Improved treatment results for childhood acute myeloid leukemia in Taiwan.

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.

Sheng mai san, a Chinese herbal medicine, protects against renal ischaemic injury during heat stroke in the rat.

1. There is evidence that the induction of inducible nitric oxide synthase (iNOS) and peroxynitrite by ischaemia/reperfusion may lead to renal cell injury. Herein, we investigated whether Sheng mai san (SMS), a Chinese herbal medicine, protects against renal ischaemic injury during heat stroke by reducing iNOS-dependent nitric oxide (NO) and peroxynitrite formation. 2. Urethane-anaesthetized rats were exposed to heat stress (ambient temperature 43 degrees C) to induce heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure and renal blood flow after the onset of heat stroke were significantly lower in heat stroke rats than in control rats. However, both colonic temperature and renal damage score were greater in heat stroke rats compared with control rats. Similarly, plasma NO, creatinine and blood urea nitrogen (BUN), as well as the renal immunoreactivity of iNOS and peroxynitrite, were significantly higher in heat stroke rats compared with their normothermic controls. 3. Pretreatment with SMS (1.2 g/day per rat for 7 consecutive days before the initiation of heat stress) significantly attenuated the heat stroke-induced arterial hypotension, hyperthermia, renal ischaemia and damage, the increased renal immunoreactivity of iNOS and peroxynitrite and the increased plasma levels of NO, creatinine and BUN. Pretreatment with SMS resulted in a prolongation of survival time in heat stroke. 4. The results of the present study suggest that SMS protects against renal ischaemic damage by reducing iNOS-dependent NO and peroxynitrite production during heat stroke.

The effect of glutamine-supplemented total parenteral nutrition on nitrogen economy depends on severity of diseases in surgical patients.

BACKGROUND: Gln is an important substrate for enterocyte and rapid proliferation cells. Studies have shown that parenteral supplementation of Gln maintains the intracellular Gln pool, improves nitrogen balance and shortens hospital stay. However, some studies showed Gln-supplemented TPN had no effect on restoring the Gln pool in critically ill patients. OBJECTIVE: To evaluate the effect of glutamine (Gln) dipeptide supplementation of total parenteral nutrition (TPN) on postoperative nitrogen balance and immune response of patients undergoing surgery. METHODS: This study is a prospective, randomized double-blind clinical trial. APACHE II score and TISS were used to evaluate the patients after admission. Forty-eight patients with major abdominal surgery were allocated to two groups to receive isonitrogenous (0.228 g nitrogen/kg/day) and isoenergetic (30 kcal/kg/day) TPN for 6 days. Two groups (Conv and Ala-Gln) were further divided to high (APACHE>or=6) and low (APACHE <6) groups. Control group (Conv) received 1.5 g amino acids/kg/day, whereas the Ala-Gln group received 0.972 g amino acids/kg/day and 0.417 g of L-alanyl-L-glutamine (Ala-Gln)/kg/day. Blood samples were collected on day 1 and day 6 after surgery for plasma amino acid and CD4, CD8 cell and T lymphocyte analysis. Cumulative nitrogen balance were also measured on day 2, 3, 4, 5 postoperatively. RESULTS: Although there was a tendency to have better cumulative nitrogen balance on the postoperative days in the Ala-Gln group, no significant difference was observed between two groups. However, a better significant cumulative nitrogen balance was observed on the 2nd, 3rd and 5th postoperative day in the Ala-Gln group than in the Conv group in patients with APACHE II <6, whereas no significant difference was noted in patients with APACHE II >or= 6. No difference in urine 3-methylhistidine excretion were observed between the 2 groups. Patients in the Ala-Gln group had significant higher T lymphocyte and CD4 cells than did those in the Conv group. CONCLUSION: TPN supplemented with Gln dipeptide had beneficial effect on enhancing the immune response. However, the effect of Ala-Gln administration on improving nitrogen economy was only observed in patients with low APACHE II scores. These results may indicate that Gln required for reversing the catabolic condition may depend on the characteristics and severity of the diseases.

The hypothermic effects of dl-tetrahydropalmatine in rats.

Systemic administration of dl-tetrahydropalmatine (THP; 10-50 mg x kg(-1) intraperitoneally) produced a proportional decrease in both colonic temperature and release of hypothalamic serotonin (5-hydroxytryptamine (5-HT)) in rats at room temperature. The hypothermia was brought about by cutaneous vasodilation and decreased metabolism. The THP- induced hypothermia was significantly attenuated in rats with brain 5-HT depletion produced by control injection of 5,7-dihydroxytryptamine or in rats with 5-HT2A receptor activation produced by 1-(2,5-dimethoxy-4-iodophenyl) -2-aminopropane, or in rats with 5-HT1A receptor antagonist produced by (-)-pindolol. The results suggest involvement of serotoninergic antagonism in the THP-induced hypothermia in rats

Involvement of brain glutamate release in pyrogenic fever.

Whether the glutamate release in the organum vasculosum laminae terminalis (OVLT) is attributable to genesis of a pyrogenic fever is unclear. The lack of information led us to evaluate the changes in glutamate concentrations of OVLT during the fever induced by staphylococcal enterotoxin A (SEA) in unanesthetized rabbits. Both the OVLT concentrations of glutamate and the colonic temperatures were simultaneously monitored during systemic injection of SEA, MK801 (an N-methyl-D-aspartate (NMDA) receptor channel blocker), ketamine (an NMDA receptor channel blocker), or normal saline. The extracellular dialysates in the brain were collected using a microdialysis probe previously placed in the OVLT region. The concentrations of glutamate in the microdialysates were measured by a high-pressure liquid chromatography in combination with a fluorescence detector. Systemic administration of SEA (30 ng x kg(-1) I.V.) increased both the concentrations of glutamate in the OVLT and the colonic temperatures. Glutamate appeared to rise slightly earlier than body temperature. Pretreatment or posttreatment with MK801 or ketamine significantly attenuated the SEA-induced augmenting glutamate release in the OVLT and fever in rabbits. The suppression of glutamate release appeared to start slightly earlier than temperature decline. In addition, the SEA-induced fever could be mimicked by direct injection of glutamate or SEA into the OVLT area. The fever induced by intra-OVLT injection of SEA or glutamate was significantly attenuated by pretreatment with an intra-OVLT dose of MK801 (5 microg) or ketamine (10 microg). The results suggest that glutamatergic pathways in the OVLT region are in pyrogenic fever genesis.

Effects of glutamine-supplemented total parenteral nutrition on cytokine production and T cell population in septic rats.

BACKGROUND: This study was designed to investigate the effects of total parenteral nutrition (TPN) enriched with glutamine (GLN) on in vivo cytokine production and cellular immune response in early and late septic stages of rats. METHODS: Male Wistar rats were divided into 2 experimental groups and received TPN solution at an energy level of 270 kcal/kg body weight. The TPN solutions were isonitrogenous and identical in nutrients composition except for differences in amino acid content. One group received 2% GLN, whereas the other group received glycine (Gly) instead. TPN was maintained for 5 or 6 days according to the sacrifice schedule of the rats. On day 5, sepsis was induced by cecal ligation and puncture (CLP). Respective groups of rats were sacrificed 2, 4, 6, and 24 hours after CLP. RESULTS: Sepsis resulted in a negative nitrogen balance in both groups, and nitrogen loss was significantly lower in the GLN than the Gly group. Interleukin (IL)-2 and interferon (IFN)-gamma in most of the samples collected at various time points were not detectable in plasma or peritoneal lavage fluid. No differences in plasma IL-6 and TNF-alpha concentrations were observed between the GLN and Gly groups. Also, there were no significant differences in IL-1beta, IL-6, and TNF-alpha concentrations in peritoneal lavage fluid between the 2 groups at various time points. The CD4+/CD8+ ratio was significantly higher in the GLN group than in the Gly group only at 4 hours after CLP, and no difference was observed at 24 hours after CLP. CONCLUSIONS: TPN preinfused with a GLN-supplemented solution had a beneficial effect in ameliorating the extent of negative nitrogen balance in septic rats. However, parenterally administered GLN did not reduce the production of inflammatory mediators systemically or at the site of injury, and the influence on enhancing cellular immunity was not obvious.

DL-Tetrahydropalmatine may act through inhibition of amygdaloid release of dopamine to inhibit an epileptic attack in rats.

DL-Tetrahydropalmatine (THP), an active component isolated from corydalis (a Chinese herbal medicine), possesses analgesic effects. Systemic administration of picrotoxin (3-4 mg/kg) produced increases of locomotion (including horizontal motion, vertical motion, and total distance traveled), elevations of turnings (including both clockwise and anticlockwise), and inhibition of postural freezing in freely moving rats, and increases of amygdaloidal release of dopamine in anesthetizes rats. All the afore-mentioned activity measures induced by picrotoxin were suppressed following THP pretreatment. The results indicate that THP may act through inhibition of amygdaloid dopamine release to inhibit an epileptic attack.

Chemical constituents from Drypetes littoralis.

Chemical investigation of Drypetes littoralis yielded three new tricyclic diterpenes, drypetenones A, B, and C (1--3), and one new xanthone (4). Spectral analyses and chemical correlations established the structures as 10S-12-hydroxy-11-methoxy-13-methylpodocarpa-1,5,8,11,13-pentaene-3,7-dione, (1), 10S-12-hydroxy-11-methoxy-13-methylpodocarpa-5,8,11,13-tetraene-3,7-dione (2), 10S-12-hydroxy-6,11-dimethoxy-13-methylpodocarpa-1,5,8,11,13-pentaene-3,7-dione (3), and 1-hydroxy-7-hydroxymethyl-6-methoxyxanthone (4). Complete (13)C NMR assignment of boehmenan D (5) is also made.

Effects of parenteral infusion with fish-oil or safflower-oil emulsion on hepatic lipids, plasma amino acids, and inflammatory mediators in septic rats.

This study was designed to investigate the effects of preinfusion with total parenteral nutrition (TPN) using fish-oil (FO) versus safflower-oil (SO) emulsion as fat sources on hepatic lipids, plasma amino-acid profiles, and inflammatory-related mediators in septic rats. Normal rats, with internal jugular catheters, were assigned to two different groups and received TPN. TPN provided 300 kcal. kg(-1). d(-1), with 40% of the non-protein energy as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fat emulsion, which was made of SO or FO. After receiving TPN for 6 d, each group of rats was further divided into control and sepsis subgroups. Sepsis was induced by cecal ligation and puncture; control rats received sham operation. All rats were classified into four groups as follows: FO control group (FOC; n = 7), FO sepsis group (FOS; n = 8), SO control group (SOC; n = 8), and SO sepsis group (SOS; n = 9). The results of the study demonstrated that plasma concentrations of triacylglycerol and non-esterified fatty acids did not differ between the FO and SO groups, regardless of whether the animals were septic. SOS had significantly higher total lipids and cholesterol content in the liver than did the SOC group. The FOS group, however, showed no difference from the FOC group. Plasma leucine and isoleucine levels were significantly lower in the SOS group than in the SOC group, whereas no difference in these two amino acids was observed between the FOC and FOS groups. Plasma arginine levels were significantly lower in both septic groups than in the groups without sepsis when either FO or SO was infused. Plasma glutamine levels, however, did not differ across groups. No differences in interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, or leukotriene B(4) concentrations in peritoneal lavage fluid were observed between the two septic groups. These results suggest that catabolic reaction in septic rats preinfused with FO is not as obvious as those preinfused with SO. Compared with SO emulsion, TPN with FO emulsion prevents liver fat accumulation associated with sepsis. However, parenterally administered FO had no beneficial effect in lowering cytokines and LTB(4) levels in peritoneal lavage fluid in septic rats induced by cecal ligation and puncture.

Heatstroke induces c-fos expression in the rat hypothalamus.

We induced heat stress in urethane-anesthetized rats (the animals were exposed to an ambient temperature at 42 degrees C), and monitored their colon temperature, mean arterial pressure and local cerebral blood flow. Rats 0, 20, 40 or 80 min after heat stress were sacrificed for determination of c-fos mRNA and protein expression in the paraventricular nucleus (PVN), supraoptic nucleus (SON) and preoptic nucleus (PON). The heatstroke, which appears as profound decreases in both mean arterial pressure and local cerebral blood flow and increases in colon temperature, is produced 80 min after heat stress. We show the c-fos mRNA and protein is strongly induced in all these nuclei of rat hypothalamus after the onset of heatstroke. We conclude that c-fos expression in the hypothalamus during rat heatstroke is associated with hyperthermia, arterial hypotension and cerebral ischemia.

Antiviral tannins from two Phyllanthus species.

Seven ellagitannins isolated from Phyllanthus myrtifolius and P. urinaria (Euphorbiaceae) have been shown, for the first time, to be active against Epstein-Barr virus DNA polymerase (EBV-DP) at the microM level. All these compounds have the same moiety of a corilagin, and differ from each other by different substitutions at C-2 and C-4 of the glucose core. SAR analysis and molecular modeling reveal that the essential pharmacophore of these tannins resides in the corilagin moiety. The outer complex carboxylic acid moieties appear to act only as auxopharmacore.

Enteral administration of glutamine in purulent peritonitis.

The intestinal hypomotility associated with purulent peritonitis is generally regarded as a contraindication to enteral nutrition. However, enteral nutrition may be feasible in suppurative peritonitis if administered with great caution, i.e., assuring the appropriate amount, delivery speed, and osmolality of the enteral formulation. Glutamine (Gln) increases muscle protein synthesis and decreases muscle protein degradation in sepsis, regardless of the route of administration. Therefore, administering small amounts of supplemental Gln via the enteral route to peritonitis patients may be beneficial. Two purulent peritonitis patients received L-Gln through a jejunostomy tube. The average amount of supplemental Gln was 16 g/d. Systemic inflammatory responses, i.e., high temperature and a high serum C-reactive protein level, persisted throughout the treatment period. Femoral arterial and venous blood samples were drawn simultaneously for determination of amino acid levels before and after 7 d of Gln supplementation. Enterally administered Gln was well-tolerated by both patients. There was an increase in plasma Gln levels after Gln supplementation. Moreover, the release of Gln, alanine, and phenylalanine from the lower extremities was lower after as compared to before Gln supplementation. Enteral administration of Gln may be feasible even in purulent peritonitis.

High-dose therapy with peripheral blood stem cell (PBSC) support using an innovative mobilization regimen in patients with high-risk primary or chemoresponsive metastatic breast cancers.

High-dose therapy followed by peripheral blood stem cell (PBSC) support was performed in 29 patients with primary high-risk (Group I) or chemoresponsive metastatic (Group II) breast cancer patients. Group I patients had received PBSC mobilization within 4 weeks of modified radical mastectomy. Group II patients had to achieve minimal residual disease (MRD) by induction chemotherapy before being considered eligible for PBSC mobilization and high-dose therapy. An innovative FE120C regimen (5-FU 600 mg/m2, i.v., day 1; epirubicin 120 mg/m2, i.v., day 1; cyclophosphamide 600 mg/m2, i.v., day 1) plus G-CSF (300 microg/day, subcutaneous injection for 9 days, from day 4 post-FE120C) was used to mobilize PBSCs. After high-dose CTCb (cyclophosphamide 6,000 mg/m2, thiothepa 500 mg/m2, carboplatin 800 mg/m2, in 4 days), patients received PBSC infusion and daily C-CSF 300 microg subcutaneous injection. There were 19 and 16 patients enrolled into Group I and Group II, respectively. Ten of the Group II patients had achieved minimal residual disease (MRD) after induction chemotherapy. The median numbers of mobilized total CD34 + cells for Group I and Group II patients were 27.3 (9.2 to 114.1) x 10(6)/kg and 17.1 (5.9 to 69.1) x 10(6)/kg respectively. The median time to neutrophil recovery (ANC > or = 500/microL) was 8 and 9 days in Group I and II, respectively. The median time to platelet recovery (> or = 50,000/microL) was 10 and 15 days in Group I and II, respectively. No major treatment-related toxicities were noted. In Group I, 13 out of 19 patients (68.4%; 43-87%, 95% C.I.) remained recurrence-free with a median follow-up of 31 months (6 + to 55 + months). In Group II, 3 out of 10 patients (30%; 7-65%, 95% C.I.) remained progression-free at 33 +, 35 +, 39 + months from induction therapy. We suggest that the FE120C plus G-CSF is an effective and innovative regimen for PBSC mobilization in breast cancer patients, and high-dose CTCb therapy with PBSC support is a safe and well-tolerated treatment modality.

Magnolol decreases body temperature by reducing 5-hydroxytryptamine release in the rat hypothalamus.

1. The effects of magnolol, isolated and purified from the cortex of Magnolia officinalis Rehd. et Wils, on thermoregulation and hypothalamic release of 5-hydroxytryptamine (5-HT) by in vivo microdialysis were assessed in normothermic rats and in febrile rats treated with interleukin-1 beta. 2. Intraperitoneal administration of magnolol (25-100 mg/kg) produced a decrease in colon temperature, an increase in foot skin temperature, a decrease in metabolic rate and a decrease in the endogenous release of 5-HT in the rat hypothalamus. 3. Depletion of rat brain 5-HT, produced by intracerebroventricular pretreatment with 5,7-dihydroxytryptamine, attenuated the magnolol-induced hypothermia, cutaneous vasodilation and decreased metabolism. 4. Intracerebroventricular administration of (+/-)-2,5-dimethoxy-4-iodoamphetamine (a 5-HT2 receptor agonist; 5-10 micrograms/5 microL) increased basal colon temperature and reversed the magnolol-induced hypothermia. 5. The increases in both colon temperature and hypothalamic 5-HT release produced by interleukin-1 beta injection were attenuated by treatment with magnolol. 6. The data suggest that magnolol decreases body temperature (due to increased heat loss and decreased heat production) by reducing 5-HT release in rat hypothalamus.

Changes in extracellular serotonin in rat hypothalamus affect thermoregulatory function.

Experiments were carried out to determine the effects of altering the serotonin (5-HT) levels in the hypothalamus on thermoregulatory function in unanesthetized restrained rats. Local perfusion of the hypothalamus with dialysis solution containing 5-hydroxytryptophan (a 5-HT precursor), fluoxetine (a 5-HT reuptake inhibitor), or high potassium significantly increased both colonic temperature (Tco) and the extracellular concentrations of 5-HT in the hypothalamus. Reciprocally, both extracellular concentration of 5-HT in the hypothalamus and Tco were decreased with a dialysis solution containing tetrodotoxin (which blocks the voltage-dependent sodium channel), zero calcium concentration, or systemic administration of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT,5-HT1A agonist). Intrahypothalamic administration of 8-OH-DPAT and (2,5-dimethoxy-4-iodophenyl)-2-aminopropane (a 5-HT2 agonist) produced hypothermic and hyperthermic effects, respectively. The results indicate that elevating the 5-HT levels in the hypothalamus activates postsynaptic 5-HT2 receptors and results in hyperthermic effects, whereas stimulation of presynaptic 5-HT1A receptors in the hypothalamus reduces the endogenous 5-HT release and results in hypothermic effects.

Effects of growth hormone and insulin-like growth factor I on opsonin receptor expression on local and systemic phagocytes in a lethal peritonitis model.

OBJECTIVE: To investigate the effects of pretreatment with growth hormone (GH) and insulin-like growth factor I (IGF-I) on phagocyte exudation and bacterial clearance, focusing on CD11b and CD32/CD16 expression on local and systemic phagocytes, in a lethal peritonitis model. DESIGN: Prospective randomized experimental study. SETTING: Research laboratory in a university hospital. SUBJECTS: Balb/c mice (n = 21). INTERVENTIONS: Mice were challenged intraperitoneally with 1 x 10(8) Escherichia coli, after 6 days of pretreatment with saline (control), GH (4.8 mg/kg/day), or IGF-I (24 mg/kg/day). Samples were harvested at 4 hrs after the challenge. MEASUREMENTS AND MAIN RESULTS: Viable bacterial counts in peritoneal lavage fluid (PLF) and blood were determined. Peritoneal exudative cells and peripheral blood leukocytes were counted and analyzed for receptor expressions by flow cytometry. GH reduced viable bacterial counts in PLF, as compared with the saline control. GH (three-fold) and IGF-I (two-fold) increased the number of peritoneal exudative neutrophils (PENs), as compared with the saline control. The number of PENs showed an inverse correlation with PLF viable bacterial counts. By contrast, there were no differences in peripheral blood neutrophil (PN) counts among the three groups, nor was there a correlation between PN and PEN counts. CD11b expression was greater on PENs than on PNs in all three groups. CD11b expression on PNs did not differ among the three groups. However, GH increased CD11b expression on PENs, as compared with saline and IGF-I, and this expression showed a positive correlation with PEN numbers and an inverse correlation with PLF viable bacterial counts. CD11b expression on peritoneal macrophages and peripheral blood monocytes did not differ among the three groups. There were no differences in phagocyte CD32/CD16 expression among the three groups. CONCLUSIONS: GH pretreatment enhanced CD11b expression on PENs, but not PNs, possibly in association with enhanced neutrophil recruitment, phagocytosis, and bacterial elimination by PENs, without activation of PNs. GH prophylaxis may be useful for reducing the frequency rate and severity of septic complications, via modulation of CD11b expression on local and systemic neutrophils.

Catecholaminergic mechanisms-mediated hypothermia induced by magnolol in rats.

Intraperitoneal administration of magnolol (25-100 mg/kg) produced a dose-related fall in rats' colonic temperature. The magnolol-induced hypothermia was attenuated by pretreatment with intracerebroventricular 6-hydroxydopamine (200 microg/rat). The L-DOPA (200 mg/kg, i.p.) plus benserazide (50 mg/kg, i.p.)-induced hyperthermia was attenuated by magnolol. On the other hand, the alpha-methyltyrosine (100 mg/kg, i.p.)-induced hypothermia was potentiated by magnolol. Furthermore, magnolol (50 mg/kg, i.p.) decreased the dopamine and norepinephrine release in the hypothalamus, but did not change the concentrations for their metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid). The data suggest that magnolol decreases colonic temperature by reducing catecholaminergic activity in rat hypothalamus.

Glutamine-enhanced bacterial killing by neutrophils from postoperative patients.

Neutrophils play an important role in host defense by phagocytosing and destroying invading bacteria. A recent investigation revealed that glutamine (Gln) augmented the in vitro bactericidal activity of neutrophils from burn patients. However, it is unclear whether Gln enhances the function of neutrophils in postoperative patients. This study was designed to investigate the effect of Gln on the in vitro Escherichia coli-killing activity of neutrophils from postoperative patients. Nine randomly selected patients were included in this study. On the morning of the first postoperative day, blood was drawn and neutrophils were isolated. Eight healthy volunteers served as controls. E. coli was opsonized with pooled normal serum. Neutrophils (5 x 10(6)), together with opsonized E. coli (5 x 10(5)), were incubated for 2 h at 37 degrees C in Hanks' balanced salt solution supplemented with 0, 100, 500, or 1000 nmol/mL of Gln. The bactericidal function of neutrophils was determined by counting the number of viable bacteria. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-8, and granulocyte elastase levels in the cell culture supernatant were measured. Plasma C-reactive protein (CRP), cortisol, and amino acids were also analyzed. The plasma concentration of Gln was significantly lower in the postoperative patients than in the controls. Following culture with patient neutrophils, the number of viable E. coli decreased by 26% as the in vitro Gln concentration was increased from 500 to 1000 nmol/mL (P < 0.01). We defined the Gln 1000/Gln 500 ratio of the number of viable bacteria as the number of viable E. coli at an in vitro Gln concentration of 1000 nmol/mL divided by the number of viable E. coli at an in vitro Gln concentration of 500 nmol/mL. A positive correlation was thus demonstrated between the plasma Gln level and the Gln 1000/Gln 500 ratio of the number of viable bacteria in the patients (r = 0.69, P = 0.04). This finding indicated that as plasma Gln fell, there was an enhancement of neutrophil E. coli-killing activity by neutrophils in in vitro tests when the Gln concentration was increased from 500 to 1000 nmol/mL. Gln supplementation caused no appreciable changes in TNF-alpha, IL-1 beta, IL-8, or granulocyte elastase levels in cell culture supernatants. A negative correlation was recognized between the patient plasma Gln level and the Gln 1000/Gln 500 ratio of the cell culture supernatant IL-8 level (r = -0.73, P = 0.025). In conclusion, Gln supplementation enhanced the in vitro bactericidal function of neutrophils from postoperative patients.

Dexamethasone administered into organum vasculosum laminae terminalis of rabbits induced antipyresis via inhibiting nitric oxide pathway in situ.

Direct administration of lipopolysaccharide (LPS) into the organum vasculosum laminae terminalis (OVLT) increased the amount of nitric oxide (NO) release and inducible NO synthase expression. These increases paralleled the increase in deep body temperature in unanesthetized rabbits. Pretreatment with dexamethasone, a synthetic glucocorticoid, not only reduced the fever but also attenuated the NO release and the inducible NO synthase expression in the OVLT following an intra-OVLT dose of LPS. The data suggest that steroids such as dexamethasone exert their antipyresis by inhibiting the NO pathway in the OVLT of rabbit brain.

Glutamine-enriched enteral diet enhances bacterial clearance in protected bacterial peritonitis, regardless of glutamine form.

BACKGROUND: The effects of glutamine (Gln)-enriched enteral diets on bacterial clearance were investigated in a rat protracted peritonitis model. The effects of the Gln form, peptide-based vs free amino acid-based, were also compared. METHODS: Twenty-three rats underwent gastrostomy. An osmotic pump was implanted in the peritoneal cavity. The rats received a continuous intragastric infusion of one of three diets: Gln-depleted (Gln 0), Gln-enriched with the Gln in free amino acid form (Gln F), or Gln-enriched with the Gln in oligopeptide form (Gln P). The three formulas were isocaloric and isonitrogenous. The pumps delivered a continuous infusion of Escherichia coli, starting at 48 hours after implantation, for 24 hours. Then, the animals were killed. RESULTS: Bacterial numbers in peritoneal lavaged fluid (PLF) and the liver were significantly lower in the Gln P and Gln F groups than in the Gln 0 group. The bacterial number in PLF correlated with that in the liver. Neither the number nor the population of peritoneal exudative cells differed among groups. Plasma levels of proline, alanine and citrulline were significantly higher in the Gln P and Gln F groups than in the Gln 0 group. Both Gln supplemented groups showed significantly greater villous height, crypt depth, and numbers of mitoses per crypt in the small intestine than the Gln 0 group. CONCLUSIONS: Supplemental Gln enhances peritoneal and hepatic bacterial clearance, regardless of Gln form. Gln-enriched may be more beneficial than Gln-depleted enteral diets in peritonitis.