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The New England Journal of Medicine Apr 1991There is no specific method of diagnosing magnesium-induced diarrhea. Therefore, the frequency and clinical importance of diarrhea caused by magnesium are unknown. The... (Clinical Trial)
Clinical Trial
BACKGROUND
There is no specific method of diagnosing magnesium-induced diarrhea. Therefore, the frequency and clinical importance of diarrhea caused by magnesium are unknown. The purposes of this study were to establish a method for diagnosing magnesium-induced diarrhea and to apply it to patients with chronic diarrhea.
METHODS
We measured fecal output of soluble magnesium and fecal magnesium concentration in 19 normal subjects with formed stools (15 collection periods), with non-magnesium-induced diarrhea (36 collection periods), and with diarrhea induced by magnesium hydroxide alone (11 collection periods) or in combination with phenolphthalein (3 collection periods), and in 359 patients with chronic diarrhea.
RESULTS
The upper limits of fecal output of soluble magnesium and fecal magnesium concentration in normal subjects were 14.6 mmol per day and 45.2 mmol per liter, respectively. When normal subjects had diarrhea due to the ingestion of magnesium hydroxide alone or in combination with phenolphthalein, fecal magnesium output was always abnormally high. For each millimole increase in fecal magnesium output, fecal weight increased by approximately 7.3 g. The fecal magnesium concentration was very high when magnesium was the only cause of diarrhea but only moderately elevated when diarrhea was induced by magnesium hydroxide plus phenolphthalein. Biochemical and clinical evidence indicated that excessive ingestion of magnesium was an important cause of chronic diarrhea in 15 of the 359 patients with chronic diarrhea (4.2 percent), if not the only cause.
CONCLUSIONS
Quantitative fecal analysis for soluble magnesium is an accurate method of diagnosing magnesium-induced diarrhea. Some patients with chronic diarrhea ingest excessive amounts of magnesium (in antacids or food supplements), and physicians may fail to discover this before embarking on an expensive and invasive diagnostic evaluation.
Topics: Adult; Aged; Child; Chronic Disease; Diarrhea; Drug Overdose; Feces; Female; Humans; Magnesium; Magnesium Hydroxide; Male; Middle Aged; Phenolphthalein; Phenolphthaleins; Reference Values
PubMed: 2005938
DOI: 10.1056/NEJM199104113241502 -
JAMA Psychiatry Aug 2020The rapidly growing legal cannabis market includes new and highly potent products, the effects of which, to our knowledge, have not previously been examined in... (Observational Study)
Observational Study Randomized Controlled Trial
IMPORTANCE
The rapidly growing legal cannabis market includes new and highly potent products, the effects of which, to our knowledge, have not previously been examined in biobehavioral research studies because of federal restrictions on cannabis research.
OBJECTIVE
To use federally compatible, observational methods to study high-∆9-tetrahydrocannabinol (THC) legal market forms of cannabis.
DESIGN, SETTING, AND PARTICIPANTS
In this cohort study with a between-groups design that was conducted in a community and university setting, cannabis flower users and concentrate users were randomly assigned to higher- vs lower-THC products within user groups. Participants completed a baseline and an experimental mobile laboratory assessment that included 3 points: before, immediately after, and 1 hour after ad libitum legal market flower and concentrate use. Of the 133 individuals enrolled and assessed, 55 regular flower cannabis users (41.4%) and 66 regular concentrate cannabis users (49.6%) complied with the study's cannabis use instructions and had complete data across primary outcomes.
EXPOSURES
Flower users were randomly assigned to use either 16% or 24% THC flower and concentrate users were randomly assigned to use either 70% or 90% THC concentrate that they purchased from a dispensary.
MAIN OUTCOMES AND MEASURES
Primary outcome measures included plasma cannabinoids, subjective drug intoxication, and neurobehavioral tasks testing attention, memory, inhibitory control, and balance.
RESULTS
A total of 121 participants completed the study for analysis: 55 flower users (mean [SD] age, 28.8 [8.1] years; 25 women [46%]) and 66 concentrate users (mean [SD] age, 28.3 [10.4] years; 30 women [45%]). Concentrate users compared with flower users exhibited higher plasma THC levels and 11-hydroxyΔ9-THC (THC's active metabolite) across all points. After ad libitum cannabis administration, mean plasma THC levels were 0.32 (SE = 0.43) μg/mL in concentrate users (to convert to millimoles per liter, multiply by 3.18) and 0.14 (SE = 0.16) μg/mL in flower users. Most neurobehavioral measures were not altered by short-term cannabis consumption. However, delayed verbal memory (F1,203 = 32.31; P < .001) and balance function (F1,203 = 18.88; P < .001) were impaired after use. Differing outcomes for the type of product (flower vs concentrate) or potency within products were not observed.
CONCLUSIONS AND RELEVANCE
This study provides information about the association of pharmacological and neurobehavioral outcomes with legal market cannabis. Short-term use of concentrates was associated with higher levels of THC exposure. Across forms of cannabis and potencies, users' domains of verbal memory and proprioception-focused postural stability were primarily associated with THC administration.
Topics: Adult; Attention; Cannabis; Cognitive Dysfunction; Dronabinol; Executive Function; Female; Flowers; Humans; Inhibition, Psychological; Male; Plant Extracts; Postural Balance; Sensation Disorders; Verbal Learning; Young Adult
PubMed: 32520316
DOI: 10.1001/jamapsychiatry.2020.0927 -
Molecules (Basel, Switzerland) Nov 2022Carrageenan is a polysaccharide of a plant origin, commonly used as a thickening and gelling agent in the food, pharmaceutical, and cosmetic industries. Due to the...
Carrageenan is a polysaccharide of a plant origin, commonly used as a thickening and gelling agent in the food, pharmaceutical, and cosmetic industries. Due to the negative charges of its sulfate groups, carrageenan macromolecules strongly interact with oppositely charged polyions. The ionic complexes of carrageenan with poly(diallyldimethylammonium chloride) were obtained at the molar ratios 4:1, 2;1, 1:1, 1:2, and 1:4. The structure and characteristics of the polyanion-polycation associates were studied by XRD, IR, optical microscopy, and via sedimentation and particle size measurements. It was found that the suspended particles flocculate and settle fastest when the molar ratio of the polyions is near 1:1. Turbidimetric titration experiments enabled us to measure the molar ratio of cationic to anionic groups at the onset of flocculation, and the value in question was found to be 1:1.32. In other words, a mass of 511 mg carrageenan corresponds to one millimole of ester sulfate (monobasic) groups. The measurement of the onset of flocculation has been employed for the accurate determination of carrageenan in real samples of food products. The color and turbidity of the sample do not interfere with the determination results.
Topics: Carrageenan; Flocculation; Cations; Sulfates
PubMed: 36432178
DOI: 10.3390/molecules27228075 -
Green Chemistry : An International... Jan 2019Automated, miniaturized and accelerated synthesis for efficient property optimization is a formidable challenge for chemistry in the 21 century as it helps to reduce...
Automated, miniaturized and accelerated synthesis for efficient property optimization is a formidable challenge for chemistry in the 21 century as it helps to reduce resources and waste and can deliver products in shorter time frames. Here, we used for the first-time acoustic droplet ejection (ADE) technology and fast quality control to screen efficiency of synthetic reactions on a nanomole scale in an automated and miniaturized fashion. The interrupted Fischer indole combined with Ugi-type reactions yielded several attractive drug-like scaffolds. In 384-well plates, a diverse set of interrupted Fischer indole intermediates were produced and reacted to the tricyclic hydantoin backbone by a 2-step sequence. Similarly, preformed Fischer indole intermediates were used to produce divers sets of Ugi products and the efficiency was compared to the method. Multiple reactions were resynthesized on a preparative millimole scale, showing scalability from nano to mg and thus synthetic utility. An unprecedented large number of building was used for fast scope and limitation studies (68 isocyanides, 72 carboxylic acids). Miniaturization and analysis of the generated big synthesis data enabled deeper exploration of the chemical space and permitted gain of knowledge that was previously impractical or impossible, such as the rapid survey of reactions, building block and functional group compatibility.
PubMed: 30686932
DOI: 10.1039/C8GC03039A -
Diabetes Care Mar 2022Consuming ≥150 g/day carbohydrate is recommended for 3 days before an oral glucose tolerance test (OGTT) for diabetes diagnosis. For evaluation of this recommendation,... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Consuming ≥150 g/day carbohydrate is recommended for 3 days before an oral glucose tolerance test (OGTT) for diabetes diagnosis. For evaluation of this recommendation, time courses of glycemic changes following transition from a very-low-carbohydrate (VLC) to high-carbohydrate diet were assessed with continuous glucose monitoring (CGM).
RESEARCH DESIGN AND METHODS
After achieving a weight loss target of 15% (±3%) on the run-in VLC diet, participants (18-50 years old, BMI ≥27 kg/m2) were randomly assigned for 10 weeks to one of three isoenergetic diets: VLC (5% carbohydrate and 77% fat); high carbohydrate, high starch (HC-Starch) (57% carbohydrate and 25% fat, including 20% refined grains); and high carbohydrate, high sugar (HC-Sugar) (57% carbohydrate and 25% fat, including 20% sugar). CGM was done throughout the trial (n = 64) and OGTT at start and end (n = 41). All food was prepared in a metabolic kitchen and consumed under observation.
RESULTS
Glucose metrics continued to decline after week 1 in the HC-Starch and HC-Sugar groups (P < 0.05) but not VLC. During weeks 2-5, fasting and 2-h glucose (millimoles per liter per week) decreased in HC-Starch (fasting -0.10, P = 0.001; 2 h -0.10, P = 0.04). During weeks 6-9, 2-h glucose decreased in HC-Starch (-0.07, P = 0.01) and fasting and 2-h glucose decreased in HC-Sugar (fasting -0.09, P = 0.001; 2 h -0.09, P = 0.003). The number of participants with abnormal glucose tolerance by OGTT remained 10 (of 16) in VLC at start and end but decreased from 17 to 9 (of 25) in both high-carbohydrate groups.
CONCLUSIONS
Physiological adaptation from a low- to high-carbohydrate diet may require many weeks, with implications for the accuracy of diabetes tests, interpretation of macronutrient trials, and risks of periodic planned deviations from a VLC diet.
Topics: Adaptation, Physiological; Adolescent; Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diet, Carbohydrate-Restricted; Dietary Carbohydrates; Humans; Middle Aged; Young Adult
PubMed: 35108378
DOI: 10.2337/dc21-1970 -
Obesity (Silver Spring, Md.) Jul 2020Lipedema is characterized by pain, fatigue, and excessive adipose tissue and sodium accumulation of the lower extremities. This case-control study aims to determine...
OBJECTIVE
Lipedema is characterized by pain, fatigue, and excessive adipose tissue and sodium accumulation of the lower extremities. This case-control study aims to determine whether sodium or vascular dysfunction is present in the central nervous system.
METHODS
Brain magnetic resonance imaging was performed at 3 T in patients with lipedema (n = 15) and control (n = 18) participants matched for sex, age, race, and BMI. Standard anatomical imaging and intracranial angiography were applied to evaluate brain volume and vasculopathy, respectively; arterial spin labeling and sodium magnetic resonance imaging were applied to quantify cerebral blood flow (CBF) (milliliters per 100 grams of tissue/minute) and brain tissue sodium content (millimoles per liter), respectively. A Mann-Whitney U test (significance criteria P < 0.05) was applied to evaluate group differences.
RESULTS
No differences in tissue volume, white matter hyperintensities, intracranial vasculopathy, or tissue sodium content were observed between groups. Gray matter CBF was elevated (P = 0.03) in patients with lipedema (57.2 ± 9.6 mL per 100 g/min) versus control participants (49.8 ± 9.1 mL per 100 g/min).
CONCLUSIONS
Findings provide evidence that brain sodium and tissue fractions are similar between patients with lipedema and control participants and that patients with lipedema do not exhibit abnormal radiological indicators of intracranial vasculopathy or ischemic injury. Potential explanations for elevated CBF are discussed in the context of the growing literature on lipedema symptomatology and vascular dysfunction.
Topics: Adipose Tissue; Adult; Brain; Brain Chemistry; Case-Control Studies; Cerebrovascular Circulation; Female; Humans; Lipedema; Magnetic Resonance Imaging; Middle Aged; Neuroimaging; Sodium
PubMed: 32568462
DOI: 10.1002/oby.22837 -
Magnetic Resonance in Medicine Jul 2000The first spatially localized NMR spectra of osmolytes and metabolites from single isolated neurons have been obtained using a combination of high magnetic field...
The first spatially localized NMR spectra of osmolytes and metabolites from single isolated neurons have been obtained using a combination of high magnetic field strengths and NMR radio frequency (RF) microcoils. The proton spectra display peaks at high concentrations (100-300 mM) assigned to betaine and choline, and other metabolite resonances including lactate at lower concentrations in the order of 10s of millimoles. The volumes examined were approximately 10 nl, over two orders of magnitude less than previously possible. In these initial experiments; the cells were unperfused and the signal intensities of the osmolytes decrease with time, a phenomenon consistent with cell swelling. This work demonstrates the technical feasibility of NMR spectroscopy of single cells, further broadening the scope of NMR spectroscopy of living tissues from application to entire living organisms (man and animal models) and isolated tissues (perfused organs and cultured assemblies of cells) and now to single cells. Magn Reson Med 44:19-22, 2000.
Topics: Acetates; Animals; Aplysia; Betaine; Choline; Lactic Acid; Magnetic Resonance Spectroscopy; Neurons; Osmolar Concentration; Taurine; Water
PubMed: 10893516
DOI: 10.1002/1522-2594(200007)44:1<19::aid-mrm4>3.0.co;2-f -
Pharmacognosy Research Mar 2016Several synthetic drugs are useful in the treatment of peptic ulcer, but almost of these drugs are used in prolonging time, it may cause several adverse reactions....
BACKGROUND
Several synthetic drugs are useful in the treatment of peptic ulcer, but almost of these drugs are used in prolonging time, it may cause several adverse reactions. However, the herbal medicines are more potent to the treatment and minimize the side effects.
OBJECTIVE
To evaluate the methanol extract of Jatropha gossypiifolia Linn. (MEJG) for gastro protective activity against Wistar rats.
MATERIALS AND METHODS
Anti-ulcer potency of MEJG (100 and 200 mg/kg, b.w.) was assessed using aspirin (200 mg/kg, p.o.) plus pylorus ligation ulcer model and the parameters studied were ulcer index (UI), gastric juice volume, pH, total acidity, and total acid output. Same extract was studied by ethanol-induced (80%, 5 mL/kg, intragastrically) ulcer model, and the UI and biochemical parameters were studied.
RESULTS
The oral administration of MEJG (100 and 200 mg/kg) significantly (P < 0.001) attenuated the ulcer score and anti-secretary parameters (such as the volume of gastric content, free acidity, total acidity, and total acid output) in the aspirin plus pylorus ligation rats. The extract also significantly attenuated (P < 0.001) ulcer score in ethanol-induced ulcer model and lipid peroxidation level and significantly increased the level of glutathione peroxides, catalase, and superoxide dismutase activity. The MEJG may possess active constituents such as alkaloids, glycosides, flavonoids, and terpenes, which may play a major role in gastroprotective effect in Wistar rats.
CONCLUSION
The present study provides scientific support for the anti-ulcer activities of extracts of JG and also claimed that antioxidant potential of the extracts. However, substantiates the traditional claims for the usage of this drug in the treatment of gastric ulcer.
SUMMARY
The methanolic extract of jatropha gossypiifolia Linn. for gastro protective activity against aspirin plus pyloric ligation and ethanol induced ulcer models was studied in Wistar rats. JG shows significantly attenuated the ulcer score in both models. And also attenuated in anti-secretory parameters in aspirin induced ulcer model. MEJG may possess active constituents such as alkaloids, glycosides, flavonoids and terpenes, which may play a major role in gastroprotective effect in Wistar rats. Abbreviation Used: MEJG: Methanolic extract of jatropha gossypiifolia, mg: Milli gram, kg: Kilogram, b.w.: Body weight, p.o.: Per oral, UI: Ulcer index, pH: Concentration of H+ ion, mL: Milli litre, JG: Jatropha gossypiifolia,USD: United States Dollar, NSAIDs: Non steroidal anti-inflammatory drugs, v/v: Volume by volume, w/v: Weight by volume, SCMC: Sodium carboxy methyl cellulose, g: Gram, h: Hour, °C: Degree centigrade, n: Number, Rpm: Rotation per minute, Min: Minute, N: Normality, NaoH: Sodium hydroxide, mM - Millimole, TBA: Thiobarbituric acid, nmol: Nanomole, nm: Nanometer, GPx: Glutathione peroxidase, GSH: Reduced glutathione, H2O2: Hydrogen peroxide, SOD: Superoxide dismutase,
ANOVA
Analysis of Variance, μmol: Micromole.
PubMed: 27114695
DOI: 10.4103/0974-8490.178640 -
Biochimica Et Biophysica Acta Nov 2002The paper reviews the evidence for apparent sodium-dependent copper (Cu) uptake across epithelia such as frog skin, fish gills and vertebrate intestine. Potential... (Review)
Review
The paper reviews the evidence for apparent sodium-dependent copper (Cu) uptake across epithelia such as frog skin, fish gills and vertebrate intestine. Potential interactions between Na(+) and Cu during transfer through epithelial cells is rationalized into the major steps of solute transfer: (i) adsorption on to the apical/mucosal membrane, (ii) import in to the cell (iii) intracellular trafficking, and (iv) export from the cell to the blood. Interactions between Na(+) and Cu transport are most likely during steps (i) and (ii). These ions have similar mobilities (lambda) in solution (lambda, Na(+), 50.1; Cu(2+), 53.6 cm(2) Int. ohms(-1) equiv(-1)); consequently, Cu(2+) may compete equally with Na(+) for diffusion to membrane surfaces. We present new data on the Na(+) binding characteristics of the gill surface (gill microenvironment) of rainbow trout. The binding characteristics of Na(+) and Cu(2+) to the external surface of trout gills are similar with saturation of ligands at nanomolar concentrations of solutes. At the mucosal/apical membrane of several epithelia (fish gills, frog skin, vertebrate intestine), there is evidence for both a Cu-specific channel (CTR1 homologues) and Cu leak through epithelial Na(+) channels (ENaC). Cu(2+) slows the amiloride-sensitive short circuit current (I(sc)) in frog skin, suggesting Cu(2+) binding to the amiloride-binding site of ENaC. We present examples of data from the isolated perfused catfish intestine showing that Cu uptake across the whole intestine was reduced by 50% in the presence of 2 mM luminal amiloride, with 75% of the overall inhibition attributed to an amiloride-sensitive region in the middle intestine. Removal of luminal Na(+) produced more variable results, but also reduced Cu uptake in catfish intestine. These data together support Cu(2+) modulation of ENaC, but not competitive entry of Cu(2+) through ENaC. However, in situations where external Na(+) is only a few millimoles (fish gills, frogs in freshwater), Cu(2+) leak through ENaC is possible. CTR1 is a likely route of Cu(2+) entry when external Na(+) is higher (e.g. intestinal epithelia). Interactions between Na(+) and Cu ions during intracellular trafficking or export from the cell are unlikely. However, effects of intracellular chloride on the Cu-ATPase or ENaC indicate that Na(+) might indirectly alter Cu flux. Conversely, Cu ions inhibit basolateral Na(+)K(+)-ATPase and may increase [Na(+)](i).
Topics: Amiloride; Animals; Anura; Binding, Competitive; Catfishes; Cation Transport Proteins; Cell Membrane; Copper; Copper Transporter 1; Down-Regulation; Epithelium; Gills; Intestinal Absorption; Intestinal Mucosa; Ion Transport; Membrane Potentials; Membrane Proteins; Oncorhynchus mykiss; Sodium; Sodium Channels; Sodium-Potassium-Exchanging ATPase
PubMed: 12421542
DOI: 10.1016/s0005-2736(02)00590-4 -
The Journal of General Physiology Jul 1960Isolated frog sartorii were immersed in Ringer's solution, which had a 2 mM magnesium concentration containing Mg(28). The uptake of the radioactive magnesium was...
Isolated frog sartorii were immersed in Ringer's solution, which had a 2 mM magnesium concentration containing Mg(28). The uptake of the radioactive magnesium was measured under steady state conditions. Although the biological variability was fairly large, it was observed that the uptake proceeded in three stages lasting respectively about 0.5, 30, and 300 minutes and accounting respectively for about 0.21, 0.71, and 0.67 millimole magnesium/kg. muscle. It was assumed that the first stage represents surface adsorption, the second stage represents extracellular water and connective tissue phases, and the third stage entry inside the cell. It is estimated that the maximum intracellular magnesium concentration is about 1.1 mM and that only about 0.6 millimole magnesium/liter intracellular water is exchanged per hour. The maximum energy required per hour to pump the magnesium out of the cell against the electrochemical gradient is calculated to be only 1.5 cal./kg. muscle. About 75 to 80 per cent of the magnesium in muscle is non-exchangeable and difficult to remove by diffusion. It appears from previous work that the exchangeable magnesium behaves similarly to exchangeable calcium.
Topics: Animals; Anura; Calcium; Diffusion; Magnesium; Muscles
PubMed: 13849994
DOI: 10.1085/jgp.43.6.1103