Effect of immobilization on skeletal muscle nicotinic cholinergic receptors in the rat

The effect of 4 weeks of hind limb immobilization on nicotinic acetylcholinergic receptors (nAChRs) in the neuromuscular junction of the soleus (SOL) and tibialis anterior (TIB) muscles was studied in rats. Quantitative measurements of the receptors was performed using [3H]alpha-bungarotoxin ([3H]alpha-BTx) receptor autoradiography. Junctional and extrajunctional nAChRs were significantly increased in the SOL and TIB after 4 weeks immobilization. However, a significant decrease in fiber cross-sectional area was observed only in the SOL muscle. Remobilization for 4 weeks reversed the changes in cholinergic receptors and muscle fibers but not in bone. Our findings suggested that lack of nerve impulses are of importance for the events that take place after immobilization leading to muscle atrophy and osteoporosis.     

High-dose edatrexate with oral leucovorin rescue: a phase I and clinical pharmacological study in adults with advanced cancer

Our objective was to determine the maximum tolerated dose and toxicity of i.v. edatrexate with p.o. leucovorin. Thirty-one adults with advanced solid tumors received edatrexate as a 2-h infusion, once a week for 3 weeks, recycled every 28 days. p.o. leucovorin (10 mg/m2, every 6 h for 10 doses) began 24 h later. All had urinary alkalinization and p.o. hydration. Nine dosage levels ranging from 120 to 3750 mg/m2 were explored. Fatigue, epistaxis, nausea/emesis, mucositis, rash, myalgias, leukopenia, thrombocytopenia, and transient elevations of serum aspartate transferase were observed. Leukoencephalopathy with clinical manifestations occurred in two patients (one had prior cranial irradiation). Pharmacokinetic studies carried out at the 120- and 1080-mg/m2 dose levels revealed no significant difference in the elimination half-life at the two dose levels studied and no significant intrapatient variability between day 1 and day 8 edatrexate administration. Serum edatrexate levels measured using a dihydrofolate reductase inhibition assay correlated with those by high-performance liquid chromatography. Three major and two minor antitumor responses occurred. The maximum tolerated dose was 3750 mg/m2, with grade 3 or 4 leukopenia (one patient), stomatitis (one patient), and leukoencephalopathy (one patient). Because of the occurrence of leukoencephalopathy, further study of high-dose edatrexate with leucovorin rescue is not recommended.     

Succession of mutations in the Sabin strain of type 3 poliovirus replicating in the central nervous system of monkeys

Pentachlorophenol (PCP), which has been used as a wood preservative, was reported to be a liver carcinogen in mice. To investigate the initial effects of PCP administration under the same conditions of exposure as in the carcinogenic study, we examined oxidative stress and cell proliferation, along with other hepatotoxicological parameters, in the livers of B6C3F1 mice fed PCP in their diet at doses of 0.03, 0.06, and 0.12% for up to 4 weeks. We observed significant increases of 8-OHdG levels in hepatic nuclear DNA at doses of 0.03% and above at 2 and 4 weeks. Likewise, dose-dependent increases in the labeling index of cells were detected by counting those that had incorporated 5-bromo-2'-deoxyuridine throughout the experimental period. Also, we found significant elevations of the liver weights, concurrent with increases in hepatic DNA content in the treated mice, which again were dose-related. Serum aspartic transferase activity at doses of 0.06% and above were significantly increased despite these changes being slight. Also, histopathological examination provided no evidence of necrotic changes, but severe hepatocyte swelling in the treated mouse livers. These data indicate that PCP might be able to induce cell proliferation in the mouse liver, as well as induce oxidative DNA damage, suggesting both changes may play an important role in hepatocarcinogenesis.     

Pregnancy complicated by diabetes mellitus, superimposed preeclampsia, and adult respiratory distress syndrome: a case study

Pregnancy complicated by insulin-dependent diabetes mellitus carries severe physiologic risks for both the mother and the fetus. This article presents a case study to illustrate disease progression through multiple systems and psychosocial complications associated with diabetes mellitus in pregnancy. The case study also illustrates the role of nursing interventions, the use of technology, and interdisciplinary collaboration in caring for the patient and her family.     

TIMP1 and adverse prognosis in non-small cell lung cancer

Antisera were developed that specifically recognize orphanin FQ/nociceptin, the 17 amino acid peptide reported to be the endogenous ligand for the orphan opioid receptor. Immunocytochemical localizations in rat spinal cord demonstrated that orphanin FQ /nociceptin-immunoreactivity (-ir) was abundant in superficial dorsal horn, lateral spinal nucleus and the region dorsal to the central canal, areas that also exhibit prominent enkephalin-and dynorphin-ir. Orphanin FQ/nociceptin-ir was not affected by dorsal rhizotomy, indicating that in spinal cord the peptide is produced by central rather than primary afferent neurons. thus, the distribution of orphanin FQ/nociceptin-ir appeared in neuronal circuits that parallel those containing enkephalin- and dynorphin-ir, with only modest co-existence of these peptides.     

Effect of phenylpropanolamine and related compounds on beta-adrenoceptor-induced activation of adenylyl cyclase

While oral administration of therapeutic doses of phenylpropanolamine (PPA) does little to cardiovascular function in humans, intravenous doses administered to experimental animals are known to alter heart rate and blood pressure. Previous in vivo and in vitro studies have documented a beta-adrenoceptor agonist action for PPA and thus it was of interest to investigate whether these effects could be partially mediated by a direct interaction with beta-adrenoceptors. Phenylpropanolamine, [1R, 2R]-(-)-norephedrine, [1S, 2S]-(+)-norephedrine, [1S, 2R]-(+)-norpseudoephedrine, [S]-(+)-amphetamine, and [1R, 2S]-(-)-ephedrine, were compared with the known beta-adrenoceptor agonists [R]-(-)-epinephrine (EPI), [R]-(-)-norepinephrine (NE), and [R*, S*]-(+/-)-isoproterenol (ISO) for their ability to increase the intracellular concentration of cyclic-3',5'-adenosine monophosphate (cAMP) in minces of rat heart. Of the compounds investigated only NE, EPI, and ISO, as well as, forskolin, which directly stimulates adenylyl cyclase, significantly (p < 0.05) increased intracellular levels of cAMP. The other phenethylamines were without effect. The results of this study demonstrate that PPA and its diastereomers do not act directly at beta-adrenoceptors to alter cardiac function and supports the hypothesis that significant agonist activity of beta-phenethylamines at the beta-adrenoceptor requires phenolic/aryl ether substitution on the phenyl-ring (typically positions 3, 4 and/or 5).     

Bacterial endophthalmitis following sutureless cataract surgery

1. The premise of this review is that many of the biological effects of Pb are reflection of tissue peroxidation. 2. Enhanced tissue levels of arachidonic acid in Pb toxicosis appear to be involved in the peroxidative changes. 3. The altered arachidonate metabolism may be related to changes in membrane structure and function. 4. The induction of enhanced glutathione levels in animal tissues by Pb may afford protection from peroxidative damage.     

Do androgens regulate growth hormone-binding protein in adult man?

To determine whether adult serum GH-binding protein (GHBP) is regulated by androgen, serum GHBP concentrations were compared between 20 normal and 18 hypogonadal men matched for age and body mass index, and the effect of im testosterone treatment (250 mg testosterone enanthate) on GHBP levels in the 18 hypogonadal men was studied. Nine of the hypogonadal subjects had coexistent GH deficiency. Serum GHBP concentration was measured by a ligand immunofunctional assay. The mean serum GHBP level in untreated hypogonadal men was not significantly different from that of normal men (0.98 +/- 0.15 vs. 1.17 +/- 0.16 nmol/L). The mean serum insulin-like growth factor I (IGF-I) level was significantly lower in the hypogonadal men (132 +/- 22 vs. 206 +/- 17 ng/mL; P < 0.01). Basal testosterone (3.7 +/- 0.7 nmol/L) in hypogonadal men increased during treatment to a mean level of 29.1 +/- 2.8 nmol/L, which was not significantly higher than that in normal men (22.6 +/- 1.9 nmol/L). The mean serum GHBP level in hypogonadal men fell significantly during treatment to 0.60 +/- 0.11 nmol/L (P = 0.0003), whereas the serum IGF-I level rose significantly to 151 +/- 26 ng/mL (P < 0.04). The decrease in GHBP level was significant in both the GH-sufficient and GH-deficient subjects (P < 0.02 in both instances), whereas the increase in IGF-I level was significant in the GH-sufficient group (199 +/- 22 to 235 +/- 29 ng/mL; P < 0.04) but not in the GH-deficient group (53 +/- 7 to 55 +/- 5 ng/mL; P > 0.8). Thus, serum GHBP is normal in hypogonadal men but is reduced by testosterone treatment irrespective of endogenous GH-secretory status. It was concluded that the effect of testosterone on GHBP is pharmacological and occurs independent of GH mediation.