This study was undertaken to examine the effects of hydrogen peroxide on stimulatory guanine nucleotide-binding protein (Gs), and coupling in the beta-adrenergic receptor-Gs-adenylate cyclase system in rat heart, in vitro. Cardiac membranes were preincubated with various concentrations (0.1, 1, and 10 mM) of hydrogen peroxide at 30 degrees C for 5, 10, 30 and 60 min. Although the assay of beta-adrenergic receptors involving [3H]-dihydroalprenolol ([3H]-DHA) binding revealed that the maximal number of binding sites (Bmax) was not altered, the dissociation constant (Kd) for [3H]-DHA was increased in the presence of 1 mM and 10 mM hydrogen peroxide (control 0.68 +/- 0.16 nM, vs 1 mM H2O2 1.13 +/- 0.16, 10 mM H2O2 1.01 +/- 0.12). Conversely, no significant changes in Gs activities were observed in hydrogen peroxide-treated groups. Adenylate cyclase activity (stimulated by forskolin) was significantly reduced by 10 mM hydrogen peroxide after a 5 min preincubation period (control 277.1 +/- 19.2 pmol cAMP/mg protein/min, H2O2 230.3 +/- 14.9). The amounts of cyclic AMP produced by the stimulation of membranes with GTP, GTP+(l)-isoproterenol, guanylimidodiphosphate (Gpp(NH)p) or Gpp(NH)p+(l)-isoproterenol were significantly lower in 10 mM hydrogen peroxide-treated groups than those in controls (GTP: control 57.6 +/- 5.6 pmol cAMP/mg protein/min vs H2O2 46.4 +/- 6.9, GTP+(l)-isoproterenol: control 83.9 +/- 10.2 vs H2O2 67.7 +/- 10.3, Gpp(NH)p: control 77.5 +/- 8.8 vs H2O2 61.0 +/- 8.6, Gpp(NH)p+(l)-isoproterenol: control 105.0 +/- 13.1 vs H2O2 83.9 +/- 12.2, forskolin: control 223.2 +/- 13.8 vs H2O2 182.8 +/- 18.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Reperfusion after reversible ischemia has been shown to result in prolonged depression of contractile function ("myocardial stunning"). Recent studies suggest that oxygen free radicals may mediate postischemic dysfunction. Since heart sarcolemmal membranes, which contain several types of enzymes, ion channels and receptors play important roles to maintain cell functions, the present study was undertaken to examine the effects of oxygen free radicals on heart sarcolemmal membrane functions in vitro. In the presence of a superoxide anion radical-generating system (2mM xanthine plus 0.03 U/ml xanthine oxidase), sarcolemmal Ca(2+)-stimulated ATPase activity and ATP-dependent Ca2+ accumulation were inhibited in an incubating time-dependent manner. Both lipid peroxidation (r = 0.82) and sulfhydryl group content (r = 0.95) showed significant correlations with Ca(2+)-stimulated ATPase activity. ATP-independent Ca2+ bindings were increased upon treating the membranes with xanthine plus xanthine oxidase. Voltage-dependent Ca(2+)-channels were also affected by oxygen free radicals. The maximal number of binding sites (Bmax) for [3H]-nitrendipine binding was depressed without any changes in dissociation constant (Kd). The effects of oxygen free radicals on adrenergic receptors were more complex. Bmax for [3H]-dihydroalprenolol (DHA) binding (beta-receptor) was increased whereas Bmax for [3H]-prazosin binding [alpha 1-receptor) was decreased after incubating the membrane with xanthine plus xanthine oxidase. Kd for [3H]-DHA or [3H]-prazosin binding was increased. Superoxide dismutase showed protective effects on the changes in these membrane functions due to xanthine plus xanthine oxidase. It is suggested that oxygen free radicals damage heart sarcolemmal membrane functions which may lead to cardiac dysfunction in the stunned myocardium.

Background: Antenatal magnesium sulphate (MgSO₄) therapy given to women at risk of preterm birth reduced the risk of cerebral palsy in early childhood. However, its effect on longer-term neurological outcomes remains uncertain. This study aimed to assess the effects of antenatal MgSO₄ therapy on school-age outcomes of preterm infants. Methods: We conducted a systematic review and meta-analysis. We searched MEDLINE, EMBASE, CENTRAL, and CINAHL for randomized controlled trials (RCTs). Two reviewers independently evaluated the eligibility for inclusion and extracted data. Results: Ten RCTs were included. Only two of them were on school-age outcomes. Antenatal MgSO₄ therapy had no impact on cerebral palsy, hearing impairment, neurosensory disability, and death at school-age. Meta-analysis on mental retardation and visual impairment was not able to be performed due to different methods of evaluation. In the analysis of short-term outcomes conducted as secondary outcomes, antenatal MgSO₄ therapy increased the risk of maternal adverse events with any symptom (3 RCTs; risk ratio 2.79; 95% confidence interval 1.10 to 7.05, low certainty of evidence) but was not associated with any neonatal symptoms. Conclusions: The number of cases was insufficient to determine the impact of antenatal MgSO₄ therapy on school-age outcomes. Further accumulation of long-term data is required.

Generalized arterial calcification of infancy (GACI) is a rare disease characterized by arterial calcification. GACI is caused by a mutation in the ENPP1 or ABCC6 genes. GACI causes severe hypertension and heart failure, and approximately 50% of patients die within the first 6 months. In particular, preterm infants with GACI often die due to immature cardiac function. Bisphosphonates are effective in treating GACI; however, no standardized treatment regimen is available. We experienced a case of a preterm infant with GACI born at 30 weeks gestation. Ultrasonography showed high-intensity lesions in the arteries, and computed tomography revealed calcification of the arteries throughout the body, leading to the diagnosis of GACI. We administered intravenous pamidronate, and her cardiac contraction improved. The initial scheduled interval between drug administrations was 2 months. However, the cardiac contraction worsened 1 month after the pamidronate administration. Therefore, we decreased the dosing interval and administered a second course of pamidronate, which improved her cardiac function. We then switched to oral etidronate. To improve the morbidity and mortality rates of preterm infants with GACI, it is important to obtain an early diagnosis of GACI by investigating high-intensity lesions in the arteries and performing early administration of an appropriate type of bisphosphonate.