bluuebunny/crossref_metadata_2025 huggingface dataset:
Organization of circadian rhythmicity and suprachiasmatic nuclei in malnourished rats
Authors: Aguilar-Roblero Raúl , Salazar-Juarez Alberto , Rojas-Castañeda Julio , Escobar Carolina , Cintra León
Published: December 2017

The present study was aimed at characterizing the effects of low-protein malnutrition (6% casein) on the circadian rhythm of drinking behavior and on suprachiasmatic nuclei immunohistochemistry in Sprague-Dawley rats. Recordings were started at 30 days of age under a 12:12-h light-dark (LD) cycle. At age 150 days, recordings were continued under constant dim red light, and finally the latency to entrain to complete and skeleton photoperiods was established. At the end of the recordings rats were processed for histological analysis. Compared with their controls, malnournished rats exhibited 1) splitting of rhythmicity under LD that 2) condensed to one component in constant dim red light, 3) delayed entrainment to skeleton photoperiod, and 4) precocious entrainment under complete photoperiod. Immunohistochemical analysis showed mainly a decrease in the immunohistochemical detection of vasoactive intestinal polypeptide and glial fibrillar acid protein cells in malnourished animals. These results indicate that in malnourished rats there is a decrease 1) in the coupling force among the oscillators and 2) in the strength of the phase lock between the oscillators and the light-dark cycle.
Hormonal control of thermogenesis in perfused muscle of Muscovy ducklings
Authors: Marmonier Florence , Duchamp Claude , Cohen-Adad Frédérique , Eldershaw Tristram P. D. , Barré Hervé
Published: December 2017

Endocrine stimulation of muscle nonshivering thermogenesis (NST) in ducklings was investigated in vitro using a perfused hindlimb preparation maintained at 25°C. Effects of flow rate, norepinephrine (NE), epinephrine, and glucagon on perfused muscle oxygen consumption (M˙o 2) and perfusion pressure were studied. Control ducklings ( Cairina moschata, 5 wk old) reared at thermoneutrality (25°C, TN) were compared with two age-matched groups exhibiting muscle NST in vivo: cold-acclimated ducklings (4°C, 4 wk, CA) and glucagon-treated ducklings (103 nmol/kg twice daily, intraperitoneally, GT). BasalM˙o 2was higher in CA than in TN or GT ducklings and increased in all groups with elevated flow rates. Catecholamines increased bothM˙o 2and perfusion pressure. The maximal effect onM˙o 2was higher in CA (+36%) and GT ducklings (+43%) than in controls (+31%), but was associated with reduced vasoconstriction. Flow rate did not consistently potentiate the NE response. At high doses, catecholamines became inhibitory onM˙o 2while a monotonous increase of pressure was still observed. Glucagon, by contrast, slightly decreased bothM˙o 2and pressure. This vasodilatory effect was greater in CA ducklings than controls in preconstricted preparations. In vivo, low-dose epinephrine induced a modest thermogenic effect (+10%) in CA ducklings. These findings showed that duckling muscle thermogenesis is directly stimulated in vitro by catecholamines but not by glucagon. Higher in vitro thermogenic effects of NE in ducklings that were expected to exhibit muscle NST in vivo suggests catecholamine involvement in muscle NST in vivo. Potential vascular control of avian muscle NST is discussed.
A finite element model for predicting the distribution of drugs delivered intracranially to the brain
Authors: Kalyanasundaram S. , Calhoun V. D. , Leong K. W.
Published: December 2017

Drug therapy to the central nervous system is complicated by the presence of the blood-brain barrier. The development of new drug delivery techniques to overcome this obstacle will be aided by a clear understanding of the transport processes in the brain. A rigorous theoretical framework of the transport of drugs delivered locally to the parenchyma has been developed using the finite element method. Magnetic resonance imaging has been used to track the transport of paramagnetic contrast markers in the brain. The information obtained by postprocessing spin-echo, T1-weighted, and proton density images has been used to refine the mathematical model that includes realistic brain geometry and salient anatomic features and allows for two-dimensional transport of chemical species, including both diffusive and convective contributions. In addition, the effects of regional differences in tissue properties, ventricular boundary, and edema on the transport have been considered. The model has been used to predict transport of interleukin-2 in the brain and study the major determinants of transport, at both early and late times after drug delivery.
Responsiveness to melatonin and its receptor expression in the aging circadian clock of mice
Authors: Benloucif Susan , Masana Monica I. , Dubocovich Margarita L.
Published: December 2017

This study determined the effect of age on the efficacy of melatonin treatment to phase shift circadian activity rhythms and on melatonin receptor expression in the suprachiasmatic nucleus (SCN) and paraventricular nucleus of the thalamus (PVNT) of C3H/HeN mice. The circadian rhythm of 2-[125I]iodomelatonin binding, assessed at three times of the day [circadian times (CT) 2, 10, and 18], showed a modest age-related decrease in the SCN but not the PVNT of old C3H/HeN mice (24 mo). There was a tendency for age to reduce Mel1a melatonin receptor mRNA expression in the suprachiasmatic nucleus during the day, but not during the night. The magnitude of phase shifts of circadian activity rhythms (advances or delays) induced by administration of melatonin at CT 10 or CT 2 was identical in young and old C3H/HeN mice. Together, these results suggest that the decrease in melatonin receptor expression in the SCN had little effect on melatonin-induced phase shifts of circadian activity rhythms. We conclude that the responsiveness of the circadian timing system to melatonin administration does not decrease with age.
First-order differential-delay equation for the baroreflex predicts the 0.4-Hz blood pressure rhythm in rats
Authors: Burgess Don E. , Hundley Jon C. , Li Sheng-Gang , Randall David C. , Brown David R.
Published: December 2017

We have described a 0.4-Hz rhythm in renal sympathetic nerve activity (SNA) that is tightly coupled to 0.4-Hz oscillations in blood pressure in the unanesthetized rat. In previous work, the relationship between SNA and fluctuations in mean arterial blood pressure (MAP) was described by a set of two first-order differential equations. We have now modified our earlier model to test the feasibility that the 0.4-Hz rhythm can be explained by the baroreflex without requiring a neural oscillator. In this baroreflex model, a linear feedback term replaces the sympathetic drive to the cardiovascular system. The time delay in the feedback loop is set equal to the time delay on the efferent side, ∼0.5 s (as determined in the initial model), plus a time delay of 0.2 s on the afferent side for a total time delay of ∼0.7 s. A stability analysis of this new model yields feedback resonant frequencies close to 0.4 Hz. Because of the time delay in the feedback loop, the proportional gain may not exceed a value on the order of 10 to maintain stability. The addition of a derivative feedback term increases the system’s stability for a positive range of derivative gains. We conclude that the known physiological time delay for the sympathetic portion of the baroreflex can account for the observed 0.4-Hz rhythm in rat MAP and that the sensitivity of the baroreceptors to the rate of change in blood pressure, as well as average blood pressure, would enhance the natural stability of the baroreflex.
Effects of aging on the circadian rhythm of wheel-running activity in C57BL/6 mice
Authors: Valentinuzzi Verónica S. , Scarbrough Kathryn , Takahashi Joseph S. , Turek Fred W.
Published: December 2017

The effects of age on the circadian clock system have been extensively studied, mainly in two rodent species, the laboratory rat and the golden hamster. However, less information is available on how aging alters circadian rhythmicity in a commonly studied rodent animal model, the mouse. Therefore, in the present study we compared the rhythm of wheel-running activity in adult (6–9 mo) and old (19–22 mo) C57BL/6J mice maintained under different lighting conditions for a period of 4 mo. During this period, mice were subjected to phase advances and phase delays of the light-dark (LD) cycle and eventually to constant darkness (DD). In LD (12 h light, 12 h dark), old mice exhibited delayed activity onset relative to light offset and an increase in the variability of activity onset compared with adult mice. After a 4-h phase advance of the LD cycle, old mice took significantly longer to reentrain their activity rhythm when compared with adult animals. Old mice also demonstrated a decline in the number of wheel revolutions per day and a tendency toward a decrease in the length of the active phase. An increase in fragmentation of activity across the 24-h day was obvious in aging animals, with bouts of activity being shorter and longer rest periods intervening between them. No age difference was detected in the maximum intensity of wheel-running activity. In DD, the free-running period was significantly longer in old mice compared with adults. In view of the rapidly expanding importance of the laboratory mouse for molecular and genetic studies of the mammalian nervous system, the present results provide a basis at the phenotypic level to begin to apply genetic methods to the analysis of circadian rhythms and aging in mammals.
Blockade of neuronal nitric oxide synthase alters the baroreflex control of heart rate in the rabbit
Authors: Murakami Hiroshi , Liu Jun-Li , Yoneyama Hirohito , Nishida Yasuhiro , Okada Kenji , Kosaka Hiroaki , Morita Hironobu , Zucker Irving H.
Published: December 2017

In previous studies we used N G-nitro-l-arginine (l-NNA) to investigate the role of nitric oxide (NO) in baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA).l-NNA increased resting mean arterial pressure (MAP), decreased HR, and did not change or slightly decreased RSNA. These changes complicated the assessment of the central effects of NO on the baroreflex control of HR and RSNA. Therefore, in the present study the effects of the relatively selective neuronal NO synthase inhibitor 7-nitroindazole (7-NI) on the baroreflex control of HR and RSNA were investigated in rabbits. Intraperitoneal injection of 7-NI (50 mg/kg) had no effect on resting HR, MAP, or RSNA. 7-NI significantly reduced the lower plateau of the HR-MAP baroreflex curve from 140 ± 4 to 125 ± 4 and from 177 ± 10 to 120 ± 9 beats/min in conscious and anesthetized preparations, respectively ( P < 0.05). In contrast, there was no significant difference in the RSNA-MAP curves before and after 7-NI administration in conscious or anesthetized preparations. These data suggest that blockade of neuronal NO synthase influences baroreflex control of HR but not of RSNA in rabbits.
Salt-sensitive hypertension in ANP knockout mice: potential role of abnormal plasma renin activity
Authors: Melo L. G. , Veress A. T. , Chong C. K. , Pang S. C. , Flynn T. G. , Sonnenberg H.
Published: December 2017

Atrial natriuretic peptide (ANP), a peptide hormone produced by the heart, exerts a chronic hypotensive effect. Knockout mice with a homozygous disruption of the pro-ANP gene (−/−) are incapable of producing ANP and are hypertensive relative to their wild-type (+/+) siblings. Previous studies showed that arterial blood pressure (ABP) was further increased in conscious −/− mice kept for 2 wk on 2% salt, but not in anesthetized −/− mice after 1 wk on 8% salt. To determine whether inconsistencies in observed effects of salt on ABP of −/− mice are due to duration of increased salt intake and/or the state of consciousness of the animals, we measured ABP from an exteriorized carotid catheter during and after recovery from anesthesia with ketamine-xylazine in adult +/+ and −/− mice kept on low (LS; 0.008% NaCl)- or high (HS; 8% NaCl)-salt diets for 3–4 wk. Conscious ABP ± SE (mmHg) of +/+ mice did not differ significantly on either diet (HS, 113 ± 3; LS, 110 ± 5). However, on HS diet −/− mice had significantly higher ABP (135 ± 3; P < 0.001) than both −/− (115 ± 2) and +/+ (110 ± 5) mice on LS diet. Anesthesia decreased ABP in all groups, but the genotype- and diet-related differences were preserved. Plasma renin activity (PRA, ng ANG I ⋅ ml−1 ⋅ h−1) in blood collected at termination of experiment was appropriately different on the 2 diets in +/+ mice (HS, 4.9 ± 1.9; LS, 21 ± 2.8). However, PRA failed to decrease in −/− mice on HS diet (HS, 18 ± 2.9; LS, 19 ± 3.7). Independent of genotype, concentration of endothelin-1 (ET-1, pg/mg protein) and endothelial constitutive NOS (ecNOS, density/100 μg protein) was significantly elevated in kidneys of mice fed on HS diet (ET-1 −/−, 31 ± 4.7 and +/+, 32 ± 4.1; ecNOS −/−, 160 ± 19 and +/+, 156 ± 19) compared with mice fed on LS diet (ET-1 −/−, 19 ± 1.9 and +/+, 21 ± 1.8; ecNOS −/−, 109 ± 13 and +/+, 112 ± 18). We conclude that, regardless of the state of alertness, −/− mice develop salt-sensitive hypertension after prolonged feeding on HS, in part due to their inability to reduce PRA, whereas the specific renal upregulation of ecNOS and ET-1 in response to HS intake may be an ANP-independent adaptive adjustment aimed at improving kidney function and counteracting the pressor effect of salt.
Effects of bright light on age-related changes in the locomotor activity of Syrian hamsters
Authors: Labyak Susan E. , Turek Fred W. , Wallen Edward P. , Zee Phyllis C.
Published: December 2017

Syrian hamsters display age-related changes in the expression of circadian rhythms and in responsiveness of the circadian system to photic and nonphotic stimuli. This study characterized the effects of age on the locomotor activity rhythm of middle-aged and old hamsters and evaluated the effects of strengthening the entraining light signal. Compared with young (4.5 mo) animals, middle-aged (11.25 mo) and old (16 mo) animals displayed increased daily bouts of activity ( P < 0.001) and reduced total daily activity and activity rhythm amplitude ( P < 0.05) in 14:10-h light-dark cycles. After the light intensity was increased from 300 to 1,500 lx during the light cycle, middle-aged hamsters demonstrated decreased daily activity bouts ( P < 0.05) and increased total daily activity ( P ≤ 0.01) and activity rhythm amplitude ( P≤ 0.001) compared with controls maintained in 300 lx. The pattern of changes in the activity rhythm of old experimental animals was similar to trends observed in middle-aged experimental hamsters, although not as robust. Thus age-related changes in the activity rhythm are occurring by middle age in hamsters, and the provision of stronger entraining signals may lead to more stable circadian organization.
Discharge patterns of Bötzinger complex neurons during cough in the cat
Authors: Bongianni Fulvia , Mutolo Donatella , Fontana Giovanni A. , Pantaleo Tito
Published: December 2017

This study was carried out on pentobarbital sodium-anesthetized, spontaneously breathing cats to address the hypothesis that Bötzinger complex (BötC) neurons are involved in the production of the cough motor pattern induced by mechanical stimulation of the tracheobronchial tree. Phrenic nerve and abdominal muscle activities as well as intratracheal pressure were monitored; single-unit extracellular recordings from BötC neurons ( n = 87) were performed. The majority of augmenting expiratory (E-Aug) neurons encountered ( n = 47) displayed excitatory responses during the expulsive phases of coughing in parallel with the main components of the abdominal bursts and the corresponding increases in tracheal pressure. We also encountered E-Aug neurons markedly depressed up to complete inhibition during coughing ( n = 14) as well as E-Aug neurons assuming a decremental pattern without any increase or even with some reduction in their peak activity ( n = 15). During the expiratory thrusts, most decrementing expiratory neurons ( n = 7) presented excitatory responses, whereas others were depressed ( n = 3) or completely inhibited ( n = 1). The results are consistent with the view that these neurons are involved in the generation of the cough motor pattern and, in particular, that some BötC E-Aug neurons convey excitatory drive to caudal expiratory neurons and, hence, to expiratory motoneurons.
Indomethacin attenuates the cerebral blood flow response to hypotension in late-gestation fetal sheep
Authors: Tong Haiyan , Wood Charles E.
Published: December 2017

Previous studies by us and others have demonstrated that PGE2 and thromboxane (Tx) B2 are produced in the fetal and neonatal brain during cerebral hypoperfusion. The present study was to test the hypotheses that indomethacin would alter the cerebral blood flow (CBF) response to reduced cerebral perfusion pressure in late-gestation fetal sheep by inhibiting the local prostanoid production. We studied eight chronically catheterized, sinoaortically denervated, 126- to 136-day gestation fetal sheep. The cyclooxygenase inhibitor indomethacin (0.2 mg/kg) or its vehicle phosphate buffer was injected intravenously 90 min before the start of a 10-min period of cerebral hypoperfusion produced by brachiocephalic artery occlusion (BCO). We found that BCO decreased fetal regional CBF (rCBF) by 65–79% in the phosphate buffer group and by 45–57% in the indomethacin-pretreated group. The decrease in fetal rCBF during BCO after indomethacin was 30–49% less than after phosphate buffer. Plasma PGE2 and TxB2 concentrations were significantly reduced by indomethacin treatment. BCO increased plasma ACTH and arginine vasopressin (AVP) concentrations; but these responses were not affected by indomethacin. These data suggested that endogenous prostanoid production is involved in the regulation of fetal CBF but, in the absence of intact baro- or chemoreflexes, not in the regulation of ACTH or AVP responses to BCO. We conclude that indomethacin has a beneficial effect on CBF during cerebral ischemia in late-gestation fetal sheep.
Compensatory sleep response to 12 h wakefulness in young and old rats
Authors: Shiromani Priyattam J. , Lu Jun , Wagner Dean , Thakkar Jolleyin , Greco Mary Ann , Basheer Radhika , Thakkar Mahesh
Published: December 2017

There is a pronounced decline in sleep with age. Diminished output from the circadian oscillator, the suprachiasmatic nucleus, might play a role, because there is a decrease in the amplitude of the day-night sleep rhythm in the elderly. However, sleep is also regulated by homeostatic mechanisms that build sleep drive during wakefulness, and a decline in these mechanisms could also decrease sleep. Because this question has never been addressed in old animals, the present study examined the effects of 12 h wakefulness on compensatory sleep response in young (3.5 mo) and old (21.5 mo) Sprague-Dawley and F344 rats. Old rats in both strains had a diminished compensatory increase in slow-wave sleep (SWS) after 12 h of wakefulness (0700–1900, light-on period) compared with the young rats. In contrast, compensatory REM sleep rebound was unaffected by age. To assess whether the reduced SWS rebound in old rats might result from loss of neurons implicated in sleep generation, we counted the number of c-Fos immunoreactive (c-Fos-ir) cells in the ventral lateral preoptic (VLPO) area and found no differences between young and old rats. These findings indicate that old rats, similar to elderly humans, demonstrate less sleep after prolonged wakefulness. The findings also indicate that although old rats have a decline in sleep, this cannot be attributed to loss of VLPO neurons implicated in sleep.
Denudations as paracellular routes for alphafetoprotein and creatinine across the human syncytiotrophoblast
Authors: Brownbill P. , Mahendran D. , Owen D. , Swanson P. , Thornburg K. L. , Nelson D. M. , Sibley C. P.
Published: December 2017

We tested two hypotheses: 1) that fibrin-containing fibrinoid-filled denudations of the syncytiotrophoblast may provide a route for paracellular diffusion and 2) that placentas from women who had elevated maternal serum alphafetoprotein (MSAFP) in midgestation had raised permeability to AFP and greater denudation than in normal pregnancy. We measured AFP and creatinine clearance across term placental cotyledons from the above groups and used light microscope morphometric analysis to determine the volume density of fibrin-containing fibrinoid deposits. There was no significant difference between the two groups in terms of AFP and creatinine clearance or volume density of fibrin-containing fibrinoid deposits. The combined data showed a significant ( P < 0.05) positive correlation between creatinine clearance, but not AFP clearance, and volume density of fibrin-containing fibrinoid. We conclude that syncytiotrophoblast denudations, with associated fibrinoid, do provide a route for diffusion of small hydrophilic solutes, but that other anatomic features of the placenta are rate limiting for transfer of AFP and similarly sized molecules.
Regulation of body temperature and energy requirements of hibernating Alpine marmots (Marmota marmota)
Authors: Ortmann Sylvia , Heldmaier Gerhard
Published: December 2017

Body temperature and metabolic rate were recorded continuously in two groups of marmots either exposed to seasonally decreasing ambient temperature (15 to 0°C) over the entire hibernation season or to short-duration temperature changes during midwinter. Hibernation bouts were characterized by an initial 95% reduction of metabolic rate facilitating the drop in body temperature and by rhythmic fluctuations during continued hibernation. During midwinter, we observed a constant minimal metabolic rate of 13.6 ml O2 ⋅ kg−1 ⋅ h−1between 5 and 15°C ambient temperature, although body temperature increased from 7.8 to 17.6°C, and a proportional increase of metabolic rate below 5°C ambient temperature. This apparent lack of a Q10 effect shows that energy expenditure is actively downregulated and controlled at a minimum level despite changes in body temperature. However, thermal conductance stayed minimal (7.65 ± 1.95 ml O2 ⋅ kg−1 ⋅ h−1 ⋅ °C−1) at all temperatures, thus slowing down cooling velocity when entering hibernation. Basal metabolic rate of summer-active marmots was double that of winter-fasting marmots (370 vs. 190 ml O2 ⋅ kg−1 ⋅ h−1). In summary, we provide strong evidence that hibernation is not only a voluntary but a well-regulated strategy to counter food shortage and increased energy demands during winter.
Gender differentiation of the chemoreflex during growth at high altitude: functional and neurochemical studies
Authors: Joseph V. , Soliz J. , Pequignot J. , Semporé B. , Cottet-Emard J. M. , Dalmaz Y. , Favier R. , Spielvogel H. , Pequignot J. M.
Published: December 2017

The effect of chronic hypoxia on gender differences in physiology and neurochemistry of chemosensory pathways was studied in prepubertal and adult rats living at sea level (SL; Lyon, France) or at high altitude (HA; La Paz, Bolivia, 3,600 m). HA adult rats had higher hematocrit (Ht%), Hb concentration, resting ventilatory rate (Ve100), and higher tyrosine hydroxylase (TH) activity in carotid bodies (CB) than SL animals. At HA and SL, adult females had lower Ht% (46.0 ± 0.8 vs. 50.4 ± 0.6% at HA, P < 0.05 and 43.8 ± 0.9 vs. 47.1 ± 0.8% at SL, P < 0.05) and Hb (16.1 ± 0.3 vs. 17.7 ± 0.2 g/dl at HA, P < 0.05 and 14.5 ± 0.3 vs. 15.6 ± 0.1 g/dl at SL, P < 0.05) than males. Females had higher Ve100 [170 ± 19 vs. 109 ± 7 ml ⋅ min− 1 ⋅ 100 g− 1 at HA, P < 0.05 and 50 ± 3 vs. 40 ± 2 ml ⋅ min− 1 ⋅ 100 g− 1 at SL, not significant (NS)] and lower CB-TH activity (1.40 ± 0.2 vs. 3.87 ± 0.6 pmol/20 min at HA, P < 0.05 and 0.52 ± 0.1 vs. 0.68 ± 0.1 pmol/20 min at SL; NS) than males at HA only. The onset of hypoxic ventilatory response during development was delayed at HA. Prepubertal HA females had higher Ve100 than males (2 wk old, +47%) and higher CB-TH activity (3 wk old, +51%). Medullary noradrenergic groups were sex dimorphic during development at SL. Rats raised at HA had a drop of TH activity between the second and the third postnatal week in all medullary groups. In conclusion, our data support the hypothesis that the CB is the major site for sexual differentiation of the ventilatory control. Ventilatory differences appeared before puberty, and the animals bred at HA had profound alterations in the developmental process of the chemoreflex and its neural pathways. Some of these alterations are under dependence of the sex of the animal, and there is an important interaction between gender and the hypoxic environmental condition during the developmental period.
Effect of hyperosmotic solutions on salt excretion and thirst in rats
Authors: Schoorlemmer G. H. M. , Johnson A. K. , Thunhorst R. L.
Published: December 2017

We investigated urinary changes and thirst induced by infusion of hyperosmotic solutions in freely moving rats. Intracarotid infusions of 0.3 M NaCl (4 ml/20 min, split between both internal carotid arteries) caused a larger increase in excretion of Na+ and K+ than intravenous infusions, indicating that cephalic sensors were involved in the response to intracarotid infusions. Intravenous and intracarotid infusions of hyperosmotic glycerol or urea (300 mM in 150 mM NaCl) had little or no effect, suggesting the sensors were outside the blood-brain barrier (BBB). Intracarotid infusion of hypertonic mannitol (300 mM in 150 mM NaCl) was more effective than intravenous infusion, suggesting that cell volume rather than Na+ concentration of the blood was critical. Similarly, intracarotid infusion (2 ml/20 min, split between both sides), but not intravenous infusion of hypertonic NaCl or mannitol caused thirst. Hyperosmotic glycerol, infused intravenously or into the carotid arteries, did not cause thirst. We conclude that both thirst and electrolyte excretion depend on a cell volume sensor that is located in the head, but outside the BBB.
Low temperature limits photoperiod control of smolting in Atlantic salmon through endocrine mechanisms
Authors: McCormick Stephen D. , Moriyama Shunsuke , Björnsson B. Thrandur
Published: December 2017

We have examined the interaction of photoperiod and temperature in regulating the parr-smolt transformation and its endocrine control. Atlantic salmon juveniles were reared at a constant temperature of 10°C or ambient temperature (2°C from January to April followed by seasonal increase) under simulated natural day length. At 10°C, an increase in day length [16 h of light and 8 h of darkness (LD 16:8)] in February accelerated increases in gill Na+-K+-ATPase activity, whereas fish at ambient temperature did not respond to increased day length. Increases in gill Na+-K+-ATPase activity under both photoperiods occurred later at ambient temperature than at 10°C. Plasma growth hormone (GH), insulin-like growth factor, and thyroxine increased within 7 days of increased day length at 10°C and remained elevated for 5–9 wk; the same photoperiod treatment at 2°C resulted in much smaller increases of shorter duration. Plasma cortisol increased transiently 3 and 5 wk after LD 16:8 at 10°C and ambient temperature, respectively. Plasma thyroxine was consistently higher at ambient temperature than at 10°C. Plasma triiodothyronine was initially higher at 10°C than at ambient temperature, and there was no response to LD 16:8 under either temperature regimen. There was a strong correlation between gill Na+-K+-ATPase activity and plasma GH; correlations were weaker with other hormones. The results provide evidence that low temperature limits the physiological response to increased day length and that GH, insulin-like growth factor I, cortisol, and thyroid hormones mediate the environmental control of the parr-smolt transformation.
Regional regulation of choroidal blood flow by autonomic innervation in the rat
Authors: Steinle Jena J. , Krizsan-Agbas Dora , Smith Peter G.
Published: December 2017

Regional influences of parasympathetic and sympathetic innervation on choroidal blood flow were investigated in anesthetized rats. Parasympathetic pterygopalatine neurons were activated by electrically stimulating the superior salivatory nucleus, whereas sympathetic neurons were activated by cervical sympathetic trunk stimulation and uveal blood flow was measured by laser Doppler flowmetry. Parasympathetic stimulation increased flux in the anterior choroid and nasal vortex veins but not in the posterior choroid. Vasodilation was blocked completely by the neuronal nitric oxide synthase inhibitor 1-(2-trifluoromethylphenyl)imidazole but was unaffected by atropine. Sympathetic stimulation decreased flux in all regions, and this was blocked by prazosin. Parasympathetic stimulation did not affect vasoconstrictor responses to sympathetic stimulation in the posterior choroid but attenuated the decrease in blood flow through the anterior choroid and vortex veins via a nitrergic mechanism. We conclude that sympathetic α-noradrenergic vasoconstriction occurs throughout the choroid, whereas parasympathetic nitrergic vasodilation plays a selective role in modulating blood flow in anterior tissues of the eye.
Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression
Authors: Layé Sophie , Gheusi Gilles , Cremona Sandrine , Combe Chantal , Kelley Keith , Dantzer Robert , Parnet Patricia
Published: December 2017

The present study was designed to determine the role of endogenous brain interleukin (IL)-1 in the anorexic response to lipopolysaccharide (LPS). Intraperitoneal administration of LPS (5–10 μg/mouse) induced a dramatic, but transient, decrease in food intake, associated with an enhanced expression of proinflammatory cytokine mRNA (IL-1β, IL-6, and tumor necrosis factor-α) in the hypothalamus. This dose of LPS also increased plasma levels of IL-1β. Intracerebroventricular pretreatment with IL-1 receptor antagonist (4 μg/mouse) attenuated LPS-induced depression of food intake and totally blocked the LPS-induced enhanced expression of proinflammatory cytokine mRNA measured in the hypothalamus 1 h after treatment. In contrast, LPS-induced increases in plasma levels of IL-1β were not altered. These findings indicate that endogenous brain IL-1 plays a pivotal role in the development of the hypothalamic cytokine response to a systemic inflammatory stimulus.
Effects of angiotensin II on cultured rat renomedullary interstitial cells are mediated by AT1A receptors
Authors: Maric C. , Aldred G. P. , Antoine A. M. , Dean R. G. , Eitle E. , Mendelsohn F. A. , Williams D. A. , Harris P. J. , Alcorn D.
Published: December 2017

Renomedullary interstitial cells (RMICs) are prominent in the inner medullary interstitium and have binding sites for several vasoactive agents, including angiotensin II (ANG II). Although the functional role of RMICs remains largely unknown, it is likely that the interaction between RMICs and vasoactive peptides is important in the regulation of renal function. The current investigation characterizes the cellular responses following treatment of RMICs with ANG II. Studies were performed on RMICs isolated from Sprague-Dawley rat kidneys. 125I-labeled [Sar1,Ile8]ANG II specifically bound to RMICs at sites determined by reverse transcription-polymerase chain reaction to be of the AT1A subtype. ANG II (10(-6) and 10(-10) M) had no effect on either basal or forskolin-stimulated adenosine 3',5'-cyclic monophosphate accumulation in RMICs but increased intracellular inositol 1,4,5-trisphosphate concentration after 10 s and intracellular calcium concentration after 18 s. For RMICs plated at low densities, ANG II (10(-6) M) induced an increase in [3H]thymidine incorporation, mediated through the AT1-receptor subtype. For RMICs plated at high densities, ANG II (10(-6) M) induced an increase in extracellular matrix synthesis as detected by trans-35S incorporation, an effect also mediated by AT1 receptors. We conclude that ANG II AT1A receptors on cultured RMICs are coupled to intracellular second messenger pathways leading to hyperplasia and synthesis of extracellular matrix.
H(+)-K(+)-ATPase mediates net acid secretion in rat terminal inner medullary collecting duct
Authors: Wall S. M. , Truong A. V. , DuBose T. D.
Published: December 2017

Studies in our laboratory have demonstrated total CO2 absorption (JtCO2) and total ammonia secretion in the terminal inner medullary collecting duct (tIMCD) perfused in vitro. The purpose of the present study was to determine whether the H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase) participates in proton secretion or JtCO2 in this segment. Tubules from the middle third of the tIMCD were dissected from rats with chronic metabolic acidosis (300 mM NH4Cl, 3-4 days in drinking water) and perfused in vitro. Perfusate and bath were symmetrical solutions containing 5 mM KCl, 6 mM NH4Cl, and 25 mM NaHCO3. Bafilomycin A1 (5 nM), a specific inhibitor of the H(+)-ATPase, did not affect JtCO2 compared with baseline (JtCO2, 3.0 +/- 1.0 and 3.0 +/- 0.8; n = 6, P = not significant) or with time controls (n = 4). With removal of luminal K+, JtCO2 fell from 2.8 +/- 0.6 to 1.6 +/- 0.4 pmol.mm-1.min-1 (n = 5, P < 0.05). To further evaluate K(+)-sensitive JtCO2, the effect of H(+)-K(+)-ATPase inhibition on JtCO2 was explored using the specific H(+)-K(+)-ATPase inhibitor, Sch-28080. Addition of 10 microM Sch-28080 to the luminal perfusate decreased JtCO2 (2.7 +/- 0.4 to 1.4 +/- 0.5 pmol.mm-1. min-1; n = 5, P < 0.05) but did not alter transepithelial membrane potential. Thus luminal Sch-28080 addition, as well as luminal K+ removal, limits apical H+ exit or OH-/HCO3- entry. These results demonstrate that net acid secretion is mediated by the H(+)-K(+)-ATPase in the tIMCD.
Pressure-mediated vasoconstriction of juxtamedullary afferent arterioles involves P2-purinoceptor activation
Authors: Inscho E. W. , Cook A. K. , Navar L. G.
Published: December 2017

This study was conducted to examine the hypothesis that P2 purinoceptors contribute to pressure-induced autoregulatory adjustments of afferent arteriolar caliber. Experiments were performed in vitro using the blood-perfused juxtamedullary nephron technique. Afferent arteriolar diameter averaged 19.2 +/- 0.6 microns (n = 51) at control perfusion pressure of 100 mmHg and decreased when perfusion pressure was increased. Desensitization of P2 purinoceptors abolished the alpha, beta-methylene ATP-mediated afferent vasoconstriction and prevented pressure-dependent autoregulatory adjustments in afferent diameter. P2-purinoceptor saturation significantly decreased afferent caliber and attenuated pressure-induced autoregulatory responses. To block P2 receptors, afferent arterioles were treated with the P2-purinoceptor antagonists, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid or suramin. P2-receptor blockade prevented the afferent arteriolar vasoconstriction evoked by increasing perfusion pressure from 100 to 130 and 160 mmHg. These data demonstrate that inhibition of P2 purinoceptor-dependent responses through receptor desensitization, receptor saturation, or purinoceptor blockade impairs normal autoregulatory behavior in rat juxtamedullary afferent arterioles. The results are consistent with the hypothesis that P2 purinoceptors participate in mediating autoregulatory adjustments in afferent arteriolar diameter.
Strength of human metatarsal bones under repetitive loading
Authors: Lease Glenn O'D. , Evans F. Gaynor
Published: December 2017

The fatigue life of 51 intact human metatarsals was tested in a Sonntag Flexure Fatigue machine equipped with an automatic counter and shutoff. Bones from eight adult males and three females were used. Nine of the individuals were white and two were Negro. No bones showed any gross pathology. Ten bones were tested wet, forty-one dry. The repetitions to failure with a 15-lb. load, the maximum applied, varied from 1,000 to 10,297,000 for the dry specimens and from 150,000 to 13,908,000 for the wet ones. The greatest variation between the minimum and maximum number of repetitions to failure was 10,287,000 and 10,966,000 repetitions for the dry and wet specimens, respectively. Metatarsals II and III had the longest fatigue life when wet while metatarsals IV and V had the greatest fatigue life when dry. No consistent relations were found between the fatigue life of the bones and their size or the age of the individual from whom they were obtained. The fractures produced were of the comminuted and oblique types found clinically. As far as is known the fatigue life of intact bones has not been previously studied.

Submitted on June 30, 1958
Demonstration of aventilatory mass flow during ventilation and apnea in man
Authors: Bartlett R. G. , Brubach H. F. , Specht H.
Published: December 2017

Use of the whole body plethysmograph has made possible the visualization of an aventilatory mass flow (AVMF) during both ventilation and apnea in man. It has been demonstrated that even short aventilatory intervals are accompanied by an observable en masse movement of ambient air into the lungs due to the diffusive uptake of O2 plus impoundment of CO2 because of the long airway. Since the basic phenomenon occurs during all phases of breathing, including the uninterrupted normal breathing rhythm, it is suggested that it be given a more descriptive name than ‘diffusion respiration’ ( Anesth. & Analg. 28: 307, 1949) or ‘apneic diffusion of oxygenation’ ( Acta chir. scandinav., Suppl. 212, 1956). Aventilatory mass flow (AVMF) is suggested as a name which includes the observable part of the phenomenon—mass flow—and which does not embody any misleading terms.
Alterations in lung compliance and functional residual capacity with posture
Authors: Lim Thomas P. K. , Luft Ulrich C.
Published: December 2017

Lung compliance and functional residual capacity were determined in the erect standing and the supine lying positions on six normal adults. Both lung compliance and functional residual capacity were proportionally reduced on resuming the supine from the standing position so that the ‘specific compliance’ remained the same at the two body positions. The correlation between lung compliance and FRC found in this study agrees well with that reported by others and the importance of considering the size of the system in assessing elastic properties of the lung is briefly discussed.

Submitted on October 17, 1958
Renal blood flow in dogs during diffusion respiration
Authors: Stone Joseph E. , Irwin Richard L. , Wood Charles D. , Draper William B. , Whitehead Richard W.
Published: December 2017

Two series of experiments were performed with appropriate controls on dogs in which respiratory arrest was produced and maintained by the injection of an overdose of thiopental or by administration of decamethonium, respectively. Renal blood flow was measured by a modification of the method of Selkurt ( Methods in Medical Research, vol. 1). A marked fall in renal blood flow coincident with apnea and anuria was found to occur consistently with diffusion respiration under thiopental. Both the renal ischemia and the anuria were preventable by renal denervation (pharmacological block). During diffusion respiration experiments in which decamethonium was used to cause and maintain apnea, a marked decline in renal blood flow or urine secretion did not occur during the first 15 minutes of apnea. It is concluded that the prompt onset of anuria in diffusion respiration under thiopental is due to a central synergism between thiopental and endogenous carbon dioxide. Further, it is reasoned that the delayed fall in renal blood flow and attendant anuria which occurred under decamethonium represent the central effects of increasing concentrations of carbon dioxide in the absence of thiopental.

Submitted on November 5, 1958
Determination of pulmonary parenchymal tissue volume and pulmonary capillary blood flow in man
Authors: Cander Leon , Forster Robert E.
Published: December 2017

The rates of disappearance of SF6, N2O, C2H2, diethyl ether and acetone from alveolar air during breath holding, following a single deep inspiration of a mixture containing one of these gases and about 15% helium, was studied in five normal seated subjects. SF6 is so insoluble that no significant change in its concentration relative to helium was found. Ether and acetone are so soluble that they dissolve in the tissues around the respiratory dead space during inspiration and evaporate during expiration, contaminating the expired alveolar gas to such an extent that the exchange of these gases cannot be properly measured at the alveolar level. N2O and C2H2 showed a) a rapid (less than 1.5 sec.) initial fall in relative alveolar concentration and b) a subsequent more gradual decrease; a) presumably results from the solution of the foreign gas in the pulmonary parenchymal tissues and can be used to calculate the pulmonary parenchymal tissue volume (Vt); b) can be used to calculate the pulmonary capillary blood flow (Qc), provided observations are not extended beyond 21 sec. The average values obtained were 3.31 l/min/m2 and 606 ml for Qc and Vt, respectively.

Submitted on December 4, 1958
Digestion of irradiated fat in vivo
Authors: Schreiber Manuel , Nasset E. S.
Published: December 2017

Lard and lean beef were irradiated separately in a beam of accelerated electrons (6 million rep in a Van de Graaff apparatus). Test meals were fed to dogs, using combinations of irradiated and unirradiated lard and beef. On the average irradiated lard, whether fed by itself or with meat, was retained in the stomach to a greater extent than normal lard (65% vs. 47%), filled the small intestine to a smaller extent (8% vs. 11%), and was less readily absorbed (27% vs. 42%) in a specified time. The difference in absorption can be accounted for by the difference in gastric evacuation. The peroxide value of lard rose abruptly on radiation from 1–2 to 176 and in 14 months of cold storage continued to rise to approximately twice this value. It is concluded that irradiation of lard is detrimental to its digestion in the dog.

Submitted on December 22, 1958
Relation of volume history of lungs to respiratory mechanics in anesthetized dogs
Authors: Mead Jere , Collier Clarence
Published: December 2017

When anesthetized dogs were allowed to breathe spontaneously or were paralyzed and ventilated in the resting tidal range by means of a pump, pulmonary compliance fell progressively. These changes were immediately reversed following forced inflations of the lungs, while forced deflations caused further compliance reductions. The appearance of the lungs post mortem suggested that closure of air-spaces was at least in part responsible for the compliance reductions. Evidence from measurements of total and ventilatory lung gas volumes indicated that the closed spaces were essentially atelectatic. These findings have been related to other observations made in experimental animals and in man.

Submitted on December 29, 1958
Mechanism of pulmonary gas exchange and CO2 transport during breath holding
Authors: Mithoefer John C.
Published: December 2017

Experiments describe the changes in PaCOCO2 and lung volume shrinkage during breath holding with O2 in man and the PaCOCO2, pH and CO2 content of arterial and mixed venous blood during breath holding in the dog. An explanation is offered for the aberrations in CO2 transport and exchange which occur during apnea. A self-perpetuating cycle is established during breath holding which is initiated by the arrest of the ventilatory output of Co2. The arterial PaCOCo2 rises rapidly as a result of decreased clearance of Co2 from venous blood, the concentrating effect of lung volume shrinkage and the Haldane effect from oxygenation of hemoglobin. The venous PaCOCO2 rises more slowly because of the uptake of Co2 by the tissues and the Haldane effect from reduction of oxyhemoglobin. By this mechanism the Co2 output into the lungs progressively falls and eventually stops. The cycle then is reversed and Co2 moves from lungs to arterial blood.

Submitted on March 2, 1959
Body temperature and heat exchange during treadmill running in dogs
Authors: Young D. R. , Mosher R. , Erve P. , Spector H.
Published: December 2017

Body temperature during treadmill running was studied in six dogs at seven different grades from 0–22 degrees of inclination. The replicate variability in the work rectal, skin and fur temperature was ±0.5℉, ±1.4℉ and ±1.3℉, respectively. At grades up to 12 degrees of inclination there is a prolonged steady state in the rectal temperature. At higher grades there is a progressive increase in rectal temperature with running time. Body surface temperatures show little affect at the lower grades. At higher work intensities there is an increase in skin and fur temperature. Maximum heat storage varied from 21.3–41.3 Cal. during short term exhaustive work. This type of calculation is discussed critically. The relationship between rate of rise in rectal temperature and maximum performance time was studied. Without regard to work load a product-moment correlation coefficient of +0.991 was found.

Submitted on September 17, 1958
Incidence of ulceration in the pylorus-ligated mouse
Authors: Ogawa Tokuo , Necheles H.
Published: December 2017

Optimal conditions for ulcer production in the pylorus-ligated mouse seem to be the following: the use of animals between 9 and 11 weeks of age, a preoperative starvation period of 15 hours, an experimental period of 8 hours, and an ambient temperature of 28℃. Under these conditions, ulcers are produced in nearly all animals. It appears that gastric acidity in ulcer formation in the mouse may be secondary to gastric distention and interference with circulation.

Submitted on December 1, 1958
Red blood cell distribution in the hypothermic ground squirrel
Authors: Lynch H. F.
Published: December 2017

The quantity and distribution of the circulating red blood cell mass were studied in the ground squirrel during immersion hypothermia of 2°–4°C esophageal temperature. Mixing of isotopically tagged erythrocytes within the total red cell mass, as determined by comparison with euthermic values, was essentially complete within 10 minutes, so that little, if any, sequestration of blood occurred. The hematocrit ratio of blood within the heart lumina was maintained throughout this cold stress. Complete mixing of Cr51-tagged red blood cells took place within 1 hour in the erythrocytes of the kidney, cardiac muscle, diaphragm and leg muscles. The liver of the cold animal picked up radioactivity, perhaps due to damage of erythrocytes in the labeling process. Splenic contraction within 2 hours of acute hypothermia was indicated by a sharp decrease in its circulating red blood cell mass and by visual observation. The total erythrocyte mass in the cheek pouch of the hypothermic ground squirrel required about 3 hours to equilibrate with labeled cells, so that a small region of very slowly flowing blood did exist in this tissue. Maintenance of red blood cell flow to tissues indicated that some vasomotor control was intact during this acute cold stress.

Submitted on January 27, 1959
Aortic grafts of polyurethane in dogs
Authors: Dreyer Barend , Akutsu Tetsuzo , Kolff Willem J.
Published: December 2017

Membranes and abdominal aortic grafts made of Polyurethane VC and of polyurethane foam were inserted in 35 dogs. The reaction of the tissues to polyurethane was studied and the functioning of the aortic grafts with smooth internal surfaces (membrane form of polyurethane) was compared to that of those with spongy internal surfaces (foam form of polyurethane). Polyurethane VC membrane became encapsulated by an envelope of fibrous tissue and appeared to lose some strength inside the body, but fibrous tissue grew into polyurethane foam, strengthening it. The nine smooth grafts made of Polyurethane VC membrane all thrombosed, but 80% of the foam grafts remained open. This confirmed the observations of other workers that a smooth internal surface is undesirable in arterial transplants. The grafts of polyurethane foam functioned well as aortic replacements. They have many of the requirements of an ideal arterial transplant and are being studied further.

Submitted on April 1, 1959