No abstract

Blastoferon, in the following referred to as the test product, is a pharmaceutical product of interferon beta la (CAS 220581-49-7) currently marketed as a biosimilar to the innovator Interferon beta la product (referred to as the reference product). Pharmacokinetics and pharmacodynamIcs assays are critically relevant to demonstrate similarity between biopharmaceuticals. The aims of the present study were to investigate the bioavailability (BA) of the test product (either absolute or relative to the innovator product) and to compare the extent of increase of neopterin concentration following administration of either product. Two studies were performed: initially, an absolute BA assay with i.v. and s.c. injection of test product to 12 healthy subjects. Second, a formal relative BA study with s.c. injections of 88 microg of both products to 24 healthy volunteers. Blood samples for pharmacokinetic and pharmacodynamic profiling were drawn at different intervals after injection. Interferon beta (IFNB) concentrations were determined by ELISA. In the absolute BA study, a single s.c. dose of 44 microg of the test product resulted in a median bioavailable fraction of 29%, a median T(max) of 4 h (4-6) and a C(max) of 3.69 (3.27-4.41) IU x ml(-1). In the relative BA study, values for the test product were: median T(max) of 3 h (2-18), C(max) of 5.39 (4.99-6.31) IU x ml(-1), AUC (0-72) of 142.86 (134.16-190.15) IU x h x ml(-1) and AUC(0-infinity) of 190.95 (174.23-303.13) IU x h x ml(-1). The corresponding values for the innovator product were: T(max) of 3 h (1-24), C(max) of 4.44 (4.12-5.40) IU x ml(-1), AUC(0-72) of 128.77 (121.18-170.92) IU x h x ml(-1) and AUC(0-affinity) of 192.61 (183.04-286.46) IU x h x ml(-1). The AUC(0-72) ratio was 111% (CI 90%: 106-116), the AUC(0-affinity) was 99% (CI 90%: 92-107) and the C(max) ratio was 121% (CI 90%: 112-131). IFNB1a increased neopterin levels in both studies. Both products induced side-effects commonly reported for IFN with no serious adverse events. This study presents pharmacokinetics parameters of the test product and demonstrates similar bioavailability of IFNB1a for both pharmaceutical products.

RNA removal was incomplete, and pigmented or oily residues were carried through with the DNA.Unicellular spores of non-rust fungi, desiccated and stored at 4°C for six months (basidiospores from a spore print of the mushroom Amanita muscaria var. formosa ; teliospores of the corn smut fungus Ustilago maydis ; and basidiospores of puffball species Lycoperdon echinatum and L. pyriforme ) yielded abundant DNA after 10 s disruption by the shaker method, whereas only small amounts of DNA were obtained from the cohesive, multicellular columns of blister rust teliospores after 10-20 s disruption (Figure 1). The overloading of DNA, residual RNA, and shearing observed in some samples after electrophoresis indicate that additional optimization could be beneficial. However, in independent tests of the shaker method, DNA from 5-25 mg U spores of the wheat leaf-rust fungus Puccinia triticina was similar in quality and quantity to our reported yields for blister rust U spores (Eric Swann, personal communication).Fresh and stored DNA obtained by dry grinding methods from U spores of four blister rust isolates (CA2.1B, ME2.9B, WI4.1B, and WY3.1B) gave consistent PCR amplification [20 µ L RAPD reactions with 10 ng DNA, 0.2 µ M 10-mer primer, and 2.5 mM MgCl 2 for 40 cycles of amplification in a 96-V-well thermal cycler with Hot Bonnet ™ (MJ Research, Waltham, MA, USA)]. RAPD bands were obtained for 60 of 72 UBC RAPD primers (University of British Columbia, Vancouver, BC, Canada) in their initial screening for use in the study of population diversity. In addition, DNA extracted from as little as 5 mg U spores of P. triticinausing the dry grinding shaker method was successfully used for AFLP (Eric Swann, personal communication). The reported protocols thus have potential for DNA extraction from fungal spores for use in PCRbased studies.

No relationships reported)Conventionally, 'nutritional' strategies to optimize cycling performance include carbohydrate and/or caffeine; the independent actions of which have been widely studied. Despite common practice, little is known about the interactive effects of carbohydrate and caffeine on high intensity cycling performance (≤ 1hr), especially in the fed state. PURPOSE:The purpose of this study was to examine the independent and combined effects of carbohydrate and caffeine ingestion on performance and various physiological parameters during high-intensity aerobic cycling (~1 hr). METHODS:Ten cyclists (28 ± 3 yr, 73.2 ± 1.9 kg) performed 20 min of steady-state cycling (SS; 60% Wmax) followed by a simulated 20-km time trial (TT) under the following four treatment conditions: placebo (PLA), carbohydrate (CHO), caffeine (CAF), and combined CHO and CAF (CHO-CAF). Prior to exercise, cyclists consumed a standardized breakfast (-2 hrs) and a placebo/caffeine capsule (-1 hr). Beverages (250 ml; placebo or 8% CHO) were consumed prior to 20-min steady-state, prior to TT, and at min 20 of TT. RESULTS: CHO-CAF improved TT performance by 3.4% (93 ± 61 sec) compared to PLA (p < 0.05), whereas no differences were detected among CHO, CAF, and PLA. Likewise, CHO-CAF improved mean TT power output by 5% (12 ± 8 W), compared to PLA. SS RER was elevated in CHO (0.92 ± 0.02), CAF (0.96 ± 0.07), and CHO-CAF (0.95 ± 0.02) compared to PLA (0.89 ± 0.03) (p < 0.05). Post-SS and post-TT blood glucose levels were elevated in CHO-CAF (SS: 88.3 ± 16.7 mg/dL, TT: 111.2 ± 33.5) compared to PLA (74.5 ± 9.8, 85.4 ± 17.6). Treatment conditions did not differentially impact VE, VO2, HR, peak quadriceps muscle strength, RPE, or blood lactate.CONCLUSIONS: CAF and CHO improve TT performance when taken together but not independently. Our findings do not implicate any obvious physiological mechanisms. However, it is worth noting that despite higher workloads and faster TT performance, CHO-CAF elicited RPE levels similar to PLA. CHO-CAF was also the only condition in which blood glucose was elevated over PLA. Although speculative, superior performance with CHO-CAF may have been mediated through both central and metabolic actions. Regardless, these data suggest that cyclists in the fed state should ingest CHO and CAF together to improve highintensity TT performance.In pursuit of success in sports, physical educators, nutritionists, and trainers employ 'energy drinks'. Several effects of such stimulants depend on the presence of caffeine in the composition. PURPOSE:To compare the effect of caffeine on exercise to the effect of drinks adding other compounds to caffeine. METHODS:The present study compared the effect of pure caffeine (PC), cola (CC) drinks, and caffeine + taurine + glucuronolactone (CTG) drinks on the performance of mice in a running wheel. Two groups of six two-month-old male C57/bl mice were housed in cages fitted with running wheels and a monitoring system. Animals were introduced to the wheel individually until all six mice were fa...