Nitric oxide induced by ketamine/xylazine anesthesia maintains hepatic blood flow during hypothermia.

Among the anesthetics influencing the nitric oxide (NO) pathway, ketamine is widely reported in the literature. We researched the variations in blood physiological parameters following ketamine/xylazine- or pentobarbital-induced anesthesia, with particular emphasis on plasmatic NO levels and oxidative stress-related factors. The effects of ketamine on hepatic blood flow during deep hypothermia were also examined. Adult male Sprague-Dawley rats were anesthetized intraperitoneally with ketamine/xylazine or with sodium pentobarbital. Animals underwent serial blood extraction to analyze acid-base balance and lactate levels in blood, as well as NO, MDA, SH groups, and AST levels in plasma samples. We demonstrated that ketamine leads to increased plasmatic NO levels, induces metabolic acidosis, and causes oxidative damage, though without reaching hepatic toxicity. When experimental hypothermia was induced, ketamine affected hepatic blood flow. Based on these results, we suggest that studies on physiological processes involving NO should exercise caution if anesthesia is induced by ketamine.     

The effects of different anaesthetic treatments on the adreno-cortical functions and glucose levels in NZW rabbits

The effects of five anaesthetics on the corticosterone, cortisol and glucose concentrations were investigated in the NZW rabbit. Sixty animals were assigned to 6 treatment groups (n= 10 per group): control ( iv saline solution injection), ketamine (10 mg/kg iv) with either xylazine (3 mg/kg iv) or diazepam (2 mg/kg iv), pentobarbitone (30 mg/kg iv), thiopentone (20 mg/kg iv) and fentanyl/droperidol (1 mg/kg sc). Plasma glucocorticoids were measured by competitive enzymeimmunoassay EIA and glucose by an autoanalyzer, previously validated for this species in both cases. Blood samples were obtained at 6 time-points: before injection, at 10, 30, 60, 120 min and 24 h after injection of the anaesthetics/saline. A significant decrease of plasma glucocorticoids at 10-60 min was observed in the pentobarbitone and fentanyl/ droperidol groups, whereas the administration of ketamine/diazepam or thiopentone stimulated plasma glucocorticoid release, principally in the recovery period. However, in the ketamine/xylazine group no changes were observed in the glucocorticoid levels, except for a significative increase of cortisol at 60-120 min. Glucose levels significantly increased after ketamine/diazepam administration and principally, after ketamine/xylazine treatment. The present data suggest that ketamine/xylazine has little effect on glucocorticoid levels and provides an adequate level of surgical anaesthesia, hence it would be the anaesthetic of choice, although the hyperglycaemic effect after injection has to be considered for any experimental procedures in rabbits.     

Effects of the anaesthetic/tranquillizer treatments on selected plasma biochemical parameters in NZW rabbits

In order to assess the response of plasma biochemical parameters to anaesthesia, 40 New Zealand White (NZW) rabbits were assigned to four treatment groups (n = 10): control (1 ml i.v. saline solution), fentanyl-droperidol (FD) (0.4 ml/kg s.c. of 'thalamonal' solution; 2.5 mg/ml droperidol, 0.05 mg/ml fentanyl), ketamine (K) (10 mg/kg i.v.) with either xylazine (X) (3 mg/kg i.v.) or diazepam (D) (2 mg/kg i.v.). Blood samples were obtained from the central ear artery at six time points: before injection, and at 10, 30, 60, 120 min and 24 h after injection of the anaesthetics/saline. Plasma ALT, AST, ALP, GGT, BUN, creatinine, phosphate and potassium levels were measured by the Hitachi 747 autoanalyser. The administration of K-X increased (P < 0.05) plasma ALT (from 11.4 +/- 0.9 to 20.2 +/- 1.7 IU/l, at 10 min), AST (from 10.5 +/- 3.3 to 34 +/- 2.1 IU/l, at 120 min), BUN (from 17.2 +/- 0.9 to 25.8 +/- 1.8 mg/dl, at 60 min) and creatinine concentrations (from 1 +/- 0.1 to 1.6 +/- 0.2 mg/dl, at 10 min). After K-D administration, we observed an increase (P < 0.05) in plasma ALT (from 11.4 +/- 0.9 to 20.2 +/- 1.1 IU/l, at 10 min), AST (from 11.4 +/- 1.6 to 28 +/- 3.7 IU/l, at 10 min), BUN (from 15.8 +/- 0.8 to 30 +/- 1.5 mg/dl, at 10 min) and creatinine levels (from 1 +/- 0.08 to 2.2 +/- 0.2 mg/dl, at 120 min). No significant changes were seen in the FD group. We conclude that K-X and K-D may affect plasma concentration of select serum enzymes and biochemical parameters. These results should be taken into account when blood samples are evaluated in treated rabbits.     

Suppression of hepatic fat accumulation by highly purified eicosapentaenoic acid prevents the progression of d-galactosamine-induced hepatitis in mice fed with a high-fat/high-sucrose diet

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains largely unknown. Here, we assessed the importance of hepatic fat accumulation on the progression of hepatitis. BALB/cA mice were fed with a standard diet (STD) or a high-fat and high-sucrose diet (HFHSD) for 14 days followed by intraperitoneal injection of d-galactosamine (DGalN) or vehicle. After 20–21 h, plasma and liver tissue were collected and analyzed. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in plasma were increased significantly in HFHSD-fed mice treated with DGalN compared to STD-fed mice treated with DGalN. This exacerbation by the HFHSD was also observed in the plasma soluble tumor necrosis factor receptor (sTNFR) levels, and hepatic levels of reactive oxygen species (ROS) and the fibrogenic gene expression, such as tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), connective tissue growth factor (CTGF) and osteopontin (OPN) in HFHSD-fed mice treated with DGalN. The triglyceride contents of the liver were significantly increased by the HFHSD. When eicosapentaenoic acid (EPA), a suppressor of sterol regulatory element binding protein 1 (SREBP-1), was administered to HFHSD-fed mice, the sensitivity of DGalN, as a result of plasma ALT and AST levels, was suppressed accompanied by reduced plasma sTNFR2 level and hepatic levels of triglyceride, ROS, and fibrogenic parameters, and by increased plasma adiponectin levels. These data suggest that the progression of steatotic liver injury closely depends on the accumulation of fat in the liver and is prevented by EPA through the suppression of the fatty liver change.     

Development of PEGylated serum albumin with multiple reduced thiols as a long-circulating scavenger of reactive oxygen species for the treatment of fulminant hepatic failure in mice

Reactive oxygen species (ROS) are involved in the pathophysiology of fulminant hepatic failure. Therefore, we developed polyethylene glycol-conjugated bovine serum albumin with multiple reduced thiols (PEG-BSA-SH) for the treatment of fulminant hepatic failure. As a long-circulating ROS scavenger, PEG-BSA-SH effectively scavenged highly reactive oxygen species and hydrogen peroxide in buffer solution. PEG-BSA-SH showed a long circulation time in the plasma after intravenous injection into mice. Fulminant hepatic failure was induced by intraperitoneal injection of lipopolysaccharide and d-galactosamine (LPS/d-GalN) into mice. The LPS/d-GalN-induced elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was significantly inhibited by a bolus intravenous injection of PEG-BSA-SH. Furthermore, the changes in hepatic lipid peroxide and hepatic blood flow were effectively suppressed by PEG-BSA-SH. In contrast, l-cysteine, glutathione, and dithiothreitol, three traditional reduced thiols, had no statistically significant effects on the serum levels of ALT or AST. These findings indicate that PEG-BSA-SH is a promising ROS scavenger and useful in the treatment of fulminant hepatic failure.     

Transplacental transfer of medetomidine and ketamine in pregnant ewes

The extent of placental transfer of medetomidine and ketamine is unknown in pregnant ewes. Date-mated singleton (n = 8) and twin (n = 8) pregnant merino cross ewes were anaesthetized for Caesarean delivery of preterm lamb fetuses. A combination of medetomidine (20 μg/kg) and ketamine (10 mg/kg) was administered by intravenous injection and surgery performed immediately thereafter. Blood samples were collected from the ewe at one, five and 10 min after intravenous injection and from the umbilical vein of the fetus at delivery. Non-pregnant ewes were also anaesthetized (n = 8). There was no difference in the plasma concentration of medetomidine or ketamine when comparing singleton and twin ewes or pregnant and non-pregnant ewes for the short duration of the study. Fetal plasma concentrations of each drug were comparable to the maternal concentrations at the same time. We conclude that both drugs cross the placenta readily and provide anaesthesia and analgesia for the fetus when it is delivered.     

Early effects of tribromoethanol, ketamine/xylazine, pentobarbitol, and isoflurane anesthesia on hepatic and lymphoid tissue in ICR mice

We investigated the effects of various anesthetic agents on hepatic and splenic injury in mice. Three and six hours after intraperitoneal injection of TBE, intramuscular injection of ketamine/xylazine combination (K/X), intraperitoneal injection of pentobarbital (PB), and inhalation of isoflurane (IF), or intraperitoneal and intramuscular injection of control saline, mice were exsanguinated and serum was obtained for measurement of hepatic aspartate transaminase (AST), alanine transaminase (ALT) and gamma-glutamyltransferase (GGT). The spleen and liver also were obtained, and sections were examined by use of routine light microscopy for pathologic changes and for apoptosis, as determined by use of the in situ terminal deoxynucleotidyl transferase-mediated dUPT nick-end-labeling (TUNEL) histochemical analysis. Three hours after TBE or K/X administration, AST activity increased three- to fourfold above that in untreated and saline-injected control animals, and remained high at six hours. Administration of PB did not effect AST activity at three hours, but there was a significant increase at six hours. Activity of ALT was non-significantly increased three hours after TBE and K/X, but not PB administration. Administration of IF had no effect on hepatic enzyme activities, and GGT was not increased after administration of any of the agents. Markedly increased apoptosis was observed in splenic follicles and in hepatic Kupffer and endothelial cells at three hours after TBE and K/X administration, but apoptosis decreased to control levels by six hours. Increased apoptosis was not observed after IF administration. Administration of TBE and K/X causes injury to lymphocytes and to hepatic Kupffer and endothelial cells within three hours, and PB administration induces changes within six hours. Thus, use of these anesthetic agents should be avoided when experiments are being designed to test short-term effects of an experimental intervention on the spleen and possibly on all lymphoid tissues. In addition, they also should be avoided in experiments testing effects on hepatic tissue.     

Hematological and serum biochemical values in cynomolgus monkeys anesthetized with ketamine hydrochloride

The effects of ketamine anesthesia on both hematological and serum biochemical variables were investigated in 19 male and 15 female cynomolgus monkeys. Blood samples were obtained from the cephalic vein within 30 minutes of an intramuscular injection of ketamine hydrochloride (10 mg/kg). Ketamine anesthesia caused a reduction in leukocyte counts and a significant reduction in lymphocytes percentages. Ketamine anesthesia also increased the serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine phosphokinase (CPK), but reduced the serum concentrations of glucose, inorganic phosphate, sodium and potassium. The alterations of hematological and serum biochemical values will be discussed. These alterations should be considered when designing studies for and interpreting data from cynomolgus monkeys.     

Identification of a QTL for Adipocyte Volume and of Shared Genetic Effects with Aspartate Aminotransferase

Plasma levels of aspartate aminotransferase (AST), a liver enzyme, are elevated in patients with visceral obesity. This study examined whether adipocyte volume is under the influence of genetic factors and evaluated its genetic correlations with AST. Fasting plasma levels of 344 pedigreed baboons from the Southwest National Primate Research Center in San Antonio, TX, USA, were assayed for AST. Adipocyte volume was measured using biopsies of omental adipose tissue. Adipocyte volume, body weight, and plasma AST were heritable. Genetic correlations between the measured adiposity-related phenotypes and AST were significant. A quantitative trait locus (LOD score 3.2) for adipocyte volume was identified on the baboon homolog of human chromosome 6 near marker D6S1028. These results suggest that omental adipocyte volume is under genetic regulation and that shared genetic factors influence adiposity-associated traits and AST.     

The effects of ketamine anesthesia on hematological and serum biochemical values in female cynomolgus monkeys (Macaca fascicularis)

The effects of ketamine anesthesia (15 mg/kg body weight) on hematological and serum biochemical values were examined in six female cynomolgus monkeys (Macaca fascicularis) who were born in the wild. As control, another six female cynomolgus monkeys of the same origin were injected with physiological saline. The white blood cell count, total protein concentration, albumin concentration and calcium concentration decreased after the injection of ketamine, whereas the red blood cell count, hematocrit value, hemoglobin concentration, total cholesterol concentration, free cholesterol concentration, triglyceride concentration, transaminase activities (GOT, GPT) and alkaline phosphatase activity were not affected. A transient increase of the serum glucose level was observed within 10 minutes after ketamine injection. The relationship between these effects of ketamine anesthesia and serum cortisol levels measured by radioimmunoassay was discussed.     

Correlation between pyridoxal-5'-phosphate levels and the percentage activation of aspartate aminotransferase enzyme in haemolysate and plasma during in vitro incubation studies with different B6 vitamers

Conflicting results using erythrocyte aminotransferase (eAST) stimulation to assess vitamin B6 nutritional status in patients with less severe B6 deficiencies are common. It has been claimed that the presence of different B6 vitamers may modify the activation of eAST by pyridoxal-5'-phosphate (PLP) leading to stimulatory or even inhibitory effects. To investigate the possible role of this phenomenon in producing inconsistent AST stimulations, aliquots of whole blood were incubated with equivalent amounts of different B6 vitamers, and the AST stimulation was correlated with the concentrations of PLP, measured by high-performance liquid chromatography. At the end of the incubation period the erythrocytes and plasma were separately analyzed. The conversion of non-PLP B6 vitamers to PLP, by the erythrocytes, was similar (approximately 70%) for all B6 vitamers used in the incubation experiments. The newly formed PLP accumulated in the erythrocytes, but the percentage activation of AST did not change significantly from the basal levels, in spite of the presence of increased levels of PLP and other B6 vitamers used for incubation. When PLP was used in the incubation studies, all of it was retained by the plasma and was associated with a marked suppression of plasma AST stimulation. To determine the degree to which plasma and erythrocyte AST was dose-dependent, plasma and haemolysates were incubated with increasing concentrations of PLP. A very significant inverse relationship was obtained in plasma between AST stimulation and PLP even at modest PLP levels, while haemolysates required incubation with much higher PLP concentrations to demonstrate the same effect. Since plasma PLP is considered to be the most reliable indicator of B6 nutritional status in man, our findings suggest that plasma percentage AST stimulation more closely reflects the B6 nutritional status than erythrocyte AST stimulation test which may reflect B6 status only in severe, longstanding B6 deficiencies. Conflicting results using erythrocyte AST stimulations may be attributed to the insensitivity of red cell AST to changes in PLP content. It is unlikely that the presence of non-PLP B6 vitamers in haemolysate may affect the percentage stimulation of aminotransferase enzymes by PLP.     

Sources of normal variation of plasma l-aspartate:2-oxoglutarate aminotransferase in Hereford range cattle

1. Plasma levels of L-aspartate:2-oxoglutarate aminotransferase (AST) were estimated in Hereford cattle, 1 month to 12 years of age, kept under range conditions and in a group of Hereford x Angus cows kept on the same range. 2. Plasma levels of AST were estimated in a group of Crossbred cows and their calves fed a constant diet and kept in individual pens in the same geographic area as the Herefords. 3. Seasonal changes in mean plasma AST were observed in the Herefords corresponding with the change from dry winter grasses/hay and well water to fresh spring and summer grasses and slough water. No seasonal changes were observed in the Crossbreds given a constant dry diet and city water. 4. Plasma AST increased with age in calves 1 to 12 months of age in the Herefords but not in the Crossbreds. Mean plasma AST did not change with age in any of the adult cattle studied. 5. Small increases in plasma AST corresponding to increases in ambient temperature above - 12 degrees C were observed in the Crossbreds. 6. An increase in plasma AST was observed near the time of first ovulation in the confined cows. 7. No relationship could be demonstrated between plasma AST and sex, breed or time to parturition in the range cattle. Breed differences were observed in the Crossbred cows.     

Transferrin fails to provide protection against Fas-induced hepatic injury in mice with deletion of functional transferrin-receptor type 2

We reported previously that Fas-induced hepatic failure in normal mice was attenuated or prevented by exogenous transferrin (Tf), particularly apoTf. Here we show in C57BL6J/129 mice with genetic inactivation of transferrin receptor 2 (TfR2^Y245X), that Fas-induced hepatotoxicity (apoptosis; rise in plasma aspartate aminotransferase (AST) levels) was comparable to that in wild-type mice, but was not modified by pretreatment with Tf. Rises in plasma AST were preceded by a decline in serum iron levels. AST elevations and iron declines were more profound in female than in male mice. Female mice also showed higher baseline levels of Bcl-xL in hepatocytes, which declined significantly upon treatment with agonistic anti-Fas antibody. These data confirm the cytoprotective function of Tf, and show a novel property of TfR2. Both apoptotic Fas responses and cytoprotective effects of Tf were associated with significant shifts in plasma iron levels, which quantitatively differed between male and female mice.     

Vitamin E Improves the Aminotransferase Status of Patients Suffering from Viral Hepatitis C: A Randomized,Double-Blind,Placebo-Controlled Study

Vitamin E has been shown to protect against liver damage induced by oxidative stress in animal experiments. Based on our previous findings of diminished vitamin E levels in patients suffering from viral hepatitis, we treated 23 hepatitis C patients refractory to a-interferon therapy with high doses of vitamin E (2 × 400 IU RRR-α-tocopherol/day) for 12 weeks. Study design: pro-spective randomized double-blind crossover design. Clinical parameters including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined for monitoring the disease state, in parallel vitamin E plasma levels and plasma lipids were determined. The plasma levels of the a-tocopherol were increased about 2-fold in all 23 patients. In 11 of 23 patients the clinical parameters indicative of liver damage were improved during the phase of vitamin E treatment (48% responders). ALT levels in responders were lowered by 46% and AST levels were lowered by 35% after 12 weeks of vitamin E treatment. Cessation of vitamin E treatment was followed by a rapid relapse of ALT and AST elevation, whereas retreatment led to a reproducible ALT decrease by 45% and AST decrease of 37% after a 6 months followup. Since vitamin E is non-toxic even at elevated doses ingested over extended periods, we suggest the treatment of patients refractory to α-interferon therapy suffering from hepatitis C with vitamin E as a supportive therapy.     

Sympathoadrenal responses to cold and ketamine anesthesia in the rhesus monkey

The effect of cold exposure on the sympathoadrenal system in primates was studied with and without ketamine anesthesia in eight adult rhesus monkeys. Each monkey was placed in a primate chair at a thermoneutral temperature (25 degrees C) for 1 h (control) followed by cold exposure (12 degrees C) for 3 h or placed in a circulating water bath (28 degrees C) to induce a decrease in core temperature (Tre) to 35 and 33 degrees C. Plasma catecholamines were analyzed by high-pressure liquid chromatography with electrochemical detection (60-65% recovery, coefficient of variation = 15%). The 3-h cold exposure was associated with a 175% increase above control levels of norepinephrine (NE) and a 100% increase in epinephrine (E). Decreases were evident in Tre (0.5 degree C), mean skin temperature (Tsk, 5.5 degrees C), and mean body temperature (Tb, 2.0 degrees C). Continuous infusion of ketamine (0.65 mg . kg-1 . min-1) resulted in no change in the plasma levels of NE and E from the control levels. Tre, Tsk, and Tb all showed greater declines with the addition of ketamine infusion to the cold exposure. Water exposure (28 degrees C) under ketamine anesthesia resulted in a drop in Tre to 33 degrees C within 1 h. Plasma levels of NE and E were unchanged from control values at Tre of 35 and 33 degrees C. The data suggest that the administration of ketamine abolished both the thermoregulatory response and the catecholamine response to acute cold exposure.     

Pronounced effect of minor changes in body temperature on ischemia and reperfusion injury in rat liver.

This study examined the effects of 1 degrees C hypo- or hyperthermia on in vivo liver ischemia and reperfusion (I/R) injury in 15 fasted male Wistar rats. Rats were ventilated, and rectal temperature was maintained at 36, 37 (normothermic), or 38 degrees C. In all rats, 70% liver ischemia was induced by clamping the afferent vessels to the median and left lateral lobes for 60 min, and reperfusion was allowed for 90 min. Changes in plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alpha-glutathione S-transferase (alpha-GST) levels were measured, hemodynamics and bile secretion were monitored, and arterial blood-gas analysis was performed. All ventilated rats showed a normal pH, arterial PCO(2), and arterial PO(2). AST, ALT, and alpha-GST levels were significantly higher in the 38 degrees C group when compared with the 36 and 37 degrees C groups after ischemia. No differences in bile secretion were found between all groups. Histopathological alterations were in agreement with AST, ALT, and alpha-GST levels in plasma. We conclude that a decrease of only 1 degrees C in body temperature significantly attenuates liver I/R injury, whereas an increase of 1 degrees C significantly increases liver I/R injury.     

Differential effects of dietary casein and soybean protein isolate on lipopolysaccharide-induced hepatitis in D-galactosamine-sensitized rats

Effects of dietary protein type on lipopolysaccharide (LPS)-induced hepatitis, as assessed by plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, were investigated in D-galactosamine (GalN)-sensitized rats. The plasma ALT and AST activities in rats fed on 25% soybean protein isolate (SPI) diet were significantly suppressed to about 1/4 and 1/5 of the values in rats fed on 25% casein diet, respectively, 8 h after the injection of LPS + GalN. Although hepatic ALT and AST activities of normal rats were also lower in the SPI group than in the casein group, this could not explain the differences in plasma enzyme activities between the two groups. The hepatic glutathione concentration of normal rats was lower in the SPI group than in the casein group, but it was reversed in rats injected with drugs. The results suggest that SPI can protect animals from LPS + GalN-induced hepatitis, and that the hepatic glutathione level may participate in the effects of SPI.     

Effects of ketamine on the cholecystokinin,somatostatin, substance P,and thyrotropin releasing hormone in discrete regions of rat brain

Intraperitoneal injection of ketamine (100 mg/kg body weight) significantly reduces the levels of cholecystokinin (CCK) somatostatin (SRIF), and substance P (SP)-like immunoreactivity in various regions of rat brain. No significant change in thyrotropin releasing hormone (TRH)-like immunoreactivity was observed. Neuropeptide systems may be involved in the neuropharmacologic effects of ketamine.     

Differential effects of N-methyl-D-aspartate receptor stimulation on growth hormone secretion at specific stages of postnatal development of the male rhesus monkey

The present study attempts to examine the role of N-methyl-D-aspartate (NMDA) receptor in the central regulation of growth hormone (GH) secretion during specific stages of pubertal development of the male rhesus monkey (Macaca mulatta). Infantile (n=4), prepubertal (n=5), peripubertal (n=5) and adult (n=5) intact male rhesus monkeys were given an agonist of NMDA receptor, N-methyl-D,L-aspartate (NMA) (15 mg/kg BW) through a teflon cannula implanted in the saphenous vein. Blood samples were collected 20-60 min before and 40-80 min after the injection of the drug at 10-20 min intervals. NMA was dissolved in normal saline immediately before use and passed through a 0.22 microm filter at the time of injection. All bleedings were carried out under ketamine hydrochloride anesthesia (initial dose 5 mg/kg BW, im followed by 2.5 mg/kg at 30 min intervals). The plasma levels of GH and testosterone (T) were determined by using specific assay systems. The hypothalamic-somatotrope activity under basal conditions was studied by averaging all the GH concentrations obtained before NMA injection, whereas the sensitivity of NMDA receptor to NMA stimulation was determined by comparing basal GH levels immediately before NMA injection at 0 min and GH concentrations obtained 10 min after the injection. The mean basal plasma concentrations of GH in the four groups of animals showed marked age-related differences. The levels of GH were found to be higher in infantile and peripubertal monkeys as compared to those of prepubertal and adult animals. A single iv injection of NMA produced differential effects on GH secretion during specific stages of postnatal development depending upon the level of GH secretion under basal conditions. Whereas NMA had no demonstrable effect on GH secretion in infantile and peripubertal animals in which the basal GH levels were high, it produced pronounced effects on GH secretion in prepubertal and adult monkeys wherein baseline GH concentrations were low. In conclusion, the present study suggests that the glutamatergic component of the control system that governs GH secretion by utilizing NMDA receptor may participate in regulation of age-related changes in the secretion of GH in the male rhesus monkey.     

Evaluation of miR-122 level in the plasma of chronically HCV infected patients

MicroRNAs (miRNAs) are small non-coding RNA molecules, which have an important function in regulating RNA stability and gene expression. They also can circulate in a cell-free form in the blood thatmakes them potential disease markers. The liver contains various classes of miRNAs in which miR-122 accounts for about 70% of all miRNAs and it has been proved that its level increases in case of liver damage. Here, we investigated plasma levels of miR-122 as a useful disease parameter in patients with chronic hepatitis C (CHC) infection. Thirty five hemophilia and thalassemia patients with CHC were studied. The total RNA was extracted from plasma samples, and miR-122 levels were measured by qPCR and then compared with the specific liver markers. The plasma levels of alanine transaminase (ALT) and aspartate transaminase(AST) were correlated with plasma miR-122 level in CHC patients, and the level of circulating miR-122 in healthy individual groups were rarely lower than those of patients with CHC. In our study, miR-122 levels correlated well with markers of liver inflammatory activity. Plasma miR-122 can be assumed to be another marker in liver similar to the currently used specific markers such as ALT and AST for evaluation of liver damage in hepatitis C virus (HCV) infected patients. Moreover, the correlation between miR-122 and ALT was shown to be higher than between miR-122 and AST.