Polychlorinated biphenyl-induced modification of lymphocyte response to plant mitogens in rats

Summary In PCB-treated rats total white cell and differential counts and lymphocyte proliferative response to PWM were unaltered. The lymphocyte response to PHA was increased in treated animals.Acknowledgements. Supported by grants from the Medical Research Council of Canada. We thank the Monsanto Chemical Co., St. Louis, Mo., for donating Aroclor 1254 and Dr.P. Cano for the protein determinations and electrophoresis.     

Effect of the polychlorinated biphenyl preparation,Aroclor 1242, on the quantity of neurosecretory material in the medulla terminalis X-organ of the fiddler crab,Uca pugilator

Summary Exposure of the fiddler crab,Uca pugilator, to the PCB preparation, Aroclor 1242, produces an increase in the quantity of neurosecretory material in the medulla terminalis X-organ. This Aroclor apparently inhibits release, but not synthesis, of one or more neurohormones.This investigation was supported by grant PCM75-03029 A01 from the National Science Foundation.     

Effect of the polychlorinated biphenyl preparation, Aroclor 1242, on the quantity of neurosecretory material in the medulla terminalis X-organ of the fiddler crab, Uca pugilator.

Exposure of the fiddler crab, Uca pugilator, to the PCB preparation, Aroclor 1242, produces an increase in the quantity of neurosecretory material in the medulla terminalis X-organ. This Aroclor apparently inhibits release, but not synthesis, of one or more neurohormones.     

Long-term depressor effects of catecholamine neuronal grafts in the third ventricle of the brain in normotensive rats

Neuronal tissue containing A-6 group noradrenalin (NA) neurons of the locus ceruleus, or A-10 group dopamine (DA) neurons of the substantia nigra, was grafted into the third ventricle at the level of the preoptic-anterior hypothalamic region, in normotensive male rats. A significant and long-lasting depressor effect was shown in rats with either graft. In rats with an NA neuron-rich graft, plasma concentrations of arginine-vasopressin (AVP), plasma renin activity (PRA), and corticosterone (CS) decreased significantly, whereas in rats with a DA neuron-rich graft, AVP and PRA concentrations also decreased significantly but CS showed no significant change. Neither NA nor adrenalin in plasma changed significantly in rats with either graft.     

Long-term depressor effects of catecholamine neuronal grafts in the third ventricle of the brain in normotensive rats

Summary Neuronal tissue containing A-6 group noradrenalin (NA) neurons of the locus ceruleus, or A-10 group dopamine (DA) neurons of the substantia nigra, was grafted into the third ventricle at the level of the preoptic-anterior hypothalamic region, in normotensive male rats. A significant and long-lasting depressor effect was shown in rats with either graft. In rats with an NA neuron-rich graft, plasma concentrations of arginine-vasopressin (AVP), plasma renin activity (PRA), and corticosterone (CS) decreased significantly, whereas in rats with a DA neuron-rich graft, AVP and PRA concentrations also decreased significantly but CS showed no significant change. Neither NA nor adrenalin in plasma changed significantly in rats with either graft.     

Differential expression of genes for uncoupling proteins 1, 2 and 3 in brown and white adipose tissue depots during rat development

The different expression patterns of genes for uncoupling proteins (UCPs) 1, 2 and 3 (ucp1, ucp2 and ucp3) were studied in interscapular brown adipose tissue (BAT) and in four white adipose tissue (WAT) depots (epididymal, inguinal, mesenteric and retroperitoneal) in male rats of different ages (18 days-12 months). UCP mRNA expression levels were determined by Northern blotting. In BAT, there were high levels of expression of UCP1 and UCP3 mRNA, but no detectable levels of UCP2 mRNA. Both ucp1 and ucp3 followed a similar expression pattern with age, with high levels in suckling rats which decreased to 50% or less in rats just under 2 months old, declining thereafter until 5 months and then recovering with age. However, an additional peak of expression was observed for ucp3 at the age of 3 months. In WAT, ucp1 expression was rare: occasional expression was found for UCP1 mRNA in the retroperitoneal depot in suckling rats and in the epididymal and inguinal depots in suckling and mature adult rats. ucp2 and ucp3 had different developmental expression patterns, but these were similar for each gene in the different depots studied. UCP3 mRNA was highly expressed in rats soon after birth, it decreased until 3 months, and increased thereafter, except for the mesenteric WAT where ucp3 expression decreased until 7 months before recovering. The fact that changes with age of both ucp1 and ucp3 expression have a similar profile in BAT, which is also similar to the ucp3 and also ucp1 profiles in some WAT depots, might reflect a common regulatory pattern for the expression of these genes, and also a common function. In contrast to ucp1 and ucp3, ucp2 had a peak of expression at about 2 months, and lower expression at 3 months, suggesting different regulation and probably a different role for this UCP.     

Effects of thyroidectomy and thyroxine replacement on the responsiveness of the anterior pituitaries from male rats to thyrotropin-releasing hormone in vitro

Summary Thyroidectomy decreased prolactin concentrations in the anterior pituitary (AP) and serum of the male rat. The amount of basal and thyrotropin-releasing hormone (TRH)-stimulated release of prolactin by AP in vitro was lower in thyroidectomized (Tx) rats than in sham Tx rats. These results suggest that the inhibitory effects of thyroidectomy on pituitary and serum prolactin in male rats are mediated in part by the reduction of the production and spontaneous release of prolactin and the responsiveness of prolactin to TRH.     

Hepatic phosphatidylcholine synthesis in deficiency of lysine and threonine: effect of malathion

Rats fed on a rice diet deficient in lysine and threonine showed increased activities of CDP-Choline pathway enzymes and incorporation of (methyl-3H)-choline into hepatic microsomal phosphatidylcholine, compared to rats fed on the same diet supplemented with lysine and threonine. However, the amount of microsomal phosphatidylcholine was significantly decreased in rats fed a deficient rice diet. These results suggest an enhanced phosphatidylcholine catabolism in rats fed on a rice diet deficient in lysine and threonine. Malathion administration reduced the amount of phosphatidylcholine in all the groups.     

Renal vascular reactivity to ATP in hyper- and hypothyroid rats

The effects of adenosine triphosphate (ATP) on the renal vasculature of isolated kidneys from control, hyper- and hypothyroid rats were characterized. ATP responsiveness was evaluated in basal tone and in raised tone (phenylephrine 10^–6 M) preparations. These responses were compared with those obtained with barium chloride or sodium nitroprusside (SNP), used respectively as nonreceptor agonists for vasoconstriction or vasodilation. In preparations at basal tone, ATP produced dose-related vasoconstriction, which was increased in hyperthyroid kidneys, and was severely attenuated in kidneys from hypothyroid rats. In raised tone preparations from control rats ATP produced a dual response: vasoconstriction at low doses, which declined with increasing doses to give way to vasodilator responses; biphasic responses were found in some kidneys. Hyperthroid kidneys showed increased pressor responses and a vasodilator response similar to those seen in kidneys from control rats. However, in hypothyroid kidneys the vasodilator response was abolished. The responses to barium chloride and to SNP were significantly increased and decreased in hyper- and hypothyroid kidneys, respectively; vasoconstrictor responses to SNP were also found in hypothyroid kidneys. Hence the abnormal responses to ATP observed in both thyroid dysfunctions may be partially explained by unspecific alterations in the contractile machinery of the renal vasculature in these kidneys. However, ATP responsiveness (vasoconstriction at low tone and vasodilation at raised tone) was more severely affected in hypothyroid kidneys, suggesting that purinergic (P_2X and P_2Y) receptor activity may be decreased in these organs.     

Hepatic phosphatidylcholine synthesis in deficiency of lysine and threonine: effect of malathion

Summary Rats fed on a rice diet deficient in lysine and threonine showed increased activities of CDP-Choline pathway enzymes and incorporation of (methyl-³H)-choline into hepatic microsomal phosphatidylcholine, compared to rats fed on the same diet supplemented with lysine and threonine. However, the amount of microsomal phosphatidylcholine was significantly decreased in rats fed a deficient rice diet. These results suggest an enhanced phosphatidylcholine catabolism in rats fed on a rice diet deficient in lysine and threonine. Malathion administration reduced the amount of phosphatidylcholine in all the groups.     

Changes in cholinesterase activity of muscle after crushing the sciatic nerve of rats

The subcellular distribution of cholinesterase (ChE) was studied in the gastrocnemius muscle of rats after strong or weak nerve crushing. The ChE activities of muscle were decreased to a greater extent by strong crushing than by weak crushing. In particular, the ChE activity of the fraction containing sarcoplasmic reticulum was most greatly decreased. These results suggest that the change in the ChE activity of the microsomal fraction most finely reflects the strength of nerve crushing.     

Role of 1,25-dihydroxyvitamin D3 in the generation of the acute-phase response in rats with talc-induced granulomatosis

Subcutaneous injection of nonspecific irritants such as magnesium silicate (talc) provokes granulomatous inflammation in the rat. Part of the acute phase response (APR) in these animals is the loss of trabecular bone at sites distant from the site of inflammation. To assess the possible involvement of vitamin D in the bone loss, we studied the development of the acute phase response in vitamin D-deprived rats. The serum APR provoked by subcutaneous inflammation in rachitic rats consisted of hypozincemia, hypercupremia, increased, alkaline phosphatase activity and adrenocorticotropic hormone (ACTH) concentration, and was similar to that in control animals except for the absence of hypoferremia. Control rats with talc-induced subcutaneous inflammation also had splenomegaly and decreased total and mononuclear peripheral blood cell counts, while subcutaneous inflammation did not induce spleen changes in rachitic rats. Subcutaneous inflammation induced the loss of trabecular bone and decreased the osteoblastic cell count in tibial metaphyses in control animals. Rachitic rats had abundant osteoid on trabecular surfaces, and the number of osteoblasts and osteoclasts was comparable to that of the controls. Subcutaneous inflammation did not affect any of the bone parameters in rachitic rats. These results indicate that vitamin D plays an important role in the generation of the acute phase response during inflammation, particularly in the induction of spleen and bone cell changes. The discrepancy of the blood on one hand and bone and spleen indices of the APR on the other, indicate that there may be divergent pathways in the generation of the inflammatory response, some of which may be dependent on vitamin D.     

The effect of hypoxia on hepatic cytochromes and heme turnover in rats in vivo

We evaluated the effect of hypoxia (7% v/v) on hepatic heme turnover in vivo and microsomal heme protein content in male Sprague-Dawley rats. Hepatic heme protein turnover, measured as 14CO-production during continuous infusion of 5-14C-aminolevulinic acid, a precursor of nonerythrogenic heme, was decreased 60% during hypoxia and returned to control levels promptly after reoxygenation. Hepatic cytochrome P-450 content was decreased in hypoxic and 24-h reoxygenated animals. We conclude that normobaric hypoxia decreases hepatic cytochrome P-450 which could contribute to decreased drug metabolism in hypoxia. This decrease is probably due to heme oxygenase-independent breakdown of hepatic heme.     

Effects of thyrotrophic-releasing hormone (TRH) on thermoregulation in the rat

At ambient temperatures (Ta) of both 8 and 22 degrees C, intraventricular administration of TRH (10-80 microgram) produced a dose-dependent hypothermia in rats. The hypothermia was due to both decreased metabolic heat production and cutaneous vasodilatation. In contrast, at 30 degrees C Ta, TRH increased metabolic heat production (due to behavioral excitation) and led to hyperthermia.     

Decreased number of asialoglycoprotein receptors in diabetic BB Wistar rat

The binding of asialoglycoproteins by hepatic binding protein was studied in freshly isolated hepatocytes from genetically diabetic BB Wistar rats. The number of cell surface asialoglycoprotein receptors was dramatically decreased (58,000 +/- 38,000 for diabetic rats compared to 267,000 +/- 70,000 for normal rats), while the association equilibrium constant was not changed. These results parallel those obtained with streptozotocin-diabetic rats and support the hypothesis that insulin deprivation is responsible for the decrease in the receptor number.     

Acid-base homeostasis and the thyro-parathyroid glands]

Chronic metabolic acidosis entails hyperparathyroidism and osteopathy. In order to elucidate the role of the thyroparathyroids in this bone lesion production the effects of acidic diet for 7 weeks were studied in parathyroidectomized (PTX), thyroparathyroidectomized (TPTX) and shamoperated (Sh-O) growing rats. In all animals urinary excretion of calcium, phosphate, ammonium and titrable acidity was similarly increased. The rise in hydroxyproline excretion and urinary 85-sr (that was injected previous to acidic feeding) was more marked in PTX and TPTX rats. Moreover, in these animals the serum calcium level was increased, the blood pH was decreased. According to these data, an acidic diet intake that is not sufficient to elicit a fall in blood pH of normal young rats can induce severe acidosis in chronically parathyroidectomized or thyroparathyroidectomized animals; moreover the bone resorption appears more marked. It is concluded that parathyroids are involved in the extra-cellular fluid defense mechanism against acidosis by a no bone resorptive mechanism. We hypothesize that the parathyroids permit the necessary and adequate supply of bicarbonates by the bone to maintain blood pH homeostasis.     

Effect of consumption of green and black tea on the level of various enzymes in rats

Summary Drinking of both green and black tea as the only liquid ingested resulted in significant decreases in the activity of transketolase in whole blood of rats both before and after the in vitro addition, of thiamin diphosphate. Liver transketolase activity was decreased only by green tea. Mucosal transketolase activity was not affected by either type of tea. The activity of lactate dehydrogenase (LDH) was not affected by either type of tea, while whole blood LDH was decreased by both green and black tea. Neither tea had any affect on mucosal alkaline phosphatase, but thiamin diphosphatase activity was decreased by both teas. An increase in liver total thiamin resulted from the drinking of both types of tea.     

Influence of castration and testosterone replacement on hypothalamic tyrosine hydroxylase activity in the rat.

Hypothalamic tyrosine hydroxylase (TH) activity of castrate rats is modulated by testosterone propionate (TP) in vivo. Kinetic studies revealed that both Vmax and Km were virtually unaltered for substrate tyrosine in the presence of an excess of DMPH4 cofactor. TP replacement to castrate rats increased the Km for added DMPH4 cofactor, while Vmax decreased. These results suggest that TP decreases TH activity of castrate rats by inhibiting the enzyme-reduced pteridine cofactor complex.     

Diabetes alters drug metabolism--in vivo studies in a streptozotozin-diabetic rat model

The influence of experimental streptozotozin-induced diabetes on hepatic drug metabolism in vivo has been studied in rats, using 14CO2-exhalation after 14C-aminopyrine injection. Male diabetic rats showed a decreased (-18%), females an increased (+19%) 14CO2-exhalation compared to controls, indicating altered hepatic drug metabolism due to diabetes.     

Urinary levels of chloroquine in relation to dietary protein

Summary When rats suffering from protein-calorie malnutrition (kwashiorkor) were given chloroquine, urinary levels of unchanged drug increased while chloroquine metabolites decreased. This qpparent inhibition of chloroquine metabolism was eliminated by refeeding the animals.