摘要:

SUMMARY1. During fetal life the lung develops as a liquid‐filled organ. This liquid is produced by the fetal lung and leaves via the trachea from where it is either swallowed or enters the amniotic sac. Fetal lung liquid plays a crucial role in the growth and development of the lungs by maintaining them in a distended state. It is now recognized that the retention of liquid within the future airways is required to maintain the lungs at an appropriate level of expansion in order to stimulate their growth. Indeed, it is likely that most, if not all, of the conditions and malformations that lead to inadequate growth of the fetal lung do so by reducing the volume of lung liquid and hence the degree of lung expansion.2. The volume of fetal lung liquid is principally regulated by the resistance to lung liquid efflux through the fetal upper airway and by the presence of diaphragmatic activity associated with fetal breathing movements (FBM). During non‐breathing periods, the relatively high resistance offered by the upper airway to the efflux of lung liquid opposes the loss of liquid from the lung, thereby maintaining fetal lung expansion. During episodes of FBM, when the larynx is actively dilated and the resistance to lung liquid efflux is reduced, lung liquid leaves the lungs at an increased rate. However, selective inhibition of diaphragmatic muscle activity in the foetus leads to a reduction in lung liquid volume, rather than an increase. This finding indicates that during periods of FBM, rhythmical contractions of the diaphragm retard the loss of lung liquid and help to maintain lung expansion when the upper airway resistance is reduced. It is now apparent that the maintenance of lung expansion by FBM is the basis for their role in promoting fetal lung growth.3. Successful transition from intra‐uterine to extra‐uterine life is dependent upon the clearance of liquid from the fetal lungs at the time of birth so that the lungs may effectively function as an organ of gas exchange. It is generally considered that, at the time of birth, increased circulating levels of the stress‐related hormones, adrenaline and arginine vasopressin (AVP), play an important role in suppressing fetal lung liquid secretion and stimulating its reabsorption. The ability of adrenaline and AVP to perform this role, however, is dependent upon the exposure of the lung to increasing levels of gluco‐corticoids late in gestation. Thus, the maturation of the fetal lung, induced by the preparturient increase in circulating cortisol levels, not only includes changes in lung compliance and surfactant synthesis, but also includes an increased ability of the lung to reabsorb liquid.4. Although it is well recognized that fetal lung growth is critically determined by the degree to which the lungs are expanded with lung liquid, the mechanisms underlying this relationship are poorly understood and are likely to be complex. The increase in fetal lung growth induced by experimentally increasing the degree of fetal lung expansion is very rapid and most probably results from an acceleration of the processes involved in normal fetal lung growth. The accelerated growth response is most likely mediated by a multitude of growth factors which act on different processes within individual cells and on different cell types within the lung to produce a coordinated growth response. Because increased fetal lung expansion rapidly increases the growth of hypoplastic fetal lungs, treatments leading to increased lung expansionin utemhave the potential to be used to treat lung hypoplasia in human foetuses before the lungs are required to function as the sole organ of gas exchange. Further experimentation is required to determine whether such lungs have the ability to function effectively

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01988.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. The effects of orally administered aqueous lyophilized extract of the leaves ofRhazya stricta(2, 4&8 g/kg) on aspects of nervous system function were investigated in mice.2. In three antinociceptive tests (hot plate, abdominal constriction, and warm water tail flick tests), the extract exhibited dose‐dependent and significant antinociceptive activity. Naloxone was ineffective in antagonizing the analgesic effect ofRhazya strictaon tail‐flick and abdominal constriction tests, possibly indicating that this effect occurs via non‐opiate pathways.3. Pretreatment of mice with the xenobiotic metabolizing enzymes inhibitor cimetidine (50 mg/kg) did not significantly alter the antinociceptive action of the extract, indicating that the effect is probably due to the parent compound(s) present in the extract and not to metabolites thereof.4.R hazy a strictaproduced dose‐dependent sedation, decreased motor activity, and impaired motor control. Time spent on a rotarod treadmill was significantly decreased after treatment with the extract.5.R hazy a strictaextract (8 g/kg) produced a degree of sedation comparable to that produced by diazepam (5–10 mg/kg), and also significantly increased the reaction time of the tail‐flick test, an action which was not produced by diazepam.6. Administration ofR. strictaextract potentiated pento‐barbitone sleeping time in a dose dependent manner. The extract did not significantly antagonize picrotoxin induced convulsions. The extract (4 and 8 g/kg) significantly decreased the rectal temperature of normothermic and hyperthermic mice.7. Pretreatment withR. strictaextract (8 g/kg) completely prevented the occurrence of aggressive behaviour in male mice.8. It is concluded that the crude extract ofR. strictahas central nervous system depressa

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01989.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. The hypothesis that endogenous adenosine could play a role in the haemodynamic response to l‐arginine is investigated.2. The study has been divided into two parts. The first part was a single blind, randomized, placebo‐controlled study in which L‐arginine i.v. infusion (0.07 mmol/kg per min) in five healthy volunteers caused a significant fall in systolic (‐14.2%, from 129.0 ± 8.2 to 110.6 ± 8.5 mmHg;F= 62.89, P<0.0l), diastolic (‐16%, from 80.0 ± 7.9 to 67.2 ± 7.0 mmHg;F= 18.97, P<0.0l) and mean (‐15.5%, from 96.4 ± 6.7 to 81.4 ± 6.5 mmHg;F= 28.78,P<0.01) arterial blood pressure, with a concomitant increase of plasma adenosine concentration (from 244.0 ± 32.2 to 637.0 ± 43.4 nmol/L;F= 79.3 P<10.01). Maximal effects were obtained at the end of L‐arginine infusion: haemodynamic parameters returned to basal values in about 30 min while adenosine concentrations normalized in about 15 min. Saline infusion had no effect on these parameters.3. In the second study the effect of L‐arginine i.v. infusion on arterial blood pressure, lower limb blood flow and plasma adenosine, before and after theophylline treatment (1000 mg/day for 3 days, p.o.) was examined. In 10 healthy volunteers the i.v. infusion of l‐arginine (0.07 mmol/kg per min) was followed by the same haemodynamic changes as reported above and by a Significant increase in lower limb blood flow (+ 36.7%, from 2.18 ± 0.40 to 2.98 ± 0.71mL/min/lOOmL;t = 4.61, P<0.01). Pretreatment with theophylline, an adenosine‐receptor antagonist, did not affect basal values of arterial pressure, lower limb blood flow and adenosine concentration. The pretreatment with theophylline reduced maximal decrease in systolic pressure (‐ 8.2vs‐15%), in mean pressure (‐ 9.9 vs ‐13.7%) and maximal increase in lower limb blood flow (+19 vs + 37%) caused by i.v. infusion of l‐arginine (0.07 mmol/kg per rnin). Such a treatment allowed a progressive restoration of basal blood pressure values and of blood flow, during the second half of l‐arginine infusion. This observation was confirmed by the analysis of the area under the curves (AUC). A significant difference in AUC values before and after treatment was obtained for systolic pressure (t = 8.25,P

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01990.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. The effects of cyclosporine A (CyA) treatment on liver morphology, bile flow and biliary secretion of bile acid, cholesterol and phospholipid and some plasma biochemical indicators of liver function were examined.2. Wistar rats were treated i.p. with 10 or 20 mg of CyA/kg per day for 1, 2, 3 or 4 weeks.3. Treatment increased bile acid and bilirubin plasma concentration. Bile flow and biliary secretion of bile acid, cholesterol and phospholipid were reduced in CyA‐treated animals.4. All these effecs of the drug appeared at 1 week after the start of treatment and were enhanced during prolonged treatment. Cyclosporine A‐induced cholestasis was due to a decrease in both the bile acid‐dependent and ‐independent fractions of bile flow.5. The reduction in cholesterol and phospholipid biliary output may be secondary to the inhibition of the hepatobiliary flux of bile acid; however, perturbations in the removal of lipids from the canalicular membrane as well as intracanalicular interaction between CyA and lipid vesicles/micelles could also be i

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01991.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. Lipid peroxidation can occur in the presence of a cellular antioxidant‐oxidant imbalance, but the role of lipid peroxides in cholestasis is not well understood.2. This study was undertaken in order to: (i) evaluate the behaviour of a product of lipid peroxidation (thiobarbituric acid‐reactive species), and of an important antioxidant tripeptide, reduced glutathione, in the course of experimental extrahepatic cholestasis; and (ii) ascertain whether there was a link between this aspect and the alterations in liver morphology.3. Forty‐five male Sprague‐Dawley rats (250–300 g) were double bile duct ligated and followed from 1 to 28 days. At the end of each experimental period, blood and liver samples were collected for thiobarbituric acid‐reactive species and glutathione determinations.4. Bile duct ligated rats showed a marked increase in liver weight which was related to cholestasis duration and to some anatomical alterations such as bile duct proliferation and dilation and liver fibrosis (periportal, perivenular, perineoductular and parenchymal).5. An increase in serum lipid peroxidation was also observed but this was not linked to hepatic thiobarbiturie acid‐reactive species. Erythrocyte and hepatic glutathione decreased in relation to cholestasis duration. Serum lipid peroxides and erythrocyte glutathione were correlated with liver cell necrosis.6. In conclusion, experimental extrahepatic cholestasis determines bile duct proliferation and fibrosis, the degree of which is directly related to the duration of cholestasis itself and to liver cell necrotic phenomena. Furthermore, extrahepatic cholestasis is associated with increased lipid peroxide formation and with a depletion of reduced glutathione both in the liver and in the erythrocytes. The alteration in the oxidative balance may be a contributory factor in necrotic liver c

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01992.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. We investigated the mechanism of decreased transmucosal calcium transport in the gut of the diabetic rat by comparing calcium uptake by brush border membrane vesicles from control and streptozotocin diabetic rats at 5 days. Brush border calcium uptake consists of saturable and non‐saturable components. Saturable uptake is mediated by a specific mobile carrier mechanism and is defined by Vmax(saturable uptake of calcium at infinite medium calcium concentration) and KT(calcium concentration at Vmax/2). Non‐saturable uptake is defined by kD(rate constant for non‐saturable uptake per unit calcium concentration), and comprises both diffusive and surface binding components of calcium uptake.2. We found both saturable and non‐saturable calcium uptake to be decreased (P<0.05) in diabetes. Comparing control and diabetic, Vmaxwas 247 compared to 152 (data are pmol/mg protein per 3 s); kDwas 285 compared to 172 (data are pmol/mg protein per 3 s at 1 mmol/L calcium); and KT(mmol/L) did not differ between groups, 0.070 compared to 0.057.3. The decreased Vmaxin the setting of unchanged Ktin vesicles from diabetics is consistent with decreased calcium transporter specific activity, rather than with altered transporter function.4. Since (i) Vmaxis decreased by vitamin D deficiency in the normal rat, and (ii) circulating 1α,25‐dihydroxycholecalciferol is decreased in the diabetic rat, decreased Vmaxin the diabetic may be related to the low 1α,25‐dihydroxycholecalciferol.5. Since vitamin D deficiency does not alter kDin the normal rat, the decreased kDin diabetes may be an effect of diabetes on the membrane. In conclusion, decreased transmucosal calcium transport in diabetes is, at least in part, the consequence of decreased brush

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01993.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01994.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. A diverse array of stressful stimuli induces changes in gene expression via post‐translational modification of transcription factors.2. Study of activator protein (AP‐1) transcription factor regulation has revealed a novel family of protein‐serine kinases. Molecular cloning and expression of these proteins have demonstrated their specific activation by stress stimuli such as UV irradiation, heat, ischaemia/reperfusion and metabolic toxins.3. Dissection of the regulation of the stress‐activated protein kinases has revealed a similar but distinct mechanism to mitogen‐activated protein kinases suggesting that cellular responses to stress may partially overlap with normal growth responses and have common nuclea

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01995.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. Current opinions on the mechanisms for glutamate‐mediated neurotoxicity are reviewed. The protective role of astrocytic high‐affinity glutamate transport is also discussed.2. Low‐density seeding of primary astrocytes from rat hemispheres was found to result in the development of reactive‐like astrocytes. Typical glial signs of amyotrophic lateral sclerosis (ALS) could not be induced in astrocyte cultures by serum from ALS‐patients.3. Glutamate (100 μmol/L) was found to induce an increase in respiratory activity in primary cultures of astrocytes. This stimulation appeared to be related to the co‐transport of Na2+with glutamate and a resulting activation of Na2+/K+‐ATPase. Both basal respiration and glutamate‐stimulated oxygen consumption was inhibited by organic solvents.4. Preliminary results show that heavy metals cause an increase in the mitochondrial DNA content at concentrations that have no effect on growth rate or morphology in a glial cell line. This increase was accompanied by an inhibition of oxygen consumption and an increased production of lactate at unal

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01996.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY1. The neuronal release of acetylcholine (ACh) and its autoregulation by neuromodulators, substance P (SP) and methionine enkephalin (MEK), have been studied using super‐fused rodent cerebral slices. Nicotine exerts significant effects on autoregulation of ACh release, which may have toxicological implications.2. Positive and negative feedback systems have been postulated for autoregulation of ACh release. The components of the positive feedback system include a muscarinic (Ms) receptor, SP, and activation of Ca2+influx. Low levels of ACh in the biophase of the cholinergic synaptic gap may trigger the positive feedback system, and high levels of ACh may trigger the negative feedback system.3. There are also neuronal pathways for direct reciprocal regulations of SP and MEK.4. Low concentrations of nicotine triggers the release of ACh followed by MEK and SP. Release of SP causes neurogenic inflammation.5. Nicotine and its metabolite, cotinine, activate platelet activating factor (PAF)‐hydrolase and thereby enhance the turnover rate of PAF. This effect may contribute to tobacco‐induced arterial thrombosis in peripheral and central nervous sy

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1995.tb01997.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY