Anatomy of diaphragmatic circulation

During progressive exercise ventilation (VI) initially increases through increases in both tidal volume (VT) and respiratory frequency (f) but at high levels of exercise further increases in VI are almost completely due to increases in f and a VT plateau is seen. We wished to determine whether the presence of the VT plateau is due to a tachypneic influence related to very high levels of exercise or whether it represents a stereotypic response of the respiratory system at high levels of VI. We therefore compared breathing pattern in six subjects during maximal incremental exercise (ME) with that in the same subjects when similar levels of VI were obtained by a combination of submaximal exercise and hypercapnia (E/CO2). A VT plateau was seen in all ME and E/CO2 tests. There was no significant difference in the level of the VT plateau between the ME (2.93 +/- 0.17 liters) and E/CO2 (2.97 +/- 0.12 liters) tests. We conclude that the presence and level of the VT plateau during ME is not due to a tachypneic stimulus related to very high levels of exercise but is a function of the level of VI.     

Induction of tyrosine aminotransferase by triamcinolone during rat liver development in vitro

Embryonic rat liver 12–21 days old exhibits low but significant tyrosine aminotransferase (TAT) activity. In organ culture for 24 hr in a nutrient medium, there is an increase in TAT levels. Addition of glucocorticoids increases TAT levels at all embryonic ages. The magnitude of the produced TAT level increases with developmental age. Glucagon also increases embryonic liver TAT, but insulin and growth hormone (somatotropin) had little effect.     

Osteoprotegerin levels increased by interleukin-1beta in human periodontal ligament cells are suppressed through prostaglandin E(2) synthesized de novo

Osteoprotegerin (OPG) is a novel tumor necrosis factor receptor superfamily that inhibits osteoclast differentiation, activity, and survival. Interleukin-1beta (IL-1beta) increases OPG expression. IL-1beta also increases prostaglandin E(2) (PGE(2)) production and stimulates bone resorption. In the present study, we examined the involvement of PGE(2) in IL-1beta-induced increases in OPG levels in human periodontal ligament cells (HPL cells) in an effort to clarify apparently conflicting IL-1beta actions on bone resorption and understand IL-1beta-induced increases in secretion of OPG and PGE(2) in HPL cells. 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole, a mRNA synthesis inhibitor, partly inhibited the increase in OPG mRNA levels induced by IL-1beta. Cycloheximide, a protein synthesis inhibitor, enhanced the stimulatory effect of IL-1beta. Etodolac, a selective cyclooxygenase-2 inhibitor, suppressed the increase in PGE(2) levels. Furthermore, etodolac reinforced the promotion of OPG expression by IL-1beta at the mRNA and protein levels. PGE(2) added to cultures of HPL cells decreased OPG mRNA levels in a dose- and time- dependent manner. These findings suggest that the increase in OPG levels induced by IL-1beta in HPL cells is suppressed through PGE(2) synthesized de novo.     

Effect of vagotomy on the duodenal mechanisms regulating gastric secretion

Gastric acid secretion, gastrin and secretin serum levels after duodenal acidification were studied in 6 dogs, before and after a troncular vagotomy was performed in each one. After duodenal acidification in normal dogs, a 45.2% inhibition of gastric acid secretion with parallel 55-84% increases in the serum secretin levels, without changes in the serum gastrin levels, was noted. When a troncular vagotomy was performed in the same dogs, duodenal acidification produced a 20% (non significant) inhibition of gastric acid secretion with parallel 34-72% increases in the serum secretin levels and without changes in the serum gastrin levels. It is concluded that vagus nerve is necessary to assess a physiological inhibition of gastric secretion after duodenal acidification and it is suggested that humoral and nervous factors are implicated and coexist in these mechanisms.     

Thyroxine elicits divergent changes in mRNA levels for two urea cycle enzymes and one gluconeogenic enzyme in tadpole liver

Thyroxine-induced metamorphosis of the tadpole to the frog (Rana catesbeiana) is marked by increased activities of the urea cycle enzymes in liver. Cloned cDNAs for two mammalian urea cycle enzymes--carbamyl-phosphate synthetase I and argininosuccinate synthetase--were shown to cross-hybridize with the corresponding mRNAs in tadpole liver. Thyroxine treatment produced nearly 10-fold, coordinate increases in hybridizable mRNA levels for these two enzymes in tadpole liver. This increase is sufficient to account for reported increases in enzyme levels and synthesis rates, demonstrating that thyroxine largely regulates concentrations of these enzymes at a pretranslational step(s). In contrast, levels of phosphoenolpyruvate carboxykinase mRNA in tadpole liver decreased by more than 90% following thyroxine treatment. This differs from the thyroxine-induced increases in synthesis rates of enzyme and mRNA reported for phosphoenolpyruvate carboxykinase in rat liver. However, the decreased levels of this mRNA in tadpole liver may represent a secondary response due to thyroxine-stimulated release of insulin.     

Blood uric acid levels during hyperthermic stress.

Non-diabetic and streptozotocin diabetic adult male Sprague-Dawley derived rats were divided into normothermic and hyperthermic groups. Hyperthermia was achieved in an environmental chamber. Blood uric acid and lactate levels were performed on all animals. Significant increases in blood uric acid levels were found in all animals during hyperthermia. Blood lactic acid was also increased during hyperthermia indicating tissue hypoxia. It has been shown that increases in the breakdown of purine nucleotides occurs during hypoxia. This study indicates that increases in blood uric acid levels is an expected response to hyperthermic stress and is probably due to tissue hypoxia.     

Regulation of Dopamine Release from PC12 Pheochromocytoma Cell Cultures During Stimulation with Elevated Potassium or Carbachol

To examine the role of cyclic AMP in the process of catecholamine release experiments have been performed with cultures of PC12 pheochromocytoma cells. Elevated potassium (56 mM) and carbamylcholine (carbachol, 10(-4) M) cause rapid increases in cyclic AMP levels in the cultures that show a time course similar to that of evoked dopamine release. These secretogogue-induced increases in cyclic AMP levels are well correlated with release in terms of relative magnitude and calcium dependence. Forskolin (a direct activator of adenylate cyclase) causes dose-related increases in cyclic AMP levels in PC12 cell cultures that are synergistic with those caused by either elevated potassium or carbachol. At low concentrations forskolin significantly increases evoked release, whereas at higher concentrations it increases both spontaneous and evoked release. These results suggest that cyclic AMP may be involved in the process of dopamine release from PC12 cells in culture.     

Role of the pituitary-adrenocortical axis in the control of agonistic behaviour after single and repeated footshock in castrated male mice

Two experiments were conducted to examine the role of the pituitary-adrenocortical axis in the mediation of the effects of single and repeated electric footshock on subsequent agonistic responding in castrated male mice. It was found that (1) preventing corticosterone responses to shock occludes the facilitatory effects of single shock on both aggressive and submissive behaviour and occludes the additional increases in submissive behaviour which normally occur after repeated shock, and (2) blocking pituitary release of ACTH by dexamethasone treatment restores aggressive behaviour after repeated shock, independently of the initial levels of corticosterone and testosterone. These findings suggest that (1) increases in aggressive and submissive behaviour in response to single shock depend on shock-induced increases in corticosterone levels; (2) further increases in submissive behaviour in response to repeated shock require further increases in the corticosterone levels; and (3) inhibition of aggressive behaviour after shock repetition appears to depend on increases in ACTH levels, and occurs independently of the initial corticosterone and testosterone levels.     

Voltage-dependent conductance induced by hemocyanin in black lipid films

When hemocyanin is added to a black lipid film, the conductance increases in discrete steps. For negative potentials the single step conductance is constant, but for positive potentials the step conductance appears to decrease as the potential increases. At high positive potentials the conductance fluctuates between several levels. These data suggest that, in lipid membranes, hemocyanin conducts ions through discrete channels. The voltage-dependent conductance observed at high levels of conductance seems to be a consequence of the properties of the conductance of the single channel.     

Light-regulated protein and mRNA synthesis in root caps of maize

Illumination of maize roots initiates changes in mRNA levels and in the activities of proteins within the root cap. Using Northern analysis we showed a 5–6-fold increase in the levels of three specific mRNAs and a 14-fold increase in plastid mRNA. This increase is rapid, occurring within 30 minutes of illumination. With prolonged periods of darkness following illumination, messages return to levels observed in dark, control caps. For two species of mRNA illumination results in a reduction in message levels. Light-stimulated increases in the levels of specific mRNAs are proportionally greater than are increases in the activities of corresponding proteins. We suggest that the light-stimulated increase in protein activity in root caps may be preceded by and occur as a consequence of enhanced levels of mRNA. Our work suggests that photomorphogenesis in roots could involve changes in the levels of a wide variety of mRNAs within the root cap.     

Glucocorticoid stimulation of tetrahydrobiopterin levels and phenylalanine hydroxylase activity in rat hepatoma cells

Incubation of H4-II-E-C3 rat hepatoma cells with either hydrocortisone or dexamethasone resulted in 3- to 5-fold increases in the levels of both phenylalanine hydroxylase and its essential cofactor, tetrahydrobiopterin. Maximum elevation of phenylalanine hydroxylase was noted after 24 h of incubation, whereas significant increases in tetrahydrobiopterin were found only after 48 h exposure of the cells to glucocorticoids. Removal of hormone from the culture medium resulted in rapid loss of cell tetrahydrobiopterin, but a much slower decline in the level of phenylalanine hydroxylase. Thus, although the levels of both phenylalanine hydroxylase and tetrahydrobiopterin in rat hepatoma cells are regulated by glucocorticoids, this regulation is apparently not strictly coordinated. Nevertheless, control of cellular tetrahydrobiopterin levels may be an important regulator of hepatic phenylalanine catabolism since significant increases in the ability of intact rat liver cells to hydroxylate phenylalanine were observed only after 48 h exposure to glucocorticoids, in correlation with increases in cell tetrahydrobiopterin content.     

The influence of level of infection of rats with Nippostrongylus brasiliensis on the haematology and phospholipase activity and mast cell numbers in the small intestine and colon

The haematology and phospholipase activity and mast cell numbers of the small intestine and colon of rats was studied 10 days after infection with various numbers of larvae of N. brasiliensis. A significant reduction in the RBC occurred after infections with 200 and 5000 larvae but not with 1000 larvae. Hb was significantly reduced after infection with 200 larvae and increases in the MCV and MCH indicated the development of a macrocytic anaemia. Reticulocyte count was increased at all levels of infection except after 200 larvae. WBC was increased at all levels of infection except in the 5000 larvae group. Lymphocytes were significantly increased in all groups except those infected with 5000 larvae. Neutrophils increased only at the lower levels of infection. The most marked changes occurred in eosinophil numbers, significant increases occurring with increasing levels of infection. However, after infection with 5000 larvae the numbers were significantly lower than after infection with 200 or 1000 larvae. Phospholipase activity, which is believed to be related to tissue eosinophil levels, was significantly increased at all infection levels in the proximal small intestine. Significant increases in the distal ileum and colon occurred mainly after infection with 1000 and 5000 larvae. Mast cell numbers did not change significantly at any infection level. It is suggested that the pathology observed, here in the form of anaemia, is multifactorial in origin and is largely a function of the immune response, the development and expression of which is dependent on the level of infection, with suppression of immune damage occurring at the high levels of infection when pathogenesis may involve a direct effect of the worms.     

Echinostoma caproni: kinetics of IgM, IgA and IgG subclasses in the serum and intestine of experimentally infected rats and mice

The kinetics of specific immunoglobulin M, A and IgG subclasses against Echinostoma caproni (Trematoda: Echinostomatidae) were analyzed in serum and intestinal fluid of two host species (Wistar rats and ICR mice) in which the course of the infection markedly differs. In rats, the worms were rapidly expelled, whereas E. caproni evokes in mice long-lasting infection. The pattern of antibody responses in both serum and intestinal samples was different in each host species. Serum responses in mice were characterized by significant increases of IgM, IgA, total IgG, IgG1 and IgG3, but not IgG2a. In contrast, serum responses in rats showed elevated levels of IgM, probably in relation to thymus-independent antigens, and slight increases of total IgG, IgG1 and IgG2a. At the intestinal level, increases of IgM and IgA levels were observed in mice. In regard to IgG subclasses, increases in both IgG1 and IgG2a were detected. Later decreases to normal values in IgG2a were also detected. In rats, only increases in total IgG and IgG2a were found. According to our results the development of long-lasting E. caproni infections in mice appears to be associated with a dominance of Th2 responses at the systemic level and balanced Th1/Th2 responses at the local level, characterized by initial increases in IgG1 and IgG2a levels. In contrast, the worm expulsion appears to be related to increases in local IgG2a levels.     

Free amino acid levels in undernourished developing rat brain

Free amino acid levels in the brains of young ones born to mothers fed a 20% protein diet ad libitum (well nourished), 7.5% protein diet ad libitum (protein restricted) and a 20% protein diet in restricted amounts (pair-fed) were investigated during brain development in the present study. The dietary protein was obtained from a cereal-legume mixture. Protein restricted animals showed increases in the levels of taurine, glycine and glutamic acid and decreases in the concentrations of methionine, leucine, isoleucine, and GABA. The pair-fed animal showed increases only in glutamic acid and glycine and a decrease only in the levels of GABA. The significance of these observations is discussed.     

The mechanisms of action of interleukin-1 on rabbit intestinal epithelial cells

Interleukin-1 (IL-1) is an inflammatory mediator that increases Cl- secretion in intestinal epithelial cells. To identify the signal transduction pathway(s) involved in IL-1's action, cells were treated with IL-1 and the levels of cyclooxygenase (COX) enzymes, prostaglandin E2 (PGE2) and phospholipase A2-activating protein (PLAP), and the activity of phospholipase A2 (PLA2) were measured. IL-1 caused concentration- and time-dependent increases in the levels of PLA2 activity, and/or in the levels of PLAP, COX-2 and PGE2. The IL-induced increase in PGE2 levels was biphasic, with the first peak due to the increase in PLAP levels, and the second peak due to the increase in COX-2 levels. This increase in PGE2 levels may provide a mechanism for acute and chronic inflammation in the intestine.     

FEMALE-BIASED SEX RATIOS IN A FACULTATIVELY SOCIAL BEE AND THEIR IMPLICATIONS FOR SOCIAL EVOLUTION

Montane populations of the Australian allodapine bee, Exoneura bicolor, are characterized by high levels of cooperative nesting and strongly female-biased sex ratios. A conspecific population from heathland shows much lower levels of cooperative nesting and lower levels of female bias. In both habitats, sex-ratio bias is greatest in the smallest brood sizes and becomes successively less biased in larger broods. Parity is approached in the largest heathland colonies, but not for any brood-size category in montane areas. Adult intracolony relatedness is moderately high for colonies in both reused and newly founded nests in the montane habitat, but probably low or zero for newly founded nests in heathland. Colony efficiency, measured as the number of brood per adult, increases with colony size in both habitats, suggesting that cooperation between females increases mean female fitness. It is argued that patterns of sex allocation are consistent with nonlinear fitness-return models, in which the mean reproductive value of daughters increases with the number of daughters produced in a brood. Such increases probably arise from a number of social interactions, including cooperative brood defense, increased task efficiency, and lower per capita costs in nest construction. The term “local fitness enhancement” is introduced here to describe these effects collectively. The female-biased ratios should lower selective thresholds for sib-directed altruism, at least in the earlier stages of colony development. It is argued that local fitness enhancement facilitates eusociality in allodapine bees and could also play a role in other haplodiploid taxa, provided cooperative nesting largely involves sisters, colony efficiency increases with colony size, and optimal colony sizes are only achieved after two or more generations after founding.     

Diverse action of acrylamide on cytochrome P450 and glutathione S-transferase isozyme activities,mRNA levels and protein levels in human hepatocarcinoma cells

Humans are exposed to acrylamide in their diet and cigarette smoke. Acrylamide is metabolized into glycidamide by CYP2E1. However, very few studies regarding the effects of acrylamide on cytochrome P450 and Glutathione S-Transferase (GST) isozymes have been pursued. The aim of this study is to elucidate the effects of acrylamide on cytochrome P450 and GST isozymes in HepG2 cell line. Treatment with 1.25 and 2.5 mM acrylamide caused 9.5- and 3.7-fold increases and 4.0- and 3.3-fold increases in CYP1A-associated ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) activities, respectively. These increases were consistent with increases in mRNA and protein levels of these isozymes. Similarly, CYP2E1-associated aniline 4-hydroxylase (ANH) activity, protein levels, and mRNA levels increased 2.1- and 2.6-fold, 2.4- and 3.2-fold, and 1.4- and 1.9-fold following 1.25 and 2.5 mM acrylamide treatments, respectively. In addition, GST-mu activity was increased 2.4- and 5.1-fold by acrylamide. Moreover, GST-mu mRNA and protein levels increased twofold as a result of acrylamide treatment. In contrast, GST-pi protein and mRNA levels decreased significantly. In conclusion, human cell exposure to acrylamide causes an increase in the levels of carcinogenicity and toxicity and a disturbance in drug metabolism, possibly due to complex effects on P450 and GST isozymes.