Number Of Physiological Conditions Research Articles

Russian Consensus “Hyperammonemia in Adults”

The human body, like any other, is an intermediate component of the nitrogen cycle in nature. Consuming nitrogen from the external environment in the form of various compounds, the body processes it into ammonia - one of the final products of exchange of nitrogen-containing substances [1], which is removed from the body in the form of urea. The most active ammonia producers are organs with high exchange of amino acids and biogenic amines - nerve tissue, liver, intestine, and muscles. In a state of nitrogen equilibrium, the adult body consumes and releases about 15 g of nitrogen per day, temporary or permanent disruption of nitrogen balance results in a great number of physiological conditions and diseases, and the need to stabilize it is well known. However, despite a huge number of studies on the role of nitrogen metabolism and its compounds in the clinic, to date we have not been able to find any conciliation document in the world literature on the classification of ammonia-ammonium levels in human blood and approaches to the correction of hyperammonemia, which was the basis for the emergence of this consensus.

Lung perfusion measured using magnetic resonance imaging: New tools for physiological insights into the pulmonary circulation

Since the lung receives the entire cardiac output, sophisticated imaging techniques are not required in order to measure total organ perfusion. However, for many years studying lung function has required physiologists to consider the lung as a single entity: in imaging terms as a single voxel. Since imaging, and in particular functional imaging, allows the acquisition of spatial information important for studying lung function, these techniques provide considerable promise and are of great interest for pulmonary physiologists. In particular, despite the challenges of low proton density and short T2* in the lung, noncontrast MRI techniques to measure pulmonary perfusion have several advantages including high reliability and the ability to make repeated measurements under a number of physiologic conditions. This brief review focuses on the application of a particular arterial spin labeling (ASL) technique, ASL-FAIRER (flow sensitive inversion recovery with an extra radiofrequency pulse), to answer physiologic questions related to pulmonary function in health and disease. The associated measurement of regional proton density to correct for gravitational-based lung deformation (the "Slinky" effect (Slinky is a registered trademark of Pauf-Slinky incorporated)) and issues related to absolute quantification are also discussed.

Ectopic expression of eIF2Bε in rat skeletal muscle rescues the sepsis-induced reduction in guanine nucleotide exchange activity and protein synthesis

Eukaryotic initiation factor 2B (eIF2B) is a guanine nucleotide exchange factor (GEF) whose activity is both tightly regulated and rate-controlling with regard to global rates of protein synthesis. Skeletal muscle eIF2B activity and expression of its catalytic epsilon-subunit (eIF2Bepsilon) have been implicated as potential contributors to the altered rates of protein synthesis in a number of physiological conditions and experimental models. The objective of this study was to directly examine the effects of exogenously expressed eIF2Bepsilon in vivo on GEF activity and protein synthetic rates in rat skeletal muscle. A plasmid encoding FLAG-eIF2Bepsilon was transfected into the tibialis anterior (TA) of one leg, while the contralateral TA received a control plasmid. Ectopic expression of eIF2Bepsilon resulted in increased GEF activity in TA homogenates of healthy rats, demonstrating that the expressed protein was catalytically active. In an effort to restore a deficit in eIF2B activity, we utilized an established model of chronic sepsis in which skeletal muscle eIF2B activity is known to be impaired. Ectopic expression of eIF2Bepsilon in the TA rescued the sepsis-induced deficit in GEF activity and muscle protein synthesis. The results demonstrate that modulation of eIF2Bepsilon expression may be sufficient to correct deficits in skeletal muscle protein synthesis associated with sepsis and other muscle-wasting conditions.

Effects of Opioid Antagonism on Prolactin Secretion and c-Fos/TH Expression During Lactation in Rats

Many studies have established that dopamine (DA) secreted by tuberoinfundibular dopaminergic (TIDA) neurons in the hypothalamus is the major inhibitory factor controlling prolactin (PRL) secretion from the anterior pituitary. Endogenous opioid peptides (EOPs), mainly the neuropeptide beta-endorphin, facilitate PRL secretion by decreasing TIDA neuronal inhibitory tone in a number of physiological conditions, including pregnancy and lactation. We have previously demonstrated that there are many more c-Fos-expressing neurons than TIDA neurons in the arcuate nucleus, and treatment with naloxone (NAL), an opioid antagonist, activated these neurons in pregnant rats. Our previous data also suggest that the rostral region of the arcuate nucleus is more important than the caudal region in regulating the nocturnal PRL surge in pregnant rats. The aim of this study was to investigate the effects of NAL in regulating TIDA neuronal activity and therefore facilitating PRL secretion during lactation in rats. NAL was continuously infused (0.2 mg/10 microL/min iv) for 1 h before the separated pups returned, and then for 2 or 5 h after the separated pups were returned. Radioimmunoassay (RIA) was used to measure plasma PRL levels, and the immunocytochemical (ICC) staining of c-Fos was performed to detect changes in transcriptional activity of neurons in the hypothalamus. ICC of tyrosine hydroxylase (TH), the rate-limiting enzyme for DA synthesis, was performed to visualize TIDA neurons in the arcuate nucleus. The results showed that the peak of the PRL response to suckling was markedly delayed and dampened in NAL-treated rats (p<0.05). The percentage of c-Fos positive TH neurons in the arcute nucleus increased in rats treated with NAL for 5 h after return of pups, but not in rats treated with NAL for 2 h.

ATP modification of serotonin-induced contraction of the rat pulmonary artery.

Serotonin (5HT) and ATP are simultaneously released from activated platelets at the site of vascular injury and are hypothesized to play a significant role in hemostasis. Our laboratory investigated the modulation of vascular contraction of arterial ring segments by 5HT plus ATP as a model of the potential regulation of localized vascular tone by platelet releasates in regions of arterial damage. This study expands our focus on how these two vasoactive components, released from platelet dense granules, regulate vascular tone. 5HT- and 5HT analog-induced vasoconstrictions were measured in the presence or absence of ATP and ATP analogs with intact or deendothelialized rat pulmonary arterial ring segments suspended in organ baths. The possible presence of 5HT2 and 5HT1A receptor types in the rat pulmonary artery was demonstrated by vasoconstrictions induced by 5HT and (+)-8-hydroxy-2-(di-N-propylamino) tetralin hydrobromide (DPAT). The DPAT response was only 30%-50% of that induced by comparable concentrations of 5HT. The 5HT-induced contraction was inhibited by the 5HT2 antagonist, ketanserin. ATP equally relaxed 5HT and DPAT contracted tissue while the P2X agonist, alphabeta-methylene ATP, increased the contracted state of DPAT-treated arteries to a significantly greater extent than observed with 5HT. The P2y agonist, 3'-O-(4-benzoyl)benzoyl ATP (BzATP), the P2X agonist betagamma-methylene ATP, and ATP all relaxed 5HT-induced contractions to similar levels under a number of physiological conditions. The final level of 5HT-induced tissue contraction was the same whether ATP was added prior to, after, or simultaneously with 5HT. ATP and the phosphodiesterase inhibitor, theophylline, inhibited 5HT-induced vasoconstriction in an additive fashion. The ATP effects were endothelium dependent, while the inhibition by theophylline was not. The distribution of 5HT and ATP receptor types, as indicated by these and numerous other studies, appears to vary within different regions of the cardiovascular system. Extracellular ATP can synergistically enhance or inhibit 5HT-contracted blood vessels differentially at localized regions, which would significantly impact on localized vascular tone, and this in turn may modulate hemostasis and thrombosis.

Structural and functional analysis of the insulin-like growth factor I receptor gene promoter.

The insulin-like growth factor I receptor (IGF-I-R) gene is expressed in most body tissues. The levels of IGF-I-R mRNA, however, are regulated by a number of physiological conditions (development, differentiation, and hormonal milieu) as well as in certain pathological states (diabetes and tumors). To understand the molecular mechanisms which control the transcription of the IGF-I-R gene, we have cloned the promoter of the rat receptor gene and have characterized its activity by transient expression assays. Different fragments of the 5'-flanking region (subcloned upstream of a luciferase reporter gene) were transfected into buffalo rat liver 3A cells (a cell line with a low number of IGF-I binding sites) and Chinese hamster ovary cells (a cell line with a higher number of cell-surface receptors). In both cell lines, most of the promoter activity was located in the proximal 416 base pairs of 5'-flanking region. However, further dissection of this proximal fragment revealed a cell type-specific pattern of promoter activity. Thus, in buffalo rat liver 3A cells, subfragments of this region each contributed to total activity, suggesting that contiguous cis-elements can act together to activate transcription. In Chinese hamster ovary cells, on the other hand, subfragments of the proximal promoter region partially substituted for the proximal 416 base pairs of 5'-flanking region. Coexpression studies using an IGF-I-R promoter reporter construct together with an Sp1 expression vector (under the control of an ADH promoter) were performed in SL2 cells, a Drosophila cell line which lacks endogenous Sp1. The results obtained showed that Sp1 can trans-activate the IGF-I-R promoter in vivo. Transient transfection assays were complemented with gel-retardation assays and DNase I footprinting experiments, which showed that transcription factor Sp1 is potentially an important regulator of IGF-I-R gene expression.

Enzyme synthesis in the regulation of hepatic "malic" enzyme activity.

A homogeneous preparation of ;malic' enzyme (EC 1.1.1.40) from livers of thyroxine-treated rats was used to prepare in rabbits an antiserum to the enzyme that reacts monospecifically with the ;malic' enzyme in livers of rats in several physiological states. Changes in enzyme activity resulting from modification of the state of the animal are hence due to an altered amount of enzyme protein. The antiserum has been used to precipitate out ;malic' enzyme from heat-treated supernatant preparations of livers from both adult and neonatal rats, in a number of physiological conditions, that had been injected 30min earlier with l-[4,5-(3)H]leucine. The low incorporations of radioactivity into the immunoprecipitable enzyme have permitted the qualitative conclusion that changed enzyme activity in adult rats arises mainly from alterations in the rate of enzyme synthesis. The marked increase in ;malic' enzyme activity that occurs naturally or as a result of thyroxine treatment of the weanling rat is likewise due to a marked increase in the rate of enzyme synthesis possibly associated with a concurrent diminished rate of enzyme degradation.

Effect of instructional conditions on rate of binocular rivalry.

When conflicting contours are projected to corresponding areas of the retinae through a stereoscopic device, S reports viewing not a stable figure but an irregular alternation that cannot be given a unitary interpretation. For example, if the conflicting contours are a vertical bar projected to the left eye and a horizontal bar projected to the right, rhen the phenomenal outcome is the periodic establishment of one bar as dominant and the total or partial suppression of the other. The experienced alternation in contour domrnance defines the phenomenon of bitaoczdm (retinal) rivaky, and the total number of reversals or alternations per unit of time has been taken as an operational measure of the rate of binocz~lar rivahy. Historically, the phenomenon of binocular was linked with sensory threshold and figure reversal and was accounted for merely as fluctuations in the (Helmholtz, 1925). However, Guilford ( 1927) demonstrated thac these three phenomena had nothing to do with attention but were a physiological function occurring only with liminal stimuli; a number of physiological conditions, both peripheral and central, were involved, among which were local adaptation, eye movements, and local-central fatigue and inhibition. McDougall ( 1903) held thac the latter, local-central fatigue and inhibition, accounted for the phenomenon of rivalry; but that the phenomenon is affected by so many other than physiological factors that no purely physiological explanation could be satisfactory. Recently, Linksz ( 1952, p. 549) has deplored the usage of the term retinal rivalry for the phenomenon and instead employs the term of processes. The of the contours, he argues, is the phenomenal counterpart of opposing neurological gradients which cannot occupy the same cortical (or retinal) locus. Because of the limited neurological and physiological data in this area, the present writers have employed the more neutral and less objectional term, binocular rivalry, to describe the phenomenon. Although a number of studies have been conducted to determine rhe effects of rnv~ronmental variables, such as illumination level, figure-ground relationships, sc~mulus content, etc., on the rate of binocular rivalry, relatively few have been concerned with the inscri~ctions. Specifically, what is the effect of insuucrions on the reversal process? In his early work, Helmholtz (1925, p. 541) observed that he could voluntarily control the persistence of one visual field over the other, but he dismissed this ubiquitous finding as simply a phenomenon of