Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Peripheral tissues”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,135 records · Page 63Linked to original sources
PubMed1986

Impact of glucose ingestion on hepatic and peripheral glucose metabolism in man: an analysis based on simultaneous use of the forearm and double isotope techniques.

The metabolic response to glucose ingestion was studied in 10 normal men (aged 21-23 yr) by the simultaneous application of the forearm and double isotope techniques. The latter consisted of a primed constant infusion of [3-3H]glucose, followed by the administration of an oral glucose load (mean +/- SE, 90.7 +/- 0.7 g) containing [1-14C]glucose. Most (80.6 +/- 8.1%) of the ingested glucose appeared systemically within 270 min, suggesting that initial splanchnic glucose extraction accounted for 19.4 +/- 3.1% (17.7 +/- 2.8 g) of the oral load. Basal hepatic glucose output (2.22 +/- 0.12 mg/kg X min) was reduced (P less than 0.005) within 30 min after glucose loading and remained suppressed throughout the study; its mean reduction from 0-270 min was 54.9 +/- 9.9%, thereby accounting for the conservation of 26.5 +/- 4.9 g glucose. Suprabasal glucose appearance from 0-270 min was 46.6 +/- 4.3 g. Forearm glucose uptake rose 8.5-fold to 0.664 +/- 0.083 mg/100 ml forearm X min at 45 min, but basal forearm oxygen uptake (6.1 +/- 0.4 mumol/100 ml forearm X min) did not change. The increment in glucose disappearance from 0-270 min was 46.4 +/- 3.8 g, of which increased glucose uptake by muscle, determined from the forearm glucose uptake data, accounted for 37.7 +/- 5.1 g (81%). If uptake of the remaining 8.7 g was shared equally by the liver and peripheral tissues, the splanchnic bed and periphery would account, respectively, for 47.1 g (52%) and 43.5 g (48%) of the ingested load. We conclude that splanchnic and peripheral tissues contribute almost equally to the total homeostatic response; in kinetic terms, decreased hepatic glucose output and increased glucose uptake (splanchnic plus peripheral) constitute 29% and 71% of the total response, respectively; restoration of basal glucose kinetics after glucose ingestion requires more than 270 min; and increased peripheral oxygen uptake is not the mechanism of glucose-induced thermogenesis which, instead, may reflect increased splanchnic oxygen consumption.

Administration, Oral↗
PubMed1990

Cellular localization of apolipoprotein D and lecithin:cholesterol acyltransferase mRNA in rhesus monkey tissues by in situ hybridization.

Apolipoprotein D (apoD) and lecithin:cholesterol acyl transferase (LCAT) are found on high density lipoprotein particles (HDLs) and have been postulated to form part of a complex involved in the transport of cholesterol from peripheral tissues to the liver for excretion. We have examined the sites of synthesis of the mRNAs for these two proteins in the rhesus monkey by in situ hybridization. ApoD mRNA-containing cells were widely distributed throughout peripheral tissues in interstitial and connective tissue fibroblasts often associated with blood vessels or capillaries. ApoD mRNA was also found localized in cells associated with peripheral nerves, neuroglial cells, cells in the subarachnoid space on the surface of the brain including the pial cells, perivascular cells, and scattered neurons in the brain. LCAT demonstrated a much more restricted pattern of synthesis and was found to be synthesized by hepatocytes, the basal cell layer of the epidermis, and in brain cell populations distinct from those that synthesize apoD. In the brain LCAT was synthesized by scattered neurons, neuroglial cells, ependymal cells, as well as a discrete cell layer in the cerebellum. ApoD has been shown to possess extensive homology to retinol binding protein, which has a binding pocket for vitamin A. We propose that apoD may also function to bind cholesterol or its derivatives in compartments not in direct contact with the blood. The findings of both apoD and LCAT synthesis in the brain suggest that they play a significant role in lipid transport in the brain.

Animals↗
PubMed2006

Lack of food anticipation in Per2 mutant mice.

Predicting time of food availability is key for survival in most animals. Under restricted feeding conditions, this prediction is manifested in anticipatory bouts of locomotor activity and body temperature. This process seems to be driven by a food-entrainable oscillator independent of the main, light-entrainable clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus . Although the SCN clockwork involves self-sustaining transcriptional and translational feedback loops based on rhythmic expression of mRNA and proteins of clock genes , the molecular mechanisms responsible for food anticipation are not well understood. Period genes Per1 and Per2 are crucial for the SCN's resetting to light . Here, we investigated the role of these genes in circadian anticipatory behavior by studying rest-activity and body-temperature rhythms of Per1 and Per2 mutant mice under restricted feeding conditions. We also monitored expression of clock genes in the SCN and peripheral tissues. Whereas wild-type and Per1 mutant mice expressed regular food-anticipatory activity, Per2 mutant mice did not show food anticipation. In peripheral tissues, however, phase shifts of clock-gene expression in response to timed food restriction were comparable in all genotypes. In conclusion, a mutation in Per2 abolishes anticipation of mealtime, without interfering with peripheral synchronization by feeding cycles.

Analysis of Variance↗
PubMed1993

Role of thyrotropin in triiodothyronine generation in hypothyroidism.

Most of the circulating T3 is generated by monodeiodination of T4 in extrathyroidal tissue with only minor contribution by the thyroid gland. Since T3 is the main active thyroid hormone and TSH is the major modulator of its synthesis and release by the thyroid gland, TSH may also play a significant role in synthesis and release of T3 by the peripheral tissues as documented in recent in vitro animal studies. However, the data regarding its influence on T4 metabolism in humans is lacking. Hypothyroidism may provide an appropriate environment for assessing the influence of TSH in synthesis and release of T3 by the extrathyroidal tissues, since circulating T3 is almost totally derived via peripheral conversion of T4, and serum TSH varies from subnormal levels in central hypothyroidism to a wide range of supernormal concentration in the primary variety. This study determined the relationship between serum TSH concentration and T3 and T4 ratio, a reliable index of conversion of T4 into T3 in peripheral tissues, in 75 subjects with hypothyroidism including both the primary and the central types. Serum T3 was significantly higher (p < 0.001) in primary hypothyroidism (1.48 +/- 0.13 mM/l) in comparison with the central type (0.71 +/- 0.09 mM/l) despite almost equally low serum T4 concentration in both groups. In primary hypothyroidism, T3:T4 ratio (0.026 +/- 0.0012) was significantly higher (p < 0.01) than normal (0.017 +/- 0.0010) along with supernormal TSH (71 +/- 6.4 mU/L) concentration prior to initiation of LT4 replacement therapy and normalized (0.015 +/- 0.0008) on achieving euthyroid state with correction of serum TSH level (3.8 +/- 0.3 mU/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

Neuronal calcium sensor protein visinin-like protein-3 interacts with microsomal cytochrome b5 in a Ca2+-dependent manner.

Visinin-like protein-3, which is one of the neuronal calcium sensors, has been shown to be mainly expressed in cerebellar Purkinje cells, but cellular function of this protein has not yet been elucidated. We examined the tissue distribution of murine visinin-like protein-3 transcripts using real-time reverse transcription-PCR. Visinin-like protein-3 mRNA was found to be expressed in peripheral tissues. Particularly, the expression of the transcript in the thymus was significantly higher than in other peripheral tissues. In addition, B6RVTC1 thymoma cells robustly expressed visinin-like protein-3 mRNA. To identify a target protein of visinin-like protein-3, we performed a pull-down experiment using glutathione S-transferase-tagged visinin-like protein-3 and two-dimensional electrophoresis. We demonstrated that microsomal cytochrome b(5) was a Ca(2+)-dependent binding partner of visinin-like protein-3. In a co-immunoprecipitation experiment, it was observed that hippocalcin, as well as visinin-like protein-3, could interact with cytochrome b(5). Furthermore, we confirmed that the sequence Val(114)-Tyr(127) at the C-terminal tail of cytochrome b(5) is the minimal structural requirement for binding to visinin-like protein-3. In addition, the loop His(19)-His(25) at the N terminus of visinin-like protein-3 is essential for binding to cytochrome b(5). Microsomal cytochrome b(5) was also shown to be a potential activator of cytochrome P450. The present findings raise the possibility that visinin-like protein-3 may link Ca(2+) signaling to the machinery of microsomal monooxygenase complex composed of cytochrome b(5), cytochrome P450, and some reductases. This report provides the first evidence of an interaction between visinin-like protein-3 and microsomal cytochrome b(5).

Amino Acid Sequence↗
PubMed2000

Orphan-receptor ligand human urotensin II: receptor localization in human tissues and comparison of vasoconstrictor responses with endothelin-1.

We have determined the distribution of receptors for human urotensin-II (U-II) in human and rat CNS and peripheral tissues. In rat, [(125)I]-U-II binding density was highest in the abducens nucleus of brainstem (139.6+/-14 amol mm(-2)). Moderate levels were detected in dorsal horn of spinal cord and lower levels in aorta (22. 5+/-6 amol mm(-2)). In human tissues density was highest in skeletal muscle and cerebral cortex ( approximately 30 amol mm(-2)), with lower levels (<15 amol mm(-2)) in kidney cortex and left ventricle. Little binding was identified in atria, conducting system of the heart and lung parenchyma. Receptor density was less in human coronary artery smooth muscle (14.6+/-3 amol mm(-2), n=10) than rat aorta with no significant difference between normal and atherosclerotic vessels. In human skeletal muscle [(125)I]-U-II bound to a single receptor population with K(D)=0.24+/-0.17 nM and B(max)=1.97+/-1.1 fmol mg(-1) protein (n=4). U-II contracted human coronary, mammary and radial arteries, saphenous and umbilical veins with sub-nanomolar EC(50) values. U-II was 50 times more potent in arteries and <10 times more potent in veins than endothelin-1 (ET-1). The maximum response to U-II ( approximately 20% of control KCl) was significantly less than to ET-1 ( approximately 80% KCl). In contrast, in rat aorta, U-II and ET-1 were equipotent with similar maximum responses. This is the first report of high affinity receptors for [(125)I]-U-II in human CNS and peripheral tissues. This peptide produces potent, low efficacy, vasoconstriction in human arteries and veins. These data suggest a potential role for U-II in human physiology.

Animals↗
PubMed2004

Brain mineralocorticoid receptors: orchestrators of hypertension and end-organ disease.

PURPOSE OF REVIEW: 'New' tasks have been discovered for aldosterone and its receptor, the mineralocorticoid receptor, within both epithelial tissues of vectorial ion and water transport, such as the kidney, and non-epithelial organs, including the brain, heart and vessels. Promising results of clinical trials using low doses of mineralocorticoid receptor antagonists to forestall end-organ disease is resulting in an increase in their use, yet the biology of the mineralocorticoid receptor is far from clear. RECENT FINDINGS: Mineralocorticoid receptors within the kidney, heart and blood vessels mediate direct effects of aldosterone, including tissue inflammation, hypertrophy and fibrosis, that are independent of blood pressure. Activation, by aldosterone, of mineralocorticoid receptors in the brain increases central sympathetic nervous system drive to the periphery, thereby producing hypertension through multiple mechanisms, and increases levels of proinflammatory cytokines in both the circulation and peripheral tissues. Blocking of the mineralocorticoid receptor of the forebrain lowers the levels of peripheral tissue cytokines, including those induced by ischemic injury in the heart. Aldosterone is produced within the heart, blood vessels and brain, potentially liberating regulation of local concentrations of the steroid from peripheral mechanisms of control. A conundrum yet to be explained is the ligand-dependent functional specificity of the mineralocorticoid receptor in some non-epithelial tissues, which may be crucial to our understanding the end-organ pathophysiology of hypertension. SUMMARY: New technology is rapidly adding layers of complexity to, rather than simplifying, our understanding of the facile terms 'hemodynamic homeostasis' and 'end-organ' disease, but within this new knowledge lies the promise of better, more precise treatment of hypertension and its sequelae.

Aldosterone↗
PubMed1998

Reduction of cold-induced hypertension by antisense oligodeoxynucleotides to angiotensinogen mRNA and AT1-receptor mRNA in brain and blood.

Rats exposed chronically to mild cold (5 degrees C/41 degrees F) develop hypertension and cardiac hypertrophy. This provides a unique model of hypertension that is environmentally induced. The blood renin-angiotensin system (RAS) has been shown to play a role in both initiating and maintaining the high blood pressure (BP) in cold-induced hypertension. The mechanism also appears to involve both the tissue and brain RAS because there is increased mRNA for angiotensinogen (AGT) and angiotensin type 1 (AT1) receptors in brain and peripheral tissues, an increased spontaneous drinking response, and an increased dipsogenic response to acute administration of angiotensin II (Ang II) in cold-treated rats. Antisense oligodeoxynucleotides (AS-ODN), targeted to the RAS, have been shown to reduce BP in spontaneously hypertensive rats. Therefore, we injected AS-ODN in rats with cold-induced hypertension to test whether antisense inhibition was effective in reducing this nongenetic nonsurgical hypertension. Sprague-Dawley rats were made hypertensive by cold exposure and injected intracerebroventricularly with AS-ODN to AGT mRNA (n=6) or AT1 receptor mRNA (n=6). Systolic BP was recorded by tail cuff 24 hours later for 2 or 7 days, respectively. Systolic BP decreased significantly in response to AGT-AS-ODN (40+/-6 mm Hg, P<0.01) within 1 day after injection and to AT1 receptor-AS-ODN (P<0.05) for 3 days after injection. The maximum decrease was 41+/-10 mm Hg. Systolic BP then gradually increased to the preinjection level. The spontaneous drinking response to cold treatment also decreased significantly (P<0.05) after AGT-AS-ODN or AT1 receptor-AS-ODN intracerebroventricular injection. Intracardiac injection of AT1-AS-ODN (n=6) reduced systolic BP by 36+/-8 mm Hg (P<0.05) and decreased AT1 receptor as measured by autoradiography in aorta, adrenal glands, and kidneys 24 hours after injection. These data show that AS-ODN reduces BP in cold-induced hypertension and that the hypertension involves both peripheral tissues and central RAS in addition to blood-borne RAS mechanisms.

Adrenal Glands↗
PubMed1980

Characterization of alpha-adrenoceptors in rat and guinea pig tissues using radiolabeled agonists and antagonists.

Tritium-labeled preparations of the selective alpha 2-adrenoceptor agonist, clonidine, and the selective alpha 1-adrenoceptor antagonists, prazosin and WB 4101, were examined for their suitability as ligands for receptor assay. In the rat brain, 3H-clonidine bound specifically with high affinity to membrane sites, and drug displacement studies indicated that these were alpha 2-adrenoceptors. The structural requirements for this receptor were defined by examining a range of clonidine analogues. 3H-Clonidine binding to peripheral tissues of the rat was very low, although peripheral tissues from guinea pig exhibited higher binding. Specific 3H-clinidine binding was not reduced after chemical sympathectomy, suggesting that the binding site, although having characteristics of an alpha 2-adrenoceptor, was not located presynaptically. Studies with 3H-WB 4101 in rat cerebral cortex indicated that this ligand bound to an alpha 1-adrenoceptor which was independent of the 3H-clonidine-binding site. 3H-Prazosin was a ligand for alpha 1-adrenoceptors in guinea pig brain and also in membranes from seminal vesicle. However, in the latter tissue, characterization of the binding site was hampered by a high degree of nonspecific binding (50% of total binding).

Animals↗
PubMed1999

Comparison of IgE and IgG antibody-dependent cytotoxicity in vitro and in a SCID mouse xenograft model of ovarian carcinoma.

Allergic reactions are mediated by IgE antibodies bound to high-affinity receptors on mast cells in peripheral tissues and are characterized by their immediacy and hypersensitivity. These properties could also be advantageous in immunotherapy against cancer growth in peripheral tissues. We have constructed chimeric IgE and IgG1 antibodies with murine V regions and human C regions corresponding to the MOv18 monoclonal antibody against the human ovarian tumor-associated antigen, folate binding protein. The antibodies exhibited the expected binding affinities for antigen and Fc receptors, and effector activities with human basophils and platelets in vitro. The protective activities of MOv18-IgE and MOv18-IgG1 were compared in a SCID mouse xenograft model of ovarian carcinoma. The beneficial effects of MOv18-IgE were greater and of longer duration than those of MOv18-IgG1. Our results suggest that the allergic reaction could be harnessed for the suppression of ovarian tumors.

Animals↗
PubMedDate not supplied

A review of evidence leading to the prediction that 1,4-butanediol is not a carcinogen.

1,4-Butanediol is an industrial chemical used primarily as an intermediate in the manufacture of other organic chemicals. It has recently been associated with deaths, addiction and withdrawal related to its promotion and use as a dietary supplement. The rapid absorption and conversion of 1,4-butanediol to gamma-hydroxybutyric acid (GHB, or date rape drug) in animals and humans is well documented and is the basis for its abuse potential. A disposition and metabolism study conducted in F344 rats by the National Toxicology Program (NTP) confirmed the rapid conversion of 1-(14)C-1,4-butanediol to (14)CO2. Because of this, the toxicological profile of 1,4-butanediol resembles that of gamma-hydroxybutyric acid. Gamma-hydroxybutyric acid occurs naturally in the brain and peripheral tissues and is converted to succinate and metabolized through the TCA cycle. Although the function of gamma-hydroxybutyric acid in peripheral tissues is not known, the presence of specific high affinity receptors for gamma-hydroxybutyric acid suggests that it functions as a neuromodulator in the brain and neuronal tissue. Gamma-hydroxybutyric acid readily crosses the blood-brain barrier and elicits characteristic neuropharmacologic responses after oral, i.p., or i.v. administration. The same responses are observed after administration of 1,4-butanediol. The cyclic lactone of gamma-hydroxybutyric acid, gamma-butyrolactone, is also rapidly converted to gamma-hydroxybutyric acid by enzymes in the blood and liver in animals and humans, and produces pharmacological effects identical to those produced by 1,4-butanediol and gamma-hydroxybutyric acid. Gamma-butyrolactone was previously evaluated by the NTP in 14-day and 13-week prechronic toxicology studies and in 2-year chronic toxicology and carcinogenesis studies in F344 rats and B6C3F1 mice. No organ specific toxicity occurred. In the carcinogenesis studies there was an equivocal response in male mice based on a marginal increase in the incidence of pheochromocytomas of the adrenal medulla. Because the absence of chronic toxicity and significant carcinogenicity of gamma-hydroxybutyric acid were established in NTP prechronic and chronic studies with gamma-butyrolactone, it is concluded that similar results would be obtained in a 2-year study with 1,4-butanediol, and that 1,4-butanediol is not a carcinogen.

4-Butyrolactone↗
PubMed1994

Nifedipine and intraoperative core body temperature in humans.

BACKGROUND: Initial anesthetic-induced hypothermia results largely from core-to-peripheral redistribution of heat. Nifedipine administration may minimize hypothermia by inducing vasodilation well before induction of anesthesia. Although vasodilation would redistribute heat to peripheral tissues, thermoregulatory responses would maintain core temperature. After equilibration, the patient would be left vasodilated, with a small core-to-peripheral temperature gradient. Minimal redistribution hypothermia may accompany subsequent induction of anesthesia, because heat flow requires a temperature gradient. In contrast, similar vasodilation concurrent with anesthetic-induced vasodilation may augment redistribution hypothermia. Accordingly, the authors tested the hypothesis that nifedipine treatment for 12 h before surgery would minimize intraoperative redistribution hypothermia, whereas nifedipine treatment immediately before induction of anesthesia would aggravate hypothermia. METHODS: Patients undergoing hip arthroplasty were randomly assigned to: (1) 20 mg long-acting nifedipine orally 12 h before surgery, and 10 mg sublingually 1.5 h before surgery (n = 10); (2) nifedipine 10 mg sublingually just before induction of anesthesia (n = 10); and (3) no nifedipine (control, n = 10). Anesthesia was maintained with isoflurane and 60% nitrous oxide. Administered intravenous fluids were heated, but the patients were not otherwise actively warmed. RESULTS: Core temperature decreased 0.8 degree C in the first hour of surgery in the patients given nifedipine the night before and the morning of surgery, which was significantly less than in the control group (1.7 degree C in the first hour). In contrast, core temperature decreased 2.0 degrees C in the first hour of surgery in the patients given nifedipine immediately before induction of anesthesia. During the subsequent 70-130 min of anesthesia, core temperature decreased at roughly comparable rates in each group. After 130 min of anesthesia, core temperature in the two nifedipine-treated groups differed by 1.6 degrees C, and the temperatures in all three groups differed significantly. CONCLUSIONS: Vasodilation induced by nifedipine well before induction of anesthesia minimized redistribution hypothermia, presumably by decreasing the core-to-peripheral tissue temperature gradient. In contrast, redistribution hypothermia was aggravated by administration of the same drug immediately before induction of anesthesia. Drug-induced modulation of vascular tone thus produces clinically important alterations in intraoperative core temperature.

Administration, Oral↗
PubMedDate not supplied

Chronic ethanol treatment decreases specific nonopiate beta-endorphin binding to hepatic and kidney membranes and lowers plasma beta-endorphin in the rat.

In a previous study we reported the presence of specific nonopiate beta-endorphin (BE) binding sites in peripheral tissues of the rat (Dave JR, Rubinstein N, Eskay RL: Evidence that beta-endorphin binds to specific receptors in rat peripheral tissue and stimulates the adenylate cyclase-adenosine 3',5'-monophosphate system. Endocrinology 117:1389-1396, 1985). The objective of this study was to determine the effect of chronic ethanol administration in vivo on specific nonopiate binding of BE in hepatic and kidney membranes. Experimental animals were exposed continuously for 14 days to ethanol vapor in an inhalation chamber at vapor levels sufficient to maintain blood ethanol levels greater than 120 mg/100 ml, whereas control animals were maintained in ethanol-free chambers. Chronic ethanol treatment decreased [125I]BE binding to hepatic and kidney membranes by approximately 35%, which was due to a decrease in the number of BE binding sites. Chronic ethanol treatment decreased immunoreactive BE in plasma by greater than 80%. In vitro exposure of hepatic and kidney membranes from control animals to ethanol resulted in a dose-related enhancement of BE binding with maximal enhancement of 50-65% being observed at 0.2% ethanol concentration. In contrast, the addition of ethanol in vitro to hepatic and kidney membranes derived from rats chronically exposed to ethanol in vivo did not affect BE binding. Our findings demonstrate that chronic alcohol exposure lowers immunoreactive BE in plasma and reduces BE binding in hepatic and kidney membranes. The observed reduction of BE binding may be due to ethanol-induced changes in membrane composition.

Alcoholism↗
PubMed1995

Use of high affinity, radioiodinated probes for identification of imidazoline/guanidinium receptive sites.

Various pharmacologically active compounds with an imidazoline or guanidinium moiety are recognized by membrane bound proteins that appear structurally and functionally distinct from known hormone receptors. Such entities are termed imidazoline binding sites, I receptors, or imidazoline/guanidinium receptive sites (IGRS). To facilitate the identification and structural analysis of IGRS, we developed functionalized molecular probes exhibiting high affinity and selectivity for IGRS. The molecular probes are structurally related to cirazoline, and imidazoline that exhibits high affinity for IGRS in both central and peripheral tissues. The parent molecule 2-[3-aminophenoxy]methyl imidazoline (125I-AMIPI), which was used to identify IGRS in brain and peripheral tissues. 125I-AMIPI was converted to the photosensitive arylazide derivative (125I-AMIPI) and used to identify the M(r) of the ligand binding subunit of IGRS in various tissues including brain, pancreas, kidney, and liver. The results of these studies indicate that there are multiple binding proteins for these molecules that differ in their apparent molecular weight, tissue distribution, intratissue location, and ligand recognition properties.

Animals↗
PubMed2003

Endothelin receptor antagonist bosentan improves microcirculatory blood flow in splanchnic organs in septic shock.

OBJECTIVE: Splanchnic ischemia is believed to play an important role in the development of multiple organ dysfunction in septic shock. The vasoconstrictor peptide endothelin can produce an intense and sustained splanchnic vasoconstriction and is increased in sepsis. The aim of this investigation was to study the effects of an endothelin antagonist on microcirculatory blood flow in multiple abdominal organs during septic shock. DESIGN: Prospective, controlled animal study. SETTING: University-affiliated research laboratory. SUBJECTS: Fifteen anesthetized and mechanically ventilated pigs. INTERVENTIONS: Septic shock was induced by fecal peritonitis. After 120 mins of sepsis, eight animals received 10 mg/kg bosentan intravenously followed by an intravenous infusion at 5 mg x kg-1 x hr-1 whereas seven (controls) received isotonic saline. At 240 mins after induction of sepsis both groups received hydroxyethyl starch, 20 mL/kg intravenously, to convert hypodynamic septic shock to hyperdynamic sepsis. MEASUREMENTS AND MAIN RESULTS: Microcirculatory blood flow was measured simultaneously and continuously in the jejunal muscularis, pancreas, liver, kidney, skeletal muscle, and gastric, jejunal, and colon mucosa by using a multiple-channel laser Doppler flow meter. After 120 mins, all animals had developed signs of hypodynamic sepsis with decreased cardiac index, mean arterial blood pressure, and gastric mucosal pH. Microcirculatory blood flow in the pancreas and liver had decreased by 20% and in the jejunal muscularis by >40% (p <.01) whereas it remained virtually unchanged in the gastric, jejunal, and colonic mucosa. After 240 mins, cardiac index, mean arterial blood pressure, gastric mucosal pH, and microcirculatory blood flow in the gastric mucosa, colon mucosa, jejunal muscularis, and pancreas had all deteriorated in the controls, whereas in the bosentan-treated group, cardiac index and microcirculatory blood flow in the pancreas, gastric, and colon mucosa improved. During hyperdynamic sepsis, cardiac index increased above baseline in both groups but significantly more in the bosentan group. In the control group, microcirculatory flow returned to baseline in most tissues except in skeletal muscle and jejunal muscularis. In the bosentan group, microcirculatory flow returned to or increased above baseline in all tissues except in the muscularis of the jejunum. CONCLUSIONS: The endothelin receptor antagonist bosentan significantly improved microcirculatory blood flow in many splanchnic organs and in peripheral tissues during septic shock. The results of this study are consistent with the hypothesis that endothelin plays an important role in the regulation of microcirculatory blood flow in splanchnic as well as in peripheral tissues during septic shock.

Acid-Base Equilibrium↗
PubMed2000

Fatty acid, carotenoid and vitamin A composition of tissues of free living gulls.

The aim of this study was to investigate fatty acid and carotenoid profile as well as vitamin A (retinol and retinol esters) content in gull (Larus fucus) tissues. Palmitic (16:0) and stearic (18:0) fatty acids were major saturates in all the tissues studied. Oleic acid (18:1n-9) was the major monounsaturate in the tissue phospholipids varying from 11.9% (liver) up to 18.2% (lung). Arachidonic acid (20:4n-6) was the major unsaturate in the phospholipid fraction in all the tissues. Liver contained the highest total carotenoid concentration which was 5 and 7 fold higher compared to kidney and pancreas. In the liver beta-carotene was major carotenoid. In contrast, in all other tissues beta-carotene was minor fraction with lutein being major carotenoid. Zeaxanthin, canthaxanthin, beta-cryptoxanthin and echinenone were also identified in the gull tissues. Liver and kidney were characterised by the highest vitamin A concentrations (1067.5 and 867.5 microg/g, respectively). Retinol comprised from 55.3% (pancreas) down to 8% (kidney) of the total vitamin A but was not detected in the abdominal fat. Retinyl palmitate was the major retinyl ester in the liver, kidney and heart (44.2; 38.1 and 46.0% of total retinyl esters). In muscles and abdominal fat retinyl stearate was the major retinyl ester fraction. Therefore high proportions of beta-carotene were found in gull liver and peripheral tissues were enriched by lutein and zeaxanthin compared to the liver, a very high concentration of retinyl esters in the kidney was observed and tissue-specificity in retinyl ester proportions in peripheral tissues was found.

Animals↗
PubMed2002

Systemic distribution of steroid sulfatase and estrogen sulfotransferase in human adult and fetal tissues.

Estrogens play a key role in various target tissues. Enzymes involved in the biosynthesis and metabolism of these sex steroids also regulate estrogenic actions in these tissues. Estrone sulfate (E1S) is a major circulating plasma estrogen that is converted into the biologically active estrogen, estrone (E1), by steroid sulfatase (STS). E1 is also sulfated and reverted into E1S by estrogen sulfotransferase (EST). These two enzymes have recently been shown to play important roles in the in situ estrogen actions of various sex steroid-dependent human tumors. However, the distribution of STS and EST in normal adult and fetal human tissues remains largely unknown. Therefore, in this study, in addition to examining the tissue distribution of both STS and EST mRNA in human adult and fetal tissues using RT followed by quantitative PCR, we studied the activity of these enzymes using (3)H-labeled E1/E1S as substrates in the homogenates of various human adult tissues. We also examined the localization of STS and EST protein in human adult and fetal tissues using immunohistochemistry, and that of EST mRNA in the adult kidney using laser dissection microscopy and PCR. STS mRNA, enzyme activity, and immunoreactivity were either absent or detected at very low levels in all adult and fetal tissues examined in this study. EST mRNA expression, however, was detected in all of the tissues examined, except for adult spleen and pancreas. EST enzyme activities were consistent with those of mRNA expression in the great majority of the tissues examined. Marked EST immunoreactivity was detected in hepatocytes, adrenal gland (adult, zona fasciculate to the reticularis; fetus, fetal zone), and epithelial cells of the gastrointestinal tract, smooth muscle cells of the tunica media in aorta, Leydig cells of the testis, and syncytiotrophoblast of the placenta. Patterns of EST immunolocalization were similar between adult and fetal human tissues, but EST immunoreactivity was detected in the urinary tubules of adult kidney, whereas in the fetal kidney, it was localized in the interstitial cells surrounding the urinary tubules. In the adult kidney, the presence of EST mRNA was also confirmed in the cells of urinary tubules using laser dissection microscopy and RT-PCR. Although the number of human tissues available for examination in this study was limited, our results suggest that between the enzymes involved in estrogen activation or inactivation, EST and not STS is the more widely expressed enzyme in various peripheral tissues in humans. We speculate that EST may play an important role in protecting peripheral tissues from possible excessive estrogenic effects.

Adult↗