Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Decompression sickness (DCS) is a complex and poorly understood systemic disease with wide interindividual resistance variability. We selectively bred rats with a threefold greater resistance to DCS than standard ones. To investigate possible physiological mechanisms underlying the resistance to DCS, including sex-related differences in these mechanisms, 15 males and 15 females resistant to DCS were compared with aged-matched standard Wistar males (n = 15) and females (n = 15). None of these individuals had been previously exposed to hyperbaric treatment. Comparison of the allelic frequencies of single nucleotide polymorphisms (SNPs) showed a difference of one SNP located on the X chromosome. Compared with nonresistant rats, the neutrophil-to-lymphocyte ratio and the plasmatic activity of coagulation factor X were significantly higher in DCS-resistant individuals regardless of their sex. The maximal relaxation elicited by sodium nitroprusside was lower in DCS-resistant individuals regardless of their sex. Males but not females resistant to DCS exhibited higher neutrophil and lymphocyte counts and higher prothrombin time but lower mitochondrial basal O2 consumption and citrate synthase activity. Principal components analysis showed that two principal components discriminate the DCS-resistant males but not females from the nonresistant ones. These components were loaded with activated partial thromboplastin time, monocyte-to-lymphocyte ratio, prothrombin time, factor X, and fibrinogen for PC1 and red blood cells count and neutrophils count for PC2. In conclusion, the mechanisms that drive the resistance to DCS appear different between males and females; lower coagulation tendency and enhanced inflammatory response to decompression stress might be key for resistance in males. The involvement of these physiological adaptations in resistance to DCS must now be confirmed.NEW & NOTEWORTHY By selective breeding of individuals resistant to decompression sickness (DCS) we previously obtained a rat model of inherited resistance to this pathology. Comparison of these individuals with nonresistant animals revealed differences in leukocyte counts, coagulation, and mitochondrial and vascular functions, but not resistance to oxidative stress. This study also reveals sex-related differences in the physiological changes associated with DCS resistance. A principal components analysis of our data allowed us to discriminate DCS-resistant males from standard ones, but not females. These differences represent possible mechanisms driving resistance to DCS. Although still far from the diver, this opens a pathway to future adaptation of personalized decompression procedures for "DCS-prone" individuals.
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PMID:Physiological characteristics associated with increased resistance to decompression sickness in male and female rats. 3270 69