A spatial modeling tool for agricultural systems

Many natural processes (heat transfer, precipitation, flow) and systems (landforms, crop distributions, water bodies) are most effectively modeled on a spatial (distributed) basis. A way of thinking about such modeling is suggested and current software is reviewed. A prototype software tool for modeling a variety of systems is developed. It consists of an interactive, high-level computer language that manipulates intelligent arrays. The language provides input distributions, mathematical/logical/positional operators, statistical analysis, various computational approaches, and graphic output. The tool\u27s use is demonstrated with three systems - surface water over a landform, pressure distribution in the cross section of a dam, and the performance of an irrigation pressure regulator. Other applications are suggested and program refinements proposed

Predicting drug interactions using cultured human hepatocytes

In previous papers we demonstrated that cyclosporin A (CsA) was specifically oxidized in rabbit and human liver by cytochrome P-450IIIA. We therefore anticipated that any drug that is an inducer or an inhibitor of this cytochrome should lead to interaction with CsA when given in association with it. In order to confirm this hypothesis, primary cultures of human hepatocytes and human liver microsomes were used to “reproduce” in vitro clinically significant interactions observed between CsA and drugs known either as specific inducers (i.e., rifampicin) or as specific inhibitors (i.e., erythromycin) of P-450IIIA. Our results were in close agreement with the clinical reports. Human hepatocytes maintained in primary cultures for 72 hr in the presence of 50 ΜM rifampicin exhibited increased levels of P-450IIIA, determined by Western blot using specific antibodies, and concomitant increase in CsA oxidase activity, determined by HPLC analysis of extra and intracellular media. Conversely, these cultures exhibited erythromycin concentrationdependent decreases in CsA oxidase activity when incubated in the presence of 5, 20, and 100 ΜM erythromycin. In addition, a Lineweaver-Burk analysis of the erythromycin-mediated inhibition of CsA oxidase activity in human liver microsomes revealed competitive inhibition (with K i of 75 ΜM) as expected, this macrolide being a specific substrate of P-450IIIA. Using this experimental approach, 59 molecules representative of 17 different therapeutic classes were screened for inducers and inhibitors of CsA oxidase activity. Our results allowed us to elucidate the molecular mechanism of previously observed, but unexplained, drug interactions involving CsA, and to detect drugs that should interfere with CsA metabolism as inducers or inhibitors. Drugs detected as potential inducers of CsA oxidase included: rifampicin, sulfadimidine, phenobarbital, phenytoin, phenylbutazone, dexamethasone, sulfinpyrazone, and carbamazepine. Drugs detected as potential competitive inhibitors included: triacetyloleandomycin, erythromycin, josamycin, midecamycin, ketoconazole, miconazole, midazolam, nifedipin, diltiazem, verapamil, nicardipine, ergotamine, dihydroergotamine, glibenclamide, bromocryptine, ethynylestradiol, progesterone, cortisol, prednisone, prednisolone, and methylprednisolone. Finally cefoperazone, cefotaxime, ceftazidime, isoniazide, doxycycline, spiramycin, sulfamethoxazole, norfloxacin, pefloxacin, vancocin, trimethoprime, amphotericine B, valproic acid, quinidine, cimetidine, ranitidine, omeprazole, diclofenac, aspirin, paracetamol, debrisoquine, guanoxan, captopril, furosemide, acetazolamide, sparteine, gliclazide, and imipramine were found not to interfere with the hepatic metabolism of CsA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38363/1/1840140231_ftp.pd

Mulberry extract to modULate Blood glucosE Responses in noRmoglYcaemic adults (MULBERRY): study protocol for a randomized controlled trial

Background: worldwide sugar consumption has tripled during the last fifty years. High sugar intake is associated with weight gain and increased incidence of diabetes and has been linked with increased cardiovascular mortality. Reducing the health impact of dietary sugar and poor quality carbohydrate intake is a public health priority. IminoNorm®, a proprietary mulberry leaf extract (ME), may reduce blood glucose responses following dietary sugar and carbohydrate intake by reducing absorption of glucose from the gut. Previous research has shown that ME can reduce blood glucose and improve insulin responses in healthy subjects and also in subjects with raised fasting blood glucose levels. Mulberry leaf has an excellent safety profile. This pilot study will test a novel, safe, water soluble product in normoglycaemic adults in the UK to determine if it can reduce glucose absorption without increasing plasma insulin concentration.Methods/design: the trial will be a double-blind, individually randomised, four-arm single-dose crossover design to test the effect of three doses of ME in order to determine efficacy, dose response relationship and gastrointestinal side effects with respect to placebo. A total of 40 subjects will participate in this study and attend for four visits receiving each of the four interventions in random order.Discussion: we aim to test the evidence that mulberry leaf extract can reduce blood glucose without a disproportionate increase in blood insulin responses in healthy individuals in a high-quality research study based in the UK. It is hoped that this will lead to further randomised controlled trials and an effective dietary supplement to lower blood glucose concentration

Spontaneous Variability and Circadian Distribution of Ectopic Activity in Patients With Malignant Ventricular Arrhythmia

Day to day variability of ventricular ectopic activity was analyzed in 45 patients with a history of malignant ventricular tachyarrhythmias who underwent two successive 24 h periods of ambulatory electrocardiographic (ECG) monitoring in the absence of antiarrhythmic drugs; 26 were male and 19 female, with a mean age of 56 years (range 15 to 76). The total number of single ventricular premature beats, couplets and ventricular tachycardia beats and runs on days 1 and 2 demonstrated a consistent overall correlation (r = 0.76 to 0.84). Individual variability was evaluated by regression analysis with determination of 95% confidence limits.The minimal decrease in arrhythmia density necessary to distinguish true drug effect from spontaneous variability was 64% for single ventricular premature beats, 83% for couplets, 90% for ventricular tachycardia runs and 93% for ventricular tachycardia beats. To meet the criteria for arrhythmia aggravation, the arrhythmia density had to increase by 400, 877, 1,500 and 2,400%, respectively. Multivariate analysis disclosed an inverse relation between day to day arrhythmia variability and baseline arrhythmia density and age. Variability was more pronounced in patients with coronary artery disease but was not influenced by the type of presenting arrhythmia or left ventricular function.The diurnal distribution of arrhythmias and heart rate followed a distinct circadian pattern. These data indicate that, despite good group reproducibility, spontaneous arrhythmia variability in individuals is substantial, necessitating standards to define both drug effect and arrhythmia aggravation

P450 3A activity and cyclosporine dosing in kidney and heart transplant recipients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109917/1/cptclpt1994135.pd

Hepatic but not intestinal CYP3A4 displays dose‐dependent induction by efavirenz in humans

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110078/1/cptclpt200260.pd

Ethanol and production of the hepatotoxic metabolite of acetaminophen in healthy adults

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109855/1/cptclpt200062.pd

Systematic review of clinical practice guidelines for acne vulgaris published between January 2017 and July 2021

Background: Acne is very common, can cause considerable negative impact on quality of life and there is increasing concern over the use of long courses of oral antibiotics for this condition. Objectives: (1) To critically appraise reporting in acne guidelines and compare this with previous systematic review of acne guidelines. (2) Examine acne treatment guidance on pre-specified acne treatments of interest and compare between acne guidelines. Methods: Searches for new or updated guidelines were carried out in MEDLINE, Embase, Google Scholar, LILACS from 1 January 2017 to 31 July 2021, supplemented by searching a guideline-specific depository and checking for updates to guidelines included in previous review. We included guidelines, consensus statements or care protocols on the medical treatment of acne vulgaris in adults and/or children and excluded those that focused on a single intervention or subgroup of acne, regional adaptations of guidelines or guidelines included in previous review. AGREE II checklist was applied to critically appraise reporting of guidelines. Results were synthesised narratively. Results: Of 807 abstracts identified nine guidelines were identified that were eligible for inclusion. All guidelines had AGREE II scores above average in at least one domain and reporting was substantially improved compared to the systematic review of acne carried out 5 years previously. There was consensus between guidelines on the key role of topical treatments as first-line acne treatment and most recommended continuing topical treatments as maintenance therapy. There was considerable variation between guidelines on classification of severity, indications for commencing oral antibiotics and on maximum duration of oral antibiotics. However, there was consensus on the need for co-prescription of a non-antibiotic topical treatment when using oral antibiotics. There were notable differences on recommendations regarding provision of information for patients on how to use topical treatments or how to mitigate against side effects. Conclusions: Substantial differences in classification of acne severity hampered comparisons between guidelines. Although development and reporting of guidelines has improved over the past 5 years, differences in key recommendations remain, possibly reflecting uncertainties in the underlying evidence base. Differences between guidelines could have substantial implications for prevalence of antibiotic prescribing for acne

Role of intestinal P‐glycoprotein ( mdr1 ) in interpatient variation in the oral bioavailability of cyclosporine

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110064/1/cptclpt1997116.pd