			Home About us Contact

Physiological Dose (physiological + dose)

Distribution by Scientific Domains

Life Sciences	70%
Medical Sciences	20%

Selected Abstracts

Renal Response to Arginine Vasopressin During the Oestrous Cycle in the Rat: Comparison of Glucose and Saline Infusion Using Physiological Doses of Vasopressin

EXPERIMENTAL PHYSIOLOGY, Issue 1 2002
David E. Hartley
The renal response to arginine vasopressin in the rat has been shown to depend on reproductive status. However there is no consensus as to when the kidney is most responsive. The varying results could depend on the protocol and the dose of hormone used. A study has been performed, with physiological doses of vasopressin, comparing the responses during infusion of hypotonic saline and glucose. After an equilibration period of 150 min, conscious rats were infused on each of the four days of the oestrous cycle with either isotonic saline (0.077 M) or 0.14 M glucose for a control period of 45 min. Vasopressin was then infused at 10-40 fmol min,1 for 1 h, followed by a recovery period of 90 min. Timed urine samples were collected for determination of volume, sodium concentration and osmolality. During the control period urine flow was greatest at oestrus and dioestrus day 2 and sodium excretion on dioestrus day 2 irrespective of the infusate. Vasopressin concentrations achieved lay within the physiological range and no difference was observed between the different days for a given dose. Infusion of vasopressin in both saline and glucose produced a dose-dependent antidiuresis, the greatest responses being seen of pro-oestrus and dioestrus day 2. It was only with the highest rate of infusion that a significant increase in sodium excretion was seen on each day of the cycle and the greatest responses were seen on pro-oestrus and dioestrus day 1 for both infusates. Thus the kidney shows the greatest response to physiological doses of vasopressin at pro-oestrus and dioestrus day 1 irrespective of the infusate employed. [source]

Androgen replacement therapy improves function in male rat muscles independently of hypertrophy and activation of the Akt/mTOR pathway

ACTA PHYSIOLOGICA, Issue 4 2009
C. Hourdé
Abstract Aim:, We analysed the effect of physiological doses of androgens following orchidectomy on skeletal muscle and bone of male rats, as well as the relationships between muscle performance, hypertrophy and the Akt/mammalian target of rapamycin (mTOR) signalling pathway involved in the control of anabolic and catabolic muscle metabolism. Methods:, We studied the soleus muscle and tibia from intact rats (SHAM), orchidectomized rats treated for 3 months with vehicle (ORX), nandrolone decanoate (NAN) or dihydrotestosterone (DHT). Results:, Orchidectomy had very little effect on the soleus muscle. However, maximal force production by soleus muscle (+69%) and fatigue resistance (+35%) in NAN rats were both increased when compared with ORX rats. In contrast, DHT treatment did not improve muscle function. The relative number of muscle fibres expressing slow myosin heavy chain and citrate synthase activity were not different in NAN and ORX rats. Moreover, NAN and DHT treatments did not modify muscle weights and cross-sectional area of muscle fibres. Furthermore, phosphorylation levels of downstream targets of the Akt/mTOR signalling pathway, Akt, ribosomal protein S6 and eukaryotic initiation factor 4E-binding protein 1 were similar in muscles of NAN, DHT and ORX rats. In addition, trabecular tibia from NAN and DHT rats displayed higher bone mineral density and bone volume when compared with ORX rats. Only in NAN rats was this associated with increased bone resistance to fracture. Conclusion:, Physiological doses of androgens are beneficial to muscle performance in orchidectomized rats without relationship to muscle and fibre hypertrophy and activation of the Akt/mTOR signalling pathway. Taken together our data clearly indicate that the activity of androgens on muscle and bone could participate in the global improvement of musculoskeletal status in the context of androgen deprivation induced by ageing. [source]

Consequences of maternal yolk testosterone for offspring development and survival: experimental test in a lizard

FUNCTIONAL ECOLOGY, Issue 3 2007
T. ULLER
Summary 1Hormone-mediated maternal effects and developmental plasticity are important sources of phenotypic variation, with potential consequences for trait evolution. Yet our understanding of the importance of maternal hormones for offspring fitness in natural populations is very limited, particularly in non-avian species. 2We experimentally elevated yolk testosterone by injection of a physiological dose into eggs of the lizard Ctenophorus fordi Storr, to investigate its roles in offspring development, growth and survival. 3Yolk testosterone did not influence incubation period, basic hatchling morphology or survival under natural conditions. However, there was evidence for increased growth in hatchlings from testosterone-treated eggs, suggesting that maternal hormones have potential fitness consequences in natural populations. 4The positive effect of prenatal testosterone exposure on postnatal growth could represent a taxonomically widespread developmental mechanism that has evolved into an adaptive maternal effect in some taxa, but remains deleterious or selectively neutral in others. 5A broader taxonomic perspective should increase our understanding of the role of physiological constraints in the evolution of endocrine maternal effects. [source]

Novel biotransformation and physiological properties of norursodeoxycholic acid in humans,,

HEPATOLOGY, Issue 6 2005
Alan F. Hofmann
Experiments were performed in 2 volunteers to define the biotransformation and physiological properties of norursodeoxycholic acid (norUDCA), the C23 (C24 -nor) homolog of UDCA. To complement the in vivo studies, the biotransformation of norUDCA ex vivo using precision-cut human liver slices was also characterized. In the human studies, both a tracer dose given intravenously and a physiological dose (7.9 mmol, 3.0 g) given orally were excreted equally in bile and urine. By chromatography and mass spectrometry, the dominant biotransformation product of norUDCA in bile and urine was the C-23 ester glucuronide. Little N -acyl amidation (with glycine or taurine) occurred. The oral dose induced a sustained bicarbonate-rich hypercholeresis, with total bile flow averaging 20 ,L/kg/min, a rate extrapolating to 2 L/d. The increased bile flow was attributed to cholehepatic shunting of norUDCA as well to the lack of micelles in bile. Phospholipid and cholesterol secretion relative to bile acid secretion decreased during secretion of norUDCA and its metabolites, presumably also because of the absence of micelles in canalicular bile. When incubated with human liver slices, norUDCA was glucuronidated, whereas UDCA was conjugated with glycine or taurine. In conclusion, in humans, norUDCA is glucuronidated rather than amidated. In humans, but not animals, there is considerable renal elimination of the C-23 ester glucuronide, the dominant metabolite. NorUDCA ingestion induces a bicarbonate-rich hypercholeresis and evokes less phospholipid and cholesterol secretion into bile than UDCA. Molecules that undergo cholehepatic shunting should be powerful choleretics in humans. (HEPATOLOGY 2005;42:1391,1398.) [source]

Fine temporal analysis of DHT transcriptional modulation of the ATM/Gadd45g signaling pathways in the mouse uterus

MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2009
Mahinè Ivanga
Abstract In rodents, the uterus of a mature female undergoes changes during the uterine cycle, under the control of steroid hormones. 5,-Dihydrotestosterone (DHT) is recognized to play an important role in the regulation of androgen action in normal endometrium. Using microarray technology, a screening analysis of genes responding to DHT in the uterus of ovariectomized mice, has allowed us to highlight multiple genes of the ATM/Gadd45g pathway that are modulated following exposure to DHT. Two phases of regulation were identified. In the early phase, the expression of genes involved in the G2/M arrest is rapidly increased, followed by the repression of genes of the G1/S checkpoint, and by the induction of transcriptional regulators. Later, i.e. from 12 to 24 hr, genes involved in G2/M transition, cytoarchitectural and lipid-related genes are stimulated by DHT while immunity-related genes appear to be differentially regulated by the hormone. These results show that a physiological dose of DHT induces the transcription of genes promoting the cell cycle progression in mice. Profile determination of temporal uterine gene expression at the transcriptional level enables us to suggest that the DHT modulation of genes involved in ATM/Gadd45g signaling in an ATM- or p53-independent manner, could play an important role in the cyclical changes of uterine cells in the mouse uterus. Mol. Reprod. Dev. 76: 278,288, 2009. © 2008 Wiley-Liss, Inc. [source]

Thromboembolic events after carotid endarterectomy are not prevented by aspirin, but are due to the platelet response to adenosine 5,-diphosphate

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2000
P. D. Hayes
Background: Aspirin therapy fails to prevent a number of postprocedural thrombotic events, yet it still remains the standard antiplatelet regimen in most vascular surgical centres. After carotid endarterectomy (CEA), thrombosis of the endarterectomized vessel is preceded by increasing numbers of microemboli that can be detected with transcranial Doppler (TCD). The number and rate of emboli is highly predictive of thrombotic stroke. It was hypothesized that a preoperative test of platelet function might identify the mechanism(s) underlying post-CEA thrombosis. Methods: Blood was taken from 120 patients using a standardized phlebotomy technique. Platelet fibrinogen binding was measured by whole blood flow cytometry, in unstimulated samples, and in response to adenosine 5,-diphosphate (ADP) (10,5,10,7 mol l,1) and thrombin (0·02,0·16 units ml,1). Platelet aggregation was measured using ADP (4,20 × 10,7 mol l,1). The ability of aspirin to inhibit platelets was assessed by the aggregation induced by arachidonic acid. For the first 3 h after operation, the number of emboli occurring was quantified using TCD. Results: Of the 120 patients studied, 110 were monitored by TCD. These were divided into patients with more than 25 postoperative emboli (n = 22) and those with fewer than 25 emboli (n = 88). The degree of platelet inhibition induced by aspirin was not significantly different between the two groups (P = 0·89). However, platelets from the group with high rates of embolization bound 58 per cent more fibrinogen on flow cytometry in response to stimulation with a physiological dose of ADP (10,7 mol l,1) (P = 0·006). Aggregation of platelets from this group was also increased in response to ADP (35 per cent) relative to the group with few emboli (P = 0·001). ADP also induced more rapid aggregation in the patients with more than 25 emboli (P = 0·04). There was no difference in the activity of resting platelets (P = 0·4) or platelets stimulated by thrombin (P = 0·43), between the two groups of patients. Conclusion: These data suggest that it is the platelet response to ADP which is important in arterial thrombotic complications rather than products of the cyclo-oxygenase pathway. This observation could have significant therapeutic implications for other vascular or interventional procedures in which the endothelium is disrupted. © 2000 British Journal of Surgery Society Ltd [source]

Androgen replacement therapy improves function in male rat muscles independently of hypertrophy and activation of the Akt/mTOR pathway

Environmental carcinogens and p53 tumor-suppressor gene interactions in a transgenic mouse model for mammary carcinogenesis

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2-3 2002
Daniel Medina
Abstract Mouse mammary tumorigenesis is greatly influenced by a variety of exogenous agents, such as MMTV, chemical carcinogens (i.e., polycyclic aromatic hydrocarbons), and radiation, as well as by endogenous/physiological factors, such as steroid hormones, tumor-suppressor genes (i.e., Brca1/2,p53), and gene products of modifier genes. In the mouse model, the most frequently used chemical carcinogen has been 7,12-dimethylbenz[a]anthracene (DMBA), which activates the Ha- ras gene but does not alter the p53 tumor-suppressor gene. However, on an existing background of p53 gene alteration, low doses of DMBA are strongly cocarcinogenic. Using a transgenic model system, in which the p53 gene was deleted in the mammary gland, we examined the carcinogenic effects of a variety of external agents and internal factors given at either low doses or physiological doses. These agents/factors included DMBA, ,-radiation, Brca2 heterozygosity, and steroid hormones. All agents/factors increased the tumorigenic response of the p53 null mammary cells, even under conditions where no tumorigenic response was observed in the p53 wildtype mammary cell. The strongest cocarcinogenic effect was observed with the steroid hormone progesterone. The majority of tumors were highly aneuploid and composed of nuclear igh-grade cells. The mechanism for the aneuploidy and secondary events associated with high tumorigenicity were examined using array technology. These results demonstrate that, on a background of underlying genetic instability, very low doses of environmental mutagens and mitogens can produce strong cocarcinogenic effects. Environ. Mol. Mutagen. 39:178,183, 2002. © 2002 Wiley-Liss, Inc. [source]

Renal Response to Arginine Vasopressin During the Oestrous Cycle in the Rat: Comparison of Glucose and Saline Infusion Using Physiological Doses of Vasopressin

Fasting modulates metabolic responses to cortisol, GH and IGF-I in Arctic charr hepatocytes

JOURNAL OF FISH BIOLOGY, Issue 6 2005
Ø. Aas-Hansen
Hepatocytes in primary culture from fed and 2 month fasted Arctic charr Salvelinus alpinus were exposed to physiological doses of either cortisol, salmon growth hormone (GH), salmon insulin-like growth factor-I (IGF-I) or a combination of salmon GH and salmon IGF-I. Fasting significantly lowered medium glucose levels compared to the fed fish, but had no significant effects on hepatocyte glycogen content or on the activities of enzymes involved in the intermediary metabolism. Cortisol treatment had no effect on hepatocyte glycogen content or on the enzyme activities investigated, but resulted in a significant increase in medium glucose concentration in hepatocytes isolated from fasted, but not fed fish. GH and IGF-I treatments, both singly and in combination, significantly increased the glycogen content of hepatocytes isolated from fed fish, with less pronounced effects on hepatocytes isolated from fasted fish. The combination of GH and IGF-I significantly increased lactate dehydrogenase activity regardless of the feeding state and significantly reduced the phosphenolpyruvate carboxykinase activity and medium glucose concentration in hepatocytes isolated from fed fish. Further, GH and IGF-I significantly increased the activities of alanine aminotransferase and aspartate aminotransferase in hepatocytes isolated from fasted fish, but not fed fish. There were no effects of GH, IGF-I, or their combination, on glucose 6-phosphate dehydrogenase or 3-hydroxyacyl-CoA dehydrogenase activities. The results demonstrated that nutritional status of the animal modulates hepatocyte responsiveness to metabolic hormones, and suggested a role for GH and IGF-I in hepatic glycogen conservation. [source]