Background:
Cladribine is an antimetabolite used for the treatment of relapsing–remitting multiple sclerosis. At present, there are no data available on its use in breastfeeding mothers and its ...transfer in human milk.
Objective:
We present a case of a lactating mother who donated her milk samples to study the transfer of cladribine following a 20-mg oral dose.
Methods:
Analysis was done using liquid chromatography–mass spectrometry.
Results:
The relative infant dose calculated in this study was 3.06%.
Conclusion:
This is the first case report suggesting the transfer of cladribine in human milk in measurable quantities. However, caution should be advised during lactation.
Trimethylamine-
-oxide (TMAO) is a product of dietary, gut microbiome, and tissues metabolism. Elevated blood TMAO levels are associated with heart attack, stroke and chronic kidney disease (CKD). ...The purpose of our study was to investigate the gut microbiota associated with trimethylamine (TMA) production, the precursor of TMAO, and the serum levels of TMAO and inflammatory biomarkers associated with type 2 diabetes mellitus (T2DM) and CKD. Twenty adults with T2DM and advanced CKD and 20 healthy adults participated in the study. Analyses included anthropometric and metabolic parameters, characterization of TMA producing gut microbiota, and concentrations of TMAO, lipopolysaccharides (LPS) endotoxin, zonulin (Zo) gut permeability marker, and serum inflammatory and endothelial dysfunction biomarkers. Diversity of the gut microbiota was identified by amplification of V3-V4 regions of the 16S ribosomal RNA genes and DNA sequencing. TMAO was quantified by Mass Spectrometry and serum biomarkers by ELISA. The significance of measurements justified by statistical analysis. The gut microbiome in T2DM-CKD patients exhibited a higher incidence of TMA-producing bacteria than control,
< 0.05. The serum levels of TMAO in T2DM-CKD patients were significantly higher than controls,
< 0.05. TMAO showed a positive correlation with Zo and LPS, inflammatory and endothelial dysfunction biomarkers. A positive correlation was observed between Zo and LPS in T2DM-CKD subjects. An increased abundance of TMA-producing bacteria in the gut microbiota of T2DM-CKD patients together with excessive TMAO and increased gut permeability might impact their risk for cardiovascular disease through elevation of chronic inflammation and endothelial dysfunction.
Dimethyl fumarate transfer into human milk Ciplea, Andrea I.; Datta, Palika; Rewers-Felkins, Kathleen ...
Therapeutic advances in neurological disorders,
2020, Letnik:
13
Journal Article
Recenzirano
Odprti dostop
Dimethyl fumarate (DMF) is approved for the treatment of relapsing-remitting multiple sclerosis. It is unknown whether DMF or its primary metabolite monomethyl fumarate (MMF) are excreted into human ...milk. We present two cases of lactating patients who donated milk samples to study the transfer of MMF into human milk following a week of 2 × 240 mg daily oral dose. Samples were analyzed using liquid chromatography mass spectrometry. The calculated relative infant dose was 0.019% and 0.007%. This is the first study to demonstrate that MMF is transferred into human milk, with only limited exposure to an infant.
Breast milk is the most beneficial nutrition a mother can give her infant. Fortunately, the dose of most drugs transferred into milk is small and does not lead to clinically significant effects on ...the infant. In almost all instances, the mother should be advised to continue breastfeeding. Certain medications are absolutely contraindicated, including anticancer agents, radioactive drugs, and those that inhibit milk production. However, most medications can be used safely. An improved understanding of the relationship between maternal and infant exposure to medications would provide a more enlightened understanding of the risk and benefit analysis for individual drugs.
The endocannabinoid system is involved in the regulation of a variety of physiological and cognitive processes. While the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide ...(N-arachidonoylethanolamine, AEA) have been found in breast milk, their role(s) have yet to be determined. This study determined the normal concentration ranges of endocannabinoids (2-AG and AEA) in breast milk and the influences, if any, of obesity and diurnal rhythms on their levels. Milk samples were collected from 36 breastfeeding mothers at 4–8 weeks postpartum at each feed over a 24-h period, and further stratified into three groups based on body mass index (BMI). The samples were analyzed using liquid chromatography mass spectrometry. AEA was below the limit of detection and 2-AG levels averaged 59.3 ± 18.3 ng/mL (± SD) in women with normal BMI. Wide-ranging 2-AG concentrations in the overweight (65.5 ± 41.9 ng/mL) /obese (66.1 ± 40.6 ng/mL) groups suggest BMI may be a contributing factor influencing its levels. Following a diurnal pattern, there was a significantly higher 2-AG concentration observed during the day, as compared to night time samples. In conclusion, our study clearly suggests that appropriate milk collection and storage conditions are critical. Further, body weight and diurnal rhythm appear to influence levels of 2-AG. Based on these results, future studies are underway to determine what specific roles endocannabinoids may play in human milk and how elevated levels of 2-AG may modulate infant appetite and health.
Background Peripartum cardiomyopathy (PPCM) is a common cause of heart failure (HF) in the peripartum. Some medications are considered safe while breastfeeding. However, sacubitril/valsartan ...(Entresto), while efficacious, is not recommended in breastfeeding women due to concerns about adverse infant development, and no published data suggest otherwise. Objectives This study aimed to assess the transfer of sacubitril/valsartan into human milk and evaluate the infant’s risk of drug exposure. Methods The InfantRisk Human Milk Biorepository released samples and corresponding health information from five breastfeeding maternal–infant dyads exposed to sacubitril/valsartan. Sacubitril, valsartan, and LBQ657 (sacubitril active metabolite) concentrations were determined using liquid chromatography-mass spectrometry (LC/MS/MS) from timed samples 0, 1, 2, 4, 6, 8, 10, and 12 h following medication administration at steady state conditions. Results Valsartan levels were below the detection limit of 0.19 ng/mL in all milk samples. Sacubitril was measurable in all milk samples of the five participants, peaking 1 h after drug administration at a mean concentration of 1.52 ng/mL for a total infant dose of 0.00049 mg/kg/12 h and a relative infant dose (RID) calculated at 0.01%. The maximum concentration of its active metabolite LBQ657 in the milk samples was observed 4 h after medication administration and declined over the remaining 12-h dosing interval, for an average concentration of 9.5 ng/mL. The total infant dose was 0.00071 mg/kg/12 h, and the RID was 0.22%. Two mothers reported continuing to breastfeed while taking sacubitril/valsartan; both mothers stated observing no negative effects in their breastfed infants. Conclusion The transfer of sacubitril/valsartan into human milk is minimal. These concentrations are unlikely to pose a significant risk to breastfeeding infants, with a combined calculated RID of <0.25%, which is far lower than the industry safety standards (RID <10%).
Domperidone is a dopamine-2 (D2) receptor antagonist that stimulates the release of stored prolactin in the anterior pituitary. It is prescribed off-label in Canada and Australia to promote lactation ...in prolactin-deficient women. The case of a 43-year-old woman taking a high daily dose of domperidone (160 mg) is described from the InfantRisk Center Human Milk Biorepository. Milk samples were analyzed using a high-performance liquid chromatography-mass spectrometry method, detecting an average domperidone concentration of 7.0 ng/mL (range 6.2 to 8.4 ng/mL). Even at high doses, the transfer of domperidone into breast milk was negligible with a relative infant dose (RID) of 0.05%. The RID estimates the infant's potential exposure to a drug via lactation as a percentage of the weight-adjusted maternal dose. The standard threshold for reasonable infant exposure is an RID of 10%.
Purpose
Buspirone, an anxiolytic with minimal risk of dependence or respiratory depression, lacks extensive published data on its transfer into human milk during lactation. The objective of this ...study was to 1) quantify the transfer of buspirone and its active metabolite 1-pyrimidinylpiperazine (1-PP) into human milk, allowing for an estimation of maternal drug exposure to the breastfed infant, and 2) report observations of the infants exposed to buspirone via breastmilk.
Methods
Milk samples and health histories were collected from nine lactating mothers who donated milk samples to the InfantRisk Human Milk Biorepository while taking buspirone. The drug concentration–time profile of buspirone and 1-PP was determined using liquid chromatography–mass spectrometry.
Results
Buspirone was below the detection level of 1.5 ng/mL in all milk samples with dosages ranging from 7.5 to 30 mg twice daily. However, low levels of active metabolite 1-PP were observed at 7.5 mg twice daily up to 30 mg twice daily. The relative infant dose (RID) calculated ranged from 0.21 to 2.17%, which is below the standard 10% threshold for infant safety. There were no reports of adverse effects in the exposed infants.
Conclusion
The levels of buspirone observed in all participants’ milk samples were exceedingly low. The subsequently low relative infant dose (RID) in the range of 0.21% to 2.17% is below the 10% threshold for infant safety, suggesting that the transfer of maternal buspirone and its active metabolite (1-PP) into human milk is clinically insignificant and poses minimal risk to a breastfed infant.
Abstract only
We hypothesized that CGP would mitigate the effect of hypoxia, cytokines (CK) and/or α‐gliadin peptide 31‐55 (α‐GP, the gluten peptide fragment of celiac disease) to increase ...transepithelial permeability. All experiments used Caco‐2 monolayers with transepithelial electrical resistance (TEER) of 600‐700 Ω/cm
2
. All agents were added to the luminal side of the cell monolayer. In normoxic cells, TEER increased at 0.69 ± 0.11% / hour and mannitol flux was 28 ± 4 dpm / hour. In hypoxic cells, TEER decreased 19.4 ± 1.31 % / hour and mannitol flux increased to 162 ± 27 dpm / hour. 10 µM CGP, reduced hypoxia induced TEER loss to 10.6±1.86 % / hour and mannitol flux to 35±dpm / hour (p<0.001 compared to normoxia or hypoxia alone). CK stimulated TEER loss was 2.1 ± 0.31% / hour and mannitol flux was 54 ± 1 dpm / hour. 10 µM CGP reduced TEER loss to 1.4 ± 0.28% / hour, and mannitol flux to 13 ±1 dpm / hour (p<0.001 compared to control or to hypoxia alone). In separate experiments, α‐GP + CK increased mannitol flux from 21±1 to 39 ± 3 dpm / hour; α‐GP + CK + CGP (1 mM) group, mannitol flux was 32 ±1 dpm / hour (p<0.05
vs α
‐GP + CK). In these same experiments, TEER loss was 2.72 ± 0.497% / hour in the peptide + CK group
vs.
1.20 ± 0.327% /hour in the α‐GP + CK + CGP group (p<0.05
vs α
‐GP + CK). E‐cadherin protein was 75.8±8.6% of control in the α‐GP + CK group, while in the α‐GP + CK + CGP treated cells, E‐cadherin was 101 ± 2.9% of control (p<0.05
vs α
‐GP + CK. In summary, CGP showed a significant time and concentration dependent effect to attenuate increased gut permeability caused by hypoxia, CK, or α‐GP an effect that was observable even at 1µM. These factors may make it worthwhile to pursue calcium glycerophosphate as an adjunct to other therapies to prevent loss of gut epithelial integrity in hypoxia or celiac disease.
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