Cent Of Control Values Research Articles

Renal fluoride excretion and plasma fluoride levels during and after enflurane anesthesia are dependent on urinary pH.

To determine the effects of urinary pH on fluoride ion excretion and the resulting plasma fluoride concentration during and after enflurane anesthesia, renal function, plasma inorganic fluoride levels, and fluoride excretion were studied in two groups of patients pretreated with either NH4Cl or acetazolamide to produce acidic or alkaline urine, respectively. During anesthesia, urinary flow rate, inulin clearance (Cin) and para-aminohippurate (PAH) clearance (CPAH) were 7, 61, and 43 per cent of control values in the acidic-urine group and 22, 74, and 57 per cent of control values in the alkaline-urine group, respectively. Fractional fluoride clearances (CF/CIN) during anesthesia and operation were 0.06 +/- 0.05 in the acidic-urine group (urinary pH 5.08) and 0.68 +/- 0.23 in the alkaline-urine group (urinary pH 8.16). Values of total fluoride excretion during the same period were 0.06 +/- 0.04 mg and 0.87 +/- 0.29 mg, respectively. Mean maximal plasma levels of fluoride were 26.3 +/- 7.3 microM in the acidic-urine group and 13.5 +/- 2.4 microM in the alkaline-urine group. The differences between groups in fluoride clearance, fluoride excretion, and plasma fluoride levels were all statistically significant. The data clearly show that renal fluoride clearance is closely related to urinary pH.

Enzymatic sulfation of steroids. X. Pharmacological progesterone effects on rat liver glucocorticoid sulfotransferases and brief study of short-term effects of hormonal steroids on the enzymes.

Abstract Hepatic cortisol sulfotransferase activity (HCSA) was elevated 126, 258 or 342 per cent (average values) in intact male rats given daily doses of 2.5, 6.0 or 12 mg progesterone (P) i.m. for 30–56 days. Examination of the effects of 12 mg doses given for intervals between 1 week and 4 months showed that HCSA nearly doubled in 7–9 days and that maximum HCSA elevations (averaging 340 per cent) occurred after 30–56 days of treatment. The elevation of P-mediated HCSA in males increased after either adrenalectomy or castration. In females, 12 mg P doses for 28–38 days did not affect HCSA. After 102–121 days of treatment, however, their HCSA decreased to 70–80 per cent of control values. Individual glucocorticoid sulfotransferase (STI, STII, and STIII) concentrations were similar in untreated and P-treated females. In males, 6.0 mg P doses elevated all three enzyme concentrations. STIII was the major enzyme present. STI and STII concentrations increased more modestly. P doses of 12 mg caused little additional STIII production, but increased the sum of STI and STII activities considerably. P elevated STI and STII higher in male castrates than in intact males. P-treated adrenalectomized and intact males, however, exhibited similar glucocorticoid sulfotransferase profiles. Thus, it appeared that P, or a closely related metabolite, mediated the observed HCSA elevation. Short-term effects of P and other hormones on STI, STII, and STIII production and possible roles for P in endocrine effects on the enzymes are discussed.

Chloroform-induced glutathione depletion and toxicity in freshly isolated hepatocytes

Chloroform hepatotoxicity was studied in hepatocytes isolated from phenobarbital-treated rats. A single dose of 6.2 μmoles ml chloroform decreased the intracellular level of GSH to about 15 per cent of control values within 60 min. Less than 5 per cent of the dose administered was recovered as water-soluble or protein-bound metabolites. The rate of metabolite formation after 60 min was low due to rapid evaporation of the chloroform. Hepatocytes exposed to a single dose of chloroform did not replenish their GSH when maintained in a medium supplemented with amino acid precursors for GSH synthesis. Their GSH level remained below 15 per cent of control values and during the second hour of incubation malondialdehyde accumulated. The accumulation of malondialdehyde was associated with cellular lysis, whereas inhibition of lipid peroxidation prevented cell destruction. It is suggested that there are two phases of importance for chloroform toxicity: a first phase characterized by chloroform metabolism, GSH depletion and protein alkylation; and a second phase characterized by GSH deficiency, lipid peroxidation and cell destruction.

An Analgesic Action of Intravenously Administered Lidocaine on Dorsal-Horn Neurons Responding to Noxious Thermal Stimulation

DOHI, S.; KITAHATA, L. M.; TOYOOKA, H.; OHTANI, M.; NAMIKI, A.; TAUB, A. Author Information

In vivo effects of pentobarbital and halothane anesthesia on levels of adenosine 3', 5'-monophosphate and guanosine 3',5'-monophosphate in rat brain regions and pituitary

The effects of two general anesthetics, pentobarbital and halothane, on in vivo levels of cyclic AMP and cyclic GMP were examined in seventeen brain regions and the pituitary in the rat. Ventilation was controlled to produce normal values of arterial pH, pCO 2 and pO 2, to eliminate changes in cerebral perfusion and oxygen delivery which occur as a result of the respiratory depressant effect of these drugs. Arterial pressure was monitored and colonie temperature was maintained within normal limits. Pentobarbital was given as a single i.p. injection of 80mg/kg. Control animals received an equivalent volume of vehicle solution. Induction of halothane anesthesia was accomplished by placing the animals in a jar flushed with 3% halothane in air. After 3 min the animals received 2% halothane in air via a nose cone. Control animals for this experiment were placed in an air-filled jar. Experimental and control animals were killed by microwave irradiation 1 hr after the start of anesthesia. Both drugs decreased levels of cyclic GMP in virtually all regions. The largest changes occurred in the cerebellum, where cyclic GMP dropped to 7.4 per cent of control with pentobarbital and to 9.8 per cent of control following halothane. Levels of cyclic AMP significantly increased in the cerebellum, brainstem and hypothalamus after halothane, by 58, 49 and 65 per cent, respectively. Both pentobarbital and halothane markedly increased cyclic AMP levels in the pituitary (to 784 and 270 per cent of control values, respectively). These results show that halothane and pentobarbital, which modify synaptic transmission, selectively alter cyclic AMP and cyclic GMP levels in specific brain regions and the pituitary.

γ-Aminobutyric acid metabolism in rat brain following chronic oral administration of ethanolamine O-sulphate

Chronic, oral EOS ∗ administration resulted in a marked inhibition of rat whole-brain GABA-T activity and a significant increase in brain GABA concentrations. The maximum degree of GABA-T inhibition attained was 83 per cent, when GABA levels were 200 per cent of control values. A fixed dose of EOS produced a steady fall in GABA-T activity over the first 7 days of administration, when enzyme activity appeared to stabilize at 20–25 per cent of control values. Concurrently, GABA levels rose to a steady maximum value of approximately 240 per cent of control values. These changes were accompanied by significant reductions in whole-brain GAD activity. Chronic EOS also produced small but significant increases in brain content of alanine and taurine. No behavioural changes were seen following chronic EOS administration.

Effects of dantrolene on adrenal cortical function

Adverse effects of dantrolene include abnormal liver function tests, hepatic injury, and alteration of the hepatic mixed function oxidase cytochrome P-450 system. The following study conducted in rats indicates that the effective dose of dantrolene that has been shown to decrease hepatic cytochrome P-450 also causes adrenal enlargement with a marked reduction in serum glucocorticoids. The ratio of adrenal wet weight/body weight was significantly (P < 0.05) increased following 5 days of injection with a minimum dose of 25 mg dantrolene/kg body weight. The minimum effective dose of dantrolene that significantly (P < 0.05) lowered serum glucocorticoids was 50 mg/kg body weight. Serum glucocorticoids were reduced by half following 5 days of treatment with 100 mg dantrolene/kg body weight. The levels of serum glucocorticoids were 80 per cent of control serum levels and the adrenal wet weight/body weight ratio was 85 per cent of control values following 3 days of recovery after 5 days of pre-treatment with 100 mg/kg of dantrolene. It appears that dantrolene acts in a manner similar to diphenylhydantoin to reduce adrenal glucocorticoid secretion, with a possible alteration or reduction in the negative feedback response to the pituitary and resultant enlargement of the adrenals.

The effect of lithium on murine hematopoiesis in a liquid culture system.

Lithium carbonate has been shown to increase granulocyte production. We studied the effect of lithium on murine hematopoiesis in a liquid culture system providing for the prolonged growth of stem cells and their progeny. After one week of incubation, lithium, at a supernatant concentration of 1 mmol per liter, increased murine pluripotent stem cells (CFU-S, or colony-forming units in spleen) to 232 per cent of control values (P less than 0.001), granulocyte-monocyte progenitor cells (CFU-C, or colony-forming units in culture) to 218 per cent of control values (P less than 0.0001), granulocytes to 125 per cent of control values (P less than 0.01), and megakaryocytes to 246 per cent of control values (P less than 0.001). These increases were associated with transient elevations in colony-stimulatory activity. Prolonged exposure to lithium (three to 12 weeks) was associated with a dose-dependent progressive depletion of stem cells and their progeny. Lithium enhancement of granulopoiesis may be explained by primary stimulation of the pluripotent stem cell. Prolonged proliferative stress induced by lithium when the stem-cell reserve is limited may be associated with diminished replicative potential of the stem cells and rapid depletion of cells.

Ventricular Function in Children During Halothane Anesthesia

The effect of halothane on ventricular function in normal children was studied with the aid of echocardiography, which offers a noninvasive method to obtain these measurements safely. Thirteen healthy children ranging in age from 19 months to 12 years (mean=6 years), undergoing elective non-cardiac surgical procedures, were studied. Secobarbital, 4 mg/kg, and morphine, 0.1 mg/ kg, were administered intramuscularly an hour prior to induction of general anesthesia. Echocardiographic measurements were obtained while the patients breathed room air (control) and following nitrous oxide, 60 per cent, and concentrations of halothane ranging from 0.5 to 2 per cent. Increasing inspired concentrations of halothane significantly altered ventricular function in a dosedependent fashion. At halothane, 2 per cent, systolic blood pressure, pulse rate, and cardiac output decreased to 82, 94, and 72 per cent of control values, respectively. Measurements of ventricular performance, ejection fraction (EF), left ventricular enddiaslolic volume (LVEDV), and mean normalized rate of circumferential fiber shortening (Vuf) showed parallel decreases. Following atropine, 0.02 mg/kg, intravenously, improvement in cardiac output and all rate-dependent variables was observed. Although V,.r improved by 18 per cent, other indices of myocardial performance (EF, LVEDV, PEP/LVET) still showed depression. It is concluded that halothane can significantly decrease ventricular function in children undergoing surgical procedures. The accompanying decrease in cardiac output was completely offset by the administration of atropine.

An Analgesic Action of Intravenously Administered Lidocaine on Dorsal-horn Neurons Responding to Noxious Thermal Stimulation

Using extracellular single-unit recording techniques, effects of intravenously administered lidocaine on dorsal-horn nociceptive neurons were studied in cats made decerebrate whose spinal cords had been transected. Thirty-seven neurons in Rexed lamina V responding to high-threshold mechanical and noxious thermal stimuli (radiant heat, using Hardy-Wolff-Goodell dolorimeter) were studied. Lidocaine hydrochloride, 2.5, 5, and 10 mg/kg, iv, produced dose-related suppression of both spontaneous activity and responses of these neurons to noxious thermal stimulation. Spontaneous discharge frequencies at maximum suppression, observed 3--7 min after administration of each of the three doses of lidocaine were 64 +/- 14 (mean +/- 1 SE), 32 +/- 8, and 25 +/- 9 per cent of control values, respectively; responses to noxious thermal stimuli were 83 +/- 5, 52 +/- 8, and 39 +/- 7 per cent of the control values, respectively. Threshold skin temperature to noxious thermal stimulation increased from 44.7 +/- 0.4 C (control) to 46.3 +/- 0.7 C with lidocaine, 5 mg/kg (P less than 0.05), to 47.8 +/- 0.8 C with lidocaine, 10 mg/kg (P less than 0.01). The times necessary for recovery varied in a dose-related fashion. Plasma lidocaine concentrations 5 min after lidocaine, 5 mg/kg, averaged 3.6 +/- 0.7 microgram/ml. These data support the clinical impression that intravenously administered lidocaine produces analgesia at plasma concentrations of 3--10 microgram/ml. It is suggested that lidocaine may block conduction of nociceptive impulses, at least in part, by suppression of spinal-cord nociceptive neurons.

Effects of methotrexate on thymidine triphosphate levels in Chinese hamster cell cultures

Chinese hamster ovary cells were incubated in medium containing hypoxanthine and glycine and supplied with 10 −5 M methotrexate to inhibit the endogenous synthesis of thymidine nucleotides. Within 1–5 min after addition of the inhibitor, incorporation of [6- 3H]deoxyuridine into DNA was as low as 1 to 1.5 per cent of control values, indicating that endogenous synthesis of thymidine nucleotides was blocked rapidly and almost completely. The cellular dTTP content was determined under various culture conditions as a function of time after addition of methotrexate. If the medium used contained undialyzed fetal calf serum, dTTP levels decreased relatively slowly in asynchronous as well as in synchronous S-phase cell populations. Similar results were obtained with asynchronous cultures incubated in medium with dialyzed serum. In contrast, if synchronous cultures consisting predominantly of cells in S phase were incubated in medium containing dialyzed serum and supplied with methotrexate, dTTP levels decreased within 15 min from control values of 15–20 pmoles/10 6 cells to levels of 1.5 to 3 pmoles/10 6 cells or lower. The previously reported failure of methotrexate to cause a rapid depletion of cellular dTTP may reflect, therefore, maintenance of thymidine nucleotide pools by cells that are not in the S phase and/or uptake by cells of thymidine present in undialyzed serum used for preparation of culture media.

Comparison of the activity of 2′-deoxycoformycin and erythro-9-(2-hydroxy-3-nonyl)adenine in vivo

The inhibition of P388 cell deamination of arabinosyladenine (ara-A) in vivo by the adenosine deaminase inhibitors 2′-deoxycoformycin (dCF) and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and their subsequent effects on ara-A metabolism were determined and compared. A single i.p. injection of EHNA (3 mg/kg, 10.9 μmoles/kg) initially inhibited ara-A deamination in vivo by 96 per cent with recovery to 50 per cent of control values within 30 min. In comparison, dCF (0.2 mg/kg, 0.75 μmole/kg) inhibition of ara-A deamination was initially low (4 per cent), but maximized (96 per cent) after 15 min. This inhibition was sustained for 2 hr and did not recover to 50 per cent of control values until after 10 hr. Injected alone, the T 1 2 of ara-A in the peritoneal ascitic fluid was less than 1 min, but was increased to 7 min when injected with EHNA and to 12 min when injected 15 min after dCF. The rate of efflux of ara-A and its metabolites from the peritoneal cavity ( T case1 2 = 15−18 min ) was not affected significantly by either deaminase inhibitor. Cellulat ara-ATP concentrations were elevated and the extent and duration of inhibition of DNA synthetic capacity were increased identically in cells of mice treated with ara-A and either deaminase inhibitor as compared with those treated with ara-A alone. Sustained deaminase inhibition after intraperitoneal concentrations of ara-A had been diminished by otherwise normal disposition did not augment the biochemically demonstrable activity of ara-A. Therefore, it appears that maintenance of the initial high concentrations of ara-A is the primary function of a deaminase inhibitor in increasing the therapeutic efficacy of this analog.

Biochemical and physiologic changes in lungs of rats exposed to a cadmium chloride aerosol.

The purpose of this study was to examine the in vivo effects of acute exposure to a cadmium chloride aerosol on the activity of pulmonary enzymes and selected physiologic parameters that are altered by exposure to oxidant agents. Male rats were exposed for 1 hour to 0.5 per cent aerosol of cadmium chloride. At 1,5, and 11 days after exposure to cadmium chloride, exposed rats compared to control rats (data expressed as per cent of control values) had lung-to-body weight ratios of 192, 174, and 140 per cent; lung glucose-6-phosphate dehydrogenase activities of 90, 107, and 135 per cent; lung superoxide dismutase activities of 96, 101, and 132 per cent; tidal volumes of 62, 63, and 89 per cent; respiratory frequencies of 170, 145, and 108 per cent; and lung weight-specific static deflation volumes at 30 cm water of 30, 13, and 31 per cent. A zero-order clearance of cadmium from whole lung was observed, with a half-time of 27.4 days. Light microscopic examination of lung tissue revealed initial pulmonary edema on day 1 that progressed to interstitial pneumonitis on day 5, with some recovery by 11 days after exposure. The cadmium induced biochemical, physiologic, and pathologic alterations were similar to the responses observed in lungs of rats exposed to a wide variety of pulmonary irritants; thus, the changes observed may represent a nonspecific response to tissue injury.

Argentine Hemorrhagic Fever

We investigated immunologic mechanisms and the role of complement in the pathogenesis of Argentine hemorrhagic fever, a disease caused by the Junin virus, a member of the arenavirus group. Total serum complement activity was reduced to 68 per cent of control values in patients with severe or moderate disease (P<0.001). C2, C3 and C5 values were also low (12 to 60 per cent) during the early acute period of the disease. However, serum C4 content was increased to 160 per cent of the control values in the same patients. Total complement activity returned to normal with clinical and laboratory recovery, at the time of detection of antibodies against Junin virus. C1q reactive material was found in four of 19 cases and no relation to the evolution of the disease could be established. These results suggest that immune complexes are not important in the pathogenesis of Argentine hemorrhagic fever, but that activation of the complement system has a role. (N Engl J Med 299:216–221, 1978)

Ventricular function in children during halothane anesthesia: an echocardiographic evaluation.

The effect of halothane on ventricular function in normal children was studied with the aid of echocardiography, which offers a noninvasive method to obtain these measurements safely. Thirteen healthy children ranging in age from 19 months to 12 years (mean=6 years), undergoing elective non-cardiac surgical procedures, were studied. Secobarbital, 4 mg/kg, and morphine, 0.1 mg/ kg, were administered intramuscularly an hour prior to induction of general anesthesia. Echocardiographic measurements were obtained while the patients breathed room air (control) and following nitrous oxide, 60 per cent, and concentrations of halothane ranging from 0.5 to 2 per cent. Increasing inspired concentrations of halothane significantly altered ventricular function in a dosedependent fashion. At halothane, 2 per cent, systolic blood pressure, pulse rate, and cardiac output decreased to 82, 94, and 72 per cent of control values, respectively. Measurements of ventricular performance, ejection fraction (EF), left ventricular enddiaslolic volume (LVEDV), and mean normalized rate of circumferential fiber shortening (Vuf) showed parallel decreases. Following atropine, 0.02 mg/kg, intravenously, improvement in cardiac output and all rate-dependent variables was observed. Although V,.r improved by 18 per cent, other indices of myocardial performance (EF, LVEDV, PEP/LVET) still showed depression. It is concluded that halothane can significantly decrease ventricular function in children undergoing surgical procedures. The accompanying decrease in cardiac output was completely offset by the administration of atropine.

Decreased cytochrome p450 and increased porphyrin concentrations in the livers of rats on a low iron diet given a single dose of desferrioxamine

The efficacy of the iron chelator desferrioxamine at a site of action in the liver was investigated. A single dose given to 48 hr starved male rats (1.56 m-moles/kg, i.p.) caused a time dependent decrease in liver ferritin iron concentrations to about 60 per cent of control values 4 to 8 hr after dosing. Concurrently with the decrease in ferritin iron levels, there was a small accumulation of porphyrins in the liver. By keeping male rats on a low iron diet for 10 days followed by 48 hr starvation, liver ferritin iron concentrations were reduced to about 5 per cent of control values. Administration of desferrioxamine to these animals caused a further decrease in liver ferritin iron levels and a marked increase in the accumulation of porphyrins in the liver. After 30 days on a low iron diet, liver ferritin iron could no longer be detected. Blood haematocrits and haemoglobin levels were severely depressed. Liver cytochrome b 5 and P450 values were similar to controls. In these animals desferrioxamine caused a substantial time dependent increase in the porphyrin content of the liver and a decrease in cytochrome P450 levels. Cytochrome b 5 concentrations were not significantly affected. It was suggested that these results were consistent with desferrioxamine blocking hepatic haem synthesis by making iron unavailable for inclusion into protoporphyrin at the ferrochelatase step. Relative to control animals, hepatic mitochondrial 5-aminolevulinic acid synthetase was significantly depressed in rats kept for 10 or 30 days on the low iron diet. Administration of desferrioxamine caused no marked increase in 5-aminolevulinic acid synthetase activities in either group of rats in the 24 hr after dosing. It was concluded that in addition to haem, iron may play a regulatory role in controlling the activity of 5-aminolevulinic acid synthetase.

The effect of xylazine and xylazine followed by insulin on blood glucose and insulin in the dairy cow.

The effect of xylazine and xylazine followed 20 minutes later by insulin upon glucose metabolism and plasma insulin concentrations was examined in three cows. After doses of 0.18 mg per kg xylazine given intramuscularly (IM) or 0.15 mg per kg given intravenously (IV) hepatic glucose production increased, plasma insulin concentrations decreased to 25 to 33 per cent of control values, and there was a prolonged hyperglycaemia. When 200 units of soluble insulin were given 20 minutes after similar doses of xylazine there was a rapid fall in blood glucose and a reduction in the rate of glucose production by the liver. Xylazine-induced hyperglycaemia arose from a combination of increased hepatic glucose production and reduced plasma insulin concentrations. Peripheral tissues were still responsive to insulin and when adequate insulin was available blood glucose concentrations rapidly decreased.

Human amnion metabolism: I. In vitro maintenance

The energy stores of human term amnion include glycogen (2.2 ± 0.3 μmoles of glucose per gram, mean ± S.E.) and ATP (0.13 ± 0.2 mM.). Histologic structure and biochemical functions were preserved during incubations of amnion for 120 minutes at 37° C, in a defined medium simulating amniotic fluid; glycogen concentrations were maintained at control values, and the concentration of ATP usually remained at 85 to 100 per cent of control values. Glucose utilization during the first 60 minutes of incubation was linear at a rate of 70.0 ± 3.0 nmoles per minute per gram of tissue. It is concluded that amnion is a highly metabolically active tissue that can be maintained in a viable state in a suitable medium.

Metabolism and renal effects of enflurane in man.

The metabolism and renal effects of enflurane were studied during and after anesthesia in ten surgical patients without renal disease; ten control patients received halothane. Enflurane was metabolized to inorganic fluoride with a mean peak serum level of 22.2 +/- 2.8 muM four hours after anesthesia. Urinary inorganic and organic fluoride excretions were increased but oxalic acid excretion was not, suggesting that the latter is not an enflurane metabolite. Postanesthetic renal function, including the response to vasopressin, was normal in both groups. During enflurane anesthesia renal blood flow, glomerular filtration rate, and urinary flow rate were 77, 79, and 67 per cent of control values, respectively. In this study of patients without renal disease, metabolism of enflurane to inorganic fluoride was insufficient to cause clinically significant renal dysfunction.

An animal model of the compartmental syndrome.

An animal model of the compartmental syndrome is presented to study the effect of elevated intracompartmental pressure on muscle histology and nutrient blood flow. Latex balloons were inserted into the anterior compartment of rabbits and the pressure within them controlled by an adjustable water column. Nutrient blood flow to the muscles of the compartment was determined by an Rb86 isotope dilution technique and showed a progressive decline with intracompartmental pressures over 50 mm Hg. At 80 mm Hg, flow was but 5 per cent of control values. An inflammatory necrosis was noted when a pressure of 60 mm Hg was exerted for 24 hours. At higher pressures an ischemic necrosis without inflammation was observed.