A study was conducted to clarify the quantitative relationship between the alteration of protein metabolism and the severity of surgical stress to further understand the mechanisms of body nitrogen losses in surgical trauma. Twenty-one patients undergoing esophagectomy for esophageal cancer (group E), and 22 undergoing gastrectomy or colorectal operations for gastric or colorectal cancer (Group GC) were studied. All patients were fed exclusively by parenteral nutrition (PN) providing 1.5 g protein.kg-1.d-1 and 35 kcal.kg-1.d-1 before and after the operation. The measurements of whole-body protein turnover, synthesis, and breakdown were performed preoperatively and on postoperative days (PODs) .3 and 10. Urinary excretion of total nitrogen and total catecholamines was also measured. Urinary excretion of the total catecholamines of group E was twice as high as that of group GC on the POD 3 and well reflected the severity of surgical stress. Negative correlation of nitrogen retention to urinary excretion of the total catecholamines was also observed (r = 0.64; P < 0.01). The correlations between the urinary excretion of the total catecholamines and the whole-body protein flux, synthesis, and breakdown were statistically significant (r = 0.57, 0.27, and 0.57, respectively; P < 0.01 in all). Rate of elevation in breakdown according to the stress level was greater than that of synthesis. Consequently the progressive aggravation of nitrogen balance according to the severity of surgical stress was observed.

Catecholamines↗

PubMedDate not supplied

The importance of warming at 37 degrees C for removal of leukocytes and platelets from reconstituted red cells.

Red cells suspended in sodium phosphate buffer (R-RBC) were incubated at 37 degrees C, and the distribution of the leukocytes and platelets in the suspension was compared to a similar suspension incubated at 22 degrees C. Following centrifugation, a more dense packing of the red cells was observed in warm R-RBC, and less leukocytes and platelets remained in the red cells below the buffy coat, than was observed in R-RBC packed at room temperature. These experiments indicate that incubation at 37 degrees C prior to separation improves the quality of leukocyte- and platelet-depleted red cells.

Blood Platelets↗

PubMedDate not supplied

Platelet factor 4 release from the platelets stored in platelet concentrates.

Many consider that granular components of platelets should remain intact during storage of platelet concentrates (PCs) in order to participate in hemostasis when infused. The present investigations were done to determine factors affecting the release of an alpha-granular component, platelet factor 4 (PF-4), from platelets stored as PCs. Sedimentation of the pelleted platelet button and stronger flat-bed agitation induced a significant PF-4 release. After 1 day of storage at 22 degrees C, the percent PF-4 release correlated roughly with a pH fall in PCs (r = 0.520, y = 0.014 + 7.204). Rates of pH fall were roughly proportional to the platelet count. In addition, there was a positive relationship between PF-4 release and the platelet count per unit volume (r = 0.615, y = 0.045 + 1.327). The results indicated that one of the critical factors which determines the amount of PF-4 release during storage is concentrated pH. Lowering the platelet count per unit volume in PCs is better for the maintenance of granular components in platelets during storage because of the intact platelet metabolism.

Adolescent↗

PubMedDate not supplied

Effects of intravenous omega-3 and omega-6 fat emulsion on cytokine production and delayed type hypersensitivity in burned rats receiving total parenteral nutrition.

BACKGROUND: The effects of fat emulsions containing omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) on fatty acid profile, cytokine production, and delayed type hypersensitivity (DTH) in burned rats receiving total parenteral nutrition (TPN) were investigated. METHODS: A fat emulsion containing only eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was prepared (omega-3 fat emulsion). Sprague-Dawley rats were fed fat-free chow for 2 weeks and were divided into three groups according to the contents of TPN. Groups C (n = 11) and C' (n = 14) received fat-free TPN. Group omega6 received safflower oil emulsion containing linoleic acid (omega-6 PUFA) (n = 11). Group omega3 (n = 11) received safflower oil emulsion (19% of total caloric intake) and fat emulsion containing only EPA and DHA (1% of total calories). On day 5, all rats except for those in group C' were subjected to a 20% full-thickness burn. Group C' did not receive burns. After 48 hours, the rats were killed. RESULTS: The interleukin (IL)-8 concentration was significantly 45% lower in group omega3 than in group C (p < .05). The IL-10 concentration was significantly 15% lower in group omega3 than in group omega6 (p < .05). The IL-6 concentration was increased in group omega6 but not in group omega3 when compared with group C. The IL-6 and IL-8 were not detected in group C'. Prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) concentrations were increased by burn injury, but there were no significant differences among the burned groups. Cell-mediated immunity was thus significantly decreased in burned groups (groups C, omega6, and omega3; p < .01). However, the decrease of DTH was smaller in group omega3 and significantly greater when compared with groups C and omega6 (p < .05). CONCLUSIONS: omega-6 PUFAs increased serum inflammatory cytokine levels in a stressed state. omega-3 fat emulsion reduced IL-8 and IL-10 levels and prevented immunosuppression in burned rats that were receiving TPN.

Animals↗

PubMedDate not supplied

Effect of IGF-1 on protein metabolism in burned rats.

The effects of insulin-like growth factor-1 (IGF-1) on the catabolic and immune response induced by thermal injury were studied in burned rats fed by TPN. An increase of synthesis greater than the increase of breakdown resulted in improved nitrogen retention in the IGF-1 group. There was no effect on the mRNA in the structural proteins of the skeletal muscle and liver. However, the gene expression of albumin and the structural proteins of the diaphragm increased significantly in the rats receiving IGF-1. The proliferation of the gut mucosa and the fractional protein synthesis rate of the small intestine increased, and the endotoxin content of the liver and spleen were smaller in the burned rats that received IGF-1. Delayed type hypersensitivity increased significantly (p < .01) in the IGF-1 group. In conclusion, IGF-1 improved the whole-body protein metabolism, and albumin and respiratory muscle protein synthesis in the burned rats. It significantly promoted the proliferation of the intestinal mucosa, and reduced the intestinal translocation of endotoxin. Cellular immunity was also enhanced.

Analysis of Variance↗

PubMedDate not supplied

Induction of apoptosis in CTLL-2 cells by protocatechualdehyde.

The purpose of this study was to investigate the possible molecular mechanisms of the antiproliferative effect induced by protocatechualdehyde (PA, a dihydroxybenzene derivative). The viability of cytotoxic T cells (CfLL-2) stimulated by IL2 was significantly inhibited at 0.12 mM PA. This inhibitory effect was associated with the induction of apoptosis detected by DNA fragmentation assay. DNA ladder appeared at 0.12 mM PA and the intensity of DNA ladder was visible at 0.3 mM PA. PA inhibited the Ib2-dependent tyrosine phosphorylation of 91, 80 and 55 KDa proteins, but did not affect IL2-dependent serine/threonine phosphorylation of proteins. The levels of bcl-2 protein and mRNA were suppressed by PA. An alteration in bax protein expression on the apoptosis process in CTLL-2 cells was not observed. However, caspase-3 activity was increased by PA. Our results demonstrate that PA inhibited cell proliferation and induced apoptosis in CTLL-2 cells. It is concluded that PA is a potent anti-proliferative agent and is expected to be a promising candidate for novel therapeutics.

Apoptosis↗

PubMedDate not supplied

Epidermolysis bullosa acquisita: correlation of IgE levels with disease activity under successful betamethasone/dapsone combination therapy.

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Adult↗

PubMedDate not supplied

Pharmacological profile of a new 5-hydroxytryptamine2 receptor antagonist, DV-7028.

The pharmacological profile of DV-7028, a pyrido triazine derivative, showed that it is a potent and selective 5-hydroxytryptamine (5-HT)2 receptor antagonist. DV-7028 bound to 5-HT2 receptors in rat brain membranes with a Ki value of 22 nM and caused shifts to the right of the concentration-contraction curves to 5-HT in rat thoracic aorta and canine femoral arteries, which are attributed to activation of 5-HT2 receptors. The compound was highly active by oral administration (0.1-10 mg/kg) based on blockade of the 5-HT-induced pressor responses in pithed rats. In contrast, DV-7028 had no affinity for 5-HT1A, 5-HT1B and 5-HT1D receptors. The affinity of the compound was 14-26 times greater for the 5-HT2 receptors when compared to 5-HT1C, adrenergic alpha 1, dopamine D2 and histamine H1 receptors. In human platelets, DV-7028 attenuated the aggregation induced by collagen and inhibited the amplifying effect of 5-HT with collagen on platelet aggregation. Furthermore, a 10-day toxicity study revealed that DV-7028 was a safe compound which did not produce lethality at repeated oral doses of 800 mg/kg/day in rats. These results indicate that DV-7028 is a selective and potent 5-HT2 receptor antagonist which is orally active and safe.

Animals↗

PubMedDate not supplied

Inhibition of farnesyl protein transferase by monoterpene, curcumin derivatives and gallotannin.

Ras proteins must be isoprenylated at a conserved cysteine residue near the carboxyl terminus (Cys-186 in mammalian Ras p21 proteins) in order to extend their biological activity. Previous studies have indicate an intermediate in the mevalonate pathway, most likely farnesyl pyrophosphate, is the donor of this isoprenyl group, and that using inhibitors of the mevalonate pathway could block the transforming properties of ras oncogene. Unfortunately, mevalonate is a precursor of various end products essential to mammalian cells, such as dolichols, ubiquinones, heme A, and cholesterol. In this study, we partially purified farnesyl protein transferase (FPTase) capable of catalyzing the farnesylation of unprocessed Ras p21 proteins in vitro from porcine kidney epithelial-like LLC-PK 1 cells, human lung adenocarcinoma A549 cells and human pancreatic cancer MIA PaCa-2 cells. This FPTase activity requires a divalent cation, such as Mg2+ or Zn2+ ions, sulfhydryl protecting agent, DTT, as well as certain pH which is linear with time and with enzyme concentration, and is present in many mammalian normal cell and tumor cell lines. Sequentially, we observed the effects of the monoterpene compound, d-limonene; curcumin derivatives, CD-I and CD-II; polyphenol compound, gallotannin; Salvia miltiorrhiza derivative, SMD; and retinoid acid derivative, RAD on FPTase activity. We found that curcumin derivatives and gallotannin had a strong inhibition on FPTase besides d-limonene, while gallotannin was the strongest among synthetic and natural compounds tested. Salivia miltiorrhiza and retinoid acid derivatives had no influence on FPTase activity. Our results suggest that compounds containing polyphenol hydroxyl may be a new source of FPTase inhibitors. The experiment also showed that availability of an in vitro farnesyl protein transferase assay could be useful in screening for potential inhibitors of ras oncogene function that will not interfere with other aspects of the mevalonate pathway.

Alkyl and Aryl Transferases↗