Insulin analog preparations and their use in children and adolescents with type 1 diabetes mellitus.

Standard or 'traditional' human insulin preparations such as regular soluble insulin and neutral protamine Hagedorn (NPH) insulin have shortcomings in terms of their pharmacokinetic and pharmacodynamic properties that limit their clinical efficacy. Structurally modified insulin molecules or insulin 'analogs' have been developed with the aim of delivering insulin replacement therapy in a more physiological manner. In the last 10 years, five insulin analog preparations have become commercially available for clinical use in patients with type 1 diabetes mellitus: three 'rapid' or fast-acting analogs (insulin lispro, aspart, and glulisine) and two long-acting analogs (insulin glargine and detemir). This review highlights the specific pharmacokinetic properties of these new insulin analog preparations and focuses on their potential clinical advantages and disadvantages when used in children and adolescents with type 1 diabetes mellitus. The fast-acting analogs specifically facilitate more flexible insulin injection timing with regard to meals and activities, whereas the long-acting analogs have a more predictable profile of action and lack a peak effect. To date, clinical trials in children and adolescents have been few in number, but the evidence available from these and from other studies carried out in adults with type 1 diabetes suggest that they offer significant benefits in terms of reduced frequency of nocturnal hypoglycemia, better postprandial blood glucose control, and improved quality of life when compared with traditional insulins. In addition, insulin detemir therapy is unique in that patients may benefit from reduced risk of excessive weight, particularly during adolescence. Evidence for sustained long-term improvements in glycosylated hemoglobin, on the other hand, is modest. Furthermore, alterations to insulin/insulin-like growth factor I receptor binding characteristics have also raised theoretical concerns that insulin analogs may have an increased mitogenic potential and risk of tumor development, although evidence from both in vitro and in vivo animal studies do not support this assertion. Long-term surveillance has been recommended and further carefully designed prospective studies are needed to evaluate the overall benefits and clinical efficacy of insulin analog therapy in children and adolescents with type 1 diabetes.

Physical parameters affecting sonoluminescence: A self-consistent hydrodynamic study

We studied the dependence of thermodynamic variables in a sonoluminescing ~SL! bubble on various physical factors, which include viscosity, thermal conductivity, surface tension, the equation of state of the gas inside the bubble, as well as the compressibility of the surrounding liquid. The numerical solutions show that the existence of shock waves in the SL parameter regime is very sensitive to these factors. Furthermore, we show that even without shock waves, the reflection of continuous compressional waves at the bubble center can produce the high temperature and picosecond time scale light pulse of the SL bubble, which implies that SL may not necessarily be due to shock waves.

Quantifying Cell Binding Kinetics Mediated By Surface-Bound Blood Type B Antigen To Immobilized Antibodies

Cell adhesion is crucial to many biological processes, such as inflammatory responses, tumor metastasis and thrombosis formation. Recently a commercial surface plasmon resonance (SPR)-based BIAcore biosensor has been extended to determine cell binding mediated by surface-bound biomolecular interactions. How such cell binding is quantitatively governed by kinetic rates and regulating factors, however, has been poorly understood. Here we developed a novel assay to determine the binding kinetics of surface-bound biomolecular interactions using a commercial BIAcore 3000 biosensor. Human red blood cells (RBCs) presenting blood group B antigen and CM5 chip bearing immobilized anti-B monoclonal antibody (mAb) were used to obtain the time courses of response unit, or sensorgrams, when flowing RBCs over the chip surface. A cellular kinetic model was proposed to correlate the sensorgrams with kinetic rates. Impacts of regulating factors, such as cell concentration, flow duration and rate, antibody-presenting level, as well as pH value and osmotic pressure of suspending medium were tested systematically, which imparted the confidence that the approach can be applied to kinetic measurements of cell adhesion mediated by surface-bound biomolecular interactions. These results provided a new insight into quantifying cell binding using a commercial SPR-based BIAcore biosensor.

Impact of carrier stiffness and microtopology on two-dimensional kinetics of P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) interactions

Mechanics and surface microtopology of the molecular carrier influence cell adhesion, but the mechanisms underlying these effects are not well understood. We used a micropipette adhesion frequency assay to quantify how the carrier stiffness and microtopology affected two-dimensional kinetics of interacting adhesion molecules on two apposing surfaces. Interactions of P-selectin with P-selectin glycoprotein ligand-1 (PSGL-1) were used to demonstrate such effects by presenting the molecules on three carrier systems: human red blood cells (RBCs), human promyelocytic leukemia HL-60 cells, and polystyrene beads. Stiffening the carrier alone or in cooperation with roughing the surface lowered the two-dimensional affinity of interacting molecules by reducing the forward rate but not the reverse rate, whereas softening the carrier and roughing the surface had opposing effects in affecting two-dimensional kinetics. In contrast, the soluble antibody bound with similar three-dimensional affinity to surface-anchored P-selectin or PSGL-1 constructs regardless of carrier stiffness and microtopology. These results demonstrate that the carrier stiffness and microtopology of a receptor influences its rate of encountering and binding a surface ligand but does not subsequently affect the stability of binding. This provides new insights into understanding the rolling and tethering mechanism of leukocytes onto endothelium in both physiological and pathological processes.

Determination of drugs used in combined cardiovascular therapy

Cardiovascular diseases are nowadays the first cause of mortality worldwide, causing around the 30% of global deaths each year. The risk of suffering from cardiovascular illnesses is strongly related to some factors such as hypertension, high cholesterol levels, diabetes, obesity The combination of these different risk factors is known as metabolic syndrome and it is considered a pandemic due to the high prevalence worldwide. The pathology of the disorders implies a combined cardiovascular therapy with drugs which have different targets and mechanisms of action, to regulate each factor separately. The simultaneous analysis of these drugs turns interesting but it is a complex task since the determination of multiple substances with different physicochemical properties and physiological behavior is always a challenge for the analytical chemist. The complexity of the biological matrices and the difference in the expected concentrations of some analytes require the development of extremely sensitive and selective determination methods. The aim of this work is to fill the gap existing in this field of the drug analysis, developing analytical methods capable of quantifying the different drugs prescribed in combined cardiovascular therapy simultaneously. Liquid chromatography andem mass spectrometry (LCMS/MS) has been the technique of choice throughout the main part of this work, due to the high sensitivity and selectivity requirements.

Influence of nutrient intake on antioxidant capacity, muscle damage and white blood cell count in female soccer players

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High-Throughput Sequencing of microRNAs in Peripheral Blood Mononuclear Cells: Identification of Potential Weight Loss Biomarkers

INTRODUCTION: MicroRNAs (miRNAs) are being increasingly studied in relation to energy metabolism and body composition homeostasis. Indeed, the quantitative analysis of miRNAs expression in different adiposity conditions may contribute to understand the intimate mechanisms participating in body weight control and to find new biomarkers with diagnostic or prognostic value in obesity management. OBJECTIVE: The aim of this study was the search for miRNAs in blood cells whose expression could be used as prognostic biomarkers of weight loss. METHODS: Ten Caucasian obese women were selected among the participants in a weight-loss trial that consisted in following an energy-restricted treatment. Weight loss was considered unsuccessful when <5% of initial body weight (non-responders) and successful when >5% (responders). At baseline, total miRNA isolated from peripheral blood mononuclear cells (PBMC) was sequenced with SOLiD v4. The miRNA sequencing data were validated by RT-PCR. RESULTS: Differential baseline expression of several miRNAs was found between responders and non-responders. Two miRNAs were up-regulated in the non-responder group (mir-935 and mir-4772) and three others were down-regulated (mir-223, mir-224 and mir-376b). Both mir-935 and mir-4772 showed relevant associations with the magnitude of weight loss, although the expression of other transcripts (mir-874, mir-199b, mir-766, mir-589 and mir-148b) also correlated with weight loss. CONCLUSIONS: This research addresses the use of high-throughput sequencing technologies in the search for miRNA expression biomarkers in obesity, by determining the miRNA transcriptome of PBMC. Basal expression of different miRNAs, particularly mir-935 and mir-4772, could be prognostic biomarkers and may forecast the response to a hypocaloric diet.

Running Pace Decrease during a Marathon Is Positively Related to Blood Markers of Muscle Damage

Background: Completing a marathon is one of the most challenging sports activities, yet the source of running fatigue during this event is not completely understood. The aim of this investigation was to determine the cause(s) of running fatigue during a marathon in warm weather. Methodology/Principal Findings: We recruited 40 amateur runners (34 men and 6 women) for the study. Before the race, body core temperature, body mass, leg muscle power output during a countermovement jump, and blood samples were obtained. During the marathon (27 uC; 27% relative humidity) running fatigue was measured as the pace reduction from the first 5-km to the end of the race. Within 3 min after the marathon, the same pre-exercise variables were obtained. Results: Marathoners reduced their running pace from 3.5 6 0.4 m/s after 5-km to 2.9 6 0.6 m/s at the end of the race (P,0.05), although the running fatigue experienced by the marathoners was uneven. Marathoners with greater running fatigue (. 15% pace reduction) had elevated post-race myoglobin (1318 6 1411 v 623 6 391 mg L21; P,0.05), lactate dehydrogenase (687 6 151 v 583 6 117 U L21; P,0.05), and creatine kinase (564 6 469 v 363 6 158 U L21; P = 0.07) in comparison with marathoners that preserved their running pace reasonably well throughout the race. However, they did not differ in their body mass change (23.1 6 1.0 v 23.0 6 1.0%; P = 0.60) or post-race body temperature (38.7 6 0.7 v 38.9 6 0.9 uC; P = 0.35). Conclusions/Significance: Running pace decline during a marathon was positively related with muscle breakdown blood markers. To elucidate if muscle damage during a marathon is related to mechanistic or metabolic factors requires further investigation.

Blood lactate in yellowfin tuna, Neothunnus macropterus, and skipjack, Katsuwonus pelamis, following capture and tagging

ENGLISH: The staff of the Inter-American Tropical Tuna Commission for several years has been investigating the life history, population structure, behavior and ecology of the yellowfin tuna, Neothunnus macropterus, and the skipjack, Katsuwonus pelamis, in the Eastern Tropical Pacific Ocean. The tagging and subsequent recovery of these tropical tunas, to provide information on population structure, migrations, mortality rates and growth rates, are important aspects of these investigations. Broadhead (1959) and Schaefer, Chatwin and Broadhead (1961) emphasize the many difficulties involved in tagging these extremely active yet delicate fish and give considerable evidence to suggest that tagging mortality is high, perhaps as great as 60 to 80 per cent. The latter authors suggest that the rather high mortality at tagging is related to the effects of hyperactivity brought about by the tagging operation. SPANISH: El personal de la Comisión Interamericana del Atún Tropical ha estado investigando durante varios años la historia natural, la estructura de la población, los hábitos y la ecología del atún aleta amarilla, Neothunnus macropterus, y del barrilete, Katsuwonus pelamis, en el Océano Pacífico Oriental Tropical. La marcación y el subsiguiente recobro de estos atunes tropicales, lo que da información sobre la estructura de la población, los movimientos migratorios y las tasas de crecimiento y de mortalidad, son importantes aspectos de estas investigaciones. Broadhead (1959) y Schaefer, Chatwin y Broadhead (1961) destacan las muchas dificultades que hay para marcar estos peces activos en extremo pero delicados, y proporcionan considerable evidencia que sugiere que la mortalidad por la marcación es bastante alta, siendo quizás de 60 a 80 por ciento. Los autores citados sugieren que esta elevada mortalidad por la marcación está relacionada con los efectos de la hiperactividad producida por la operación de marcación.

Some factors affecting the distribution and apparent abundance of yellowfin and skipjack tuna in the Eastern Pacific Ocean

ENGLISH: Since 1951, the Inter-American Tropical Tuna Commission has been investigating the biology, ecology and population dynamics of the yellowfin tuna, Thunnus albacares, and the skipjack tuna, Katsuwonus pelamis, in the Eastern Pacific Ocean. Of particular importance has been the study of the effects of fishing and of fishery-independent factors on the abundance and distribution of these tunas. For yellowfin tuna there is, on the average, an inverse relationship between total fishing effort and apparent abundance (Schaefer, 1957a). For skipjack there is no evidence to suggest that fishing effort has ever been sufficiently intense to affect measurably the abundance (Schaefer, 1961). Rather, it appears that the year-to-year fluctuations in apparent abundance are independent of the activities of the fishing fleets. SPANISH: Desde 1951 la Comisión Interamericana del Atún Tropical se ha dedicado a la investigación de la biología, ecología y la dinámica de las poblaciones del atún aleta amarilla, Thunnus albacares, y del barrilete, Katsuwonus pelamis, en el Océano Pacífico del Este. De importancia especial ha sido el estudio de los efectos de la pesca y de los factores independientes de las pesquerías sobre la abundancia y la distribución de esos atunes. En cuanto al atún aleta amarilla, existe, en promedio, una relación inversa entre el esfuerzo total de pesca y la abundancia aparente (Schaefer, 1957a) . Con respecto al barrilete, no hay evidencia que haga pensar que el esfuerzo de pesca haya sido nunca lo suficientemente intenso como para afectar sensiblemente la abundancia (Schaefer, 1961). Más bien parece que las fluctuaciones de un año a otro en su abundancia aparente, son independientes de las actividades de las flotas pesqueras.

Muscle glycogen and blood lactate in yellowfin tuna, Thunnus albacares, and skipjack, Katsuwonus pelamis, following capture and tagging

ENGLISH: Tagging and the recovery of tagged yellowfin (Thunnus albacares) and skipjack (Katsuwonus pelamis) tunas are important aspects of the investigations conducted by the Inter-American Tropical Tuna Commission in the Eastern Tropical Pacific Ocean. The results of the tagging program provide information on population structures, migrations, mortality rates and growth rates of these two species. The present experimental program was undertaken to study the relationship between muscular fatigue and high tagging mortalities in yellowfin and skipjack. SPANISH: La marcación del atún aleta amarilla (Thunnus albacares) y del barrilete (Katsuwonus pelamis), y el recobro de estos atunes marcados, son aspectos importantes de la investigación que efectúa la Comisión Interamericana del Atún Tropical en el Océano Pacífico Oriental Tropical. Los resultados del programa de marcación proporcionan información sobre la estructura de las poblaciones, migraciones, tasas de mortalidad y tasas de crecimiento de estas dos especies. El programa experimental presente fue emprendido para estudiar la relación entre la fatiga muscular y la alta mortalidad causada por la marcación en el atún aleta amarilla y el barrilete. (PDF contains 52 pages.)