Effect Of Hypo Research Articles

Different effect of hypo- and hypermetabolism on cognition in dementia with Lewy bodies: are they coupled or independent?

Patients with dementia with Lewy bodies (DLB) show widespread brain metabolic changes. This study investigated whether brain hypo- and hypermetabolism in DLB have differential effects on cognition. We enrolled 55 patients with DLB (15 prodromal DLB [MCI-LB] and 40 probable DLB) and 13 healthy controls who underwent 18F-fluorodeoxyglucose positron emission tomography and detailed neuropsychological tests. Metabolic indices reflecting associated changes in regional cerebral glucose metabolism were calculated as follows: index(-) for hypometabolism [DLB-hypo] and index(+) for hypermetabolism [DLB-hyper]. The effects of DLB-hypo or DLB-hyper on cognitive function were assessed using a multivariate linear regression model. Additionally, a linear mixed model was used to investigate the association between each index and the longitudinal cognitive decline. There was no correlation between DLB-hypo and DLB-hyper in the disease group. The multivariate linear regression model showed that DLB-hypo was associated with language, visuospatial, visual memory, and frontal/executive functions; whereas DLB-hyper was responsible for attention and verbal memory. There was significant interaction between DLB-hypo and DLB-hyper for verbal and visual memory, which was substantially affected by DLB-hyper in relatively preserved DLB-hypo status. A linear mixed model showed that DLB-hypo was associated with longitudinal cognitive outcomes, regardless of cognitive status, and DLB-hyper contributed to cognitive decline only in the MCI-LB group. The present study suggests that DLB-hypo and DLB-hyper may be independent of each other and differentially affect the baseline and longitudinal cognitive function in patients with DLB.

The reaction of blood microcirculation in the skin of various parts of the body after performing yoga breathing exercises

Introduction. Yoga breathing exercises make it possible to change the minute ventilation (MV) within a wide range, reaching states of hyper- and hypoventilation with corresponding shifts in gas exchange. In this work, the interrelations between external respiration, parameters of gas metabolism and the skin microcirculation were evaluated. Materials and methods: 22 experienced volunteers performed yoga breathing exercises at a frequency of 3–3.5 times per minute and 1–1.5 times per minute for 5 minutes, as well as free breathing for 6 minutes before and after breathing exercises. Respiratory rate (RR), minute ventilation (MV), tidal volume (TV), partial pressure of CO2 in exhaled air at the end of exhalation (PetCO2), percentage of O2 in exhaled air (FeO2 ) were recorded using spirometry and gas analysis; by laser Doppler flowmetry and a distributed system of wearable analyzers parameters of skin microcirculation such as index of microcirculation (IM), nutritive blood flow (Imn ), amplitudes of endothelial (Ae), neurogenic (An), myogenic (Am), respiratory (Ar) and cardiac (Ac) oscillations were recorded in six body areas. Results. After the breathing exercises, the index of microcirculation of the supraorbital artery pool increased from 14.7 p. u. to 16.7 p. u., in the fingers from 24.8 p. u. to 29.4 p. u. and in toes from 8.2 p. u. to 10.2 p. u. with hypoventilation (RR=1–1.5 ­times/ minute) and in the skin of the supraorbital artery pool from 14.7 p. u. to 16.0 p. u., in the fingers from 27.1 p. u. to 29.8 p. u. and in toes from 11.5 p. u. to 13.5 p. u. with hyperventilation (RR=3–3.5 times / minute), nutritional blood flow increased from 14.4 p. u. and 14.3 p. u. to 17.8 p. u. and 16.9 perf.u. on the upper and from 4.7 p. u. and 6.1 p. u. to 6.8 p. u. and 7.5 p. u. on the lower extremities with hypo- and hyperventilation, respectively; an increase of the amplitude of endothelial blood oscillations after a hypoventilation and an increase of the amplitude of neurogenic oscillations after both types of breathing in the forehead skin were observed. Conclusion. The absence of differences between the effect of hypo- and hyperventilation exercises on Im suggests that the main mechanism of action may not be shifts in MV and gas exchange, but the depth of breathing; the influence of cognitive mechanisms (conscious control of breathing in both modes) is also discussed. The absence of changes in nutritive blood flow in the head can be explained by regional features of microcirculation regulation. The hypoventilatory mode of breathing significantly activates the endothelial mechanism of regulation; the neurogenic (sympathetic) mechanism of regulation is activated by both hypo- and hyperventilation respiratory modes.

Effect of hypo– and hypersaline stress conditions on physiological, metabolic, and immune responses in the oyster Crassostrea corteziensis (Bivalvia: Ostreidae)

Salinity in the oceans is changing due to climate change and global warming. Intense rainfalls and freshwater runoff decrease salinity along the coastal areas. In contrast, intense drought seasons and river damming have certainly increased salinity in lagoons and estuaries. Few studies have focused on aspects of the biology and culture of oyster Crassostrea corteziensis, but until now, physiological and immunological responses in this species have not been assessed under acute hypo– and hypersaline stress conditions. Oysters obtained from a local farm were acclimated for three weeks in laboratory conditions. To avoid closure of oyster valves during salinity induced–stress conditions, a notch was done on each organism shell not only to facilitate oyster tissue exposure to rearing water but also for sampling hemolymph. Oysters (N = 180) were abruptly exposed to three salinity treatments: (HO) hypo–, (C) control, and (HP) hypersaline stress conditions (10, 35, and 50 PSU, respectively). Four oysters per treatment were sampled at 1, 2, 3, 6, 12, 24, and 48 h after exposure. Hemolymph osmolality, water content and total protein concentration in tissues, metabolic and immune responses were assessed for each organism. Oyster survival was not different among treatments and was maintained above 96% at the end of the experimental trial. Hemolymph osmolality reached the value of rearing water at 6 and 48 h of exposure to HP and HO stress conditions, where oysters exposed to salinity increase showed less resilience than those to decrease. Higher glucose levels in plasma and lower ones of hemocyanin were assessed in the oysters exposed to HP compared to HO conditions, suggesting more stressful conditions or susceptibility of oysters during salinity increase. Total hemocyte (THC), hyalinocyte (HC), and granulocyte (GC) counts decreased in oysters exposed to HP condition, while total and differential hemocyte counts were similar among oysters exposed to HO and control conditions. Despite hemocyte phagocytosis was not different among treatments, viability decreased in those exposed to HP condition. Contrastingly, superoxide anion (SOA) production (oxidative capacity) increased in oysters exposed to both induced salinity–stress conditions, which suggest susceptibility increase in oysters, particularly during salinity increase. The results show that HP condition is particularly stressful for C. corteziensis. In turn, this condition could increase both their vulnerability to other environmental stressors, such as temperature and/or acidification or susceptibility to opportunistic pathogenic microorganisms that cause the most common oyster diseases.

Водно-электролитные нарушения при тяжелой черепно-мозговой травме

Эта обзорная статья освещает актуальность проблемы современных критериев диагностики водно-электролитных нарушений при черепно-мозговой травме. Приведен перечень клинических и визуализационных, лабораторных диагностических критериев возникновения центрального несахарного диабета при открытых или закрытых травматических поражениях гипоталамо-гипофизарной области головного мозга. Современная диагностика, прогнозирование и своевременная коррекция водно-электролитного дисбаланса у данных пациентов минимизируют повреждающее действие гипо-/гипернатриемии при первичном повреждении головного мозга и гипоталамо-гипофизарной системы различной этиологии и способствуют более быстрому эффекту терапии в динамике заболевания пациента.

Effect of serum calcium status at calving on survival, health, and performance of postpartum Holstein cows and calves under certified organic management

The study objective was to assess the effect of hypocalcemia (HYPO; ≤2.0 mmol/L) of the dam at calving on survival, health, and performance of lactating dairy cows and their calves under certified organic management. Prepartum dairy cows (primiparous, n = 445; multiparous, n = 328) from 1 dairy herd were monitored (prepartum pen) for imminent signs of parturition (appearance of amniotic sac outside the vulva) until birth. All calves were subject to the same newborn care, colostrum management, and failure of passive transfer assessment (serum total protein ≤5.5 mg/dL). Serum total calcium of cows was determined in samples taken within 2 h after calving. To define HYPO cows after calving, a cut-point of total serum Ca concentration with optimal sensitivity and specificity to predict metritis or calf diarrhea was established by using the receiver operator characteristic. The effect of HYPO on survival (died or culled within 60 DIM), health status, and pregnancy per artificial insemination (PAI) for first services of lactating cows were analyzed using the GLIMMIX procedure of SAS. Additionally, the effect of HYPO at calving on days in milk (DIM) at first service (DIMFS), milk yield (kg), milk components (percent fat and protein), and somatic cell count were analyzed for the first 3 Dairy Herd Improvement Association (DHIA) tests using the MIXED procedure of SAS (SAS Institute Inc., Cary, NC). The effect of parity (primiparous and multiparous), body condition score at calving, and manure hygiene score at calving were also included in the statistical models. The effect of HYPO at calving on calf survival, serum total protein, and diarrhea within 10 d of age were assessed using GLIMMIX procedure of SAS. The overall prevalence of HYPO was 14.6% (2.7% for primiparous and 30.8% for multiparous cows). Cows experiencing HYPO at calving had greater proportion of metritis (25.1 vs. 14.7%) and culling within 60 DIM (15.9 vs. 6.8%) compared with non-HYPO cows, respectively. For the first 3 DHIA tests, milk yield and components did not differ between HYPO and non-HYPO cows. The DIMFS as well as proportion of cows with dystocia, births of twins, mastitis, and PAI at first service were not different between HYPO and non-HYPO cows. The proportion of stillbirth, weaned calves, and serum total protein did not differ between calves born from HYPO or non-HYPO cows. However, calves born from HYPO cows had greater incidence of diarrhea (49%) than calves born (33.3%) from non-HYPO cows. Findings from the present study showed that HYPO at calving had significant health implications for both dams and calves under certified organic management.

In vitro anticholinestarase and cholinergic effect of the aqueous extract of Trema guineensis on rabbit duodenum

Purpose: In previous studies, the aqueous extract of Trema guineensis (Ulmaceae) was shown to increase rabbit duodenal contractions. The aim of this study was to evaluate the mechanism of the stimulation of the rabbit duodenum by the aqueous extract of Trema guineensis (Ulmaceae). Methods: The in vitro organ bath method was used in our experiments. The enzyme was extracted from rabbit duodenum. The acetylcholinesterase (AChE) activity was determined by Ellman\'s assay using acethylthiocholine iodide as substrate. The rate of hydrolysis of acetylcholinesterase was monitored at 412 nm using a spectrophotometer. Results: The effective concentration which induces 50% effect of Hypo+ (EC50) was obtained with 8 x 10-2 mg/ml of Hypo+. The tests carried out in the presence of atropine showed a considerable reduction in the amplitudes of intestinal contractions. Hypo+ exerted mixed competitive inhibition on acetylcholinesterase (Vmax = 8.33 μM/min and KM= 6.25 x 10-4 M). These results indicate that the crude extract of Trema guineensis contains anti-AChE and cholinomimetic substances. These two properties can explain the increase of duodenal contraction by Hypo+. Conclusion:These results support the use of Trema guineensis as a laxative due to its stimulating effects on duodenal contractility. Keywords: Trema guineensis, Myostimulation, Acetylcholinesterase, Hypo+, Duodenal contractionTropical Journal of Pharmaceutical Research Vol. 8 (1) 2009: pp. 11-17

Effect of hypo- and hyper-saline conditions on osmolarity and fatty acid composition of juvenile shrimp Litopenaeus vannamei (Boone, 1931) fed low- and high-HUFA diets

Litopenaeus vannamei (Boone) grown in ponds are exposed to salinities of less than 5 g L−1 during inland shrimp culture or to more than 40 g L−1 from evaporation and reduced water exchange in dry, hot climates. However, dietary requirements for shrimp grown in low or high salinities are not well defined, particularly for fatty acids. Feeding shrimp postlarvae with highly unsaturated fatty acids (HUFA) enhances tolerance to acute exposure to low salinity, as a result of better nutritional status, or/and specific effects of HUFA on membrane function and osmoregulation mechanisms. This study analysed the effect of HUFA supplementation (3% vs. 34%) on L. vannamei juveniles reared for 21 days at low (5 g L−1), medium (30 g L−1) and high salinities (50 g L−1). Juveniles grown at 5 g L−1 had lower survival compared with controls (30 g L−1) or shrimp grown at 50 g L−1, but no significant effect on survival was observed as a result of HUFA enrichment. In contrast, growth was significantly lower for shrimp grown at 50 g L−1, but this effect was compensated by the HUFA-enriched diet. Osmotic pressure in haemolymph was affected by salinity, but not by HUFA enrichment. Shrimp fed HUFA-enriched diets had significantly higher levels of eicosapentaenoic acid and docosahexaenoic acid in hepatopancreas and gills. These results demonstrate that growth at high salinities is enhanced with diets containing high HUFA levels, but that HUFA-enriched diets have no effect on shrimp reared at low salinities.

Effect of hypo- and hypersaline conditions on osmolality and Na+/K+-ATPase activity in juvenile shrimp (Litopenaeus vannamei) fed low- and high-HUFA diets

Fatty acid composition of cellular membranes can modify permeability and can modulate the activity of Na(+)/K(+)-ATPase. Although highly unsaturated fatty acids (HUFA) improve survival and osmoregulatory capacity to low salinities in penaeid shrimp, the possible mechanisms have not been established. For this purpose the influence of HUFA supplementation in diet (2.9 vs. 34% HUFA proportion to total fatty acids) on osmoregulatory responses of juvenile Litopenaeus vannamei submitted to an acute (15 h) or chronic exposure (21 days), to low (5 g L(-1)) and high salinities (50 g L(-1)) was analyzed. Shrimp fed the high-HUFA diet, had higher concentration of main HUFA (20:5n-3 and 22:6n-3) in polar lipids of gills. Osmotic pressure in hemolymph was significantly affected by salinity in acute (640, 751, 847 mOsm/kg for 5, 30 and 50 g L(-1), respectively), and chronic exposure (645, 713, 814 mOsm/kg), but variations between them were small compared to environmental salinity (206, 832, 1547 mOsm/kg), indicating that osmoregulation was achieved in a matter of hours. An increase in Na(+)/K(+)-ATPase activity was observed only after a chronic exposure to low salinity. Free amino acids (FAA), mainly alanine and arginine, were higher at 30 (control) and 50 g L(-1) in accordance to their role as organic osmolites. Neither osmotic pressure, Na(+)/K(+)-ATPase activity, nor FAA was affected by HUFA supplementation. However, higher water content in gills of shrimp exposed to low salinities was counteracted by increased HUFA content, which could be a result of changes in water permeability of gills. The osmoregulatory capacity of penaeid shrimp to low and high salinities was achieved within 15 h of acclimation and did not depend on HUFA supplementation in the diet.

Hypothermia and hyperthermia decrease the anticoagulant potency of low molecular weight heparin measured with thrombelastgraphy

BACKGROUND: It is a fact that anticoagulant potency of low molecular weight heparin (LMWH) is well established under normothermic conditions. The aim of our study was to evaluate the effect of hypo- and hyperthermia on LMWH anticoagulation as measured by thrombelastography. METHODS: Blood from 10 healthy volunteers was investigated before and after subcutaneous administration of 5000 IE of LMWH (dalteparin). Thrombelastography was performed with recalcified citrated whole blood with and without heparinase incubation at different test temperatures. RESULTS: Mean ± SD reaction time was within the normal range before LMWH administration (18 ± 5.4 mm at 37° C). LMWH prolonged reaction time to 35 mm at 37° C, but non-normothermic test temperatures significantly decreased reaction time to 28 mm at 33° C, to 33 mm at 35° C, to 21 mm at 38° C, and to 20 mm at 41° C. Similarly, clot formation time was decreased from 24 mm at 37° C to 19 mm at 33° C, to 22 mm at 35° C, to 21 mm at 38° C, and to 20 mm at 41° C (P < 0.05). CONCLUSIONS: These results show that both hypo- and hyperthermic conditions significantly decreased the anticoagulant potency of LMWH when assessed by TEG® analysis. These findings may be of clinical relevance in non-normothermic patients.

Effect of hypo-, iso- and hypertonic saline irrigation on secretory mucins and morphology of cultured human nasal epithelial cells

Conclusion. We speculate that isotonic saline is the most physiological irrigation solution in terms of mucus secretion and the cellular morphology of nasal epithelial cells. Objective. To determine the most physiologic and effective saline concentration for nasal irrigation in terms of mucus secretion and cellular morphology by using normal human nasal epithelial cells treated with hypo-, iso- and hypertonic saline. Material and methods. Fully differentiated passage-2 normal human nasal epithelial cells were treated with pure water and with 0.3% (hypotonic), 0.9% (isotonic) and 3% (hypertonic) saline solutions. mRNA expression levels of MUC5AC and MUC5B, which are known to be major airway mucins, were analyzed after 30 min using reverse transcriptase polymerase chain reaction. Total mucin and MUC5AC and MUC5B mucin secretions were analyzed using dot-blotting. Cellular morphology was observed with light microscopy after hematoxylin–eosin staining and with scanning electron microscopy. Results. MUC5AC and MUC5B mRNA levels did not change after treatment with pure water and various concentrations of saline. Total mucin and MUC5AC mucin secretions only increased following pure water treatment, while MUC5B mucin secretion increased with pure water, hypo- and hypertonic saline treatment. Morphologic analysis revealed that pure water severely damaged normal human nasal epithelial cells and that only isotonic saline did not affect their morphology.

Recirculatory model of fentanyl disposition with the brain as the target organ

The factors affecting the concentrations of fentanyl in the brain after intravenous administration have not been completely quantified. A model integrating the role of brain, lung and systemic kinetics was developed based on data from conscious instrumented sheep. Brain kinetics were inferred from arterio-sagittal sinus concentration gradients and cerebral blood flow, and lung kinetics from the pulmonary artery-aortic gradient and cardiac output. The best models of the lung and brain were incorporated into a recirculatory model of the whole-body disposition of fentanyl. The validity of the model structure was tested by its ability to describe published data on the effect of hypo-, normo- and hypercarbia on the blood and brain concentrations of fentanyl in anaesthetized dogs. The cerebral kinetics of fentanyl were consistent with partial membrane limitation: the time to 50% equilibration with arterial blood was 10.0 min. Lung kinetics had two distinct components: a shallow compartment that was 50% equilibrated with blood in 0.72 min, and a loss term probably representing sequestration. Despite its simplicity, the recirculatory model was an adequate description of the sheep data. The dog data could be described if cerebral blood flow and cardiac output in the model were allowed to differ between hypo-, normo- and hypercarbic states. The required flow changes were in good agreement with the known effect of these states in the dog. A recirculatory model with the brain as a target organ defined the quantitative relationship between the brain concentrations of fentanyl and the circulatory state.

Effect of hypo- and hyperthyroid states on phospholipid composition in developing rat heart.

The aim of this study was to examine the effect of hypo- and hyperthyroidism on the phospholipid composition in developing rat heart. The hypothyroid state (PTU) was induced by 0.05% 6-n-propyl-2-thiouracil in drinking water given to nursing mothers from the postnatal day 2-21. The hyperthyroidism (T3) was made by daily injection of 3,3',5-triiodo-L-thyronine (10 microg/100 g body wt) to newborns in the same time period. Age matched intact littermates were taken as euthyroid controls. PTU decreased the concentration of total phospholipids (PL), choline phosphoglycerides (PC), ethanolamine phosphoglycerides (PE) and diphosphatidylglycerol (DPG) and increased the proportion of plasmalogen component of PE (PLPE). T3 increased the concentration of PL, PC, PE, DPG and decreased PLPE in comparison with euthyroid controls. The ratio of saturated/unsaturated fatty acids (FA) in PE was decreased in PTU and increased in T3 group. The ratio of n-6/n-3 polyunsaturated FA in PC, PE and phosphatidylinositol (PI) was increased in PTU due to increase of 18:2n-6 and decrease of 22:6n-3 proportion. T3 decreased this ratio because of decline in 20:4n-6 and rise in 22:6n-3 proportion. Both hypo- and hyperthyroidism decreased the ratio of 20:4n-6/18:2n-6 in the majority of phospholipids. PTU decreased the unsaturation index in PC, PI and phosphatidylserine. It is concluded that thyroid state plays an essential role in the development of membrane phospholipid components in cardiac membranes during the early postnatal period.

Effect of hypo- and hyperthyroidism on gastric myoelectrical activity.

Although hypo- and hyperthyroid patients have different symptoms in the gastrointestinal tract, the mechanism of thyroid action on the gut remains poorly understood. Thus the aim of this study was to investigate the effect of hypo- and hyperthyroidism on gastric myoelectrical activity, gastric emptying, dyspeptic symptoms. Twenty-two hyperthyroid (median age 45, 15 females) and 11 hypothyroid (median age 42, 10 females) patients were included into the study. Dyspepsia score, hypo- and hyperthyroid symptom scale, abdominal ultrasonography and upper gastrointestinal endoscopy were performed. Gastric myoelectrical activity was measured by electrogastrograpy (EGG) before and after therapy both preprandially and postprandially and compared with age, gender, and body-matched controls (12 for hypothyroid, 15 for hyperthyroid patients). Radionuclide gastric emptying studies were performed with a solid meal. Hypothyroid patients revealed a significant increase in preprandial tachygastria as compared with controls (12.3% vs 4.8%). The percentage of preprandial normal slow waves (2.4-3.7 cpm) was below 70% (dysmotility) in 7 of 11 hypothyroid patients versus 2 of 12 controls (P < 0.05). Hyperthyroid patients revealed a significantly higher preprandial (3.1 vs 2.8) and postprandial (3.4 vs 3) DF when compared with the controls (P < 0.05). A higher percentage of postprandial taschygastria (7.9 vs 0) was present in hyperthyroid patients than in the controls (P < 0.05). The decrease on postprandial EGG power (power ratio < 1) was observed in 7 patients the in hyperthyroid group and 1 in controls (P < 0.05). The percentage of postprandial normal slow waves was below 70% in 10 of 20 hyperthyroid patients vs 1 of 15 controls (P < 0.05). After therapy these differences disappeared in the euthyroid state. The hypo- and hyperthyroid symptom scale correlated to dyspepsia score. Dyspepsia score in hyperthyroidism correlated to power ratios in hyperthyroid patients. We detected some correlations between serum levels of fT3 or fT4 and some EGG parameters in hypo- and hyperthyroidism. Dyspepsia score and hypo- and hyperthyroid symptom scale were improved significantly after therapy in the euthyroid state. In conclusions, we showed gastric dysrhythmia by EGG in both hypo- and hyperthyroid patients. Dyspeptic symptoms correlated to the activity of thyroid disease. After therapy, these findings and dyspeptic symptoms improved in the euthyroid state. Abnormalities of power ratios may be responsible of dyspeptic symptoms in hyperthyroid patients. EGG may be a useful and noninvasive tool for detecting gastric disturbances during hypo- and hyperthyroidism.

The Effect of Hypo- and Hyperthyroidism on Uterine and Cervical Collagens and Glycosidases in Albino Rats

The effect of hypo- and hyperthyroidism on uterine and cervical collagen and glycosidases were studied in mature albino rats. Hypothyroidism significantly increased the salt-soluble, acid-soluble, insoluble and total collagen in the uterus and cervix. However, all of these collagens were significantly decreased in the hyperthyroid condition. The activities of β- and β-galactosidases and glucosidases were significantly decreased in the uterus and cervix of hypothyroid rats, whereas, in hyperthyroid rats, all of these enzymes were significantly increased in the uterus and cervix. The data obtained in the present study suggested that the increase in lysosomal enzymes increased the degradation of uterine and cervical collagen. In contrast, the decrease in lysosomal enzymes in hypothyroid condition increased uterine and cervical collagen by decreasing degradation.

Effect of hypo- and hyperthyroidism on the function and metabolism of macrophages in rats

The effect of thyroid hormones on monocyte migration, phagocytic capacity and hydrogen peroxide production by macrophages and the effect of these hormones on glutamine and glucose metabolism was investigated. The experiments were performed on resident, thioglycollate- and BCG-stimulated cells from hypo- and hyperthyroid rats. High plasma levels of thyroid hormones suppressed the migration of monocytes and hydrogen peroxide production, whereas hypothyroidism did not affect cell migration but raised the phagocytic capacity and the hydrogen peroxide production. Hyperthyroidism increased the activities of glutaminase and hexokinase and the rates of decarboxylation of [U-14C]-glutamine and [U-14C]-glucose in inflammatory and activated cells. Hypothyroidism stimulated glucose metabolism and had only a slight effect on glutaminolysis. The activity of the TCA cycle was, however, diminished in the presence of high plasma levels of thyroid hormones and enhanced by the hypothyroid state. These findings suggest that the functional changes are more likely to be related to the activity of the TCA cycle rather than to glutaminolysis and glycolysis.

Immunocytochemical Demonstration of Chicken Hypophyseal Thyrotropes and Development of a Radioimmunological indicator for Chicken TSH Using Monoclonal and Polyclonal Homologous Antibodies in a Subtractive Strategy

The production and characterization of monoclonal antibodies (mAbs) toward the chicken pituitary glycoproteins are described. MAbs were first subdivided on an immunocytochemical (ICC) basis: one category of mAbs reacts with both thyrotropic and gonadotropic cells whereas another stains exclusively gonadotropic cells. The hypothesis that the former are anti-glycoprotein α and that the latter are anti-βLH and/or anti-βFSH mAbs was further elaborated in a homologous tracer binding assay. The putative anti-β gonadotropin mAbs exclusively recognize iodinated USDA-cLH-I-1, whereas the supposed anti-α mAbs react with both USDA-cLH-I-1 and USDA-cFSH-I-1. The ICC localization of pituitary thyrotropes has been achieved in a double-staining protocol using an anti-LH mAb to subtract specifically the gonadotropic cells from the complete α-subunit-containing cell population. The result is a strictly cephalic cell population that is densely granulated in hyperthyroid and hardly detectable in hypothyroid birds. A similar subtractive approach was used to develop a thyroid-stimulating hormone (TSH)-indicator in RIA. The total titer of α-containing molecules is first quantified with an anti-α mAb. The contribution of both LH and FSH to this titer is then measured by homologous USDA-RIA and subtracted from the total α-immunoreactivity to give an indication of the TSH level of the sample. The direct effect of thyroid-releasing hormone on pituitary TSH release in vitro in juvenile chicks and the effect of hypo- and hyperthyroidism on circulating TSH levels in vivo in juvenile broilers have been demonstrated.

Effect of Hypo and Hyperprolactinemia on the Testicular Maturation of Wistar Rats During Puberal Transition

In Wistar rats, the structural and metabolic organization of the testis was influenced by the blood concentration of prolactin. The androgen dependent enzyme activities in plasma as well as in testis were higher under hyperprolactinemia and lower under hypoprolactinemia, as induced by bromocriptine. While prolactin had direct effect on the testicular functions, bromocriptine seemed to exert its influence through blocking hypophysial prolactin.

Effect of Hypothyroidism on Methylmalonate Excretion and Hepatic Vitamin B-12 Levels in Rats

The effect of hypo- and hyperthyroidism on vitamin B-12 metabolism in the rat was studied by measuring methylmalonic acid excretion, B-12 content of liver and oxidation of 2-[14C]histidine. Ten percent pectin was added to increase severity of B-12 deficiency. The addition of thiouracil to a diet containing 10% pectin decreased the excretion of methylmalonic acid suggesting an amelioration of the B-12 deficiency. It was found that part of this decreased methylmalonic acid excretion was due to a decreased food consumption with a correspondingly decreased intake of branched-chain amino acids which are precursors of methylmalonic acid. When attempts were made to increase the protein intake of animals receiving thiouracil so their amino acid intake was equal to that of the control animals, methylmalonic acid excretion was still lower than that of the controls. It was also found that the vitamin B-12 content of the liver was higher in the animals receiving thiouracil than in the controls. Thyroidectomy had the same effect as feeding thiouracil. Liver B-12 levels are rapidly depleted on a B-12 deficient diet containing 10% pectin. It appears that hypothyroidism, induced either by thyroidectomy or by feeding thiouracil, slows the rate of depletion of hepatic B-12 which in turn facilitates the metabolism of methylmalonic acid and decreases its excretion in the urine.

Experimental hyperthyroidism does not induce hepatic insulin resistance in the miniature pig.

The effect of hypo- and hyper-thyroidism on insulin-mediated alterations in tracer-determined glucose kinetics and the arterial concentration of gluconeogenic precursors were investigated in 24 h-starved conscious unrestrained miniature pigs. Hyperinsulinaemia (about 40 microunits/ml) decreased blood glucose and, transiently, glucose output at unaltered glucose utilization in all thyroid states: this effect was pronounced in hyperthyroid (-50%) and less in hypothyroid pigs (-25%) compared with euthyroid controls (-35%). We conclude that moderate experimental hyperthyroidism does not induce hepatic insulin resistance, whereas hypothyroidism slightly impairs insulin action with respect to the regulation of glucose output.

Effect of thyroid state on cyclic AMP-mediated induction of hepatic phosphoenolpyruvate carboxykinase.

Hepatic phosphoenolpyruvate carboxykinase (PEPCK) is significantly increased in the hyperthyroid starved rat, and moderately decreased in the hypothyroid starved rat. As tri-iodothyronine by itself has only a small and sustained effect on the induction of this enzyme, as was previously shown in the isolated perfused organ, the effect of hypo- and hyper-thyroidism on the increase in cytosolic PEPCK provoked by dibutyryl cyclic AMP (Bt2cAMP) was investigated in vivo and in the isolated perfused liver. Compared with euthyroid fed controls, in hypothyroid fed rats Bt2cAMP provoked in 2 h only a small increase in translatable mRNA coding for PEPCK. In contrast, in hyperthyroid animals PEPCK mRNA as measured by translation in vitro was already increased in the fed state, and further enhanced by Bt2cAMP injection to values as in euthyroid controls. Under all thyroid states a close correlation between PEPCK mRNA activity and PEPCK synthesis was observed. In the isolated perfused liver from the hyperthyroid fed rat, the increase in PEPCK provoked by Bt2cAMP or Bt2cAMP + isobutylmethylxanthine was considerably enhanced compared with those obtained in livers of hypothyroid rats. Also, adrenaline provoked a stimulated induction of PEPCK in hyperthyroid rats compared with hypothyroid rats. To summarize, our data indicate that the primary action of thyroid hormones on the synthesis of hepatic cytosolic PEPCK is to accelerate the cyclic AMP- or adrenaline-induction of the enzyme, acting primarily at a pretranslational level.