The effect of calcium overdosages on the rate of eruption and periodontal ligament of lower incisor in albino rats

Thermal enhancement of cis-diamminedichloroplatinum (II) (DDP)-mediated antitumour activity and normal tissue toxicities by whole body hyperthermia were compared in a F344 rat model under different anaesthetic conditions. Whole body hyperthermia (WBH: 120 min at 41.5 degrees C) enhanced both DDP-mediated antitumour activity and toxic side-effects. Our present study shows that anaesthetics might influence the thermal enhancement ratios (TER) calculated for DDP-mediated normal tissue toxicity but did not influence the TER calculated for antitumour activity. The TER calculated for DDP-mediated antitumour activity was 2.9. As a result of the anaesthetics used, the TER calculated for kidney and gastrointestinal toxicity ranged from 1.8 to 4.5 and from 1.2 to 2.3, respectively. The TER estimated for DDP-mediated general toxicities varied between 2.9 and 4.0 for weight loss, and from 2.0 to 2.3 based on the LD50. The differential effect of anaesthetics on TER calculated for antitumour activity and normal tissue toxicity led to different therapeutic ratios. For example the therapeutic ratio for combined WBH and DDP, using kidney damage as an end-point for normal tissue damage, ranged from 0.6 (without anaesthesia) to 1.6 (using nembutal as anaesthetic). The significantly elevated platinum levels in serum, kidney, jejunum and tumour tissue after WBH treatment may explain the thermal enhancement of DDP-mediated antitumour activity and side-effects but no correlation could be found for the differences in DDP-mediated normal tissue toxicities induced by the anaesthetics.     

Skeletal muscle cell-derived insulin-like growth factor (IGF) binding proteins inhibit IGF-I-induced myogenesis in rat L6E9 cells

The insulin-like growth factors (IGFs) stimulate the differentiation of skeletal muscle cells. IGF binding proteins (IGFBPs), which are expressed by skeletal muscle cells, may enhance or inhibit IGF actions. To explore the role of skeletal muscle-derived IGFBPs in IGF-induced myogenesis, we compared the differentiation-inducing effects of IGF-I and des(1-3)IGF-I in rat L6E9 skeletal myoblasts. Des(1-3)IGF-I is a naturally occurring IGF-I analog with markedly reduced affinity for IGFBPs but with an affinity for the IGF-I receptor that is comparable to that for native IGF-I. We find that rat L6E9 cells produce principally IGFBP-4 and BP-6, with a minor component of IGFBP-5. Both IGFBP-4 and BP-6 accumulate during differentiation and increase further in response to IGF-I or des(1-3)IGF-I treatment. We find that an IGF-I analog with reduced affinity for IGFBPs is significantly more potent than native IGF-I in stimulating myogenesis (as assessed by myogenin messenger RNA abundance and muscle creatine kinase activity), indicating that IGFBPs expressed by skeletal muscle cells inhibit differentiation induced by IGF-I. In view of the relative abundance of IGFBP-4, its relatively high affinity for IGF-I and the low affinity of IGFBP-6 for IGF-I, it is likely that the inhibitory effect of rat skeletal muscle-derived IGFBPs on IGF-I-induced myogenesis is mediated principally by IGFBP-4.     

Application of Raney nickel to measure adducts of styrene oxide with hemoglobin and albumin

BACKGROUND: Although peripheral cryotherapy decreases the incidence of unfavorable anatomic outcomes in threshold retinopathy of prematurity (ROP), apnea, bradycardia, and lid edema can occur. Argon laser indirect ophthalmoscope photocoagulation has been used as an alternative to cryotherapy, with fewer adverse effects. Retinal lesions placed with diode lasers are deeper than similar argon laser lesions, and it is not known whether this difference could influence the response to ablative therapy. METHODS: Patients were enrolled under a prospective, randomized protocol. One eye of each patient with symmetric, threshold ROP was treated with an 814/815 nm diode laser, while the other eye was treated with cryotherapy. Patients with asymmetric diseases also were randomized for treatment in the threshold eye. RESULTS: Nineteen infants (33 eyes) were treated, ranging from 485 to 863 g birth weight (23 to 27 weeks gestational age); 18 patients (32 eyes) were followed for 3 months or longer. Four patients (8 eyes) had bilateral zone 1 disease. Postconceptional age was 36 to 45 weeks at the time of treatment. The diode laser treatment was better tolerated than cryotherapy, and the treatment apparatus was more easily transported. Apneic episodes requiring intubation resulted from two cryotherapy sessions but no diode laser sessions. Five cryotherapy-treated eyes required retreatment because of persistent disease with adjacent skip areas. In the group followed for 3 to 15 months, 1 cryotherapy-treated eye and 1 diode laser-treated eye progressed to stage 5 retinal detachment. CONCLUSION: Compared with cryotherapy, the diode laser was more convenient, technically easier to administer, and better tolerated by the patient. Although the number of patients was too small for meaningful statistical analysis of outcome, diode laser peripheral retinal ablation appeared to be as effective as cryotherapy for the treatment of threshold ROP.     

D2 receptors may modulate the function of the striatal transporter for dopamine: kinetic evidence from studies in vitro and in vivo

Recently it was hypothesized by others that the D2 dopamine receptor can regulate the uptake of dopamine. However, the evidence in support of this hypothesis, although compelling, was not based on observations related to direct measures of the kinetic activity of the transporter itself. Here kinetic evidence in support of this hypothesis is shown. The apparent time-resolved initial velocity of the transport of 1.0 microM dopamine into striatal suspensions, measured using rotating disk electrode voltammetry, was found to increase in the presence of the D2 receptor agonist, quinpirole, at 100 nM. This effect was reversed by sulpiride. In separate studies it was shown that acute and chronic treatments with haloperidol at 0.5 mg/kg, i.p., reduced the reuptake transport of dopamine in vivo following intrastriatal stimulation of its release by K+. Thus, it appears that D2 receptors may influence the functioning of the striatal transporter for dopamine. These results are consistent with a model in which presynaptically released dopamine may feed back onto the function of its transporter to increase the velocity of the clearance of synaptic dopamine following an action potential, suggesting the existence of a mechanism, in addition to release and synthesis modulation, for fine-tuning dopaminergic chemical signaling.