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Activation of endogenous c-Src or a related tyrosine kinase by intracellular (pY)EEI peptide increases voltage-operated calcium channel currents in rabbit ear artery cells.

The effect of activation of endogenous c-Src tyrosine kinase by (pY)EEI peptide was examined on voltage-operated calcium channel (VOC) currents in arterial smooth muscle cells. In single rabbit ear artery cells intracellular application of (pY)EEI peptide increased calcium channel currents. Inactive, non-phosphorylated YEEI peptide had no effect on currents. Peptide-A, a 21 amino acid inhibitor of c-Src inhibited currents and prevented the effect of (pY)EEI peptide on calcium channel currents. These results indicate that activation of intrinsic c-Src increases VOC and support a role for c-Src in the regulation of VOC in vascular smooth muscle cells.

Animals↗

[Clinical study on treatment of 40 cases of malignant brain tumor by elemene emulsion injection].

OBJECTIVE: To investigate the effect of elemene emulsion injection (EEI) in treating malignant brain tumor. METHODS: By conducting a retrospective study of 40 patients with brain tumor, 29 of malignant glioma and 11 metastatic tumor, who were treated with EEI from January 1994 to May 1998. EEI 0.4-1.2 g/d was given to each patient by intravenous dripping or/and intravenous infusion by pumps, and directly injected into carotid artery or infused through a carotid artery catheter with pumps. The total dosage of 6-12 g was given in 2-6 therapeutic courses with an interval of 1-1.5 months between courses. The effectiveness of treatment was accessed according to the changes of tumor size, Karnofsky Performance Status (KPS) and survival time of patients. The control group consisted of 29 cases of malignant brain tumor (22 of primary and 7 of metastatic) was treated with chemotherapy 2-3 therapeutic courses with an interval of 1-1.5 months between them. RESULTS: (1) In the EEI treated group the mean tumor size was changed from 6.70 cm3 (before treatment) to 2.67 cm3 (after treatment), t = 3.02, P < 0.01, it was reduced by 61%; (2) In the EEI treated group 4 cases was CR, 26 PR, the total effective rate being 75.0% (95% credibility interval +/- 13.4%), while in the control group, 2 of CR, 10 PR, and the total effective rate 41.4% (95% credibility interval +/- 17.9%), the difference between the two groups was significant, chi 2 = 3.867, P < 0.05; (3) KPS decreased in the EEI group from 94.7 scores (before treatment) to 88.2 scores (after treatment), the decrement was 6.5 scores (t = 3.5313, P < 0.01); (4) The survival time in the EEI treated group was 25.4 months, and that in the control group was 17.4 months (t = 3.74, P < 0.01). CONCLUSION: Elemene has significant effect on treatment of malignant brain tumor. It could prolong the high quality survival time of patients and is worthy of further investigation.

Adult↗

Energy expenditure index of walking for normal children and for children with cerebral palsy.

Energy expenditure indices (EEI) based on oxygen uptake and heart rate were used to compare the economy of walking at various speeds by normal and cerebral-palsied children. At low walking speeds, EEI values were high, indicating poor economy. At higher speeds the EEI values decreased until a range of maximum economy was reached. For normal children who were capable of walking beyond this range at higher speeds, the EEI increased again. This pattern was noted for both oxygen-uptake and heart-rate indices. Mean EEI values based on oxygen uptake and heart rate for normal children were significantly lower and occurred at faster walking speeds than values for children with cerebral palsy. EEI based on either oxygen uptake or heart rate can be used clinically to provide objective information to help evaluate the influence on gait function of surgical intervention, ambulatory aids or orthotics.

Adolescent↗

Energy expenditure of diplegic ambulation using flexible plastic ankle foot orthoses.

In order to determine whether flexible plastic ankle foot orthoses (AFOs) really have functional advantage for children with spastic diplegia (CP children). Six CP children (13.2 +/- 1.9 years) who showed moderate spasticity walked on a treadmill at relative speeds that ranged from slow to fast for three minutes at each speed. While walking with and without flexible plastic AFOs, oxygen uptake (VO2) was measured. Then an energy expenditure index (EEI) was calculated by taking the VO2 value divided by walking speed. A curve EEI-walking speed relationship was approximated to a parabolic curve. Then, the lowest value of EEI, as an economical EEI, was derived from the curve. In four of the six CP children, the EEI while walking with flexible plastic AFOs were larger than without flexible plastic AFOs. The economical EEI while walking with and without flexible plastic AFOs was 0.56 +/- 0.26 ml/kg/m and 0.42 +/- 0.14 ml/kg/m, respectively. The ambulation with flexible plastic AFOs required more energy than without flexible plastic AFOs (p < 0.05). From these results, flexible plastic AFOs do not seem to provide a functional advantage for CP children.

Adolescent↗

Insulin sensitizing property of Indigofera mysorensis extract.

Indigofera mysorens is a shrub used for its antidiabetic activity in rural India. Here, we elucidate the antidiabetic potential of Indigofera mysorensis extract. Ethanolic extract of the whole shrub of Indigofera (EEI) at 300 mg/kg for 10 days, produced a 63% reduction in plasma glucose, 41% reduction in plasma triglyceride and 77% reduction in plasma insulin levels in insulin resistant db/db mice, which is better than insulin sensitizer, troglitazone (400 mg/kg). EEI unlike sulphonylureas failed to show any acute hypoglycemic effect in normoglycemic Swiss albino mice (SAM). Even in a chronic study (10 days) in SAM, EEI (300 mg/kg) like insulin sensitizers showed no effect on plasma glucose, but an 81% reduction in plasma insulin levels. When challenged with 3 gm/kg sucrose, SAM treated with EEI (300 mg/kg, 7 days) failed to show any effect on the absorption of sugar, whereas standard drug, acarbose (10 mg/kg) showed 52% reduction in the area under the plasma glucose curve. EEI failed to show any significant transactivation of PPARgamma, a proposed target of synthetic insulin sensitizers. Taken together, our data indicate that the antidiabetic effect of the ethanolic extract of Indigofera is due to its insulin sensitizing property and is clearly different from that of sulfonylurea or acarbose.

Animals↗

Functional interaction of AT1 and AT2 receptors in fructose-induced insulin resistance and hypertension in rats.

The present study was performed to evaluate the potential role and functional interaction of angiotensin II AT1 and AT2 receptors (AT1R and AT2R) in the regulation of blood pressure and glucose homeostasis in fructose-induced insulin-resistant, hypertensive rats. Male Sprague-Dawley rats on fructose-enriched or regular diets for 4 weeks were subjected to 2-step euglycemic euinsulinemic (EEI) and euglycemic hyperinsulinemic (EHI) clamp studies with [3-3H]glucose infusion. After a 40-minute basal period, selective AT1R and AT2R antagonists, losartan (LOS, 10 mg/kg IV bolus) and PD123319 (PD, 50 microg/kg/min), alone or in combination were separately given to control and fructose-fed groups in the 2 clamp periods. The results showed that during the EEI period, LOS significantly reduced the elevated blood pressure in fructose-fed rats, whereas PD further increased fructose-induced high blood pressure. Coadministration of LOS and PD did not alter the elevated blood pressure in fructose-fed rats. Administration of LOS and/or PD failed to change the blood pressure in control rats. During the EHI period, blockade of both AT1R and AT2R eliminated the insulin-induced blood pressure elevation in control and fructose-fed rats. Hepatic glucose production (HGP) did not alter among groups in the basal and EEI periods. Insulin infusion (EHI period) markedly suppressed HGP in control rats, but this suppressive effect was significantly attenuated in fructose-fed rats. LOS administration further reduced the insulin-induced suppression of HGP in fructose-fed rats. The whole-body glucose uptakes (rates of glucose disappearance, Rd) during the basal and EEI periods were similar among groups. During the EHI period, Rd was markedly increased in all groups and the magnitude of increase was significantly greater in control rats than in fructose-fed rats except those with LOS treatment. LOS treatment also redirected Rd in favor of glycolysis in fructose rats, but not in control rats, during the EEI and EHI periods. The effects of LOS on glycolysis during the 2 clamp periods and on HGP during the EHI period were reversed when PD was concomitantly administered, but PD alone did not alter glucose metabolism throughout the experiment in fructose-fed rats. Administration of LOS and/or PD did not change the glucose metabolism in control rats. Our data suggest that AT2R can counterbalance the AT1R-mediated effects on blood pressure and glucose metabolism in fructose-induced insulin-resistant, hypertensive rats. Furthermore, AT1R- and AT2R-mediated effects on blood pressure are disassociated with their actions on glucose metabolism in this hypertensive model.

Animals↗

Progesterone augments copper-prostaglandin E2 stimulation of the release of gonadotropin-releasing hormone from explants of the median eminence of immature female rats: an estrogen-dependent process.

We have previously shown that extracellular copper (Cu) amplifies prostaglandin E2 (PGE2) stimulation of LHRH release from explants of the median eminence area (MEA) of adult male rats, and that amplification is a post-PGE2 receptor event involving the adenylate cyclase system. We addressed the question: Is the process of Cu-amplified PGE2 stimulation of LHRH release regulated by ovarian steroids and, if so, is the regulatory steroid estrogen and/or progesterone? Immature female rats (30-32 days old) were ovariectomized and 6 days later treated with a combination of these steroids: E, sc implant of 17 beta-estradiol in a Silastic capsule for 3 days; EEi, E plus im injection of 17 beta-estradiol (2 micrograms/rat) 24 h before killing; and P, either im injection of 0.08 mg/kg progesterone 1 h before killing or 10(-9) M P included in the incubation buffer starting 1 h before Cu/PGE2 exposure. Controls were treated with the vehicle. MEAs were incubated for 5 min with 150 microM Cu, for 15 min with 10 microM PGE2, and then for 45 min with buffer (Cu/PGE2); LHRH release into the medium was measured by RIA. Cu/PGE2-stimulated LHRH release from MEA of intact rats was about 10 times greater than basal release. Ovariectomy led to a 50% reduction in Cu/PGE2-stimulated release [sham, 20.6 +/- 2.0 (mean +/- SE); ovariectomized, 9.4 +/- 1.8], pg/30 mm/MEA; and neither E, EEi, nor P significantly altered this response. In contrast, administration of P to either E- or EEi-primed rats augmented Cu/PGE2 stimulation of LHRH release 3.5-fold (E vs. EP or EEi vs. EEiP); however, P did not augment stimulation of LHRH release by Cu alone or PGE2 alone. Also, inclusion of P in the incubation buffer was as effective as in vivo P in augmenting Cu/PGE2 stimulation of LHRH release from the MEA of EEi-primed rats. On the other hand, in vitro P by itself did not alter LHRH release. These effects of P on the response of the MEA to Cu/PGE2 were not accompanied by a significant increase in the MEA content of LHRH. The process of Cu/PGE2 stimulation of LHRH release is regulated by ovarian steroids, so that ovariectomy leads to a marked reduction of the response of the MEA to Cu/PGE2, and P augments this response in an estrogen-dependent manner. Moreover, it is the secretory process elicited by the combined effects of Cu and PGE2 that is augmented by P.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The energy expenditure index: a method to quantitate and compare walking energy expenditure for children and adolescents.

We used heart rate and walking speed to calculate an energy expenditure index (EEI), the ratio of heart rate per meter walked, for 102 normal subjects, age 6-18 years. Heart rate was measured at self-selected slow, comfortable, and fast walking speeds on the floor and on a motor-driven treadmill. At slow walking speeds (37 +/- 10 m/min) the EEI was elevated (0.71 +/- 0.32 beats/m), indicating poor economy. At comfortable speeds (70 +/- 11 m/min) the EEI values decreased to the maximum economy (0.47 +/- 0.13 beats/m). At fast speeds (101 +/- 13 m/min), the EEI increased (0.61 +/- 0.17 beats/m), indicating poor economy relative to comfortable speeds. A graph of the EEI versus walking speed provides a way to evaluate and compare energy expenditure in a clinical setting.

Adolescent↗

Within- and between-day stability of treadmill walking VO2 in children with hemiplegic cerebral palsy, stability of walking VO2 in children with CP.

Within- and between-day stability in locomotor energy use was quantified in 13 children with hemiplegic cerebral palsy (CP). During testing, subjects were familiarized with the laboratory environment (Session 1), performed three 5 min level treadmill walks (Trials 1-3) at 0.67 m*s(-1) (Session 2), and completed a single 5 min walk (Trial 4) at 0.67 m*s(-1) (Session 3). In Sessions 2 and 3, heart rate (HR) was assessed and expired air was collected and analyzed to determine VO2. Data analyses revealed no significant difference (P > 0.05) in either net VO2 (ml kg(-1)*min(-1)) or EEI(HR) (b*m(-1)) across the three trials performed in Session 2 and between average measures of net VO2 and EEI(HR) quantified in Session 2 and those obtained in Session 3. Mean within-day coefficient of variation (CV) values for net VO2 and EEI(HR) were 8.6% +/- 8.5% and 13.9% +/- 7.8%, respectively. Analysis of between-day variability and energy expenditure revealed a between-day CV value of 13.1% for net VO2 and 24.0% for EEI(HR). In addition, significant inverse relationships between Gross Motor Function Measure (GMFM) scores and within- (r = -0.61) and between-day (r = -0.58) CV values for net VO2 were detected. Viewed in concert, these data suggest that fairly stable within- and between-day measures of locomotor energy expenditure during level treadmill walking can be achieved in subjects with hemiplegic CP if testing is preceded by a short period of treadmill accommodation. However, children with greater motor dysfunction may require an extended period of treadmill accommodation to reduce trial-to-trial variability in walking energy use.

Adolescent↗

[Tracheal intubation in prehospital resuscitation: importance of rapid-sequence induction anesthesia].

OBJECTIVE: To investigate complications of emergency endotracheal intubation (EEI), possibly facilitated by rapid-sequence induction, in the prehospital critical care setting: 1) the difficulty of intubation; 2) the cardiorespiratory consequences of intubation; 3) the relationship between the occurrence of complications and prognosis. STUDY DESIGN: Prospective non randomized, open study. PATIENTS: All patients treated over a 5-month period by a physician-manned ambulance service and requiring EEI. METHODS: Patients were allocated either in with cardiac arrest (CA) group or a group with maintained spontaneous circulation (SC). Difficulty of intubation was assessed by the number of attempts. RESULTS: Two hundred and twenty-four consecutive EEI were carried out by physicians (46%) and residents (38%) not trained in anaesthesia, anaesthetists (8%), or nurse anaesthetists (7%). Trachea was intubated after a maximum of three attempts in all patients. Success rate at the first attempt was 91%. It was 92% in CA patients (n = 76) and 90% in SC patients (P = 0.59). Anaesthetic induction, with (n = 112) or without (n = 12) succinylcholine, was used to facilitate 84% of intubations in SC patients. Complications occurred in 30 patients (20%). There was no relationship between the latter and hospital mortality, duration of ventilatory support, duration of stay in the intensive care unit. CONCLUSION: In this study, EEI in SC patients was frequently facilitated by rapid sequence induction and was associated with a high success rate at the first attempt, as in CA patients. Morbidity was low. All physicians involved in emergency airway management should be skilled in this technique.

Adolescent↗