Aspirin treatment of the low-dose-endotoxin-treated pregnant rat: pathophysiologic and immunohistologic aspects

In the present study, we evaluated the effect of low-dose aspirin (acetylsalicylic acid (ASA); 1.0 mg/kg daily) on blood pressure, albumin excretion, glomerular fibrinogen deposits, and glomerular (basement) membrane-bound adenosine diphosphatase (ecto-ADPase) activity, as well as on glomerular inflammation in pregnant rats infused with low-dose endotoxin (1.0 mg/kg). Rats (day 14 of pregnancy) were infused with endotoxin (ET rats) or saline (control rats) and received ASA in their drinking water. These rats were compared with non-ASA-treated rats. Blood pressure and albumin excretion were measured from day 15 to day 21, and glomerular fibrinogen and ecto-ADPase activity were measured at day 21. Glomerular inflammation was evaluated at various times after the start of the infusion. The results show that treatment with ASA had a significant beneficial effect on hypertension and inflammation induced by endotoxin in pregnant rats, whereas it reduced albumin excretion and glomerular fibrinogen deposits in some of the rats.     

Prevention of bone loss by percutaneous estradiol implants in ovariectomized rats

This study was conducted to investigate whether hydroxyapatite (HAP) is appropriate as a percutaneous drug carrier for estradiol (E2) for the suppression of bone loss. Ten-week-old female Sprague-Dawley rats were subjected either to bilateral ovariectomy (OVX) or to sham surgery (control). Ovariectomized rats were implanted percutaneously with E2-HAP disks containing low, medium or high doses of estradiol (50, 250, or 500 micrograms E2/rat, respectively). Ovariectomized rats without implant and OVX rats implanted only with HAP served as additional controls. All rats were sacrificed 90 days after surgery. At the end of the experiment, bone mineral density of the lumbar spine was measured by dual energy X-ray absorption, and serum E2 was assayed by radioimmunoassay. The bone mineral density of OVX and HAP-treated OVX rats decreased by 18% compared to sham surgery rats, but decreased by only 13, 7, and 3% in rats treated with 50, 250, and 500 micrograms E2/rat, respectively. The in vitro release of E2 from E2-HAP devices was determined by an HPLC method. Estradiol release from the HAP devices followed almost a zero-order kinetics. Estradiol remained intact in E2-HAP implants for up to six months when stored at 5, 25, and 40 degrees C. This study indicates that E2-HAP implants are effective in suppressing bone loss in the spine of OVX rats in a dose-dependent manner.     

How should the efficacy of prenatal care be tested in twin gestations?

The aim of the present study was to test the hypothesis that the decreased renal tubular reabsorption of calcium observed in estrogen deficiency is associated with a local regulation of either PTHrP or PTH/PTHrP receptor genes in the kidney. Rats were randomly sham-operated (S) or ovariectomized receiving either vehicle (OVX) or 4 microg E2/kg/day (OVX+E4) or 40 microg E2/kg/d (OVX+E40) during 14 days using alzet minipumps. Plasma PTH and calcium levels were lower in untreated OVX animals than in all other groups (P < 0.01). Plasma PTH was higher in OVX+E40 than in OVX+E4 (P < 0.05). PTHrP mRNA expression in the kidney was unaffected by ovariectomy but was increased in OVX+E40 (0.984 +/- 0.452 for PTHrP/GAPDH mRNAs expression vs. 0.213 +/- 0.078 in sham, P < 0.01). PTH/PTHrP receptor mRNA expression and the cAMP response of renal membranes to PTH were unaffected by ovariectomy and estrogen substitution. In conclusion, renal PTHrP and PTH/PTHrP receptor mRNAs are not modified by ovariectomy. However, 17beta-estradiol increases renal expression of PTHrP mRNA without evident changes in its receptor expression and function. This may help to explain the pharmacological action of estrogen in the kidney, especially how it prevents the renal leak of calcium in postmenopausal women.     

Influence of ovariectomy on bone metabolism in very old rats

Twenty-five 30-month-old Lou rats fed a diet (6 g/100 g BW/day) containing 0.9% Ca and 0.8% Pi were divided into five groups. Four groups were surgically ovariectomized. From day 2 until day 29 after ovariectomy, they were S.C. injected either with 17 beta estradiol (E2; 10 micrograms/kg BW/48 hours) or progesterone (P; 140 micrograms/kg BW/48 hours), or 17 beta estradiol + progesterone (E2P) at the same doses, or solvent alone (OVX). The fifth group was sham operated (SH) and injected with solvent. Urine was collected in metabolic cages from day 24 to 29 after ovx, and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) excretion (markers of bone resorption) was measured by HPLC. All animals were killed 30 days after ovariectomy. Serum was then collected for measurement of osteocalcin (OC), alkaline phosphatase (ALP), parathyroid hormone (PTH), and calcitonin (CT). At necropsy, the success of ovariectomy was checked by marked atrophy of the uterine horns. Left and right femur were harvested for densitometric and mineral analysis, respectively. Ovariectomy had no significant effect upon plasma calcium and PTH concentrations. E2 or E2P treatment significantly increased plasma PTH and calcitonin concentrations. Plasma OC concentrations and ALP were not different in any of the groups. In contrast, urinary excretion of PYD and DPD was higher in OVX than in SH rats. Bone mineral density (BMD) of the distal femur was decreased by OVX, but was not different in the E2P and SH groups. A similar pattern was observed for the mineral or Ca content of whole femur. Thus, OVX decreased BMD and bone mineral content (BMC) in very old female rats. Plasma OC concentration and ALP activity failed to demonstrate any significant effect of OVX, whereas PYD and DPD were elevated. These results suggest that bone resorption is increased in OVX rats, even when supplemented with E2 or P alone. However, no significant difference was observed between SH and OVX rats treated with supplementation of both E2 and P. Thus, in very old rats, a combination of E2 and P is much more effective than E2 or P alone to prevent bone loss following ovariectomy.     

Effects of the bisphosphonate tiludronate on bone resorption, calcium balance, and bone mineral density

Bone resorption inhibitors, such as bisphosphonates, are potentially useful in treatments aimed at increasing bone mass. Among bisphosphonates, tiludronate has proven efficacious in preventing bone loss in postmenopausal women. However, it is not clearly established whether bisphosphonates are more potent when given intermittently or continuously. We investigated the effects of tiludronate on (1) retinoid-stimulated bone resorption in thyroparathyroidectomized rats, (2) calcium balance in intact rats, and (3) bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry at the levels of the lumbar spine, tail, and tibia in 6-month-old rats made osteoporotic by ovariectomy (OVX), in which an intermittent cyclic schedule of treatment was compared to continuous administration. Tiludronate induced a dose-dependent decrease in retinoid-stimulated bone resorption. It increased the intestinal absorption and body retention of calcium. In OVX rats it caused a time- and dose-dependent increase in BMD at the level of the three investigated sites, the effects being maintained for at least 8 weeks after the end of therapy. Continuous and intermittent cyclic regimens appeared to induce similar increases in BMD. These results indicate that tiludronate is efficacious in decreasing bone resorption and increasing calcium balance and bone mineral density in rats.     

Influence of aging on cortical and trabecular bone response to estradiol treatment in ovariectomized rats

Three groups (n = 15/group) of 6-, 12- and 30-month-old (mature, old and senescent animals, respectively) female Wistar rats on a diet (6 g/100 g BW/ day) containing 0.8% calcium and 0.8% inorganic phosphorus were studied. Within each group, 10 rats were ovariectomized surgically and 5 injected s.c. with 17 beta-estradiol (E rats, 10 micrograms/kg BW/48 h) and 5 with solvent alone (OVX rats) from day 2 until day 60 after ovariectomy. Five other rats were sham-operated (SH rats) and received solvent only. All rats were killed by exsanguination 60 days after ovariectomy. Neither ovariectomy nor estradiol treatment had a significant effect upon tibial mechanical properties in 6-, 12- and 30-month-old animals. Bone mineral density (BMD) and bone mineral content (BMC) of the distal femur and BMC of the whole femur were decreased by ovariectomy in 6- and 12-month-old rats, but were not different in the SH and E groups. In senescent animals, in which the lowest BMD and BMC were measured, estradiol treatment was more effective in increasing these parameters than in adult and old rats. Image analysis of the distal femoral diaphysis showed that estradiol treatment prevented trabecular bone loss induced by senescence and/or ovariectomy. In each group, urinary deoxypyridinoline excretion and plasma osteocalcin concentration were higher in the OVX animals than in the controls, consistent with increased bone turnover in the estrogen-deficient state. Both biochemical turnover markers were reduced in the estrogen-treated groups. These results indicate that 17 beta-estradiol is particularly effective at preventing high-turnover-induced osteopenia in 30-month-old animals.     

Withdrawal of [corrected] estrogen increases hypothalamic neuropeptide Y (NPY) mRNA expression in ovariectomized obese rat

We determined the changes in neuropeptide Y (NPY) mRNA expression of the arcuate nucleus (ARC) in sham-operated (SHAM) and bilaterally ovariectomized (OVX) rats with estradiol (E2) supplement. Ovariectomy increases body weight gain for 3 weeks, accompanied by an increase of daily food intake. Ovariectomy significantly reduced serum corticosterone levels. E2 supplement reversed the effects of ovariectomy on body weight gain, food intake and serum corticosterone levels. Ovariectomy significantly increased NPY mRNA expression in the ARC. E2 supplement decreased NPY mRNA expression in the ARC of OVX rats. The present findings indicated that hypothalamic NPY mRNA expression, which involves the regulation of feeding behavior, are in parallel with circulating estrogen levels. Hypothalamic NPY mRNA expression may be important in the induction of hyperphagia after the withdrawal of estrogen by bilateral ovariectomy.     

Alterations in the postovariectomy increases in gonadotropin secretion in middle-aged persistent-estrous rats: correlation with pituitary gonadotropin subunit gene expression

This study compared the changes in pituitary and serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) at various times following ovariectomy (OVX) between young cyclic and middle-aged persistent-estrous (PE) rats and related these to the relative gene expression of the pituitary gonadotropin subunits. In intact animals, both pituitary and serum levels of LH were similar between these two age groups, while the LH beta mRNA expression was significantly (p < 0.05) greater in young rats. Following OVX in young rats, the serum LH levels markedly increased (p < 0.05) beginning on day 7 and reaching a maximum fourfold increase by day 9. In contrast, the post-OVX increases in serum LH in middle-aged females were significantly delayed. OVX significantly (p < 0.05) increased pituitary LH contents of young rats by day 5, but had no effect on LH contents in middle-aged females until day 30 post-OVX. These changes were associated with increases in LH beta mRNA expression in both young and middle-aged females, but the levels were significantly (p < 0.05) lower in middle-aged females. Both pituitary and serum levels of FSH were significantly (p < 0.05) higher in middle-aged PE than in young rats prior to OVX, while the FSH beta mRNA expression was similar in both age groups. Following OVX in young rats, serum FSH levels rapidly increased (p < 0.05) on day 3 and attained tenfold higher values by day 30.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of estrogen and progesterone on the escalation of cocaine self-administration in female rats during extended access.

Estrogen increases and progesterone decreases the acquisition and reinstatement of cocaine-seeking behavior in female rats. Here estrogen and progesterone were studied for their effects on the escalation of cocaine self-administration in female rats. The rats received ovariectomy (OVX) or sham (SH) surgery and were treated with estradiol benzoate (0.05 mg/kg sc) and/or progesterone (0.5 mg/kg) or vehicle (indicated by E, P, and V), resulting in 5 groups: SH+V, SH+P, OVX+V, OVX+E, OVX+E+P. Rats self-administered intravenous cocaine (0.4 mg/kg) under a fixed ratio 1 (FR 1) schedule during 2-hr sessions and were then given 6-hr sessions (long access; LgA) (FR 1) for 21 days. After LgA, self-administration was reassessed with 2-hr sessions under the FR 1 and a progressive ratio schedule with 4 cocaine doses. There were no differences among the 5 groups in cocaine self-administration during initial 2-hr sessions. During LgA, the SH+V, OVX+E, and OVX+V groups escalated their cocaine self-administration, whereas the OVX+E+P and SH+P groups did not. Estradiol increased escalation in the OVX+E group compared with the OVX+V group, and progesterone (SH+P) reduced escalation compared with the SH+V group. When estrogen and progesterone were both administered in OVX rats (OVX+E+P), escalation was significantly lower than in the OVX+E group. Cocaine infusions during the 2-hr sessions were significantly higher after escalation than before in all groups except the progesterone-treated groups (SH+P and OVX+E+P). Estrogen promoted and progesterone inhibited escalation of cocaine self-administration, illustrating the importance of female gonadal hormones in drug-seeking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of clodronate on increased bone turnover and bone loss due to ovariectomy in rats

The present study was carried out to investigate the ability of clodronate to inhibit ovariectomy-induced bone loss and increased bone turnover in rats. Estradiol was administered as a reference compound. Seventy Sprague-Dawley rats were ovariectomized (OVX) or sham-operated (Sham) at the age of 90 days and divided into seven groups. Two Sham and two OVX groups received subcutaneously either the vehicle of clodronate or the vehicle of estradiol. Other OVX groups were given s.c. either disodium clodronate at two dose levels (5 mg/kg or 12.5 mg/kg twice a week) or 17 beta-estradiol (10 micrograms/kg five times a week) for 8 weeks. Femur length, volume, dry weight, and ash weight were determined, and proximal ends of tibiae were used for bone histomorphometry. Markers of bone metabolism were measured from urine and serum. A significant loss of 54% of trabecular bone area of proximal tibial metaphysis was found at 8 weeks after ovariectomy. Clodronate and estradiol inhibited (p < 0.001) this osteopenia. Both drugs prevented the decrease in ash weight/volume of the femur. The inhibitory effect of clodronate and estradiol on bone resorption in OVX rats could be detected also in decreased urinary excretion of hydroxyproline and lysylpyridinoline (p < 0.001). Clodronate and estradiol decreased (p < 0.001) the ovariectomy-induced enhanced tibial endocortical mineral apposition rate (Ec.MAR) on the lateral cortex to the level of the Sham group. In contrast, periosteal MAR analyzed on the medial side of tibial cortical bone did not change significantly in the OVX/Veh group. Estradiol decreased periosteal MAR to below the level in the Sham group (p < 0.01). These results suggest that ovariectomy of growing rats resulted in tibial and femoral osteopenia two months later. Clodronate as well as estradiol can suppress bone resorption and turnover in ovariectomized rats, inhibiting the development of osteopenia. Both clodronate doses (5 and 12.5 mg/kg) had beneficial effects in ovariectomized animals.     

The effects of spaceflight on mRNA levels for cytokines in proximal tibia of ovariectomized rats

BACKGROUND: Bone resorption was elevated in ovariectomized rats during a 14-d orbital spaceflight over and above that caused by gonadal hormone deficiency. Locally produced cytokines are believed to have an important role in normal as well as abnormal bone resorption. METHODS: The purpose of the present study in the same rats was to determine whether spaceflight results in altered expression of cytokines in cancellous bone. The mRNA levels for selected cytokines were determined in proximal tibial metaphysis using ribonuclease (RNase) protection assays. RESULTS: The message for interleukin 1 receptor antagonist, interleukins 1alpha, 10, and 12, macrophage migration inhibitory factor, and tumor necrosis factor-alpha was below the limit of detection for all groups. Interleukin 6 and transforming growth factor-beta2 were expressed in bone but the mRNA levels for these cytokines were not altered by either ovariectomy or spaceflight. There was a tendency for interleukin-1beta message to be increased following ovariectomy (OVX) and this tendency achieved statistical significance following spaceflight. Finally, spaceflight resulted in an increase in the message level for interferon gamma in OVX rats. In summary, spaceflight results in increases in mRNA levels of two cytokines in OVX rats which have been shown to increase bone resorption.     

Hemichorea-hemiballism: an explanation for MR signal changes

Studies were performed to determine if the nonsteroidal anti-inflammatory drug ibuprofen alters bone and mineral metabolism in female rats. In experiment 1, four groups of growing rats underwent either sham operation or ovariectomy (OVX). One week later, controlled-release pellets with ibuprofen or placebo were implanted subcutaneously at the back of the neck. Following 3 weeks of treatment, rats were sacrificed and blood and bone samples were removed for serum assays and histomorphometric analysis. Body growth rate and the static cortical bone measurements made at the tibial diaphysis did not change in response to OVX. OVX, however, did increase radial bone growth, lowered serum 17beta-estradiol, reduced uterine weight, and decreased the cancellous bone area of the tibial metaphysis in the rats. Ibuprofen did not alter serum 17beta-estradiol or uterine weight but reduced radial bone growth as well as cancellous bone area of the tibial metaphysis in both sham-operated and OVX animals. In experiments 2 and 3, we tested the influence of ibuprofen on the effects of the tissue-selective estrogen agonist tamoxifen and of exogenous 17beta-estradiol in the OVX rat. Ibuprofen completely blocked the effects of tamoxifen and partially blocked the effects of 17beta-estradiol to prevent cancellous osteopenia. In contrast, ibuprofen did not influence the effects of tamoxifen and 17beta-estradiol to reduce radial bone growth. Besides the skeletal effects, ibuprofen suppressed estrogen-induced uterine growth. Our data suggest that ibuprofen blocks selective estrogen receptor-mediated activities in the rat.     

Angiotensin II receptor blockade limits kidney injury in two-kidney, one-clip Goldblatt hypertensive rats with special reference to phenotypic changes

Recent evidence indicates that tubulointerstitial injury plays an important role in hypertensive kidney injury and that phenotypic changes contribute to this pathology. Moreover, angiotensin II is known to be actively involved in the pathogenesis of progressive kidney injury induced by hypertension. The present study was undertaken to see the effect of a newly developed angiotensin II type I receptor (AT1 receptor) antagonist on hypertension-induced kidney injury and to determine the contribution of phenotypic changes to morphologic alterations. Two-kidney, one-clip (2K1C), Goldblatt hypertensive rats (n = 27) were made by clipping the left renal artery. These animals were orally administered 57G709 (a selective non-peptide AT1 receptor antagonist)(10 mg/kg/day), captopril (20 mg/kg/day), or vehicle alone for 23 days beginning 4 weeks after clipping. In the non-clipped kidney of vehicle-treated 2K1 C rats, marked tubulointerstitial injury as well as glomerular sclerosis and/or hyalinosis was found in association with phenotypic changes, as shown by the neoexpression of vimentin in periglomeruli, perivascular walls, distal tubuli, and injured interstitium. Renin expression was markedly suppressed in the non-clipped kidneys of vehicle-treated 2K1C rats as compared with renin expression in normotensive control kidneys of sham-operated rats. Both 57G709 and captopril markedly ameliorated hypertensive kidney injury as reflected by the glomerular sclerosing index and by the tubulointerstitial index as determined by the point-counting method, and this improvement was accompanied by a significant decrease in blood pressure, urinary protein excretion, kidney/body weight ratio, and heart/body weight ratio. In addition, the vimentin neoexpression mentioned above was also suppressed with an inhibition of angiotensin II. These results suggest that in 2K1C Goldblatt hypertensive kidney injury, the AT1 receptor antagonist 57G709 exerts a potent renal protective effect associated with the inhibition of phenotypic changes.     

Renoprotective differences between perindopril and enalapril in the diabetic hypertensive rat do not reflect glomerular angiotensin-converting enzyme activity

1. The various angiotensin-converting enzyme inhibitors have structural differences which affect their affinities for the catalytic sites on converting enzyme. We postulated that such differences might result in differences in renoprotective efficacy. We investigated this in the diabetic spontaneous hypertensive rat. We also investigated whether these differences might reflect variations in glomerular or plasma angiotensin-converting enzyme activity. 2. One week after induction of diabetes, rats were started on antihypertensive therapy: enalapril, 10 mg.day-1.kg-1, or perindopril, 4 mg.day-1.kg-1, in the drinking water. After 3 months, the rats were killed, blood samples were taken and tissues were harvested. Angiotensin-converting enzyme activity in isolated glomeruli and plasma was measured by fluorimetric assay. Glomerular protein content was also determined. 3. Urinary protein excretion was significantly lower in perindopril-treated rats than in either controls (P < 0.0005) or enalapril-treated rats (P < 0.05). Glomerular protein content was also lower in perindopril-treated rats (P < 0.05 versus enalapril; P < 0.005 versus control). There was no difference in glomerular angiotensin-converting enzyme activity between the two inhibitors although both were lower than control values (enalapril P < 0.025; perindopril P < 0.025). Plasma angiotensin-converting enzyme activity was significantly lower in the perindopril group than in either control (P < 0.005) or the enalapril group (P < 0.01). 4. We conclude that in the spontaneous hypertensive rat with streptozotocin-induced diabetes, perindopril is more effective than enalapril in reducing proteinuria and glomerular protein accumulation. This difference does not result from differences in glomerular-converting enzyme activity.     

Antibacterial activity of the derivatives of cholic acid (author''s transl)

Serum and urinary myo-inositol and urinary glucose were estimated by means of gas-liquid chromatography in 54 patients with glomerulonephritis with and without renal failure. myo-Inositol clearance was calculated and an index was formulated which reflected changes in glomerular filtration, tubular reabsorption and catabolism of myo-inositol by the kidney. Serum and urinary myo-inositol levels were increased in glomerulonephritis with a close correlation to the degree of renal failure. In advanced forms of glomerulonephritis, glomerular filtration, tubular reabsorption and catabolism of myo-inositol were shown to be markedly deranged. Evidence obtained showed further that a derangement of tubular reabsorption and catabolism of myo-inositol also accompany milder forms of glomerulonephritis without decreased glomerular filtration. The myo-inositol index value, especially, was increased in patients with signs of disease activity as indicated by a histological examination of the kidney tissue. The index can also be regarded as a highly sensitive test of renal failure. Low grade glucosuria was shown to be frequently associated with glomerulonephritis with renal failure. Evidence was produced which suggested that the tubular reabsorption of myo-inositol was deranged earlier than glucose reabsorption in glomerulonephritis, although they may share a common step in the reabsorption process. The data suggest that the estimation of serum and urinary myo-inositol has advantages in the evaluation of kidney function.     

Inhibition of eotaxin-mediated human eosinophil activation and migration by the selective cyclic nucleotide phosphodiesterase type 4 inhibitor rolipram

Epidemiological studies suggest that moderate consumption of alcoholic beverages may be beneficial for bone in postmenopausal women. To investigate prospectively these uncontrolled observations, female rats were divided in four groups of 10 animals each and treated with 1) ovariectomy (OVX) and 2.5% ethanol diet (OVX-ETOH group), 2) OVX and control diet (OVX-C group), 3) sham surgery and 2.5% ethanol diet (SHAM-ETOH group), or 3) sham surgery and control diet (SHAM-C group). Three weeks after surgery, bone histomorphometry revealed that the OVX-C group, as expected, had lower trabecular bone volume and higher parameters of bone formation and resorption than the SHAM-C group (p < 0.01). Intake of ethanol did not change these parameters in the SHAM rats, but in the OVX rats it was associated with sharp reduction in parameters of bone resorption (p < 0.01) without a concomitant effect on parameters of bone formation. The cytokines are believed to contribute to accelerated bone resorption during the early postmenopausal period. Indeed, the peripheral blood monocytic cells (PBMC) from the OVX-C rats produced higher amounts of TNF-alpha than the PBMC from the SHAM-C rats (p < 0.05) and administration of ethanol prevented this increase in OVX rats but had no effect in SHAM rats. In summary, short-term intake of moderate doses of ethanol was associated with markedly different effects in rats with and without ovarian function. Although ethanol had no significant effect on the bone tissue and TNF-alpha production of the SHAM rats, it was associated with markedly lower parameters of bone resorption and less TNF-alpha production in the OVX animals. This suggests that exposure to low-dose ethanol may protect from osteopenia following cessation of ovarian function.     

Localization of glycogen synthase activity in liver of fasted normal and adrenalectomized rats after injection of dexamethasone

Hepatic glycogen synthase activity was localized in normal and adrenalectomized (ADX) rats after fasting overnight and in fasted ADX rats after injection of dexamethasone (DEX) 2-8 h prior to sacrifice to stimulate glycogen synthesis. Cryostat sections were incubated in medium containing substrate to demonstrate glycogen synthase activity as indicated by glycogen synthesized during incubation. Sections from fasted normal rats showed limited dispersed glycogen synthase activity in both periportal and centrilobular regions. In contrast, activity for glycogen synthase in hepatocytes from fasted ADX rats appeared as large aggregates in random hepatocytes throughout the lobule. Two hours after injection of DEX the reaction product appeared as aggregates in some hepatocytes, but other cells revealed dispersed enzyme activity. Glycogen synthase activity was evident in more hepatocytes after 4 h treatment with DEX and after 8 h virtually all hepatocytes contained abundant reaction product. The results suggest that synthase activity becomes concentrated in limited regions of selected hepatocytes in fasted ADX rats. DEX stimulation of glycogen synthesis for 4-8 h results in increased enzyme activity.     

Inhibition of neutrophil elastase by the alpha1-proteinase inhibitor-immunoglobulin A complex

Effect of spaying on liver and plasma phospholipid components was studied in 4-day cyclic rats (Haffkin Institute Strain). Rats were ovariectomized during diestrous stage of estrous cycle. Ovariectomy (OVX) was shown to increase the total phospholipid content in both the liver lobes after 24 hr interval, it remained higher in spigelian lobe up to 72 hr but it was lowered in the right lobe at 48 hr interval. Concentration of sphingomyelin (SHP) in total phospholipids, as assessed by TLC, was slightly increased in both lobes after 48 hr of spaying. It declined significantly by 72 hr only in the spigelian lobe. Phosphotidylcholin, phosphatidylserine and phosphatidylethanolamine concentrations showed fluctuating pattern up to 48 hr of spaying, but most of these changes were seen to be restored to the normal level by 72 hr interval. Results indicate that the relative lack of ovarian hormones due to ovariectomy have obvious influence on hepatic lipid metabolism particularly that of phospholipid components. There appears to be an inverse relationship between hepatic lipid components and blood plasma. Spigelian lobe exhibits distinctly different responses to ovariectomy as compared to those of the right lobe. Maximal alterations are observable by 48 hr post-OVX interval.