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Chronic and acute ammonia toxicity in mudskippers, Periophthalmodon schlosseri and Boleophthalmus boddaerti: brain ammonia and glutamine contents, and effects of methionine sulfoximine and MK801

Ip YK, Leong MW, Sim MY, Goh GS, Wong WP, Chew SF

J Exp Biol, 2005 May;208(Pt 10):1993-2004.
PMID: 15879078

The objective of this study was to elucidate if chronic and acute ammonia intoxication in mudskippers, Periophthalmodon schlosseri and Boleophthalmus boddaerti, were associated with high levels of ammonia and/or glutamine in their brains, and if acute ammonia intoxication could be prevented by the administration of methionine sulfoximine [MSO; an inhibitor of glutamine synthetase (GS)] or MK801 [an antagonist of N-methyl D-aspartate type glutamate (NMDA) receptors]. For P. schlosseri and B. boddaerti exposed to sublethal concentrations (100 and 8 mmol l(-1) NH4Cl, respectively, at pH 7.0) of environmental ammonia for 4 days, brain ammonia contents increased drastically during the first 24 h, and they reached 18 and 14.5 micromol g(-1), respectively, at hour 96. Simultaneously, there were increases in brain glutamine contents, but brain glutamate contents were unchanged. Because glutamine accumulated to exceptionally high levels in brains of P. schlosseri (29.8 micromol g(-1)) and B. boddaerti (12.1 micromol g(-1)) without causing death, it can be concluded that these two mudskippers could ameliorate those problems associated with glutamine synthesis and accumulation as observed in patients suffering from hyperammonemia. P. schlosseri and B. boddaerti could tolerate high doses of ammonium acetate (CH3COONH4) injected into their peritoneal cavities, with 24 h LC50 of 15.6 and 12.3 micromol g(-1) fish, respectively. After the injection with a sublethal dose of CH3COONH4 (8 micromol g(-1) fish), there were significant increases in ammonia (5.11 and 8.36 micromol g(-1), respectively) and glutamine (4.22 and 3.54 micromol g(-1), respectively) levels in their brains at hour 0.5, but these levels returned to normal at hour 24. By contrast, for P. schlosseri and B. boddaerti that succumbed within 15-50 min to a dose of CH3COONH4 (15 and 12 micromol g(-1) fish, respectively) close to the LC50 values, the ammonia contents in the brains reached much higher levels (12.8 and 14.9 micromol g(-1), respectively), while the glutamine level remained relatively low (3.93 and 2.67 micromol g(-1), respectively). Thus, glutamine synthesis and accumulation in the brain was not the major cause of death in these two mudskippers confronted with acute ammonia toxicity. Indeed, MSO, at a dosage (100 microg g(-1) fish) protective for rats, did not protect B. boddaerti against acute ammonia toxicity, although it was an inhibitor of GS activities from the brains of both mudskippers. In the case of P. schlosseri, MSO only prolonged the time to death but did not reduce the mortality rate (100%). In addition, MK801 (2 microg g(-1) fish) had no protective effect on P. schlosseri and B. boddaerti injected with a lethal dose of CH3COONH4, indicating that activation of NMDA receptors was not the major cause of death during acute ammonia intoxication. Thus, it can be concluded that there are major differences in mechanisms of chronic and acute ammonia toxicity between brains of these two mudskippers and mammalian brains.
Comparative Demographics and Outcomes of Minimally Invasive Transforaminal Lumbar Interbody Fusion in Chinese, Malays, and Indians

Goh GS, Yue WM, Guo CM, Tan SB, Chen JL

Clin Spine Surg, 2021 Mar 01;34(2):66-72.
PMID: 33633059 DOI: 10.1097/BSD.0000000000001020

STUDY DESIGN: This study carried out a retrospective review of prospectively collected registry data.
OBJECTIVE: This study aimed to determine whether (1) utilization rates; (2) demographics and preoperative statuses; and (3) clinical outcomes differ among Chinese, Malays, and Indians undergoing minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF).
SUMMARY OF BACKGROUND DATA: There is a marked racial disparity in spine surgery outcomes between white and African American patients. Comparative studies of ethnicity have mostly been carried out in American populations, with an underrepresentation of Asian ethnic groups. It is unclear whether these disparities exist among Chinese, Malays, and Indians.
METHODS: A prospectively maintained registry was reviewed for 753 patients who underwent primary MIS-TLIF for degenerative spondylolisthesis between 2006 and 2013. The cohort was stratified by race. Comparisons of demographics, functional outcomes, and patient satisfaction were performed preoperatively and 1 month, 3 months, 6 months, and 2 years postoperatively.
RESULTS: Compared with population statistics, there was an overrepresentation of Chinese (6.6%) and an underrepresentation of Malays (5.0%) and Indians (3.5%) who underwent MIS-TLIF. Malays and Indians were younger and had higher body mass index at the time of surgery compared with Chinese. After adjusting for age, sex, and body mass index, Malays had significantly worse back pain and Indians had poorer Short-Form 36 Physical Component Summary compared with Chinese preoperatively. Chinese also had a better preoperative Oswestry Disability Index compared with the other races. Although significant differences remained at 1 month, there was no difference in outcomes up to 2 years postoperatively, except for a lower Physical Component Summary in Indians compared with Chinese at 2 years. The rate of minimal clinically important difference attainment, satisfaction, and expectation fulfillment was also comparable. At 2 years, 87.0% of Chinese, 76.9% of Malays, and 91.7% of Indians were satisfied.
CONCLUSION: The variations in demographics, preoperative statuses, and postoperative outcomes between races should be considered when interpreting outcome studies of lumbar spine surgery in Asian populations.
LEVEL OF EVIDENCE: Level III-nonrandomized cohort study.

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