Niosomes based formulation containing tenoxicam: A newer solution for the rheumatic diseases.

OBJECTIVE: This investigation aimed to explore the potential of non-ionic surfactant based niosomal vesicles encapsulating tenoxicam (TN; anti-rheumatic drug) for the treatment of rheumatic diseases. MATERIAL AND METHODS: Mechanical dispersion technique with controlled pressure was employed to prepare different niosomal formulations. The effects of different ratios of surfactant (span-60), lipid, and sodium deoxycholate on noisome's physicochemical properties have been examined. Moreover, inhibition of TNF-α in lipopolysaccharide-activated cultured Human leukemia monocytic (THP-1) cells were demonstrated to assess the in vitro inflammation profile. Finally, the optimized niosomal formulation (TN3) was prepared in gel matrix consist of carbopol 934 (termed as TN34) and stability was also tested at 4±2 ÌŠC, 25±2 ÌŠC, 37±2 ÌŠC and 45±2 ÌŠC for 6 months. RESULTS: The optimized niosomal formulation exhibited a small vesicle size (165±14nm) and high drug encapsulation (79.64±1.5%). Niosomal gel formulation TN34 showed pH (6.7), viscosity (6810±3.34 cps), spreadability (19.11±1.87gm.cm/sec) and also displayed sustained release pattern of drug release (98.16±0.07% TN released from gel matrix in 24h) in vitro release study. TN34 exhibited substantial anti-inflammatory response, with ∼75% inhibition of TNF-α in 48h. Stability investigation revealed that refrigerator temperature is most suitable for the storage of niosomal gel. CONCLUSION: Transdermal niosomal formulation displayed promising potential in the treatment of rheumatic diseases.

D-optimal mixture design inspired modified release tablet formulation of lamotrigine for the treatment of seizures: An in-depth characterization.

OBJECTIVE: Lamotrigine (LTG) an anticonvulsant drug with a dissociation constant (pKa: 5.7), suffers from enhanced blood plasma spike after each dose, when administered as fast release tablet. Being BCS class-II candidate and pH dependent solubility, development of release-controlled tablets of LTG is a major challenge. This investigation aims at designing the release-controlled tablet (RCT) formulation of LTG using a solid dispersion (SD) technique via addressing its solubility and release problems. MATERIAL AND METHODS: RCT of LTG was fabricated using SD blend of Eudragit RL and Eudragit RS and PVP K-30 with different polymer blend ratio (1:5 and 1:7). The optimization of RCT of LTG was performed using D-optimal mixture design with three independent variables, three response variables, and one constraint. The dissolution rate was determined and data were then fitted to different mathematical models. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) studies and tableting parameters were analyzed. RESULT: In vitro studies of predicted optimized batches (POBs) have shown that drug release over a period of 12hours was 88.05±3.4% in media I, 86.10±3.7% in media II and 85.84±4.2% in media III. An in vitro kinetic model equating R2-value for all the tested models indicated that the first order and Higuchi release kinetics model were the most appropriate. CONCLUSION: Based on the optimized formulation consisting of SD of LTG with Eudragit RL, Eudragit RS and PVP K-30, the release rate was consistently similar throughout the GI tract, regardless of the pH of the environment.

Development of engineered transferosomal gel containing meloxicam for the treatment of osteoarthritis.

OBJECTIVE: .In this study, we investigated the potential of meloxicam (MLX) developed as transferosomal gel as a novel lipidic drug delivery system to address osteoarthritis (OTA), a degenerative joint disease that causes pain and stiffness. By incorporating meloxicam into a transferosomal gel, our aim was to provide a targeted and efficient delivery system capable of alleviating symptoms and slowing down the progression of OTA. MATERIAL AND METHODS: Classical lipid film hydration technique was utilized to formulate different transferosomal formulations. Different transferosomal formulations were prepared by varying the molar ratio of phospholipon-90H (phosphodylcholine) to DSPE (50:50, 60:40, 70:30, 80:20, and 90:10) and per batch, 80mg of total lipid was used. The quality control parameters such as entrapment efficiency, particle size and morphology, polydispersity and surface electric charge, in vitro drug release, ex vivo permeation and stability were measured. RESULTS: The optimized transferosomal formulations revealed a small vesicle size (121±12nm) and greater MLX entrapment (68.98±2.3%). Transferosomes mediated gel formulation MLX34 displayed pH (6.3±0.2), viscosity (6236±12.3 cps), spreadability (13.77±1.77 gm.cm/sec) and also displayed sustained release pattern of drug release (81.76±7.87% MLX released from Carbopol-934 gel matrix in 24h). MLX34 revealed close to substantial anti-inflammatory response, with ∼81% inhibition of TNF-α in 48h. Physical stability analysis concluded that refrigerator temperature was the preferred temperature to store transferosomal gel. CONCLUSION: MLX loaded transferosomes containing gel improved the skin penetration and therefore resulted into increased inhibition of TNF-α level.

Cardiovascular regulation: associations between exercise and head-up tilt.

It was hypothesized that faster cardiorespiratory kinetics during exercise are associated with higher orthostatic tolerance. Cardiorespiratory kinetics of 14 healthy male subjects (30 ± 4 years, 179 ± 8 cm, 79 ± 8 kg) were tested on a cycle ergometer during exercise with changing work rates of 30 and 80 W. Pulmonary oxygen uptake ( ) was measured breath-by-breath and heart rate (HR), mean arterial blood pressure (MAP), and total peripheral resistance (TPR) were measured beat-to-beat. Muscular oxygen uptake ( ) was estimated from HR and . Kinetic parameters were determined by time-series analysis, using cross-correlation functions (CCFmax(x)) between the parameter and the work rate. Cardiovascular regulations of MAP, HR, and TPR during orthostatic stress were measured beat-to-beat on a tilt seat. Changes between the minima and maxima during the 6° head-down tilt and the 90° head-up tilt positions were calculated for each parameter (Δtilt-up). correlated significantly with ΔTPRtilt-up (r = 0.790, p ≤ 0.001). CCFmax(HR) was significantly correlated with ΔHRtilt-up (r = -0.705, p = 0.002) and the amplitude in HR from 30 to 80 W (rSP = -0.574, p = 0.016). The observed correlations between cardiorespiratory regulation in response to exercise and orthostatic stress during rest might allow for a more differential analysis of the underlying mechanisms of orthostatic intolerance in, for example, patient groups.

Selective and validated kinetic spectrophotometric method for the determination of irbesartan in pure and pharmaceutical formulations.

A novel-coupling reagent is used for the simple and sensitive kinetic spectrophotometric determination of irbesartan (IRB) in pure or pharmaceutical formulations. The method utilizes an oxidative coupling reaction based on oxidation of 3-methyl-2-benzothiazolinone hydrazone hydrochloride monohydrate (MBTH) with Ce(IV) in 2% sulfuric acid medium, followed by coupling the produced electrophilic intermediate (diazonium salt of the reagent) with IRB to give greenish-blue colored product (1:1, stoichiometry) having maximum absorption at 629nm and the colored species is stable for more than 1h. The initial rate and fixed time (at 35min) methods are adopted for determination of IRB concentration. The linearity is in the ranges of 5.0-40.0µg/mL and 2.0-45.0µg/mL and the limit of detection is 0.46 and 0.40µg/mL for initial rate and fixed time methods, respectively. Molar absorptivity for the method was found to be 1.50×104L/molcm. The validated kinetic methods can be successfully applied to the analysis of IRB in bulk and tablet dosage form and in the routine quality control analysis. The percentage recoveries were above 100% for both methods. The excipients did not interfere in the analysis.

Development and application of degradation kinetics of thin layer chromatographic densitometry and conductometric methods for butoconazole nitrate determination.

Two simple methods were developed for determination of butoconazole nitrate (BN). The first developed method was stability-indicating HPTLC-densitometric method (method A) which is based on the quantitative densitometric separation of butoconazole nitrate (BN) from its degradation products on silica gel 60 F254 and measurement of the bands at 290nm. The developed stability study of BN was performed under different stress conditions including oxidative, hydrolytic, thermal and photolytic. Degradation was observed under acidic hydrolytic and oxidative conditions. Moreover, the HPTLC method was used to study the kinetics of BN acid degradation, determining as first order kinetics. The degradation rate constant of BN was found to be 0.076 hr-1 and t 1/2 value was determined at 9.12 hr in acidic medium. The second method (Method B) was conductometric method which is based on the reaction of BN with phosphotungstic acid (PTA) to form an ion associate in 50% methanol-water system. Validation of the proposed methods was carried out. All proposed methods were successfully applied for the commercial dosage form of BN. Statistical analysis of the results has been carried out revealing high accuracy and good precision.

Kinetics of pyrite, pyrrhotite, and chalcopyrite dissolution by Acidithiobacillus ferrooxidans.

The main objective of this study was to investigate the dissolution kinetics of pyrite, pyrrhotite, and chalcopyrite. Crushed minerals were reacted with Acidithiobacillus ferrooxidans (25 °C). The kinetics of dissolution was investigated by monitoring pH and Fe(2+) and Fe(3+) ion concentrations in the leaching solutions. Pyrite, pyrrhotite, and chalcopyrite dissolution by A. ferrooxidans was found to be a chemically controlled process. With bacteria, the dissolution rates of the minerals increased in the order of pyrrhotite, pyrite, and chalcopyrite. The number of cells attached to mineral surfaces increased in the same order. Acidithiobacillus ferrooxidans was found to enhance the dissolution rates of the minerals. The acid-insoluble trait of pyrite and acid-soluble trait of the other 2 minerals affected the pH changes in the leaching solutions.

Equilibrium and kinetic studies on biosorption of Pb(II) by common edible macrofungi: a comparative study.

In this work, we studied the natural bioaccumulation and biosorption of Pb(II) in several common edible macrofungi. The macrofungi include the following species: Lentinus edodes, Pleurotus eryngii, Flammulina velutipes, Hypsizygus marmoreus, and Agrocybe cylindracea. The present analysis of Pb(II) revealed distinct capabilities of metal accumulation among individual species. Moreover, the natural concentrations of lead did not reach a health risk level when cultivated in uncontaminated soil. In the biosorption experiment by edible macrofungi, we found that the equilibrium data of living sporocarp (P. eryngii and H. marmoreus) and the homogenate of L. edodes and F. velutipes fit the Freundlich model well. Other data samples exhibited a better fit to the Langmuir model. The edible macrofungi showed a higher lead removal capacity than did other biosorbents. Furthermore, the pseudo-second-order kinetics model exhibited the best fit to the biosorption processes. The effectiveness of edible macrofungi as biosorbents for Pb(II) was confirmed.

Long-term sequelae treatment of peripheral facial paralysis with botulinum toxin type A: Repartition and kinetics of doses used.

STUDY OBJECTIVES: Botulinum toxin is a key therapeutic tool in the comprehensive treatment of peripheral facial paralysis. It fights spasms, synkinesis and overactivity of the different skin muscles responsible of facial expressions. Even though injection techniques as well as target muscles have been well identified, doses used remain quite imprecise and often not detailed muscle by muscle, further more dosage progression has not been monitored over time. Our retrospective study is the first one to refine the repartition of botulinum toxin doses on each of the relevant skin muscles and assess dosage kinetics. PATIENTS AND METHODS: Thirty patients were included since 2008 with a mean follow-up of 2.3years. Each patient had at least 3 injections, with a delay of 4 to 6months between each injection. RESULTS: Mean doses are indicated for each muscle injected on the paralyzed and healthy sides. Dose kinetics suggests an initial dosage increase after the first injection followed by a decrease over time. No treatment resistance was observed. CONCLUSION: Our study represents a didactic help in using botulinum toxin for sequelae of peripheral facial paralysis by providing more details on the effective mean doses for each muscle and their progression over time.

Comparison of the growth kinetics and proteolytic activities of Chryseobacterium species and Pseudomonas fluorescens.

The effect of temperature on the growth kinetics and proteolytic activity of Chryseobacterium joostei and Chryseobacterium bovis was determined during this study. The results were compared with the activities of Pseudomonas fluorescens, which is regarded to be a major food spoilage psychrotolerant microorganism. For the growth studies, cultures were incubated in nutrient broth in a temperature gradient incubator (from 9 to 50 °C) and separately at 4 °C, and the optical density was measured at different time intervals. Growth temperature profiles for each organism were constructed. For determination of proteolytic activity, the cultures were incubated in fat-free ultra-high temperature processed milk in the temperature gradient incubator for 72 h (temperature range as above). Cell-free extracts were used to determine the proteolytic activity using the azocasein method. Results of the growth studies showed that C. joostei had the ability to grow over a wider temperature range than C. bovis and P. fluorescens without being affected by changes in the temperature. For the proteolytic activity, C. joostei had significantly (p < 0.001) higher activity per milligram of protein at 15.5 °C, followed by C. bovis and P. fluorescens. The results showed that C. joostei potentially has an even greater spoilage capacity in milk on the basis of growth rate and proteolytic activity than did P. fluorescens.

Genetic characterization, nickel tolerance, biosorption, kinetics, and uptake mechanism of a bacterium isolated from electroplating industrial effluent.

Electroplating industries in Madurai city produce approximately 49,000 L of wastewater and 1200 L of sludge every day revealing 687-5569 ppm of nickel (Ni) with other contaminants. Seventeen Ni-tolerant bacterial strains were isolated from nutrient-enriched effluents. Among them one hyper Ni accumulating strain was scored and identified as Bacillus cereus VP17 on the basis of morphology, biochemical tests, 16S rDNA gene sequencing, and phylogenetic analysis. Equilibrium data of Ni(II) ions using the bacterium as sorbent at isothermal conditions (37 °C) and pH 6 were best adjusted by Langmuir (R(2) = 0.6268) and Freundlich models (R(2) = 0.9505). Experimental validation reveals Ni sorption takes place on a heterogeneous surface of the biosorbent, and predicted metal sorption capacity is 434 ppm. The pseudo-second-order kinetic model fitted the biosorption kinetic data better than the pseudo-first-order kinetic model (R(2) = 0.9963 and 0.3625). Scanning electron microscopy, energy dispersive X-ray, and Fourier transform infrared spectroscopy studies of the bacterial strain with and without Ni(II) ion reveals the biosorption mechanism. The results conclude possibilities of using B. cereus VP17 for Ni bioremediation.

Acute hyperaminoacidemia does not suppress insulin-mediated glucose turnover in healthy young men.

Elevated circulating amino acids (AA) concentrations are purported to cause insulin resistance (IR) in humans. To quantify hyperaminoacidemia effects on insulin-mediated glucose turnover in healthy men, we performed 2-stage pancreatic clamps using octreotide with glucagon and growth hormone replacement. In the basal stage, insulin was infused to maintain euglycemia at postabsorptive levels. During the clamp stage, insulin was raised to postprandial levels, glycemia clamped at 5.5 mmol/L by glucose infusion, and branched-chain AA (BCAA) maintained at either postabsorptive (Hyper1; n = 8) or postprandial (Hyper2; n = 7) by AA infusion. Glucose turnover was measured by d-3-[3H]glucose dilution. Octreotide suppressed C-peptide; glucagon, growth hormone, and glycemia were maintained at postabsorptive levels throughout. Insulin did not differ at postabsorptive (72 ± 5 vs. 60 ± 5 pmol/L; Hyper1 vs. Hyper2) and increased to similar concentrations at basal (108 ± 11 vs. 106 ± 14) and clamp stages (551 ± 23 vs. 540 ± 25). Postabsorptive BCAA were maintained during Hyper1 and increased >2-fold (830 ± 26 µmol/L) during Hyper2. Endogenous glucose production was similarly suppressed (0.95 ± 0.16 vs. 1.37 ± 0.23 mg/kg lean body mass/min; Hyper1 vs. Hyper2) and basal glucose disposal (3.44 ± 0.12 vs. 3.67 ± 0.14) increased to similar levels (10.89 ± 0.56 vs. 11.11 ± 1.00) during the clamp. Thus, acute physiological elevation of AA for 3 h did not cause IR in healthy men. Novelty: A 2-step pancreatic clamp was used to quantify the effect of AA on insulin sensitivity in humans. Acute physiological elevation of circulating AA to postprandial levels does not cause IR in healthy men.

Similar maximal oxygen uptake assessment from a step cycling incremental test and verification tests on the same or different day.

The present study aimed to compare maximal oxygen uptake of a step incremental test with time to exhaustion verification tests (TLIM) performed on the same or different day. Nineteen recreationally trained cyclists (age: 23 ± 2.7 years; maximal oxygen uptake: 48.0 ± 5.8 mL·kg-1·min-1) performed 3 maximal tests as follows: (i) same day: an incremental test with 3-min stages followed by a TLIM at 100% of peak power output of the incremental test (TLIM-SAME) interspaced by 15 min; and (ii) different day: a TLIM at 100% of peak power output of the incremental test (TLIM-DIFF). The maximal oxygen uptake was determined for the 3 tests. The maximal oxygen uptake was not different among the tests (incremental: 3.83 ± 0.41; TLIM-SAME: 3.72 ± 0.42; TLIM-DIFF: 3.75 ± 0.41 L·min-1; P = 0.951). Seven subjects presented a variability greater than ±3% in both verification tests compared with the incremental test. The same-day verification test decreased the exercise tolerance (240 ± 38 vs. 310 ± 36 s) compared with TLIM-DIFF (P < 0.05). In conclusion, the incremental protocol is capable of measuring maximal oxygen uptake because similar values were observed in comparison with verification tests. Although the need for the verification phase is questionable, the additional tests are useful to evaluate individual variability. Novelty Step incremental test is capable of measuring maximal oxygen uptake with similar values during TLIM on the same or different day. Although the necessity of the verification phase is questionable, it can allow the determination of variability in maximal oxygen uptake.

Wavelet and principal component analysis of electromyographic activity and slow component of oxygen uptake during heavy and severe cycling exercise.

The aim of the study was to investigate whether the slow component of oxygen uptake was concurrent with the recruitment of large α-motoneuron muscle fibres by using wavelet and principal component analysis (PCA) of electromyography (EMG) during heavy and severe cycling exercise. Eleven male subjects participated in the study. After establishing each subject's maximum value of oxygen uptake through an incremental test on the cycle ergometer, the subjects performed 6-min cycling tests at heavy and severe intensity. EMG signals were collected from rectus femoris, biceps femoris long head, tibialis anterior, and medial gastrocnemius and processed by combined use of wavelet and PCA analysis. The time delays to the onset of slow component occurred significantly earlier during severe (105.22 ± 5.45 s) compared with during heavy (138.78 ± 15.09 s) exercise. ANOVA with repeated measures showed that for all muscles tested, the angle θ formed by the first and second principal components decreased significantly between time windows during heavy and severe exercise. However, significant increases of EMG mean power frequency (MPF) were found only during heavy exercise. Our results show the concurrence of the oxygen uptake slow component with the additional recruitment of muscle fibres, presumably less efficient large α-motoneuron fibres. Novelty The expected rise in MPF may be offset by muscle fatigue occurring in the later time windows of the slow component during severe exercise. The gradual shift to higher EMG frequencies throughout the slow-component phase was reflected in the progressive and significant decrease of angle θ.

Prolonged static stretching causes acute, nonmetabolic fatigue and impairs exercise tolerance during severe-intensity cycling.

We tested the hypothesis that static stretching, an acute, nonmetabolic fatiguing intervention, reduces exercise tolerance by increasing muscle activation and affecting muscle bioenergetics during cycling in the "severe" intensity domain. Ten active men (age, 24 ± 2 years; body mass, 74 ± 11 kg; height, 176 ± 8 cm) participated in identical constant-load cycling tests of equal intensity, of which 2 tests were carried out under control conditions and 2 were done after stretching. This resulted in a 5% reduction of maximal isokinetic sprinting power output. We measured (i) oxygen consumption, (ii) electromyography, (iii) deoxyhemoglobin, (iv) blood lactate concentration; (v) time to exhaustion, and (vi) perception of effort. Finally, oxygen consumption and deoxyhemoglobin kinetics were determined. Force reduction following stretching was accompanied by augmented muscle excitation at a given workload (p = 0.025) and a significant reduction in time to exhaustion (p = 0.002). The time to peak oxygen consumption was reduced by stretching (p = 0.034), suggesting an influence of the increased muscle excitation on the oxygen consumption kinetics. Moreover, stretching was associated with a mismatch between O2 delivery and utilization during the isokinetic exercise, increased perception of effort, and blood lactate concentration; these observations are all consistent with an increased contribution of the glycolytic energy system to sustain the same absolute intensity. These results suggest a link between exercise intolerance and the decreased ability to produce force. Novelty We provided the first characterization of the effects of prolonged stretching on the metabolic response during severe cycling. Stretching reduced maximal force and augmented muscle activation, which in turn increased the metabolic response to sustain exercise.

Faster oxygen uptake, heart rate, and ventilatory kinetics in stepping compared with cycle ergometry in patients with COPD during moderate-intensity exercise.

Step tests are a stressful and feasible cost-effective modality to evaluate aerobic performance. However, the eccentric in addition to concentric muscle contractions of the legs on stepping emerge as a potential speeding factor for cardioventilatory and metabolic adjustments towards a steady-state, since eccentric contractions would prompt an earlier and stronger mechanoreceptor activation, as well as higher heart rate/cardiac output adjustments to the same metabolic demand. Moreover, shorter tests are ideal for exercise-limited subjects. Nine subjects with chronic obstructive pulmonary disease were invited to participate in comprehensive lung function tests and constant work tests performed on different days at a 90% gas exchange threshold for 6 min, in single-step tests or cycle ergometry. After careful monoexponential regression modelling, statistically relevant faster phase II time constants for oxygen uptake (45 ± 18 s vs 53 ± 17 s, p = 0.017) and minute ventilation (61 ± 13 s vs 74 ± 17 s, p = 0.027) were observed in the 6-min step tests compared with cycle ergometry, respectively. Despite an absence of heart rate time constant difference (43 ± 20 s vs 69 ± 46 s, p = 0.167), there was a significantly faster rate constant toward a steady state for heart rate (p = 0.02). In addition, 4-min compared with 6-min analysis presented similar results (p > 0.05), providing an appropriate steady-state. We conclude that step tests might elicit faster time constants compared with cycle ergometry, at the same average metabolic level, and 4-min analysis has similar mean errors compared with 6-min analysis within an acceptable range. New studies, comprising mechanisms and detailed physiological backgrounds, are necessary.

Muscular contraction frequency does not affect plasma homocysteine concentration in response to energy expenditure- and intensity-matched acute exercise in sedentary males.

Acute exercise seems to increase total plasma homocysteine (tHcy); since this variable associated with cardiovascular risk, it is important to understand the determinants of its response to all types of exercise. The aim of this study was to examine the impact of cycling at 2 different rates of muscle contraction on the complete tHcy kinetics. Eight young sedentary males were required to complete 2 isocaloric (400 kcal) acute exercise trials at 50% peak oxygen uptake on separate occasions at 50 or 80 rpm. Blood samples were drawn at different points before (4 h before exercise and immediately before exercise), during (10, 20, 30, 45, and 60 min during exercise), and after exercise (immediately and 19 h after exercise). Dietary and lifestyle factors were controlled during the research. Maximum tHcy occurred during exercise for both conditions (50 rpm: 11.4 ± 2.7 µmol·L-1; 80 rpm: 10.8 ± 3.2 µmol·L-1). From this point onwards tHcy declined until the cessation of exercise and continued descending below pre-exercise values at 19 h postexercise (p < 0.05). No hyperhomocysteinemia were observed at any sampling point in both trials. In conclusion, the different muscular contraction frequency during exercise has no impact on tHcy during an acute bout of exercise in sedentary individuals, when at least 400 kcal are spent during exercise and the nutritional status for folate, B12, and B6 is adequate. This information is relevant to further inform healthy exercise prescription, not only in terms of duration and intensity of exercise, but also taking into account frequency of contraction.

Impact of l-citrulline supplementation on oxygen uptake kinetics during walking.

Supplementation with l-citrulline (Cit) has been shown to improve muscle oxygenation and oxygen uptake kinetics during moderate- to high-intensity cycling in young men. The aim of this study was to test the hypothesis that Cit would improve oxygen uptake kinetics during walking in older and young adults. In a randomized, double-blind study, 26 (15 women, 11 men) adults between the ages of 20-35 years (n = 15) and 64-86 years (n = 11) completed 7-day periods of taking placebo and Cit (6 g/day) in a crossover manner. Participants walked on a treadmill at 40% heart rate reserve while pulmonary oxygen uptake was measured using indirect calorimetry. Net oxygen cost, mean response time (MRT), and the oxygen deficit were calculated before and after each supplement period. There was no significant change (P > 0.05) in net oxygen cost, MRT, or the oxygen deficit after Cit in older adults, while young adults showed a decrease (P = 0.05) in the oxygen deficit after Cit that tended (P = 0.053) to be different than the change after placebo. Sex-stratified analysis revealed that Cit decreased MRT (P = 0.04, Cohen's d = 0.41) and the oxygen deficit (P < 0.01, Cohen's d = 0.56) in men with the change after Cit being greater than the change after placebo (MRT: -4.5 ± 2.1 vs. 3.4 ± 2.1 s, P = 0.01; deficit: -0.15 ± 0.05 vs. 0.01 ± 0.05 L, P = 0.02). All oxygen uptake parameters were unchanged (P > 0.05) following Cit and placebo in women. Cit does not alter the oxygen cost of moderate-intensity walking in young or older adults, but Cit improved the rate of rise in oxygen uptake at exercise onset in men.

Evaluation of a graded exercise test to determine peak fat oxidation in individuals with low cardiorespiratory fitness.

The maximal capacity to utilise fat (peak fat oxidation, PFO) may have implications for health and ultra-endurance performance and is commonly determined by incremental exercise tests employing 3-min stages. However, 3-min stages may be insufficient to attain steady-state gas kinetics, compromising test validity. We assessed whether 4-min stages produce steady-state gas exchange and reliable PFO estimates in adults with peak oxygen consumption < 40 mL·kg-1·min-1. Fifteen participants (9 females) completed a graded test to determine PFO and the intensity at which this occurred (FATMAX). Three short continuous exercise sessions (SCE) were then completed in a randomised order, involving completion of the graded test to the stage (i) preceding, (ii) equal to (SCEequal), or (iii) after the stage at which PFO was previously attained, whereupon participants then continued to cycle for 10 min at that respective intensity. Expired gases were sampled at minutes 3-4, 5-6, 7-8, and 9-10. Individual data showed steady-state gas exchange was achieved within 4 min during SCEequal. Mean fat oxidation rates were not different across time within SCEequal nor compared with the graded test at FATMAX (both p > 0.05). However, the graded test displayed poor surrogate validity (SCEequal, minutes 3-4 vs. 5-6, 7-8, and 9-10) and day-to-day reliability (minutes 3-4, SCEequal vs. graded test) to determine PFO, as evident by correlations (range: 0.47-0.83) and typical errors and 95% limits of agreement (ranges: 0.03-0.05 and ±0.09-0.15 g·min-1, respectively). In conclusion, intraindividual variation in PFO is substantial despite 4-min stages establishing steady-state gas exchange in individuals with low fitness. Individual assessment of PFO may require multiple assessments.

Using ramp-incremental V̇O2 responses for constant-intensity exercise selection.

Despite compelling evidence to the contrary, the view that oxygen uptake (V̇O2) increases linearly with exercise intensity (e.g., power output, speed) until reaching its maximum persists within the exercise physiology literature. This viewpoint implies that the V̇O2 response at any constant intensity is predictable from a ramp-incremental exercise test. However, the V̇O2 versus task-specific exercise intensity relationship constructed from ramp-incremental versus constant-intensity exercise are not equivalent preventing the use of V̇O2 responses from 1 domain to predict those of the other. Still, this "linear" translational framework continues to be adopted as the guiding principle for aerobic exercise prescription and there remains in the sport science literature a lack of understanding of how to interpret V̇O2 responses to ramp-incremental exercise and how to use those data to assign task-specific constant-intensity exercise. The objectives of this paper are to (i) review the factors that disassociate the V̇O2 versus exercise intensity relationship between ramp-incremental and constant-intensity exercise paradigms; (ii) identify when it is appropriate (or not) to use ramp V̇O2 responses to accurately assign constant-intensity exercise; and (iii) illustrate the technical and theoretical challenges with prescribing constant-intensity exercise solely on information acquired from ramp-incremental tests. Actual V̇O2 data collected during cycling exercise and V̇O2 kinetics modelling are presented to exemplify these concepts. Possible solutions to overcome these challenges are also presented to inform on appropriate intensity selection for individual-specific aerobic exercise prescription in both research and practical settings.