Pharmacokinetics of a test dose of intravenous busulfan guide dose modifications to achieve an optimal area under the curve of a single daily dose of intravenous busulfan in children undergoing a reduced-intensity conditioning regimen with hematopoietic stem cell transplantation.

We studied 30 pediatric patients with malignant (n = 16) or nonmalignant (n = 14) conditions. The preparative regimen consisted of fludarabine, intravenous (IV) busulfan (Bu) for 2 daily doses, and antithymocyte globulin before stem cell transplantation. A test dose of IV Bu (0.8 mg/kg), anticipated to target an area under the concentration-time curve (AUC) of 800 to 1200 micromol.min, was followed later by 2 daily doses adjusted according to the pharmacokinetics (PK) to target an AUC of 3200 to 4800 micromol.min. The median test dose AUC was 953 micromol.min (range, 439-1315 micromol.min). The median AUC of single daily doses was 3798 micromol.min (range, 1511-7254 micromol.min). PK-based dose modification was required in 20 patients: 12 were adjusted to a higher dose, and in 8 the dose was decreased. Nausea and vomiting were noted in 15 patients. No patient developed hepatic veno-occlusive disease or seizures. Full donor chimerism was attained in 20 patients (mean of 24.5 days), 3 achieved partial chimerism, 5 did not engraft, and in 2 it is too early to assess chimerism. Acute graft-versus-host disease developed in 11 patients, grades I to II developed in 10 patients, and grade III developed in 1. Four patients died of infection and 5 of progressive disease. Thus, PK of a test dose of IV Bu provided information to adjust subsequent daily doses of IV Bu: this resulted in a regimen that was feasible, safe, and convenient for administration to children.     

Use of a capillary input function with cardiac output for the estimation of lesion pharmacokinetic parameters: preliminary results on a breast cancer patient

The objective of this work was to propose and demonstrate a novel technique for the assessment of tumour pharmacokinetic parameters together with a regionally estimated vascular input function. A breast cancer patient T2*-weighted dynamic contrast enhanced MRI (DCE-MRI) dataset acquired at high temporal resolution during the first-pass bolus perfusion was used for testing the technique. Extraction of the lesion volume transfer constant K(trans) together with the intravascular plasma volume fraction v(p) was achieved by optimizing a capillary input function with a measure of cardiac output using the principle of intravascular indicator dilution theory. For a region of interest drawn within the breast lesion a v(p) of 0.16 and a K(trans) of 0.70 min(-1) were estimated. Despite the value of v(p) being higher than expected, estimated K(trans) was in accordance with the literature values. In conclusion, the technique proposed here, has the main advantage of allowing the estimation of breast tumour pharmacokinetic parameters from first-pass perfusion T2*-weighted DCE-MRI data without the need of measuring an arterial input function. The technique may also have applicability to T1-weighted DCE-MRI data.     

Liver regeneration in partially hepatectomized rats infused with carnitine and lipids.

Male Wistar rats were subjected to 65-70% hepatectomy. Immediately after surgery a 6-hour infusion was given containing 115 kJ/kg b.w. of long-chain fatty acids (Nutralipid Spofa) (N) or N combined with L-carnitine (Carnitene Sigma Tau) in doses 8 mg (12.4 mumol), 40 mg (62 mumol) and 200 mg (310 mumol)/kg b.w. The rats were killed 6, 18, 21, 24 and 30 h after surgery. The results of our study demonstrate that infusion of lipids combined with carnitine, has a stimulating dose-dependent effect on liver regeneration in partially hepatectomized rats, excluding the low dose of carnitine--8 mg/kg. The dose of carnitine of 40 mg/kg had the highest stimulating effect on the course of the liver DNA synthesis, culminating 21 h after partial hepatectomy. Later, 24 and 30 h after hepatectomy, the mitotic activity of hepatocytes was highest in rats infused with carnitine in doses of 200 mg/kg b.w.     

Developmental neurotoxicity after penconazole exposure at embryo pre- and post-implantation in mice

ABSTRACT

The present study was conducted to evaluate the effect of penconazole fungicide at a low dose (2.5 mg/kg b.w.) during embryogenesis in either the pre- or post-implantation of embryos. Females were determined pregnant according to the presence of vaginal plug and then grouped into control and penconazole-exposures at high doses (30, 20, 10, and 5 mg/kg b.w.). These high doses provoked foetoresorptionin the first experiment. Thus, a low dose (2.5 mg/kg b. w.) was used in either the pre- or post-implantation of embryos to clarify the embryotoxicity without mortality on the developing brain and eye. Results indicate a developmental delay of the cerebral hemisphere, hippocampus, cerebellum (lobulation) and induced retinopathy during eye development in post-implantation of penconazole treated group. Also, the effect of penconazole at low dose provoked a decrease in the expression of α-synuclein in the hippocampus, cerebellum, and ganglion cell layer of the developing brain and eye. In conclusion, exposure to PEN fungicide during pregnancy at a dose (2.5 mg/kg) induces alterations in the developing brain and eye tissues.     

The effects of histamine on skeletal muscle vasculature in cats.

1. Experiments have been made to determine the vascular effects of histamine and the mechanism of histamine-induced oedema formation in cat skeletal muscle. 2. Histamine caused dose-dependent dilatation of resistance vessels and increased intravascular volume over the dose range 1 X 10(-10)-1 X 10(-8) mol/kg min. The dilatation of resistance vessels resulted in dose-dependent increases in capillary hydrostatic pressure. 3. Histamine increased vascular permeability, as measured by accumulation of [131I]human serum albumin in the tissue, during infusions at 1 X 10(-8) mol/kg min but no albumin accumulation could be detected at lower infusion rates. 4. Oedema formation during histamine infusion of 1 X 10(-10) and 1 X 10(-9) mol/kg min seemed to be due to increases in capillary hydrostatic pressure and independent of increased vascular permeability. During infusions of histamine 1 X 10(-8) mol/kg min oedema was due predominantly to increased vascular permeability and to a lesser extent, the increase in capillary hydrostatic pressure.     

The time-course of ribavirin-provoked changes of basal and AMPH-induced motor activities in rats

The time-course of changes of basal and amphetamine (AMPH)-induced locomotor and stereotypic activities in adult male Wistar rats after a single ribavirin injection was studied. In the first set of experiments, 10, 20 or 30 mg ribavirin/kg body weight (b.w.) were injected i.p. to rats and their basal motor activities were recorded every 10 min for 2 h and compared with those of saline-treated controls. In the second set of experiments, the animals were pretreated with ribavirin and 20 min later i.p. injected with AMPH (1.5 mg/kg b.w.). The controls received AMPH 20 min after the saline injection. Motor activity was recorded after the first injection and until 120 min after AMPH administration. Ribavirin did not significantly affect the time-course of either basal locomotor or stereotypic activities. Pretreatment with any of the applied ribavirin doses decreased the AMPH-induced hyperlocomotor response. However, the most pronounced effect was observed with ribavirin doses of 20 mg/kg and 30 mg/kg when administered during the first 10 min and 30 min after the AMPH injection respectively. In contrast, the stereotypic activities of these animals were only slightly changed. These results indicate a different susceptibility of regions in the basal ganglia to ribavirin.     

Pharmacokinetics and individualized dose adjustment of intravenous busulfan in children with advanced hematologic malignancies undergoing allogeneic stem cell transplantation.

We investigated the pharmacokinetics (PK) of a recently approved intravenous busulfan (IVBU) formulation as a part of the preparative regimen in 20 children with advanced hematologic malignancies undergoing allogeneic hematopoietic stem cell transplantation. Seventeen patients received a thiotepa, IVBU, and cyclophosphamide-based regimen, and 3 patients received an IVBU and cyclophosphamide-based regimen. All patients received IVBU 0.8 mg/kg for the first 2 doses; thereafter, the IVBU dose was modified, if required, to achieve a final area under the concentration-time curve (AUC) at steady state of 1150 micromol/L/min per dose (range, 1000-1300 micromol/L/min per dose; SD +/-13%) based on the first-dose PK determination. PK studies were repeated on subsequent doses to verify the final AUC. Initial mean IVBU clearance and half-life were 3.96 mL/min/kg and 1.98 hours, respectively. Sixteen (80%) of the 20 patients received dose adjustments: 14 patients required dose escalations, and 2 required dose reductions. Overall, thirteen (72%) of 18 available sample sets at final follow-up PK analysis showed the IVBU exposure to be within the targeted range. IVBU PK was linear, and interpatient variability was much lower than that observed with oral busulfan. IVBU was well tolerated, and no case of hepatic veno-occlusive disease was encountered. Mild and transient hyperbilirubinemia was observed in 7 patients. Thirteen of the 20 patients were alive at a median follow-up of 651 days (range, 386-1555 days). We conclude that a standardized IVBU dose of 0.8 mg/kg in children does not always result in an AUC within the reference range defined in this study. Therapeutic drug monitoring with dose adjustment based on first-dose PK can optimize the systemic busulfan exposure for children undergoing allogeneic hematopoietic stem cell transplantation.     

Cyclooxygenase-inhibition enhances the effects of rSP-C surfactant therapy in a rat lavage model of Acute Respiratory Distress Syndrome (ARDS)

The effects of additional i.v. therapy with a cyclooxygenase-inhibitor Eltenac to a recombinant surfactant protein C (rSP-C) based surfactant were investigated in a rat lung lavage model of acute lung injury. Treatment was done at 60 min after the induction of acute lung injury by lavage. The influence of the different treatments were tested with regard to improving oxygenation, histopathological changes (hyaline membrane formation and alveolar influx of neutrophil leukocytes). These effects were further compared to a fixed combination of Eltenac with rSP-C surfactant which was administered intratracheally (i.tr.), 60 min after lavage. To prove that fibrinogen is involved in the formation of hyaline membranes in this animal model confocal microscopy was applied. Furthermore, for selected cases the influence of Eltenac or rSP-C surfactant on fibrinogen leakage was investigated by using confocal microscopy. Results of additional i.v. therapy exhibited an improved oxygenation with rSP-C surfactant, while a high dose of Eltenacalone did not influence oxygenation as compared to untreated controls. Addition of Eltenac lead to improved oxygenation using the low dose of rSP-C surfactant. The rSP-C surfactant prevented further hyaline membrane formation. Furthemore, addition of Eltenac to the low dose of rSP-C surfactant lead to improved hyaline membrane formation at a dose of 100 micromol/kg b.w. Results of combined i.tr. therapy confirmed the results of the additional therapy. Again, rSP-C surfactant improved oxygenation and further hyaline membrane formation, while even the high dose of i.tr. administered Eltenacalone only prevented further hyaline membrane formation. Using the low dose of rSP-C surfactant, combined treatment with Eltenac showed additional effects on oxygenation and inhibition of hyaline membrane formation. The maximum therapeutic effect of combined treatment was achieved at 0.3 mg Eltenac per kg b.w. which is equivalent to approximately 1 micromol. The inflammatory cell infiltration into the lung was not influenced by any of the therapeutic approaches. Confocal microscopy gave evidence that fibrinogen is involved in hyaline membrane formation in this animal model. Furthermore, as was shown by the explorative investigations with confocal microscopy, addition of the cyclooxygenase-inhibitor decreases the diffuse interstitial leakage of fibrinogen into the lung while surfactant monotherapy did not exhibit any influence on the fibrinogen influx into the alveoli. CONCLUSIONS: Confocal microscopy may be an effective method to investigate the connection between fibrinogen leakage and hyaline membrane formation. Effects of additional or combined treatment were superior when compared to each treatment alone leading to the conclusion that a rSP-C surfactant containing a cyclooxygenase-inhibitor, acts synergistically in this animal model of acute lung injury. Lower doses of Eltenac could be used to reach similar effects on oxygenation and prevention of hyaline membrane after combined i.tr. treatment than after additional i.v. treatment together with surfactant. This leads to the conclusion that a fixed combination of rSP-C surfactant and a cyclooxygenase-inhibitor may be an effective treatment. Further testing may be warranted to prove whether this is a promising treatment for patients with acute lung injury.     

Ocular Albumin Fluorophotometric Quantitation of Endotoxin-Induced Vascular Permeability

Bacterial endotoxin (lipopolysaccharide; LPS) is known to alter systemic vascular permeability, but this effect is difficult to monitor and quantitate in vivo. The ocular vessels of the rabbit are particularly sensitive to LPS. Using a slit lamp equipped with a fluorophotometer, we have adapted a method to quantitate endotoxin-induced ocular vascular permeability by measuring the accumulation of fluorescein isothiocyanate-conjugated albumin into the anterior chamber of the eye. After intravenous administration of Salmonella typhimurim LPS, the anterior chamber fluorescence and blood fluorescence were measured at intervals of 15 min and 1 h, respectively, over 4 h. In controls, maximal fluorescence in the anterior chamber was 3.1 ± 0.8% of blood fluorescence. Doses of LPS as low as 0.25 μg/kg produced an ocular/serum fluorescence ratio of 17.6 ± 4.9. A dose of 2.5 μg of LPS per kg tended to produce a higher ratio (68.0 ± 7.1) than a larger dose of 50 μg/kg (30.5 ± 16.6). Permeability changes began within 30 min after LPS, and the rate of dye accumulation varied over time, with maximal leakage usually occurring 90 min after LPS, but occasionally occurring much later. Repeated doses produced tolerance. By conjugating albumin to rhodamine and utilizing a second filter with the slit lamp to measure accumulation of this dye, we demonstrated the persistence of marked permeability during a period when intraocular fluorescein isothiocyanate and albumin levels were relatively constant. This methodology indicates that extremely low doses of LPS induce ocular permeability changes and that neither the time course nor the dose response of this effect is linear. Ocular fluorophotometry is a sensitive, noninvasive technique to study the dynamics and pharmacology of LPS-induced permeability changes.     

Metabolic effects of low and high doses of insulin during beta-receptor blockade in dogs

Metabolic effects of low and high doses of insulin during beta-receptor blockade were studied in eight dogs. Beta-receptor blockade was induced by 0.5 mg/kg propranolol which caused depression of heart performance. This was accompanied by a significant reduction in myocardial blood-flow and oxygen consumption. There was also a significant reduction in arterial concentrations and myocardial uptake of free fatty acids, while arterial concentrations and myocardial uptake of glucose and lactate were not significantly changed. Fifteen minutes after beta receptor blockade, an intravenous (i.v.) bolus injection of 0.5 IU/kg, of insulin, free of glucagon and calcium, was given followed by a continuous infusion of 0.5 IU/kg/h. Glucose and potassium were given to maintain constant levels of these factors. After 30 min another bolus dose of 300 IU insulin was injected. Thirty minutes after a low dose of insulin, a significant increase in heart performance was recorded at unaltered myocardial oxygen consumption. Arterial concentrations of free fatty acids were significantly reduced while levels of glucose and lactate were unchanged. Myocardial uptake of glucose increased significantly while uptake of lactate and free fatty acids was unchanged. After a high dose of insulin there was a considerable improvement in heart performance. Myocardial blood-flow and oxygen consumption were not changed, nor were there alterations in arterial concentrations and myocardial uptake of glucose, lactate and free fatty acids. It is concluded that, during beta-receptor blockade high doses of insulin improve the mechanical performance of the heart through mechanisms that are independent of insulin's effects on substrate metabolism.     

Haemodynamic effects of low and high doses of insulin during beta receptor blockade in dogs

Haemodynamic effects of small and high doses of insulin during beta receptor blockade were studied in nine dogs. Beta receptor blockade was induced by 0.5 mg/kg propranolol and caused depression of cardiac performance with a significant increase in left ventricular end-diastolic pressure (LVEDP) and a significant decrease in heart rate; maximum rate of left ventricular (LV) pressure rise (LVdP/dtmax), stroke volume and cardiac output. At 15 min, after beta receptor blockade, a bolus injection of 0.5 IU/kg of insulin, free of glucagon and calcium, was given followed by a continuous infusion of 0.5 IU/kg/h. After 30 min another bolus dose of 300 IU insulin was injected. Glucose and potassium were given to maintain physiological levels of these factors. Five minutes after a low dose of insulin there was a significant decrease in LVEDP (P less than 0.01), and a significant increase in LVdP/dtmax (P less than 0.01), in stroke volume (P less than 0.01) and in cardiac output (P less than 0.01). The other haemodynamic variables were not significantly changed. Administration of a high dose of insulin further, significantly, improved performance of the beta receptor blocked heart and caused a significant reduction in total peripheral resistance. In conclusion, insulin exerts inotropic and vasodilator effects which are dose-dependent and not related to adrenergic mechanisms.     

Differential effect of frusemide on renal medullary and cortical blood flow in the anaesthetised rat

In addition to its known effect on renal tubular transport, frusemide (furosemide) has been shown to affect renal circulation. This study in the anaesthetised rat examined the influence of frusemide (bolus 0.25 or 0.5 mg kg(-1) I.V., then infusion delivering the same dose over 1 h) on renal cortical and medullary circulation measured as laser-Doppler blood (cell) flux. The responses were compared with simultaneously measured changes in renal excretion and in the tissue admittance, an index of medullary ionic hypertonicity of the interstitium. Renal vascular responses to frusemide were significant but not dose dependent. During low-dose frusemide infusion cortical flux decreased 11.5 +/- 0.9% and medullary flux decreased 32.3 +/- 3.5% (difference significant at P < 0.001). During high-dose infusion the decreases were by 13.5 +/- 1.4 and 29.3 +/- 3.8%, respectively (difference significant at P < 0.001). Sodium excretion increased 15-fold (by 3.7 +/- 0.4 micromol x min(-1)) and 30-fold (by 5.9 +/- 1.1 micromol x min(-1)) during low- and high-rate infusion of frusemide, respectively. By contrast, medullary tissue admittance decreased similarly with the two doses: maximally by 13.4 +/- 1.4 and 10.9 +/- 0.9%, respectively. The observations that an exaggerated post-frusemide decrease in blood flow within the medulla coincided with decreasing tissue admittance in this zone and that neither medullary blood flow nor admittance changes were related to the dose suggest a causal relationship between interstitial ionic hypertonicity and vascular resistance. We propose that the post-frusemide decrease in medullary tissue NaCl depressed medullary circulation by inhibiting local generation of vasodilator prostaglandins.     

Studies of cerebral osmoreceptors in anesthetized dogs: the effect of intravenous and intracarotid infusion of hyper-osmolar sodium chloride solutions during sustained water diuresis.

The function of the suggested hypothalamic osmoreceptors was investigated in dogs during light chloralose anesthesia. The dogs were subjected to an i.v. load of 40 ml/kg b.w.t. of a hypo-osmolar solution of sodium chloride and glucose. This degree of hydration was kept constantly by a specially constructed servo system based on the weight of the animal. During water diuresis the renal free water clearance remained essentially constant for several hours (mean about 0.2 ml/kg b.w.t. min). Renal sodium excretion was low (mean 0.82 mumol/kg b.w.t. min) and decreased continuously throughout the experimental period. I.v. infusion of hyperosmolar sodium chloride solution (1.33 mmol/kg b.w.t. in 30 min) was followed by prolonged parallel increases in free water clearance and sodium excretion, without any detectable change in the excretion of osmoles and potassium. The renal response to bilateral infusion of hyper-osmolar NaCl (1.33 mmol/kg b.w.t. in 30 min) into the common carotid arteries was identical to the response to i.v. infusion. The estimated increase in the osmolality of the carotid blood was 2.2%. In seven out of eight experiments intracarotid infusion of NaCl (1.33 mmol/kg b.w.t. in 8 min) did not elicit any reduction in free water clearance. On the contrary, an increase was found similar to that obtained after i.v. infusion. The estimated increase in the osmolality of the carotid blood was 8.4%. The present results question the validity of the currently held view that hypothalamic osmoreceptors play an important role in the control of the osmolality of plasma.     

Intravascular large B-cell lymphoma with hemophagocytic syndrome (Asian variant) in a Caucasian patient

Intravascular lymphoma is an aggressive and extremely rare extranodal lymphoma with neoplastic lymphoid cells confined exclusively within intravascular spaces. The histopathologic findings are subtle due to the rarity of the neoplastic cells in blood vessels. Clinical presentations are non-specific and focal space-occupying lesions or lymphoadenopathy are always lacking. It is a diagnostic challenge. Secondary hemophagocytic syndrome is uncommon and is typically associated with infection, malignancy, and suppressed immune states. Intravascular lymphoma has a strong association with hemophagocytic syndrome in Asian patients, the so-called "Asian variant", but not in Western patients. We report a case of intravascular B-cell lymphoma in a Caucasian patient associated with secondary hemophagocytic syndrome. The patient was diagnosed by core liver biopsy and successfully treated. This case demonstrates the importance of high index of suspicion and astute histopathologic examination in recognition of this unusual clinical and pathologic combination.     

Hepatic and intestinal first-pass effects of a new hepatoprotective agent, YH439, in rats

First-pass effects of YH439 were evaluated after intravenous, intraportal, oral, and intraduodenal administration of the drug, 100 mg/kg body weight, to rats. The first-pass effects of YH439 in the lung and heart seemed to be negligible based on total body clearance values after intravenous and intraportal administration of the drug to rats compared with cardiac output in rats. Approximately 60% of orally and intraduodenally administered YH439 was not absorbed from rat gastrointestinal tract and the F values of YH439 were less than 0.22% after both administration of the drug to rats. Therefore, it could be concluded that approximately 40% of orally and/or intraduodenally administered YH439 could disappeared by hepatic and/or gastrointestinal first-pass effects. The hepatic first-pass effect of YH439 absorbed into the portal vein was approximately 45% (AUC difference between intravenous and intraportal administration) in rats. The AUC0-8hr values of YH439 after oral (18.7 microg min/ml) and intraduodenal (23.4 microg min/ml) administration were significantly smaller than that after intraportal administration (3260 microg min/ml), however, the values were not significantly different between oral and intraduodenal administration, suggesting that the gastric first-pass effect seemed to be negligible and intestinal first-pass effect was considerable in rats. The low F of YH439 in rats could be mainly due to unabsorption (approximately 60%) and hepatic and intestinal first-pass effect (approximately 40%).     

Hypophysectomy and saralasin on mesenteric vasoconstrictor response to vasopressin.

The dose-response relationship of the mesenteric resistance vessels to vasopressin was studied in anesthetized laparotomized cats before and after hypophysectomy and again during the plateau phase of the response to a prolonged infusion of [Sar1-Ala8] angiotensin II (saralasin), a competitive antagonist of angiotensin II. Hypophysectomy and saralasin each caused an increase in superior mesenteric arterial conductance. Before hypophysectomy infusion of 0.5 mU/(min.kg) of vasopressin caused mesenteric conductance to decrease from 0.168 to 0.156 ml/(min.kg.mmHg), a change of only 0.012 units. After hypophysectomy, the same dose reduced conductance from 0.227 to 0.179 mU/(min.kg.mmHg), a change of 0.048 units. During the plateau phase of the response to saralasin, 0.5 mU/(min.kg) of vasopressin reduced conductance from 0.281 to 0.201 ml/(min.kg.mmHg), a change of 0.079 units. Hypophysectomy and saralasin had little effect on the mesenteric vasoconstrictor response to high doses of vasopressin (2.0-10 mU/(min.kg). The ineffectiveness of low doses of vasopressin on the mesenteric resistance vessels of the intact anesthetized, surgically stressed animal may be due in part to the already constricted state of the bed caused by endogenous vasopressin and angiotensin and in part due to an opposing vasodilator influence, the reflex withdrawal of the vasoconstrictor effect of endogenous vasopressin.     

Comparison of the effects of dexmedetomidine and propofol on hypothermia in patients under spinal anesthesia: a prospective,randomized, and controlled trial

Background: Redistribution hypothermia caused by vasodilation during anesthesia is the primary cause of perioperative hypothermia. Propofol exerts a dose-dependent vasodilatory effect, whereas dexmedetomidine induces peripheral vasoconstriction at high plasma concentrations. This study compared the effects of dexmedetomidine and propofol on core temperature in patients undergoing surgery under spinal anesthesia.Methods: This prospective study included 40 patients (aged 19-70 years) with American Society of Anesthesiologists Physical Status class I-III who underwent elective orthopedic lower-limb surgery under spinal anesthesia. Patients were randomly allocated to a dexmedetomidine or propofol group (n = 20 per group). After induction of spinal anesthesia, patients received dexmedetomidine (loading dose: 1 μg/kg over 10 min; maintenance dose: 0.2-0.7 μg/kg/h) or propofol (loading dose: 75 μg/kg over 10 min; maintenance dose: 12.5-75 μg/kg/min). The doses of sedatives were titrated to maintain moderate sedation. During the perioperative period, tympanic temperatures, thermal comfort score, and shivering grade were recorded.Results: Core temperature at the end of surgery did not differ significantly between the groups (36.4 ± 0.4 and 36.1 ± 0.7°C in the dexmedetomidine and propofol groups, respectively; P = 0.118). The lowest perioperative temperature, incidence and severity of perioperative hypothermia, thermal comfort score, and shivering grade did not differ significantly between the groups (all P > 0.05).Conclusions: In patients undergoing spinal anesthesia with moderate sedation, the effect of dexmedetomidine on patients'' core temperature was similar to that of propofol.     

Intravascular ultrasound findings of coronary wall morphology in a child with Kawasaki disease

Intravascular ultrasound (IVUS) imaging was performed to assess the coronary wall morphology in detail at 22 months after the onset of Kawasaki disease in a girl who had developed coronary aneurysms at 4 yr of age. The sites of persistent aneurysms demonstrated a dilated lumen with a marked symmetrical or asymmetrical thickening of the intima-media complex. This pathologic finding was also present in angiographically normal vessels near an aneurysm but with a mild thickening. Coronary artery calcification was observed at one site in the aneurysms. The sites of normal coronary artery far from an aneurysm showed normal intravascular ultrasound findings with no measurable intima-media complex. Our case indicates that the healing process may continue via cell proliferation, with extension to the proximity of the coronary aneurysms. IVUS is useful to evaluate the coronary wall morphology and may be valuable in the long-term follow-up of coronary lesions due to Kawasaki disease.     

β-Caryophyllene,a natural sesquiterpene,modulates carbohydrate metabolism in streptozotocin-induced diabetic rats

The study was designed to evaluate the antihyperglycemic effects of β-caryophyllene (BCP), a natural sesquiterpene from spices on streptozotocin (STZ) induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (40 mg/kg b.w.) in adult male Wistar rats. Diabetic rats exhibited an increase in glucose and HbA_1c with a significant fall in insulin and hemoglobin levels. Aberrations in carbohydrate metabolic enzymes were noticed in liver, kidney and skeletal muscle of diabetic rats. A fall in liver and skeletal muscle glycogen with alterations in glycogen synthase and phosphorylase activities was also observed. Oral administration of BCP in dose dependent manner and glibenclamide (600 μg/kg b.w.), a standard oral hypoglycemic drug to diabetic rats for 45 days significantly decreased glucose with increased plasma insulin levels and ameliorated the altered activities of carbohydrate metabolic enzymes to near normal. The insulinotropic effect of BCP was supported by immunohistochemical studies. BCP at a dose of 200 mg/kg b.w. exerted significant antidiabetic effects than other two doses (100 and 400 mg/kg b.w.). We conclude that administration of BCP has beneficial effects in glucose homeostasis in diabetic rats.     

Post-transfusion survival of hydroxyethyl starch 450/0·70 in man: a long-term study

Intravascular persistence concomitant with changes occurring in the circulating molecular size distribution were determined in five healthy normovolaemic men dosed with 7 ml/kg of a 6% (w/v) solution of a species of hydroxyethyl starch (HES 450/0·70) possessing a M_w- of 450 000 daltons combined with a molar hydroxyethyl group substitution (MS) of 0·70 (70 hydroxyethyl groups/100 glucose residues). The concentration of HES 450/0·70 in serum fell to 24% of its peak value (measured 2 minutes post injection) one week after the infusion. By 17 weeks after injection, < 1·0% remained in the intravascular space. The HES 450/0·70 material recovered from the bloodstream 2 minutes after injection was shown by gel filtration on a column of Sepharose CL-4B to be less polydisperse than the injected solution. The K_av calculated for the peak of material eluted after one week showed a definite shift of molecular size toward that of a lower molecular weight composition. However, at four weeks the value of K_av indicated a shift toward the high molecular weight region of the injected solution, and by seven weeks this movement was quite pronounced. These data clearly indicate the complex nature of the removal of HES 450/0·70 from the intravascular space of man and appear to substantiate previous clinical studies reporting that the MS plays the major role influencing the rate of elimination of this material from the bloodstream.