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We studied the correlation between the in vitro contracture test (IVCT) performed in malignant hyperthermia (MH) and the muscle fiber type composition in 29 human vastus lateralis (VL) biopsy samples (from 12 women and 17 men) using a semiautomated image analyzer. Relative number, lesser diameter, global area, and spatial distribution of the muscle fibers were measured. In these and in 26 additional VL muscle biopsy samples of patients with other myopathies, we compared our morphometric data with the observations made by the pathologist. Among the MH group, type 1 fibers were larger in both malignant hyperthermia susceptible (MHS) men and women reaching statistical significance only in the latter. The relative number and global area were unchanged. In MHS patients relative number and global area of type 2A fibers were smaller. No changes in the parameters of type 2B fibers were found. In a minority of sections (14%) clustering was observed. Sex-related alterations in type 2 fiber characteristics were found between MHS patients. However, our findings do not clearly point towards a syndrome-induced alteration of size, number, global area, or distribution of type 1, 2A, and 2B muscle fibers in VL of MH patients. By morphometric analysis, we found several additional biopsy samples that met the interpretation of "abnormal" size and number of muscle fibers in human malignant hyperthermia than were reported by the pathologist.

Nephron loss leads to increased production of reactive oxygen intermediates. We measured the effect of carvedilol, a beta-blocking drug with radical scavenging properties, on renal function, glomerulosclerosis, antioxidant enzyme status and in vivo hydrogen peroxide (H2O2) production in rats with chronic renal failure caused by 5/6 nephrectomy (remnant kidney) and compared results to data obtained with propranolol, a beta-blocking drug without scavenging characteristics. Carvedilol and propranolol were administered during 11 weeks following reduction of nephron number. Kidneys were examined using enzymatic and histological techniques. Both carvedilol and propranolol decreased systolic blood pressure. Compared to propranolol, carvedilol offered some additional beneficial effects on renal function, particularly with regard to glomerulosclerosis. Lipid peroxidation, evaluated by malonaldehyde and 4-hydroxynonenal concentration in cortex homogenates, was decreased in carvedilol-treated rats only. Superior beneficial effect of carvedilol treatment is not linked to a significant up-regulation of the activities of the remnant kidney antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase) or to a decreased in vivo H2O2 production.

We report a patient with fibrinogen storage disease in which there was proliferation of normal-sized peroxisomes in the hepatocytes. this phenomenon has previously been described in several acquired liver diseases. We believe that this is an adaptation response due to decreased microsomal isoenzyme activity as a result of the excess accumulation of fibrinogen in the endoplasmic reticulum.

C 26:0/C 22:0 ratio can be experimentally increased in serum of normal rats by oral administration of hexacosanoic acid (C 26:0) or of thioridazine, an inhibitor of peroxisomal beta-oxidation. This causes a decreased corticosterone response as well as decreased mobilization of cholesterol esters in zona fasciculata interna cells following ACTH administration. Zona fasciculata interna cells and their nuclei are enlarged and contain more Feulgen DNA in thioridazine-fed rats. The similarity of adrenocortical response to inhibition of peroxisomal beta-oxidation and to C 26:0 administration points to raised VLCFA as the common factor which is also operative in many peroxisomal diseases accompanied by adrenocortical function defects.

We investigated hepatic catalase activity, and morphologic and morphometric alterations of hepatocellular peroxisomes after catalase cytochemistry, in mice given a diet supplemented with 10% Beromegan, a commercial fish oil preparation, for up to three days. Fish oil is rich in docosahexaenoic acid (C22:6 (n-3)) and in eicosapentaenoic acid (20:5 (n-3)). Hepatic catalase activity showed a gradual increase in mice fed this diet, being significantly increased (136 +/- 10 UB/g liver) after three days when compared top controls (85 +/- 11 UB/g liver). Light microscopy indicated an increase in peroxisomal staining and peroxisomal proliferation. The latter observation was confirmed by ultrastructural morphometry: number, volume density and surface density of the peroxisomes were more than doubled after a three day diet containing fish oil. Peroxisomal size was not changed. These alterations are suggestive for an increased peroxisomal metabolism induced by a diet rich in poly-unsaturated fatty acids.

Chlorpromazine and related drugs including trifluoperazine, clopenthixol, and fluphenazine are in vitro inhibitors of mitochondrial carnitine palmitoyltransferase and cytochrome c oxidase and of peroxisomal carnitine octanoyltransferase from mouse heart and liver. By contrast with 0.1% ethyl 2(5(4-chlorophenyl)pentyl) oxiran-2-carboxylic acid or 0.1% clofibrate-containing diets, the treatment of mice with 0.1% chlorpromazine-containing diet fails to induce peroxisomal proliferation in liver and heart. An 0.5% chlorpromazine-containing diet did induce peroxisomal proliferation. Inhibition of peroxisomal beta-oxidation presumably via the reduction of carnitine octanoyltransferase by chlorpromazine elicits the appearance in liver of lamellar structures resembling those seen in human peroxisomal disorders and induces accumulation of very long-chain fatty acids in plasma. The peroxisomal proliferation induced by administration of high dose chlorpromazine is ascribed to its ability to depress mitochondrial fatty acid oxidation by impairing cytochrome c oxidase and carnitine palmitoyltransferase activities.

Evidence is given that phenothiazines depress hepatic peroxisomal fatty acid oxidation in vivo. After oral administration to rats thioridazine and chlorpromazine inhibit peroxisomal β-oxidation, evaluated by H2O2 production, during 2 weeks. In mice, this effect could not be demonstrated. However, in both species VLCFA are increased after short and long term drug administration. Electron microscopy reveals the presence of membranous structures in liver cytoplasm or lysosomes. The inhibition by thioridazine of peroxisomal β-oxidation does not lead to hepatic peroxisome proliferation. The activities of enzymes related to fatty acid breakdown are not increased and liver peroxisomes are microscopically normal.

1. 1. In hypoxic conditions Artemia salina L. forms 3 hemoglobins, which until now had only been characterized by their electrophoretic mobility. 2. 2. We have analysed the oxygen-binding properties of these 3 hemoglobins. 3. 3. HbI shows the lowest oxygen affinity, has an almost negligible Bohr effect and it has no physiological adaptation to temperature changes. 4. 4. HbII shows an intermediate oxygen affinity and a pronounced positive Bohr effect. 5. 5. HbIII has a very high affinity for oxygen, an almost negligible Bohr effect and a good physiological adaptation to temperature changes. 6. 6. By combining the 3 hemoglobins in different proportions Artemia salina L. must be able to withstand diverging environmental conditions.

Publisher Summary This chapter discusses the respiratory physiology of adult Artemia sauna L. in relation to oxygen availability. At constant temperature, a zone of respiratory independence above a critical oxygen tension is found. The production of lactic acid in low environmental oxygen concentration is only important in animals acclimated to high partial oxygen pressures. In animals acclimated to low oxygen concentrations, the adaptation consists of the formation of more hemoglobin and especially of hemoglobin III. Hemoglobin III has the highest oxygen affinity and at a physiological pH, it has the lowest Bohr effect and the lowest temperature sensitivity. While lactic acid production probably constitutes a short term or stress response to hypoxic conditions, the long term adaptational mechanism consists in the formation of new hemoglobin and in a change in the proportions of each of the three types of this respiratory pigment.

It has been shown previously that, by using methanol and a catalase inhibitor, 3-amino-1, 2, 4,-triazole, changes in hepatic H2O2 production in vivo can be detected. Using this method in guinea pigs and rats we could demonstrate increased H2O2 production during metabolism in vivo of aminopyrine, especially in phenobarbital-pretreated animals. In contrast, administration of antipyrine does not lead to H2O2 production. In the guinea pigs, phenobarbital induction also stimulates the H2O2 production in vivo without administration of exogenous substrates. The rate and extent of this additional H2O2 production depend on the induction state, drug metabolism and species; the major findings are in agreement with and extend previous research in vitro on microsomes, isolated hepatocytes and perfused liver.

Publisher Summary This chapter present a study on the aerobic metabolism of Artemia spec . In the study, the aerobic metabolism of the brine shrimp Artemia spec was measured with the Warburg constant volume respirometer technique. The experiments, as a part of the study, were carried out in air saturated artificial seawater and the respiratory rate was expressed as QO 2 . The most striking phenomenon in the biology of Artemia is the diapause of the dry cysts in the gastrula stage. This is characterized by the absence of any activity and no respiration can be detected. After hydration of the cysts, the development starts again and respiration increases fast. QO 2 is about 4μ1/h mg W D at the breaking stage and still rises after hatching up to a maximum of about 20 μl/h mg W D during the molting phase between instar II and instar III. After this molting, the QO 2 decreases slowly until the characteristic adult QO 2 is reached. The respiratory rate during ontogeny of Artemia shows several peaks that could all be correlated with molting stages. The chapter also presents a study on the respiratory pigment in Artemia .

A methodology was developed for fully automated measurements of nuclear features in Feulgen-stained tissue sections by means of videomicroscopy and image analysis. Segmentation is performed within one minute on 512 X 512 optical density (OD) images covering about 75 nuclei, resulting in a graphic contour overlay. The corresponding image subset is scanned by an object data extraction program, producing the raw figures for statistical interpretation. The segmentation software was evaluated by three tests, involving comparison with manual delineation and assessment of the influence of OD. Two case studies (ACTH-stimulated adrenal cortex and pancreatic carcinoma) illustrate the biologic accuracy and medical significance of the described methodology.

This paper gives an application of the knowledge of the parameters which have the greatest influence on the occupancy and the loss of a finite capacity queue. We show that it is possible to fit the decisive parameters of an SSMP(N) (special semi-Markov process with N states) to those of the measured data, which has been measured on a LAN-network located at the EPFL (Swiss Federal Institute of Technology). The SSMP is a discrete-time process and is a generalization of the Markov modulated Poisson process: each state is characterized by a general probability density function. The example taken to verify this affirmation is the comparison of the expected cell loss in a SSMP(N)/G/1/c queue and the expected cell loss of the converted LAN traffic/G/1/c queue which can be used as model of a LAN-MAN interconnection. The comparisons show that it is possible to correctly model the slotted traffic during a short period of time. >

Reactive oxygen intermediates play a role in chronic renal injury and glomerulosclerosis. We investigate changes in renal cortex antioxidant enzyme gene expression in the rat remnant-kidney model of chronic renal failure and compare the new data to enzyme activities published earlier. Antioxidant enzyme gene expression is evaluated by Northern blot analysis of cortex mRNA, using cDNA probes for catalase, copper/zinc-containing superoxide dismutase, and glutathione peroxidase. Catalase gene expression decreases during development of renal failure; this decrease is accompanied by decreased catalase activity during the glomerulosclerosis phase of the remnant-kidney model. Copper/zinc superoxide dismutase and glutathione peroxidase gene expression remain at a normal level during progression of the model, whereas their activities show a temporary decrease in the early remnant kidney. In the remnant-kidney model, catalase seems to be more vulnerable to reactive oxygen intermediates than superoxide dismutase and glutathione peroxidase. Our results show that antioxidant enzyme activity and gene expression do not change in the same direction at all times during disease development and that all antioxidant enzymes do not respond in the same way. Copyright 2000 S. Karger AG, Basel.