Biochemical effects of two promoters of hepatocarcinogenesis in rats

The effects of two promoters of hepatocarcinogenesis--phenobarbital and butylated hydroxytoluene (BHT)--on five hepatic biochemical parameters were examined in adult female rats. Phenobarbital given orally in two doses each of 110 mg/kg 21 and 4 hr before the rats were killed caused large increases in hepatic ornithine decarboxylase (ODC) activity and cytochrome P-450 content. Extending the number of phenobarbital treatments to five increased the hepatic enzyme induction and also caused a minor decrease in hepatic glutathione and a small increase in serum alanine aminotransferase activity. Two oral doses of 700 mg BHT/kg (20% of the LD50) caused hepatic DNA damage and induction of both ODC activity and cytochrome P-450 content. When the dose of BHT was reduced from 700 to 140 mg/kg no significant effects on the biochemical parameters were found. Both promoters of hepatocarcinogenesis were identified by their induction of ODC, a marker for promotional potential, but only BHT showed a potential for carcinogenic initiation. The biochemical parameters examined, particularly the alkaline elution technique for DNA damage, ornithine decarboxylase activity and serum alanine aminotransferase, may constitute a useful assay system for examining a compound's potential for carcinogenic initiation, carcinogenic promotion and cellular toxicity.     

Food deprivation and hypothalamic neuropeptide gene expression: effects of strain background and the diabetes mutation.

We have used a novel method to identify genes expressed in the hypothalamus which may be potentially involved in controlling food intake and energy metabolism. We assumed that food deprivation, a powerful stimulus of food intake, would stimulate the activity of neural pathways involved in feeding behavior which should be reflected in an increase in the synthesis of any relevant neuropeptide and its messenger RNA. A study of 5 neuropeptides in 5 strains of mice has identified neuropeptide Y (NPY) as a gene whose expression in the hypothalamus is controlled by nutritional status, suggesting that hypothalamic NPY neurons are a link in the neural network regulating feeding behavior and energy metabolism. In addition, we have studied the effect of the diabetes mutation on neuropeptide gene expression during fasting and refeeding. Our findings suggest that abnormal NPY and enkephalin gene expression in the hypothalamus may be two important determinants of the expression of the diabetes mutation.     

Glutamate receptor antagonists block cocaine-induced convulsions and death.

The involvement of excitatory amino acid (EAA) receptors in mediation of the toxic effects of cocaine was studied in male ICR mice. Cocaine HCl (90 mg/kg, IP) induced seizures in 95% and death within 24 h in 68% (n = 135) of the animals. There was a significant correlation (r = .54) between the time to onset of convulsions and the time to death in mice which died within 30 min of injection (n = 84). Pretreatment with selected EAA receptor antagonists 15 min prior to cocaine differentially blocked cocaine toxicity. Selective N-methyl-D-aspartic acid (NMDA) receptor antagonists (MK-801, dextrorphan, CPP) decreased both the incidence of seizures and mortality. A nonselective EAA antagonist, kynurenic acid, decreased lethality in doses which did not reduce convulsions. A similar action was observed following pretreatment with the selective kainic acid/AMPA receptor antagonist, GDEE. Antagonists at EAA receptors can provide significant protection against cocaine-induced toxicity. Moreover, the data provide evidence for the involvement of both NMDA and non-NMDA receptor subtypes in aspects of cocaine toxicity.     

Plasma beta-endorphin immunoreactivity during graded cycle ergometry

The present study was undertaken to define the response of plasma beta-endorphin immunoreactivity (ir-BE) to exercise of increasing intensity. Nineteen healthy males performed continuous exercise for 32 min on a cycle ergometer, comprised of 8-min bouts at %VO2max approximating 25, 50, and 75% of maximal exercise. Venous blood samples were collected before exercise (T = -20 and 0 min), during exercise (T = 8, 16, 24, and 32 min), and in recovery (T = +15, +30 min). Ir-BE in plasma was measured by radioimmunoassay using Immuno Nuclear assay kits. Plasma ir-BE level (pg X ml-1) was not altered from pre-exercise (18.3 +/- 1.3) after 8 min of exercise at 25 and 50% VO2max intensity; however, ir-BE rose significantly after 8 min of 75% VO2max work intensity (27.1 +/- 2.4) and was further elevated at maximal exercise (74.1 +/- 8.6). Ir-BE level remained elevated 15 min (60.9 +/- 8.1) and 30 min (35.2 +/- 5.2) post-exercise. The response pattern was further characterized by a significant (P less than 0.05) inter-individual variation, both at rest and during exercise; also, regression analysis indicated the ir-Be levels attained at maximal exercise were inversely related to the relative VO2max (ml X kg-1 X min-1) of the subject (predicted ir-BE = 248.2 - 3.39 VO2max; r = -0.397, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Percutaneous management of lymphatic fluid collections

Eight lymphatic fluid collections were drained percutaneously. There were no immediate or late complications. Seven patients had follow-up; 1 required surgical drainage of a residual or recurrent lymphocele, and another had reaccumulated fluid in a lymphocele which was detected on autopsy. The remaining lymphatic collections responded to percutaneous drainage. Percutaneous drainage is safe and can be an effective tool in the management of lymphatic collections.     

A comparison of Nd:YAG laser damage thresholds for PMMA and silicone intraocular lenses

Power density producing damage at a probability of 0.5 (ie, damage threshold, DT-50) was determined for PMMA (with/without UV absorber) and Silicone intraocular lenses. Scattered light from a collinear diagnostic He:Ne beam was one of four damage monitors deployed to enhance the sensitivity of the system. In order of increasing laser resistance the following results were obtained: injection molded PMMA (1.9/GW/cm2) Silicone (2.63 GW/cm2) Lathe-cut PMMA (4.47 GW/cm2), Lathe-cut PMMA with UV absorber (8.32 GW/cm2), Cast-molded PMMA (12.30 GW/cm2). An analysis of variance revealed interclass differences significant at the .01 level. Cast-molded PMMA was the most laser-resistant IOL material.     

Human osteoblasts' proliferative responses to strain and 17beta-estradiol are mediated by the estrogen receptor and the receptor for insulin-like growth factor I.

The mechanism by which mechanical strain and estrogen stimulate bone cell proliferation was investigated using monolayer cultures of human osteoblastic TE85 cells and female human primary (first-passage) osteoblasts (fHOBs). Both cell types showed small but statistically significant dose-dependent increases in [3H]thymidine incorporation in response to 17beta-estradiol and to a single 10-minute period of uniaxial cyclic strain (1 Hz). In both cell types, the peak response to 17beta-estradiol occurred at 10(-8) - 10(-7) M and the peak response to strain occurred at 3500 microstrain ((mu)epsilon). Both strain-related and 17beta-estradiol-related increases in [3H]thymidine incorporation were abolished by the estrogen receptor (ER) modulator ICI 182,780 (10-8 M). Tamoxifen (10(-9) - 10(-8) M) increased [3H]thymidine incorporation in both cell types but had no effect on their response to strain. In TE85 cells, tamoxifen reduced the increase in [3H]thymidine incorporation associated with 17beta-estradiol to that of tamoxifen alone but had no such effect in fHOBs. In TE85 cells, strain increased medium concentrations of insulin-like growth factor (IGF) II but not IGF-I, whereas 17beta-estradiol increased medium concentrations of IGF-I but not IGF-II. Neutralizing monoclonal antibody (MNAb) to IGF-I (3 microg/ml) blocked the effects of 17beta-estradiol and exogenous truncated IGF-I (tIGF-I; 50 ng/ml) but not those of strain or tIGF-II (50 ng/ml). Neutralizing antibody to IGF-II (3 microg/ml) blocked the effects of strain and tIGF-II but not those of 17beta-estradiol or tIGF-I. MAb aIR-3 (100 ng/ml) to the IGF-I receptor blocked the effects on [3H]thymidine incorporation of strain, tIGF-II, 17beta-estradiol, and tIGF-I. HOBs and TE85 cells, act similarly to rat primary osteoblasts and ROS 17/2.8 cells in their dose-related proliferative responses to strain and 17beta-estradiol, both of which can be blocked by the ER modulator ICI 182,780. In TE85 cells (as in rat primaries and ROS 17/2.8 cells), the response to 17beta-estradiol is mediated by IGF-I, and the response to strain is mediated by IGF-II. Human cells differ from rat cells in that tamoxifen does not block their response to strain and reduces the response to 17beta-estradiol in TE85s but not primaries. In both human cell types (unlike rat cells) the effects of strain and IGF-II as well as estradiol and IGF-I can be blocked at the IGF-I receptor.     

Endoscopic pterygopalatine space surgery

Although lesions of the pterygopalatine space are uncommon, there are instances in which this relatively inaccessible region must be entered for biopsy or excision of masses. Traditional open approaches to the pterygopalatine space, involving external or intraoral incisions, provide limited visualization and carry associated morbidities. The evolution and advancement of endoscopic sinus surgical technique in recent years has led to its application to anatomic areas outside the strict limits of the sinonasal cavities. Such minimally invasive approaches are safe, effective, and spare unnecessary discomfort to the patient. This article describes the authors' method for performing an endoscopic approach to the pterygopalatine space.