摘要:

SUMMARY1. We investigated the effect of SA3443, a novel cyclic disulfide compound, on alpha‐naphthyl isothiocyanate (ANIT)‐induced intrahepatic cholestasis in rats.2. SA3443 given orally at doses of 100 or 300 mg/kg, three times at 4h intervals, dosedependently suppressed the elevation of serum total bilirubin, alkaline phosphatase activity and transaminase activities induced by administration of ANIT (80 mg/kg) 3 h before the second dosages of SA3443.3. SA3443 also significantly inhibited the reduction of bile flow in the ANIT‐treated rats.4. These findings indicated that SA3443 had a markedly inhibitory effect on ANIT‐induced intrahepatic cholestasis

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01739.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. Computerized postural sway measurement systems have been used recently in human physiology and pharmacology for determining postural stability, but their applicability for the assessment of the effects of exposure to neurotoxic agents is lacking.2. We have examined the feasibility of using a computerized postural sway measurement system to assess the postural sway parameters of manganese exposed workers compared with a control group.3. Sway parameter data were collected using a kislter multicomponent measuring platform (Type 9281B) connected to vicon motion analysis system for 13 exposed and 16 control subjects.4. Significant differences in several of the sway parameters (Px, Py—mean distance (mm), from the centre of the platform along theX‐axis [anterior‐posterior movement] andY‐axis [lateral movement], respectively) between the exposed and control groups were observed even after adjustment for possible confounders. Computerized postural sway measurement system may be a useful method of assessing workers exposed to neurotoxic agents affecting

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01740.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. The aim of this study was to determine whether the brain contains an alternative ligand for angiotensin II (AII) receptors.2. A radioreceptor assay based upon bovine cerebellar membranes (Type 2 AII receptors) was used to monitor the partial purification of an AII‐like material from sheep hypothalami.3. This material displaces125I‐[Sar1, Ala8I‐AII from both type 1 (rat adrenal capsuIar membranes) and Type 2 AII receptors in a manner parallel to that of AIL It has a size of ∼30000 Da, is strongly cationic, is stable to boiling but is destroyed by trypsin. It is not recognized by AII antisera.4. These data provide direct evidence for a non‐angiotensin endogenous ligand for brain AII receptors. This novel ligand may play a role in the regulation of blood pressure and other actions mediated by brain AII

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01741.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. Red blood cells can store glucose and may thus participate in blood glucose homeostasis. We investigated if a defect in this process exists in non‐insulin dependent diabetes (NIDD).2. Blood was obtained in fasting conditions from 10 normal and 10 newly diagnosed NIDD patients (before and after 4 weeks Metformin therapy). Washed erythrocytes were resuspended in media containing various glucose concentrations (4.4, 6.6, 8.8 and 13.2 mmol/L). Total glucose uptake was calculated as the sum of the measurements of lactate as well as free glucose, the latter being determined before and after addition of amyloglucosidase to the pellet.3. Cells from diabetics showed a pronounced reduction in glucose uptake, particularly in their capacity to store glucose as glycogen (reactive to amyloglucosidase). Metformin treatment almost normalized glycogen levels, whereas lactate declined concomitantly in the pellet.4. Our data demonstrate that a defect in glucose uptake exists in erythrocytes from NIDD patients, affecting both free and stored glucose, and that this defect is reversed by Metformin treatment, indicating that this drug can increase glycogen levels even in insulin‐insensitive cells.5. Thus, in view of their total mass, erythrocytes may be important in the impaired glucose homeostasis in NIDD, in particular in marked hyperglycaemia such as after a m

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01742.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. The effects of intravenous infusions of arginine vasopressin (AVP), parathyroid hormone‐related protein (PTHrP) and AVP + PTHrP on renal function in intact ovine foetuses at 100–125 days of gestation were examined.2. A low dose of AVP (5.5 ± 0.9 pmol/h) increased plasma AVP concentrations from 0.6 pmol/L to 2.1 ± 0.4 pmol/L (mean ± s.e.m;n= 8). This dose caused a significant reduction in free water clearance (CH2O;P<0.001), without any significant change in fetal arterial blood pressure, glomerular filtration rate (GFR), or the urinary excretion rates of sodium, calcium or 3', 5'‐cyclic adenosine monophosphate (CAMP).3. Infusions of PTHrP (1 nmol/h), with or without 1 nmol bolus dose, significantly increased (P<0.05) urine osmolality (Uosm), but did not synergize with AVP in reducing CH2O.4. It is concluded that AVP and PTHrP do not act synergistically on the kidney of the intact ovin

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01743.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. We investigated the effects of new xanthine derivatives, 1‐methyl‐3‐propyl xanthine (MPX) and 1,3‐dipropyl xanthine (DPX), and several other xanthine derivatives on N‐formyl‐methionyl‐leucyl‐phenylalanine‐induced superoxide and lysozyme release from human polymorphonuclear leucocytes (PMN).2. MPX and DPX at low concentrations (10−8‐10−9mol/L) inhibited superoxide release from PMN by a maximum of 31.2 ± 10.6% and 49.8 ± 10.4% (mean ± s.d.), respectively, and 10−3mol/L concentrations completely inhibited the release reactions (4.8 ± 1.2 and 7.6 ± 2.5% of control level). At 10−5mol/ L, however, the inhibition did not occur (99.9 ± 7.3 and 110.2 ± 15.8% of control level). When PMN was pre‐incubated with adenosine deaminase (ADA, 0.1 U/mL), superoxide release from PMN was inhibited in a dose‐dependent manner by MPX and DPX and the interruption of the inhibition at 10−5mol/L was not observed.3. Lysozyme release from PMN was inhibited by MPX at low concentrations (10−7‐10−6mol/L) and high concentrations (10−3mol/L). However 10−4mol/L of MPX facilitated the release (23.7 ± 27.0%). When pretreated with ADA (0.1 U/mL), MPX suppressed lysozyme release in a dose‐dependent manner and the facilitation of the release at 10−4mol/L was not observed.4. When comparing effects of some other xanthine derivatives on superoxide release, the interruption of the inhibition of superoxide release at 10−5mol/L was commonly observed among xanthine derivatives with adenosine A2antagonism.5. The results suggest that adenosine A2antagonism of xanthine derivatives may interfere with their anti‐inflamma

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01744.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. Free Ca2+([Ca2+]i) and Mg2+([Mg2+]i) were measured in peripheral lymphocytes from stroke‐prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar‐Kyoto rats (WKY) at the age of 5, 7 and 17 weeks, from various antihypertensive agents‐treated SHRSP, and from secondary hypertensive WKY.2. At the age of 5 weeks, no difference was observed in systolic blood pressure (SBP), or lymphocyte [Ca2+]i and [Mg2+]i between SHRSP and WKY. At the age of 7 or 17 weeks, SBP and [Ca2+]i of SHRSP were significantly higher than in WKY, and at the age of 17 weeks, [Mg2+]i of SHRSP was significantly lower than in WKY. Further, [Ca2+]i or [Mg2+]i was positively or negatively correlated to SBP, and [Mg2+]i was negatively correlated to [Ca2+]i.3. SBP of SHRSP fell significantly after antihypertensive treatment with calcium antagonist, angiotensin‐converting enzyme (ACE) inhibitor or hydralazine for 40 days. [Ca2+]i was significantly lower in calcium antagonist and hydralazine groups, and tended to be low in ACE inhibitor group. These four groups showed no difference in [Mg2+]i.4. After 40‐day administration ofNG‐nitro‐l‐arginine (l‐NNA), WKY developed severe hypertension, but there were no significant differences in lymphocyte [Ca2+]i and [Mg2+]i between the l‐NNA treated and non‐treated groups.5. These results suggested that increased lymphocyte [Ca2+]i and decreased [Mg2+]i observed in SHRSP are not only secondary to hypertension but possibly related to a basic genetic abnormality of div

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01745.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. This study aimed to characterize the effect of nicorandil (NC) on myocardial stunning and the role of ATP‐sensitive K+(Katp) channel opening property in its cardioprotective action.2. In open‐chest anaesthetized rabbits, myocardial stunning was induced by 10 min of coronary occlusion followed by 30 min of reperfusion. As an index of regional contractile function, systolic thickening fraction (TF) was measured by an epicardial Doppler sensor. The doses of NC (10 μg/kg per min) and nitroglycerin (TNG) (1 μg/kg per min) were selected not to lower the systemic blood pressure significantly.3. In the untreated controls, TF at 30 min after reperfusion was 46.4 ± 2.9% of the baseline value, indicating myocardial stunning. Both NC and TNG significantly improved post‐ischaemic recovery of TF when administered during the pre‐ischaemic and post‐ischaemic periods (TF = 68.2 ± 6.4%, 64.7 ± 2.3%, respectively). However, when their infusion was restricted to a pre‐ischaemic 10 min period, TF recovery was improved by NC, but not by TNG (63.4 ± 7.9%, 40.9 ± 6.2%, respectively).4. Pretreatment with glibenclamide (GL; 0.3 mg/kg) did not influence the recovery of TF after the 10 rnin ischaemia (TF = 52.4 ± 3.9% at 30 min after reperfusion). However, after the GL injection, a cardioprotective effect from nicorandil pretreatment was not detected (TF = 51.3 ± 1.7%).5. These results suggest that nicorandil protects the myocardium against stunning by opening the Katpchannel when it is given before ischaemia, and that the nitrate property of nicorandil may also play a role during the reperfusion period in attenuation of post‐ischaemic c

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01746.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SUMMARY1. The human placental lobule, perfused with a constant flow (5 mL/min) of Krebs’ solution after delivery at term, released into the fetal perfusate a digoxin‐like substance, as measured by a fluorescence polarization immunoassay.2. Initially the venous concentration was 360 ± 66.7 pmol/ L digoxin equivalents. This level did not change significantly during fetal vasoconstriction induced by prostaglandinF2αinfusion and persisted for the duration of the experiment (1.5–2h).3. Infusion into the fetal circulation of Fab fragments of sheep antibodies to digoxin caused vasodilatation, indicated by a fall in perfusion pressure.4. Thus a digoxin‐like immunoreactive substance, previously reported to be present in the placenta, is released into the fetal circulation and may play a role in placental control of fetal vasc

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1993.tb01747.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY