Statistical optimization of gastric floating system for oral controlled delivery of calcium

The development of an optimized gastric floating drug delivery system is described. Statistical experimental design and data analysis using response surface methodology is also illustrated. A central, composite Box-Wilson design for the controlled release of calcium was used with 3 formulation variables: X₁ (hydroxypropyl methylcellulose [HPMC] loading), X₂ (citric acid loading), and X₃ (magnesium stearate loading). Twenty formulations were prepared, and dissolution studies and floating kinetics were performed on these formulations. The dissolution data obtained were then fitted to the Power Law, and floating profiles were analyzed. Diffusion exponents obtained by Power Law were used as targeted response variables, and the constraints were placed on other response variables. All 3 formulation variables were found to be significant for the release properties (P<,05), while only HPMC loading was found to be significant for floating properties. Optimization of the formulations was achieved by applying the constrained optimization. The optimized formulation delivered calcium at the release rate of 40 mg/hr, with predicted n and T_50% values at 0.93 and 3.29 hours, respectively. Experimentally, calcium was observed to release from the optimized formulation with n and T_50% values of 0.89 (±0.10) and 3.20 (±0.21) hours, which showed an excellent agreement. The quadratic mathematical model developed could be used to further predict formulations with desirable release and floating properties.     

The Influence of Internal Time,Time Awake,and Sleep Duration on Cognitive Performance in Shiftworkers

To date, studies investigating the consequences of shiftwork have predominantly focused on external (local) time. Here, we report the daily variation in cognitive performance in rotating shiftworkers under real-life conditions using the psychomotor vigilance test (PVT) and show that this function depends both on external and internal (biological) time. In addition to this high sensitivity of PVT performance to time-of-day, it has also been extensively applied in sleep deprivation protocols. We, therefore, also investigated the impact of shift-specific sleep duration and time awake on performance. In two separate field studies, 44 young workers (17 females, 27 males; age range 20–36 yrs) performed a PVT test every 2?h during each shift. We assessed chronotype by the MCTQ^Shift (Munich ChronoType Questionnaire for shiftworkers). Daily sleep logs over the 4-wk study period allowed for the extraction of shift-specific sleep duration and time awake in a given shift, as well as average sleep duration (“sleep need”). Median reaction times (RTs) significantly varied across shifts, depending on both Local Time and Internal Time. Variability of reaction times around the 24 h mean (≈ ±5%) was best explained by a regression model comprising both factors, Local Time and Internal Time (p < .001). Short (15th percentile; RT_15%) and long (85th percentile; RT_85%) reaction times were differentially affected by Internal Time and Local Time. During night shifts, only median RT and RT_85% were impaired by the duration of time workers had been awake (p?<?.01, consistent with the highest sleep pressure), but not RT_15%. Proportion of sleep before a test day (relative to sleep need) significantly affected median RT and RT_85% during morning shifts (p?<?.01). RT_15% was worst in the beginning of the morning shift, but improved to levels above average with increasing time awake (p < .05), whereas RT_85% became worse (p < .05). Hierarchical mixed models confirmed the importance of chronotype and sleep duration on cognitive performance in shiftworkers, whereas the effect of time awake requires further research. Our finding that both Local Time and Internal Time, in conjunction with shift-specific sleep behavior, strongly influence performance extends predictions derived from laboratory studies. (Author correspondence: roenneberg@lmu.de)     

DIURNAL VARIATION IN WINGATE TEST PERFORMANCES: INFLUENCE OF ACTIVE WARM-UP

The purpose of the present study was to examine the effects of active warm-up duration on the diurnal fluctuations in anaerobic performances. Twelve physical education students performed a medical stress test (progressive test up to exhaustion) and four Wingate tests (measurement of peak power [P_peak], mean power [P_mean], and fatigue index during an all-out 30 s cycling exercise). The tests were performed in separate sessions (minimum interval?=?36?h) in a balanced and randomized design at 08:00 and 18:00?h, either after a 5?min (5-AWU) or a 15?min active warm-up (15-AWU). AWU consisted of pedaling at 50% of the power output at the last stage of the stress exhausting test. Rectal temperature was collected throughout the sessions. A two-way ANOVA (warm-up?×?time of day) revealed a significant interaction for P_peak (F_(1.11)?=?6.48, p?<?0.05) and P_mean (F_(1.11)?=?5.84, p?<?0.05): the time-of-day effect was significant (p?<?0.001) in contrast with the effect of warm-up duration (p?>?0.05). P_peak and P_mean improved significantly from morning to afternoon after both 5-AWU and 15-AWU, but the effect of warm-up duration was significant in the morning only. Indeed, the values of P_peak or P_mean were the same after both warm-up protocols in the afternoon. For rectal temperature, there was no interaction between time-of-day and warm-up duration. Rectal temperature before and after both the warm-up protocols was higher in the afternoon, and the effect of warm-up duration on temperature was similar at 08:00 and 18:00?h. In conclusion, the interpretation of the results of the anaerobic performance tests should take into account time-of-day and warm-up procedures. Longer warm-up protocols are recommended in the morning to minimize the diurnal fluctuations of anaerobic performances. (Author correspondence: n_souissi@yahoo.fr)     

Effects of vitamin C,vitamin E,zinc gluconate,and selenomethionine supplementation on muscle function and oxidative stress biomarkers in patients with facioscapulohumeral dystrophy: A double-blind randomized controlled clinical trial

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by progressive weakness and atrophy of specific skeletal muscles. As growing evidence suggests that oxidative stress may contribute to FSHD pathology, antioxidants that might modulate or delay oxidative insults could help in maintaining FSHD muscle function. Our primary objective was to test whether oral administration of vitamin C, vitamin E, zinc gluconate, and selenomethionine could improve the physical performance of patients with FSHD. Adult patients with FSHD (n=53) were enrolled at Montpellier University Hospital (France) in a randomized, double-blind, placebo-controlled pilot clinical trial. Patients were randomly assigned to receive 500 mg vitamin C, 400 mg vitamin E, 25 mg zinc gluconate and 200 μg selenomethionine (n=26), or matching placebo (n=27) once a day for 17 weeks. Primary outcomes were changes in the two-minute walking test (2-MWT), maximal voluntary contraction, and endurance limit time of the dominant and nondominant quadriceps (MVC_QD, MVC_QND, T_limQD, and T_limQND, respectively) after 17 weeks of treatment. Secondary outcomes were changes in the antioxidant status and oxidative stress markers. Although 2-MWT, MVC_Q, and T_limQ were all significantly improved in the supplemented group at the end of the treatment compared to baseline, only MVC_Q and T_limQ variations were significantly different between groups (MVC_QD: P=0.011; MVC_QND: P=0.004; T_limQD: P=0.028; T_limQND: P=0.011). Similarly, the vitamin C (P<0.001), vitamin E as α-tocopherol (P<0.001), vitamin C/vitamin E ratio (P=0.017), vitamin E γ/α ratio (P=0.022) and lipid peroxides (P<0.001) variations were significantly different between groups. In conclusion, vitamin E, vitamin C, zinc, and selenium supplementation has no significant effect on the 2-MWT, but improves MVC_Q and T_limQ of both quadriceps by enhancing the antioxidant defenses and reducing oxidative stress. This trial was registered at clinicaltrials.gov (number: NCT01596803).     

Formulation and evaluation of ATP-containing liposomes including lactosylated ASGPr ligand

An original ligand (Lac-10-Chol) designed to interact with asialoglycoprotein receptors to potentially target hepatocyte was synthesised by grafting a lactose head to a cholesteryl structure, which was then included in liposomes. Preliminary formulation tests led to the selection of conventional formulations based on soybean phosphatidylcholine/cholesterol/DOTAP (± DOPE) (± Lac-10-Chol) that present reproducible absolute entrapment value (1.45?±?0.10%), with a size of 109?±?7?nm and a slight positive charge (3.77?±?1.59?mV). Cell viability (via the MTT test), expressed as the percentage of nontreated cells in HepG2 cells, was very close to the control. Internalization tests evidenced an intracellular penetration of fluorescent liposomes, but no specific ligand effect was demonstrated (P?>?0.05). Nevertheless, regarding the adenosine triphosphate (ATP) assay, a slight increase was obtained with liposome loaded with ATP incorporating Lac-10-chol after 24 hours (P?<?0.05).     

Estimation of Photorespiration Rate by Simultaneous Measurements of CO2, Gas Exchange Rate,and Chlorophyll Fluorescence Quenching in the C3 Plant Vigna Radiata (L.) Wilczek and the C4 Plant Amaranthus Mongostanus L.

So far the photorespiration rate (R _P) in a leaf has been determined as the difference between the net photosynthetic rates (P _N) measured in 21 % O₂ air (P _N21%) and 3 % O₂ air (P _N3%). In the C₃ plant Vigna radiata and the C₄ plant Amaranthus mongostanus L., P _N and chlorophyll fluorescence quenching in leaves were monitored simultaneously. R _P of leaves in situ was estimated as termed R _PE from the electron transport rates through photosystem 2 (PS2), and compared with R _PO (P _N3% – P _N21%). In V. radiata R _PO was 11.9 µmol(CO₂) m^–2 s^–1 and the ratio of R _PO to P _N21% was 42.2 %, whereas the ratio of R _PE to P _N21% was 25.7 %. This suggests that R _PO may be over-estimated for the real R _P in normal air. In A. mongostanus, P _N was almost not changed with a decrease in O₂ concentration from 21 to 3 %, whereas the quantum yield of PS2 was evidently affected by the change in O₂ concentration. This fact shows the presence of photorespiration in this C₄ species, where R _PE was equivalent to 3.8 % of P _N21%.     

Physiological effects of variations in spontaneously chosen crank rate during incremental upper-body exercise

The aims of the present study were: first, to assess the interindividual variations of a spontaneously chosen crank rate (SCCR) in relation to the power developed during an incremental upper body exercise on an arm ergometer set at a constant power regime, and second, to compare heart rate (HR) responses, expired minute ventilation (V˙ _E) and oxygen consumption (V˙O₂) when the pedal rates were chosen spontaneously (T_SCCR) or set at ±10% of the freely chosen rates (T_+10% and T_−10%, respectively). The mean pedal rate values were linearly related (P < 0.01) with the power developed during arm cranking (r = 0.96), although large variations of pedalling rate strategies were observed between subjects. Maximal power (MP) and time to exhaustion values were significantly higher (P < 0.05) during T_SCCR than during T_+10% and T_−10%. Peak V˙O₂ values were significantly higher (P < 0.05) in T_+10% than in T_SCCR and T_−10%. The increase in HR, V˙ _E, and V˙O₂ mean values, in relation to the increase in the power developed, was significantly higher (P < 0.05) when the pedal rate was set at plus 10% of the SCCR (T_±10%) than in the two other conditions. The findings of the present study suggest that the use of an electromagnetically braked ergometer, which automatically adjusts the resistance component to maintain a constant work rate, should be used in order to achieve the highest MP values during an incremental upper body exercise. A 10% increase of the SCCR should be used in order to provide the highest peak V˙O₂ value. Accepted: 5 May 1997     

Prostaglandin Endoperoxide H Synthase-2 (PGHS-2) Variants and Risk of Obesity and Microvascular Dysfunction Among Tunisians: Relevance of rs5277 (306G/C) and rs5275 (8473T/C) Genetic Markers

The purpose of this study was to determine the impact of six PGHS-2 genetic variants on obesity development and microvascular dysfunction. The study included 305 Tunisian subjects (186 normal weights, 35 overweights and 84 obeses). PCR analyses were used for allelic discrimination between polymorphisms. Prostaglandin (PGE2, PGI2), leptin, and matrix metalloproteinase (MMP1, 2, 3, 9) levels were evaluated by ELISA. Fatty acid composition was performed by gas chromatography–mass spectrometry. Our results revealed that subjects carrying the PGHS-2 306CC (rs5277) and 8473CC (rs5275) genotypes present higher anthropometric values compared to wild-type genotypes (306GG, BMI (Kg/m²): 27.11?±?0.58; WC (cm): 93.09?±?1.58; 306CC, BMI: 33.83?±?2.46; WC: 109.93?±?5.41; 8473TT, BMI: 27.75?±?0.68; WC: 93.96?±?1.75; 8473CC, BMI: 33.72?±?2.2; WC: 117.89?±?2.94). A reduced microvascular reactivity and a higher PGE2 level were also found in individuals with the 306CC and 8473CC genotypes in comparison to 306GG and 8473TT carriers (306GG, Peak Ach-CVC (PU/mmHg): 0.46?±?0.03; PGE2 (pg/ml): 7933.1?±?702; 306CC, Peak Ach-CVC: 0.24?±?0.01; PGE2: 13,380.3?±?966.2; 8473TT, Peak Ach-CVC: 0.48?±?0.05; PGE2: 7086.41?±?700.31; 8473CC, Peak Ach-CVC: 0.23?±?0.01; PGE2: 13,175.7?±?1165.8). Fatty acid analysis showed a significant increase of palmitic acid (PA) (34.2?±?2.09 vs. 16.82%?±?1.76, P?<?0.001), stearic acid (SA) (25.76?±?3.29 vs. 9.05%?±?2.53, P?<?0.001), and linoleic acid (LA) (5.25?±?1.18 vs. 0.5%?±?0.09, P?<?0.001) levels in individuals carrying the PGHS-2 306CC genotype when compared to GG genotype individuals. Subjects with the 8473CC genotype showed also a significant increase of PA, SA ,and LA levels when compared to TT genotype carriers (PA: 38.02?±?1.51 vs. 12.65%?±?1.54, P?<?0.001; SA: 32.96?±?1.87 vs. 1.38%?±?0.56, P?<?0.001; LA: 26.84?±?2.09 vs. 3.7%?±?1.54, P?<?0.001). Logistic regression analysis revealed that PGHS-2 306CC and 8473CC variants are significantly associated with obesity status (OR 6.25, CI (1.8–21.6), P?=?0.004; OR 3.01, CI (1.13–8.52), P?=?0.03, respectively). Haplotypes containing the C₃₀₆:T₈₄₇₃ (OR 2.91; P?=?0.01) and G_306:C₈₄₇₃ (OR 5.25; P?=?0.002) combinations were associated with an enhanced risk for obesity development in the studied population. In conclusion, our results highlight that PGHS-2 306G/C and 8473T/C variants could be useful indicators of obesity development, inflammation, and microvascular dysfunction among Tunisians.

     

Effects of interval training at the ventilatory threshold on clinical and cardiorespiratory responses in elderly humans

This study assessed clinical and cardiorespiratory responses after an interval training programme in sedentary elderly adults using the ventilatory threshold (V _th) as the index of exercise training intensity. A selection of 22 subjects were randomized into two groups: 11 subjects served as the training group (TG) and the others as controls (CG). Maximal exercise tests were performed on a treadmill before (T₀), each month (T₁, T₂) and after the 3-month interval training programme period (T₃). The TG subjects were individually trained at the heart rate corresponding to V _th measured at T₀, T₁ and T₂ as the breakpoint in the oxygen uptake-carbon dioxide production relationship. Their training programme consisted of walking/jogging sessions on a running track twice a week. The sessions consisted of varying durations of exercise alternating with active recovery in such a way that the subjects slowly increased their total exercise time from an initial duration of 30 min to a final duration of 1 h. During training the heart rate was continuously monitored by a cardiofrequency meter. Compared with the daily activities of the controls, no training programme-related injuries were observed in TG. Moreover, programme adherence (73%) and attendance (97.3%) were high. The maximal oxygen uptake and V _th were increased in TG, by 20% (P<0.05) and 26% (P<0.01), respectively. Interval training at V _th also significantly increased maximal O₂ pulse (P<0.05) and maximal ventilation (P<0.01). A significant decrease in submaximal ventilation (P<0.05) and heart rate (P<0.01) was also noted. These results would suggest that for untrained elderly adults, an interval training programme at the intensity of V _th may be well-tolerated clinically and may significantly improve both maximal aerobic power and submaximal exercise tolerance. Accepted: 6 January 1998     

Sulfosalicylate mediates improved vinorelbine loading into LUVs and antineoplastic effects

Liposomal vinorelbine formulation is desirable, as it might improve the therapeutic activity of vinorelbine. However, because of its lipophilic and membrane-permeable properties, vinorelbine is hard to be formulated into liposomes using conventional drug-loading technologies. To improve vinorelbine retention, ammonium salts of several anionic agents were employed to prepare liposomal vinorelbine formulations. It was found that 5-sulfosalicylate (5ssa) could form stable complexes with vinorelbine and stabilize entrapped vinorelbine. The resultant vesicles had an in vitro release t_1/2 of ~12.49 hours in NH₃-containing media, which is longer than those of sulfate and phytate vesicles (~0.57 hours). The circulation half-life of vinorelbine after the injection of 5ssa vesicles into normal mice was ~13.01 hours, accounting for ~2-fold increase relative to that of sulfate vesicles. Improved drug retention correlated with enhanced antitumor efficacy. In the RM-1/c57 model, 5ssa vesicles were more efficacious than sulfate vesicles (P?<?0.05). In RM-1/BDF1 and Lewis lung cancer/c57 models, antitumor efficacy was also considerably improved after vinorelbine encapsulation into 5ssa vesicles. For instance, in the RM/BDF1 model, liposomal vinorelbine was at least 4-fold more therapeutically active than free vinorelbine. Our results demonstrated that 5ssa could stabilize vinorelbine relative to other anions, resulting in the formulation with improved drug retention and efficacy. Improved vinorelbine retention might be associated with the formation of insoluble precipitate, which could be proved by precipitation study and decreased drug-release rate at a high D/L ratio.     

Interaction Between Central Opioidergic and Glutamatergic Systems on Food Intake in Neonatal Chicks: Role of NMDA,AMPA and mGLU1 Receptors

The present study was designed to examine the role of opioidergic and glutamatergic systems on feeding behavior in neonatal meat-type chicken. In experiment 1, FD₃ neonatal broilers ICV injected with (A) saline, (B) DAMGO (µ-opioid receptor agonist, 125 pmol), (C) MK-801 (NMDA glutamate receptors antagonist, 15 nmol) and (D) combination of DAMGO plus MK-801. Experiments 2–5 were similar to experiment 1, except FD₃ chicks ICV injected with CNQX (AMPA glutamate receptors antagonist, 390 nmol), AIDA (mGLU₁ receptors antagonist, 2 nmol), LY341495 (mGLU₂ receptors antagonist, 150 nmol) and UBP1112 (mGLU₃ receptors antagonist, 2 nmol) instead of MK-801, respectively. In experiments 6–10, FD₃ chicks ICV injected as the same as procedure to the experiments 1–5, except to inject with DPDPE (δ-opioid receptor agonist, 40 nmol) instead of the DAMGO. The experiments 11–15 were similar to the experiments 1–5, except neonatal broilers ICV injected with U-50488H (κ-opioid receptor agonist, 30 nmol) instead of DAMGO. Then the cumulative food intake measured until 120 min post injection. According to the results, ICV injection of DAMGO, significantly decreased food intake (P?<?0.05) while DPDPE and U-50488H increased feeding behavior compared to the control group (P?<?0.05). Co-injection of the DAMGO?+?MK-801 and DAMGO?+?AIDA, significantly decreased DAMGO-induced hypophagia in neonatal chicks (P?<?0.05). Also, co-injection of the DPDPE?+?CNQX significantly amplified DPDPE induced feeding behavior (P?<?0.05). These results suggested interconnection between central opioidergic and glutamatergic systems on feeding behavior mediates via µ- and δ-opioid receptor with NMDA, AMPA and mGLU₁ receptors in FD₃ neonatal broilers. These findings may shed light on the circuitry underlying interconnection between central opioidergic and glutamatergic systems on feeding behavior.     

Liposomal-based lidocaine formulation for the improvement of infiltrative buccal anaesthesia

This study describes the encapsulation of the local anaesthetic lidocaine (LDC) in large unilamellar liposomes (LUV) prepared in a scalable procedure, with hydrogenated soybean phosphatidylcholine, cholesterol and mannitol. Structural properties of the liposomes were assessed by dynamic light scattering, nanoparticle tracking analysis and transmission electron microscopy. A modified, two-compartment Franz-cell system was used to evaluate the release kinetics of LDC from the liposomes. The in vivo anaesthetic effect of liposomal LDC 2% (LUV_LDC) was compared to LDC 2% solution without (LDC_PLAIN) or with the vasoconstrictor epinephrine (1:100 000) (LDC_VASO), in rat infraorbital nerve blockade model. The structural characterization revealed liposomes with spherical shape, average size distribution of 250?nm and low polydispersity even after LDC incorporation. Zeta potential laid around –30?mV and the number of suspended liposomal particles was in the range of 10¹² vesicles/mL. Also the addition of cryoprotectant (mannitol) did not provoke structural changes in liposomes properties. In vitro release profile of LDC from LUV fits well with a biexponential model, in which the LDC encapsulated (EE%?=?24%) was responsible for an increase of 67% in the release time in relation to LDC_PLAIN (p?<?0.05). Also, the liposomal formulation prolonged the sensorial nervous blockade duration (～70?min), in comparison with LDC_PLAIN (45?min), but less than LDC_VASO (130?min). In this context, this study showed that the liposomal formulations prepared by scalable procedure were suitable to promote longer and safer buccal anaesthesia, avoiding side effects of the use of vasoconstrictors.     

Feeding habits of two sympatric loliginid squids,Uroteuthis (Photololigo) chinensis (Gray, 1849) and Uroteuthis (Photololigo) duvaucelii (d’Orbigny, 1835), in the lower part of the South China Sea

The feeding habits of two sympatric squid species, Uroteuthis (Photololigo) chinensis and Uroteuthis (Photololigo) duvaucelii from the southwestern Gulf of Thailand were studied. They fed on low numbers of food types (AF) and had a low diet breadth; 1.18 and 0.01 for U. (P.) chinensis and 1.49 and 0.05 for U. (P.) duvaucelii, respectively. Three major prey types (fishes, crustaceans and molluscs) were always detected and cannibalism was observed. Fish was the greatest contributor to the diet of both species, contributing 89.5% for U. (P.) chinensis and 69.9% for U. (P.) duvaucelii. Fish size significantly affected fullness index (FL) and AF for U. (P.) chinensis (P?<?0.001) and U. (P.) duvaucelii (P?<?0.001). Depth affected the FL of U. (P.) chinensis (P?<?0.001) but not of U. (P.) duvaucelii (P?>?0.05). Maturity stages of both male and female U. (P.) chinensis influenced FL (male: P?<?0.001; female: P?<?0.05) and AF (male: P?<?0.05; female: P?<?0.01). The FL of squid from cast nets was higher than those from trawls. The multivariate results showed dietary grouping between size classes of both species.     

Design of a novel type IV lipid-based delivery system for improved delivery of drugs with low partition coefficient

Abstract

Context: The physicochemical properties of drugs such as partition coefficient play a major role in the development of lipid-based drug delivery systems. The major obstacle lies in encapsulation of a drug with low partition coefficient into these systems.

Objective: The objective of this study was to design and optimize a novel lipid-based delivery system with higher loading, improved pharmacokinetics consequently enhancing the oral bioavailability of drugs with low partition coefficient like valsartan.

Materials and methods: The optimized formulation consists of Capryol 90, Cremophor RH 40, and Transcutol HP. Pseudo ternary phase diagrams were used to optimize the components and their concentrations in the formulation. Dissolution studies of the selected formulations were compared with plain drug and marketed product at three pH conditions (pH 1.2, 4.5 and 6.8). Pharmacokinetic parameters of optimized formulations were determined in Wistar rats and compared with that of plain drug.

Results and discussion: The optimized formulation with a mean particle size of 50?nm showed significant improvement (p?<?0.05) in dissolution rate with pH independence compared to plain drug and marketed product. The in vivo studies in Wistar rats revealed about 2.30- and 1.68-fold increase in the oral bioavailability and C_max of valsartan from lipid-based formulation compared to plain drug.

Conclusion: The engineered formulation strategy by type IV lipid-based formulations can be successfully exploited to improve the dissolution rate and oral deliverability of drugs like valsartan.     

Arterial hypoxemia and performance during intense exercise

In order to determine the level of hypoxemia which is sufficient to impair maximal performance, seven well-trained male cyclists [maximum oxygen consumption (VO_2max)51·min^–1 or 60 ml·kg^–1·min^–1] performed a 5-min performance cycle test to exhaustion at maximal intensity as controlled by the subject, under three experimental conditions: normoxemia [percentage of arterial oxyhemoglobin saturation (%S _a O₂)>94%], and artificially induced mild (%S _aO₂=90±1%) and moderate (%S _aO₂=87±1%) hypoxemia. Performance, evaluated as the total work output (Work_tot) performed in the 5-min cycle test, progressively decreased with decreasing %S _aO₂ [mean (SE) Work_tot=107.40 (4.5) kJ, 104.07 (5.6) kJ, and 102.52 (4.7) kJ, under normoxemia, mild, and moderate hypoxemia, respectively]. However, only performance in the moderate hypoxemia condition was significantly different than in normoxemia (P=0.02). Mean oxygen consumption and heart rate were similar in the three conditions (P=0.18 andP=0.95, respectively). End-tidal partial pressure of CO₂ was significantly lower (P=0.005) during moderate hypoxemia compared with normoxemia, and ventilatory equivalent of CO₂ was significantly higher (P=0.005) in both hypoxemic conditions when compared with normoxemia. It is concluded that maximal performance capacity is significantly impaired in highly trained cyclists working under an %S _aO₂ level of 87% but not under a milder desaturation level of 90%.     

Bronchial response to breathing dry gas at 3.7 MPa ambient pressure

In diving, pulmonary mechanical function is limited by the increased density of the gas breathed. Breathing cold and dry gas may cause an additional increase in airways resistance. We have measured forced vital capacity, forced expired volume in 1 s (FEV₁) and forced midexpiratory flow rate (FEF_25%–75%) before and after breathing dry or humid gas at 29–32°C during a standardized exercise intensity on a cycle ergometer at an ambient pressure of 3.7 MPa. The atmosphere was a helium and oxygen mixture with a density of 6.8 kg · m^–3. Six professional saturation divers aged 26–37 years participated in the study. There were no significant differences in convective respiratory heat loss between the exposures. The mean evaporative heat loss was 67 W (range 59–89) breathing dry gas and 37 W (range 32–43) breathing humid gas, corresponding to water losses of 1.7 g · min^–1 (range 1.5–2.2) and 0.9 g · min^–1 (range 0.8–1.1), respectively. There was a significant reduction in FEV₁ of 4.6 (SD 3.6)% (P<0.05), and in FEF_25%–75% of 5.8 (SD 4.7)% (P<0.05) after breathing dry gas. There were no changes after breathing humid gas. By warming and humidifying the gas breathed in deep saturation diving bronchoconstriction may be prevented.     

Changes in Sodium,Calcium, and Magnesium Ion Concentrations That Inhibit Geobacillus Biofilms Have No Effect on Anoxybacillus flavithermus Biofilms

This study investigated the effects of varied sodium, calcium, and magnesium concentrations in specialty milk formulations on biofilm formation by Geobacillus spp. and Anoxybacillus flavithermus. The numbers of attached viable cells (log CFU per square centimeter) after 6 to 18 h of biofilm formation by three dairy-derived strains of Geobacillus and three dairy-derived strains of A. flavithermus were compared in two commercial milk formulations. Milk formulation B had relatively high sodium and low calcium and magnesium concentrations compared with those of milk formulation A, but the two formulations had comparable fat, protein, and lactose concentrations. Biofilm formation by the three Geobacillus isolates was up to 4 log CFU cm⁻² lower in milk formulation B than in milk formulation A after 6 to 18 h, and the difference was often significant (P ≤ 0.05). However, no significant differences (P ≤ 0.05) were found when biofilm formations by the three A. flavithermus isolates were compared in milk formulations A and B. Supplementation of milk formulation A with 100 mM NaCl significantly decreased (P ≤ 0.05) Geobacillus biofilm formation after 6 to 10 h. Furthermore, supplementation of milk formulation B with 2 mM CaCl₂ or 2 mM MgCl₂ significantly increased (P ≤ 0.05) Geobacillus biofilm formation after 10 to 18 h. It was concluded that relatively high free Na⁺ and low free Ca²⁺ and Mg²⁺ concentrations in milk formulations are collectively required to inhibit biofilm formation by Geobacillus spp., whereas biofilm formation by A. flavithermus is not impacted by typical cation concentration differences of milk formulations.     

Development and Statistical Optimization of Solid Lipid Nanoparticles of Simvastatin by Using 2<Superscript>3</Superscript> Full-Factorial Design

The objective of this study was to develop solid lipid nanoparticles (SLNs) of simvastatin and to optimize it for independent variables (amount of glycerol monostearate, concentration of poloxamer, and volume of isopropyl alcohol) in order to achieve desired particle size with maximum percent entrapment efficiency (% EE) and percent cumulative drug release (% CDR). To achieve our goal, eight formulations (F ₁–F ₈) of SLNs were prepared by solvent injection technique and optimized by 2³ full-factorial design. The design was validated by extra design checkpoint formulation (F ₉), and the possible interactions between independent variables were studied. The responses of the design were analyzed using Design Expert 7.1.6. (Stat-Ease, Inc, USA), and the analytical tools of software were used to draw Pareto charts and response surface plots. On the basis of software analysis, formulation F ₁₀ with a desirability factor of 0.611 was selected as optimized formulation and was evaluated for the independent parameters. Optimized formulation showed particle size of 258.5 nm, % EE of 75.81%, with of 82.67% CDR after 55 h. The release kinetics of the optimized formulation best fitted the Higuchi model, and the recrystallization index of optimized formulation was found to be 65.51%.     

Grassland responses to grazing: effects of grazing intensity and management system in an Inner Mongolian steppe ecosystem

The major aims of this study were, firstly, to analyse the grazing-induced steppe degradation process and, secondly, to identify an efficient and sustainable grazing management system for the widely degraded Inner Mongolian typical steppe ecosystem. From 2005?C2008 a grazing experiment was conducted to compare two grazing management systems, the Mixed System (MS) and the Traditional System (TS), along a gradient of seven grazing intensities, i.e. ungrazed (GI0), very-light (GI1), light (GI2), light-moderate (GI3), moderate (GI4), heavy (GI5), and very-heavy (GI6). Each grazing intensity treatment was considered a production unit comprising two adjacent plots, one for hay-making (single-cut system) and one for grazing. Hay-making and grazing alternated annually in the MS, while in the TS the same plots were used either for hay-making or for grazing. Effects of management system, grazing intensity, and year on end-of-season standing biomass (ESSB), aboveground net primary production (ANPP), relative difference in ANPP between 2005 and 2008 (ANPP_Diff), relative growth rate (RGR), and sward characteristics (litter accumulation, soil coverage) were analysed. Litter accumulation of production units was affected by grazing intensity (P?<?0.001) and decreased from GI0 to GI6 by 83%. Correspondingly, soil coverage decreased (P?<?0.001) from GI0 to GI6 by 43%, indicating an increased vulnerability to soil erosion. We found varying compensatory growth responses to grazing intensity among years, probably because of temporal variability in precipitation. The ability of plants to partially compensate for grazing damage was enhanced in years of greater seasonal precipitation. The ANPP of production units was negatively affected by grazing intensity and decreased from GI0 to GI6 by 37, 30, and 55% in 2006 (P?<?0.01), 2007 (P?<?0.05), and 2008 (P?<?0.001), respectively. The effect of management system × grazing intensity interaction on ANPP (P?<?0.05) and ANPP_Diff (P?<?0.05) suggested greater grazing resilience of the MS as compared to the TS at GI3 to GI6.