Energy cost and running mechanics during a treadmill run to voluntary exhaustion in humans

The aim of the present study was to examine the physiological and mechanical factors which may be concerned in the increase in energy cost during running in a fatigued state. A group of 15 trained triathletes ran on a treadmill at velocities corresponding to their personal records over 3000m?[mean 4.53 (SD 0.28) m?·?s^?1] until they felt exhausted. The energy cost of running (C _R) was quantified from the net O₂ uptake and the elevation of blood lactate concentration. Gas exchange was measured over 1?min firstly during the 3rd–4th?min and secondly during the last minute of the run. Blood samples were collected before and after the completion of the run. Mechanical changes of the centre of mass were quantified using a kinematic arm. A significant mean increase [6.9 (SD 3.5)%, P?C _R from a mean of 4.4 (SD 0.4) J?·?kg^?1?·?m^?1 to a mean of 4.7 (SD 0.4) J?·?kg^?1?·?m^?1 was observed. The increase in the O₂ demand of the respiratory muscles estimated from the increase in ventilation accounted for a considerable proportion [mean 25.2 (SD 10.4)%] of the increase in C_R. A mean increase [17.0 (SD 26.0)%, P?C _M) from a mean of 2.36 (SD 0.23) J?·?kg^?1?·?m^?1 to a mean of 2.74 (SD 0.55) J?·?kg^?1?·?m^?1 was also noted. A significant correlation was found between C _R and C _M in the non-fatigued state (r?=?0.68, P?r?=?0.25, NS). Furthermore, no correlations were found between the changes (from non-fatigued to fatigued state) in C _R and the changes in C _M suggesting that the increase in C _R is not solely dependent on the external work done per unit of distance. Since step frequency decreased slightly in the fatigued state, the internal work would have tended to decrease slightly which would not be compatible with an increase in C _R. A stepwise regressions showed that the changes in C _R were linked (r?=?0.77, P?C _R was due to an increase in the step variability. The underlying mechanisms of the relationship between C _R and step variability remains unclear.     

An immunochemical procedure to evaluate the degree of desialylation of alpha 1-acid glycoprotein in rat serum

When radial immunodiffusion (RID) and electroimmunodiffusion (EID) were used for the determination of rat alpha 1-acid glycoprotein (alpha 1-AGP) a significant discrepancy in the results was encountered depending on the degree of sialylation. When alpha 1-AGP was desialylated, the amounts estimated by EID were much lower than those actually present as assayed by the RID method. The relationship between the percentage of desialylation of alpha 1-AGP and the percentage of its underestimation by EID relative to RID was determined and a calibration curve was plotted to evaluate the degree of desialylation of rat alpha 1-AGP. When compared to other procedures (rat membrane inhibition assay and isoelectrofocusing), the proposed method was easier to perform and allowed the specific evaluation of the degree of undersialylation of the glycoprotein.     

Chromatographic approach to study beta-cyclodextrin as a promoter of the penetration of bifonazole into keratinic tissue

A high-performance liquid chromatographic method for the determination of bifonazole in dimethyl sulfoxide solvent was developed to study its penetration into sheephoof. The analytical method was linear over the concentration range studied, i.e., from 0.1 mg/ml to 1 mg/ml. The relative standard deviation was less than 2%. The data obtained showed that complex forming with beta-cyclodextrin greatly improved the penetration of bifonazole.     

Study and development of encapsulated forms of 4, 5′, 8‐Trimethylpsoralen for topical drug delivery

Trimethylpsoralen (TMP) is often used to treat skin diseases (i.e., psoriasis, vitiligo, etc.). This drug permeates moderately the skin barrier. In the present study, we investigated the effect of formulation on the improvement of TMP skin bioavailability. Three formulations were performed. Each form (liposomes, nanospheres, and EtOH solution) contained 0.05% of TMP. For each preparation, the quantity deposited on the skin surface was 250 µg (Q₀). The TMP percutaneous penetration through ex‐vivo human skin was processed by Franz^® cells (n=4) using a human albumin solution (1.4% w/v) as receiver medium. The percentages of the extracted TMP that permeated through the skin and that were retained in the skin over 24 h, were calculated with respect to Q₀. The values obtained were reported, respectively, as follows: EtOH solution (1.33 vs. 0.08%), liposomes (0.93 vs. 0.93%), and PLG‐nanospheres (0.79 vs. 3.01%). So, considering the correlation between the cumulated amounts of TMP permeated through the skin and the TMP stocked in the skin, the nanosphere form showed the higher quantity of TMP accumulated in the skin structures. On the other hand, the maximum value of the flux (ng/cm²/h) in the steady state of TMP incorporated in each formulation was at 6 h for all formulations: 173.5±1.06 (EtOH solution) > 120.4±1.06 (liposomes) > 93.82±0.88 (PLG‐nanospheres). These results indicate that the controlled release of TMP by incorporation in PLG‐nanospheres may increase drug content in the skin, while maintaining a minimal percutaneous absorption. Finally, this work shows that the PLG‐nanospheres could constitute a promising approach for controlling TMP release in order to maintain its topical activity. Drug Dev. Res. 61:86–94, 2004. © 2004 Wiley‐Liss, Inc.     

Oocyte quality in polycystic ovaries revisited: Identification of a particular subgroup of women

Purpose: Our purpose was to assess the endocrine status of women with polycystic ovaries (PCO) undergoing IVF, and to compare oocyte quality with endocrine markers of the syndrome, in an attempt to define a subpopulation with poor quality oocytes. Methods: This was a retrospective study. Patients were first endocrinologically analyzed: serum levels of androgens (T, androstenedione, DHEAS), FSH, and LH as well as glucose and insulin after an oral glucose tolerance test (OGTT) were recorded and are expressed as absolute values and area under the curve (AUC). Subsequently, they were followed over a 2-year period in which patients underwent several attempts of IVF as well as serving as oocyte donors. Patients were divided into three groups: group I (n=4) was women who displayed embryos unable to implant in 15 IVF cycles and 10 ovum donation cycles in which they served as donors; group II (n=16) was PCO patients in whom IVF (n=38) and/or oocyte donation cycles (n=42) resulted in pregnancies; and group III (n=13) was IVF patients with normal appearance of the ovaries by ultrasound. The endocrine status was compared with the IVF results. Results: There was no difference among groups in the endocrinological parameters tested, except for the OGTT which identified women in group I as having higher serum glucose and insulin levels than patients in groups II and III. Similarly, the OGTT showed higher serum glucose values in group II compared to group III. Women in group I were also obese. Patients in group III were older than PCO patients and needed more gonadotropins to reach an ovarian response which resulted in a reduced number of oocytes retrieved. Fertilization was also impaired in group I, in which no pregnancy was recorded. Conclusions: This study shows that there is a particular subgroup of PCO patients with lower fertilization rates and embryos unable to implant. These patients are obese and nonhyperandrogenic and show derangements of insulin secretion.     

Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols

In order to study the biological activities of tea preparations and purified tea polyphenols, their growth inhibitory effects were investigated using four human cancer cell lines. Growth inhibition was measured by [3H]thymidine incorporation after 48 h of treatment. The green tea catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)- epigallocatechin (EGC) displayed strong growth inhibitory effects against lung tumor cell lines H661 and H1299, with estimated IC50 values of 22 microM, but were less effective against lung cancer cell line H441 and colon cancer cell line HT-29 with IC50 values 2- to 3- fold higher. (-)-Epicatechin-3-gallate, had lower activities, and (-)- epicatechin was even less effective. Preparations of green tea polyphenols and theaflavins had higher activities than extracts of green tea and decaffeinated green tea. The results suggest that the growth inhibitory activity of tea extracts is caused by the activities of different tea polyphenols. Exposure of H661 cells to 30 microM EGCG, EGC or theaflavins for 24 h led to the induction of apoptosis as determined by an annexin V apoptosis assay, showing apoptosis indices of 23, 26 and 8%, respectively; with 100 microM of these compounds, the apoptosis indices were 82, 76 and 78%, respectively. Incubation of H661 cells with EGCG also induced a dose-dependent formation of H2O2. Addition of H2O2 to H661 cells caused apoptosis in a manner similar to that caused by EGCG. The EGCG-induced apoptosis in H661 cells was completely inhibited by exogenously added catalase (50 units/ml). These results suggest that tea polyphenol-induced production of H2O2 may mediate apoptosis and that this may contribute to the growth inhibitory activities of tea polyphenols in vitro.      

Characterization of xenobiotic-metabolizing enzymes and nitrosamine metabolism in the human esophagus

Esophageal cancer has been associated with tobacco smoking, and nitrosamines are possible causative agents for this cancer. The present study investigated the metabolism of the tobacco carcinogens N'- nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK), and N-nitrosodimethylamine (NDMA), as well as the presence of xenobiotic-metabolizing enzymes in human esophageal tissues from individuals in the United States and Huixian, Henan Province, China (a high-risk area for esophageal cancer). All esophageal microsomal samples activated NNN and the metabolic rate was 2-fold higher in the esophageal samples from China than the USA. All microsomal samples activated NDMA. However, most of the microsomal samples did not activate NNK. Troleandomycin (an inhibitor of cytochrome P450 3A) decreased the formation of NNN-derived keto acid by 20-26% in the esophageal microsomes. The activities for NADPH: cytochrome c reductase, ethoxycoumarin O-deethylase, NAD(P)H: quinone oxidoreductase and glutathione S-transferase were present in the esophageal samples. Coumarin 7-hydroxylase (a representative activity for P450 2A6) activity was not detected in the esophageal microsomal samples. The activities for nitrosamine metabolism and xenobiotic- metabolizing enzymes were decreased (by 30-50%) in the squamous cell carcinomas compared with their corresponding non-cancerous mucosa. The presence of activation and detoxification enzymes in the esophagus may play an important role in determining the susceptibility of the esophagus to the carcinogenic effect of nitrosamines. Our results suggest that P450s 3A4 and 2E1 are involved in the activation of NNN and NDMA, respectively, in the human esophagus.      

Le trouble obsessionnel-compulsif,un nouveau modèle de dysfonction des noyaux gris centraux ? Apports de la stimulation cérébrale profonde

Deep brain stimulation was first developed for movement disorders but is now being offered as a therapeutic alternative in severe psychiatric disorders after the failure of conventional therapies. One of such pathologies is obsessive-compulsive disorder. This disorder which associates intrusive thoughts (obsessions) and repetitive irrepressible rituals (compulsions) is characterized by a dysfunction of a cortico-subcortical loop. After having reviewed the pathophysiological evidence to show why deep brain stimulation was an interesting path to take for severe and resistant cases of obsessive-compulsive disorder, we will present the results of the different clinical trials. Finally, we will provide possible mechanisms for the effects of deep brain stimulation in this pathology.