Impact of prenatal opioids on cardiac and autonomic development: systematic review and meta-analysis.

Prenatal opioid exposure has recently risen four-fold with limited data on the developmental effects on neonatal physiology. The objective of this systematic review is to develop an association between prenatal opioid exposure and fetal and neonatal cardiac and autonomic development and function. The review was conducted in accordance with PRISMA Guidelines, and searches were conducted using PubMed, Embase, CINAHL, and Web of Science between May 25 and October 27, 2020. Twenty studies fit inclusion criteria, in four categories: (1) fetal cardiac outcomes, (2) neonatal cardiac outcomes, (3) noninvasive autonomic outcomes, and (4) clinical and behavioral measures. For the meta-analysis, three studies (total of 210 subjects) were included. Effect sizes were measured as the mean difference in fetal heart rate between opioid-exposed and non-exposed groups. Mothers with prenatal opioid use had a significantly lower fetal heart rate as compared to mothers without prenatal opioid use, requiring further studies to determine clinical significance.

Insights into the Mechanisms of Fetal Growth Restriction-Induced Programming of Hypertension.

In recent decades, both clinical and animal studies have shown that fetal growth restriction (FGR), caused by exposure to adverse uterine environments, is a risk factor for hypertension as well as for a variety of adult diseases. This observation has shaped and informed the now widely accepted theory of developmental origins of health and disease (DOHaD). There is a plethora of evidence supporting the association of FGR with increased risk of adult hypertension; however, the underlying mechanisms responsible for this correlation remain unclear. This review aims to explain the current advances in the field of fetal programming of hypertension and a brief narration of the underlying mechanisms that may link FGR to increased risk of adult hypertension. We explain the theory of DOHaD and then provide evidence from both clinical and basic science research which support the theory of fetal programming of adult hypertension. In addition, we have explored the underlying mechanisms that may link FGR to an increased risk of adult hypertension. These mechanisms include epigenetic changes, metabolic disorders, vascular dysfunction, neurohormonal impairment, and alterations in renal physiology and function. We further describe sex differences seen in the developmental origins of hypertension and provide insights into the opportunities and challenges present in this field.

Sphingolipids and Kidney Disease: Possible Role of Preeclampsia and Intrauterine Growth Restriction (IUGR).

Sphingolipids are now considered not only as constitutional components of the cellular membrane but also as essential bioactive factors regulating development and physiologic functions. Ceramide is a vital intermediate of sphingolipid metabolism, synthesized by de novo and salvage pathways, producing multiple types of sphingolipids and their metabolites. Although mutations in gene-encoding enzymes regulating sphingolipid synthesis and metabolism cause distinct diseases, an abnormal sphingolipid metabolism contributes to various pathologic conditions, including kidney diseases. Excessive accumulation of glycosphingolipids and promotion of the ceramide salvage and sphingosine-1-phosphate (S1P) pathways are found in the damaged kidney. Acceleration of the sphingosine kinase/S1P/S1P receptor (SphK/S1P/S1PR) axis plays a central role in deteriorating kidney functions. The SphK/S1P/S1PR signaling impairment is also found during pregnancy complications, such as preeclampsia and intrauterine growth restriction (IUGR). This mini-review discusses the current state of knowledge regarding the role of sphingolipid metabolism on kidney diseases, and the possible involvement of preeclampsia and IUGR conditions.

Inhibition of biofilm formation in Mycobacterium smegmatis by Parinari curatellifolia leaf extracts.

BACKGROUND: Tuberculosis (TB) is a serious public health problem worldwide. Mycobacterium tuberculosis (M. tuberculosis) grows as drug tolerant pellicles. Agents that inhibit biofilm formation in M. tuberculosis have the potential to reduce the disease treatment period and improve the quality of tuberculosis chemotherapy. Parinari curatellifolia (P. curatellifolia) leaf extracts are claimed to treat symptoms similar to tuberculosis in ethnomedicinal practices. Mycobacterium smegmatis (M. smegmatis) is a surrogate organism used in antimycobacterial drug discovery assays. In this study, the effect of the leaf extracts of P. curatellifolia on M. smegmatis growth and biofilm formation was investigated in order to determine the basis of its use in traditional medicinal use. METHODS: Phytochemicals from P. curatellifolia leaves were prepared using a mixture of 50% dichloromethane (DCM): 50% methanol and by serial exhaustive extraction using different solvents of decreasing polarity. The solvents were used in the following order, hexane > dichloromethane > ethyl acetate > acetone >ethanol > methanol > water. The micro-broth dilution method was used as an antimycobacterial susceptibility test to screen for the extract that effectively inhibited M. smegmatis growth and biofilm formation. Biofilm quantification was performed by staining the biofilms with crystal violet and determining the amount of the stain using a spectrophotometer. In addition, the effects of combining the most active extract with kanamycin were also investigated. RESULTS: The minimum inhibitory concentrations (MIC) of the extracts were found to be 6.2 µg/ml for the acetone extract, 12.5 µg/ml for both the ethanol and the total extract and 50 µg/ml for both the methanol and ethyl acetate extracts. The ethanol extract, dichloromethane extract and water extract were the only extracts that effectively inhibited biofilm formation in M. smegmatis. Combining the ethanol extract with kanamycin enhanced the effect of the ethanol extract in terms of inhibition of biofilm formation. CONCLUSIONS: P. curatellifolia leaves contain phytochemicals that have the potential to be used both as antimycobacterial and anti-biofilm formation compounds.