An assessment of the routes of incorporation of opiates into beard hair after a single oral dose of codeine.

The time course of appearance of immunoreactive opiates was monitored in saliva, sweat, and beard hair in six healthy whites who were not opiate users after oral administration of 60 mg of codeine phosphate. The opiate concentration in saliva peaked within 30 min of drug administration and returned to near the predose level within 24 h. Ninety-one percent of the total secretion of opiates in sweat was collected by the skin-collection patch worn during the first 24 h after drug administration.

Oxidative metabolism in a rat hepatoma (N13) and isolated rat hepatocytes: a flow cytometric comparative study.

Recently, we have developed a new and fast kinetic method for assessing mitochondrial membrane potential by flow cytometry, based on the quantitation of the initial rate of rhodamine 123 (Rh123) uptake by living cells. This test has proved suitable to detect metabolic and toxic effects on mitochondria. To characterize energy metabolism in a rat hepatoma cell line (N13), we applied this method to assess several metabolic pathways that eventually generate mitochondrial membrane potential.

Protein kinase C-mediated phosphorylation does not regulate drug transport by the human multidrug resistance P-glycoprotein.

P-glycoprotein (P-gp) is an active transporter that can confer multidrug resistance by pumping cytotoxic drugs out of cells and tumors. P-gp is phosphorylated at several sites in the "linker" region, which separates the two halves of the molecule. To examine the role of phosphorylation in drug transport, we mutated P-gp such that it could no longer be phosphorylated by protein kinase C (PKC).

Small round cell tumors of bone and soft tissue. A morphometric and stereometric comparative analysis of 119 cases.

Objective: To analyze the discriminative capability of morphometric assessment of nuclear morphology in the differential diagnosis of small round blue cell tumors (SRCTs) of bone and soft tissue.

Study Design: The study material consisted of glutaraldehyde-fixed, resin-embedded, semithin sections from 119 human tumors. Nuclear area, perimeter, maximum diameter, form factors and nuclear density were measured in at least 300 nuclei per case.

Opiates inhibit ion conductances elicited by cell swelling and cAMP in cultured cells.

The effect of several opiate compounds on I- efflux was investigated in cultured cell lines. I- efflux was evoked by two distinct stimuli, namely cell swelling and elevation of cellular cAMP levels by prostaglandin E2. Cells expressing the multidrug resistance P-glycoprotein were found to have increased I- efflux in response to hypo-osmotic challenge.

Radial scar versus tubular carcinoma of the breast. A comparative study with quantitative techniques (morphometry, image- and flow cytometry).

The present study is focused on the differential diagnosis between radial scar (RS) and tubular carcinoma (TC) using morphometrical and cytophotometrical analysis (static and flow cytometry) of a number of histologically well-established RS cases (17 lesions) compared with 6 early infiltrating small TC with sclerotic stroma and pseudo-RS fields. One case displayed both RS and TC foci in contiguity. Mean nuclear area was larger in the group of tubular carcinomas (51.

Collateral sensitivity of multidrug resistant cells to narcotic analgesics is due to effects on the plasma membrane.

It has previously been demonstrated that opiates interact directly with P-glycoprotein in drug resistant Chinese hamster ovary (CHO) cells (Callaghan, R. and Riordan, J.R.

Interaction of tamoxifen with the multidrug resistance P-glycoprotein.

Tamoxifen is an anti-oestrogen which is currently being assessed as a prophylactic for women at high risk of breast cancer. Taxoxifen has also been shown to reverse multidrug resistance in P-glycoprotein (P-gp)-expressing cells, although the mechanism of action is unknown. In this study we demonstrate that tamoxifen interacts directly with P-gp.

Evaluating the long-term performance of a foam-core hospital replacement mattress.

Many hospitals have begun replacing their standard mattresses with pressure-reducing foam mattresses to eliminate the costly overlays that have been used for comfort and to protect patients at risk for development of pressure ulcers. Although researchers have tested the performance of new mattresses and have shown that many may be of use with patients at high risk, no information is available on the pressure-reducing capabilities of used mattresses. This study was designed to evaluate changes with use in the support characteristics of foam-core hospital replacement mattresses.

Factors affecting the hepatic elimination of oxidized and of glucoronidated high clearance drugs following acute administration of carbon tetrachloride.

The factors affecting drug elimination following acute administration of carbon tetrachloride (CCl4) were investigated using a perfused rat liver system. Morphine and pethidine were used as markers of hepatic glucuronidation and oxidation, respectively. Hepatoxicity of CCl4 was indicated by widespread cellular necrosis and raised serum asparatate aminotransferase levels.

The effect of a nutritional model of chronic liver injury on the hepatic glucuronidation of morphine in rats.

The effect of a choline-deficient diet on the hepatic glucuronidation of morphine was investigated using a rat perfused liver system. Rats fed a choline-deficient diet developed a fatty liver with minimal necrosis. Despite the morphological changes, neither hepatic extraction ratio (0.

Synthetic and natural opiates interact with P-glycoprotein in multidrug-resistant cells.

The ability of P-glycoprotein (P-gp) to transport naturally occurring and synthetic opiate analgesics was investigated. Multidrug-resistant Chinese hamster ovary cells (B30) were found to accumulate significantly lower amounts of morphine than their drug-sensitive counterparts (B1). This decreased accumulation was reversed upon depletion of cellular stores of ATP.

Hepatic enzyme activity is the major factor determining elimination rate of high-clearance drugs in cirrhosis.

The relative importance of alterations in hepatic enzyme activity, blood flow and drug binding to drug elimination in patients with liver disease remains controversial. In addition, liver disease appears to selectively impair drug oxidation pathways while leaving glucuronidation preserved. These studies using isolated perfused rat livers were designed to examine the effects of liver disease on the hepatic extraction and clearance and intrinsic clearance of morphine, a glucuronidated drug, and meperidine, an oxidized drug, under controlled blood flow and drug-binding conditions.

Increased accumulation of drugs in a multidrug resistant cell line by alteration of membrane biophysical properties.

Growth of CHRC5 multidrug resistant cells in media enriched in a saturated C-17 fatty acid, heptadecanoic acid, resulted in these cells accumulating vinblastine at a rate and to an extent comparable to that of the parental cell line AB1. The fatty acid-enriched growth media had no effect on the ability of AB1 cells to take up vinblastine. The action of amphiphiles on the uptake of rhodamine dyes by CHRC5 cells was compared with the increased dye accumulation affected by verapamil.

A comparison of membrane properties and composition between cell lines selected and transfected for multi-drug resistance.

Cell lines selected (CHRC5) and transfected (LR-73-1A) for multi-drug resistance have total lipid compositions which are indistinguishable between resistant and parental cells. Lipid composition was evaluated by 1H NMR and the total fatty acid content by GLC. No change in surface hydrophobicity, as measured with the fluorescent probe dansyl-PE, was observed as a result of transfection of CHO cells with the mdr1 gene.

Cytogenetics, flow cytometry, cytophotometry and morphometry of 22 cases of primary breast carcinoma. A comparative study.

Cytogenetic, flow cytometric, cytophotometric and morphometric analyses were performed on 22 previously untreated, primary solid breast carcinomas. Although the cell nuclei as the primary object of these studies were the same in all the tumors, distinct features were evaluated in each case to determine to what degree the results obtained by these techniques are comparable. From the cytogenetic viewpoint, six tumors had a modal number in the diploid range, seven were in the triploid range, and two in the tetraploid range; seven tumors had no modal number.

Cytophotometric analysis of glycogen, protein and DNA of a glycogen-storing rat hepatoma (N13) cell line.

This study examines the behavior of glycogen-storing rat hepatoma (N13) in vitro using cytophotometric techniques. A significant increase in glycogen is observed in these cells after 30 min incubation in a buffered solution containing 0.1 mM glucose, that is 80 times lower than the physiological glucose concentration in rat blood.

Morphometric and cytophotometric nuclear analysis of altered hepatocyte foci induced by N-nitrosomorpholine (NNM) and aflatoxin B1 (AFB1) in liver of Wistar rats.

The progressive morphological changes in the liver during neoplastic transformation have been studied by histological, cytophotometric and morphometric methods in male Wistar rats treated with two carcinogens: N-nitrosomorpholine (NNM) and aflatoxin B1 (AFB1). Cytophotometric and morphometric analysis of hepatocyte nuclei using Feulgen-stained tissue sections were performed in morphologically normal hepatic parenchyma and in early preneoplastic foci composed of altered hepatocytes. Foci of clear cells, mixed cells and large basophilic cells possessed a ploidy distribution similar to the surrounding non-transformed parenchyma, while the small hyperbasophilic cell foci were predominantly diploid.

Sexual differentiation of play behavior in the ferret.

Three experiments were performed to elucidate the endocrine mechanisms responsible for sex differences in the prepubertal play behavior of ferrets. In Experiment 1, gonadally intact adolescent males exhibited higher levels of "stand-over" behavior than females did in tests between 63 and 123 days of age with gonadally intact female partners of the same age. In Experiment 2, ferrets exposed to androgen or to ovarian steroids over Days 5-20 of postnatal life subsequently exhibited significantly higher levels of stand-over behavior in tests with female partners than did control females gonadectomized on Day 5 and not subsequently given any steroids.

Oxidized p-phenylenediamine: observations on the staining reaction in epoxy embedded tissues.

p-Phenylenediamine (PPD) is easily oxidized to brown compounds which stain acidic substrates. On account of the spontaneous oxidation process, the colour of PPD increases and becomes ochre-brown in a few days, showing an absorption peak at lambda = 510 nm with shoulder at about 440 to 460 nm. Studies on the application of oxidized PPD as a stain for semi-thin sections revealed that some tissue components could be clearly visualized.

Effects of neonatal castration and testosterone treatment on sexual partner preference in the ferret.

Groups of male and female ferrets were tested in a T maze to determine whether they preferred to approach and interact with a sexually active male or an estrous female. Control male and female ferrets gonadectomized (GX) on postnatal Day 35 and tested in adulthood while receiving no hormone or testosterone (T) displayed no significant preference. When given estradiol benzoate (EB), however, control males preferred stimulus females whereas control females preferred stimulus males.

Prostaglandin synthesis inhibition reverses the gastric antisecretory activity of somatostatin in anaesthetized rats.

The inhibitory action on somatostatin (ST) on the spontaneous and stimulated (pentagastrin 18 micrograms/kg/h i.v. and histamine 5 mg/kg/h i.

[Cytophotometric study of the DNA content of the liver of rats poisoned with N-nitrosomorpholine].

The evolution of ploidy of liver cells during malignant transformation by N-nitrosomorpholine was studied cytophotometrically. It was observed an increased ploidy that was due to the toxic action of the product and lasted six weeks, and a gradual return to normal values after the administration of the drug was discontinued.