RESUMEN
Maintaining acid-base homeostasis is critical for normal physiological function. The kidneys are essential for regulating acid-base homeostasis through maintaining systemic bicarbonate concentration. Chronic metabolic acidosis is an independent risk factor for chronic kidney diseases. Renal inwardly rectifying potassium channel Kir5.1 plays an essential role in maintaining resting membrane potential. Patients with loss-of-function mutations in KCNJ16 gene, which encodes Kir5.1, reveal tubulopathy with hypokalemia, salt wasting, and hearing loss. Importantly, these mutations also disrupt acid-base balance, particularly causing metabolic acidosis. This study aimed to use Dahl salt-sensitive rats with a knockout of the Kcnj16 gene (SSKcnj16-/-) to investigate how the deletion of Kir5.1 affects the regulation of acid-base balance in salt-sensitive hypertension. Results indicated that SSKcnj16-/- rats displayed metabolic acidosis under a normal salt (NS) diet. Further analysis using RNA-Sequncing and Western blotting showed unchanged expression of proteins responsible for ammonia metabolism in the kidney of SSKcnj16-/- rats despite observed acidosis. However, there was a significant increase in the expression of bicarbonate transporter NBCe1 while a significant decrease in pendrin. In conclusion, the current study demonstrated that the loss of Kir5.1 impairs the sensitivity of ammonia metabolism in the kidney in response to metabolic acidosis, which provides mechanistic insights into developing potential therapeutics for conditions involving hypokalemia and acid-base abnormalities.
RESUMEN
BACKGROUND: Paclitaxel-induced peripheral neuropathy (PIPN) is a disabling side effect of paclitaxel with few effective preventive strategies. We aim to determine the efficacy of pharmacological and non-pharmacological neuroprotective interventions in preventing PIPN incidence. METHODS: Biomedical literature databases were searched from years 2000 to 2021 for trials comparing neuroprotective interventions and control. Meta-analysis was performed using the random-effects model. The primary outcome was the incidence of PIPN. RESULTS: Of 24 relevant controlled trials, 14 were eligible for meta-analysis. Pooled results from seven non-pharmacological trials were associated with a statistically significant 48% relative reduction of PIPN risk with low heterogeneity. Conversely, pooled results from six pharmacological trials were associated with a significant 20% relative reduction of PIPN risk with moderate heterogeneity. Both pharmacological and non-pharmacological approaches appear effective in reducing PIPN incidence in the treatment arm compared to control (pooled RR < 1). CONCLUSION: Current evidence suggests that both interventions may reduce PIPN risk. Non-pharmacological interventions appear more effective than pharmacological interventions.
RESUMEN
PURPOSE: This study aimed to assess the clinical outcomes and adverse events among patients with implantable cardiac defibrillators (ICDs) in cardiac rehabilitation programs. METHODS: Data were compared for 42 consecutive patients with ICDs and 42 control patients matched by age, gender, and left ventricular ejection fraction without ICDs and enrolled in the same program. RESULTS: The number of cardiac rehabilitation exercise sessions for each group was 828 and 925, respectively. Only 1 patient experienced an ICD firing during exercise; there were no cardiac arrests and no deaths in either group. Compliance with cardiac rehabilitation was similar in both groups with most dropouts for nonmedical reasons and similar rates for cardiac-related reasons. Improvements in exercise capacity were similar between groups (30% in ICD patients and 37% in controls). CONCLUSIONS: Although larger studies are needed, these data suggest that supervised exercise training in patients with ICDs appears to be safe and effective.
