Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM): Crossover pilot study (J-VICTORIA study)

Background

The role of Lipoprotein (a) cholesterol {Lp(a)-C}as an additional and/or independent risk factor for cardiovascular disease (CVD) is not clear. We evaluated the associations between Lp(a)-C and other CVD risk factors including plasma lipoprotein concentrations and body fatness in overweight and obese African American children.

Methods

A cross-sectional analysis was carried out using data from a sample of 121 African American children aged 9-11 years with Body Mass Index (BMI)'s greater than the 85th percentile. Body height, weight and waist circumference (WC) were measured. Fasting plasma concentrations of Lp(a)-C, Total cholesterol (TC), High density lipoprotein cholesterol (HDL-C), Very low density lipoprotein cholesterol (VLDL-C), Intermediate density lipoprotein cholesterol (IDL-C), Low density lipoprotein cholesterol (LDL-C), and Triacylglycerides (TAG) were analyzed using the vertical auto profile (VAP) cholesterol method.

Results

After adjusting for child age, gender, and pubertal status, Lp(a)-C was positively associated with both HDL-C and TC, and negatively associated with VLDL-C and TAG. Including BMIz and WC as additional covariates did not alter the direction of the relationships between Lp(a)-C and the other lipoproteins. Finally, after adjusting for the other plasma lipoproteins, Lp(a)-C remained strongly associated with HDL-C, whereas the associations of Lp(a)-C with the other lipoproteins were not significant when HDL-C was simultaneously included in the regression models.

Conclusions

Lp(a)-C was positively associated with HDL-C and this association is not influenced by other lipoprotein subclasses or by the degree of obesity. We conclude that Lp(a) cholesterol is not an independent risk factor for CVD in African American children.     

Comparison of cimetidine 800 mg once daily and 400 mg twice daily in acute duodenal ulceration.

A double blind trial was conducted in seven centres to evaluate the safety and efficacy of cimetidine 800 mg given at night compared with 400 mg given at breakfast and at bedtime. Altogether 197 patients with active duodenal ulcer confirmed by endoscopy entered the study, of whom 187 were eligible for analysis. After four weeks'' treatment the ulcer was healed in 76 of 91 patients (84%) receiving the once daily regimen and in 65 of the 96 patients (68%) receiving the twice daily regimen (p less than 0.05). Both dosage regimens were equally effective in reducing ulcer pain and consumption of antacids. Pain relief was considerable within the first two weeks, and most of the patients were free of symptoms by the end of treatment. No patients were withdrawn because of adverse events as these were few and mild, consistent with the proved safety profile of cimetidine. Cimetidine 800 mg given at night is as effective as 400 mg twice daily; the single dose regimen may improve patient compliance, thus facilitating treatment.     

Reproducible fabrication of miniaturized glucose sensors: preparation of sensing membranes for continuous monitoring.

The immobilization process of glucose oxidase(GOx) in the poly(1,3-diaminobenzene) (poly(1,3-DAB)) network was closely investigated in situ using an electrochemical quartz crystal microbalance(EQCM). GOx captured in approximately 50 nm thick poly-1,3-DAB layer causes a 514 Hz frequency increase, corresponding to 541 ng, and distributes mostly in the outer part of the polymer film. The presence of poly-L-lysine and glutaraldehyde during electropolymerization of poly(1,3-DAB) improves sensitivity by raising the amount of GOx immobilized. Adding a protective membrane on to the enzyme layer from poly(tetrafluoroethylene) (PTFE) dispersed in aqueous media lets the entire fabrication procedure finish perfectly without nonaqueous solvent. The finalized needle-type glucose sensors show competent functions in sensitivity, stability, biocompatibility, lifetime, interference and reproducibility.     

Combination of microdialysis and Glucosensor permits continuous (on line) s.c. glucose monitoring in a patient operated device: I. In vitro evaluation.

A device for continuous glucose monitoring in fluids was obtained by combining the microdialysis technique with a measuring flow chamber of the "Glucosensor Unitec Ulm" using the GOD method for determining amperometrically blood glucose profiles. The in vitro experiments demonstrate that the relative recovery of glucose by this device is inversely related to the flow rate of the microdialysis perfusion fluid, which, in turn, is inversely related to the response time of the device. The glucose signal increases linearly with the area of the microdialysis working membrane (r = 0.98), and with the glucose concentrations of the standard solutions (r greater than 0.95). The variation coefficient for repeated measurements is below 8%. The accuracy of the device as demonstrated by mean measuring deviation ranges between 1 and 3.8%.     

Studies of glucose production in sheep using (6-3H)glucose and (U-14C)glucose.

Simultaneous primed-continuous intravenous infusions of [6-3H]glucose and [U-14C]glucose were performed on 13 fed, 4 fasted, and 4 dexamethasone-treated sheep. In 10 of the experiments on fed sheep, glucagon or insulin was infused intraportally for 2 h after control values were obtained. The 3H-labeled glucose gave glucose production values that were only 4.4 +/- 0.5, 5.4 +/- 1.0, and 5.8 +/- 0.8% higher than 14C-labeled glucose in the normal fed, fasted, and dexamethasone-treated sheep, respectively. Glucagon or insulin infusions did not significantly alter this recycling. It is condluced that a recycling of glucose carbon through metabolic intermediates is minimal in the sheep as compared with other species and also that it is not significantly altered by fasting or by hormones that affect glucose production.     

Combination of microdialysis and glucosensor permits continuous (on line) SC glucose monitoring in a patient operated device. II. Evaluation in animals.

The microdialysis technique was used for following the glucose content of the extracellular subcutaneous (SC) fluid under varying blood glucose levels in rats. The glucose content in the microdialysis perfusion fluid was continuously analyzed by means of the measuring flow chamber of an ex vivo glucose monitor. In six ChBB rats blood glucose levels were varied between 40 mg/dl and 575 mg/dl by intravenous (IV) infusion of glucose and by SC injections of insulin, respectively. After a running-in period of about half an hour, the glucose content in the perfusion fluid was closely related to the blood glucose concentration (r > 0.92) up to a time period of 6 hrs. The "relative recovery" rate of glucose by the microdialysis probe in the SC tissue varied within the 6 experimental sessions. The relative recovery rate could be shown to be not dependent on the absolute blood glucose levels in the individual rat within the glucose concentration range tested.     

Efficacy of intra-lesional injections of meglumine antimoniate once a week vs. twice a week in the treatment of cutaneous leishmaniasis caused by L. tropica in Iran: A randomized controlled clinical trial

Treatment of Cutaneous leishmaniasis (CL) is based on using antimoniate derivatives; patients’ compliance for systemic injections is low due to the pain and systemic complications. In this randomized open trial, the efficacy of intra-lesional (IL) injections of meglumine antimoniate (MA) once a week vs. twice a week in the treatment of Anthrpoponothic CL caused by L. tropica was studied. Eligible volunteer patients were selected according to inclusion/exclusion criteria. The included patients were randomly allocated to receive IL-MA injections once a week or twice a week. The primary outcome was set as complete healing of the lesion(s), and defined as complete re-epithelialization and absence of induration in the lesions. A total of 180 parasitologicaly proven CL patients caused by L. tropica were recruited, 90 patients were treated with weekly IL-MA and 90 patients received IL-MA twice a week. The complete cure was 87.9% vs. 89.2% in the group received weekly and twice a week IL-MA injections, respectively (P = 0.808). Patients’ compliance was acceptable and side effects were limited to a few local allergic reactions to MA. Median time to healing was significantly shorter in patients who received IL-MA twice a week (median ± SE) 37±3.8, (CI: 29.6–44.4) days compared to whom received IL-MA once a week 60±2.3, (CI: 55.6–64.5) days (P< 0.001), however the number of injections was higher in group who received IL-MA twice a week (12 vs. 9 injections). In conclusion, the rate of cure in the group of CL patients with IL-MA twice a week was not significantly different from the group who received IL-MA once a week shorten, but the duration of healing was shorter in the group who received IL-MA twice a week while the group received more injections so is recommended to use IL-MA once a week due to the fact the compliance is acceptable with limited side effects.Clinical Trial Registration: IRCT20081130001475N13; https://en.irct.ir/.     

An interference-free biosensor based on glucose oxidase electrochemically immobilized in a non-conducting poly(pyrrole) film for continuous subcutaneous monitoring of glucose through microdialysis sampling

A glucose biosensor, based on glucose oxidase immobilized in a non-conducting (overoxidised) polypyrrole film, is described which proved practically immune from faradaic interference arising from endogeneous (ascorbate, urate, cysteine) and exogeneous (acetaminophen) electroactive interferents. The bias introduced in the measurement of 5 mM glucose by the given interferents at their maximum physiological levels never exceeded 2% which is, by far, the lowest value ever reported. The biosensor has been used for continuous subcutaneous monitoring of glucose in a rabbit implanted with a microdialysis probe. The potential and limits of this approach are discussed.     

Selected ion monitoring gas chromatography/mass spectrometry using uniformly labelled (13C)glucose for determination of glucose turnover in man

An optimized method is described for the mass fragmentographic determination of uniformly labelled (13C)glucose in human plasma using a butylboronic acid acetate derivative, and capillary gas chromatography. The advantages of the method are the ease and speed of the derivatization procedure, the small sample size, high precision (interassay coefficient of variation 5.7%), and applicability of a relatively low-cost mass spectrometer. This method allows glucose tracer experiments to be performed in man using the bolus injection technique, necessitating analysis of many samples. The results on glucose turnover obtained in a clinical experiment were in full agreement with previously published data.     

On-line monitoring of glucose in mammalian cell culture using a flow injection analysis (FIA) mediated biosensor

A flow injection analysis (FIA) biosensor system has been developed for on-line determination of glucose during mammalian cell cultivation. The culture sample was peristaltically withdrawn from the bioreactor and after cell separation by a steam sterilizable ceramic microfilter, the filtrate was continuously fed to the FIA mediated-biosensor system at 4 mLh(-1), whereas the cell-containing retentate was recirculated to the bioreactor. In the amperometric biosensor system, glucose oxidase was covalently immobilized onto a preactivated nylon membrane and attached to the sensing area of a platinum working electrode. The enzyme reaction was coupled with the mediator 1,1'-dimethylferricinium (DMFe(+))-cyclodextrin inclusion complex to recycle the reduced glucose oxidase to its original active state. 1,1'-Dimethylferrocene (DMFe) was then reoxidized to DMFe(+) at the surface of the platinum electrode poised at + 0.15 V vs silver/silver chloride. The FIA mediated-biosensor was linear up to 6 mM glucose, with a detection limit of 0.1 mM, and possessed excellent reproducibility (+/- 0.4 %, 95 % confidence interval) over 123 repeated analyses during a 62 h continuous operation. The immobilized glucose oxidase was stable for up to 7 days when applied to glucose measurement during 5-10 day fed-batch cultivation of 293S mammalian cells. The results obtained from the mediated-biosensor system compared well with the hexokinase and HPLC data. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 497-504, 1997.     

Measuring anterior trunk deformity in scoliosis: development of asymmetry parameters using surface topography (a pilot study)

Background

Clinicians who assess and treat patients for scoliosis typically use parameters that are all visible from the posterior view. Radiographs assess the internal spinal deformity, but do not directly evaluate body shape, either posterior or anterior. This is problematic, as the patient is most concerned about the way they appear in the mirror. An objective set of anterior measurements is needed to help quantify the anterior asymmetry that is present in scoliosis.

Methods

The design of this system of assessment was developed as a consensus of thinking from four points of view. A spine surgeon provided the musculoskeletal structural perspective. A plastic surgeon specializing in breast reconstruction provided the aesthetic and soft tissue perspective. A surface topography researcher provided the imaging perspective, and a scoliosis patient provided the self-perception and emotional perspective.Using an iterative process, a series of potential measurement parameters using surface topography measurements were considered, debated, and ultimately selected to be part of a system of measurement that provides an overall assessment of anterior trunk asymmetry.

Results

An anterior surface topography scan in the relaxed, standing position was taken of the scoliosis patient. The computer provides a 3D topographical model that is used to complete measurements that can be combined to achieve an Anterior Aesthetic Deformity Score. Shoulder parameters, including shoulder height difference and shoulder slope difference, make up 40 % of the total score. Breast asymmetry, including nipple height difference and sternal notch-to-nipple distance, make up 30 % of the total score. Waist asymmetry makes up the final 30 % of the score, providing an objective and quantifiable measure of anterior trunk deformity.

Conclusions

These measurements provide an objective, systematic evaluation of anterior trunk asymmetry that can be used in the assessment of patients with scoliosis. Clinical research should now be done to validate this system and show that it is reproducible in a variety of settings and patients.

     

Diurnal changes in concentration of rumen ciliates and in occurrence of dividing forms in water buffalo (Bubalus bubalus) fed once daily.

When buffalo were fed once daily, significant diurnal variations in concentration of rumen ciliates and occurrence of dividing protozoa were found. Differences in proportions of dividing Entodinium- and Diplodinium-type ciliates were also observed. Results obtained suggest that the range of diurnal fluctuations in rumen protozoa concentration may be related to the percentage of dividing cells in populaitons of these organisms.     

Diurnal changes in concentration of rumen ciliates and in occurrence of dividing forms in water buffalo (Bubalus bubalus) fed once daily.

When buffalo were fed once daily, significant diurnal variations in concentration of rumen ciliates and occurrence of dividing protozoa were found. Differences in proportions of dividing Entodinium- and Diplodinium-type ciliates were also observed. Results obtained suggest that the range of diurnal fluctuations in rumen protozoa concentration may be related to the percentage of dividing cells in populaitons of these organisms.     

Evaluation of Crocus sativus L. (saffron) on male erectile dysfunction: A pilot study

In this study, the effect of Crocus sativus (saffron) was studied on male erectile dysfunction (ED). Twenty male patients with ED were followed for ten days in which each morning they took a tablet containing 200 mg of saffron. Patients underwent the nocturnal penile tumescence (NPT) test and the international index of erectile function questionnaire (IIEF-15) at the start of the treatment and at the end of the ten days. After the ten days of taking saffron there was a statistically significant improvement in tip rigidity and tip tumescence as well as base rigidity and base tumescence. ILEF-15 total scores were significantly higher in patients after saffron treatment (before treatment 22.15±1.44; after treatment 39.20±1.90, p<0.001). Saffron showed a positive effect on sexual function with increased number and duration of erectile events seen in patients with ED even only after taking it for ten days.     

Comparison of water ingestion between black flies (Simuliidae) and a mosquito (Aedes aegypti; Culicidae) using radiolabelled glucose

Ingestion of water by larvae of the black flies Simulium verecundum, Prosimulium mixtum/fuscum and Cnephnia dacotensis and by larvae of the mosquito Aedes aegypti was studied with radiolabelled glucose as a tracer. Extremely low ( 200 dpm/3 h) radiolabel uptake occurred in the black flies species, while Aedes aegypti, a species that is known to drink, had high radiolabel counts (> 6000 dpm/3 h). Radiolabel uptake by S. verecundum did not change for larvae fed in absence of current or with plugged mouthparts versus normal larvae. Radiolabel uptake by Aedes aegypti larvae with plugged mouthparts was < 3% of radiolabel uptake in normal larvae. Aedes aegypti was able to ingest the soluble glucose. Simulium verecundum, Prosimulium mixtum/fuscum and Cnephia dacotensis were unable to ingest the soluble sugar. The rationale for this difference is in the different filter-feeding mechanism of Culicidae and Simuliidae.     

Comparison of methods for rooting phylogenetic trees: A case study using Orcuttieae (Poaceae: Chloridoideae)

DNA sequence data (cpDNA trnL intron and nrDNA ITS1 and ITS2) were analyzed to identify relationships within Orcuttieae, a small tribe of endangered grasses endemic to vernal pools in California and Baja California. The tribe includes three genera: Orcuttia, Tuctoria, and Neostapfia. All three genera carry out C₄ photosynthesis but aquatic taxa of Orcuttia lack Kranz anatomy. The unusual habitat preference of the tribe is coupled with the atypical development of C₄ photosynthesis without Kranz anatomy. Furthermore, the tribe has no known close relatives and has been noted to be phylogenetically isolated within the subfamily Chloridoideae. In this study we examine the problem of inferring the root of the tribe in the absence of an identified outgroup, analyze the phylogenetic relationships of the constituent taxa, and evaluate the evolutionary development of C₄ photosynthesis. We compare four methods for inferring the root of the tree: (1) the outgroup method, (2) midpoint rooting, the imposition of a molecular clock for both (3) maximum likelihood (ML) and (4) Bayesian analysis. We examine the consequences of each method for the inferred phylogenetic relationships. Three of the methods (outgroup rooting and the ML and Bayesian molecular clock analyses) suggest that the root of Orcuttieae is between Neostapfia and the Tuctoria/Orcuttia lineage, while midpoint rooting gives a different root. The Bayesian method additionally provides information about probabilities associated with other possible root locations. Assuming that the true root of Orcuttieae is between Neostapfia and the Tuctoria/Orcuttia lineage, our data indicate Neostapfia and Orcuttia are both monophyletic, while Tuctoria is paraphyletic (with no synapomorphies in either dataset) and forming a grade between the other two genera and needs taxonomic revision. Our data support the hypothesis that Orcuttieae was derived from a terrestrial ancestor and evolved specializations to an aquatic environment, including C₄ photosynthesis without Kranz anatomy.