Distribution by Scientific Domains
Distribution within Medical Sciences

Terms modified by Basal

  • basal activity
  • basal apparatus
  • basal area
  • basal area increment
  • basal body
  • basal branch
  • basal cell
  • basal cell carcinoma
  • basal cell carcinoma syndrome
  • basal cell layer
  • basal clade
  • basal component
  • basal concentration
  • basal condition
  • basal core promoter
  • basal defence
  • basal defence response
  • basal dendrite
  • basal diameter
  • basal diet
  • basal distance
  • basal end
  • basal epidermis
  • basal epithelial cell
  • basal expression
  • basal expression level
  • basal forebrain
  • basal forebrain cholinergic neuron
  • basal ganglia
  • basal ganglia calcification
  • basal ganglia lesion
  • basal group
  • basal ice
  • basal insulin
  • basal insulin analogue
  • basal keratinocyte
  • basal lamina
  • basal layer
  • basal level
  • basal lineage
  • basal lipolysi
  • basal medium
  • basal member
  • basal membrane
  • basal metabolic rate
  • basal metabolism
  • basal node
  • basal nucleus
  • basal part
  • basal plane
  • basal plate
  • basal portion
  • basal position
  • basal promoter activity
  • basal rate
  • basal region
  • basal regions
  • basal release
  • basal resistance
  • basal respiration
  • basal segment
  • basal side
  • basal spacing
  • basal state
  • basal surface
  • basal synaptic transmission
  • basal taxa
  • basal tone
  • basal transcription
  • basal value
  • basal zone

  • Selected Abstracts

    Evidence against a sexual dimorphism in glucose and fatty acid metabolism in skeletal muscle cultures from age-matched men and post-menopausal women

    ACTA PHYSIOLOGICA, Issue 3 2009
    A. Rune
    Abstract Aim:,In vivo whole body differences in glucose/lipid metabolism exist between men and women. Thus, we tested the hypothesis that intrinsic sex differences exist in skeletal muscle gene expression and glucose/lipid metabolism using cultured myotubes. Methods:, Myotube cultures were prepared for gene expression and metabolic studies from vastus lateralis skeletal muscle biopsies obtained from age-matched men (n = 11; 59 ± 2 years) and post-menopausal women (n = 10; 60 ± 1 years). Results:, mRNA expression of several genes involved in glucose and lipid metabolism was higher in skeletal muscle biopsies from female vs. male donors, but unaltered between the sexes in cultured myotubes. Basal and insulin-stimulated glucose uptake, as well as glucose incorporation into glycogen, was similar in myotube cultures derived from male vs. female donors. In males vs. females, insulin increased glucose uptake (1.3 ± 0.1 vs. 1.5 ± 0.1-fold respectively) and incorporation into glycogen (2.3 ± 0.3 vs. 2.0 ± 0.3-fold respectively) to the same extent. Basal fatty acid oxidation and rate of uptake/accumulation was similar between sexes. In response to the 5,AMP-activated protein kinase activator AICAR, lipid oxidation was increased to the same extent in myotubes established from male vs. female donors (1.6 ± 0.6 vs. 2.0 ± 0.3-fold respectively). Moreover, the AICAR-induced rate of uptake/accumulation was similar between sexes. Conclusion:, Differences in metabolic parameters and gene expression profiles between age-matched men and post-menopausal women noted in vivo are not observed in cultured human skeletal muscle cells. Thus, the sexual dimorphism in glucose and lipid metabolism is likely a consequence of systemic whole body factors, rather than intrinsic differences in the skeletal muscle proper. [source]

    Expression of Neural Cell Adhesion Molecule (CD56) in Basal and Squamous Cell Carcinoma

    No abstract is available for this article. [source]

    Losartan modifies glomerular hyperfiltration and insulin sensitivity in type 1 diabetes

    S. Nielsen
    Aim: The effect of the angiotensin II receptor antagonist losartan on renal haemodynamics and insulin-mediated glucose disposal was examined in normotensive, normoalbuminuric type 1 diabetic patients using a double-blind, placebo-controlled, cross-over design. Methods: Diurnal blood pressure, glomerular filtration rate (GFR, determined using [125I]-iothalamate), renal plasma flow (RPF, determined using [131I]-hippuran) and urinary albumin excretion rate (UAE) were measured, and a hyperinsulinaemic, euglycaemic clamp with indirect calorimetry was performed in nine patients (age 30 ± 7 years (mean ±,s.d.), HbA1c 8.1 ± 1.1%) following 6 weeks' administration of either losartan 50 mg/day or placebo. Results: Diurnal blood pressure was significantly reduced after losartan compared with placebo (122/70 ± 11/8 vs. 130/76 ± 12/6 mmHg, p <,0.05). A significant decline in GFR (133 ± 23 vs. 140 ± 22 ml/min, p < 0.05) and filtration fraction (FF; GFR/RPF) (24.6 ± 3.5 vs. 26.2 ± 3.6%, p <,0.05) was observed in the losartan vs. placebo groups. RPF and UAE did not change. Isotopically determined glucose disposal rates were similar after losartan and placebo in the basal (2.61 ± 0.53 vs. 2.98 ± 0.93 mg/kg/min) and insulin-stimulated states (6.84 ± 2.52 vs. 6.97 ± 3.11 mg/kg/min). However, the glucose oxidation rate increased significantly after losartan vs. placebo in the basal state (1.72 ± 0.34 vs. 1.33 ± 0.18, mg/kg/min, p <,0.01) and during insulin stimulation (2.89 ± 0.75 vs. 2.40 ± 0.62 mg/kg/min, p <,0.03). Basal and insulin-stimulated non-oxidative glucose disposal tended to decrease after losartan; however, this was not significant. Endogenous glucose production and lipid oxidation were unchanged after treatment and similarly suppressed during hyperinsulinaemia. Glycaemic control, total cholesterol, high-density lipoprotein (HDL)-cholesterol and triglycerides were stable in both losartan and placebo groups. Conclusions: Losartan reduces blood pressure, glomerular hyperfiltration and FF, and improves basal and insulin-stimulated glucose oxidation in normotensive, normoalbuminuric type 1 diabetic patients. [source]

    Paraoxonase-1 (PON1) activity as a risk factor for atherosclerosis in chronic renal failure patients

    Saeed Abdelwhab SAEED
    Abstract Paraoxonase is a high-density lipoprotein-associated enzyme and has been shown to reduce the susceptibility to low-density lipoprotein peroxidation. This study aimed to investigate the activity of serum paraoxonase in uremic patients on hemodialysis (HD) and in the predialysis period, and to evaluate the correlations of vascular disease with paraoxonase activity. Thirty patients with chronic renal failure (CRF) undergoing HD (group 1), 30 patients with CRF under conservative treatment (group 2), and 30 healthy controls (group 3) were included. Basal, salt-stimulated, and arylesterase activity were tested by UV spectrophotometry. Serum lipid parameters were determined. B-Mode Doppler ultrasound was used to assess common carotid intima-media thickness (IMT). Basal paraoxonase, salt-stimulated, and arylesterase activity showed no significant difference between group 1 and group 2. However, it was significantly lower in group 1 and in group 2 than controls. Carotid IMT was significantly higher in group 1 than group 2 and both were significantly higher than controls. Basal paraoxonase-1 (PON1), salt-stimulated PON1, and arylesterase activity correlate with BUN, but only basal PON1 and salt-stimulated PON1 correlate with serum albumin. Linear regression showed that the most significant determinant of carotid IMT was PON1 arylesterase activity in group 1 and arylesterase activity and basal PON1 activity in group 2. Patients with CRF, whether under HD or conservative treatment, have reduced basal and stimulated paraoxonase activities, and this could be an important factor causing increased vascular disease in those patients. Modifying this factor can be of great value to protect against this common complication. [source]

    Cell adhesion regulates platelet-derived growth factor,induced MAP kinase and PI-3 kinase activation in stellate cells

    HEPATOLOGY, Issue 3 2002
    Vinicio Carloni
    The biologic effects of growth factors are dependent on cell adhesion, and a cross talk occurs between growth factors and adhesion complexes. The aim of the present study was to evaluate the influence of cell adhesion on the major intracellular signaling pathways elicited by platelet-derived growth factor (PDGF) in hepatic stellate cells (HSC). PDGF signaling was investigated in an experimental condition characterized by lack of cell adhesion for different intervals of time. Basal and PDGF-induced focal adhesion kinase (FAK) tyrosine phosphorylation was maintained in a condition of cell suspension for 2, 4, and 6 hours, whereas it was completely lost after 12 and 24 hours. We examined MAP kinase activity at 2 and 24 hours, corresponding to the higher and lower levels of FAK phosphorylation. In these experiments, MAP kinase activity correlated with FAK phosphorylation. Stimulation with PDGF was able to cause Ras-GTP loading only in adherent cells. The ability of PDGF to induce phosphatidylinositol 3-kinase (PI 3-K) activity was abrogated in cells maintained in suspension. The Ser473 phosphorylation of Akt was only marginally affected by the lack of cell adhesion. We then evaluated the association of FAK with c-Src. This association was found to be cell adhesion dependent, and it did not appear to be dependent from phosphorylated FAK. These changes in PDGF-induced intracellular signaling were associated with a remarkable reduction of PDGF-proliferative potential in nonadherent cells, although no marked differences in the apoptotic rate were observed. In conclusion, these results suggest that cell adhesion differentially regulates major signaling pathways activated by PDGF in HSC. [source]

    Raw potato starch and short-chain fructo-oligosaccharides affect the composition and metabolic activity of rat intestinal microbiota differently depending on the caecocolonic segment involved

    G.M. Le Blay
    Abstract Aims:In vitro studies have suggested that fructo-oligosaccharides (FOS) and resistant starch (two fermentable non-digestible carbohydrates) display different fermentation kinetics. This study investigated whether these substrates affect the metabolic activity and bacterial composition of the intestinal microflora differently depending on the caecocolonic segment involved. Methods and Results: Eighteen rats were fed a low-fibre diet (Basal) or the same diet containing raw potato starch (RPS) (9%) or short-chain FOS (9%) for 14 days. Changes in wet-content weights, bacterial populations and metabolites were investigated in the caecum, proximal and distal colon and faeces. Both substrates exerted a prebiotic effect compared with the Basal diet. However, FOS increased lactic acid-producing bacteria (LAPB) throughout the caecocolon and in faeces, whereas the effect of RPS was limited to the caecum and proximal colon. As compared with RPS, FOS doubled the pool of caecal fermentation products, while the situation was just the opposite distally. This difference was mainly because of the anatomical distribution of lactate, which accumulated in the caecum with FOS and in the distal colon with RPS. Faeces reflected these impacts only partly, showing the prebiotic effect of FOS and the metabolite increase induced by RPS. Conclusions: This study demonstrates that FOS and RPS exert complementary caecocolonic effects. Significance and Impact of the study: The RPS and FOS combined ingestion could be beneficial by providing health-promoting effects throughout the caecocolon. [source]

    Simplified System for Absolute Fracture Risk Assessment: Clinical Validation in Canadian Women,

    William D Leslie
    Abstract Absolute 10-yr fracture risk based on multiple factors is the preferred method for risk assessment. A simplified risk assessment system from sex, age, DXA, and two clinical risk factors (CRFs),prior fracture and systemic corticosteroid (CS) use-has been used in Canada since 2005. This study was undertaken to evaluate this system in the Canadian female population. A total of 16,205 women ,50 yr of age at the time of baseline BMD (1998,2002) were identified in a database containing all clinical DXA test results for the Province of Manitoba, Canada. Basal 10-yr fracture risk from age and minimum T-score (lumbar spine, femur neck, trochanter, total hip) was categorized as low (<10%), moderate (10,20%), or high (>20%). Health service records since 1987 were assessed for prior fracture codes (N = 5224), recent major CS use (N = 616), and fracture codes after BMD testing (mean, 3.1 yr of follow-up) for the hip, vertebrae, forearm, or humerus (designated osteoporotic, N = 757). Fracture risk predicted from age and minimum T-score alone showed a significant gradient in observed fracture rates (low 5.1 [95% CI, 4.1,6.4], moderate 11.5 [95% CI, 10.1,13.0], high 25.4 [95% CI, 23.2,27.9] per 1000 person-years; p -for-trend <0.0001). There was an incremental increase in incident fracture rates from a prior fracture (13.9 [95% CI, 11.3,16.4] per 1000 person-years) or major CS use (11.2 [95% CI, 4.1,18.2] per 1000 person-years). This simplified fracture risk assessment system provides an assessment of fracture risk that is consistent with observed fracture rates. [source]

    Microbial levan in the diet of Labeo rohita Hamilton juveniles: effect on non-specific immunity and histopathological changes after challenge with Aeromonas hydrophila

    S K Gupta
    Abstract A 60-day feeding trial was conducted to study the immuno-protective effect of microbial levan on Labeo rohita juveniles challenged with Aeromonas hydrophila. Six purified diets were prepared with different levels of microbial levan: control (no levan), T1 (Basal + 0.25%), T2 (Basal + 0.50%), T3 (Basal + 0.75%), T4 (Basal + 1%) and T5 (Basal + 1.25%), fed to six groups of fish in triplicate. Among the treatment groups the haemoglobin content and total leucocyte count were increased with a dietary supplementation of levan at 1% or more. An increasing trend for total erythrocyte count was observed with increasing level of dietary levan. Lower levan-supplemented groups showed a higher albumin/globulin ratio. As the levan supplementation was increased, there was a gradual increase in serum lysozyme activity and respiratory burst activity [nitroblue tetrazolium (NBT) assay] reduction values. The highest lysozyme activity and NBT were observed in the T5 group although this was similar to the T4 group (P > 0.05). No significant histo-architectural changes were associated with dietary levan levels. After challenge with A. hydrophila, moderately degenerated hepatocytes, oedema and leucocytic infiltration in parenchymatous tissues, and extensive haemorrhage and haemosiderosis in the kidney were observed in the control group. However, the T5 group supplemented with 1.25% levan showed infiltrating leucocytes in the liver while the kidney showed only moderate degeneration of renal tubules. The relative survival per cent of juveniles after challenge with A. hydrophila was the highest in the T5 group followed by T4. This suggests that microbial levan at 1.25% can be used as dietary immunostimulant for L. rohita juveniles. [source]

    Basal and residual lower esophageal pressures increase in old age in classic achalasia, but not vigorous achalasia

    Kee Wook Jung
    Abstract Background and Aim:, The relationship between age and esophageal motility parameters (i.e. basal and residual pressure of the lower esophageal sphincter [LES]) remains to be established in achalasia patients, possibly because most previous studies did not distinguish between classic and vigorous achalasia patients. We investigated the relationship between age and esophageal motility parameters in both classic and vigorous achalasia patients. Methods:, A retrospective review of esophageal manometry data in a single center was undertaken. Basal and residual pressure for LES was analyzed. A total of 103 achalasia patients were enrolled, comprising 84 classic and 19 vigorous types. They were subdivided into three different age groups as follows: 21,40 years old (group A), 41,60 years old (group B), and over 60 years old (group C). Results:, In classic achalasia patients (M : F = 27:57, mean age = 44 ± 15 years old) the older age group showed a significantly higher basal LES pressure (49.62 ± 19.63 mmHg) than the younger age group (P < 0.0001). Moreover, the older age group also showed significantly high residual LES pressure (20.46 ± 8.61 mmHg) than the younger age group (P = 0.0006). In contrast, in vigorous achalasia patients (M : F = 12:7, mean age: 47 ± 15 years old) there were no difference between age and motility indices (all P > 0.05). Conclusion:, In classic achalasia patients there appears to be a correlation between age and esophageal motility indices, especially basal and residual LES pressure. Such correlations do not appear to exist for vigorous achalasia patients. [source]

    Improving glycemic control in medical inpatients: A pilot study

    BCPS, Jennifer M. Trujillo PharmD
    Abstract BACKGROUND Inpatient hyperglycemia is associated with poor patient outcomes. Current guidelines recommend that in an inpatient non-ICU setting there be treatment to achieve a glucose level below 180 mg/dL. METHODS Objectives of this prospective quality-improvement pilot study were to implement a subcutaneous insulin protocol on a general medicine service, to identify barriers to implementation, and to determine the effect of this protocol on glycemic control. Eighty-nine patients with a preexisting diagnosis of type 2 diabetes or inpatient hyperglycemia were eligible. Study outcomes included resident acceptance of the protocol, insulin-ordering practices, and mean rate of hyperglycemia (glucose > 180 mg/dL) per person. Results were compared with those of a previously conducted observational study. RESULTS Residents agreed to use the protocol in 56% of cases. Reasons for declining the protocol included severity of a patient's other disease states, desire to titrate oral medications, and fear of hypoglycemia. Basal and nutritional insulin were prescribed more often in the pilot group compared with at baseline (64% vs. 49% for basal, P = .05; 13% vs. 0% for nutritional, P < .001). Basal insulin was started after the first full hospital day in 42% of patients, and only one-third of patients with any hypo- or hyperglycemia had any subsequent changes in their insulin orders. The mean rate of hyperglycemia was not significantly different between groups (31.6% of measurements per patient vs. 33.3%, P = .85). CONCLUSIONS Adherence to a new inpatient subcutaneous insulin protocol was fair. Barriers included fear of hypoglycemia, delays in starting basal insulin, and clinical inertia. Quality improvement efforts likely need to target these barriers to successfully improve inpatient glycemic control. Journal of Hospital Medicine 2008;3:55,63. © 2008 Society of Hospital Medicine. [source]

    Basal and stimulated lactate fluxes in primary cultures of astrocytes are differentially controlled by distinct proteins

    Fumihiko Maekawa
    Abstract Lactate release by astrocytes is postulated to be of importance for neuroenergetics but its regulation is poorly understood. Basigin, a chaperone protein for specific monocarboxylate transporters (MCTs), represents a putatively important regulatory element for lactate fluxes. Indeed, basigin knockdown by RNA interference in primary cultures of astrocytes partially reduced both proton-driven lactate influx and efflux. But more strikingly, enhancement of lactate efflux induced by glutamate was prevented while the effect of sodium azide was significantly reduced by treatment of cultured astrocytes with anti-basigin small interfering RNA. Enhancement of glucose utilization was unaffected under the same conditions. Basal lactate uptake and release were significantly reduced by MCT1 knockdown, even more so than with basigin knockdown, whereas glutamate-driven or sodium azide-induced enhancement of lactate release was not inhibited by either MCT1, 2, or 4 small interfering RNAs. In conclusion, MCT1 plays a pivotal role in the control of basal proton-driven lactate flux in astrocytes while basigin is only partly involved, most likely via its interaction with MCT1. In contrast, basigin appears to critically regulate the enhancement of lactate release caused by glutamate (or sodium azide) but via an effect on another unidentified transporter at least present in astrocytes in vitro. [source]

    Effects of chronic paroxetine treatment on dialysate serotonin in 5-HT1B receptor knockout mice

    A. M. Gardier
    Abstract The role of serotonin (5-HT)1B receptors in the mechanism of action of selective serotonin re-uptake inhibitors (SSRI) was studied by using intracerebral in vivo microdialysis in conscious, freely moving wild-type and 5-HT1B receptor knockout (KO 5-HT1B) mice in order to compare the effects of chronic administration of paroxetine via osmotic minipumps (1 mg per kg per day for 14 days) on extracellular 5-HT levels ([5-HT]ext) in the medial prefrontal cortex and ventral hippocampus. Basal [5-HT]ext values in the medial prefrontal cortex and ventral hippocampus, ,,20 h after removing the minipump, were not altered by chronic paroxetine treatment in both genotypes. On day 15, in the ventral hippocampus, an acute paroxetine challenge (1 mg/kg i.p.) induced a larger increase in [5-HT]ext in saline-pretreated mutant than in wild-type mice. This difference between the two genotypes in the effect of the paroxetine challenge persisted following chronic paroxetine treatment. Conversely, in the medial prefrontal cortex, the paroxetine challenge increased [5-HT]ext similarly in saline-pretreated mice of both genotypes. Such a challenge produced a further increase in cortical [5-HT]ext compared with that in saline-pretreated groups of both genotypes, but no differences were found between genotypes following chronic treatment. To avoid the interaction with raphe 5-HT1A autoreceptors, 1 µm paroxetine was perfused locally through the dialysis probe implanted in the ventral hippocampus; similar increases in hippocampal [5-HT]ext were found in acutely or chronically treated wild-type mice. Systemic administration of the mixed 5-HT1B/1D receptor antagonist GR 127935 (4 mg/kg) in chronically treated wild-type mice potentiated the effect of a paroxetine challenge dose on [5-HT]ext in the ventral hippocampus, whereas systemic administration of the selective 5-HT1A receptor antagonist WAY 100635 did not. By using the zero net flux method of quantitative microdialysis in the medial prefrontal cortex and ventral hippocampus of wild-type and KO 5-HT1B mice, we found that basal [5-HT]ext and the extraction fraction of 5-HT were similar in the medial prefrontal cortex and ventral hippocampus of both genotypes, suggesting that no compensatory response to the constitutive deletion of the 5-HT1B receptor involving changes in 5-HT uptake capacity occurred in vivo. As steady-state brain concentrations of paroxetine at day 14 were similar in both genotypes, it is unlikely that differences in the effects of a paroxetine challenge on hippocampal [5-HT]ext are due to alterations of the drug's pharmacokinetic properties in mutants. These data suggest that there are differences between the ventral hippocampus and medial prefrontal cortex in activation of terminal 5-HT1B autoreceptors and their role in regulating dialysate 5-HT levels. These presynaptic receptors retain their capacity to limit 5-HT release mainly in the ventral hippocampus following chronic paroxetine treatment in mice. [source]

    Chronic Prenatal Ethanol Exposure Increases Glucocorticoid-Induced Glutamate Release in the Hippocampus of the Near-Term Foetal Guinea Pig

    U. Iqbal
    Exposure to high cortisol concentration can injure the developing brain, possibly via an excitotoxic mechanism involving glutamate (Glu). The present study tested the hypothesis that chronic prenatal ethanol exposure (CPEE) activates the foetal hypothalamic-pituitary-adrenal axis to produce high cortisol exposure in the foetal compartment and alters sensitivity to glucocorticoid-induced Glu release in the foetal hippocampus. Pregnant guinea pigs received daily oral administration of ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding from gestational day (GD) 2 until GD 63 (term, approximately GD 68) at which time they were euthanised, 1 h after their final treatment. Adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined in foetal plasma. Basal and electrically stimulated Glu and ,-aminobutyric acid (GABA) efflux in the presence or absence of dexamethasone (DEX), a selective glucocorticoid-receptor agonist, were determined ex vivo in foetal hippocampal slices. Glucocorticoid receptor (GR), mineralocorticoid receptor (MR) and N -methyl- d -aspartate (NMDA) receptor NR1 subunit mRNA expression were determined in situ in the hippocampus and dentate gyrus. In the near-term foetus, CPEE increased foetal plasma ACTH and cortisol concentrations. Electrically stimulated glutamate, but not GABA, release was increased in CPEE foetal hippocampal slices. Low DEX concentration (0.3 µM) decreased stimulated glutamate, but not GABA, release in both CPEE and control foetal hippocampal slices. High DEX concentration (3.0 µM) increased basal release of Glu, but not GABA, in CPEE foetal hippocampal slices. GR, but not MR, mRNA expression was elevated in the hippocampus and dentate gyrus, whereas NR1 mRNA expression was increased in the CA1 and CA3 fields of the foetal hippocampus. These data demonstrate that CPEE increases high glucocorticoid concentration-induced Glu release in the foetal hippocampus, presumably as a consequence of increased GR expression. These effects of CPEE, coupled with increased glutamate release and increased NMDA receptor expression, may predispose the near-term foetal hippocampus to GR and Glu-NMDA receptor-mediated neurodevelopmental toxicity. [source]

    Central Administration of Orexin A Suppresses Basal and Domperidone Stimulated Plasma Prolactin

    S. H. Russell
    Abstract Orexin immunoreactive fibres are abundant in the hypothalamus suggesting a neuroendocrine regulatory role. Intracerebroventricular (ICV) administration of orexin A suppressed plasma prolactin in male rats by 71% at 20 min post-injection and 83% at 90 min post-injection (P < 0.005 vs saline at both time points). To investigate whether this effect was through the tuberoinfundibular dopaminergic (TIDA) system, a supra-maximal dose of domperidone, a dopamine receptor antagonist, was injected intraperitoneally (i.p.) prior to ICV injection of orexin A. ICV orexin A significantly suppressed domperidone (9 mg/kg)-stimulated plasma prolactin levels, by up to 40% (i.p. domperidone + ICV orexin A 3 nmol 34.5 ± 7.4 ng/ml and i.p. domperidone + ICV orexin A 20 nmol 43.5 ± 4.3 ng/ml, both P < 0.005 vs i.p. domperidone + ICV saline 57.9 ± 2.7 ng/ml). Orexin A, 100 nM, significantly stimulated release of neurotensin, vasoactive intestinal polypeptide, somatostatin, corticotropin releasing factor and luteinizing hormone releasing hormone, but had no effect on release of dopamine, thyrotropin releasing hormone (TRH), vasopressin or melanin-concentrating hormone from hypothalamic explants in vitro. Orexin A did not alter basal or TRH stimulated prolactin release in dispersed pituitary cells harvested from male rats. The data suggest that ICV administration of orexin A suppresses plasma prolactin in part through a pathway independent of the dopaminergic system. [source]

    Selegiline, an MAO-B inhibitor, attenuates airway smooth muscle contraction in the rat trachea

    Maki Yoshimura
    Selegiline is widely used for Parkinson's disease and sometimes for Alzheimer's disease. It is reported to affect intracellular Ca2+ concentration. Since intracellular Ca2+ is partly regulated by phosphatidylinositol (PI) response and is important for smooth muscle contraction, selegiline may affect airway smooth muscle tension. We examined the effects of selegiline on acetylcholine (ACh)- and KCl-induced contractile and PI responses in rat trachea. The trachea was cut into 3-mm-wide ring segments or 1-mm-wide slices. ACh (3 ,M, 50% effective dose) or KCl (40mM) was added, and ring relaxation was induced by the addition of selegiline. Tracheal slices were incubated with [3H]myo -inositol and 3 ,M ACh in the presence of selegiline, and [3H]inositol monophosphate (IP1) was measured. Selegiline dose-dependently attenuated ACh- and KCl-induced tracheal ring contractions. Fifty-percent inhibitory doses (ID50) of selegiline against ACh- and KCl-induced contraction were 120±30 ,M and 80±20 ,M, respectively. Basal and ACh-induced IP1 accumulation were 2.20±0.20 Bq and 7.88±0.23 Bq, respectively, and selegiline at a dose of 1000 ,M attenuated ACh-induced IP1 accumulation (5.44±0.30 Bq). These results suggest that selegiline inhibits contractile responses through the inhibition of voltage-operated Ca2+ channels and the PI response. [source]

    Impact of organic manures with and without mineral fertilizers on soil chemical and biological properties under tropical conditions

    Kulvinder Kaur
    Abstract Soils receiving organic manures with and without chemical fertilizers for the last 7 yr with pearlmillet,wheat cropping sequence were compared for soil chemical and biological properties. The application of farmyard manure, poultry manure, and sugarcane filter cake alone or in combination with chemical fertilizers improved the soil organic C, total N, P, and K status. The increase in soil microbial-biomass C and N was observed in soils receiving organic manures only or with the combined application of organic manures and chemical fertilizers compared to soils receiving chemical fertilizers only. Basal and glucose-induced respiration, potentially mineralizable N, and arginine ammonification were higher in soils amended with organic manures with or without chemical fertilizers, indicating that more active microflora is associated with organic and integrated system using organic manures and chemical fertilizers together which is important for nutrient cycling. [source]

    The Glycine Reuptake Inhibitor Org 25935 Interacts With Basal and Ethanol-Induced Dopamine Release in Rat Nucleus Accumbens

    ALCOHOLISM, Issue 7 2009
    Helga Höifödt Lidö
    Background:, The mesolimbic dopamine (DA) projection from the ventral tegmental area to nucleus accumbens (nAc), a central part of the reward system, is activated by ethanol (EtOH) and other drugs of abuse. We have previously demonstrated that the glycine receptor in the nAc and its amino acid agonists may be implicated in the DA activation and reinforcing properties of EtOH. We have also reported that the glycine transporter 1 inhibitor, Org 25935, produces a robust and dose-dependent decrease in EtOH consumption in Wistar rats. The present study explores the interaction between EtOH and Org 25935 with respect to DA levels in the rat nAc. Methods:, The effects of Org 25935 (6 mg/kg, i.p.) and/or EtOH (2.5 g/kg, i.p.) on accumbal DA levels were examined by means of in vivo microdialysis (coupled to HPLC-ED) in freely moving male Wistar rats. The effect of Org 25935 on accumbal glycine output was also investigated. Results:, Systemic Org 25935 increased DA output in a subpopulation of rats (52% in Experiment 1 and 38% in Experiment 2). In Experiment 2, EtOH produced a significant increase in DA levels in vehicles (35%) and in Org 25935 nonresponders (19%), whereas EtOH did not further increase the DA level in rats responding to Org 25935 (2%). The same dose of Org 25935 increased glycine levels by 87% in nAc. Conclusions:, This study demonstrates that Org 25935, probably via increased glycine levels, (i) counteracts EtOH-induced increases of accumbal DA levels and (ii) increases basal DA levels in a subpopulation of rats. The results are in line with previous findings and it is suggested that the effects observed involve interference with accumbal GlyRs and are related to the alcohol consumption modulating effect of Org 25935. [source]

    Alcohol Effects on Central Nervous System Gene Expression in Genetic Animal Models

    ALCOHOLISM, Issue 2 2005
    William J. McBride
    This article summarizes the proceedings of a symposium presented at the 2004 annual meeting of the Research Society on Alcoholism in Vancouver, British Columbia, Canada. The organizers and chairs were William J. McBride and Michael F. Miles. The presentations were (1) Molecular Triangulation on Gene Expression Patterns in Behavioral Responses to Acute Ethanol, by Robnet T. Kerns; (2) Gene Expression in Limbic Regions After Ethanol Self-Infusion Into the Posterior Ventral Tegmental Area, by Zachary A. Rodd; (3) Microarray Analysis of CNS Limbic Regions of Inbred Alcohol-Preferring and -Nonpreferring rats and Effects of Alcohol Drinking, by Wendy N. Strother and Howard J. Edenberg; and (4) Microarray Analysis of Mouse Lines Selected for Chronic Ethanol Withdrawal Severity: The Convergence of Basal, Ethanol Regulated, and Proximity to Ethanol Quantitative Trait Loci to Identify Candidate Genes, by Joel G. Hashimoto and Kristine M. Wiren. [source]

    Muco-ciliary differentiation of nasal epithelial cells is decreased after wound healing in vitro

    ALLERGY, Issue 8 2009
    D. S. Lazard
    Background:, Epithelial damage and modifications of cell differentiation are frequent in airway diseases with chronic inflammation, in which transforming growth factor-,1 (TGF-,1) plays an important role. The aim of this study was to evaluate the differentiation of human nasal epithelial cells (HNEC) after wound healing and the potential effects of TGF-,1. Methods:, Basal, mucus, and ciliated cells were characterized by cytokeratin-14, MUC5AC, and ,IV tubulin immunodetection, respectively. Their expression was evaluated in situ in nasal polyps and in an in vitro model of wound healing in primary cultures of HNEC after wound closure, under basal conditions and after TGF-,1 supplementation. Using RT-PCR, the effects of TGF-,1 on MUC5AC and DNAI1 genes, specifically transcribed in mucus and ciliated cells, were evaluated. Results:,In situ, high TGF-,1 expression was associated with low MUC5AC and ,IV tubulin expression. In vitro, under basal conditions, MUC5AC expression remained stable, cytokeratin-14 expression was strong and decreased with time, while ,IV tubulin expression increased. Transforming growth factor-,1 supplementation downregulated MUC5AC and ,IV tubulin expression as well as MUC5AC and DNAI1 transcripts. Conclusion:, After a wound, differentiation into mucus and ciliated cells was possible and partially inhibited in vitro by TGF-,1, a cytokine that may be involved in epithelial remodeling observed in chronic airway diseases. [source]


    NEPHROLOGY, Issue 3 2000
    G. Dogra
    OBJECTIVE: To test the hypothesis that endothelial dysfunction occurs in nephrotic range proteinuria primarily as a consequence of dyslipidaemia. METHODS: Brachial artery and forearm microcirculatory endothelial function was compared among patients with nephrotic range proteinuria (NRP, n = 14 ), primary hyperlipidaemia (HL, n = 15) and normal controls (NC, n = 16). Endothelial function was studied by measuring post-ischaemic flow-mediated dilatation (FMD) of the brachial artery using high resolution ultrasonography. Endothelium-independent, glyceryl trinitrate (GTN) mediated brachial artery vasodilatation was also measured. Basal and post-ischaemic blood flow of the forearm microcirculation was measured using venous-occlusion strain gauge plethysmography. RESULTS: Serum creatinine was similar among groups. The proteinuric group had a mean albumin of 27.6g/L(1.8) and 24-hour urinary protein excretion of 6.3g(1.3). Plasma lipids and lipoproteins were not statistically different between the NRP and HL groups. Brachial artery FMD was significantly lower in the NRP and HL groups compared with the controls (NRP 4.7%(1.3)*, HL 4.9%(0.7)* and NC 8.3%(0.6), *p = 0.012 vs. NC); GTN mediated dilatation and basal and post-ischaemic forearm blood flow were not statistically different among the three groups. CONCLUSION: Patients with nephrotic range proteinuria have endothelial dysfunction of conduit arteries in the peripheral circulation, similar to that observed in patients with primary hyperlipidaemia. This suggests dyslipoproteinaemia is the principal cause of endothelial dysfunction of conduit arteries in nephrotic range proteinuria. Confirmation of this should be sought with an intervention trial of lipid-regulating therapy. [source]

    Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans

    Y. Falkén
    Abstract Background, Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short-term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis during a 6-h infusion in humans. Methods, Ghrelin (15 pmol kg,1 min,1) or saline was infused intravenously for 360 min after intake of radio-opaque markers, acetaminophen, and lactulose after a standardized breakfast in 12 male volunteers. Gastric emptying, orocecal transit, colonic transit, postprandial plasma concentrations of glucose, insulin, glucagon-like peptide-1 (GLP-1), and peptide YY were assessed. In vitro studies of gastrointestinal muscle contractility were performed. Key Results, The gastric emptying rate was faster for ghrelin compared to saline (P = 0.002) with a shorter half-emptying time (50.3 ± 3.9 vs 59.9 ± 4.4 min, P = 0.004). There was no effect of ghrelin on orocecal or colonic transit. Postprandial elevations of plasma glucose, insulin, and GLP-1 occurred 15 min earlier and were higher with ghrelin. The insulinogenic index did not change during ghrelin infusion. Basal in vitro contractility was unaffected by ghrelin. Conclusions & Inferences, The effect of a 6-h ghrelin infusion on gastrointestinal motility is limited to the stomach without affecting orocecal or colonic transit. Plasma glucose, insulin, and GLP-1 are elevated postprandially, probably as a result of the hastened gastric emptying. Changes in glucose homeostasis as a consequence of stimulated gastric emptying and hormone release, need to be taken into account in the use of pharmacological stimulants for the treatment of motility disorders. [source]

    Immunohistochemical detection of BH3-only proteins in ameloblastic tumors

    ORAL DISEASES, Issue 6 2008
    H Kumamoto
    Objective:, To evaluate expression of BH3-only proteins in odontogenic tumors, expression of Bid, Bim, Bad, Noxa, and Puma was analyzed in ameloblastic tumors as well as in tooth germs. Methods:, Nine tooth germs, 37 ameloblastomas, and five malignant ameloblastic tumors were examined immunohistochemically with antibodies against Bid, Bim, Bad, Noxa, and Puma. Results:, Immunohistochemical reactivity for Bid, Bim, Bad, Noxa, and Puma was detected in the cytoplasm of cellular components in normal and neoplastic odontogenic tissues. Expression of these BH3-only proteins was evident in odontogenic epithelial cells near the basement membrane in tooth germs and ameloblastic tumors. Acanthomatous ameloblastomas showed no reactivity for Bid, Bim, Bad, Noxa, or Puma in keratinizing cells, whereas granular cells in granular cell ameloblastomas reacted with these BH3-only proteins. Basal and desmoplastic ameloblastomas and ameloblastic carcinomas showed immunoreactivity for the BH3-only proteins in most neoplastic cells. Conclusion:, Expression of Bid, Bim, Bad, Noxa, and Puma in tooth germs and ameloblastic tumors suggests that the BH3-only proteins have a role in apoptotic cell death of normal and neoplastic odontogenic epithelium. Distinctive expression patterns of these BH3-only proteins in ameloblastoma variants suggest that the BH3-only proteins might be involved in tumor cell differentiation of ameloblastomas. [source]

    Characterization of the Electroanatomic Substrate for Monomorphic Ventricular Tachycardia in Patients with Nonischemic Cardiomyopathy

    HSIA, H.H., et al.: Characterization of the Electroanatomic Substrate for Monomorphic Ventricular Tachycardia in Patients with Nonischemic Cardiomyopathy. Ventricular arrhythmias are common in the setting of nonischemic cardiomyopathy. The etiology for the cardiomyopathy is frequently not identified and the label of "idiopathic" is applied. Interstitial fibrosis with conduction system involvement and associated left bundle branch block characterizes the disease process in some patients and the mechanism for monomorphic ventricular tachycardia is commonly bundle branch reentry. However, most patients with nonischemic cardiomyopathy have VT due to myocardial reentry and demonstrate marked myocardial fibrosis and electrogram abnormalities. Although patient specific, the overall distribution of electroanatomic abnormalities appears to be equal on the endocardium and epicardium. The extent of electrogram abnormalities appears to parallel arrhythmia presentation and/or inducibility. Patients with sustained uniform morphology VT have the most extensive endocardial and epicardial electrogram abnormalities. Magnetic electroanatomic voltage mapping provides a powerful tool to characterize the location and extent of the arrhythmia substrate. Basal left ventricular myocardial involvement, as indexed by the location of contiguous electrogram abnormalities, is common in patients with sustained VT and left ventricular cardiomyopathy. The relatively equal distribution of electrogram abnormalities on the endocardium and epicardium, and the results of mapping and ablation attempts, suggest that critical parts of the reentrant circuit may be epicardial. Unique features of the electroanatomic substrate associated with cardiomyopathy due to Chagas' disease, sarcoidosis, and arrhythmogenic right ventricular dysplasia are also discussed. [source]

    Intrinsic subtype-associated changes in the plasma proteome in breast cancer

    Harikrishna Nakshatri
    Abstract Breast cancers are classified into five intrinsic subtypes: Luminal subtype A, Luminal subtype B, HER2+, Basal, and Normal-like. In this study, we compared the plasma proteome of patients with Luminal A, Luminal B, HER2+, and Basal subtype with plasma from healthy individuals. Protein changes were considered significant if q -value (false discovery rate) was less than 5%. The highest number of changes in the plasma proteome was observed in patients with Luminal type B followed by Basal type breast cancers. The plasma proteome of Luminal A and HER2+ breast cancer patients did not differ significantly from healthy individuals. In Basal breast cancer, a significant number of plasma proteins were downregulated compared with healthy individuals. Acute phase-response proteins ,-glycoprotein orosomucoid 1 and serum amyloid protein P were specifically upregulated in the plasma of Luminal B breast cancer patients, suggesting prevalence of low-grade inflammation. Proteins involved in immune response and free radical scavenging were downregulated in the plasma of Luminal B patients, which is in agreement with defective immune system observed in cancer patients. These results reveal intrinsic subtype specific changes in the plasma proteome that may influence tumor progression as well as the systemic effects of cancer. [source]

    Effects of FSH and LH on Steroid Production by Buffalo (Bubalus bubalis) Granulosa Cells Cultured In Vitro Under Serum-Free Conditions

    M Shanmugam
    Contents The objective of this study was to examine the effects of FSH and LH on oestradiol-17, and progesterone production by buffalo granulosa cells cultured under serum-free conditions. Granulosa cells (3 × 105) from small (,5 mm diameter) follicles were cultured for up to 4 days in 48-well plates coated with 3.3 ,g/cm2 fibronectin in Dulbecco's modified Eagle's medium (DMEM) : nutrient mixture F-12 Ham (1 : 1 ratio) supplemented with 10,7 m androstenedione, 5 ,g/ml human apo-transferrin and 0.1% bovine serum albumin, in the presence or absence of FSH or LH (0, 1, 2, 4, 8, 16, 32 or 64 ng/ml each). Basal oestradiol-17, production by granulosa cells from small follicles reduced (p < 0.01) from days 1 to 2 of culture and became undetectable by day 3 and basal progesterone production increased (p < 0.05) from day 1 through day 4 of the culture. Although there was no effect of FSH on day 1 of the culture, FSH at 2, 4, 8 and 16 ng/ml increased (p < 0.05) oestradiol-17, production by granulosa cells from small follicles on day 2. Progesterone secretion was increased (p < 0.05) by all doses of FSH on all days of culture. All doses of LH had no effect on oestradiol-17, or progesterone production by granulosa cells from small follicles on any day of the culture. The results of this study demonstrate a serum-free culture system for buffalo granulosa cells and stimulatory effect of FSH but not LH on steroid hormone production by buffalo granulosa cells under these conditions. [source]

    ORIGINAL ARTICLE: Effect of Sulfasalazine on Basal and Bacteria-Stimulated Interleukin-8 Production by Endocervical Epithelial Cells

    Morgan R. Peltier
    Problem, Sulfasalazine (SASP) inhibits lipopolysaccharide-induced nuclear-factor kappa B activation and interleukin-8 (IL-8) production by cultured explants of placenta, amnion and choriodecidua. Bacteria-induced IL-8 production in the cervix is a potential mechanism for premature cervical ripening that may lead to preterm birth. Our objective was to determine if SASP inhibits IL-8 production by endocervical cells stimulated with bacterial pathogens associated with preterm birth. Method of study, Human endocervical cells were incubated with 0,1.6 mm SASP and then stimulated with Ureaplasma parvum, Escherichia coli, or Gardnerella vaginalis. Conditioned medium was then harvested and production of IL-8 was quantified by ELISA. Viability of the cells was ascertained at the end of the experiment with the MTT-assay. Results, At the highest concentration tested (1.6 mm), SASP significantly inhibited IL-8 production by cultures stimulated with E. coli (P < 0.001), U. parvum (P < 0.001), and G. vaginalis (P < 0.001). Viability of the cells, however, was significantly reduced by SASP at 0.8 and 1.6 mm in both the presence and absence of bacteria for all experiments. Conclusion, Although high concentrations of SASP inhibit IL-8 production by cultures of endocervical cells stimulated with pathogens associated with preterm birth, this effect may be because of toxicity of the antibiotic on the cells. [source]

    Hsp90 mediates insulin-like growth factor 1 and interleukin-1, signaling in an age-dependent manner in equine articular chondrocytes

    ARTHRITIS & RHEUMATISM, Issue 7 2007
    Amber K. Boehm
    Objective Many metabolic processes in chondrocytes thought to contribute to age-related changes in the extracellular matrix are influenced by known roles of Hsp90. Age-related decreases in the level of Hsp90 have been documented in numerous cell types and could contribute to cartilage degeneration. The aim of this study was to investigate the roles of age and Hsp90 in insulin-like growth factor 1 (IGF-1) and interleukin-1, (IL-1,) signaling in chondrocytes. Methods Levels of Hsp90 messenger RNA (mRNA) and protein, with respect to age, were determined by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. The Hsp90 inhibitor geldanamycin (50 nM, 100 nM, or 500 nM) was used to assess age-related responses to Hsp90 with concurrent IGF-1 or IL-1, stimulation of chondrocytes. Quantitative real-time PCR was used to measure COL2A1 and matrix metalloproteinase 13 (MMP13) gene expression; Western blot analysis was performed to determine the phosphorylation status of p42/44 and Akt/protein kinase B. Results The effects of Hsp90 inhibition with geldanamycin were concentration dependent. Inhibition of Hsp90 with 100 nM or 500 nM geldanamycin blocked IGF-1,induced cell proliferation, Akt and p42/44 activation, and COL2A1 expression. Basal and IL-1,,induced up-regulation of MMP13 mRNA was blocked by all concentrations of geldanamycin tested. Gain-of-function assays with Hsp90 resulted in increased expression of MMP13 mRNA. Conclusion These results suggest that Hsp90 is involved in opposing signaling pathways of cartilage homeostasis, and that catabolic responses are more sensitive to Hsp90 inhibition than are anabolic responses. Further studies are needed to determine the role of Hsp90 inhibition in osteoarthritis in order to assess its potential as a therapeutic target. [source]

    Protein kinase C modulation of the regulation of sarcoplasmic reticular function by protein kinase A-mediated phospholamban phosphorylation in diabetic rats

    Satoko Watanuki
    The goal of this study was to elucidate the possible mechanisms by which protein kinase A (PKA)-mediated regulation of the sarcoplasmic reticulum (SR) via phospholambin protein phosphorylation is functionally impaired in streptozotocin-induced diabetic rats. Phospholamban (PLB) protein and mRNA levels were 1.3-fold higher in diabetic than in control hearts, while protein expression of cardiac SR Ca2+ -ATPase (SERCA2a) was unchanged. Basal and isoprenaline-stimulated phosphorylation of PLB at Ser16 or Thr17 was unchanged in diabetic hearts. However, stronger immunoreactivity was observed at the basal level in diabetic hearts when antiphosphoserine antibody was used. Basal 32P incorporation into PLB was significantly higher in diabetic than in control SR vesicles, but the extent of the PKA-mediated increase in PLB phosphorylation was the same in the two groups of vesicles. Stimulation of Ca2+ uptake by PKA-catalyzed PLB phosphorylation was weaker in diabetic than in control SR vesicles. The PKA-induced increase in Ca2+ uptake was attenuated when control SR vesicles were preincubated with protein kinase C (PKC). PKC activities were increased by more than two-fold in the membranous fractions from diabetic hearts in comparison with control values, regardless of whether Ca2+ was present. This was associated with increases in the protein content of PKC,, PKC,, PKC,, and PKC, in diabetic membranous fractions. The changes observed in diabetic rats were reversed by insulin therapy. These results suggest that PKA-dependent phosphorylation may incompletely counteract the function of PLB as an inhibitor of SERCA2a activity in diabetes in which PKC expression and activity are enhanced. British Journal of Pharmacology (2004) 141, 347,359. doi:10.1038/sj.bjp.0705455 [source]

    Comparison of three doses of leuprolide acetate in the treatment of central precocious puberty: preliminary results

    Verónica Mericq
    Summary Objective, Depot luteinizing-hormone releasing hormone (LHRH) agonist have been widely used for the treatment of central precocious puberty (CPP), but the optimal doses to obtain hormonal suppression are still unknown, especially in patients with higher weights. The goal of our study was to compare the efficacy of three leuprolide acetate (LA) preparations, suppressing gonadotropin secretion in patients with CPP. Design, In an open 12-month protocol, we evaluated LA 7·5 mg/month, 11·25 and 22·5 every 3 months. Patients, Fourteen girls with CPP and weights over 30 kg. Measurements: Clinical, radiological and laboratory follow-up: GnRH test plus LH, FSH 40 min post analogue was performed periodically. Results, Pretreatment basal and LHRH stimulated LH levels between groups were not different. Basal and LHRH stimulated LH levels decreased significantly between baseline and from 3 up to 12 months of therapy in all groups (P = 0·001). GnRH stimulated LH peak <2 IU/l, the main efficacy criterion was met in 80, 75 and 100% of the children at 6 months in the 7·5, 11·25, 22·5 mg doses respectively. By 12 months, 100% of patients had LH suppressed to <2 IU/l. Conclusions These results affirm that 3-month injections may be a satisfactory alternative for the therapy of children with CPP to avoid monthly injections. In addition, suppression of LH occurs sooner in the 3-month 22·5 mg LA dose compared to the 3-month 11·5 mg; therefore, adequate dosing may be important for optimal outcome. Further investigation is needed in more patients over 30 kg, with longer treatment duration, and ultimately final height consideration. [source]

    Aldosterone synthase gene variation and adrenocortical response to sodium status, angiotensin II and ACTH in normal male subjects

    Brian Kennon
    Summary objective, Aldosterone synthase, a key enzyme in the terminal steps of aldosterone synthesis, is encoded by the CYP11B2 gene. A polymorphism in the 5, coding region of this gene (,344 C/T) is associated with hypertension, particularly with elevation of the aldosterone to renin ratio. A second polymorphism (a conversion in intron 2 to resemble that of the neighbouring 11,-hydroxylase (CYP11B1) gene) is found in close linkage dysequilibrium with the variant at ,344 C/T. The mechanism by which these variants predispose to cardiovascular disease and the precise intermediate phenotype associated with them remains speculative. design, We performed a focused physiological study in normal volunteers stratified by CYP11B2 genotype. patients, Twenty-three subjects homozygous for the T allele and 21 homozygous for the C allele of the ,344 C/T polymorphism of CYP11B2 were studied. measurements, Basal and angiotensin II stimulated plasma and 24-h urinary steroid excretion during low (60 mmol/day) and high (160 mmol/day) sodium intake and plasma steroids after ACTH stimulation were measured. results, No influence of polymorphic variation on basal or stimulated plasma cortisol or aldosterone or other plasma steroid concentrations during either dietary phase was seen. However, excretion of tetrahydro-11-deoxycortisol (the urinary metabolite of 11-deoxycortisol), which is the precursor of cortisol) was increased in TT subjects during sodium restriction, consistent with impairment of zona fasciculata 11,-hydroxylation. conclusions, We conclude that this polymorphism has no major influence on normal zona glomerulosa function but is associated with a change in 11,-hydroxylation in the zona fasciculata. The mechanism remains uncertain, but alteration of 11-deoxycortisol levels without change in cortisol suggests altered efficiency of 11,-hydroxylation. In the long term, this may lead to a minor but chronic increase in ACTH drive to the gland, which may have consequences for steroid synthesis and predispose to the risk of cardiovascular disease. [source]