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PubMed1987

Clinical significance of antibodies against peripheral nerve tissue in inflammatory polyneuropathy.

With the use of a mixed hemagglutination test (MHT), circulating antibodies against human peripheral nerve tissue (PNT) were found in 22 of 38 patients with Guillain-Barré syndrome (GBS) or chronic relapsing demyelinating inflammatory polyneuropathy (CR-DIP). The antibodies were found in only 1 of 34 patients with polyneuropathy of other origin, and in 3 of 32 patients without polyneuropathy. The presence of antibodies was related to response to intravenous gamma globulin treatment in CR-DIP patients. Antibodies against PNT may be pathogenic.

Antigen-Antibody Complex↗
PubMed2000

[The expression of cell adhesion molecules on lymphatic endothelial cells in rectum adenocarcinoma of human].

This study was conducted to explore the mechanism of lymphatic dissemination and metastasis of cancer cells; the specific aim was to investigate the expression of cells adhesion molecules on lymphatic endothelial cells. Immunohistochemical method was used. The rectum tissues and lymphnodes were taken from five normal human subjects. The cancer peripheral tissues and lymphnodes, and the metastasized lymphnodes were taken from eight patients with rectum adenocarcinoma. The result showed that the intercellular adhesion molecule-1 (ICAM-1) and carcinoma embryonic antigen (CEA) were expressed on lymphatic endothelial cells in cancer peripheral tissues and metastasized lymphnode. The expression of ICAM-1 and CEA in cancer peripheral tissues and lymphnodes was much more remarkable than that in metastasized lymphnodes. These data suggest that ICAM-1 and CEA be cell adhesion molecules between cancer cells and lymphatic endothelial cells.

Adenocarcinoma↗
PubMed1993

Identification and partial characterization of a glycoprotein species with high affinity for methylmercury in peripheral nervous tissues of man and experimental animals.

A small amount of a glycoprotein species (21-kDa glycoprotein) with high affinity for methylmercury (MeHg) was detected in the post-nuclear or post-mitochondrial supernatant fraction of the homogenate of rat sciatic nerve on electrophoresis and autoradiography after binding of Me203Hg to the fraction. The 21-kDa glycoprotein was also found in the subcellular fractions of mouse, hamster, guinea pig, rabbit and human peripheral nervous tissues. Experiments with the cellular fractions of the tissues revealed that the 21-kDa glycoprotein is localized mainly in the myelin fraction, whereas it was not found in the cellular fractions of brain, spinal cord and nonneural tissues, such as kidney and liver. The specific binding activity of the 21-kDa glycoprotein with MeHg was 12-15 fold that of the major myelin protein, Po. It was shown that the interaction of the 21-kDa glycoprotein with MeHg was mediated through sulfhydryl groups in experiments with iodoacetamide and dithiothreitol. The amino acid compositions of the rat and human 21-kDa glycoproteins were similar but very different from that of a typical metallothionein. The N-terminal amino acid sequences of the two components of the rat 21-kDa glycoprotein were identical to those of P0 and PMP-22, respectively. The in vitro binding of MeHg was also observed in the myelin fraction obtained from the sciatic nerves of MeHg-dosed rats.

Amino Acid Sequence↗
PubMed1997

Steroidogenic factor 1 messenger ribonucleic acid expression in steroidogenic and nonsteroidogenic human tissues: Northern blot and in situ hybridization studies.

Steroidogenic factor-1 (SF-1), a tissue-specific orphan nuclear receptor, regulates the genes of several steroidogenic enzymes, Mullerian inhibiting substance, and the gonadotrophins. Also, this transcription factor is crucial for hypothalamic, adrenal, and gonadal organogenesis in the mouse. We recently cloned the human SF-1 (hSF-1) complementary DNA (cDNA) and now report the distribution of this factor's messenger RNA (mRNA) in human tissues. Northern blot analyses of peripheral tissues revealed high hSF-1 mRNA expression in the adrenal cortex and the gonads, but no hSF-1 mRNA was detected in the placenta. High hSF-1 mRNA expression also was seen in the spleen. In this tissue, in addition to the main transcript of 3.5-4 kb seen in the adrenal and gonads, two additional transcripts of 4.4 kb and 8 kb were noted. The additional 4.4-kb transcript also was seen in several peripheral tissues and various components of the brain. However, adult liver and heart showed only the 4.4-kb transcript. In the human brain, hSF-1 mRNA expression was widespread, including several components of the limbic system. In situ hybridization studies confirmed the strong expression of hSF-1 mRNA in adrenal cortex, ovary, testis, and the spleen, primarily within reticuloendothelial cells. Thus, in the human, the hSF1 mRNA is present in both steroidogenic and nonsteroidogenic tissues, albeit not in the placenta. In the central nervous system, the expression of hSF-1 mRNA is widespread. It is composed of several different mRNA species distributed in a tissue-specific fashion. These findings suggest that hSF-1 may play a role in reticuloendothelial/immune cell maturation and/or function, as well as nervous system development and/or neurosteroid biosynthesis.

Adult↗
PubMed2005

Propionibacterium acnes is the most common bacterium commensal in peripheral lung tissue and mediastinal lymph nodes from subjects without sarcoidosis.

BACKGROUND: In studies of the unknown etiology of sarcoidosis, Propionibacterium acnes (a possible agent) was found in the lungs and lymph nodes of many sarcoidosis patients and some control subjects. P. acnes might be commensal not only to the skin, conjunctivae, and intestine, but also to the lungs and lymph nodes of individuals without sarcoidosis. METHODS: We cultured peripheral lung tissue and various lymph nodes obtained from patients with diseases other than sarcoidosis. DNA of 45 isolates of P. acnes from these patients, 67 isolates from normal skin, conjunctiva, and intestine, and 39 isolates from sarcoid lymph nodes were compared by random amplified polymorphic DNA analysis. RESULTS: P. acnes was isolated from half of 43 lungs and 8 of 11 mediastinal lymph nodes, mostly in pure culture. P. acnes was isolated from half of 20 gastric and 3 of 12 intestinal lymph nodes; intestinal bacteria were also numerous. In general, fewer than 500 colony-forming units of P. acnes per gram tissue were isolated, but 4 lung tissue specimens, 2 of which had a few granulomas, had many more. P. acnes strains from a particular site (lung, lymph node, skin or conjunctivae, and intestine) were genetically similar, more than isolates obtained from different sites. Lymph-node isolates from subjects with and without sarcoidosis differed little. CONCLUSION: These results suggest that P. acnes normally resides in peripheral lung tissue and mediastinal lymph nodes and that the strains of P. acnes isolated from sarcoid lymph nodes were not specific to sarcoidosis.

Adult↗
PubMed1988

Choline as an agonist: determination of its agonistic potency on cholinergic receptors.

These experiments examined the potency of choline as a cholinergic agonist at both muscarinic and nicotinic receptors in rat brain and peripheral tissues. Choline stimulated the contraction of isolated smooth muscle preparations of the stomach fundus, urinary bladder and trachea and reduced the frequency of spontaneous contractions of the right atrium at high micromolar and low millimolar concentrations. The potency of choline to elicit a biological response varied markedly among these tissues; EC50 values ranged between 0.41 mM in the fundus to 14.45 mM in the atrium. Choline also displaced [3H]quinuclidinyl benzilate binding in a concentration-dependent manner although, again, its potency varied among different brain regions (Ki = 1.2 to 3.5 mM) and peripheral tissues (Ki = 0.28 to 3.00 mM). Choline exhibited a comparable affinity for nicotinic receptors. It stimulated catecholamine release from the vascularly perfused adrenal gland (EC50 = 1.3 mM) and displaced L-[3H]nicotine binding to membrane preparations of brain and peripheral tissues (Ki = 0.38 to 1.17 mM). However, the concentration of choline required to bind to cholinergic receptors in most tissues was considerably higher than serum levels either in controls (8-13 microM) or following the administration of choline chloride (200 microM). These results clearly demonstrate that choline is a weak cholinergic agonist. Its potency is too low to account for the central nervous system effects produced by choline administration, although the direct activation of cholinergic receptors in several peripheral tissues may explain some of its side effects.

Acetylcholine↗
PubMed1993

Adequacy of tissue oxygenation in cardiac surgery: regional measurements.

OBJECTIVE: The aim of the study was to measure visceral and peripheral perfusion and oxygenation during and immediately after cardiac surgery. METHODS: Central hemodynamics, blood gases, core temperature, visceral and peripheral tissue perfusion, and oxygenation were studied in eight patients undergoing coronary artery bypass grafting and in the early postoperative period in another group of ten coronary artery bypass grafting patients. DESIGN: The variables were measured after induction of anesthesia, after sternotomy, during cardiopulmonary bypass, after rewarming and after closing the wounds. Postoperatively, the measurements were carried out hourly up to 8 hrs after the arrival of patients in the ICU. PATIENTS: The patients were operated on under moderate hemodilution and systemic hypothermia. The inspired oxygen concentration was maintained at 30 volumes percent during the postoperative study. MEASUREMENTS: Visceral perfusion was indirectly assessed by determining the gastric intramucosal pH. Peripheral tissue perfusion was assessed in the upper extremity by continuous recording of subcutaneous tissue PO2, laser-Doppler skin erythrocyte flux, transcutaneous PO2, and fingertip temperature. Transcutaneous PO2 index (transcutaneous PO2/PaO2) was calculated. MAIN RESULTS: Gastric intramucosal pH, PaO2, and transcutaneous PO2 reached maximum values during cardiopulmonary bypass at the deepest level of hypothermia, and gastric intramucosal pH reached its minimum at the end of the operation. During the first 3 hrs after admission of patients to the ICU, gastric intramucosal pH decreased progressively, reached its minimum value at 5 hrs, and increased slowly thereafter. Subcutaneous tissue PO2, laser-Doppler skin erythrocyte flux, and fingertip temperature decreased markedly during cardiopulmonary bypass, increased during rewarming, and decreased again at the end of surgery. The peripheral vascular bed was vasoconstricted on ICU admission, as indicated by the low values of subcutaneous tissue PO2, transcutaneous PO2, transcutaneous PO2 index, laser-Doppler skin erythrocyte flux, and fingertip temperature. These variables began to increase over the next 2 to 4 hrs and reached their maximum value by the end of the 8-hr postoperative study period, indicating complete vasodilation of the peripheral vascular bed. CONCLUSIONS: These data suggest that the visceral perfusion of patients is well maintained during cardiopulmonary bypass, while, at the same time, these patients develop hypoperfusion and hypoxia of peripheral tissues. After closing the wounds, gastric intramucosal pH, transcutaneous PO2 index (transcutaneous PO2/PaO2), and other peripheral tissue perfusion variables were at the lowest values, indicating impending residual hypothermia and tissue hypoperfusion after rewarming. During the first few hours in the ICU, both the visceral and peripheral oxygenation and perfusion variables reflected hypoperfusion of tissues coinciding in time with the period most vulnerable for hemodynamic disasters and cardiac arrhythmias.

Blood Gas Analysis↗
PubMed2004

Effects of a circulating-water garment and forced-air warming on body heat content and core temperature.

BACKGROUND: Forced-air warming is sometimes unable to maintain perioperative normothermia. Therefore, the authors compared heat transfer, regional heat distribution, and core rewarming of forced-air warming with a novel circulating-water garment. METHODS: Nine volunteers were each evaluated on two randomly ordered study days. They were anesthetized and cooled to a core temperature near 34 degrees C. The volunteers were subsequently warmed for 2.5 h with either a circulating-water garment or a forced-air cover. Overall, heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Average arm and leg (peripheral) tissue temperatures were determined from 18 intramuscular needle thermocouples, 15 skin thermal flux transducers, and "deep" hand and foot thermometers. RESULTS: Heat production (approximately 60 kcal/h) and loss (approximately 45 kcal/h) were similar with each treatment before warming. The increases in heat transfer across anterior portions of the skin surface were similar with each warming system (approximately 65 kcal/h). Forced-air warming had no effect on posterior heat transfer, whereas circulating-water transferred 21+/-9 kcal/h through the posterior skin surface after a half hour of warming. Over 2.5 h, circulating water thus increased body heat content 56% more than forced air. Core temperatures thus increased faster than with circulating water than forced air, especially during the first hour, with the result that core temperature was 1.1 degrees +/- 0.7 degrees C greater after 2.5 h (P < 0.001). Peripheral tissue heat content increased twice as much as core heat content with each device, but the core-to-peripheral tissue temperature gradient remained positive throughout the study. CONCLUSIONS: The circulating-water system transferred more heat than forced air, with the difference resulting largely from posterior heating. Circulating water rewarmed patients 0.4 degrees C/h faster than forced air. A substantial peripheral-to-core tissue temperature gradient with each device indicated that peripheral tissues insulated the core, thus slowing heat transfer.

Body Temperature↗
PubMed1999

IFN-beta suppresses experimental autoimmune neuritis in Lewis rats by inhibiting the migration of inflammatory cells into peripheral nervous tissue.

The putative prophylactic and therapeutic effect of interferon-beta (IFN-beta) on autoimmune inflammation of the peripheral nervous system was evaluated in experimental autoimmune neuritis (EAN), a well-known animal model of the human Guillain-Barré syndrome (GBS). We report that treatment of rats with 300,000 U of recombinant rat IFN-beta (rrIFN-beta) given every other day starting at the day of immunization prevented clinical signs of EAN. When treatment was started at the onset of disease development, the cytokine clearly ameliorated EAN. Both B- and T-cell responses towards peripheral myelin were suppressed by the IFN-beta, and immunohistochemical analyses revealed a strong decrease in the numbers of infiltrating CD4(+) T cells, macrophages, and other inflammatory cells as well as a significant reduction in MHC class II antigen expression and monocyte chemotactic protein-1 (MCP-1) production, which induces chemotaxis and chemokinesis of leukocytes from blood. It is concluded that the observed suppression of EAN by rrIFN-beta is associated with a decrease in the migration of inflammatory cells into peripheral nervous tissue.

Adjuvants, Immunologic↗
PubMed1984

[Peripheral soft tissue sarcomas. A retrospective study on 90 primary treatment patients].

Between 1960 and 1982, 90 patients treated primarily for peripheral soft tissue sarcomas received a postoperative irradiation at the Irradiation Department of the Städtische Krankenhaus Passau. Five patients (6%) were inoperable for internistic reasons and were treated only by radiotherapy. The local recurrence rate after combined therapy was 26%. 44% of the patients (40/90) developed metastases, preponderantly in the lung and within the first year (70% each). The age-corrected survival rate was 63% after five years and 43% after ten years in 79 patients with complete postoperative irradiation. Important prognostic factors are the degree of malignancy (five-year survival times of 57 patients: almost 90% for G1 tumors, 50% for G2 tumors, and 17% for G3 tumors, statistically significant) as well as the completeness of surgery. It is shown by the available results that conservative surgical interventions combined with radiotherapy are not less effective than more radical operations.

Adolescent↗
PubMed2001

Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery.

Potassium channels are amongst the most heterogeneous class of ion channels known and are responsible for mediating a diverse range of biological functions. The most recently described family of K+ channels, the 'two pore-domain family', contain four membrane spanning domains and two pore-forming domains, suggesting that two channel subunits associate to form a functional K+ pore. Several sub-families of the two pore domain potassium channel family have been described, including the weakly inward rectifying K+ channel (TWIK), the acid-sensitive K+ channel (TASK), the TWIK-related K+ channel (TREK) and the TWIK-related arachidonic acid stimulated K+ channel (TRAAK). However, comparison of the mRNA expression of these channels has been difficult due to the differences in methods used and the species studied. In the present study, we used a single technique, TaqMan semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), to investigate the mRNA distribution of all currently known two pore potassium channels in human central nervous system (CNS) and peripheral tissues. TWIK-1 and the TWIK-1-like channel KCNK7 were predominantly expressed in the CNS, in contrast to TWIK-2 which was preferentially expressed in peripheral tissues such as pancreas, stomach, spleen and uterus. TASK-1 was expressed in the CNS and some peripheral tissues, whereas TASK-2 was exclusively expressed in the periphery except for mRNA expression observed in dorsal root ganglion and spinal cord. In addition, mRNA expression of the recently identified TASK-3, was almost completely exclusive to cerebellum with little or no mRNA detected in any other tissues. TREK-1 and TRAAK mRNA expression was predominantly CNS specific in contrast to the closely related TREK-2, which was expressed in both CNS and peripheral tissues. Studying the mRNA expression profiles of known two pore domain K+ channels will aid in the understanding of the biological roles of these channels. Furthermore, identification of common areas of expression may help identify which channels, if any, associate to form heteromeric K+ channel complexes.

Central Nervous System↗
PubMed1991

Heterogeneity of [3H]-mepyramine binding sites in guinea pig cerebellum and lung.

The nature of histamine receptors in peripheral tissues is still controversial. However, evidence of heterogeneous classes of binding sites for [3H]-mepyramine are reported in the literature. The aim of our study was, therefore, to investigate the nature of this heterogeneity by comparing [3H]-mepyramine binding in a central tissue (cerebellum) and in a peripheral tissue (lung) obtained from guinea pigs and to assess its dependence upon the temperature of incubation. The results revealed that the [3H]-mepyramine interaction in both tissues is temperature-dependent. At 25 degrees C, the interaction between [3H]-mepyramine and the receptors was biphasic in the lung while only a single class of binding site was found in the cerebellum. At 0 degrees C, [3H]-mepyramine interacted with three binding sites in the lung and two in the cerebellum. The behaviour of the reference compounds (clemastine, promethazine and histamine) also supported this temperature-dependence. Moreover, two new compounds (DF 11062 and DF 11113), synthesized in our laboratories and endowed with antihistamine activity, can differentiate between the low affinity site seen at 25 degrees C in the lung and that seen in the cerebellum at 0 degrees C.

Animals↗
PubMed1999

Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR.

The tumor necrosis factor (TNF) and TNF receptor (TNFR) gene superfamilies regulate diverse biological functions, including cell proliferation, differentiation, and survival [1] [2] [3]. We have identified a new TNF-related ligand, designated human GITR ligand (hGITRL), and its human receptor (hGITR), an ortholog of the recently discovered murine glucocorticoid-induced TNFR-related (mGITR) protein [4]. The hGITRL gene mapped to chromosome 1q23, near the gene for the TNF homolog Fas/CD95 ligand [5]. The hGITR gene mapped to chromosome 1p36, near a cluster of five genes encoding TNFR homologs [1] [6]. We found hGITRL mRNA in several peripheral tissues, and detected hGITRL protein on cultured vascular endothelial cells. The levels of hGITR mRNA in tissues were generally low; in peripheral blood T cells, however, antigen-receptor stimulation led to a substantial induction of hGITR transcripts. Cotransfection of hGITRL and hGITR in embryonic kidney 293 cells activated the anti-apoptotic transcription factor NF-kappaB, via a pathway that appeared to involve TNFR-associated factor 2 (TRAF2) [7] and NF-kappaB-inducing kinase (NIK) [8]. Cotransfection of hGITRL and hGITR in Jurkat T leukemia cells inhibited antigen-receptor-induced cell death. Thus, hGITRL and hGITR may modulate T lymphocyte survival in peripheral tissues.

Amino Acid Sequence↗
PubMed1991

Lipoproteins of human peripheral lymph. Apolipoprotein AI-containing lipoprotein with alpha-2 electrophoretic mobility.

Evidence from diverse sources has implicated a central role of apolipoprotein AI (apo AI), the most abundant protein of plasma high-density lipoproteins, in the transport of cholesterol from peripheral tissues to the liver (reverse cholesterol transport). Particles containing only apo AI appear to be more effective as cholesterol acceptors in tissue culture than do particles which also contain apo AII. The apo AI-containing lipoproteins of plasma have been extensively studied, but there is less information on those in tissue fluids, to which most peripheral cells are exposed. In the present study the heterogeneity of apo AI-containing particles in human peripheral lymph, collected from the dorsum of the foot, has been examined by starch block electrophoresis, exclusion chromatography and immunoelectrophoresis. The apo AI-containing particles of lymph were found to be more variable in both electrophoretic mobility and size than those of plasma from the same subjects. Of particular interest was a subpopulation which migrated on electrophoresis with the same mobility as alpha-2-macroglobulin. This fraction accounted for approximately 7% (range: 4-12%; n = 5) of lymph apo AI, contained no immunodetectable apo AII, and by exclusion chromatography was composed of particles the size of, or smaller than, albumin. Such physicochemical properties suggest that these alpha-2 migrating particles may function as the principal primary acceptors of cell cholesterol in the extracellular matrix of human peripheral tissues. By isoelectric focusing, lymph apo AI was found to contain a higher proportion of more negatively charged isoforms than the apo AI of plasma.

Adult↗
PubMed1992

Biguanides and NIDDM.

The main biguanides, metformin and phenformin, were introduced in 1957 as oral glucose-lowering agents to treat non-insulin-dependent diabetes mellitus (NIDDM). Phenformin was withdrawn in many countries because of an association with lactic acidosis, but metformin does not have the same risk if appropriately prescribed. Metformin is now widely used as a monotherapy and in combination with a sulfonylurea. Unlike sulfonylureas, metformin is not bound to plasma proteins, is not metabolized, and is eliminated rapidly by the kidney. The glucose-lowering effect occurs without stimulation of insulin secretion and results mainly from increased glucose utilization. The presence of insulin is required, and enhancement of insulin action at the postreceptor level occurs in peripheral tissues such as muscle. In peripheral tissues metformin increases insulin-mediated glucose uptake and oxidative metabolism. Metformin also increases glucose utilization by the intestine, primarily via nonoxidative metabolism. The extra lactate produced is largely extracted by the liver and serves as a substrate to sustain gluconeogenesis. This limits the extent to which metformin reduces hepatic glucose production but provides a safeguard against excessive glucose lowering. Because metformin does not cause clinical hypoglycemia, it is actually an antihyperglycemic drug. It does not cause weight gain, it helps combat hypertriglyceridemia, and it has been ascribed some vasoprotective properties. Metformin offers a useful treatment for insulin-resistant overweight NIDDM patients.

Adipose Tissue↗
PubMed1995

Vein conduits with interposition of nerve tissue for peripheral nerve defects.

Vein conduits with interposition of autogenous nerve tissue were used in 16 peripheral nerves to reconstruct defects of between 2.0 and 5.8 cm. This technique was applied in nine digital nerves, four ulnar nerves, two median nerves, and one radial sensory nerve. A single vein conduit was used in digital nerve defects and two or three vein segments were used in defects of nerve trunks. Nerve tissue was sectioned from the proximal nerve stump and inserted inside the vein conduits. Follow-up of 2.5 to 3.5 years has revealed motor recovery to M4 in three nerves, M3+ in three, M2 in one nerve, and sensory recovery to S4 in two nerves, S3+ in five, S3 in four, S2+ in three and S0 in two nerves. Signs of muscle reinnervation of the repaired nerves were noted on electromyography. Two digital nerves with defects of over 5.0 cm did not show any signs of sensory recovery. Sectioning and placement of autogenous nerve tissue is thought to create fresh and additional sources for the release of neurotropic factors, and may serve to convey the neurotropic effect over a longer distance. This clinical study suggests that vein conduits with the interposition of nerve tissue is a practical and reliable procedure for nerve defects between 2.0 cm and 4.5 cm.

Adolescent↗
PubMed1975

The influence of serum calcium and parathyroid hormone upon glucose metabolism in uremia.

The alterations in carbohydrate metabolism which attend the uremic syndrome have been recognized for some time. Recently, an interaction between hyperparathyroidism and these alterations in intermediary metabolism has been postulated. To further define any such interaction, 6 stable dialysis patients with significant secondary hyperparathyroidism were studied prior to and after subtotal parathyroidectomy. Glucose utilization and insulin secretion were estimated by use of a standard intravenous glucose tolerance test and the resistance of peripheral tissues to exogenous insulin was evaluated by insulin tolerance testing. All of peripheral tissues to exogenous insulin was evaluated by insulin tolerance testing. All patients were studied under baseline conditions, as well as induced hyper- and hypocalcemia, prior to and at least 2 months after surgery. Parathyroidectomy, per se, had no significant effect upon glucose utilization, insulin secretion, or the resistance of peripheral tissues to the action of exogenous insulin. Both induced hyper- and hypocalcemia, on the other hand, significantly diminished glucose utilization as judged by a reduced glucose disappearance rate during intravenous glucose tolerance testing. Hypocalcemia was associated with a markedly reduced insulin secretory response and normal tissue insulin sensitivity, while hypercalcemia was associated with a normal insulin response but reduced tissue sensitivity. The data suggest that calcium ion concentration may affect both glucose utilization and insulin secretion. As such, it must be adequately controlled in furture metabolic studies.

Adult↗