Dataset Information

Combined Statin and Glucocorticoid Therapy for the Safer Treatment of Preterm Birth.

ABSTRACT:

Background

Prematurity is strongly associated with poor respiratory function in the neonate. Rescue therapies include treatment with glucocorticoids due to their anti-inflammatory and maturational effects on the developing lung. However, glucocorticoid treatment in the infant can increase the risk of long-term cardiovascular complications including hypertension, cardiac, and endothelial dysfunction. Accumulating evidence implicates a molecular link between glucocorticoid excess and depletion of nitric oxide (NO) bioavailability as a mechanism underlying the detrimental effects of postnatal steroids on the heart and circulation. Therefore, combined glucocorticoid and statin therapy, by increasing NO bioavailability, may protect the developing cardiovascular system while maintaining beneficial effects on the lung.

Methods

We investigated combined glucocorticoid and statin therapy using an established rodent model of prematurity and combined experiments of cardiovascular function in vivo, with those in isolated organs as well as measurements at the cellular and molecular levels.

Results

We show that neonatal glucocorticoid treatment increases the risk of later cardiovascular dysfunction in the offspring. Underlying mechanisms include decreased circulating NO bioavailability, sympathetic hyper-reactivity, and NO-dependent endothelial dysfunction. Combined neonatal glucocorticoid and statin therapy protects the developing cardiovascular system by normalizing NO and sympathetic signaling, without affecting pulmonary maturational or anti-inflammatory effects of glucocorticoids.

Conclusions

Therefore, combined glucocorticoid and statin therapy may be safer than glucocorticoids alone for the treatment of preterm birth.

SUBMITTER: Kane AD

PROVIDER: S-EPMC10017302 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Combined Statin and Glucocorticoid Therapy for the Safer Treatment of Preterm Birth.

Kane Andrew D AD Herrera Emilio A EA Niu Youguo Y Camm Emily J EJ Allison Beth J BJ Tijsseling Deodata D Lusby Ciara C Derks Jan B JB Brain Kirsty L KL Bronckers Inge M IM Cross Christine M CM Berends Lindsey L Giussani Dino A DA

Hypertension (Dallas, Tex. : 1979) 20230201 4

<h4>Background</h4>Prematurity is strongly associated with poor respiratory function in the neonate. Rescue therapies include treatment with glucocorticoids due to their anti-inflammatory and maturational effects on the developing lung. However, glucocorticoid treatment in the infant can increase the risk of long-term cardiovascular complications including hypertension, cardiac, and endothelial dysfunction. Accumulating evidence implicates a molecular link between glucocorticoid excess and deple ...[more]

PMID: 36724801

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Project description:BACKGROUND:Immunoglobulin G4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated systemic disease. Despite its good response to steroid therapy, its treatment protocol is not standardized and the long-term outcome is controversial. The study was conducted to determine the short-term and long-term outcomes of IgG4-RS patients treated with glucocorticoids and steroid-sparing immunosuppressive agents, to analyze secretory function, serological and radiological changes in salivary glands and to assess the usefulness of serum IgG4 level as an indicator of disease activity. METHODS:IgG4-RS patients who were treated for more than 3 months were enrolled. Serological tests, salivary gland function assessment and computed tomography (CT) were performed before treatment and during follow up. The treatment outcomes in the short and the long term were evaluated, and the relationship between serum IgG4 level and salivary gland volume was analyzed. RESULTS:Glucocorticoids were used in all 43 patients and steroid-sparing immunosuppressive agents in 38 patients (88.4%). The follow-up period was 24.6 ± 14.9 months. Clinical remission was achieved in all patients after induction therapy. During short-term observation, salivary gland secretion significantly increased, and the serum IgG4 levels, the volumes and CT values of submandibular and parotid gland decreased significantly (P < 0.001). For long term, relapse occurred in 32.5% patients within 55 months in the regularly treated group, while all seven irregularly treated patients relapsed. However, the relapse-free survival curves were not significantly different between the steroid monotherapy and the combination therapy groups (P = 0.566). Submandibular glands, lacrimal glands, sublingual glands, nasal and paranasal cavity were commonly relapsing organs. In clinically stable patients, a serologically unstable condition occurred in 54.9% patients within 55 months and medication adjustment was performed accordingly. Volume changes in the submandibular and parotid glands were associated with serum IgG4 levels and time of follow up (R2adjusted = 0.905, P < 0.0001 and R2adjusted = 0.9334, P < 0.0001, respectively). CONCLUSIONS:The combination of glucocorticoid and steroid-sparing agents could be effective for treating IgG4-RS, and restoring salivary gland function. Serum IgG4 levels could predict disease activity.

Project description:BackgroundPeriodontitis during pregnancy is associated with an increased risk of preterm birth (<37 weeks of gestation) or low birthweight (<2500 g) offspring. Beyond periodontal disease, the risk of preterm birth varies both by previous history of preterm birth and in association with social determinants prevalent among vulnerable and marginalized populations. This study hypothesized that the timing of periodontal treatment during pregnancy and/or social vulnerability measures modified the response to dental scaling and root planing for the treatment of periodontitis and prevention of preterm birth.ObjectiveThis study aimed to determine the association of timing of dental scaling and root planing for gravidae with a diagnosed periodontal disease on the rates of preterm birth or low birthweight offspring among subgroups or strata of gravidae as part of the Maternal Oral Therapy to Reduce Obstetric Risk randomized controlled trial. All participants in the study had clinically diagnosed periodontal disease and differed by the timing of the periodontal treatment (dental scaling and root planing at <24 weeks [per protocol] or after delivery) or by baseline characteristics. Although all participants met the well-accepted clinical criteria for periodontitis, not all participants acknowledged a priori that they had periodontal disease.Study designThis was a per-protocol analysis of data from 1455 participants of the Maternal Oral Therapy to Reduce Obstetric Risk trial evaluating dental scaling and root planing on the risk of preterm birth or low birthweight offspring. Adjusted multiple logistic regression to control for confounders was used to estimate associations comparing the timing of periodontal treatment in pregnancy to receiving treatment after pregnancy (referent control) on rates of preterm birth or low birthweight among subgroups of gravidae with known periodontal disease. Study analyses were stratified, and the associations with the following characteristics-body mass index, self-described race and ethnicity, household income, maternal education, recency of immigration, and self-acknowledgment of poor oral health, were explored.ResultsDental scaling and root planing during the second or third trimester of pregnancy were associated with an increased adjusted odds ratio of preterm birth among those at the lower body mass index strata (18.5 to <25.0 kg/m2) (adjusted odds ratio, 2.21; 95% confidence interval, 1.07-4.98), but not among individuals who were overweight (body mass index of 25.0 to <30.0 kg/m2; adjusted odds ratio, 0.68; 95% confidence interval, 0.29-1.59) or obese (body mass index of ≥30 kg/m2; adjusted odds ratio, 1.26; 95% confidence interval, 0.65-2.49). There was no significant difference in pregnancy outcomes related to the other evaluated variables: self-described race and ethnicity, household income, maternal education, immigration status, or self-acknowledgment of poor oral health.ConclusionIn this per-protocol analysis of the Maternal Oral Therapy to Reduce Obstetric Risk trial, dental scaling and root planing had no preventive benefit against adverse obstetrical outcomes and were associated with increased odds of preterm birth among individuals at lower body mass index strata. There was no significant difference in the occurrence of preterm birth or low birthweight after dental scaling and root planing periodontitis treatment concerning other analyzed social determinants of preterm birth.

Dataset Information

Combined Statin and Glucocorticoid Therapy for the Safer Treatment of Preterm Birth.

Background

Methods

Results

Conclusions

Publications

Combined Statin and Glucocorticoid Therapy for the Safer Treatment of Preterm Birth.

Similar Datasets

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