32 research outputs found

    Dosing and safety profile of aficamten in symptomatic obstructive hypertrophic cardiomyopathy: results from from SEQUOIA‐HCM

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    Background: Aficamten, a novel cardiac myosin inhibitor, reversibly reduces cardiac hypercontractility in obstructive hypertrophic cardiomyopathy. We present a prespecified analysis of the pharmacokinetics, pharmacodynamics, and safety of aficamten in SEQUOIA‐HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). Methods and Results: A total of 282 patients with obstructive hypertrophic cardiomyopathy were randomized 1:1 to daily aficamten (5–20 mg) or placebo between February 1, 2022, and May 15, 2023. Aficamten dosing targeted the lowest effective dose for achieving site‐interpreted Valsalva left ventricular outflow tract gradient <30 mm Hg with left ventricular ejection fraction (LVEF) ≥50%. End points were evaluated during titration (day 1 to week 8), maintenance (weeks 8–24), and washout (weeks 24–28), and included major adverse cardiac events, new‐onset atrial fibrillation, implantable cardioverter‐defibrillator discharges, LVEF <50%, and treatment‐emergent adverse events. At week 8, 3.6%, 12.9%, 35%, and 48.6% of patients achieved 5‐, 10‐, 15‐, and 20‐mg doses, respectively. Baseline characteristics were similar across groups. Aficamten concentration increased by dose and remained stable during maintenance. During the treatment period, LVEF decreased by −0.9% (95% CI, −1.3 to −0.6) per 100 ng/mL aficamten exposure. Seven (4.9%) patients taking aficamten underwent per‐protocol dose reduction for site‐interpreted LVEF <50%. There were no treatment interruptions or heart failure worsening for LVEF <50%. No major adverse cardiovascular events were associated with aficamten, and treatment‐emergent adverse events were similar between treatment groups, including atrial fibrillation. Conclusions: A site‐based dosing algorithm targeting the lowest effective aficamten dose reduced left ventricular outflow tract gradient with a favorable safety profile throughout SEQUOIA‐HCM

    Levels of obestatin in euthyroid patients receiving levothyroxine replacement therapy

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    To investigate the relationship between obestatin and TSH levels in patients who received thyroid hormone replacement and were in the euthyroid state. Included 30 patients who were followed up in the endocrinology outpatient clinic in 2020, who received L-thyroxine replacement, and 30 healthy individuals without any chronic disease who did not receive thyroid hormone replacement. Blood samples were taken from both groups for obestatin, thyroid-stimulating hormone (TSH) and free T4 hormone (fT4) levels. There is significant difference in TSH levels (p = 0.007) was found between the two groups. The obestatin levels of the L-thyroxine replacement group were lower than those of the control group (p = 0.001). No correlation was observed between the TSH and obestatin levels in the control and L-thyroxine replacement groups. In this study, obestatin levels were significantly lower in patients who received L-thyroxine replacement therapy and were in euthyroid status than those in the control group. No correlation was found between obestatin and TSH levels in the control and patient groups. As a result of this study, the thyroid gland may play a more important role in the synthesis or regulation of obestatin synthesis beyond our current knowledge. [Med-Science 2022; 11(1.000): 131-4

    The Impaired Balances of Oxidant/Antioxidant and COX-1/COX-2 in Ovarian Ischemia-Reperfusion Injury and Prevention by Nimesulide

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    WOS: 000321086300017The aims of this study were to investigate the association of ovarian I/R injury with oxidant/antioxidant and cyclooxygenase activity and to examine the effect of nimesulide in I/R injury. Rats were divided into four groups: sham group, ischemia-reperfusion group (IR), nimesulide 25 mg/kg group (NIM 25), and nimesulide 50 mg/kg group (NIM 50). The severe oxidative stress and inflammation that occurred in the ovarian tissue treated I/R were recovered by treatment of nimesulide. The histopathological findings, severe haemorrhage, oedema, vascular congestion accompanied with migration and adhesion of polimorphonuclear leukocytes in the endothelium were observed in the IR group that MDA, MPO and COX-2 levels were found high whereas GSH and COX-1 levels were found low. The severe histopathological findings in IR group were moderate in NIM-25 group whereas those were slight in NIM-50 group. This finding suggests that nimesulide prevents injury due to reperfusion following ischemia better when used with dosage 50 mg/kg

    Effects of Hypericum perforatum and Hippophae rhamnoides extracts on indomethacin-induced gastric oxidative stress in rats

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    WOS: 000322308100005We investigate the effects of Hypericum perforatum (HP) and Hippophae rhamnoides (HR) extracts on indomethacin-induced gastric injury. Rats were divided into five groups each containing 10 animals. the first group received HP extract, the second group received HR, and the third group received a combination of HP: HR extract at a ratio of 60:40. Fourth group had indomethacin (control group). Fifth group was untreated healthy group. First four groups of animals were gavaged indomethacin and the degree of gastric injury was recorded. Glutathione (GSH), malondialdehyde (MDA) and DNA injury products from the gastric tissue were measured. in the indomethacin-treated control group, the ulcer area was 78.8 +/- 2.5/mm(2) and was significantly larger than the animals of HP, HR, HP+HR groups. When the groups were compared with the indomethacin-treated control group for GSH, MDA and DNA injury, the differences between all the groups were statistically significant. the mixture of HP and HR extracts showed maximum protective effects on indomethacin-induced gastric injury

    The effect of Lacidipine on Ischemia-Reperfusion Induced oxidative damage in ovaries of female rats.

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    WOS: 000318217500006In this study, we investigated the effects of lacidipine on XO, MDA, MPO, and GSH levels in ovarian tissues of rats, which are subjected to ischemia and post-ischemic reperfusion. In ovarian ischemia (OI), ovarian ischemia-reperfusion (OIR), 2 mg/kg lacidipine + ovarian ischemia (LOI-2), 4 mg/kg lacidipine + ovarian ischemia (LOI-4), 2 mg/kg lacidipine + ovarian ischemia-reperfusion (LOIR-2), 4 mg/kg lacidipine + ovarian ischemia-reperfusion (LOIR-4) and sham-operated healthy control group (HCG); XO 23.8 +/- 0.94, 13.6 +/- 0.76, 8 +/- 0.57, 5.8 +/- 0.60, 4.5 +/- 0.42, 3.6 +/- 0.55, 2.8 +/- 0.30 u/g, respectively, whereas MDA, 4.8 +/- 0.47, 13.33 +/- 0.66, 3.5 +/- 0.35, 3.4 +/- 0.42, 6.0 +/- 0.57, 5.3 +/- 0.61,2.8 +/- 0.22 mu mol/g protein, respectively. MPO, 6.1 +/- 0.60, 14.1 +/- 0.94, 6.3 +/- 0.66, 6.0 +/- 0.73, 8.8 +/- 0.60, 7.5 +/- 0.76, 6 +/- 1.06 u/g protein, respectively, while GSH 8.0 +/- 0.73, 3.1 +/- 0.47, 8.6 +/- 0.95, 8.9 +/- 0.91, 7.1 +/- 0.60, 7.5 +/- 0.76 ,9.1 +/- 0.47 nmol/g protein, respectively. The present study, conducted on the basis of the mechanism of formation of IR injury, demonstrated that lacidipine prevents ischemia-reperfusion injury in the ovarian tissues
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