Slight Increase In Plasma Concentrations Research Articles

Remote Intestinal Injury Early After Experimental Polytrauma and Hemorrhagic Shock.

Dysfunction of the gut-blood barrier plays an important role in many diseases, such as inflammatory bowel disease, hemorrhagic shock (HS), or burn injury. However, little is known about gut barrier dysfunction after hemodynamically instable polytrauma (PT). Therefore, we aimed to evaluate the effects of PT and HS on remote intestinal damage and barrier dysfunction, especially regarding the role of zonula occludens protein 1 (ZO-1) as an important tight junction protein.Male C57BL/6 mice were subjected to either PT (thorax trauma, closed head injury, soft tissue injury, and distal femoral fracture), 60 min of pressure-controlled HS (30 ± 5 mmHg), or PT+HS, or sham procedures.Animals of all trauma groups showed an increase in abdominal girth and dilation of the intestine during the experimental period, which was largest in the PT+HS group. Increased blood-tissue permeability to albumin (assessed by Evans blue dye) was found in the HS group. Experimental groups showed a slight increase in plasma concentration of intestinal fatty acid binding protein and some intestinal damage was histologically detectable. Of note, PT+HS animals revealed significantly reduced expression of ZO-1 in intestinal epithelial cells. In an in-vitro model, stimulation of human colon epithelial cells with peptidoglycan, but not with lipopolysaccharide, resulted in elevated secretion of pro-inflammatory cytokines, reflecting inflammatory activity of the intestinal epithelium.Taken together, PT and HS lead to increased permeability of the gut-blood barrier. Bacterial components may lead to production of inflammatory and chemotactic mediators by gut epithelial cells, underlining the role of the gut as an immunologically active organ.

Inflammatory Mediators Associated With Pressure Ulcer Development in Individuals With Pneumonia After Traumatic Spinal Cord Injury: A Pilot Study

ObjectiveTo identify the inflammatory mediators around the time of pneumonia onset associated with concurrent or later onset of pressure ulcers (PUs). DesignRetrospective. SettingAcute hospitalization and inpatient rehabilitation unit of a university medical center. ParticipantsIndividuals (N=86) with traumatic spinal cord injury (SCI) were included in the initial analyses. Fifteen of the 86 developed pneumonia and had inflammatory mediator data available. Of these 15, 7 developed PUs and 8 did not. InterventionsNot applicable. Main Outcome MeasuresTwenty-three inflammatory mediators in plasma and urine were assayed. The differences in concentrations of plasma and urine inflammatory mediators between the closest time point before and after the diagnosis of pneumonia were calculated. ResultsInitial chi-square analysis revealed a significant (P=.02) association between pneumonia and PUs. Individuals with SCI and diagnosed pneumonia had nearly double the risk for developing PUs compared with those with no pneumonia. In individuals with pneumonia, Mann-Whitney U exact tests suggested an association (P<.05) between the formation of a first PU and a slight increase in plasma concentrations of tumor necrosis factor-alpha (TNF-α), and a decrease in urine concentrations of TNF-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin (IL)-15 after onset of pneumonia. ConclusionsThese findings suggest that a relatively small increase in plasma TNF-α, and decreases in urine TNF-α, GM-CSF, and IL-15 from just before to just after the diagnosis of pneumonia could be markers for an increased risk of PUs in individuals with pneumonia after traumatic SCI.

Fentanyl with ropivacaine infusion for postoperative pain relief in infants and children. Kinetics of epidural fentanyl.

The aim of the study was to evaluate pharmacokinetics of fentanyl administered as continuous epidural infusion with 0.2% ropivacaine for postoperative pain relief in infants and toddlers, and older children undergoing major abdominal and urological procedures. Thirteen infants and toddlers (median age 14 [range 3-36]months, 11 [5-17]kg, Group I) and 11 children (68 [45-131]months, 21 [16-52] kg, Group II) participated in the study. Epidural catheter was placed under general anesthesia in the L1-L2, L2-L3, or L3-L4 epidural space and threaded up to 4cm into the epidural space. Bolus dose of 0.2% ropivacaine, 0.5ml·kg(-1) and fentanyl, 2μg·kg(-1) was given, then followed by continuous infusion of 0.2% ropivacaine, 0.15ml·kg(-1) ·h(-1) with fentanyl 1.12μg·kg(-1) ·h(-1) . In the postoperative period, fentanyl dose was reduced to 0.375μg·kg(-1) ·h(-1) . With this dosing regimen, fentanyl concentration in plasma was within the range of analgesic concentrations, and did not exceed 1.0ng·ml(-1) . After discontinuation of epidural infusion, pharmacokinetics of fentanyl was complicated by a slight increase in plasma concentration during the elimination phase. Both elimination half-life of fentanyl (t1/2, MRT ) and mean residence time (MRT) were much longer than those observed after single IV bolus dose, and longer in Group I than in Group II (t1/2 MRT 15.9 [3.6-31.5]h vs 8.0 [7.1-13.3]h, P<0.05, MRTstop-last 22.9 [5.1-45.5]h vs 11.5 [10.2-19.1]h, P<0.05). Therefore, monitoring of vital signs seems warranted for several hours after the termination of the epidural infusion because risk of respiratory depression may persist, especially in the younger age group.

Early changes induced by environmental stresses in insulin sensitivity-related genes

Although adipocytes have been shown to secrete various adipocytokines, the factors that influence them are not clearly understood. We investigated whether repeated exposure to mild stresses affects the expression of adipocytokines in white adipose tissue (WAT). Male ICR mice were exposed to repeated restraint and tail-pinch (10 min/day) for 2 weeks. The exposure to restraint and tail-pinch stresses did not cause any change in body or liver weight, decreased the weight of WAT, and resulted in a slight increase in plasma concentration of corticosterone, indicating that mild stress did not result in any changes in blood glucose and insulin. Enhanced gene expression of adiponectin, which is associated with increased insulin sensitivity, and resistin and tumor necrosis factor-α (TNF-α), which are associated with decreased insulin sensitivity, was observed in the WAT of stressed mice. These results indicate that WAT is sensitive to mild stress, which may cause changes in the expression of adipocytokines, both improving and decreasing insulin sensitivity even during the normal stage of glucose metabolism. Thus, stress may be a factor that modulates insulin sensitivity.

Absorption and enterohepatic circulation of baicalin in rats

Pharmacokinetics of baicalin, in form of its parent drug (BG) and conjugated metabolites (BGM), were studied following intravenous and oral administration of baicalin to intact rats. The enterohepatic circulation of BG and BGM was also assessed in a linked-rat model. Multiple plasma and urine samples were collected, and concentrations of BG and BGM were determined using a liquid chromatography/tandem mass spectrometry method. The concentration of BGM was assayed in the form of baicalein after treatment with β-glucuronidase/sulfatase. After i.v. administration, plasma concentration of BG rapidly declined with the elimination half-life ( T 1 / 2 ) of 0.1 till 4 h post dose, followed by slight increase from 4–8 h in plasma concentrations after drug administration. These plasma concentrations resulted in a significant prolongation of the terminal elimination half-life of BG ( T 1 / 2 TER , 9.7 h). BG also displayed slight increase in plasma concentrations (12–24 h) after oral administration, with T 1 / 2 TER of 12.1 h. Based on the AUC of BG and BGM, the absolute bioavailability of baicalin was 2.2 ± 0.2% and 27.8 ± 5.6%, respectively. The exposure of baicalin to the systemic circulation was approximately 118-fold lower than that of BGM after oral administration (AUC 0− t , 4.43 versus 523.97 nmol·h/mL). The high extent of glucuronidation suggested the possible presence of enterohepatic circulation, which was confirmed in the linked-rat model since plasma concentrations of BG and BGM were observed in bile-recipient rats at 4 to 36 h. The extent of enterohepatic circulation after intravenous administration of baicalin was 4.8% and 13.3% for BG and BGM, respectively. It was determined that 18.7% and 19.3% of the administered baicalin were subjected to enterohepatic circulation for BG and BGM, respectively, after oral administration. These results confirm that BG undergoes extensive first-pass glucuronidation and that enterohepatic circulation contributes significantly to the exposure of BG and BGM in rats.

Studies on Regulatory Mechanisms for Gonadotropins Secretion in Lactating Rats

The present study was designed to clarify mechanisms responsible for regulation of FSH and LH secretion and ovarian follicular maturation during lactation in rats. Throughout lactation in rats, plasma levels of follicle-stimulating hormone (FSH) remain within the range normally found during the diestrous phase of the estrous cycle, regardless of litter size, although levels of luteinizing hormone (LH) in plasma are consistently lower in dams nursing 8 pups than in dams nursing 2 pups. All antral follicles larger than 401μm in diameter degenerate during the first half of lactation and do not reappear until the second half of lactation in rats nursing 8 pups. Healthy follicles of this size, however, are always present in mothers nursing 2 pups. These changes in follicular degeneration corresponded with a decrease in concentrations of plasma LH in the first half of lactation, and follicular development was noted with an increase in basal levels of plasma LH in the second half of lactation. Corpora lutea formed after postpartum ovulation secrete a large amount of progesterone under the influence of prolactin released as a result of suckling. Despite continued suckling, plasma concentrations of prolactin and progesterone decline gradually and a slight increase in plasma concentrations of estradiol-17β occurs during the second half of lactation. Concentrations of bioactive and immunoreactive inhibin in plasma vary with the number of healthy antral follicles and no positive correlation has been observed with luteal function throughout lactation in the rat.On the basis of the present results it is indicated that 1) tonic secretion of LH is an important factor in normal follicular maturation and maintenance in lactating rats, 2) the suckling stimulus, rather than ovarian factors, is mainly responsible for the suppression of FSH as well as LH secretion during the first half of lactation in rats nursing 8 pups. On the other hand, during the second half of lactation in rats nursing 8 pups, ovarian inhibin plays a primary role in the suppression of FSH secretion, whereas ovarian steroids act to suppress LH secretion. The present findings also indicate that 3) the suckling stimulus alone suppressed the secretion of both LH and FSH and this effect may be mediated by the inhibition of LH releasing hormone (LH-RH) secretion from the hypothalamus, 4) the suckling-induced inhibition of LH-RH may be primarily mediated by endogenous corticotropin-releasing hormone and opioid peptides and 5) the pituitary-adrenal system is capable of influencing the maintenance of a normal secretion of gonadotropins and prolactin as well as the maintenance of ovarian function during the lactation in the rat.

Na, K, Ca, and Mg ion action on coronary vascular resistance in the dog heart.

Local effects of major cations on coronary vascular resistance were studied in the beating dog heart. This was accomplished by shunting the blood around the heart and lungs, clamping the arch of the aorta and perfusing arterial blood at a constant rate into the ascending aorta. Perfusion pressure was measured during intracoronary infusion of isotonic solutions of NaCl, KCl, CaCl2, MgCl2, and MgSO4 and hypertonic solutions of NaCl and KCl at rates which raised cation concentrations in coronary blood without significantly affecting concentrations generally within the body. Coronary vascular resistance decreased as a function of the infusion rate of isotonic solutions of KCl, MgCl2, and MgSO4 and increased as a function of the infusion rate of an isotonic solution of CaCl2. Isotonic NaCl had no effect. Resistance changes occurred before measurable change in the proportion of a minute spent in electrical systole by the ventricle. These findings, together with those previously reported for the dog foreleg, suggest that the coronary vascular bed is actively dilated by localized slight increase in plasma concentration of K or Mg and actively constricted by localized slight increase in plasma concentration of Ca.