proguanil act against a target other than the reductase moiety of the P. falciparum bifunctional DHFR-thymidylate synthase enzyme, we have transformed P. falciparum with a variant form of human DHFR selectable by methotrexate. Human DHFR was found to fully negate the antiparasitic effect of WR99210, thus demonstrating that the only significant action of WR99210 is against parasite DHFR. Although the human enzyme also resulted in greater resistance to cycloguanil, no decrease was found in the level of susceptibility of transformed parasites to proguanil, thus providing evidence of intrinsic activity of this parent compound against a target other than DHFR. The transformation system described here has the advantage that P. falciparum drug-resistant lines are uniformly sensitive to methotrexate and will complement transformation with existing pyrimethamine-resistance markers in functional studies of P. falciparum genes. This system also provides an approach for screening and identifying novel DHFR inhibitors that will be important in combined chemotherapeutic formulations against malaria.     

Sensitivity to insulin in thyrotoxicosis

Insulin and glucose-insulin sensitivity of peripheral tissues is studies in patients with thyrotoxicosis of different severity and duration. Three main types of the curves, characterizing exogenic insulin sensitivity, were detected. It was determined that a decrease in insulin sensitivity and insulin resistance prevailed in patients with disturbed glucose tolerance (the doubtful type of glycemic curve, latent diabetes). The results obtained do not eliminate the significance of insulin sensitivity failure in the affection of adaptive characteristics of the pancreatic insulin-producing apparatus in thyrotoxicosis.     

Compartment pressure in association with closed tibial fractures. The relationship between tissue pressure, compartment, and the distance from the site of the fracture

We studied twenty-five consecutive patients who had a closed tibial fracture to determine whether there was a relationship between compartment pressure and the distance at which the pressure was measured from the site of the fracture. Tissue pressure was measured in all four compartments of the leg at the level of the fracture and at five-centimeter increments proximal and distal to the fracture. The peak pressure was usually found at the level of the fracture and was always located within five centimeters of the fracture. The highest pressures were recorded in the anterior and the deep posterior compartments in twenty patients, including all five of those who had had a fasciotomy. The measured pressure decreased steadily when sampled at increasing distances proximal and distal to the site of the highest recorded pressure. Decreases of twenty millimeters of mercury (2.67 kilopascals) five centimeters adjacent to the site of the peak pressure were common. Compartment syndrome was diagnosed in five patients on the basis of clinical findings, and the diagnosis was confirmed when peak compartment pressures of more than the critical threshold (within twenty millimeters of mercury [2.67 kilopascals] of the diastolic blood pressure) were recorded. Three of these five patients had measured pressures that were less than the critical threshold within five centimeters of the site of the peak pressure. Failure to measure tissue pressure within a few centimeters of the zone of peak pressure may result in a serious underestimation of the maximum compartment pressure. Our results suggest that measurements should be performed in both the anterior and the deep posterior compartments at the level of the fracture as well as at locations proximal and distal to the zone of the fracture to determine reliably the location of the highest tissue pressure in a lower extremity when a compartment syndrome is suspected clinically. The highest pressure should be used in the decision-making process.     

Improved surgical technique for the establishment of a murine model of aortic transplantation

The Scope of Professional Practice states that nurses may respond to the needs of patients by expanding their practice. Performing skin biopsies for cancer diagnosis is one such area. The provision of appropriate education, training and updating is essential. Clear guidelines for practice are required for all such procedures.