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What rate of infusion of intravenous nutrition solution is required to stimulate uptake of amino acids by peripheral tissues in depleted patients?

We examined the effect of varying the quantities (0, 0.1, 0.2, 0.3, and 0.4 gN.kg-1.[day]-1) of nitrogen input on N balance, 3-methylhistidine (3MH) excretion, plasma amino acid concentration and the net flux of amino acids across the leg in depleted patients requiring parenteral nutrition. The calorie-to-nitrogen ratio was 140 to 1 (kcal:1 gN) and consequently the patients received varying amounts of calories (8, 14, 28, 42, and 56 kcal.kg-1.[day]-10. There was negative nitrogen balance and net loss of amino acids from the limb during fasting. An infusion of 0.2 gN.kg-1.[day]-1 of IVN reversed the net catabolic process and resulted in equilibrium of peripheral total amino acid flux and of tyrosine flux without a decrease in 3MH excretion. Net uptake of total amino acids and tyrosine in peripheral tissues was achieved with 0.4 gN.kg-1.[day]-1 and 56 kcal.kg-1.[day]-1. This was associated with a fivefold increase in 3MH excretion (p less than 0.01), indicating that net anabolism occurred with increased protein turnover. Fifty per cent of the amino acids taken up by peripheral tissues during infusions of 0.4 gN.kg-1.[day]-1 was due to the uptake of glutamate (Glu) and 20% was due to the uptake of branched chain amino acids (BCAA). Plasma Glu concentration, [Glu], did not increase with increasing IVN infusion, but BCAA concentrations did. Although the mean plasma [Glu] did not change with IVN infusion, there was an independent effect of plasma [Glu] (p less than 0.0001) and of N input (p less than 0.0001) on Glu flux, indicating that even at high infusion rates the maximal capacity of peripheral tissues to take up Glu had not been reached.

Amino Acids↗

Differential effect of guanethidine on dopamine and norepinephrine in rat peripheral tissues.

The changes of dopamine (DA) and norepinephrine (NE) were investigated in rat peripheral tissues after guanethidine treatment (50 mg/kg i.p. five days each week) during one week (group 1, n = 10, five injections) and during 2.5 weeks (group 2, n = 8, 13 injections). Guanethidine greatly reduced NE levels in all the analyzed tissues but only partially depleted DA in kidney, bladder, stomach, intestine, lung and liver and in sympathetic ganglia. The differential pattern of changes between DA and NE induced by guanethidine suggests that peripheral DA is distributed in several neuronal or non-neuronal pools, whose presence, nature and contribution varies in the different tissues. Both noradrenergic cell bodies and small intensely fluorescent cells (SIF cells) can contribute to the DA in the superior cervical ganglion. Noradrenergic neurons seem to be the main sources of DA in seminal vesicles, vas deferens, heart and spleen. In addition to noradrenergic nerves, extraneuronal sources could account for a meaningful portion of DA in kidney, gastrointestinal tract, lung and liver. The bladder is the peripheral tissue where DA exhibits the highest resistance to the neurotoxin. Accordingly, these tissues may provide meaningful sources of non-precursor DA pools.

Animals↗

Distribution of substance K (neurokinin A) in the brain and peripheral tissues of rats.

The regional distribution of substance P (SP) and substance K (SK) in the central nervous system and peripheral tissues of rats was studied. High levels of SK-like immunoreactivity (SK-LI) and of SP-like immunoreactivity (SP-LI) were found in the substantia nigra, nucleus tractus solitarius and nucleus habenula. Neonatal treatment of rats with capsaicin caused a significant decrease in the SK-LI content in the submaxillary gland, but capsaicin had no effect on SK-LI content in any area of the brain. These observations suggest that SK in the brain and peripheral tissues may have significant physiological roles.

Animals↗

Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus.

In mammals, circadian oscillators exist not only in the suprachiasmatic nucleus, which harbors the central pacemaker, but also in most peripheral tissues. It is believed that the SCN clock entrains the phase of peripheral clocks via chemical cues, such as rhythmically secreted hormones. Here we show that temporal feeding restriction under light-dark or dark-dark conditions can change the phase of circadian gene expression in peripheral cell types by up to 12 h while leaving the phase of cyclic gene expression in the SCN unaffected. Hence, changes in metabolism can lead to an uncoupling of peripheral oscillators from the central pacemaker. Sudden large changes in feeding time, similar to abrupt changes in the photoperiod, reset the phase of rhythmic gene expression gradually and are thus likely to act through a clock-dependent mechanism. Food-induced phase resetting proceeds faster in liver than in kidney, heart, or pancreas, but after 1 wk of daytime feeding, the phases of circadian gene expression are similar in all examined peripheral tissues.

Animals↗

Decreased susceptibility to fatty acid-induced peripheral tissue insulin resistance in women.

Elevation of plasma nonesterified fatty acid (NEFA) levels has been shown in various studies to induce peripheral tissue insulin resistance and impair the suppression of endogenous glucose production (EGP). These studies have been conducted predominantly in men. We compared the effects of elevated plasma NEFA levels on basal and insulin-stimulated glucose metabolism in 8 normal women (age 42 +/- 8 years [mean +/- SD], BMI 25 +/- 3 kg/m(2)) and 10 normal men (35 +/- 6 years, 24 +/- 3 kg/m(2)). Each subject underwent two 5-h 80 mU. m(-2). min(-1) hyperinsulinemic-euglycemic clamps with measurement of glucose kinetics (intravenous [3-(3)H]glucose) and substrate oxidation. Plasma NEFA levels were elevated in one study for 3 h before and during the clamp ( approximately 1 mmol/l in both groups) by infusion of 20% Intralipid (60 ml/h) and heparin (900 U/h). In the control studies, the men and women had similar insulin-stimulated glucose disposal rates (R(d)) and substrate oxidation rates. In the men, elevated NEFA levels decreased insulin-stimulated glucose R(d) during the final 40 min of the clamp by 23% (P < 0.001). By contrast, no significant change in glucose R(d) was found in the women (control 10.4 +/- 1.1, lipid study 9.9 +/- 1.3 mg. kg(-1). min(-1)). Glucose R(d) was also unchanged in six women studied at a lower insulin dose (40 mU. m(-2). min(-1)). During the last 40 min of the high-insulin dose clamps with elevated NEFA, glucose oxidation was decreased by 33% in the men (P < 0.001) and by 23% in the women (P < 0.02). Nonoxidative glucose R(d) at this time was decreased by 15% in the men (P = 0.02) but was not significantly affected in women. Basal EGP was unaffected by elevation of plasma NEFA levels in both groups. Suppression of EGP during the glucose clamps, however, was impaired. At the insulin infusion rate used, the magnitude of this defect was comparable in men and women. In summary, our findings suggest that although the effects on EGP appear comparable, the inhibitory effects of NEFA on peripheral tissue insulin sensitivity are observed in men but cannot be demonstrated in women.

Adult↗

Nitric oxide synthase imunolabeling in the molluscan CNS and peripheral tissues.

NOS immunoreactivity was assayed in CNS and peripheral tissues of the sea slugs Pleurobranchaea californica, Tritonia diomedea and Aplysia californica using different antisera against mammalian nitric oxide synthase in Western blots. Polyclonal anti-nNOS labeled at 250, 185, 170, 155, 100, 75, and 65 kD in extracts of Pleurobranchaea CNS, salivary gland and esophagus but not of gills or muscle. The labeling pattern for Tritonia in bands at 250, 200, 120/110, 100, 69, 65, and 60 kD differed somewhat. Anti-nNOS labeling in Aplysia was markedly different, with bands labeled only at 69 and 60 kD in CNS extracts, and at 200, 190, 69 and 60 kD in salivary and esophagus extracts. The wide variation in NOS immunoreactivity is consistent with species differences in tissue localization and biochemical properties of molluscan NOS isoforms.

Animals↗

Postnatal development of peripheral-type benzodiazepine receptors in rat brain and peripheral tissues.

We examined the postnatal development of peripheral-type benzodiazepine receptors (PBRs), labelled with [3H]PK 11195, in rat brain and peripheral tissues. Specific [3H]PK 11195 binding exhibited a heterogeneous patterns of postnatal development in the rat: three patterns of increase, decrease and no change. Hence, the density of the PBRs can be independently regulated in each tissue during postnatal development, and the postnatal alterations in the density might be parallel with the functional activities coupled to the receptors.

Adrenal Glands↗

[Fuzzing pattern recognition study on Raman spectrum of tumor peripheral tissue].

On the basis of some theories about fuzzing pattern recognition, the present article studied the data preprocessing of the Raman spectrum of tumor peripheral tissue, and feature extraction and selection. According to these features the authors improved the leaning towards the bigger membership function of trapezoidal distribution. The authors built the membership function of Raman spectrum of tumor peripheral tissue which belongs to malignant tumor on the basis of 40 specimens, and designed the classifier. The test of other 40 specimens showed that the discrimination of malignant tumor is 82.4%, while that of beginning tumor is 73.9%.

Humans↗

Microinjection of leptin into the ventromedial hypothalamus increases glucose uptake in peripheral tissues in rats.

We studied the effects of microinjection of leptin into the ventromedial hypothalamus (VMH) and lateral hypothalamus (LH) on glucose uptake in peripheral tissues in unanesthetized rats. The rate of glucose uptake was assessed in vivo by 2-[3H]deoxyglucose incorporation. Single injection of leptin into VMH increased glucose uptake in brown adipose tissue (BAT), heart, skeletal muscles, and spleen but not in white adipose tissue or skin. On the other hand, microinjection of leptin into LH had little effect on glucose uptake in those tissues. The plasma concentrations of glucose and insulin were unaltered by intrahypothalamic injection of leptin into either VMH or LH. Among skeletal muscles, the increase in glucose uptake induced by intrahypothalamic injection of leptin was greater in the soleus than in the extensor digitorum longus. Likewise, the increased glucose uptake in the gastrocnemius in response to leptin was more prominent in the red part than in the white part of the tissue. When surgical sympathetic denervation of the interscapular BAT was performed, the enhanced glucose uptake by BAT in response to intrahypothalamic leptin was completely suppressed. These findings suggest that intrahypothalamic injection of leptin preferentially increases glucose uptake by some peripheral tissues through activation of the VMH-sympathetic (or its neighboring medial hypothalamus-sympathetic) nervous system, thereby contributing to the maintenance of energy balance.

Adipose Tissue, Brown↗

Localization of specific binding sites for atrial natriuretic factor in peripheral tissues of the guinea pig, rat, and human.

Specific, high affinity atrial natriuretic factor (ANF) binding sites were identified and localized by autoradiographic techniques in peripheral tissues of the guinea pig, rat, and human. In the guinea pig kidney, high concentrations of ANF binding sites were located in the glomerular apparatus, outer medulla, and small renal arteries. Other peripheral tissues containing ANF binding sites included the zona glomerulosa of the adrenal cortex, the smooth muscle layer of the aorta and gallbladder, the lung parenchyma, the posterior lobe of the pituitary, the ciliary body of the eye, and the leptomeninges and choroid plexus of the brain. The distribution of ANF binding sites in the rat and human kidney was nearly identical to those seen in the guinea pig kidney; high concentrations were present in the glomerular apparatus, outer medulla, and small renal arteries. These results are consistent with earlier physiological and pharmacological studies that suggested that ANF plays a functional role in the regulation of extracellular fluid volume and blood pressure. There appears to be little species variation in the location and concentration of renal ANF binding sites, suggesting that, at least in the kidney, the results in experimental animals are relevant to the actions of ANF in humans. The finding that ANF binding sites were stable and present in high concentrations in human postmortem kidneys further suggests that these tissues may be amenable to testing for the involvement of ANF receptor dysfunction in diseases such as hypertension and congestive heart failure.

Adrenal Glands↗

Clock genes in mammalian peripheral tissues.

For many years, neurons of the suprachiasmatic nucleus (SCN) in the hypothalamus were thought to contain the unique mammalian clock controlling circadian rhythmicity of peripheral tissues via neural and humoral signals. Surprisingly, the cloning and characterisation of mammalian clock genes have revealed that they are expressed in a circadian manner throughout the body. It is generally accepted now that peripheral cells contain a circadian clock which is similar to the one present in SCN neurons, although only the latter seems to be self-sustained. It is still unclear how these peripheral clocks are synchronised by the central SCN clock, albeit humoral signals appear to be crucial. Interestingly, peripheral clocks can be uncoupled from the central clock in particular conditions such as restricted-feeding, allowing peripheral tissues to adapt themselves to cues incompatible to other cues perceived by the SCN (mainly the photoperiod). Whereas circadian clocks have been intensively dissected, little is known about the mechanisms by which these clocks regulate the expression of clock-controlled genes. Direct regulation for some of them by the products of clock genes was recently documented, but this probably represents the exception rather than the rule. We should soon be able to describe complete circadian transcriptional cascades from clock genes to enzymes and structural proteins. In addition to circadian humoral and neural signals, these cascades should help us to understand how gene expression, physiology and behaviour are influenced by the rotation of the Earth around its axis.

Animals↗

Peripheral tissue metabolism in man with varied disease states and similar weight loss.

The purpose of this study was to identify the effects of tumor burden and benign inflammatory disease on peripheral tissue metabolism independent of antecedent weight loss. This was accomplished by comparing forearm substrate flux profiles in cachectic cancer and benign disease patients to those of normal subjects before and after 10 days of total protein calorie depletion. Tumor-bearing patients (CA), benign disease patients (BD), and starved (ST) normal volunteers had similar weight loss. Resting energy expenditure was not significantly different between the study populations. Efflux of total amino acids (TAA [nmole/100 ml tissue-min]) decreased significantly (P less than 0.05) in the normals after 10 days of starvation (-886 +/- 185 postabsorptive (PA) vs -278 +/- 60 (ST]. CA patients had TAA efflux of -428 +/- 52 which was significantly (P less than 0.05) less than PA normals. In contrast, BD patients had a significantly (P less than 0.05) elevated TAA efflux of -895 +/- 165 compared to ST normals. CA patients had a significantly (P less than 0.05) elevated glucose uptake and lactate efflux compared to ST normals (glucose: +1.12 +/- 0.21 (CA) vs +0.11 +/- 0.09 (ST), lactate: -0.84 +/- 0.13 (CA) vs -0.38 +/- 0.13 (ST) [mumole/100 ml tissue-min]). The data suggest that tumor-bearing patients are able to maintain their peripheral tissue protein sparing adaptation to nutritional depletion in the presence of accelerated glucose utilization. However, clinically stable patients with benign disease do not demonstrate this adaptation and may be at greater risk for lean tissue dissolution than previously appreciated.

Adult↗

Effect of streptozotocin-induced diabetes mellitus on serotonin measures of peripheral tissues in rats.

The present study was conducted to examine whether experimental diabetes (streptozotocin-induced) promotes changes in serotonin (5HT) measures of peripheral tissue. Platelet-free plasma 5HT, tryptophan and 5-hydroxyindolacetic acid (5HIAA), whole blood 5HT and renal, liver, intestinal and lung 5HT and 5HIAA levels were measured in rats of four experimental groups: control, diabetic, diabetic+insulin and non-diabetic+insulin. Several serotonin measures were unaltered in all four experimental groups, i.e. plasma, liver and lung 5HT and 5HIAA levels. Whole blood 5HT levels descended about 50% in diabetic rats, then recovered their proper levels after 1 week of insulin therapy. Diabetic animals had a significantly greater intestinal 5HT concentration (+50% versus control), while intestinal 5HIAA levels did not achieve statistical significance despite a -26% decrement in their value. Both renal 5HT and 5HIAA levels were decreased in diabetic animals and recovered with insulin therapy. Peripheral tissue 5HT measures were not varied by insulin administration to non-diabetic animals. The results are consistent with a 5HT release, which is diminished in enterochromaffin cells and enhanced in platelet concomitantly to a minor platelet 5HT uptake, for explaining alterations of plasma/blood 5HT measures in experimental diabetes, and with a diminished synthesis of 5HT for explaining renal changes.

Animals↗

Variability in surface antigen expression of human breast epithelial cells cultured from normal breast, normal tissue peripheral to breast carcinomas, and breast carcinomas.

Single-cell heterogeneity and variability in expression of several surface antigens on human mammary epithelial cells in short-term culture were studied with immunofluorescence techniques, using polyclonal and monoclonal antibodies. The cultures, derived from normal breast, a fibroadenoma, a gynecomastia, normal breast tissue peripheral to breast carcinomas, and breast carcinomas and their metastases, were studied after one passage in vitro. The percentage of positive cells varied considerably from one tissue sample to another in all categories from normal to malignant, although there was an overall trend toward a decreasing percentage of positive cells of malignant tissues. The relative antigen content varied 3- to 8-fold among individual samples of cells from normal, peripheral, and carcinoma tissue, while the mean values in the three categories were similar. The single-cell variability in relative antigen content was considerable in all individual samples of normal, peripheral, and carcinoma tissues, as reflected in the high coefficients of variation. However, the coefficients of variation were significantly higher for cells from carcinoma and peripheral tissues [69 +/- 10% (S.E.) and 75 +/- 9%, respectively] than for cells from normal breast (48 +/- 5%). By analyzing in clonal colonies the appearance of quantitative variants in expression of a specific surface antigen, detected with a monoclonal antibody, the carcinoma cells were found to have a 10-fold higher rate of phenotypic variability (mean, 1.21 X 10(-2)/cell/generation) than did cells from normal breast (mean, 0.119 X 10(-2)) and one gynecomastia (0.045 X 10(-2)). Mammary epithelial cells from apparently "normal" tissue peripheral to a carcinoma had an intermediate rate of phenotypic variability (mean, 0.310 X 10(-2)) that was significantly higher than that of the normal tissue.

Adenofibroma↗

Distribution of neurokinin B in rat spinal cord and peripheral tissues: comparison with neurokinin A and substance P and effects of neonatal capsaicin treatment.

In the present study, highly specific radioimmunoassays were developed and used to measure neurokinin B, neurokinin A and substance P in the rat spinal cord and various peripheral tissues. The results are as follows. (1) Neurokinin B and neurokinin A were distributed all along the rostrocaudal axis of the spinal cord, as is substance P, and were more concentrated in the dorsal than in the ventral region. (2) Substance P was more abundant in the central and peripheral nervous tissues than neurokinin A, while in certain peripheral organs, neurokinin A was more abundant than substance P. In the spinal cord, neurokinin B concentrations were lower than those of the other two tachykinins. (3) In contrast to neurokinin A and substance P, neurokinin B was not detected in any of the peripheral tissues examined. (4) Capsaicin treatment reduced by half neurokinin A and substance P concentrations in the dorsal region of the spinal cord, the dorsal root ganglia and the sciatic nerve, but was without effect on neurokinin B concentrations in the spinal cord. Neurokinin A, like substance P, may therefore have an important function in the transmission of sensory information, particularly in nociceptive transmission from the periphery to the spinal cord and in peripheral neurogenic inflammation. In contrast, since neurokinin B was not found in the sensory neurons, it is not likely to have these functions, but may perhaps control them.

Animals↗

Chemokine-mediated control of T cell traffic in lymphoid and peripheral tissues.

Antigen-driven T cell education and subsequent pathogen elimination present particular challenges for the immune system. Pathogens generally enter the body at peripheral sites such as the skin, gastrointestinal tract or lung, areas from which naïve T cells are largely excluded. Instead, naïve T cells constantly recirculate through secondary lymphoid organs, such as lymph nodes and Peyer's patches, in search for antigen brought to these locations by means of afferent lymphatic channels. Here, antigen-loaded dendritic cells present antigen-peptide-MHC complexes to clonotypic T cells and provide appropriate co-stimulatory signals for immune response initiation. As a result, short-lived effector T cells and long-lived memory T cells are generated that reach the peripheral tissue for participation in immune responses and immune surveillance. Effector and memory T cell relocation is non-random, due to tissue-specific "address codes" that allow proper tissue homing. This process involves adhesion molecules, including selectins, integrins, and corresponding vascular ligands as well as the large family of chemokines and their receptors. Here, we discuss the changes in chemokine receptor expression that occur during T cell activation and differentiation, and the ways in which these changes impact on the migration potential of naïve, effector, and memory T cells. We summarize our current understanding of T cell homing to the T zone and B cell follicles within secondary lymphoid tissues and highlight the two chemokine receptors CCR7 and CXCR5 that recognize chemokines constitutively present either in the T zone (CCR7 ligands CCL19/ELC and CCL21/SLC) or follicular compartment (CXCR5 ligand CXCL13/BCA-1). CCR7 is characteristic for naive and central memory T (T(CM)) cells whereas CXCR5 distinguishes follicular B helper T (T(FH)) cells. In addition, we further subdivide long-lived memory T cells into CCR7-negative effector memory T (T(EM)) cells and peripheral immune surveillance T (T(PS)) cells. The latter term designates the extraordinarily large subset of memory T cells with primary residence in normal (healthy) peripheral tissues. Our current understanding of T(PS) cell migration and function is highly fragmentary, but these cells are thought to provide immediate protection locally at the site of pathogen entry. Here, we propose that the tissue distribution of T(PS) cells is determined by a distinct set of chemokines and corresponding receptors that differs from those operating in secondary lymphoid tissues and inflammatory sites.

Animals↗

Minireview. Evidence that dopamine is a neurotransmitter in peripheral tissues.

In the CNS, dopamine (DA) is a recognized neurotransmitter as well as a precursor for norepinephrine (NE) and epinephrine (EPI). In contrast to the CNS, DA has been assumed to be only a precursor in peripheral tissues. There is now, however, considerable evidence to support the hypothesis that it may function as a neurotransmitter and/or cotransmitter in peripheral tissues in addition to being a precursor. In this minireview we summarize evidence supporting the view that DA plays a role of its own in peripheral neurotransmission.

Animals↗

The pineal gland is not essential for circadian expression of rat period homologue (rper2) mRNA in the suprachiasmatic nucleus and peripheral tissues.

To investigate the functional involvement of the pineal gland in circadian expression of the rat period homolog gene (rPer2) in the suprachiasmatic nucleus (SCN) and peripheral tissues, we performed Northern blot analysis in tissues from pinealectomized rats. The ectomy did not have any significant effects on rPer2 mRNA expression patterns both in a daily light-dark condition and in a constant darkness. These results suggest that the rhythmic secretion of pineal melatonin is not essential for the circadian expression of clock genes in the SCN and other peripheral tissues of rats.

Animals↗