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Zhongguo Dang Dai Er Ke Za Zhi =... Jul 2021To study the characteristics of gut microbiota and its association with the activity of β-glucuronidase (β-GD) in neonates with hyperbilirubinemia.
OBJECTIVE
To study the characteristics of gut microbiota and its association with the activity of β-glucuronidase (β-GD) in neonates with hyperbilirubinemia.
METHODS
A total of 50 neonates with hyperbilirubinemia who were admitted in January to December, 2018, were enrolled as the hyperbilirubinemia group, and 30 neonates without hyperbilirubinemia were enrolled as the control group. The 16S rRNA high-throughput sequencing method was used to compare gut microbiota between the two groups. The phenolphthalein-glucuronic acid substrate method was used to measure the activity of β-GD in the intestinal tract of neonates with hyperbilirubinemia before and after treatment.
RESULTS
The comparison of the distribution of gut microbiota at the genus level showed a significant difference in the abundance of 52 bacteria between the hyperbilirubinemia and control groups before treatment ( < 0.05), as well as a significant difference in the abundance of 42 bacteria between the hyperbilirubinemia group on day 3 after treatment and the control group on day 3 after enrollment ( < 0.05). After treatment, the hyperbilirubinemia group had significant reductions in the content of and in the intestinal tract ( < 0.05) and the activity of β-GD in feces ( < 0.05). The activity of β-GD in feces was positively correlated with the abundance of and before and after treatment in the neonates with hyperbilirubinemia (=0.5948-0.7245, < 0.01).
CONCLUSIONS
There are differences in gut microbiota between the neonates with hyperbilirubinemia and those without hyperbilirubinemia. The activity of β-GD in feces is positively correlated with the abundance of and in neonates with hyperbilirubinemia. Gut microbiota may affect the development of neonatal hyperbilirubinemia by regulating the activity of β-GD. The determination and analysis of gut microbiota and β-GD activity may have certain clinical significance for the early assessment of the development of neonatal hyperbilirubinemia.
Topics: Feces; Gastrointestinal Microbiome; Glucuronidase; Humans; Hyperbilirubinemia, Neonatal; Infant, Newborn; RNA, Ribosomal, 16S
PubMed: 34266523
DOI: 10.7499/j.issn.1008-8830.2102039 -
F1000Research 2023Dental caries is a major non-communicable disease of public health concern caused due to freely available dietary sugars. We aimed to compare the sugar content and...
Dental caries is a major non-communicable disease of public health concern caused due to freely available dietary sugars. We aimed to compare the sugar content and erosive potential with duration of use and drug classes of orodispersible tablets (ODTs). We conducted an evaluation of the total sugar content (TSC), Potential of Hydrogen (pH), solubility, and Titratable Acidity (TA) of commonly prescribed 62 ODTs. TA was measured by titrating the samples with known amount of. 0.1N sodium hydroxide (NaOH) with phenolphthalein indicator and pH was determined by digital pH meter. TSC was evaluated by phenol sulphuric acid. Solubility was assessed by filtration. Out of the 62 ODTs, majority were Antimicrobials (n=30). One-quarter of the ODTs (26%) had a mean pH below ≤5.5. No significant difference was seen in the mean pH with respect to different drug classes (p=0.082) and duration of use of ODTs. A significant difference was seen in the mean percentage solubility with respect to drug classes (p<0.001). Antimicrobials had the least percentage of solubility as compared to other drug classes. Antiemetics and proton pump inhibitors (24.33 ± 17.34) had significantly higher mean percentage sugar content than Antimicrobials (23.25 ± 17.16). No significant difference was seen in the mean TSC with respect to various drug classes (p=0.718) and between the duration of use of drugs (P=0.568) respectively. No significant difference was seen in the mean percentage TA with respect to drug class (p=0.123) and duration of use of drugs (p=0.424). Overall, we can conclude that one in four ODT formulations had a pH below 5.5 (critical pH). Only one ODT formulation did not have a sugar content. No difference was seen in the mean pH, sugar content, and TA with respect to duration of use of drugs and drug classes.
Topics: Humans; Sugars; Dental Caries; Tablets; Solubility
PubMed: 37089132
DOI: 10.12688/f1000research.130786.2 -
Environmental Toxicology and Chemistry Dec 2023The US Environmental Protection Agency (USEPA) is faced with long lists of chemicals that require hazard assessment. The present study is part of a larger effort to...
The US Environmental Protection Agency (USEPA) is faced with long lists of chemicals that require hazard assessment. The present study is part of a larger effort to develop in vitro assays and quantitative structure-activity relationships applicable to untested chemicals on USEPA inventories through study of estrogen receptor (ER) binding and estrogen-mediated gene expression in fish. The present effort investigates metabolic activation of chemicals resulting in increased estrogenicity. Phenolphthalin (PLIN) was shown not to bind rainbow trout (Oncorhynchus mykiss) ER (rtER) in a competitive binding assay, but vitellogenin (Vtg) expression was induced in trout liver slices exposed to 10 and 10 M PLIN. Phenolphthalein (PLEIN), a metabolite of PLIN, was subsequently determined to be formed when slices were exposed to PLIN. It binds rtER with a relative binding affinity to 17β-estradiol of 0.020%. Slices exposed to PLEIN expressed Vtg messenger RNA (mRNA) at 10 , 10 , and 10 M, with no detectable PLIN present. Thus, Vtg expression noted in PLIN slice exposures was explained by metabolism to PLEIN in trout liver slices. A second model chemical, 4,4'-methylenedianiline (MDA), was not shown to bind rtER but did induce Vtg mRNA production in tissue slices at 10 , 10 , and 10 M in amounts nearly equal to reference estradiol induction, thus indicating metabolic activation of MDA. A series of experiments were performed to identify a potential metabolite responsible for the observed increase in activity. Potential metabolites hydroxylamine-MDA, nitroso-MDA, azo-MDA, and azoxy-MDA were not observed. However, acetylated MDA was observed and tested in both ER-binding and tissue slice Vtg induction assays. Environ Toxicol Chem 2023;42:2747-2757. © 2023 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Topics: Humans; Animals; Activation, Metabolic; Xenobiotics; Estradiol; Vitellogenins; Oncorhynchus mykiss; RNA, Messenger
PubMed: 37712519
DOI: 10.1002/etc.5748 -
Journal of Clinical Pharmacology Aug 2022The US Food and Drug Administration created the Tainted Dietary Supplement Database in 2007 to identify dietary supplements adulterated with active pharmaceutical... (Review)
Review
Continued Risk of Dietary Supplements Adulterated With Approved and Unapproved Drugs: Assessment of the US Food and Drug Administration's Tainted Supplements Database 2007 Through 2021.
The US Food and Drug Administration created the Tainted Dietary Supplement Database in 2007 to identify dietary supplements adulterated with active pharmaceutical ingredients (APIs). This article compares the determination of API adulteration in dietary supplements from the 10-year time period of 2007 through 2016 to the most recent 5-year period of 2017 through 2021. From 2007 through 2021, 1068 unique products were found to be adulterated with APIs. Sexual enhancement and weight loss dietary supplements are the most common products adulterated with APIs. Phosphodiesterase-5 inhibitors are commonly included in sexual enhancement dietary supplements and a single product can include up to 5 APIs. Sibutramine, a drug removed from the market due to cardiovascular adverse events, is the most included adulterant API in weight loss products, although sibutramine analogues, phenolphthalein (which was removed from the US market because of cancer risk), and fluoxetine were also included. While muscle-building dietary supplements were commonly adulterated before 2016, since 2017 no additional adulterated products have been identified. The lack of disclosure of APIs in dietary supplements, circumventing the normal procedure with clinician oversight of prescription drug use, and the use of APIs that are banned by the Food and Drug Administration or used in combinations that were never studied are important health risks for consumers.
Topics: Dietary Supplements; Drug Contamination; Humans; Pharmaceutical Preparations; United States; United States Food and Drug Administration; Weight Loss
PubMed: 35285963
DOI: 10.1002/jcph.2046 -
The Turkish Journal of Gastroenterology... Mar 2019Fixed drug eruption (FDE) is a type of drug reaction characterized by localized erythema, hyperpigmentation, and bullous at the same site(s), generally observed... (Review)
Review
Fixed drug eruption (FDE) is a type of drug reaction characterized by localized erythema, hyperpigmentation, and bullous at the same site(s), generally observed following every intake of a causative drug. Delayed-type cellular hypersensitivity (Type IVC) is considered to play a role in FDE etiology. Several antibiotics, barbiturates, oral contraceptives, nonsteroidal anti-inflammatory drugs, laxative-containing phenolphthalein, metronidazole, and quinine are known to be the primary drugs responsible for FDE. Bullous FDE, on the other hand, is a relatively rare form of FDE. Hepatitis B is a significant worldwide health problem, and entecavir is a common nucleoside (deoxyguanosine) analog used for treating hepatitis B; however, it has various side effects, such as lactic acidosis, myalgia, azotemia, hypophosphatemia, headache, diarrhea, pancreatitis, and neuropathy, and, in rare cases, cutaneous drug eruption. Our aim is to present a case of entecavir-associated bullous drug reaction, which has not been reported in the literature. Furthermore, we performed a review of literature to compile previously reported entecavir-associated drug reactions.
Topics: Antiviral Agents; Drug Eruptions; Female; Guanine; Hepatitis B; Hepatitis B virus; Humans; Middle Aged
PubMed: 30459136
DOI: 10.5152/tjg.2018.17887 -
Frontiers in Microbiology 2022The aim of this study was to investigate the effects of subsp VHProbi YB11 (YB11) on attenuating sucralfate-induced constipation in BALB/c mice. The strain of YB11...
INTRODUCTION
The aim of this study was to investigate the effects of subsp VHProbi YB11 (YB11) on attenuating sucralfate-induced constipation in BALB/c mice. The strain of YB11 exhibited favorable tolerance of simulated gastrointestinal (GI) juice. Only 0.42 Log value declined when the live cells of YB11 were co-incubated with simulated GI juice. Meanwhile, this strain also displayed perfect ability to adhere the intestinal epithelium Caco-2 cells with adhesion index of 18.5. 24 of female mice were randomized into four groups.
METHODS
The normal group (NOR) was fed with a normal diet, whereas the placebo group (PLA), positive group (POS), and probiotic group (PRO) were fed with sucralfate to induce constipation. After first successfully establishing the constipation model, groups NOR and PLA received the oral administration of saline solutions. Meanwhile, the POS and PRO groups were orally administered phenolphthalein and YB11 suspensions, respectively. Several indices, including fecal water content, GI transit time, short-chain fatty acids (SCFAs), intestinal neuropeptides level, and histopathology of colonic tissues, were investigated.
RESULTS AND DISCUSSION
Compared with PLA, YB11 had a positive effect in increasing the fecal water content and intestinal peristalsis. Some positive trends, including the acetic and total acids level of fecal samples, and the colonic tissue histopathology, were also observed. Furthermore, YB11 had an ability to upregulate the levels of gut excitatory neuropeptides including motilin, gastrin, and substance P, whereas it downregulated the levels of inhibitory neuropeptides including endothelin-1, somatostatin, and vasoactive intestinal peptide. We conclude that the strain YB11 has a positive impact on improving gastrointestinal mobility and reducing the severity of constipation.
PubMed: 36532450
DOI: 10.3389/fmicb.2022.1040371 -
Se Pu = Chinese Journal of... Sep 2023Electrophoresis titration (ET) based on the moving reaction boundary (MRB) theory can detect the analyte contents in different samples by converting content signals into...
Electrophoresis titration (ET) based on the moving reaction boundary (MRB) theory can detect the analyte contents in different samples by converting content signals into distance signals. However, this technique is only suitable for on-site qualitative testing, and accurate quantification relies on complex optical equipment and computers. Hence, applying this method to real-time point-of-care testing (POCT) is challenging. In this study, we developed a smartphone-based ET system based on a visual technique to achieve real-time quantitative detection. First, we developed a portable quantitative ET device that can connect to a smartphone; this device consisted of five components, namely, an ET chip, a power module, a microcontroller, a liquid crystal display screen, and a Bluetooth module. The device measured 10 cm×15 cm×2.5 cm, weighed 300 g, and was easy to hold. Thus, it is suitable for on-site testing with a run time of only 2-4 min. An assistant mobile software program was also developed to control the device and perform ET. The colored electrophoresis boundary can be captured using the smartphone camera, and quantitative detection results can be obtained in real time. Second, we proposed a quantitative algorithm based on ET channels. The software was used to recognize the boundary migration distance of three channels, a standard curve based on two given contents of the standards was established using the two-point method, and the content of the test sample was calculated. Human serum albumin (HSA) and uric acid (UA) were used as a model protein and biosample, respectively, to test the performance of the detection system. For HSA detection, different HSA solutions were mixed with a polyacrylamide gel (PAG) stock solution, phenolphthalein was added as an indicator, and sodium persulfate and tetramethyl ethylenediamine (TEMED) were used to promote polymerization to form a gel. For UA detection, agarose gel was filled into the ET channel, the UA sample, urate oxidase, and leucomalachite green were added into the anode cell and incubated for 20 min. ET was then performed. The fitting goodness () values of HSA and UA were 0.9959 and 0.9935, respectively, with a linear range of 0.5-35.0 g/L and a log-linear range of 100-4000 μmol/L. The limits of detection for HSA and UA were 0.05 g/L and 50 μmol/L, respectively, and the corresponding relative standard deviations (RSDs) were not greater than 2.87% and 3.21%, respectively. These results demonstrate that the detection system has good accuracy and sensitivity. Clinical samples collected from healthy volunteers were used as target blood samples, and the developed system was used to measure serum total protein and UA levels. Serum samples from five volunteers were selected, standard curves of total serum protein and UA were established, and the test results were compared with hospital standard testing results. The relative errors for serum total protein and UA were less than 6.03% and 6.21%, respectively, and the corresponding RSDs were less than 3.72% and 5.84%, respectively. These findings verify the accuracy and reliability of the proposed detection system. The smartphone-based ET detection system introduced in this paper presents several advantages. First, it enables the portable real-time detection of total serum protein and UA. Second, compared with traditional ET strategies based on colored boundaries, it does not rely on optical detection equipment or computers to obtain quantitative detection results; as such, it can reduce the complexity of the operation and provide portability and real-time metrics. Third, the detection of two biomarkers, serum total protein and UA, is achieved on the same device, thereby improving the multitarget detection potential of the ET method. These advantages render the developed method a promising detection platform for clinical applications and real-time POCT.
Topics: Humans; Smartphone; Reproducibility of Results; Electrophoresis; Electrodes; Blood Proteins
PubMed: 37712539
DOI: 10.3724/SP.J.1123.2023.06001 -
The Journal of Steroid Biochemistry and... Jul 2022Most members of the aldo-keto reductase (AKR) 1 C subfamily are hydroxysteroid dehydrogenases (HSDs). Similarly to humans, four genes for AKR1C proteins (AKR1C1-AKR1C4)...
Most members of the aldo-keto reductase (AKR) 1 C subfamily are hydroxysteroid dehydrogenases (HSDs). Similarly to humans, four genes for AKR1C proteins (AKR1C1-AKR1C4) have been identified in the pig, which is a suitable species for biomedical research model of human diseases and optimal organ donor for xenotransplantation. Previous study suggested that, among the porcine AKR1Cs, AKR1C1 and AKR1C4 play important roles in steroid hormone metabolism in the reproductive tissues; however, their biological functions are still unknown. Herein, we report the biochemical properties of the two recombinant enzymes. Kinetic and product analyses of steroid specificity indicated that AKR1C1 is a multi-specific reductase, which acts as 3α-HSD for 3-keto-5β-dihydro-C/C-steroids, 3β-HSD for 3-keto-5α-dihydro-C-steroids including androstenone, 17β-HSD for 17-keto-C-steroids including estrone, and 20α-HSD for progesterone, showing K values of 0.5-11 µM. By contrast, AKR1C4 exhibited only 3α-HSD activity for 3-keto groups of 5α/β-dihydro-C-steroids, 5β-dihydro-C-steroids and bile acids (K: 1.0-1.9 µM). AKR1C1 and AKR1C4 also showed broad substrate specificity for nonsteroidal carbonyl compounds including endogenous 4-oxo-2-nonenal, 4-hydroxy-nonenal, acrolein, isocaproaldehyde, farnesal, isatin and methylglyoxal, of which 4-oxo-2-nonenal was reduced with the lowest K value of 0.9 µM. Moreover, AKR1C1 had the characteristic of reducing aliphatic ketones and all-trans-retinal. The enzymes were inhibited by flavonoids, synthetic estrogens, nonsteroidal anti-inflammatory drugs, triterpenoids and phenolphthalein, whereas only AKR1C4 was activated by bromosulfophthalein. These results suggest that AKR1C1 and AKR1C4 function as 3α/3β/17β/20α-HSD and 3α-HSD, respectively, in metabolism of steroid hormones and a sex pheromone androstenone, both of which also play roles in metabolism of nonsteroidal carbonyl compounds.
Topics: 20-Hydroxysteroid Dehydrogenases; 3-Hydroxysteroid Dehydrogenases; Aldo-Keto Reductases; Animals; Estrone; Hydroxysteroid Dehydrogenases; Progesterone; Substrate Specificity; Swine
PubMed: 35398259
DOI: 10.1016/j.jsbmb.2022.106113 -
Talanta May 2021Herein, an easy assembled colorimetric and ''turn-on'' fluorescent sensor (probe P4SC) based on phenolphthalein was developed for carbonate ion (CO) sensing in a mixture...
Herein, an easy assembled colorimetric and ''turn-on'' fluorescent sensor (probe P4SC) based on phenolphthalein was developed for carbonate ion (CO) sensing in a mixture of EtOH/HO (v/v, 80/20, pH = 7, Britton-Robinson buffer) media. The probe P4SC demonstrated high sensitive and selective monitoring toward CO over other competitive anions. Interaction of CO with the probe P4SC resulted in a significant increment in emission intensity at λ = 498 nm (λ = 384 nm) due to the strategy of blocking the photo induced electron transfer (PET) mechanism. H NMR titration and Job's methods, as well as the theoretical study were carried out to support the probable stoichiometry of the reaction (1:2) between P4SC and CO. The binding constant of the probe P4SC with CO was calculated as 2.56 × 10 M. The probe P4SC providing rapid response time (~0.5 min) with a satisfactorily low detection limit (14.7 nM) may be useful as a valuable realistic sensor. The imaging studies on the liver cancer cells (HepG2) shows the great potential of the probe P4SC for the sensation of intracellular CO anions. Furthermore, the satisfactory recovery and RSD values obtained for water application confirming that the probe P4SC could be applied to sensing of CO ion.
Topics: Anions; Colorimetry; Fluorescent Dyes; Phenolphthalein; Water
PubMed: 33676708
DOI: 10.1016/j.talanta.2021.122166 -
Journal of Nuclear Medicine : Official... Mar 2015We report the design, testing, and in vivo application of pH-sensitive contrast agents designed specifically for Cerenkov imaging. Radioisotopes used for PET emit...
UNLABELLED
We report the design, testing, and in vivo application of pH-sensitive contrast agents designed specifically for Cerenkov imaging. Radioisotopes used for PET emit photons via Cerenkov radiation. The multispectral emission of Cerenkov radiation allows for selective bandwidth quenching, in which a band of photons is quenched by absorption by a functional dye. Under acidic conditions, (18)F-labeled derivatives emit the full spectrum of Cerenkov light. Under basic conditions, the dyes change color and a wavelength-dependent quenching of Cerenkov emission is observed.
METHODS
Mono- and di-(18)F-labeled derivatives of phenolsulfonphthalein (phenol red) and meta-cresolsulfonphthalein (cresol purple) were synthesized by electrophilic fluorination. Cerenkov emission was measured at different wavelengths as a function of pH in vitro. Intramolecular response was measured in fluorinated probes and intermolecular quenching by mixing phenolphthalein with (18)F-FDG. Monofluorocresol purple (MFCP) was tested in mice treated with acetazolamide to cause urinary alkalinization, and Cerenkov images were compared with PET images.
RESULTS
Fluorinated pH indicators were produced with radiochemical yields of 4%-11% at greater than 90% purity. Selective Cerenkov quenching was observed intramolecularly with difluorophenol red or monofluorocresol purple and intermolecularly in phenolphthalein (18)F-FDG mixtures. The probes were selectively quenched in the bandwidth closest to the indicator's absorption maximum (λmax) at pHs above the indicator pKa (the negative logarithm of the acid dissociation constant). Addition of acid or base to the probes resulted in reversible switching from unquenched to quenched emission. In vivo, the bladders of acetazolamide-treated mice exhibited a wavelength-dependent quenching in Cerenkov emission, with the greatest reduction occurring near the λmax. Ratiometric imaging at 2 wavelengths showed significant decreases in Cerenkov emission at basic pH and allowed the estimation of absolute pH in vivo.
CONCLUSION
We have created contrast agents that selectively quench photons emitted during Cerenkov radiation within a given bandwidth. In the presence of a functional dye, such as a pH indicator, this selective quenching allows for a functional determination of pH in vitro and in vivo. This method can be used to obtain functional information from radiolabeled probes using multimodal imaging. This approach allows for the imaging of nonfluorescent chromophores and is generalizable to any functional dye that absorbs at suitable wavelengths.
Topics: Acetazolamide; Animals; Contrast Media; Disease Models, Animal; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Hydrogen-Ion Concentration; Mice; Models, Chemical; Multimodal Imaging; Optics and Photonics; Phenolphthalein; Phenolsulfonphthalein; Photons; Positron-Emission Tomography; Radioisotopes; Radiopharmaceuticals
PubMed: 25655631
DOI: 10.2967/jnumed.114.146605