Evidence for increased formation of preprothrombin and the noninvolvement of vitamin K-dependent reactions in sex-linked hyperprothrombinemia in the rat.

The rate of appearance of plasma prothrombin was measured in vitamin K-deficient male and female rats after the administration of vitamin K₁, and the disappearance of prothrombin was measured in normal rats after injection of cycloheximide. The results suggest that hyperprothrombinemia in female rats is due to a faster rate of formation of the clotting protein rather than to a slower rate of its degradation. Preprothrombin activity in liver microsomes was higher in warfarin-treated female rats than in warfarintreated male rats; but the activity of preprothrombin in liver disappeared at approximately the same rate in both sexes after administration of vitamin K. The rate and extent of vitamin K-dependent formation of γ-carboxyglutamic acid and the appearance of prothrombin activity in vitro were not significantly different between the sexes. These results suggest that elevated levels of plasma prothrombin in female rats are probably due to a higher rate of synthesis of preprothrombin and not to any difference in the vitamin K-dependent step. A difference was observed in the amount of cycloheximide required to inhibit synthesis of liver microsomal protein in the two sexes.     

The effects of endotoxaemia on protein metabolism in skeletal muscle and liver of fed and fasted rats.

The response of muscle and liver protein metabolism to either a single or three successive daily injections of an endotoxin (Escherichia coli lipopolysaccharide, serotype 0127 B8; 1 mg/ml, 0.3 mg/100 g body wt.) was studied in vivo in the fed rat, and at 24 and 30 h after endotoxin treatment during fasting. In the fed rats there was a catabolic response in muscle, owing to a 60-100% increase in muscle protein degradation rate, and a 52% fall in the synthesis rate. Although there was a 20% decrease in food intake, the decrease in protein synthesis was to some extent independent of this, since rats treated with endotoxin and fasted also showed a lower rate of muscle protein synthesis, which was in excess of the decrease caused by fasting alone. The mechanism of this decreased protein synthesis involved decreased translational activity, since in both fed and fasted rats there was a decreased rate of synthesis per unit of RNA. This occurred despite the fact that insulin concentrations were either maintained or increased, in the fasted rats, to those observed in fed rats. In the liver total protein mass was increased in the fed rats by 16% at 24 h, and the fractional synthesis rate at that time was increased by 35%. In rats fasted after endotoxin treatment the liver protein mass was not decreased as it was in the control fasted rats, and the fractional synthesis rate was increased by 22%. In both cases the increased synthesis rate reflected an elevated hepatic RNA concentration. The extent of this increase in hepatic protein synthesis was sufficient at one point to compensate for the fall in estimated muscle protein synthesis, so that the sum total in the two tissues was maintained.     

Effect of stress experienced during pregnancy on the rate of lipid peroxidation in erythrocytes and brain tissue of newborn rat pups

The rate of lipid peroxidation (LPO) in erythrocytes and brain homogenate has been assessed by the accumulation of malondialdehyde, the degree of erythrocyte autohemolysis, the content of hydrogen peroxide and catalase activity observed in newborn rats aged 1 hour, 1, 15, 20 and 30 days. Pregnant rats were exposed to emotional stress (aggressive interaction of two pregnant rats in an unavoidable conflict situation provoked by nociceptive irritation. Significant age-dependent differences in the rate of LPO (both in erythrocytes and cerebral tissue) have been found. The highest rate was noted in rats 15 days of age. The emotional stress of pregnant females resulted in the changes of behavioural reactions of newborn rats and LPO activity that was characterized by the increase in LPO rate in 1-hour- and 1-day-old rats and by slowing of LPO rate in 15-day-old rats. These phenomena were observed in erythrocytes and brain tissues of test animals.     

The nature of the sex-linked differences in glutathione peroxidase activity and aerobic oxidation of glutathione in male and female rat liver

1. Glutathione peroxidase activity in the livers of sham-operated female rats was about 60% higher than in similarly treated male rats. The value in the ovariectomized female was about the same as that in the castrated or sham-operated male. 2. Glutathione peroxidase activity changed during the oestrous cycle. The highest value was in oestrus, and was about 50% higher than the lowest activity, which was found in dioestrus. The activity in proestrus and in metoestrus was respectively about 20 and 30% higher than in dioestrus. 3. In the pregnant female 1 or 2 days before term, glutathione peroxidase activity was about 20% higher than that in the female in oestrus. 4. Subcutaneous implants of both oestra-diol and progesterone in the gonadectomized rats increased the glutathione peroxidase activity approximately to the values found in the female at oestrus. 5. The rate of aerobic oxidation of GSH in the female rat liver was about 80% higher than in the male and about 110% higher than in the gonadectomized rats. Treatment of gonadectomized rats with subcutaneous implants of oestradiol and of progesterone increased the rate of oxidation of GSH by about 100%. 6. In the presence of azide the rate of GSH oxidation in the male and in the female was respectively about 3.5- and 2.1-fold that in the absence of azide. In castrated or ovariectomized rats the increase due to the presence of azide was about 2.4-fold. In the gonadectomized rats treated with oestradiol or progesterone the rate of GSH oxidation in the presence of azide was about 2.2-fold that in its absence. 7. The rate of lipid peroxidation in female was 15-30-fold that in male or in gonadectomized rats. Treatment of the gonadectomized rats with oestradiol or with progesterone increased the rate of lipid peroxidation up to values that were even higher than in the female. In the presence of GSH the formation of malonaldehyde from peroxides was virtually eliminated. 8. The results suggest that the sex-linked differences in glutathione peroxidase activity, in the rate of GSH oxidation and in the rate of lipid peroxidation are due to the female sex hormones. 9. It is suggested that both the catalase activity and the rate of hydrogen peroxide formation are higher in the male than in the female. 10. Sex-linked changes in glutathione peroxidase, in the rate of GSH oxidation and in the rate of lipid peroxide formation are discussed in relation to the metabolism of oestrogens in the liver and also to the possible nature of those sex-linked changes.     

Effect of age and dietary restriction on protein synthesis by isolated kidney cells

The influence of age and food restriction on kidney protein synthesis was studied in Fischer F344 rats. The rate of total protein synthesis by suspensions of kidney cells declined 60% between 4 and 31 months of age. The rate of protein synthesis by kidney cells isolated from 19-month old rats fed a restricted diet (60% of diet consumed by rats fed ad libitum) was 45% higher than the rate of protein synthesis by kidney cells isolated from 19-month old rats fed ad libitum. The excretion of protein in the urine was measured to assess the effect of the age related decline in protein synthesis on kidney function. A dramatic increase in proteinuria was observed with increasing age, and rats fed the restricted diet excreted significantly less protein in the urine than rats fed ad libitum.     

遗传性大鼠脐疝模型的选育

目的近交繁殖先天性脐疝大鼠获得能稳定遗传的大鼠脐疝模型,大鼠脐疝结构观察及治疗。方法每代大鼠全同胞交配,记录产子数及脐疝情况,分析大鼠脐疝率;取F2代6月龄脐疝雌雄大鼠各6只,其中雌雄各2只进行解剖观察,雌雄大鼠各4只进行外科手术缝合。结果随近交系数增大,大鼠脐疝率升高,F12、F13代大鼠均为脐疝;F1代至F13代雌性大鼠总体脐疝率显著高于雄性大鼠（x2=11.1,P=0.001）;雌雄大鼠脐疝结构一致,手术后3~4周痊愈无复发。结论经连续13代全同胞交配获得了遗传性状稳定的大鼠脐疝模型。     

Strain dependence of the metabolism of cis- and trans-isomers of 9-octadecenoic acid in perfused liver and cell-free preparation in rats

Hepatic metabolism of cis- and trans-9-octadecenoic acid was compared in various strains of rats and under different nutritional states. In Wistar rats triacylglycerol secretion was consistently higher in livers perfused with the cis isomer than with the trans isomer, while the difference was considerably attenuated in Sprague-Dawley rats. The difference in the hepatic triacylglycerol secretion disappeared when rats were fasted for 2 days. The rate of oxidation of trans fatty acid to ketone bodies was remarkably much higher than the cis isomer in Wistar but not in Sprague-Dawley rats. After fasting, the difference in the ketone body production disappeared in Wistar rats, whereas the oxidation rate was rather lower in the trans isomer than in the cis isomer in Sprague-Dawley rats. In isolated mitochondria, ketogenesis from trans-9-octadecenoic acid was markedly lower than that from the cis counterpart, irrespective of the nutritional states or strains of rats, and correlated well with the substrate specificity of carnitine acyltransferase. The molar concentration of malonyl-CoA to cause 50% inhibition of ketogenesis, the rate of peroxisomal beta-oxidation and the activity of acyl-CoA oxidase were all comparable, irrespective of the substrate sources. The Km value for acyl-CoA oxidase to the trans-acyl-CoA was 2-times higher than that of the cis counterpart in both strains of rats. Thus, peroxisomal as well as mitochondrial fatty acid oxidation systems apparently discriminated between the geometrical differences of the fatty acid substrate.     

Autonomic control in rats with overactivity of tissue renin-angiotensin or kallikrein-kinin system

The renin-angiotensin system (RAS) plays an important role in the regulation of the cardiovascular system and the kallikrein-kinin system (KKS) appears to counteract most of the RAS effects. In this study the vagal and the sympathetic influences on the heart rate and the baroreflex control of the heart rate were evaluated in transgenics rats with human tissue kallikrein gene expression [TGR(hKLK1)], and transgenics rats with tissue renin overexpression [TGR(mREN2)27]. Heart rate was similar in all groups but mean arterial pressure was higher in mREN2 rats than in kallikrein and control rats (149+/-4 vs. 114+/-3 vs. 113+/-3 mm Hg, respectively). The intrinsic heart rate was lower in mREN2 rats than in kallikrein and control rats (324+/-5 vs. 331+/-3 vs. 343+/-7 bpm). The HR response to atropine was similar but the response to propranolol was higher in kallikrein rats than control group (61+/-7 vs. 60+/-9 vs. 38+/-7 bpm, respectively). The vagal tonus was lower in mREN2 than in SD and hKAL rats (18+/-3 vs. 40+/-6 vs. 35+/-6 bpm) whereas the sympathetic tonus was higher in kallikrein rats (118+/-7 vs. 96+/-1 vs. 81+/-9 bpm in the mREN2 and SD rats), respectively. Baroreflex sensitivity to bradycardic responses was attenuated in mREN2 rats (0.37+/-0.05 vs. 1.34+/-0.08 vs. 1.34+/-0,13 bpm/mm Hg) while the tachycardic responses were unchanged. The bradycardic responses to electrical stimulation of the vagal nerve were depressed in both renin and kallikrein rats (129+/-47 vs. 129+/-22 vs. 193+/-25 bpm in control group in response to 32 Hz). In conclusion: 1.The rats with overexpression of renin showed decreased intrinsic heart rate and impairment of vagal function, characterized by decreased vagal tonus, reduced response of HR to electrical stimulation of vagus nerve, and depressed reflex bradycardia provoked by increases of blood pressure. 2. The rats with overexpression of kallikrein showed an increase of sympathetic activity that regulates the heart rate, characterized by increased HR response to propranolol and increased sympathetic tonus, accompanied by decreased bradycardic responses to electrical vagal stimulation.     

老年大鼠脊髓小胶质细胞分选新方法及功能特征观察*

目的: 建立分离纯化老年大鼠小胶质细胞的改良方法,并初步观察老年大鼠脊髓小胶质细胞的生物学特性。方法: 以年轻SD大鼠(2月龄)为对照组,采用胰酶、胰酶替代物和机械网搓法等不同的制备方法,制备大鼠小胶质细胞的单细胞悬液,通过检测细胞纯度、存活率,观察细胞形态特征,分析细胞的炎性功能特征等,确定老年大鼠(20月龄)小胶质细胞的分离纯化方法,观察老年大鼠脊髓小胶质细胞功能特征。结果: 胰酶消化所得细胞的存活率低(年轻大鼠83%,老年大鼠60%);机械网搓法虽得到的存活率较高(95%),但是细胞获取率最低(年轻大鼠((0.207±0.020)×10⁶,老年大鼠(0.243±0.023)×10⁶);采用胰酶替代物解离、密度梯度离心方法分选出的老年大鼠脊髓小胶质细胞数量多、活性好、存活率高,细胞纯度可达85%以上,我们采用此方法分选纯化不同年龄大鼠脊髓小胶质细胞,与年轻大鼠相比,老年鼠脊髓组织量大,所需消化液多,但消化时间缩短;与年轻大鼠小胶质细胞相比,老年大鼠脊髓小胶质细胞其胞体较大较圆,突起少且粗短,形态上偏向于激活状态,老年大鼠小胶质细胞促炎因子IL-1β表达降低(P＜0.05),而抗炎因子IL-10(P＜0.01)表达升高。结论: 成功建立胰酶替代物解离结合密度梯度离心法从大鼠脊髓组织中分离纯化小胶质细胞,老年大鼠脊髓内小胶质细胞整体表现出抗炎表型。     

Hepatic conversion of thyroxine to triiodothyronine in obese and lean Zucker rats

The in vitro conversion of thyroxine (T4) to triiodothyronine (T3) was studied in liver homogenates from fed and fasted lean and obese Zucker rats. T3 generation was decreased in fed young (2 month) obese rats as compared to values in fed lean controls. This was not corrected by the addition of dithiothreitol (DTT), suggesting a deficiency in 5'-deiodinase activity in young obese rats. Both lean and obese 2 month old rats responded to a 2 day fast by decreasing hepatic T3 generation as is always observed in other strains of rats. The hepatic conversion rate was not decreased in older (5 month) fed obese rats when compared to age-matched lean controls. Hepatic conversion of T4 to T3 was markedly decreased in 5 month old lean Zucker rats fasted for 4 days. In contrast, a 4 day fast had no effect on the hepatic conversion rate in the 5 month old obese rats. The hepatic conversion rate was assessed in 5 month old obese rats fasted for up to 28 days and hepatic conversion still did not decrease. This paradoxical response of the 5 month old obese rat may provide a new model to further evaluate the control of hepatic T3 generation from T4.     

Incorporation of glucose into lipid of perirenal and subcutaneous adipocytes of rats and sheep: influence of insulin

Adipocytes were prepared by collagenase digestion of perirenal and subcutaneous fat from rats and sheep and were incubated in vitro with various concentrations of glucose and insulin. The lipogenic rate of perirenal and subcutaneous adipocytes of rats showed a quadratic response to glucose concentration. The addition of 10 nM insulin increased lipogenesis, especially at low lipogenic rates. At constant glucose concentrations, insulin concentrations up to 50 nM stimulated lipogenesis a similar amount in adipocytes from both depots. The rate of lipogenesis increased relative to cell volume in perirenal adipocytes only. The lipogenic rate of perirenal and subcutaneous adipocytes of sheep showed a positive linear response to glucose concentration, but insulin did not affect the rate of lipogenesis in adipocytes from either depot. In both rats and sheep, the rate of lipogenesis was higher in the perirenal adipocytes. It was concluded that insulin is unlikely to be the agent responsible for the differential growth rates of subcutaneous and perirenal fat depots in rats or sheep.     

Effects of sex hormones on fulminant hepatitis in LEC rats: a model of Wilson's disease.

LEC rats, which have hereditary hepatitis and have recently been proposed as an animal model for Wilson's disease, were examined to determine the effects of sex hormones on fulminant hepatitis. After the rats had undergone ovariectomies or orchidectomies (castration) and were compared with intact rats, the age at the onset of fulminant hepatitis was not substantially altered but the survival rates decreased from 50% to 12.5% for females and 75% to 14.3% for males, indicating that sex hormones did not influence the occurrence of fulminant hepatitis but influenced mortality due to fulminant hepatitis. When testosterone was administered to the ovariectomized or orchidectomized rats, the survival rate increased to over 90% in both sexes. In contrast, estradiol did not affect the survival rate of either sex but affected the onset of fulminant hepatitis. That is, with the administration of estradiol, the age at which serum GPT activity reached its maximum was delayed 4 weeks in ovariectomized rats and 6 weeks in orchidectomized rats as compared with intact rats. A similar but somewhat weaker tendency appeared in rats given progesterone. The results of our study indicate that sex hormones have no effect on the rate of occurrence of hepatitis but affect the progression of hepatitis. In particular, testosterone increased the survival rate of rats with fulminant hepatitis, and exogenous estradiol delayed the onset of hepatitis for several weeks.     

近交系MIJ和HFJ大鼠部分生理数据测定和分析

目的测定近交系大鼠MIJ、HFJ和封闭群Wistar大鼠的脏器系数、体温、呼吸频率、肠管长度,观察两个近交系大鼠的生理表型。方法 采用常规方法对大鼠脏器系数、体温、呼吸频率及肠管长度进行测定,并对HFJ、MIJ、Wistar大鼠三者间进行比较。结果①体重:HFJ、MIJ、Wistar大鼠同性别间比较差异无显著性。②脏器系数:HFJ与Wistar大鼠雄性间心脏、肺,雌性间子宫、肝;MIJ与Wistar大鼠雄性间肺、脾,雌性间脑、脾,差异均有显著性。HFJ与MIJ大鼠雄性间脑,雌性间脑和脾差异有显著性。HFJ大鼠不同性别间肝、脑、眼球差异有显著性。MIJ大鼠不同性别间,脑、心脏、肾、肺、脾和眼球差异均有显著性。③体温:HFJ雌性大鼠明显高于Wistar雌性,雄性间差异无显著性。HFJ大鼠雌性高于雄性,差异有显著性。④呼吸频率:HFJ雌性大鼠低于同性Wistar大鼠,MIJ大鼠雌性和雄性均高于同性别Wistar大鼠,差异有显著性。⑤肠管长度:HFJ与Wistar同性别间比较,肠管总长和小肠差异有显著性。MIJ与Wistar大鼠雄性间肠管总长、大肠、小肠、盲肠差异均有显著性,雌性间肠管总长、小肠、盲肠差异有显著性。HFJ与MIJ大鼠同性别间差异均无显著性,不同性别的HFJ和MIJ的肠管总长、大肠和小肠差异有显著性。结论 MIJ和HFJ近交系大鼠的脏器系数、体温、呼吸频率、肠管长度都各有其独特的生理概貌。     

Telemetered heart rate responses of the rat during free and learned behavior

To assess the effect of recording on the heart rate and on the behavior of the free moving rat, the electrocardiogram was recorded with the aid of radiotelemetry or through wire leads attached to the animal in different behavioral situations. Adaptation of heart rate both within and across sessions in the home cage and in a novel environment (open-field) was observed in rats bearing a transmitter. No adaptation occurred in rats attached to wire leads. The pattern of heart rate changes appeared to be independent of the mode of recording during passive avoidance behavior and when the rats displayed various motor activities like walking, sniffing, rearing or grooming in the open-field. The heart rate of rats attached to wire leads, however, was always higher. These data indicate that radiotelemetry is preferable to the use of wire connections for recording cardiac activity during behavioral studies in the rat.     

Effect of isoproterenol on phosphorylase activation in the hyperthyroid rat heart.

Pretreatment of rats for 3 days with triiodothyronine produced an increase in rate in the right atrium and a decrease in force of contraction in the right ventricle and Langendorff heart. Isoproterenol administration produced a time-dependent increase in rate and tension. The increase in rate was consistently greater in atria from hyperthyroid rats, and the increase in tension consistently greater in tissues from euthyroid rats. Isoproterenol also produced a time- and dose-dependent increase in phosphorylase a activity. In the isolated atria and ventricles enzyme activity was similar in the two groups. In the Langendorff hearts, however, there was an enhancement of the isoproterenol-induced increase in phosphorylase activity in hearts from hyperthyroid rats. Reduction of the coronary blood flow to the level found in euthyroid animals did not reduce the potentiation of phosphorylase activation found in hearts from hyperthyroid rats. It is concluded that the potentiation of phosphorylase activation in hearts from hyperthyroid rats is not due to the increase in coronary blood flow.     

Glucose turnover in the post-absorptive rat and the effects of halothane anaesthesia.

1. Rates and rate coefficients of glucose utilization and replacement in post-absorptive rats, either conscious or under halothane anaesthesia, were determined in a thermoneutral environment by using [5-3H]- and [U-14C]glucose. Label was not injected into rats under halothane until about 0.5h after anaesthesia was initiated. 2. Comparison with the results for 24h-starved rats in the preceding paper [Heath et al. (1977) Biochem. J. 162, 643-651] showed that insulin concentrations were considerably higher but rate coefficients for glucose utilization were little altered in post-absorptive rats. Sensitivity to insulin was thus considerably increased by a 24h period of starvation in the rat. 3. Fractional recycling of glucose carbon in post-absorptive rats was under one-half of that in starved rats, reflecting the larger contribution of liver glycogenolysis to glucose production in the former. 4. In post-absorptive rats halothane decreased the mean rate of glucose utilization by about 17%. This decrease was associated with an increase in mean plasma insulin concentration, showing that halothane decreased sensitivity to insulin. 5. Recycling was slightly increased by halothane, indicating that the contribution of liver glycogen to the total glucogenic rate was decreased, probably because liver glycogen concentration were about 40% lower throughout the rate determinations in halothane. 6. Comparison of our results with earlier work shows that during and shortly after induction of halothane anaesthesia glucose turnover must have been greatly increased whereas from about 0.5h after induction it was decreased.     

Nucleotide sequences of genes encoding the type II chloramphenicol acetyltransferases of Escherichia coli and Haemophilus influenzae, which are sensitive to inhibition by thiol-reactive reagents.

A gastric [U-14C]glucose load (4.8 mg/g body wt.) was delivered to unrestrained post-absorptive or 30 h-starved rats bearing peripheral and portal vein catheters and continuously perfused with [3-3H]glucose, in order to compare their metabolic and hormonal responses. In the basal state, portal and peripheral glycaemia were less in starved rats than in rats in the post-absorptive period (P less than 0.01), whereas blood lactate was similar. Portal insulinaemia (P less than 0.05) and protal glucagonaemia (P less than 0.005) were lower in starved rats, but insulin/glucagon ratio was higher in post-absorptive rats (P less than 0.005). The glucose turnover rate was decreased by starvation (P less than 0.005). After glucose ingestion, blood glucose was similar in post-absorptive and starved rats. A large portoperipheral gradient of lactate appeared in starved rats. Portal insulinaemia reached a peak at 9 min, and was respectively 454 +/- 68 and 740 +/- 65 mu-units/ml in starved and post-absorptive rats. Portal glucagonaemia remained stable, but was higher in post-absorptive rats (P less than 0.05). At 60 min after the gastric glucose load, 30% of the glucose was delivered at the periphery in both groups. The total glucose appearance rate was higher in starved rats (P less than 0.05), as was the glucose utilization rate (P less than 0.05), whereas the rate of appearance of exogenous glucose was similar. This was due to a non-suppressed hepatic glucose production in the starved rats, whereas it was totally suppressed in post-absorptive rats. At 1 h after the glucose load, the increase in both liver and muscle glycogen concentration was greater in starved rats. Thus short-term fasting induces an increased portal lactate concentration after a glucose load, and produces a state of liver insulin unresponsiveness for glucose production, whereas the sensitivity of peripheral tissues for glucose utilization is unchanged or even increased. This might allow preferential replenishment of the peripheral stores of glycogen.     

The effect of surgical trauma on muscle protein turnover in rats.

The rate of synthesis and catabolism of sarcoplasmic- and myofibrillar-muscle protein was measured in operated, sham-operated and food-restricted rats by using Na2 14CO3. The food-restricted group underwent sham operations and were limited to the food intake of the operated animals. Protein synthesis and catabolism were increased in the sarcoplasmic-muscle fraction in operated rats compared with that in sham-operated or food-restricted rats. The rate of synthesis of the myofibrillar protein decreased in operated animals, but the rate of catabolism was not altered in the myofibrillar-muscle fraction of the operated animals compared with that in food-restricted and sham-operated animals. In the operated animals, there was a net loss of protein from the muscle. Thus the rats that underwent surgery lost muscle protein, primarily as a result of a decrease in synthesis of myofibrillar protein. The changes in protein turnover in operated animals were not due to decreases in food intake, since protein turnover in sham-operated animals that were restricted to the food intake of the operated rats was not different from that in sham-operated rats fed ad libitum.     

Effect of ethanol administration on metabolism of lipids in heart and aorta in isoproterenol induced myocardial infarction in rats

Effect of ethanol administration on the severity of myocardial infarction induced by isoproterenol in rats was studied. Even though serum CPK and GOT levels as well as the extent of myocardial damage as revealed by histopathological studies, were similar, the survival rate was higher in rats administered ethanol. Concentration of cholesterol and triglycerides in the serum and heart in rats given ethanol and isoproterenol seems to be the additive effect caused individually by ethanol and isoproterenol. Myocardial alcohol dehydrogenase and aldehyde dehydrogenase both showed increased activity in rats treated with ethanol. The rate of recovery from myocardial infarction however, was slower in rats treated with ethanol as judged from the serum CPK value.