bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of diabetes on intestinal magnesium absorption in the rat
Authors: Miller DL , Schedl HP
Published: December 2017

Control and streptozotocin-diabetic rats were studied at 5, 12, and 32 days after induction of diabetes. Magnesium absorption was measured by in situ perfusion of duodenum and ileum. At 5 days, duodenal mucosal growth is similar in controls and diabetics. At 12 days, mucosal growth is 50% greater in diabetics, and at 32 days, 100% greater. Ileal mucosal growth followed the same pattern but was half that of duodenum. Therefore, absorption data were expressed per centimeter segment length to define absorptive capacity of the segment and per gram dry weight of mucosa to define absorptive specific activity. Mean absorptive specific activity was lower in diabetics than controls at all time intervals. The difference was significant only for duodenum of diabetics at 32 days, when magnesium absorption declined to half that of controls. In contrast, absorptive capacity for both segments remained the same in both groups, attributable to the greater mucosal growth in diabetics. These findings for magnesium contrast with effects of diabetes on calcium transport: specific absorption and segment absorptive capacity are depressed in diabetics at both 5 and 11 days. Thus, although transport of magnesium and calcium usually tend to change in parallel in diabetes, transport of magnesium is depressed later and to a lesser degree than calcium, and segment transport capacity is maintained. The findings suggest differences in mechanism of regulation of magnesium and calcium transport.
Failure of NaHCO3 and KHCO3 to inhibit renin in the rat
Authors: Kotchen TA , Galla JH , Luke RG
Published: December 2017

To evaluate the contribution of chloride to NaCl- and KCl-induced renin inhibition, renin responses to NaCl or NaHCO3 and to KCl or KHCO3 loading were compared in NaCl-deprived rats. Sodium balance in animals drinking isotonic NaHCO3 and NaCl for 9 days did not differ (P greater than 0.40); K+ balance was less positive in NaHCO3-drinking animals (P less than 0.005). Plasma renin activity (PRA) in NaCl-loaded (16.5 ng/ml per h +/- 4.4 SE), but not in NaHCO3-loaded rats (57.2 +/- 9.8), was lower (P less than 0.005) than in NaCl-deprived controls (44.8 +/- 4.7). Renal renin content (RRC) of NaCl but not of NaHCO3-drinking animals was also decreased (P less than 0.02). Both PRA and RRC of KCl- but not of KHCO3-loaded rats (5 meq K+/10 g diet) were lower (P less than 0.01) than in NaCl-deprived controls. After acute intravenous expansion with isotonic NaCl or NaHCO3, increases of plasma volume and plasma K+ did not differ (P greater than 0.05). However, PRA of NaCl-expanded rats (11.8 +/- 3.8) was lower (P less than 0.05) than in NaHCO3-expanded animals (29.7 +/- 8.5). The failure of NaHCO3 and KHCO3 to inhibit renin suggests a role for chloride in mediating the renin responses to Na+ and K+.
Oxygen delivery in perfused rat kidney: NADH fluorescence and renal functional state
Authors: Franke H , Barlow CH , Chance B
Published: December 2017

Changes in steady-state levels of reduced pyridine nucleotide (PN) recorded by continuous monitoring of surface fluorescence were correlated with changes in physiological function of perfused rat kidneys when subjected to anoxia, ischemia, hypothermia, variations in perfusion pressure, inhibition of Na-K ATPase, and uncoupling of oxidative phosphorylation. Biphasic responses of PN reduction and oxidation during ischemic cycles at varying temperatures and anoxic cycles at different perfusion pressures demonstrated the presence of two different cell populations in the kidney cortex, those with sufficient oxygen and those without. The magnitude of PN fluorescence change during ischemia increased with decreasing temperature demonstrating better tissue oxygenation during hypothermia. The measurement of mitochondrial NADH oxidation in the perfused kidney during transitions from CO anoxia to normoxia was made possible by flash photolytic activation of mitochondrial electron transport. The half time for NADH oxidation (125 ms) was independent of the rate of oxygen delivery while the initial rate and extent of reaction was faster and steeper, respectively, at higher perfusion pressure, due to a better tissue oxygenation and faster CO washout.
Bile acid conjugation in fetal hepatic organ cultures
Authors: deBelle RC , Blacklow NR , Baylan M , Little JM , Lester R
Published: December 2017

A new technique has been developed in which mammalian fetal liver can be maintained in organ culture for prolonged periods with intact structure and function. Near-term rat fetal liver explants were incubated in vitro for periods of up to 3 wk with preservation of normal cellular morphology and intercellular (organ) relationships. [14C]cholate was incorporated into tissue and medium conjugates at a constant rate during 21 days in vitro. During a 24-h incubation with radioactively labeled cholic acid, bile acid conjugates accumulated in tissues to a maximum value by 6 h and maintained this value through 24 h. During the same 24-h incubation with [14C]cholate, conjugates were secreted into the medium at a constant rate. Addition of 8 X 10(-4) M taurine to the medium during a 4-day incubation produced a threefold enhancement in the rate of conjugate formation in tissues and medium. Enhanced conjugation in the presence of additional taurine was due almost entirely to increased taurocholate formation and no significant difference was observed in the amount of glycocholate formed. Exposure of explants to 3.6 X 10(-4) M cycloheximide for prolonged periods resulted in inhibition of conjugate formation, but when this concentration of cycloheximide was maintained for only 24 h a significantly (P less than 0.001) increased rate of conjugate formation was observed. The results indicate that metabolic processes in the organ-culture system are in a state of dynamic equilibrium and that morphologic integrity and specific hepatocytic function are maintained after 21 days in vitro. Preferential taurocholate formation was demonstrated in rat fetal liver, and the data suggest that glycine and taurine interact with separate enzymatic systems in bile acid conjugation. The possible mechanisms that mediate the effect of cycloheximide are discussed.
NAD glycohydrolase activity in hearts with acute experimental infarction
Authors: Nunez R , Calva E , Marsch M , Briones E , Lopez-Soriano F
Published: December 2017

Myocardial ischemia was produced in dogs by occluding the descending coronary artery. NAD decreased in the ischemic tissue taken 2 h after the arterial ligature, and an equivalent amount of nicotinamide was detected instead. A further breakdown occurred when fragments of ischemic and nonischemic tissue were incubated at 37 degrees C. In contrast, NAD concentration remained unchanged for as long as 60 min in incubated fragments from normal heart. When normal tissue was homogenized, an immediate hydrolysis of NAD was observed with the formation of stoichiometric amounts of nicotinamide. An excess of nicotinamide completely inhibited the NAD degradation. The NAD glycohydrolase activity assayed in vitro was similar in normal, ischemic, and nonischemic cardiac homogenates. The conclusions are that the NAD loss in the ischemic heart is due to the tissue NAD glycohydrolase activity and that the cell disorganization provoked by the occlusion of the coronary artery seems to facilitate the reaction between the substrate and the enzyme.
Renal hydrogen ion secretion after release of unilateral ureteral obstruction
Authors: Thirakomen K , Kozlov N , Arruda JA , Kurtzman NA
Published: December 2017

The effect of 24 h of unilateral ureteral obstruction on HCO3 reabsroption and urinary acidification was studied in dogs. The postobstructed kidney (EK) had a significantly lower glomerular filtration rate and renal plasma flow than the contralateral kidney (CK). Urinary pH prior to HCO3 loading was significantly higher in the EK as was maximal HCO3 reabsorption. Saline loading depressed HCO3 reabsorption to the same degree in both kidneys. Urinary PCO2, during HCO3 loading, and during phosphate infusion, was significantly lower in the EK than the CK. Fractional Na excretion was significantly higher in the EK than the CK after deoxycorticosterone acetate administration. Na2SO4 administration enhanced acid excretion only in the CK. K excretion was significantly lower in the EK than the CK both during HCO3 loading and Na2SO4 administration. There was redistribution of cortical blood flow from the outer cortex toward the inner cortex in the EK as compared to the CK. There was no difference in plasma renin activity from both renal veins. These data demonstrate enhanced proximal H+ secretion (which is abolished by volume expansion) and impaired distal H+ secretion by the postobstructed kidney. The distal defect is likely an effect of a generalized disorder of distal transport in that both K secretion and steroid-responsive Na reabsorption were impaired in the postobstructed kidney.
Postsplenectomy blood values, marrow cytology, erythrocyte life-span, and sequestration in mice
Authors: Anosa VO
Published: December 2017

Studies in mice indicated that splenectomy influenced neither the erythrocyte and leukocyte total and differential values nor the erythrocyte survival. The right femoral marrow erythrocyte and nucleated cell counts were also not altered by splenectomy, and compensation for the important splenic contribution to erythropoiesis was in the form of marrow erythroid hyperplasia with a drop in the myeloid:erythroid ratio from 2.79:1.00 in intact mice to 1.44:1.00 in splenectomized mice. The spleen was the most important site for the sequestration of erythrocytes as monitored by tissue localization of 51Cr-labeled erythrocytes, and this function was assumed by the liver in splenectomized mice by almost doubling its activity. The total residual body count was, however, significantly decreased (P less than 0.01) by splenectomy.
Inner medullary plasma flow in the kidney with ureteral obstruction
Authors: Solez K , Ponchak S , Buono RA , Vernon N , Finer PM , Miller M , Heptinstall RH
Published: December 2017

To test the thesis that ureteral obstruction causes medullary ischemia, we determined inner medullary plasma flow (IMPF) in rats with bilateral or unilateral ureteral obstruction, and after relief of obstruction, by the intravenous 125I-albumin infusion technique. A progressive decline in IMPF was observed during obstruction of 18 h duration, greater in bilateral obstruction (7% of normal at 5h) than in unilateral obstruction (28% of normal at 5 h). The elevation in ureteral pressure was greater and more sustained in bilateral obstruction. After relief of obstruction, IMPF rose to 69-78% of normal in both groups within 2 h. Histologic studies showed tubular necrosis in portions of the inner and outer medulla immediately beneath the renal pelvic epithelium after bilateral or unilateral obstruction of 18 h duration, and India ink perfusion studies showed very poor filling of vasa recta in these areas. The concentrating defect in the postobstructive kidney may be related, at least in part, to damage inflicted by medullary ischemia during obstruction.
Phosphorylation of cardiac regulatory proteins by cyclic AMP-dependent protein kinase
Authors: Reddy YS
Published: December 2017

Cardiac myofibrils were purified from canine myocardium, and the regulatory proteins (troponin + tropomyosin) were extracted and shown to contain endogenous cyclic AMP-dependent protein kinase activity. Other cyclic nucleotide stimulated the protein kinase activity but only at higher concentrations. The enzyme was able to catalyze phosphorylation of conventional substrates such as histones and casein as well as a component of the regulatory protein fraction with a molecular weight of 28,000 daltons. Endogenous phosphorylation required the presence of Mg2+ and was inhibited by Ca2+. A protein kinase inhibitor obtained from skeletal muscle inhibited the cyclicAMP-dependent phosphorylation. Escherichia coli alkaline phosphatase dephosphorylated the endogenous substrates. The level of phosphorylation found is severalfold higher than we have previously reported. A protein kinase, with its close association with the regulatory proteins, seems to be well suited to transmitting the message from the cyclic AMP to the regulatory proteins, a phenomenon that may influence the cardiac contractility via the troponin phosphorylation. The inhibitory effect of troponin on actomyosin might be changed by its state of phosphorylation.
Protein composition of lung fluids in anesthetized dogs with acute cardiogenic edema
Authors: Vreim CE , Snashall PD , Staub NC
Published: December 2017

We measured the protein composition of plasma and lung fluids from nine dogs with cardiogenic edema. To produce the edema, we increased left atrial pressure an average of 36 cmH2O by inflating a balloon catheter in the left atrium, infusing norepinephrine, and infusing large volumes of saline or saline-diluted blood. Blood samples were collected every 15 min, and airway fluid was collected from five dogs that developed severe edema. Terminally, the chest was opened and the lungs were removed. Samples of alveolar fluid were taken from the excised lung by direct pleural puncture with micropipettes. The lungs were frozen in liquid nitrogen and samples of free interstitial fluid were taken from the perivascular and peribronchial cuffs. Plasma and lung fluids were analyzed for total protein by the Lowry method and for albumin-globulin fractions by cellulose acetate electrophoresis. The average total protein concentrations (g/100 ml) were--plasma, 2.65; free interstitial fluid, 1.05; alveolar fluid, 1.23; and airway fluid, 1.29. The average albumin fraction of plasma was 0.40; of alveolar fluid, 0.43; and of airway fluid, 0.43. The protein concentrations in the three lung fluids were nearly identical to each other, but were less than half that of plasma. We conclude that in high-pressure pulmonary edema with alveolar flooding, the capillary endothelium retains the ability to restrict protein relative to fluid filtration, but the alveolar epithelium becomes freely permeable to protein.
pH environmental of red cells in the spleen
Authors: Levesque MJ , Groom AC
Published: December 2017

Intrasplenic pH in vivo was deduced from measurements on blood drained from cat spleen during contraction with the inflow occluded. The pH of blood in the red pulp is normally 7.20, but stasis or reduced flow through the pulp causes pH to fall toward 6.8. The splenic pulp contains blood of high hematocrit. To evaluate the role of buffering by the red cells themselves, intrasplenic p/ in red cell-free spleens was, therefore, estimated atering and leaving the spleen during red cell washout. At inflow pH less than 6.8 the outflow pH was raised, at inflow pH = 6.8 there was no change, b,t at inflow pH greater than 6.8 the outflow pH was lowered. These results indicate that the pH environment of red cells in the spleen results indicate that the pH environment of red cells in the spleen results from the interplay of two separate factors: i) pH-determining elements of the splenic tissue that buffer at 6.8, and ii) buffering provided by red cells passing through the pulp.
Contributions of pressure and flow sensitivity to autoregulation in mesenteric arterioles
Authors: Johnson PC , Intaglietta M
Published: December 2017

The relative influence of presence and flow on dilation of arterioles with pressure reduction was examined in preparations of cat mesentery. Erythrocyte velocity and diameter were measured in individual arterioles during stepwise reduction in mesenteric arterial pressure. Volume flow was calculated from velocity and diameter data. Approximately half of the arterioles which dilated with pressure reduction also showed an increase in volume flow. In a second series of experiments, a graded reduction of flow in single arterioles was produced by local downstream occlusion. Graded occlusion caused dilation. In a third series, flow in single arterioles was completely stopped by downstream occlusion, and arterial pressure was then lowered. Most arterioles dilated with pressure reduction. In a fourth series, flow in the total preparation was completely stopped and static intravascular pressure set by a reservoir. Elevation of static pressure typically produced arteriolar constriction. We conclude from these studies that the mesenteric arteriole is sensitive both to intravascular pressure and flow, with the former probably more important than the latter in the phenomenon of autoregulation.
Lithium-induced diuretic effect of antidiuretic hormone in rats
Authors: Dousa TP , Barnes LD
Published: December 2017

The effect of a low dose of lithium (1 meq/kg per day) on renal function and its response to antidiuretic hormone (ADH) was studied in unanesthetized rats. This dose of lithium itself had no influence on renal water and electrolyte excretion, but lithium-treated rats responded paradoxically to exogenous ADH by increases in urinary volume, excretion of total solutes, sodium, potassium, and phosphate. Administration of ADH in the presence of lithium led to a lowering of urine osmolality, but free water clearance was not significantly reduced. Adenylate cyclase from the renal medulla of animals treated with ADH and lithium had a lower response to synthetic vasopressin in vitro than in animals treated with lithium alone. The results suggest that exogenous ADHis diuretic in the presence of a low concentration of lithilm. The predominant mechanism for this diuresis is probably inhibition of electrolyte and isomotic water reabbsorption in various nephron segments, including those proximal to the collecting ducts. ADH also markedly increased urinary excretion of lithium and appears to promote accumulation of lithium in the renal medulla.
Ion transport across isolated antral mucosa of the rabbit
Authors: Fromm D , Schwartz JH
Published: December 2017

Isotopic fluxes of Na, Cl, and K were measured across isolated antral mucosa under short-circuit conditions. HCO3 fluxes were also measured with either isotopic and/or pH-stat methods. Net secretion of all four ions was observed. HCO3 secretion is due to a transmural process requiring metabolic energy. Secretion of endogenous HCO3 was not observed, and the unidirectional mucosal-to-serosal flux of HCO3 was negligible. There appears to be a close relationship between HCO3 secretion and the unidirectional mucosal-to-serosal Cl flux, but not relationships were observed between the unidirectional serosal-to-mucosal flux or either unidirectional Na flux. The bulk of HCO3 secretion is independent of the unidirectional Cl fluxes, but there is a fraction of HCO3 transport that is dependent on unidirectional Cl transport. However, HCO3 transport is not measurably influenced by inhibition of net Cl (and Na) transport per se.
Extracellular space of swine aorta measured with [14C]inulin and [14C]sucrose
Authors: Harrison RG , Massaro TA
Published: December 2017

Measurements of the extracellular space (ECS) of the isolated swine thoracic aorta were performed with both [14C]inulin and transient measurements and appeared to have better access to available tissue water than the [14C]sucrose gave more consistent results in available tissue water than the [14C]inulin. With [14C]sucrose as the tracer, no significant difference in the ECS was found when the tissue was incubated for 1.5 h in the presence of oxygen and glucose as compared to an incubation in which both oxygen and glucose were absent. However, the ion contents were markedly altered by this change in incubation medium. When oxygen and glucose were present tissue K+ was significantly higher and tissue Na+ was significantly lower than when these metabolites were deleted from the medium. Thus, significant alteration in ion content did not lead to substantial cell damage or bursting.
In vivo control of mitochondrial enzyme concentrations and activity by oxygen
Authors: Mela L , Goodwin CW , Miller LD
Published: December 2017

Newborn and adult dog heart mitochondria were prepared from animals chronically adjusted to varying arterial oxygen tensions. Similarly, rat liver and heart mitochondria were isolated from animals acutely exposed to lowered inspired oxygen. After isolation, all mitochondrial samples were assayed under normoxic conditions. These experiments illustrated the following effects of oxygen on mitochondrial function: 1) respiratory activity in State 3 or in the uncoupled state increased after hypoxia and decreased after increased in vivo oxygenation; 2) similarly, the turnover of cytochrome oxidase increased in hypoxia and decreased after increased oxygenation; 3) after chronic hypoxia cytochrome oxidase, cytochrome c and b concentrations decreased per miligram of mitochondrial protein; 4) all mitochondrial preparations were well coupled and exhibited normal capabilities to perform oxidative phosphorylation. The data are interpreted to indicate sensitive control of mitochondrial respiratory capacities by oxygen in vivo.
Regulation of avian insulin secretion by isolated perfused chicken pancreas
Authors: King DL , Hazelwood RL
Published: December 2017

Chicken insulin secretory responses to glucose, glucagon, tolbutamide, and lack of Mg2+ were measured using isolated perfused in situ chicken pancreata. Although elevating perfusate glucose concentration from 100 to 250 mg/100 ml failed to increase insulin release, 500 mg glucose/100 ml provoked a transient 5-min insulin response. Additionally, 700 mg glucose/100 ml resulted in both a transient response and subsequent elevation in secretory rate that continued throughout the following 50-min stimulatory period. Glucagon (500 microgram/ml) and omission of perfusate Mg2+ potentiated glucose-stimulated insulin output by 6 and 25%, respectively. A faster release of insulin (less than 1 min) occurred during tolbutamide infusion (0.13 mg/ml) than with either 500 or 700 mg glucose per 100 ml (2-3 min); however, secretory rates declined to near basal levels within 5 min. Mammalian-like insulin responses to glucose, glucagon, Mg2+ lack, and tolbutamide suggest similarities between avian and mammalian beta-cell insulin secretory mechanisms. Nevertheless, the relatively high chicken insulin release threshold and low insulin output to glucose indicate that chicken pancreata are relatively glucose insensitive.
Energy state, pH, and vasomotor tone during hypoxia in precontracted pulmonary and femoral arteries
Authors: Leach R. M. , Sheehan D. W. , Chacko V. P. , Sylvester J. T.
Published: December 2017

To assess effects of smooth muscle energy state and intracellular pH (pHi) on pulmonary arterial tone during hypoxia, we measured ATP, phosphocreatine, Pi, and pHi by31P-NMR spectroscopy and isometric tension in phenylephrine-contracted rings of porcine proximal intrapulmonary arteries. Hypoxia caused early transient contraction followed by relaxation and late sustained contraction. Energy state and pHi decreased during relaxation and recovered toward control values during late contraction. Femoral arterial rings had higher energy state and lower pHi under baseline conditions and did not exhibit late contraction or recovery of energy state and pHi during hypoxia. In pulmonary arteries, glucose-free conditions abolished late hypoxic contraction and recovery of energy state and pHi, but endothelial denudation abolished only late hypoxic contraction. NaCN had little effect at 0.1 and 1.0 mM but caused marked vasorelaxation and decreases in energy state and pHi at 10 mM. These results suggest that 1) regulation of tone, energy state, and pHidiffered markedly in pulmonary and femoral arterial smooth muscle, 2) hypoxic relaxation was mediated by decreased energy state or pHidue to hypoxic inhibition of oxidative phosphorylation, 3) recovery of energy state and pHi in hypoxic pulmonary arteries was due to accelerated glycolysis mediated by mechanisms intrinsic to smooth muscle, and 4) late hypoxic contraction in pulmonary arteries was mediated by endothelial factors that required hypoxic recovery of energy state and pHi for transduction in smooth muscle or extracellular glucose for production and release by endothelium.
Electrical behavior of guinea pig tracheal smooth muscle
Authors: Bramich Narelle J.
Published: December 2017

Intracellular recordings were taken from the smooth muscle of the guinea pig trachea, and the effects of intrinsic nerve stimulation were examined. Approximately 50% of the cells had stable resting membrane potentials of −50 ± 1 mV. The remaining cells displayed spontaneous oscillations in membrane potential, which were abolished either by blocking voltage-dependent Ca2+channels with nifedipine or by depleting intracellular Ca2+stores with ryanodine. In quiescent cells, stimulation with a single impulse evoked an excitatory junction potential (EJP). In 30% of these cells, trains of stimuli evoked an EJP that was followed by oscillations in membrane potential. Transmural nerve stimulation caused an increase in the frequency of spontaneous oscillations. All responses were abolished by the muscarinic-receptor antagonist hyoscine (1 μM). In quiescent cells, nifedipine (1 μM) reduced EJPs by 30%, whereas ryanodine (10 μM) reduced EJPs by 93%. These results suggest that both the release of Ca2+ from intracellular stores and the influx of Ca2+ through voltage-dependent Ca2+channels are important determinants of spontaneous and nerve-evoked electrical activity of guinea pig tracheal smooth muscle.
Oxygen induction of epithelial Na+transport requires heme proteins
Authors: Rafii Bijan , Coutinho Chris , Otulakowski Gail , O'Brodovich Hugh
Published: December 2017

Fetal distal lung epithelial (FDLE) cells exposed to a postnatal O2concentration of 21% have higher epithelial Na+channel (ENaC) mRNA levels and Na+transport relative to FDLE cells grown in a fetal O2concentration of 3%. To investigate the mechanism of this process, FDLE monolayers were initially cultured in 3% O2, and then some were switched to a 21% O2environment. Incubation of FDLE cells with the iron chelator deferoxamine, CoCl2, NiCl2, or an inhibitor of heme synthesis prevented or diminished the O2induction of amiloride-sensitive short-circuit current in FDLE cells. Similarly, defer- oxamine and cobalt prevented O2-induced ENaC mRNA expression. Exposure of FDLE cells grown under hypoxic conditions to carbon monoxide increased both ENaC mRNA expression and amiloride-sensitive short-circuit current. We therefore concluded that induction of ENaC mRNA expression and amiloride-sensitive Na+transport in FDLE cells by a physiological increase in O2concentration seen at birth requires iron and heme proteins.
S-nitrosoglutathione-induced decrease in calcium sensitivity of airway smooth muscle
Authors: Pabelick Christina M. , Warner David O. , Perkins William J. , Jones Keith A.
Published: December 2017

The purpose of this study was to examine whether the nitric oxide donor S-nitrosoglutathione (GSNO) relaxes canine tracheal smooth muscle (CTSM) strips by decreasing Ca2+sensitivity [i.e., the amount of force for a given intracellular Ca2+concentration ([Ca2+]i)]. We further investigated whether GSNO decreases Ca2+sensitivity by altering the relationship between regulatory myosin light chain (rMLC) phosphorylation and [Ca2+]iand the relationship between force and rMLC phosphorylation. GSNO (100 μM) relaxed intact CTSM strips contracted with 45 mM KCl by decreasing Ca2+sensitivity in comparison to control strips without significantly decreasing [Ca2+]i. GSNO reduced the amount of rMLC phosphorylation for a given [Ca2+]ibut did not affect the relationship between isometric force and rMLC phosphorylation. These results show that in CTSM strips contracted with KCl, GSNO decreases Ca2+sensitivity by affecting the level of rMLC phosphorylation for a given [Ca2+]i, suggesting that myosin light chain kinase is inhibited or that smooth muscle protein phosphatases are activated by GSNO.
Fas cross-linking induces apoptosis in human airway smooth muscle cells
Authors: Hamann Kimm J. , Vieira Joaquim E. , Halayko Andrew J. , Dorscheid Delbert , White Steven R. , Forsythe Sean M. , Camoretti-Mercado Blanca , Rabe Klaus F. , Solway Julian
Published: December 2017

Hypertrophy and hyperplasia lead to excess accumulation of smooth muscle in the airways of human asthmatic subjects. However, little is known about mechanisms that might counterbalance these processes, thereby limiting the quantity of smooth muscle in airways. Ligation of Fas on the surface of vascular smooth muscle cells and nonmuscle airway cells can lead to apoptotic cell death. We therefore tested the hypotheses that 1) human airway smooth muscle (HASM) expresses Fas, 2) Fas cross-linking induces apoptosis in these cells, and 3) tumor necrosis factor (TNF)-α potentiates Fas-mediated airway myocyte killing. Immunohistochemistry using CH-11 anti-Fas monoclonal IgM antibody revealed Fas expression in normal human bronchial smooth muscle in vivo. Flow cytometry using DX2 anti-Fas monoclonal IgG antibody revealed that passage 4 cultured HASM cells express surface Fas. Surface Fas decreased partially during prolonged serum deprivation of cultured HASM cells and was upregulated by TNF-α stimulation. Fas cross-linking with CH-11 antibody induced apoptosis in cultured HASM cells, and this effect was reduced by long-term serum deprivation and synergistically potentiated by concomitant TNF-α exposure. TNF-α did not induce substantial apoptosis in the absence of Fas cross-linking. These data represent the first demonstration that Fas is expressed on HASM and suggest a mechanism by which Fas-mediated apoptosis could act to oppose excess smooth muscle accumulation during airway remodeling in asthma.
Amiodarone induces apoptosis of human and rat alveolar epithelial cells in vitro
Authors: Bargout Raed , Jankov Aleksandar , Dincer Erhan , Wang Rongqi , Komodromos Themis , Ibarra-Sunga Olivia , Filippatos Gerasimos , Uhal Bruce D.
Published: December 2017

The antiarrhythmic amiodarone (AM) and its metabolite desethylamiodarone (Des) are known to cause AM-induced pulmonary toxicity, but the mechanisms underlying this disorder remain unclear. We hypothesized that AM might cause AM-induced pulmonary toxicity in part through the induction of apoptosis or necrosis in alveolar epithelial cells (AECs). Two models of type II pneumocytes, the human AEC-derived A549 cell line and primary AECs isolated from adult Wistar rats, were incubated with AM or Des for 20 h. Apoptotic cells were determined by morphological assessment of nuclear fragmentation with propidium iodide on ethanol-fixed cells. Necrotic cells were quantitated by loss of dye exclusion. Both AM and Des caused dose-dependent necrosis starting at 2.5 and 0.1 μg/ml, respectively, in primary rat AECs and at 10 and 5 μg/ml in subconfluent A549 cells ( P < 0.05 and P < 0.01, respectively). AM and Des also induced dose-dependent apoptosis beginning at 2.5 μg/ml in the primary AECs ( P < 0.05 for both compounds) and at 10 and 5 μg/ml, respectively, in the A549 cell line ( P < 0.01). The two compounds also caused significant net cell loss (up to 80% over 20 h of incubation) by either cell type at drug concentrations near or below the therapeutic serum concentration for AM. The cell loss was not due to detachment but was blocked by the broad-spectrum caspase inhibitor Z-Val-Ala-Asp-fluoromethylketone. Furthermore, the angiotensin-converting enzyme inhibitor captopril (500 ng/ml) and the angiotensin-receptor antagonist saralasin (50 μg/ml) significantly inhibited both the induction of apoptosis and net cell loss in response to AM. These results are consistent with recent work from this laboratory demonstrating potent inhibition of apoptosis in human AECs by captopril (Uhal BD, Gidea C, Bargout R, Bifero A, Ibarra-Sunga O, Papp M, Flynn K, and Filippatos G. Am J Physiol Lung Cell Mol Physiol 275: L1013–L1017, 1998). They also suggested that the accumulation of AM and/or its primary metabolite Des in lung tissue may induce cytotoxicity of AECs that might be inhibitable by angiotensin-converting enzyme inhibitors or other antagonists of the renin-angiotensin system.
ETA-receptor blockade and ETB-receptor stimulation in experimental congenital diaphragmatic hernia
Authors: Thébaud Bernard , de Lagausie Pascal , Forgues Dominique , Aigrain Yves , Mercier Jean-Christophe , Dinh-Xuan A. Tuan
Published: December 2017

The aim of this study was to assess the role of nitric oxide (NO) and endothelin (ET)-1 in the pathophysiology of persistent pulmonary hypertension of the newborn in fetal lambs with a surgically created congenital diaphragmatic hernia (CDH). The pulmonary vascular response to various agonists and antagonists was assessed in vivo between 128 and 132 days gestation. Age-matched fetal lambs served as control animals. Control and CDH lambs had similar pulmonary vasodilator responses to acetylcholine, sodium nitroprusside, zaprinast, and dipyridamole. The ETA-receptor antagonist BQ-123 caused a significantly greater pulmonary vasodilatation in CDH than in control animals. The ETB-receptor agonist sarafotoxin 6c induced a biphasic response, with a sustained pulmonary vasoconstriction after a transient pulmonary vasodilatation that was not seen in CDH animals. We conclude that the NO signaling pathway in vivo is intact in experimental CDH. In contrast, ETA-receptor blockade and ETB-receptor stimulation significantly differed in CDH animals compared with control animals. Imbalance of ET-1-receptor activation favoring pulmonary vasoconstriction rather than altered NO-mediated pulmonary vasodilatation is likely to account for persistent pulmonary hypertension of the newborn in fetal lambs with a surgically created CDH.
Exercise, dietary obesity, and growth in the rat
Authors: Pitts G. C. , Bull L. S.
Published: December 2017

Four regimens: high-fat diet, exercised (I); chow, exercised (II); high-fat sedentary (III); and chow, sedentary (IV) were initiated in 35-day-old male rats. Growth was exponential in I and II and exponential progressing to rectilinear in III and IV. The exponential model predicted the decreasing rank order in asymptotic weight to be: III, IV, I, II. Body composition data (9 components) showed rank order in masses of fat and the fat-free body mass compartment (FFBM) to be the same as for asymptotic live weight. The rectilinear growth mode probably reflected fat accretion. High-fat diet increased and treadmill exercise decreased FFBM, the latter being reversible. These effects depended on regimen initiations by the 5-7th wk of age. During growth, masses of H2O, muscle, and skin increased as functions of body size; bone as a function of age; and heart, liver, gut, testevity, and diet. Growth in body size was expressed more precisely with FFBM, instead of live weight, as the index of size.
Sympathetic inhibition of thermogenesis in the infant rat: possible glucostatic control
Authors: Bignall K. E. , Heggeness F. W. , Palmer J. E.
Published: December 2017

Nonshivering thermogenesis (NST) was examined during cold exposure (30 degrees C) in 5-day-old rats, during food deprivation. NST in the fed state doubled the O2 consumption observed at neutral temperatures. With fasting, the additional O2 consumption stimulated by cold dropped to that observed at thermoneutrality within 6 h, and colonic temperature (Tco) dropped concomitantly. Blood glucose (BG) concentration was halved. Oxygen consumption and Tco in the cold varied linearly with BG changes during food deprivation. 6-Hydroxydopamine transiently stimulated norepinephrine release and elevated metabolism nonadditively with cold stimulation in fed animals, and also stimulated O2 consumption. The drug also partially restored BG concentration, after it had declined during fasting. NST and BG were also restored by gastric infusion of glucose. These data suggest that the decline of NST, and the subsequent hypothermia during food deprivation, is in large part a sympathetically mediated reflex response to low cerebral BG concentration. However, glucose injection in doses sufficient to restore BG after fasting did not restore NST, nor was NST abolished by intracellular glucoprivation with 2-deoxy-D-glucose in fed rats. Thus, it is not argued that BG concentration is in itself an adequate signal for controlling NST.
Comparison of metabolic alterations in hypothalamic and high fat diet-induced obesity
Authors: Inoue S. , Campfield L. A. , Bray G. A.
Published: December 2017

The heterogeneous nature of the experimental obesities induced by ventromedial hypothalamic (VMH) lesion and high fat diet (HFD) have been demonstrated by comparing VMH-lesioned and sham-operated rats fed a HFD or low fat diet (LFD). VMH rats had increased fat mass serum insulin and serum triglycerides but lower serum glucagon and smaller salivary glands than sham-operated animals. The body weight of HFD obese rats was intermediate between VMH and sham-operated animals on the LDF. Liver and fat pad weights showed effects of lesions and diet. Diet did not affect plasma glucagon or insulin. Pair-feeding VMH rats with sham-operated rats prevented weight gain but did not prevent the increase in insulin and fall in glucagon. Studies of insulin secretion from isolated perifused islets showed that basal and both phases of stimulated secretion were significantly increased in VMH groups. The changes in plasma insulin, plasma glucagon, and salivary gland weight in VMH groups are interpreted as showing decreased activity of the sympathetic nervous system following VMH lesions.
Levels and reduction
Authors: Bunge M.
Published: December 2017

This paper addresses the problem of reconciling pluralism with reductionism, i.e., acknowledging both the variety of the world and the need and possibility to explain it. First the various kinds of monism and pluralism that litter the scientific and philosophical literature are examined cursorily. Then certain maligned notions are examined, mainly those of novelty, self-assembly, level, and levels "hierarchy." They are shown to be amenable to analysis and even mathematization. Then the logic of reduction is analyzed. Two kinds of reduction are distinguished: full or straight, and partial or roundabout. And three stands on reduction are examined: anti-, radical, and moderate reductionism. The former is dismissed for being obscurantist and the second for being quixotic. Moderate reductionism, aiming at the (partial) reduction of higher levels to lower ones without skipping any intermediate levels, is adopted. Finally moderate reductionism is found to be consistent with a certain variety of pluralism, characterized as naturalistic.
Response to glucose loading of the lean squirrel monkey in unrestrained conditions
Authors: Ausman L. M. , Gallina D. L.
Published: December 2017

The response of blood glucose (BG), free fatty acids (FFA), and insulin (IRI) to both intravenous (IVGTT) and oral (OGTT) glucose tolerance tests was evaluated in unrestrained, permanently catheterized squirrel monkeys. The mean glucose assimilation rate (K value) for 25 IVGTT was 7.75 +/- 2.84. FFA maximally decayed 54 percent from a mean basal of 1,008 +/- 221 mueq/l associated with a onefold increment inIRI from basal (7.5 +/- 3.5 muU/ml) at 2-5 min. No significant changes were found during intravenous saline loading alone. OGTT (4g/kg) produced peak BG levels at 15-30 min with an immediate FFA decrease of 63 percent and a onefold IRI increment. Carcass composition analyses from 17 animals showed a total extractable lipid content of 6.2 percent. The K value, significantly higher than previously reported, appears to fit well with that expected for the species. The rapid decrease in FFA and BG concentrations demonstrate an apparent high efficiency of a low IRI increment. The association of the low IRI after loading with a low triglyceride depot is discussed.
Blood flow distribution in the duck lung and its control by respiratory gases
Authors: Holle J. P. , Heisler N. , Scheid P.
Published: December 2017

Blood flow to subunits of the lung was studied in the duck by use of radioactive microspheres. In spontaneously breathing, unanesthetized animals (series I) neopulmo was slightly better perfused than the average lung and along the paleopulmonic parabronchi, blood flow was found to decrease in the direction of ventilatory gas flow and thus of decreasing PO2 and increasing PCO2 in lung gas. The effects of respiratory gases on regional lung perfusion were investigated in unidirectionally ventilated animals (series II) in which gas mixtures offered to both lungs could be controlled independently. Local hypoxia resulted in reduction of local blood flow, whereas effects from hyperoxia or CO2 could not be substantiated. Reversal of the direction of unidirectional ventilatory flow (series III), and thus reversal of the profiles of respired gas concentrations along the parabronchi, suggest that the inhomogeneity in blood flow observed in spontaneously breathing animals of series I can only in part be explained as an acute adjustment to the local hypoxia. Calculations show that this inhomogeneity of blood flow constitutes an only minor impairment of the overall gas exchange efficacy of the parabronchial lung.
Hypothalamic thermosensitivity in conscious Pekin ducks
Authors: Simon-Oppermann C. , Simon E. , Jessen C. , Hammel H. T.
Published: December 2017

Conscious Pekin ducks with chronically implanted hypothalamic thermodes were submitted to thermoneutral (Ta 25 degrees C), cold (Ta 5 degrees C), and warm (Ta 33 degrees C) ambient temperatures. Hypothalamic temperature (Thy) was varied in nine steps between 27.9 and 43.5 degrees C in repeated experiments. Cooling of the hypothalamus induced a fall of core temperature (Tc) that was linearly related to Thy and amounted to 1.1--1.3 degrees C at highest cooling intensity. The decrease of Tc was caused by inhibition of metabolic heat production and/or vasodilatation in the skin at cold and thermoneutral Ta and by activation of panting at warm Ta. After the end of cooling a temporary overshoot of heat production occurred, the degree of which depended on the degree of cooling and on Ta, and led to a rapid normalization of Tc. Warming of the hypothalamus induced a slight fall of Tc due to a reduction of metabolic heat production at cold and thermoneutral Ta and to an activation of panting at warm Ta. It is concluded that no specific cold reception and a weak specific warm reception exist in the duck's hypothalamus. A "nonsensory" temperature susceptibility of hypothalamic control functions is responsible for those reactions of thermoregulatory effector activities which do not fall into the categories of adequate thermoregulatory responses to a central thermal stimulus.
Evidence that the amount of food consumed in early life fixes appetite in the rat
Authors: Oscai L. B. , McGarr J. A.
Published: December 2017

Rats were raised in litters of 22 (low caloric intake) or litters of 4 (high caloric intake). At the end of 62 wk, rats from large litters were approximately 140 g lighter than those from small litters even though all animals were permitted unrestricted access to food after weaning. One factor responsible for the smaller body size was a lower voluntary food intake after weaning (8,188 +/- 205 g vs. 9,808 +/- 193 g; P less than 0.001). These results provide evidence that the amount of food consumed during suckling plays an important role in determining the habitual food intake of rats in later life. In a separate experiment, rats were raised in litters of 4, 13, 17, or 22. The results show that as litter size increased from 4 to 22, a corresponding reduction in the voluntary intake of food occurred. These results provide evidence that by controlling the food intake of the newborn rat it is possible to "program" the animal for a desired voluntary food intake in later life.
Proton semiconductors and energy transduction in biological systems
Authors: Morowitz H. J.
Published: December 2017

Energy transduction processes in biology are analyzed in terms of ordered chains of hydrogen bonds. The theory is an extension of studies on proton conductance in ice and is stimulated by current ideas on the role of hydrogen ions in oxidative phosphorylation and photophosphorylation. The possibility of a protochemistry paralleling electrochemistry is presented along with experimental evidence. The theory relating transmembrane electrochemical potential difference of hydrogen ion concentration to the synthesis of ATP is reviewed. The thermodynamics of hydrogen transfer across a membrane is treated including electrochemical and electromechanical factors. As a prelude to considering ATP synthesis, the acid-base dissociation reactions of ATP, ADP, and phosphate are analyzed. The thermodynamics of ATP synthesis is discussed and a detailed model is presented coupling the synthesis to proton transport. The model assumes a gated proton semiconductor that carries protons and allows them to interact specifically with well-defined substrate molecules. The physics of proton transport is outlined and various methods examined in the context of biological membranes. Emphasis is placed on solid-state proton semiconductors and the present theory of such structures is given. A section is included on possible biological applications of these semiconductors.
Endogenous ultradian rhythms in rats exposed to prolonged continuous light
Authors: Honma K. I. , Hiroshige T.
Published: December 2017

Circadian rhythms of locomotor activity, body temperature, and plasma corticosterone were determined simultaneously in individual rats that were exposed to 200 lx continuous light for over 3 mo. Free-running circadian rhythms of locomotor activity persisted for about 2 mo under continuous light and then the rhythms gradually decomposed. After 3 mo of exposure, circadian rhythms disappeared and activity bursts of 1- to 2-h duration manifested themselves several times during a 24-h period. Body temperature also exhibited several bursts of fluctuation and these bursts were closely correlated in their temporal sequence with those of locomotor activity. A least-squares spectrum analysis revealed that the burst had regular 4- to 6-h periods. Plasma corticosterone, determined by serial sampling at 2-h intervals from individual rats, also exhibited several secretion episodes in a day. These episodic secretions synchronized with bursts of locomotor activity. These results suggest that the ultradian component, manifested under prolonged continuous light, is a fundamental unit of the circadian rhythm and an oscillator for the ultradian rhythm is common to the three functions examined.
Body water compartments with human aging using fat-free mass as the reference standard
Authors: Lesser G. T. , Markofsky J.
Published: December 2017

Forty-five healthy men and women aged 16-39 and 59-89 yr were studied for total body water (TBW) and extracellular water (ECW); intracellular water (ICW) was calculated as the difference (ICW = TBW - ECW). An independent measurement of total body fat by inert gas uptake provided a value (+/- 2%) for fat-free mass (FFB is wt minus body fat). Results agreed with observations by others that TBW and ICW are lower in the aged and lower in women, whether expressed as absolute volumes or per unit of weight, surface area, or height. However, with FFB as the reference standard very different aging trends appeared. TBW/FFB remained constant to our oldest measured subjects (704 +/- 7 ml/kg). ICW/FFB was slightly lower at advanced age, but the 4-5% decrease for each sex was within statistical variability. With age ECW increased slightly and its proportion within the fat-free body (ECW/FFB) was significantly higher. Based upon FFB, the distribution, proportions, and aging trends of body water compartments were similar for men, women, and male rats. Although its potential limitations must be appreciated, the FFB appears widely useful as a reference standard. The stability of ICW volume and of fat-free mass in aging man does not support the hypothesis that cellular mass is lost by healthy mammals with age.