Prescription drug use is prevalent during pregnancy, yet there is limited knowledge about maternal-fetal safety and efficacy of this drug use because pregnant individuals have historically been excluded from clinical trials. Underrepresentation has resulted in a lack of data available to estimate or predict fetal drug exposure. Approaches to study fetal drug pharmacology are limited and must be evaluated for feasibility and accuracy. Anatomic and physiological changes throughout pregnancy fluctuate based on gestational age and can affect drug pharmacokinetics (PK) for both mother and fetus. Drug concentrations have been studied throughout different stages of gestation and at or following delivery in tissue and fluid biospecimens. Sampling amniotic fluid, umbilical cord blood, placental tissue, meconium, umbilical cord tissue, and neonatal hair present surrogate options to quantify and characterize fetal drug exposure. These sampling methods can be applied to all therapeutics including small molecule drugs, large molecule drugs, conjugated nanoparticles, and chemical exposures. Alternative approaches to determine PK have been explored, including physiologically based PK modeling, in vitro methods, and traditional animal models. These alternative approaches along with convenience sampling of tissue or fluid biospecimens can address challenges in studying maternal-fetal pharmacology. In this narrative review, we 1) present an overview of the current understanding of maternal-fetal drug exposure; 2) discuss biospecimen-guided sampling design and methods for measuring fetal drug concentrations throughout gestation; and 3) propose methods for advancing pharmacology research in the maternal-fetal population.
The objectives of the current study were to determine the effects of supplementing a blend of probiotic bacteria (Provida Calf, MB Nutritional Sciences, Lubbock, TX) on the pathophysiological response to an oral Salmonella enterica serotype Typhimurium challenge in neonatal Jersey calves. Twenty-four Jersey bull calves within 24 h of birth were acquired from a local calf ranch, blocked by total serum protein and initial body weight, and randomly assigned to 1 of 3 treatments (n = 8). Calves were assigned to either (1) Control (CON); base milk replacer, (2) Control + Salmonella Typhimurium (CON+ST); base milk replacer and challenged with Salmonella Typhimurium on d 7; or (3) Provida Calf probiotics + Salmonella Typhimurium (PRO+ST); same milk replacer supplemented with a proprietary blend of Lactobacillus casei and Enterococcus faecium strains and challenged with Salmonella Typhimurium on d 7. The PRO+ST calves were supplemented for the first 3 d with 2 × 10 10 cfu/d and then with 2 × 10 9 cfu/d for the remainder of the study. The CON+ST and PRO+ST calves were each challenged with approximately 5 × 10 6 cfu of Salmonella Typhimurium (ATCC# 14028), which was a mild challenge that did not cause scours in the calves. Peripheral blood samples were collected on d 0, 7, 10, 14, and 21 and analyzed for hematology; serum was collected and analyzed for haptoglobin, glucose, and urea N. Rectal temperatures were collected daily from d 6 to 21, when all calves were killed, so that persistent colonization of Salmonella Typhimurium and histomorphology of both the duodenum and ileum could be determined. Serum haptoglobin and urea N concentrations were increased among CON+ST on d 10. In contrast, the peak rectal temperature on d 10 in PRO+ST calves was 40.4°C, which was greater than that for CON and CON-ST (38.9°C and 39.7°C, respectively). The neutrophil percentage in peripheral circulation in PRO+ST calves was 55.4%, which was greater than that for CON and CON+ST (34.8 and 41.8%, respectively). Seven of the 8 PRO+ST calves had elevated neutrophil percentages on d 10 compared with d 7, whereas 4 of the 8 CON+ST calves had reduced neutrophil percentages on d 10 compared with d 7. Villus height-to-crypt depth ratios in the duodenum were greater among CON and PRO+ST calves, being 1.38, 0.84, and 1.43 for CON, CON+ST, and PRO+ST, respectively. In the ileum, the PRO+ST calves had greater villus height-to-crypt depth ratios than both the CON and CON+ST calves (1.64, 1.53, and 2.43 for CON, CON+ST, and PRO+ST, respectively). These data indicate that supplementing neonatal calves with the blend of probiotic bacteria used in the current study can influence the pathophysiological response to a mild enteric Salmonella Typhimurium challenge.
Urinary tract infections (UTIs) are a significant clinical problem that pregnant women and children commonly experience. Escherichia coli is the primary causative organism, along with several other gram-negative and gram-positive bacteria. Antimicrobial drugs are commonly prescribed to treat UTIs in these patients. Conventional treatment can range from using broad-spectrum antimicrobial drugs for empirical or prophylactic therapy or patient-tailored therapy based on urinary cultures and sensitivity to prospective antibiotics. The ongoing emergence of multi-drug resistant pathogens has raised concerns related to commonly prescribed antimicrobial drugs such as those used routinely to treat UTIs. Consequently, several natural medicines have been explored as potential complementary therapies to improve health outcomes in patients with UTIs. This review discusses the effectiveness of commonly used natural products such as cranberry juice/extracts, ascorbic acid, hyaluronic acid, probiotics, and multi-component formulations intended to treat and prevent UTIs. The combination of natural products with prescribed antimicrobial treatments and use of formulations that contained high amounts of cranberry extracts appear to be most effective in preventing recurrent UTIs (RUTIs). The incorporation of natural products like cranberry, hyaluronic acid, ascorbic acid, probiotics, Canephron® N, and Cystenium II to conventional treatments of acute UTIs or as a prophylactic regimen for treatment RUTIs can benefit both pregnant women and children. Limited information is available on the safety of natural products in these patients’ populations. However, based on limited historical information, these remedies appear to be safe and well-tolerated by patients.
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