• Publikační typ
• abstrakty MeSH

OBJECTIVE: The aim of the present study was to validate the limited sampling strategies (LSS:s) for prediction of AUC of cyclosporine A (CsA) after the first dose in rheumatologic patients. METHODS: 22 patients suffering from rheumathoid arthritis, systemic lupus erythematodus, ankylosing spondylitis dermato(poly)myositis or seronegative spondylarthritis were treated with Neoral® (female/male: 11/3, mean ± SD: age 49 ± 14 y, body weight 75 ± 12 kg, height 166 ± 7 cm, dose 71 ± 25 mg, dose per kg 1.0 ± 0.3 mg/kg), or Consupren® (7/1, 78 ± 36, 175 ± 8, 82 ± 22, 1.1 ± 0.3). Two patients whose C12h were missing were excluded from the AUC0-12 calculation. Whole blood levels of CsA were analyzed with HPLC. Blood samples were collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after taking the first dose. Altogether 115 LSS:s obtained from the literature were validated. A linear trapezoidal rule was used as a reference method. Mean percentage prediction error (%PE) < ± 15% and maximal one value of absolute %PE > 30% were considered to be acceptable. The root mean squared error (RMSE) was evaluated for equations that passed the criteria. RESULTS: The best performance with all values of the absolute %PE < 30% was found in three LSS:s for AUC0-12 and two for AUC0-8: AUC0-12 = 123.792 + 1.165 × C1h + 3.021 × C3h + 7.33 × C8h; 97.6 + 1.27 × C1h + 3.14 × C3h + 4.06 × C6h; or 124.3 + 1.34 × C1h - 0.16 × C2h + 3.27 × C3h + 3.96 × C6h; AUC0-8 = -19.8 + 1.99 × C2h + 2.38 × C4h + 3.15 × C6h or -22.4 + 2.51 × C2h + 5.49 × C6h. Validation criteria were further fulfilled in AUC0-12 = 24 + 3.66 × C0h + 2.11 × C1.5h + 4.54 × C4h or 0.2 + 2 × C2h + 10.2 × C6h; AUC0-8 = 55.37 + 2.89 × C0h + 1.08 × C1 + 0.9 × C2h + 2.23 × C3h; and AUC0-4 = -41 + 1.17 × C1h + 1.85 × C2h. Only one equation proposed for AUC0-6 did not pass the validation criteria. CONCLUSIONS: Equations validated for prediction of AUC0-12, AUC0-8 and AUC0-4 might be used for LSS:s of CsA independently of the length of treatment, indication, dosage or galenic formulation.

• MeSH
• antirevmatika aplikace a dávkování   farmakokinetika   MeSH
• cyklosporin aplikace a dávkování   farmakokinetika   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• plocha pod křivkou MeSH
• prediktivní hodnota testů MeSH
• reprodukovatelnost výsledků MeSH
• revmatické nemoci metabolismus   MeSH
• senioři MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Area under the concentration-time curve (AUC) has been advocated as a better parameter to monitor cyclosporine A than trough concentrations. Up to now, more than 100 equations to estimate AUC using a limited sampling strategy have been published, but not all have been validated. MATERIAL AND METHODS: Eight equations for AUC0-12h and two for AUC0-8h were validated. Concentrations of cyclosporine A were analyzed by high-performance liquid chromatography (HPLC) and a specific radioimmunoassay (RIA) method. Forty male renal transplant patients were included in the study. Blood samples were taken predose and at 0.5, 1, 1.5, 2, 3, 5, 8, and 12 hours after the morning dose when the patient was in steady state. The percentage prediction error (%pe) was used for an assessment of the performance of the equations. Mean %pe less than + 15% and absolute %pe less than 30% in 95% of predictions were considered to be acceptable. Other possibilities such as %pe less than 25%, 20%, and 15% were also tested. RESULTS: Eight equations for AUC0-12h met the requirements using both assays, six in the HPLC set only and four in the RIA set only. The highest precision was obtained with AUC0-12h = 123.792 + 1.165*C1h + 3.021*C3h + 7.33*C8h proposed by de Mattos et al. The mean %pe was 1% + 8% (-16 to 19) for HPLC (values given as mean + standard deviation [range]) and -1 + 5 (-17 to 10) for RIA. Mean absolute %pe was 7 + 5 (0.0 to 19) for HPLC and 4 + 4 (0.0 to 17) for RIA. For clinical use, the most suitable equation was AUC0-12h = 363.078 + 8.77*C1h + 3.07*C3h proposed by Wacke et al, which produced the second lowest %pe and used two sampling points in the period of 1 to 3 hours after dose. The mean %pe was -7 + 10 (-25 to 25) for HPLC and 2.3 + 6 (-10 to 17) for RIA. Mean absolute %pe was 10 + 7 (0.4 to 25) for HPLC and 5 + 4 (0.0 to 17) for RIA. The equation: AUC0-8h = 55.37 + 2.89*C0h + 1.08*C1h0.9*C2h + 2.23*C3h proposed by Foradori et al met the criteria with 95% of prediction with absolute %pe less than 15% in the HPLC set and 10% in the RIA set. CONCLUSION: The validation of equations is of major importance for prediction precision, whereas the analytical method for limited sampling strategy proposals had no influence. Because of the wide interassay variability, it is also important to know which analytical method was used for AUC calculation when interpreting the results.

• MeSH
• časové faktory MeSH
• cyklosporin farmakokinetika   krev   terapeutické užití   MeSH
• imunosupresiva farmakokinetika   krev   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• odběr vzorku krve MeSH
• plocha pod křivkou MeSH
• radioimunoanalýza MeSH
• transplantace ledvin MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

OBJECTIVE: To find limited sampling strategies (LSS) for prediction of the real AUC using the RIA analytical method. METHOD: Blood samples of 40 male renal transplant patients taken pre-dose and after 0.5, 1, 1.5, 2, 3, 5, 8, and 12 h in the steady-state were analyzed with HPLC and the specific RIA method. I. Eight equations for AUC0-12 and one for AUC0-8 obtained from the literature, that produced the mean percentage prediction error (%PE) < ± 15% and absolute %PE < 30% in 95% of predictions, were analyzed for possibility to predict the real AUC of CsA. II. Multiple regression analysis (MRA) was provided for the AUC equation proposal. Patients were divided into two groups according to the AUC0-12. Group I was used for LSS : s proposals while Group II for validation. The bias and precision were expressed as %PE, r2 and RMSE. The relationship of %PE interassay and with LSS:s was expressed as Pearson correlation r. GraphPad InStatt Software was used for MRA and Pearson r calculation. RESULTS: None of the equations described in the literature predicts AUC of CsA proprietarily. Seven equations for AUC0-12 and five for AUC0-8 were proposed with MRA for prediction of real AUC from RIA values. CONCLUSIONS: LSS:s can moderate the interassay %PE in AUC of CsA. New patients should be tested with both RIA and HPLC for the level of overestimation. The conversion factors should be calculated for patients with an overestimation higher than 90%. Our equation 251.09 + 0.5195 × C1h + 4.926 × C3h or 196.13 + 4.526 Â× C0h + 2.089 × C1.5h for AUC0-12, and 171.80 + 0.4759 × C1h + 4.132 × C3h for AUC0-8 may be used in patients with medium or low RIA and HPLC differences. Repeated analysis with HPLC is thus suggested in cases with AUC:s results close to the lower or upper margin of the therapeutic window.

• MeSH
• cyklosporin farmakokinetika   MeSH
• dospělí MeSH
• imunosupresiva farmakokinetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• plocha pod křivkou MeSH
• radioimunoanalýza metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Numerous physiological processes are cyclical, but sampling these processes densely enough to perform frequency decomposition and subsequent analyses can be challenging. Mathematical approaches for decomposition and reconstruction of sparsely and irregularly sampled signals are well established but have been under-utilized in physiological applications. We developed a basis pursuit denoising with polynomial detrending (BPWP) model that recovers oscillations and trends from sparse and irregularly sampled timeseries. We validated this model on a unique dataset of long-term inter-ictal epileptiform discharge (IED) rates from human hippocampus recorded with a novel investigational device with continuous local field potential sensing. IED rates have well established circadian and multiday cycles related to sleep, wakefulness, and seizure clusters. Given sparse and irregular samples of IED rates from multi-month intracranial EEG recordings from ambulatory humans, we used BPWP to compute narrowband spectral power and polynomial trend coefficients and identify IED rate cycles in three subjects. In select cases, we propose that random and irregular sampling may be leveraged for frequency decomposition of physiological signals. Trial Registration: NCT03946618.

• MeSH
• algoritmy MeSH
• elektroencefalografie metody   MeSH
• elektrokortikografie metody   MeSH
• epilepsie * patofyziologie   diagnóza   MeSH
• hipokampus patofyziologie   fyziologie   MeSH
• lidé MeSH
• modely neurologické MeSH
• počítačové zpracování signálu MeSH
• výpočetní biologie metody   MeSH
• záchvaty patofyziologie   diagnóza   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Zoonotic pathogen transmission is considered a leading threat to the survival of non-human primates and public health in shared landscapes. Giardia spp., Cryptosporidium spp. and Microsporidia are unicellular parasites spread by the fecal-oral route by environmentally resistant stages and can infect humans, livestock, and wildlife including non-human primates. Using immunoassay diagnostic kits and amplification/sequencing of the region of the triosephosphate isomerase, small ribosomal subunit rRNA and the internal transcribed spacer genes, we investigated Giardia, Cryptosporidium, and microsporidia infections, respectively, among humans, domesticated animals (livestock, poultry, and dogs), and wild nonhuman primates (eastern chimpanzees and black and white colobus monkeys) in Bulindi, Uganda, an area of remarkably high human-animal contact and spatial overlap. We analyzed 137 fecal samples and revealed the presence of G. intestinalis assemblage B in two human isolates, G. intestinalis assemblage E in one cow isolate, and Encephalitozoon cuniculi genotype II in two humans and one goat isolate. None of the chimpanzee and colobus monkey samples were positive for any of the screened parasites. Regular distribution of antiparasitic treatment in both humans and domestic animals in Bulindi could have reduced the occurrence of the screened parasites and decreased potential circulation of these pathogens among host species.

• Publikační typ
• časopisecké články MeSH

Camera trapping with capture-recapture analyses has provided estimates of the abundances of elusive species over the last two decades. Closed capture-recapture models (CR) based on the recognition of individuals and incorporating natural heterogeneity in capture probabilities are considered robust tools; however, closure assumption is often questionable and the use of an Mh jackknife estimator may fail in estimations of real abundance when the heterogeneity is high and data is sparse. A novel, spatially explicit capture-recapture (SECR) approach based on the location-specific capture histories of individuals overcomes the limitations of closed models. We applied both methods on a closed population of 16 critically endangered Western Derby elands in the fenced 1,060-ha Fathala reserve, Senegal. We analyzed the data from 30 cameras operating during a 66-day sampling period deployed in two densities in grid and line arrays. We captured and identified all 16 individuals in 962 trap-days. Abundances were estimated in the programs CAPTURE (models M0, Mh and Mh Chao) and R, package secr (basic Null and Finite mixture models), and compared with the true population size. We specified 66 days as a threshold in which SECR provides an accurate estimate in all trapping designs within the 7-times divergent density from 0.004 to 0.028 camera trap/ha. Both SECR models showed uniform tendency to overestimate abundance when sampling lasted shorter with no major differences between their outputs. Unlike the closed models, SECR performed well in the line patterns, which indicates promising potential for linear sampling of properly defined habitats of non-territorial and identifiable herbivores in dense wooded savanna conditions. The CR models provided reliable estimates in the grid and we confirmed the advantage of Mh Chao estimator over Mh jackknife when data appeared sparse. We also demonstrated the pooling of trapping occasions with an increase in the capture probabilities, avoiding violation of results.

• MeSH
• hustota populace * MeSH
• přežvýkavci * MeSH
• teoretické modely * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Senegal MeSH

C(2) or AUC sparse sampling methods are widely recommended for therapeutic monitoring of cyclosporin A (CsA). One additional reason for promoting the C(2) sampling time in place of commonly used C(0) is that the C(2) level may actually provide more accurate measurement of parent drug concentration by immunoassays, as lower portion of metabolites has been formed 2 hours post-dose than at the steady-state trough time point. HPLC and RIA whole blood levels of CsA and its main metabolites AM1, AM9 and AM4N were compared during 12 hours profile after chronic administration. 40 stable renal transplant male patients (age 49 +/- 6 years, body weight 76 +/- 7 kg) were treated with CsA (Sandimmun Neoral, Novartis s.r.o, Prague, Czech Republic) in doses 198 +/- 56 mg twice daily. Samples were collected in steady state (after 2 weeks of regular treatment regimen) as follows: pre-dose, 0.5, 1, 1.5, 2, 3, 5, 8 and 12 hours after dose. CsA concentrations were determined both specific RIA assay (Cyclo-Trac SP Whole, Dia Sorin) and HPLC method, where concentrations of metabolites AM1, AM9 and AM4N were simultaneously analyzed. The AUC(0-12) was calculated by the linear trapezoidal rule. The percentage prediction error defined as [(RIA value-HPLC value)/HPLC value] x 100 was used for estimation of differences. C(max), t(max), and C(avg) were compared using Student's t-test. RIA produced significantly higher CsA levels than HPLC method in the period of 0.5 - 5 hours after application. The greatest differences (43 - 56%) occurred between 1 and 3 hours after dose. AUC(0-12), C(max) a C(avg) calculated from RIA results were consequently significantly higher. Only t(max) remained unchanged. The ratio of metabolites/parent drug after CsA intake is decreasing but their absolute concentrations are significantly increasing. Mean levels at C(0)/C(2) were CsA-RIA 82/612, CsA-HPLC 89/425, AM1 121/179, AM9 4.1/81.4, AM4N 9.5/21.0 ng/ml. TDM using C(2) and AUC sparse sampling may cause misleading interpretation using both methods alternately for the same patient.

• MeSH
• časové faktory MeSH
• cyklosporin farmakokinetika   terapeutické užití   MeSH
• dospělí MeSH
• imunosupresiva farmakokinetika   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• plocha pod křivkou MeSH
• radioimunoanalýza metody   MeSH
• transplantace ledvin MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

Standard pharmacokinetic (PK) assessments are demanding for persons with hemophilia A, requiring a 72-hour washout and 5 to 11 timed blood samples. A no-washout, single-clinic visit, sparse sampling population PK (PPK) protocol is an attractive alternative. Here, we compared PK parameters obtained with a traditional washout, 6-sampling time point PPK protocol with a no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol in persons with severe hemophilia A (SHA) receiving ADVATE. A total of 39 inhibitor-negative males with SHA (factor VIII activity [FVIII:C] < 2%) were enrolled in a prospective sequential design PK study. Participants completed a washout, 6-sampling time point PPK protocol as well as a no-washout, reverse 2-sampling time point protocol, with samples taken during a single 3-hour clinic visit 24 hours post home infusion of FVIII and then 3 hours post infusion in clinic. FVIII:C levels were analyzed by one-stage and chromogenic assays; blood group and von Willebrand factor antigen (VWF:Ag) were determined; and PK parameters were analyzed using the ADVATE myPKFiT dosing tool. There was moderate to almost perfect agreement for the PK parameters obtained with the 2- and the 6- point PPK protocols using a one-stage FVIII:C assay and a substantial to almost perfect agreement using a chromogenic FVIII:C assay. Significant associations between specific PK parameters and blood group and VWF:Ag were observed. The no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol can be used in the routine clinical setting since it demonstrates sufficient accuracy compared with the more demanding and less practical washout, 6-sampling time point PPK protocol in persons with SHA receiving ADVATE.

• MeSH
• ambulantní péče MeSH
• biologické modely MeSH
• dítě MeSH
• dospělí MeSH
• faktor VIII aplikace a dávkování   farmakokinetika   MeSH
• hemofilie A krev   diagnóza   farmakoterapie   MeSH
• hemokoagulace účinky léků   MeSH
• klinické protokoly MeSH
• koagulancia aplikace a dávkování   krev   farmakokinetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• monitorování léčiv * MeSH
• prediktivní hodnota testů MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• srovnávací studie MeSH
• Geografické názvy
• Austrálie MeSH
• Česká republika MeSH
• Kanada MeSH

A strategy for complete backbone and side-chain resonance assignment of disordered proteins with highly repetitive sequence is presented. The protocol is based on three resolution-enhanced NMR experiments: 5D HN(CA)CONH provides sequential connectivity, 5D HabCabCONH is utilized to identify amino acid types, and 5D HC(CC-TOCSY)CONH is used to assign the side-chain resonances. The improved resolution was achieved by a combination of high dimensionality and long evolution times, allowed by non-uniform sampling in the indirect dimensions. Random distribution of the data points and Sparse Multidimensional Fourier Transform processing were used. Successful application of the assignment procedure to a particularly difficult protein, δ subunit of RNA polymerase from Bacillus subtilis, is shown to prove the efficiency of the strategy. The studied protein contains a disordered C-terminal region of 81 amino acids with a highly repetitive sequence. While the conventional assignment methods completely failed due to a very small differences in chemical shifts, the presented strategy provided a complete backbone and side-chain assignment.

• MeSH
• algoritmy MeSH
• deuterium MeSH
• Fourierova analýza MeSH
• izotopy dusíku MeSH
• izotopy uhlíku MeSH
• molekulární sekvence - údaje MeSH
• nukleární magnetická rezonance biomolekulární metody   MeSH
• proteiny chemie   MeSH
• repetitivní sekvence nukleových kyselin MeSH
• sekundární struktura proteinů MeSH
• sekvence aminokyselin MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH