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 343 records · Page 19Linked to original sources

Advanced analysis of a cryptochrome mutation's effects on the robustness and phase of molecular cycles in isolated peripheral tissues of Drosophila.

BACKGROUND: Previously, we reported effects of the cry(b) mutation on circadian rhythms in period and timeless gene expression within isolated peripheral Drosophila tissues. We relied on luciferase activity driven by the respective regulatory genomic elements to provide real-time reporting of cycling gene expression. Subsequently, we developed a tool kit for the analysis of behavioral and molecular cycles. Here, we use these tools to analyze our earlier results as well as additional data obtained using the same experimental designs. RESULTS: Isolated antennal pairs, heads, bodies, wings and forelegs were evaluated under light-dark cycles. In these conditions, the cry(b) mutation significantly decreases the number of rhythmic specimens in each case except the wing. Moreover, among those specimens with detectable rhythmicity, mutant rhythms are significantly weaker than cry+ controls. In addition, cry(b) alters the phase of period gene expression in these tissues. Furthermore, peak phase of luciferase-reported period and timeless expression within cry+ samples is indistinguishable in some tissues, yet significantly different in others. We also analyze rhythms produced by antennal pairs in constant conditions. CONCLUSIONS: These analyses further show that circadian clock mechanisms in Drosophila may vary in a tissue-specific manner, including how the cry gene regulates circadian gene expression.

5' Flanking Region↗

Histochemical localisation of a galactose-containing glycoconjugate expressed by sensory neurones innervating different peripheral tissues in the rat.

The plant lectin Bandeiraea simplicifolia I-isolectin B4 (BSI-B4) identifies a galactose-containing, membrane-associated glycoconjugate expressed by a discrete subpopulation of unmyelinated primary sensory neurones in the rat. We have previously suggested that BSI-B4 selectively binds to primary sensory neurones that innervate the skin. However, in that study, the tracer diamidino yellow was applied to the cut ends of peripheral nerves to identify neurones innervating particular target tissues. In this study, we have avoided axotomy by retrogradely labelling primary sensory neurones from peripheral tissues using the carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbacyanine perchlorate (DiI). DiI was injected into the plantar skin, gastrocnemius muscle, and pyloric region of the stomach in rats. Corresponding ganglia were sectioned, incubated in BSI-B4 conjugated to fluorescein isothiocyanate, and examined with a fluorescence microscope. DiI-labelled cells were identified by red fluorescence within the cytoplasm, whereas cells binding BSI-B4 displayed green fluorescence associated with the plasma membrane and Golgi apparatus. Quantitative analysis revealed that 36.2% of cutaneous neurones, 7.6% of muscle neurones, and 6.8% of visceral neurones expressed the BSI-B4-binding site, indicating that a small but significant proportion of small-diameter primary sensory neurones innervating muscle and viscera also express BSI-B4-binding sites.

Animals↗

Peripheral tissue BDNF expression is affected by promoter IV defect and enriched environments in mice: negative hippocampus-intestine and positive thymus-serum-muscle correlations.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) expression is reduced in the brain of various central nervous system (CNS) disorders, but its relation to peripheral expression remains unclear. This study aimed to determine peripheral BDNF expression affected by BDNF promoter IV defect and enriched environment treatment (EET). Promoter IV defect is associated with CNS disorders and chronic stress, whereas EET increases hippocampal BDNF expression and ameliorates CNS dysfunctions. METHODS: Enzyme-linked immunosorbent assay measured BDNF protein levels in eleven regions (hippocampus, frontal cortex, heart, lung, liver, spleen, intestine, kidney, intestine, thymus, muscle, serum) in wild-type and knock-in promoter IV (KIV) mice with or without 3 weeks of EET provided after weaning. RESULTS: Knock-in promoter IV resulted in BDNF levels significantly decreased in muscle, but significantly increased in intestine, liver, thymus, and serum, which suggests compensatory upregulation of other promoters in those tissues. EET increased BDNF levels in muscle and serum of KIV mice and thymus of wild-type mice, suggesting EET's beneficial effects in muscle motor and adaptive immune regulation. EET increased hippocampal BDNF levels in both genotypes, which significantly negatively correlated with intestine BDNF levels, suggesting its role in the brain-gut axis. EET reduced wild-type heart BDNF levels, possibly through parasympathetic regulation. Significant positive BDNF correlations were observed among serum-muscle, serum-thymus, lung-spleen, and intestine-liver, suggesting inter-organ interaction and regulation of BDNF. Partial Least Squares discriminant analyses (PLS-DA) identified that variations in BDNF levels in intestine, liver, frontal cortex, and serum contribute most to classify promoter IV defect, and those in hippocampus, serum, heart, thymus, and liver contribute most to classify EET effects. CONCLUSION: This is the first study to demonstrate how genetic and environmental factors affect BDNF expression in peripheral tissues, highlighting the complex BDNF correlations across organ systems and suggesting usefulness of multivariate BDNF analyses for detecting promoter IV defect and enriched environment effects. Elucidation of BDNF's role and regulatory mechanisms in peripheral organ systems may help better our understanding of its connection to CNS disorders and their treatments.

Animals↗

Influence of positive end-expiratory pressure ventilation on peripheral tissue perfusion evaluated by measurements of tissue gases and pH. An experimental study in pigs with oleic acid lung injury. .

UNLABELLED: Measurements of subcutaneous oxygen tension (PscO(2)), subcutaneous carbon dioxide tension (PscCO(2)) and subcutaneous pH (pHsc) were used for evaluation of peripheral oxygenation in pigs subjected to oleic acid-induced lung injury during ventilation with increasing levels of positive end-expiratory pressure (PEEP). Lung injury resulted in a decrease of arterial oxygen tension (PaO(2)) from 93 to 37 mm Hg (p<0.01) with maintained cardiac output. PscO(2) decreased from 45 to 17 mm Hg (p<0.01) and pHsc from 7.47 to 7.39 (p<0.05), and PscCO(2) increased from 46 to 59 mm Hg (p<0.05). Increase of PEEP level between 5 and 20 cm H(2)O resulted in a continuous increase of PaO(2) from 45 to 145 mm Hg and a decrease of cardiac output from 4.1 to 2.0 liters/min (p<0.01). PscO(2) increased up to a PEEP level of 15 cm H(2)O, reaching 26 mm Hg. Further increase of PEEP level up to 20 cm H(2)O resulted in an increase of PscCO(2) from 65 to 71 mm Hg (p<0.05) and a decrease of pHsc from 7.31 to 7.29 (p<0.05). IN CONCLUSION: measurements of tissue gases and pH can be used to evaluate optimum peripheral tissue oxygenation during titration of PEEP level. Whether these measurements can be used as the only indicator to guide therapy in an individual case remains to be studied.

Animals↗

Autoregulation of growth hormone receptor and growth hormone binding protein transcripts in brain and peripheral tissues of the rat.

Growth hormone (GH) differs from other pituitary hormones in that it can affect a wide spectrum of cellular activities in many different tissues. These disparate actions are, however, mediated by a common receptor, suggesting tissue-specific differences in the post-receptor mechanisms and/or tissue sensitivities to GH stimulation may confer specificity. Tissue sensitivity depends upon the abundance of GH receptors (GHRs) and may be modulated by the amplitude and pulsatility of GH secretion. It may also be dependent upon the presence of non-signal transducing GH-binding proteins (GHBPs), which result from the alternate splicing of GHR gene transcripts. Tissue-specific autoregulation of GHRs and GHBPs could, therefore, contribute to differential tissue responsiveness to GH action. The autoregulation of GHR and GHBP gene transcription in novel central (hypothalamus, brainstem, and cortex/neocortex) and peripheral (spleen) tissues was therefore examined in adult, male Sprague-Dawley rats. For comparative purposes, GHR/GHBP gene expression was also examined in the liver, which has traditionally been considered the major GH-target site. Chronic hyposomatotropism, induced by hypophysectomy, exerted tissue-specific effects on the abundance of GHR gene products 10 days post-hypophysectomy. Both GHR and GHBP transcripts were reduced in the hypothalamus of hypophysectomized rats by 20% (P < 0.001), although neither transcript was affected in the liver, spleen, cortex/neocortex or brainstem. In contrast, 2 h after a single bolus GH injection that was designed to simulate a pulsatile increase in circulating GH concentrations, GHR and GHBP mRNA content was significantly increased by 25-30% (P < 0.001) in all brain regions and in the spleen of hypophysectomized or sham-hypophysectomized rats. Production of the two transcripts was differentially regulated, however, as GHBP, but not GHR, transcripts were increased in the liver (P < 0.001), whereas the GHR:GHBP ratio was decreased in the hypothalamus of GH-treated rats (P < 0.001). These results suggest that GHR gene transcription and splicing are acutely autoregulated in a tissue-specific way.

Animals↗

Glutamate signaling in peripheral tissues.

The hypothesis that l-glutamate (Glu) is an excitatory amino acid neurotransmitter in the mammalian central nervous system is now gaining more support after the successful cloning of a number of genes coding for the signaling machinery required for this neurocrine at synapses in the brain. These include Glu receptors (signal detection), Glu transporters (signal termination) and vesicular Glu transporters (signal output through exocytotic release). Relatively little attention has been paid to the functional expression of these molecules required for Glu signaling in peripheral neuronal and non-neuronal tissues; however, recent molecular biological analyses show a novel function for Glu as an extracellular signal mediator in the autocrine and/or paracrine system. Emerging evidence suggests that Glu could play a dual role in mechanisms underlying the maintenance of cellular homeostasis - as an excitatory neurotransmitter in the central neurocrine system and an extracellular signal mediator in peripheral autocrine and/or paracrine tissues. In this review, the possible Glu signaling methods are outlined in specific peripheral tissues including bone, testis, pancreas, and the adrenal, pituitary and pineal glands.

Amino Acid Transport System X-AG↗

Cytokine mRNA levels in brain and peripheral tissues of the rat: relationships with plus-maze behavior.

There is evidence that interleukin (IL)-2 may be related to anxiety as measured in the elevated plus-maze. Recently, we showed that normal adult male Wistar rats can differ systematically in this test of avoidance behavior, that is, time spent on the open arms of the elevated plus-maze. Rats with low open arm time had higher striatal levels of IL-2 mRNA than those with high open arm time, but did not differ significantly in expression of other striatal cytokine mRNA. Here, we investigated whether these expression effects are anatomically specific to the striatum. Therefore, we asked in this double-blind study whether elevated plus-maze behavior may also be related to endogenous levels of cytokine mRNA in other brain regions, which play a role for anxiety, namely the amygdala, hippocampus, and the prefrontal cortex. Additionally, and as peripheral controls, immuno-neuro-endocrine relevant tissues (adrenal glands, spleen) were analyzed. Based on open arm time in the elevated plus-maze, male Wistar rats were divided into sub-groups with either low or high open arm time behavior. Then, IL-1beta, IL-2, IL-6, and tumor necrosis factor (TNF)-alpha cDNA levels were measured post-mortem using semi-quantitative, competitive, reverse transcription polymerase chain reaction. First, we found that cytokine expressions differed considerably between and within these central and peripheral tissues. Secondly, rats with high compared to low open arm time behavior showed higher IL-2 mRNA levels in the prefrontal cortex, which is an inverse pattern to what we recently found in the striatum. These results provide new evidence indicating that cytokine mRNA in the brain can be related to elevated plus-maze behavior and that this relationship is site (prefrontal cortex, striatum)- and cytokine mRNA-specific (IL-2).

Adrenal Glands↗

Cardiovascular effects of Althesin. Changes in systolic time intervals and peripheral tissue blood flow.

Systolic time intervals were studied and peripheral blood flow measurements made in twelve healthy patients before and after intravenous induction of anaesthesia with Althesin 0.05 ml per kg. The changes in systolic time intervals observed were considered to reflect the cardio-depressive properties of the drug. The reduction in peripheral blood flow which occurs in Althesin anaesthesia was confirmed. Measurement of systolic time intervals and peripheral blood flow constitute a simple and sensitive method for the evaluation of the effects of drugs on the cardiovascular system.

Adult↗

Differential roles of splanchnic and peripheral tissues in determining diurnal fluctuation of glucose tolerance.

To identify the mechanisms and the sites of the diurnal fluctuation in glucose tolerance in humans, we selectively quantitated the components of net splanchnic glucose balance, i.e., splanchnic glucose uptake and hepatic glucose output, as well as peripheral glucose uptake, by combining tritiated glucose infusion with hepatic and femoral venous catheterization. The studies were carried out in 11 healthy volunteers at 8:00 A.M. and at 6:00 P.M. on different days after 12 h of fasting. After intravenous glucose infusion (6.5 mg.kg-1.min-1 for 120 min) blood glucose rose twofold at 8:00 A.M. and threefold at 6:00 P.M. (P less than 0.01). Insulin levels did not differ significantly between the two series of tests. Splanchnic glucose balance switched from the net output of the basal state to a net uptake in both morning and afternoon studies. However, this effect was more marked at 6:00 P.M. than at 8:00 A.M. (at 60-120 min, P less than 0.05). The different pattern of splanchnic glucose balance was entirely accounted for by a greater rise in splanchnic glucose uptake in the afternoon, as the suppression of endogenous glucose output by the glucose load was practically complete in both series of studies. In contrast, glucose uptake by leg tissues increased less at 6:00 P.M. than at 8:00 A.M. (at 30-60 min, P less than 0.05; at 75 and 90 min, P less than 0.01; at 105 and 120 min, P less than 0.005). These data indicate that the mechanism responsible for the reduced glucose tolerance later in the day resides in the peripheral tissues whose ability to dispose of a glucose load is drastically decreased.

Adult↗

CD5+ B cells predominate in peripheral tissues of rabbit.

Restricted usage of VH genes is observed in rabbit B lymphocytes and in human and murine CD5 B lymphocytes. This observation raised the possibility that most rabbit B lymphocytes were CD5+. To investigate this we cloned the CD5 gene from a rabbit cosmid library, using a probe derived from human CD5 cDNA. The rabbit CD5 gene was transfected into a murine T cell line and then we used the transfectants to develop anti-rabbit CD5 mAb. By Western blot analysis, the mAb reacted with a 67-kDa protein in lysates prepared from mesenteric lymph node and spleen cells. We determined the frequency of CD5+ B lymphocytes in peripheral lymphoid tissues of adult rabbits by two-color immunofluorescence analysis using anti-CD5 mAb and anti-L chain antibodies. The analysis showed that essentially all peripheral B lymphocytes in adult rabbits express CD5. The observation that CD5 is expressed on nearly all rabbit B lymphocytes contrasts markedly to mouse and human, where only a small number of B lymphocytes express CD5. We propose that most peripheral B lymphocytes in rabbit, as in chicken, develop early in ontogeny and are maintained throughout life by a self-renewing process.

Animals↗

Influence of enterectomy on peripheral tissue glutamine efflux in critically ill patients.

Glutamine and alanine are dominant nitrogen carriers from skeletal muscle stores to splanchnic organs. In addition, these amino acids may also serve as a primary energy source for the gastrointestinal tract during injury. To investigate these contributions, we studied extremity amino acid efflux during hypocaloric dextrose feedings and during total parenteral nutrition in a population of normal volunteers (NL VOL) (n = 9), a group of patients with sepsis who had undergone laparotomy without bowel resection and were in the intensive care unit (ICU) (n = 7), and patients with sepsis after laparotomy (PT) (n = 2) who had recently undergone greater than 80% bowel resection. Circulating alanine and glutamine levels were significantly lower in the patients compared with NL VOL under both feeding conditions. The peripheral output of alanine was higher in the ICU group than in the NL VOL during hypocaloric feedings. Glutamine efflux, however, was independent of either the counterregulatory hormone or substrate background. By contrast, enterectomy was associated with a marked decrease of extremity glutamine efflux compared with NL VOL or the ICU patients who did not undergo enterectomy (-62 +/- 9 nmol/min/dl tissue in the PT vs -265 +/- 32 nmol/min/dl tissue in the NL VOL and -311 +/- 58 nmol/min/dl tissue in the ICU group) during the dextrose feedings; this difference persisted during subsequent total parenteral nutrition (+12 +/- 13 nmol/min/dl tissue in PT vs -178 +/- 56 nmol/min/dl tissue in the NL VOL and -287 +/- 81 nmol/min/dl tissue in the ICU group). These data suggest that distinct mechanisms regulate peripheral alanine and glutamine balance and that the gastrointestinal tract provides a feedback signal to peripheral tissues to maintain glutamine mobilization under both nonstressed and stressed conditions.

Adult↗

The multiple untranslated first exons and promoters system of the oestrogen receptor gene in the brain and peripheral tissues of the rat and monkey and the developing rat cerebral cortex.

Recent studies on the human oestrogen receptor (ER) gene have revealed the complex system with the multiple untranslated first exons and promoters in the ER gene expression. Little information is however available on the system in the ER gene of the rat or nonhuman primate. The rat genomic library was first screened by the rat ER cDNA (0-1) probe. One of the four positive clones (lambda rEgE1) was subcloned and sequenced. The nucleotide sequence was found to contain the exon 0, the intron 0, and the exon 1 with its 3'-ends. The novel untranslated first exons, the exon ON and the exon OS, were further identified. These results indicated the presence of at least four subtypes of the rat ER mRNAs; the messages transcribed from promoter P-0 (ER mRNA (0-1)), putative promoter P-1 (ER mRNA (1-1)), promoter P-ON (ER mRNA (ON-1)) and promoter P-OS (ER mRNA (OS-1)). The P-O- or P-1 driven message (0-1) or (1-1) appeared to be expressed most strongly in major oestrogen central- (anterior pituitary, AP, hypothalamus-preoptic area, HPOA, and amygdala, AMG) and peripheral targets (uterus and ovary). The message (ON-1) was strongly expressed in the liver and kidney, but not in the HPOA, AMG, cerebral cortex, CC, and cerebellum, Ce. The OS-1 message was expressed variably but generally in the tissues examined except for the CC and Ce. Thus, the region- and tissue specific expression of the rat ER gene is likely to be regulated by the multiple untranslated exons and promoters system. Furthermore, when the ER mRNA subtypes were examined in the rat neonatal CC where the ER protein level rose transiently, considered as a model for the development of the ER or progestin receptor A and B isoforms, the expression of the ER mRNAs seemed to be differential postnatally, implicating some stage dependent usage of the promoters in the development. In the monkey, we identified the untranslated first exon OS, the homologue of the rat exon OS. Interestingly, the exon C was found to consist of two different exons, the exon OK and the exon OG. By the alternative usage of the promoters and the alternative splicing, at least six ER mRNA subtypes, that is, ER mRNAs (0-1), (1-1), (OS-1), (OS-OG-1), (OK-1) and (OK-OG-1) were identified in the monkey tissues. These messages were also differentially distributed in the monkey brain and other tissues. It was noteworthy that the P-OK driven messages were expressed almost exclusively in the monkey liver. These results have suggested that the systems of the multiple untranslated first exons and promoters and the alternative splicing are involved in the regulation of the region- and tissue specific expression of the ER gene in the brain and peripheral tissues of the rat and monkey. Stage-related usage of the promoters was also suggested in the ER gene expression in the CC of the postnatal rat in development.

Amino Acid Sequence↗

Leptin--from a signal of adiposity to a hormonal mediator in peripheral tissues.

The biology of leptin has been studied most extensively in the central nervous system for the regulation of food intake and energy balance. In recent years, a growing number of publications have reported several activities of this adipose-secreted protein in different organs. These effects appear to be independent of the regulation of food intake or at least not directly correlated to it, but rather related to the hormonal regulation of these particular tissues. Thus leptin is now also considered to be a hormonal factor that informs several hormonal circuits and biological peripheral functions of the nutrition status of the organism. Different systems are involved in leptin activity, such as the pituitary, male and female reproductive organs, the mammary gland, the immune system, the gut, the kidney and the lung. Functional leptin receptors and/or leptin protein have been shown to be expressed in these tissues. Furthermore, interesting interactions have been reported with classical hormones involved in the regulation of activities in such organs. These observations give more detailed evidence of the relationship between nutrition and tissue differentiation in peripheral sites, possibly mediated by classical hormonal circuits. This work aims to review the most important functional findings on leptin's effects in these peripheral sites, and potential future studies are suggested, based on currently available data.

Adipose Tissue↗

Use of [3H]-clozapine as a ligand of the dopamine D4 receptor subtype in peripheral tissues.

1. Molecular biology studies have documented the presence of peripheral dopamine D4 receptors. This site has not been characterized yet with classical radioligand binding assay techniques because of the lack of selective radioligands. 2. The atypical neuroleptic clozapine labelled with tritium ([3H]-clozapine) has been proposed and sold as a radioligand for brain dopamine D4 receptors. However, the selectivity of [3H]-clozapine for D4 receptor subtypes, and its specificity for brain dopamine receptors, have been questioned. 3. In this study dopamine D4 receptors were assayed in peripheral organs known to express them, such as rat atria and kidney, by using a radioligand binding assay technique with [3H]-clozapine as the radioligand. Parallel experiments were performed using Chinese hamster ovary (CHO) cells transfected with the D4 receptor clone (variant D4.2). 4. [3H]-Clozapine was bound to sections of rat atria and kidney. After appropriate blockade of sites other than dopamine receptors to which it can bind (i.e. muscarinic cholinergic, serotonergic and alpha-adrenergic receptors), the radioligand was bound to a site displaying a pharmacological profile similar to that expressed by CHO cells transfected with the D4 receptor. 5. The above findings indicate that with appropriate protocols, [3H]-clozapine may represent a radioligand for peripheral dopamine D4 receptors.

Animals↗

Morphine application to peripheral tissues modulates nociceptive jaw reflex.

This study assessed the effect of peripherally applied opioids on the electromyographic activity reflexly evoked in digastric and masseter muscles by injection of the small-fiber excitant and inflammatory irritant mustard oil (MO) into the temporomandibular joint. In 39 anaesthetized rats, local pretreatment of joint tissues with morphine (15 nmol) significantly depressed the jaw muscle responses compared with saline, and the depression was antagonized by simultaneous local injection of the opiate antagonist naloxone (2.7 nmol); systemic morphine pretreatment (15 nmol, i.v.) did not influence the muscle responses. The naloxone-reversible depression of the MO-evoked muscle responses by local, but not systemic morphine, supports the presence of peripheral opioid receptors that may have a role in modulating nociceptive responses.

Animals↗

Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans.

BACKGROUND: The central and peripheral inflammatory response to surgery may influence patient outcomes. This study examines the time course and clinical relevance of changes in prostaglandin E2 and cytokines in cerebrospinal fluid, local tissue (surgical site), and circulating blood during and after total hip replacement. METHODS: Thirty osteoarthritis patients undergoing primary total hip arthroplasty with spinal anesthesia were randomly allocated to three groups (n = 10/group): placebo for 4 days before surgery and on the morning of surgery; placebo for 4 days before surgery and oral rofecoxib 50 mg on the morning of surgery; oral rofecoxib 50 mg for 4 days before surgery and the morning of surgery. Cerebrospinal fluid and plasma were collected before surgery and up to 30 h after incision for measurement of prostaglandin E2 and interleukins. When hip replacement was complete, a drain was placed in the hip wound and exudates were collected at 3 to 30 h after incision. RESULTS: Cerebrospinal fluid showed an initial increase in interleukin 6 and a later rise in prostaglandin E2 concentration after surgery; interleukin 1beta and tumor necrosis factor alpha were undetectable. Hip surgical site fluid evidenced an increase in prostaglandin E2, interleukin 6, interleukin 8, and interleukin 1beta; tumor necrosis factor alpha decreased at 24 and 30 h. Preoperative administration of the cyclooxygenase 2 inhibitor rofecoxib reduced cerebrospinal fluid and surgical site prostaglandin E2 and cerebrospinal fluid interleukin 6. Cerebrospinal fluid prostaglandin E2 was positively correlated with postoperative pain and cerebrospinal fluid interleukin 6 with sleep disturbance. Poorer functional recovery was positively correlated with increased surgical site prostaglandin E2. CONCLUSIONS: These results suggest that upregulation of prostaglandin E2 and interleukin 6 at central sites is an important component of surgery induced inflammatory response in patients and may influence clinical outcome.

Aged↗

Rapid pituitary and peripheral tissue responses to intravenous L-triiodothyronine in hypothyroidism.

Acute cardiovascular, renal, pulmonary, metabolic, and pituitary responses to therapy of hypothyroidism with 25 micrograms iv T3 (group I G-I, n = 11) or 50 micrograms iv T3 (group II, G-II, n = 10)/day for 1 week have been studied. Serum T3 levels were acutely normalized in both groups with the mean basal serum T3 levels (X +/- SE) after 7 days, 98 +/- 10 micrograms/dl and 229 +/- 19 ng/dl, respectively. Myocardial performance, noninvasively assessed by the pulse wave arrival time (QKd) and the phonocardiographic systolic time interval ratio was significantly altered after 1 day of therapy (QKd for G-I = -10 +/- 4 msec, P less than 0.05; and for G-II = -18 +/- 14 msec, P less than 0.01). After 7 treatment days, both the mean QKd (203 +/- 7 msec, P less than 0.001) and phonocardiographic systolic time interval ratio (0.41 +/- 0.02, P less than 0.01) were within the normal range in G-II. Abnormal pretreatment renal excretion of an oral water load (G-I, 65 +/- 6%; and G-II, 57 +/- 6%) was also reversed after 1 week (G-I, 84 +/- 5%, P less than 0.05; and G-II, 89 +/- 5%, P less than 0.01). Patients with blunted hypercapnic (n = 6) and hypoxic (n = 4) ventilatory drives were improved in both groups after 6 days. The mean basal metabolic rate, serum cholesterol, and serum creatine phosphokinase were altered by the week of therapy in a dose-response manner, and were in the normal range in G-II. Pituitary TSH secretion was promptly suppressed in both groups. Two hours after the first T3 dose, the mean serum TSH for G-I and G-II decreased to 85% (P less than 0.02) and 70% (P less than 0.001) of their respective pretreatment values. After 7 days of therapy, the mean basal TSH levels had declined to 75% (P less than 0.001) and 5% (P less than 0.001%) of pretreatment, respectively. In comparison with previous observations of responses to 100 micrograms/day iv T4 for 1 week, the 25 micrograms dose T3 was equivalent in terms of changes in basal serum T3 and peripheral (nonpituitary) tissue responses, but less effective than T4 in lowering serum TSH. Based on these parameters, 50 micrograms/day iv T3 was the most effective of the three regimens within this time frame. The implications of these observations in the clinical management of severe complicated myxedema are discussed.

Adult↗