Cardiovascular responses to gastric hypo-osmolar stimulation in anesthetized dogs

We compared the cardiovascular response to the gastric infusion of distilled water (DI) with that to the gastric infusion of 0.9% saline (SI) and gastric ballooning with 37 degrees C water (BA) through a gastric fistula in splenectomized mongrel dogs (n = 7). DI, and SI amounting to 5% of body wt and the same volume of water were infused in approximately 20 s through the tube and responses in mean arterial pressure (MAP), CVP, heart rate (HR), and intra-esophageal pressure (EP) were monitored continuously. After DI, SI, and BA, the measured variables showed significant increases and attained maximal increases at about 2 min after the treatments. After DI, the maximum elevation in MAP was 21.3 +/- 1.9 mmHg and 2 times higher than in SI and BA. The corresponding value in CVP was 5.0 +/- 0.3 mmHg and 2-3 times higher than with SI and BA, and HR increased by 26.1 +/- 3.0 beats/min showing 3 to 6 times larger increases compared with SI and BA. These gastro-cardiovascular reflexes were abolished after subdiaphragmatic truncal vagotomy. These findings suggest that both the mechanical and osmotic stimuli to the stomach induce cardiovascular reflexes and that the vagus is involved in the reflex.     

Neuroanatomical changes in the rat bladder after bladder outlet obstruction

OBJECTIVE: To evaluate the perinatal and 2-year outcomes in pregnancies complicated by preterm premature rupture of membranes (PROM) during the second trimester. METHODS: Fifty-three consecutive singleton pregnancies with PROM at 14 to 28 weeks of gestation were studied retrospectively. Management goals were to prolong the pregnancies to 32 weeks through expectant management and to avoid fetal compromise through closer monitoring and active intervention, when necessary, after 23 weeks. Outcome of the surviving infants was based on neurologic, audiometric, and ophthalmologic examinations at 2 years of corrected age. RESULTS: Rupture of membranes occurred at 14-19 weeks (mean 17.4 weeks) in 10 women, at 20-25 weeks (mean 24.0 weeks) in 24, and at 26-28 weeks (mean 27.6 weeks) in 19. The median latency periods to delivery were 72 days, 12 days, and 10 days when rupture of membranes occurred at 14-19 weeks, 20-25 weeks, and 26-28 weeks, respectively. The overall incidence of chorioamnionitis was 28%. There were no fetal deaths and nine neonatal deaths. When rupture of membranes occurred at 14-19 weeks, 20-25 weeks, and 26-28 weeks, the perinatal survival rates were 40%, 92%, and, 100%, respectively. Pulmonary hypoplasia accounted for seven deaths. Of the live-born infants, 81% were alive at 2 years of corrected age. Survival without major impairment was observed in 75%, 80%, and 100% of the survivors when rupture of membranes occurred at 14-19 weeks, 20-25 weeks, and 26-28 weeks, respectively. CONCLUSION: Expectant management of second-trimester PROM offers better perinatal and long-term survival than previously thought.     

Reflex control of cardiac sympathetic nerve activity in anesthetized rats

Reflex control of sympathetic outflow to the heart was evaluated by recording the efferent discharges of the interior cardiac sympathetic nerves in anesthetized rats. The reflex responses of inferior cardiac sympathetic nerve activity (ICNA) to arterial baroreceptor loading by phenylephrine and to arterial/atrial baroreceptor unloading by hemorrhagic hypotension were compared with those of renal sympathetic nerve activity (RNA) and adrenal sympathetic nerve activity (ANA). The reflex decrease in ICNA to the phenylephrine-induced graded increase in arterial blood pressure was smaller than that of RNA or ANA. Thus ICNA is less sensitive to arterial baroreceptor stimulation. Hemorrhage produced a volume-dependent decrease in ICNA. The response was significantly smaller than that in RNA and was directionally opposite to that in ANA. Cervical vagotomy but not sinoaortic denervation abolished the hemorrhage-induced ICNA response, suggesting an important role of vagal pathways. These findings demonstrate that the reflex responses of sympathetic outflow to the heart were quantitively and qualitatively different from those to the kidney and the adrenal gland, indicating the regional control of sympathetic nerve activity in the regulation of cardiovascular functions.     

Late responses after transcranial magnetic stimulation in stroke

In addition to early responses after transcranial magnetic stimulation, usually designated as Motor Evoked Potentials (MEP), several late responses have been reported in intervals up to 500 ms following stimulus. Our attention in this work was focused on the response in interval 150-300 ms after stimulus output, which is also designated as S > 150 response. We monitored longitudinally late S > 150 response in group of 19 stroke patient with verified hemispherical ischemic lesion. Our results have shown that the presence of late S > 150 response on the first day after stroke predicts an excellent improvement of clinical deficit and that late S > 150 response is more sensitive to hemispheric lesion than early MEPs. From this point of view, recording of late responses can supplement early MEP recording. Our study demonstrated that supratentorial structures are involved in the origin of the S > 150 response. According to the observation that in some patients a normal early response was present and an S > 150 response was absent on the hemiparetic side, and both responses were present on the unaffected side, we hypothesize that cortical structures play an important role in S > 150 response.     

Estrous cycle phase variations in visceromotor and cardiovascular responses to colonic distension in the anesthetized rat

When no anaesthetic is used, even 3-5 short-term disturbances of the myocardium supply with blood (during a few days) are enough for its initial necrosis and for damage of its vascular bed. In acute experiments on rats rutin discovers the ability to resist such damages, but on the chronic model of stenocardia in dogs its therapeutic effect can be found only under conditions of limitation of the ischemic effect by purposefully chosen complex medicinal therapy.     

Heart rate, blood pressure, and running speed responses to mesencephalic locomotor region stimulation in anesthetized rats

Responses of aging brain to physical training was evaluated by quantifying the substrates, glucose, lactic acid, and nucleic acids in cerebral cortex (CC) and medulla oblongata (MO) of the brain in rats. Rats of 1 month (young), 6 months (adult), 12 months (middle-aged) and 18 months (old) of age were swim-trained for 30 days. Glucose content of CC and MO increased with training whereas blood glucose decreased in trained young and adult animals with middle-aged and old animals maintaining constant blood glucose. Brain lactate in these two regions decreased with training in all age groups. However, the old animals showed an elevation in blood lactic acid in trained state, while the other age groups showed a decrease. Nucleic acid content, decreased with age, especially the RNA content in MO showing a larger depletion. However, there was no discernible influence of physical exercise on these parameters. Physical training has influenced the aging brain's adaptability, as seen by increase in its glucose content in young animals and also possible utilization of lactate as an additional substrate in old animals as evidenced by an increase in blood lactic acid.     

Neuropeptide Y-mediated pressor responses following high-frequency stimulation of the rat sympathetic nervous system

Recombinations between c-myc and immunoglobulin (Ig) sequences that typically occur in pristane-induced mouse plasmacytomas were detected in secondary lymphoid tissues from normal mice, chiefly in the gut-associated lymphoid tissue. Based on the analysis of recombination sequences as clonotypic markers, migration of c-myc recombination-positive cells was observed between Peyer's patches and into the intestine. Treatment of plasmacytoma-susceptible BALB/cAn mice with pristane induced proliferation and migration of these cells into mesenteric lymph node, spleen, and oil granuloma within 7 days. Plasmacytoma-resistant strains of mice (DBA/2N, C3H/HeJ, C57BL/6) differed in that (1) they harbored fewer clones (Ig/c-myc recombinations were detected in 33% of resistant mice versus 91% of BALB/cAn mice after pristane treatment); (2) Ig/c-myc-positive cells were rarely detected in the oil granuloma, and (3) c-myc recombined predominantly with the Ig alpha locus in BALB/cAn mice (72%), but with the Ig mu locus in DBA/2N and in C57BL/6 (67%). The results demonstrate that normal mice generate a large number of lymphocytes with aberrant c-myc in intestinal tissues without developing tumors.     

Morphological responses and molecular modifications in tomato plants after mechanical stimulation

Study of the growth responses of Lycopersicon esculentum (Mill. cv. VFN8) to mechanical stimulation applied to a single young internode showed a rapid and sharp decrease in stem elongation and an inhibition of elongation of several internodes, indicative of information transmission in the plant. A new tomato cDNA partial clone encoding calmodulin was isolated and used to study the time course of the gene induction in response to the rubbing treatment. Northern blot analysis showed a maximum accumulation of calmodulin mRNA 2 h after mechanical stimulation, not only in the rubbed internode, but also in upper and lower internodes and in young leaves. Treatment of the plant with calcium and EGTA showed the involvement of calcium and, in particular, intracellular calcium in calmodulin gene expression and cellular response.     

The action of tyramine on the hypertensive responses induced by sympathetic stimulation in the pithed rat

This study has evaluated the changes in the characteristics of the H-reflex induced by distention of the urinary bladder in patients with complete lesions of the spinal cord. These findings were compared to induced changes in the systolic blood pressure and some degree of correlation was noted. It is well recognised that distention of the urinary bladder can exert a significant influence on the state of both somatic and autonomic reflex activity in spinal man. Although the mode of action of this stimulus has not been fully delineated, it is of some clinical importance since it may intensify muscular spasticity and autonomic hyperreflexia. This study was undertaken to further explore this relationship utilising the H-wave as a measure of segmental reflex activity. When appropriate, the effect of bladder distention on arterial blood pressure was also measured and an attempt made to correlate these observations with the H-wave findings.     

Selective in vivo stimulation of stress-activated protein kinase in different rat tissues by immobilization stress

The quaternary structure of Lumbricus terrestris hemoglobin was investigated by small-angle x-ray scattering (SAXS). Based on the SAXS data from several independent experiments, a three-dimensional (3D) consensus model was established to simulate the solution structure of this complex protein at low resolution (about 3 nm) and to yield the particle dimensions. The model is built up from a large number of small spheres of different weights, a result of the two-step procedure used to calculate the SAXS model. It accounts for the arrangement of 12 subunits in a hexagonal bilayer structure and for an additional central unit of clylinder-like shape. This model provides an excellent fit of the experimental scattering curve of the protein up to h = 1 nm-1 and a nearly perfect fit of the experimental distance distribution function p(r) in the whole range. Scattering curves and p(r) functions were also calculated for low-resolution models based on 3D reconstructions obtained by cryoelectron microscopy (EM). The calculated functions of these models also provide a very good fit of the experimental scattering curve (even at h > 1 nm-1) and p(r) function, if hydration is taken into account and the original model coordinates are slightly rescaled. The comparison of models reveals that both the SAXS-based and the EM-based model lead to a similar simulation of the protein structure and to similar particle dimensions. The essential differences between the models concern the hexagonal bilayer arrangement (eclipsed in the SAXS model, one layer slightly rotated in the EM model), and the mass distribution, mainly on the surface and in the central part of the protein complex.     

Laryngeal-receptor responses to phasic CO2 in anesthetized cats

We compared the effects of CO2 applied continuously and during expiration on laryngeal-receptor activity in paralyzed, artificially ventilated and nonparalyzed, spontaneously breathing cats by using an isolated larynx, artificially ventilated to approximate a normal respiratory cycle. The majority of quiescent negative-pressure and all cold receptors were excited by 5 and 9% CO2 applied both continuously and during expiration. In general, quiescent positive-pressure, tonic negative-pressure, and tonic positive-pressure receptors were inhibited by 5 and 9% CO2 applied continuously and during expiration. There were no significant differences between responses to 5 and 9% CO2 or to continuous and expired CO2 or between paralyzed and nonparalyzed preparations. In conclusion, laryngeal receptors respond to changes in CO2 concentration occurring during a normal respiratory cycle. Because laryngeal-receptor stimulation exerts reflex effects on ventilation and upper airway muscle activity, these results suggest that airway CO2 plays a role in reflex regulation of breathing and upper airway patency.     

Cholinergic responsiveness of neurons in the ventroposterior thalamus of the anesthetized rat

Acetylcholine has been implicated as an important neurotransmitter in the mechanisms of thalamic activation. Cholinergic mechanisms are thought to directly underlie the high level of excitability observed in thalamic relay neurons during waking and rapid eye movement sleep. We sought to determine if the cholinergic responsiveness of neurons in the ventroposterior nuclei of the thalamus in rat is consistent with this view. Neurons in the chloral hydrate-anesthetized rat were studied with extracellular recording and microiontophoretic application of cholinergic agents. In most cases (63% of 63 cells), the ejection of the agonist, carbachol, had no observable effect on spontaneous activity. Facilitation (25%), inhibition (8%) and inhibition followed by facilitation (3%) were also observed. Carbachol ejections that by themselves were ineffective in altering spontaneous activity proved capable, in 93% of 28 cells, of antagonizing the uniformly facilitatory responses produced by glutamate ejection. The putative M1-selective, cholinergic agonist, McN-A-343, was also ineffective alone in altering spontaneous activity in the majority of cases (74% of 27 cells) and produced only inhibitory responses in the remaining seven neurons studied. Interacting applications of McN-A-343 and glutamate resulted, in all cases, in antagonism of glutamate facilitation (N = 12). The various responses to applied cholinergic agonists were all capable of being antagonized by muscarinic receptor-blocking agents. Both the high proportion of inhibitory responses and the antagonism of glutamate facilitatory responses suggest that ventroposterior neurons in the rat differ from other thalamocortical relay neurons in the rat and cat with regard to cholinergic responsiveness. Additionally, the lack of predominantly facilitatory responding renders it unlikely that cholinergic mechanisms directly underlie increases in excitability of ventroposterior neurons observed during waking and rapid eye movement sleep.     

Stereotyped yawning responses induced by electrical and chemical stimulation of paraventricular nucleus of the rat

Yawning was evoked by electrical or chemical stimulation in the paraventricular nucleus (PVN) of anesthetized, spontaneously breathing rats. To evaluate physiological aspects of yawning, we monitored polygraphic measures as follows; a coordinated motor pattern of yawning was assessed by monitoring breathing [intercostal electromyogram (EMG)], mouth opening (digastric EMG), and stretching of the trunk (back EMG). We also recorded blood pressure (BP), heart rate, and the electrocorticogram (ECoG) to evaluate autonomic function and arousal responses during yawning. A stereotyped yawning response was reproducibly evoked by electrical stimulation or microinjection of -glutamate or NOC-7, a nitric oxide (NO)-releasing compound, into the PVN. The stereotyped yawning response consisted of two sequential events, an initial response represented a depressor response and an arousal shift in the ECoG to lower voltage and faster rhythms. These initial changes were followed by a yawning behavior characterized by a single large inspiration with mouth opening and stretching of the trunk. A similar sequence of events occurred during spontaneous yawning; a fall in BP and ECoG arousal preceded a yawning behavior. An increase in the frequency of spontaneous yawns was also observed after microinjection of -glutamate or NOC-7 into the PVN. Intravenous administration of NG-monomethyl--arginine, an inhibitor of nitric oxide synthase (NOS), prevented the stereotyped yawning response evoked by chemical stimulation of the PVN. Histological examination revealed that effective sites for the yawning responses were located in the medial part of the rostral PVN, the site of parvocellular and magnocellular neurons. NADPH-diaphorase histochemistry showed the existence of NOS-containing cells in yawning-evoked sites of the PVN. In summary, the sequential events of yawning may be generated by NOS-containing parvocellular neurons in the medial part of the rostral PVN projecting to the lower brain stem.     

Enhanced motility of the vagotomized canine stomach by electrical stimulation

Functional impairment of the vagotomized stomach used as a substitute oesophagus seriously deteriorates the quality of life of patients following oesophageal cancer surgery. We speculated that if the enteric neurons of the reconstructed gastric tube survived functionally, the motility of the gastric tube could be facilitated and the recovery process after operation would improve as a consequence. In the present study we investigated whether direct electrical stimulation was effective for facilitating the motility of the canine vagotomized stomach. Dogs underwent truncal vagotomy by transabdominal approach and, in some cases, arteries to the upper stomach and the oesophagus were also ligated and resected to resemble the blood supply and surgical invasion of the reconstructed gastric tube. Electrical stimulation, a few minutes of positive rectangular current pulses, amplitude 20 V (or 15 mA), duration 0.5 ms and frequency between 0.2 and 7 Hz, was delivered on the greater curvature of the mid corpus. Changes in mechanical contractions were recorded using strain gauge force transducers. Electrical stimulation successfully enhanced the mechanical force of the phasic ring contractions of the vagotomized stomach in a frequency dependent manner. Aboral propagation and periodicity of the contractions, impaired by surgical procedures, were restored during stimulation. These excitatory effects were inhibited by atropine, hexamethonium and tetrodotoxin, suggesting that electrical stimulation acts on intramural cholinergic nerves that have survived functionally. These results suggest that electrical stimulation could be an effective method for improving the motility of the vagotomized stomach.     

Effects of locus coeruleus stimulation on the responses of SI neurons of the rat to controlled natural and electrical stimulation of the skin

Recent epidemiologic data demonstrate a dramatic increase in the incidence of end-stage renal disease (ESRD) in patients with non-insulin-dependent diabetes mellitus (NIDDM), thus dispelling the mistaken belief that renal prognosis is benign in NIDDM. Currently, the leading cause of ESRD in the United States, Japan, and in most industrialized Europe is NIDDM, accounting for nearly 90% of all cases of diabetes. In addition to profound economic costs, patients with NIDDM and diabetic nephropathy have a dramatically increased morbidity and premature mortality. NIDDM-related nephropathy varies widely among racial and ethnic groups, genders and lifestyles; and gender may interact with race to affect the disease progression. While the course of insulin-dependent diabetes mellitus (IDDM) progresses through well-defined stages, the natural history of NIDDM is less well characterized. NIDDM patients with coronary heart disease have a higher urinary albumin excretion rate at the time of diagnosis and follow-up. This greater risk may also be associated with hypertension and hyperlipidemia, and genes involved in blood pressure are obvious candidate genes for diabetic nephropathy. Hyperglycemia appears to be an important factor in the development of proteinuria in NIDDM, but its role and the influence of diet are not yet clear. Tobacco smoking can also be deleterious to the diabetic patient, and is also associated with disease progression. Maintaining euglycemia, stopping smoking and controlling blood pressure may prevent or slow the progression of NIDDM-related nephropathy and reduce extrarenal injury. Treatment recommendations include early screening for hyperlipidemia, appropriate exercise and a healthy diet. Cornerstones of management should also include: (1) educating the medical community and more widely disseminating data supporting the value of early treatment of microalbuminuria; (2) developing a comprehensive, multidisciplinary team approach that involves physicians, nurses, diabetes educators and behavioral therapists; and (3) intensifying research in this field.     

Reflex reversal of apnoeic episodes by electrical stimulation of upper airway in cats

Respiratory effects of electrical stimulation of the upper airways (UAW) before and during apnoeic episodes induced by nitrogen inhalation were studied in 9 anaesthetized cats. In eupnoeic animals these electrically-evoked reflexes comprise rapid and powerful inspiratory efforts characterized by strong maximal airway occlusion pressures (Pmax = 635 +/- 39 mm H2O) and rapid peak inspiratory flow rates (PIF = 536 +/- 36 ml.sec-1) similar to the sniff-like aspiration reflex elicited mechanically. Electrical stimulation of the UAW mucosa can elicit reflex inspirations and sniff-like aspiration reflexes even during reversible hypoxic apnoea but their intensity and reproducibility are transiently reduced. When repeated adequately, the electrically-induced reflexes can increase the reactivity of respiratory centre and interrupt or terminate apnoeic episodes as do other types of UAW stimulation. Reflex mechanisms and respiratory centre activations seem to be involved in these effects. The results suggest that electrical stimulation of UAW could be useful for testing the respiratory centre reactivity as well as for reflex reversal of apnoeic episodes and restoration of normal breathing in animal experiments and clinico-physiological studies. Such investigation of the role of UAW reflexes in the pathogenesis and therapy of apnoeic syndromes might also be possible by using a cardiostimulator adapted as respiratory pacemaker.     

Optical responses recorded after local stimulation in rat neostriatal slice preparations: effects of GABA and glutamate antagonists, and dopamine agonists

Congenital syphilis has been diagnosed very seldom in ancient populations. The case that we examined comes from San Jeronimo's Church (17th and 18th centuries AD; Mexico City). Coffin 43 contained an incomplete skeleton of an approximately 2-year-old infant. The pathological lesions of this skeleton include bilateral osteochondritis, diaphyseal osteomyelitis, and osteitis and/or periostitis on the long bones. The radiographic appearance depicts symmetrical osteomyelitic foci, particularly at the proximal extremity of both tibiae (Wimberger's sign). The skull exhibits hydrocephaly and periosteal changes on the vault, and the unerupted upper incisors evince dental hypoplasia and other pathological alterations reminiscent of Hutchinson's incisors. All these features strongly suggest a case of early congenital syphilis.     

Neural mechanism of pupillary dilation elicited by electro-acupuncture stimulation in anesthetized rats

The neural mechanisms to reflex dilation elicited by electro-acupuncture stimulation were investigated in anesthetized rats. Two needles, with 160 microns diameter and about 5 mm apart, were inserted into the skin and underlying muscle of a hindpaw. Repetitive 20 Hz, 0.5 ms electrical pulses at various intensities were used for stimulation for 30s. The pupil size was magnified about 44 times via a microscope and was continuously recorded on a videotape. Electro-acupuncture stimulation at more than 0.5 up to 6 mA induced stimulus intensity-dependent pupil dilation. These responses were abolished by the severance of the sciatic and saphenous nerve of the stimulated hindlimb. Compound action potentials were recorded from the distal cut end of the tibial of a saphenous nerve following electro-acupuncture stimulation of the hindpaw. The mean threshold of the compound action potentials of the myelinated fibers in saphenous nerves was 0.18 mA, while that of unmyelinated fibers was 3.0 mA. The mean threshold of the compound action potentials of the myelinated fibers in the tibial nerve was 0.20 mA of unmyelinated fibers was 3.3 mA. Severance of bilateral trunks did not affect the response, while severance of the third cranial nerves abolished the responses. In conclusion, electro-acupuncture stimulation applied to the hindpaws of the anesthetized rats induced excitation of myelinated or of both myelinated and unmyelinated afferent fibers of the tibial and saphenous nerve, and involved a reflex response of pupil dilation through the third cranial parasympathetic efferent nerve.