| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Kim, M, et al.
(författare)
-
Susceptibility of the developing brain to acute hypoglycemia involving A1 adenosine receptor activation
- 2005
-
Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 289:4, s. E562-E569
-
Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that the developing brain is less vulnerable to the adverse effects of hypoglycemia than the mature brain; however, this issue remains controversial. We also do not know the magnitude or duration of hypoglycemia needed to trigger hypoglycemic brain injury during development. To address this issue a series of in vivo and in vitro studies were performed. First, we established an acute model of insulin-induced hypoglycemia in mice by administering 3 U/kg of neutral-protamine Hagadorn insulin subcutaneously. When we examined degenerating neurons in hippocampus and striatum by TUNEL labeling, injury was observed after 4 h of hypoglycemia in postnatal day ( P)7 mice, and we observed more cell injury in animals rendered hypoglycemic at P 7 than at P21. Studies of hippocampal slice cultures revealed that reduction in glucose concentration induced more neuronal injury in slices prepared from P3 and P7 than from P14 and P21 mice. Treatment of slices with an adenosine A1 receptor (A1AR) antagonist reduced the hypoglycemic damage, whereas agonists increased damage, particularly in slices prepared from very young pups. This suggests a critically important role for A1ARs, which was further demonstrated by the reduction of hypoglycemic damage in hippocampal slices prepared from A1AR−/− mice. Furthermore, insulin-induced hypoglycemia in P7 A1AR−/− mice did not increase TUNEL-positive cells, but a major increase was seen in A1AR+/− mice. These observations show that the developing nervous system is indeed sensitive to acute hypoglycemic injury and that A1AR activation contributes to damage induced by hypoglycemia, particularly in immature mouse brain.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Ruilope, LM, et al.
(författare)
-
Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
-
Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
-
Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
