inositol-1-4-5-trisphosphate and Burns

In order to study the mechanism of abnormal macrophage (Mϕ) function in pro-inflammatory cytokine changes after burn, the inositol lipid signal system and its role in tumour necrosis factor-alpha (TNF-α) secretion by peritoneal Mϕs was observed in severely scalded mice.. Eighteen percent total body surface area (TBSA) full-thickness scalded mice were used as animal model in this experiment. Peritoneal Mϕs stimulated by lipopolysaccharide in vitro were collected at different time intervals (0, 2, 6, 12, 24 and 48 after burn hour (PBH)), The activities of phosphatidylinositol-phospholipase C (PI-PLC), inositol-1, 4,5, -triphosphate (IP(3)), protein kinase C (PKC), diacylglycerol (DAG) and TNF-α and the level of Ca(2+) concentration in peritoneal Mϕs were measured, and the effects of specific PKC inhibitor H-7 and calmodulin antagonist W-7 on the production of TNF-α were also observed.. After scald, increased activities of TNF-α and PLC of Mϕ were observed and peaked at 12 PBH. The activities of DAG and IP(3) and the concentration of Ca(2+) were markedly increased and reached their peaks at 24 PBH simultaneously. Membrane PKC activity was up-regulated after scald and showed a positive correlation with the change of DAG (r=0.83, P<0.05). There was also positive correlation between IP(3) and Ca(2+) activity (r=0.946, P<0.01). When 12 PBH was chosen as the time point for in vitro intervention with the pre-treatment by H-7, both membrane PKC and TNF-α activity decreased significantly. There was no obvious change of TNF-α activity with the application of W-7.. These results indicated that the abnormal activity of TNF-α of Mϕs might be regulated by the inositol lipid signal system following severe burn. The DAG-PKC signal pathway showed closer relationship than IP(3)-Ca(2+) in TNF-α production and could be the optimal target in the prevention and treatment of the systemic inflammatory response syndrome.

Topics: Animals; Burns; Calcium; Diglycerides; Inositol 1,4,5-Trisphosphate; Macrophages; Mice; Models, Animal; Peritoneum; Phosphatidylinositols; Protein Kinase C; Tumor Necrosis Factor-alpha

In this report, we have used a multiple stepwise regression analysis to determine the best derived multivariate equation between a dependent and multiple independent parameters. All parameters were derived from harvested gastrocnemius muscle subjected to chronic burn trauma. Correlations between seven different parameters were tested. Physiologic tension, calcium, adenosine 3':5' cyclic monophosphate (cAMP), inositol 1,4,5-triphosphate (IP3) and its catabolites comprised one large data matrix. From it, the various parameters were substituted as the dependent variable. The remaining parameters all comprised a multiple independent group. From such a format, the stepwise regression was run. The simultaneous co-governing of independent parameters over one dependent parameter provides a means of mathematically proving multiple correlations. Such findings provide a new perspective in interpreting chemical signalling.

Topics: Animals; Burns; Calcium; Cyclic AMP; Disease Models, Animal; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Male; Mice; Muscle, Smooth; Regression Analysis; Second Messenger Systems

Aberrant signal transduction processes within the diaphragm contribute to the weakness of this primary muscle involved in respiration. The importance of this report emphasizes how scald burn injury manifests distant systemic effects which impact on respiration. Scald burn injury from hot water is a common type of thermal injury in three specific patient groups: young children, the elderly, and the mentally and physically handicapped. Multivariate and vectorial analyses are presented within this paper with application to the effects of burn trauma on pharmacological signal transduction systems in the diaphragm. Multivariate equations showed the dependence of IP, on three to five independent variables. The independent variables included: burn size, glycerophosphate, and other polyinositols (inositol 1,4 biphosphate (I1,4P2), inositol 1 phosphate (I1P) and inositol). Graphic illustration of the equations used vectorial analysis. The multivariate analysis gives rise to a wider class of contributing factors than those observed using standard univariate relationships. This may be useful clinically in the identification of therapeutic agents for the treatment of respiratory problems in burn patients.

Topics: Animals; Burns; Diaphragm; Glycerophosphates; Inositol; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Mice; Multivariate Analysis; Signal Transduction; Specific Pathogen-Free Organisms

In this report, we have used multivariate and vectorial analyses to aid in understanding perturbations in diaphragmatic signal transduction in consequence to burn trauma. This trauma results from shock emanating from skin scald burn. Its respiratory complications are well-known. Relational matrices derived from experimental animal groups of varying body surface area (% BSA) burn size were subjected to individual multiple linear regression and vectorial analyses. Such individual matrices tested the simultaneous dependency of inositol 1,4,5-triphosphate (IP3) on inositol 1,4-biphosphate (I1,4P2), inositol 1-phosphate (I1P) and inositol. Understanding the contribution of multiple independent parameters simultaneously co-governing the dependency of IP3 offers new insight in regulating signal transduction mechanisms under the duress of burn trauma.

Topics: Analysis of Variance; Animals; Body Surface Area; Burns; Diaphragm; Disease Models, Animal; Inositol; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Male; Mice; Multivariate Analysis; Ointments; Polymers; Regression Analysis; Signal Transduction; Silver Sulfadiazine

The systemic effects of trauma from large body surface area (% BSA) burns were evaluated in terms of second messenger levels involving polyinositol phosphates as they related to adenosine 3':5'-cyclic monophosphate (cAMP), myoplasmic Ca2+, and active tension. Gastrocnemius muscles were harvested after muscle twitch at postburn day 21. Levels of polyinositols were measured by incorporation of myo-[2-3H]-inositol, with separation of the phosphates by anion-exchange chromatography. Analysis of variance was used for statistical evaluation. Multivariate relationships between the: 1) independent polyinositol forms (3H-inositol, I1P, and I1,4,P2) and dependent I1,4,5,P3 existed for control (R2 = 0.71) and 20% BSA burn (R2 = 0.67) groups; 2) the independent polyinositol forms (I1P, I1,4,P2, and I1,4,5,P3) and dependent cAMP for control (R2 = 0.73), 20% BSA (R2 = 0.99), and 50% BSA (R2 = 0.99) groups; 3) independent polyinositol forms (I1P, I1,4,P2, and I1,4,5,P3) and dependent 45Ca2+ for the control (R2 = 0.99), 20% BSA (R2 = 0.44), and 50% BSA (R2 = 0.82) groups; and 4) independent polyinositol forms (I1P, I1,4,P2, and I1,4,5,P3) and dependent active tension for 20% BSA (R2 = 0.97) and 50% BSA (R2 = 0.64) burn groups. Numerous interrelationships existed with each of the multivariate tests. These analyses confirm that several independent polyinositols contribute to changes in the second messengers of I1,4,5,P3, cAMP, and Ca2+ in skeletal muscle as a result of the systemic trauma of burn injury.

Topics: Animals; Burns; Calcium; Chromatography, Ion Exchange; Cyclic AMP; Glycerophosphates; Inositol; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Male; Mice; Muscle Contraction; Second Messenger Systems

Skeletal muscle weakness associated with burn trauma prolongs the time of rehabilitation of burn patients. Understanding the underlying chemical changes that impact on physiological tension may provide new therapeutic options for the treatment of burn patients. This report demonstrates the novelty of applying 3-dimensional graphic capabilities, involving area and vector changes to understand variations in inositol derivatives and their co-modulating influence on physiological tension in skeletal muscle. This muscle was distant from the primary anatomical burn site. It was subjected to circulatory shock emanating from burn trauma. Burn injury was achieved by scalding of predefined areas (0, 20% and 50%) on the dorsal and ventral surfaces of mice. At day 21, tension studies via muscle twitch analyses were performed. Through multiple regression, the dependency of physiologic tension was determined with respect to three poly-inositol forms each representing independent parameters simultaneously. The contribution of each of these parameters was assigned to a three-dimensional axis. Relationships of tension on three fixed independent parameters were found only for the 20% and 50% burn groups. Vector analysis on a plane in three-dimensional space determined the relationship of tension to each of the independent parameters in 20% and 50% burn groups. No significant relationship of tension dependency on three fixed poly-inositol variables was found in the control group. Such vector analysis, using solid and differential analytical geometry, allowed for a clear visualization of the interrelationships that existed between secondary messenger systems (viz, IP3) and a resulting physiologic manifestation (viz, tension). This clear visualization allows for a greater understanding of messenger systems that may lead to more effective treatment of skeletal muscle weakness associated with the systemic effects of severe burn trauma.

Topics: Animals; Burns; Disease Models, Animal; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Male; Mice; Mice, Inbred Strains; Multivariate Analysis; Muscle Contraction; Muscles; Regression Analysis; Signal Transduction

The purpose of this report was to see if changes in polyinositol phosphates occurred with increasing percentage body surface area (% BSA) burn. Burn injury was applied to predefined areas of the dorsal and ventral skin surface of mice. After a 10-min stimulation period involving muscle twitch, polyinositol phosphate levels at 3 weeks postburn were measured by the incorporation of myo[2-3H]inositol with separation of the phosphates by anion-exchange chromatography. Analysis of variance was used for all statistical evaluations. In gastrocnemius muscle an increase (P < 0.001) occurred for levels of [3H]inositol, inositol-1, phosphate (I1P), and inositol-1,4,5-trisphosphate (I1,4,5P3) for the 50 per cent BSA burn group. However, levels of inositol-1;4,biphosphate (I1,4P2) decreased (P < 0.001). Positive correlations were found between [3H]inositol, I1P and IP3 and 50 per cent BSA burn. A negative correlation between I1,4P2 and percentage BSA burn was found. These data provide evidence that polyinositol phosphate metabolism in skeletal muscle was altered due to large burn size.

Topics: Animals; Body Surface Area; Burns; Calcium; Hindlimb; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Male; Mice; Muscles