Treatment with soy isoflavones during early adulthood improves metabolism in early postnatally overfed rats

Purpose: The incidences of obesity and related diseases have reached epidemic proportions, and new therapeutic approaches are needed. Soy isoflavones have been identified as an important dietary factor for preventing and treating metabolic dysfunction. This study examined the effects of high doses of isoflavone on glucose and fat metabolism in a model of programmed obesity and evaluated its effects on the autonomic nervous system.

Methods: Litters of Wistar rats were standardized at nine pups per dam in normal litters (NL) or reduced to three pups per dam at the third day of life (P3) in small litters (SL) to induce postnatal overfeeding. Gavage with a soy bean isoflavone mixture (1?g/day) diluted in water was started at P60 and continued for 30 days. The control animals received vehicle gavage. At P90, biometric and metabolic parameters as well as direct autonomic nerve activity were measured.

Results: Increases in glycaemia and insulinaemia observed in SL rats were reduced by isoflavone treatment, which also caused lower glucose-induced insulin secretion by pancreatic islets. Sympathetic activity in the major splanchnic nerve was increased, while vagus nerve activity was reduced by isoflavone treatment. The dyslipidaemia induced by overfeeding in SL rats was restored by isoflavone treatment.

Conclusion: The present study shows that treatment with isoflavone reduces adiposity and improves glucose and lipid metabolism. Collectively, these effects may depend on autonomic changes.     

Nanodesign of new self-assembling core-shell gellan-transfersomes loading baicalin and in vivo evaluation of repair response in skin

Gellan nanohydrogel and phospholipid vesicles were combined to incorporate baicalin in new self-assembling core-shell gellan-transfersomes obtained by an easy, scalable method. The vesicles were small in size (~107 nm) and monodispersed (P.I. ≤ 0.24), forming a viscous system (~24 mPa/s) as compared to transfersomes (~1.6 mPa/s), as confirmed by rheological studies. Gellan was anchored to the bilayer domains through cholesterol, and the polymer chains were distributed onto the outer surface of the bilayer, thus forming a core-shell structure, as suggested by SAXS analyses. The optimal carrier ability of core-shell gellan-transfersomes was established by the high deposition of baicalin in the skin (~11% in the whole skin), especially in the deeper tissue (~8% in the dermis). Moreover, their ability to improve baicalin efficacy in anti-inflammatory and skin repair tests was confirmed in vivo in mice, providing the complete skin restoration and inhibiting all the studied inflammatory markers.     

Oral biopsy in dental practice

The conclusions drawn from the study of an oral biopsy are considered essential for the definitive diagnosis of diseases of the oral mucosa, and for the subsequent planning of appropriate treatment. Although the obtainment of biopsies is widely used in all medical fields, the practice is not so widespread in dental practice--fundamentally because of a lack of awareness of the procedure among dental professionals. In this context, it must be taken into account that the early diagnosis of invasive oral malignancy may be critical for improving the patient prognosis. However, in some cases the results are adversely affected by incorrect manipulation of the biopsy material. The present study provides an update on the different biopsy sampling techniques and their application. Such familiarization in turn will contribute to knowledge of the material and instruments required for correct biopsy performance in dentistry, as well as of the material required for correct sample storage and transport.     

Influence of the cyto-protective agent amifostine on the pharmacokinetics of low-dose Paclitaxel

BACKGROUND: Pharmacokinetic parameters (PHK) of low-dose weekly paclitaxel (PAC) are not well known, particularly when administered with the cytoprotective agent amifostine (AMI). METHODS: Patients with non-small cell lung cancer (NSCLC) received PAC alone or PAC + AMI. Blood samples were drawn at the end of the infusion at 0, 0.25, 0.5, 1, 2 and 4 h for the measurement of plasma PAC using HPLC. Area under the concentration-time curve (AUC), the peak plasma concentrations (Cmax) and the residence time of paclitaxel in plasma at concentrations >0.1 microM (TPP >or=0.1) and >0.05 microM (TPP >or=0.05) were calculated using a two-compartmental model. ANOVA was used for statistical analysis. RESULTS: Pharmacokinetic studies were completed for 43 doses among 11 patients receiving PAC alone and for 26 doses among 8 patients receiving the combination AMI + PAC (from the first to the fifth week). Statistically significant differences in all parameters except AUC were observed between the 2 treatment groups. A significantly higher Cmax was observed for patients receiving PAC + AMI versus PAC alone. Both TPP >or=0.1 and TPP >or=0.05 were also more prolonged in AMI + PAC cycles. CONCLUSION: AMI produces a prolongation in PAC plasma circulation time. Further specifically designed studies are needed to quantify the resultant effects on PAC's efficacy and toxicity.     

Reconstructing the ancestor of Mycobacterium leprae: the dynamics of gene loss and genome reduction

We have reconstructed the gene content and order of the last common ancestor of the human pathogens Mycobacterium leprae and Mycobacterium tuberculosis. During the reductive evolution of M. leprae, 1537 of 2977 ancestral genes were lost, among which we found 177 previously unnoticed pseudogenes. We find evidence that a massive gene inactivation took place very recently in the M. leprae lineage, leading to the loss of hundreds of ancestral genes. A large proportion of their nucleotide content ( approximately 89%) still remains in the genome, which allowed us to characterize and date them. The age of the pseudogenes was computed using a new methodology based on the rates and patterns of substitution in the pseudogenes and functional orthologous genes of closely related genomes. The position of the genes that were lost in the ancestor's genome revealed that the process of function loss and degradation mainly took place through a gene-to-gene inactivation process, followed by the gradual loss of their DNA. This suggests a scenario of massive genome reduction through many nearly simultaneous pseudogenization events, leading to a highly specialized pathogen.     

Pulmonary versus systemic delivery of levofloxacin. The isolated lung of the rat as experimental approach for assessing pulmonary inhalation

The present work was aimed to compare levofloxacin pulmonary disposition after systemic or inhalatory delivery and to evaluate the influence of respiratory pattern on lung distribution. An experimental model of the isolated lung of the rat was used. Twenty-four Wistar rats were distributed in four groups receiving levofloxacin under different experimental conditions including systemic or pulmonary delivery and higher or lower respiratory frequency with lower or higher tidal volume, respectively. Levofloxacin (500 microg) was administered as a bolus injection or by inhalation. Lung tissue samples as well as efferent and broncoalveolar fluid were collected. Quantification of levofloxacin levels in all samples was performed by a high-performance liquid chromatography (HPLC) technique. Pulmonary distribution coefficient of levofloxacin after systemic delivery showed mean values of 1.19+/-0.13 and 3.34+/-0.61 ml/g for each respiratory pattern assayed. The partition coefficients estimated from simultaneous drug level in lung tissue and efferent fluid (EF) are in agreement with the above values. Comparison of systemic and pulmonary administration reveals statistical significant differences between partition coefficients showing much higher values for the latter route (8.01+/-5.53 versus 2.86+/-1.35). In conclusion, inhalation compared to systemic administration improves levofloxacin access to the lung tissue; the experimental approach used here to assess the pulmonary drug disposition may be a useful model for biopharmaceutical studies of inhaled therapeutics.     

Haemorheological parameters in young patients with acute myocardial infarction

The role played by hemorheological alterations on acute myocardial infarction (AMI) in young patients remains a question of debate. We have carried out a case-control study of 84 AMI patients aged <45 years and 135 sex and age matched controls, in which blood viscosity (BV), plasma viscosity (PV), erythrocyte aggregation (EA) performed with the Myrenne (EA0, EA1) and the Sefam aggregometer (Ta, AI10, gammaD), erythrocyte deformability (ED) along with fibrinogen (Fbg), C-reactive protein (CRP) and plasmatic lipids i.e. total cholesterol (T-Chol) and triglycerides (TG) were determined. AMI patients showed higher, Fbg, TG, EA0, EA1, IA10, gammaD and lower Ta than controls (p=0.029, p<0.001, p=0.013, p=0.003, p=0.010, p=0.025) respectively. No differences in the other rheological parameters were observed. No differences in any rheological parameter were observed regarding the AMI type, number and score of stenosed vessels and the time elapsed since the thrombotic event. After multivariate adjustment, Fbg>380 ml/dl and TG>185 ml/dl were independently associated with a higher risk of erythrocyte hyperaggregability (OR: 5.5 CI 95% 1.04-29.27 and OR: 7.3 CI 95% 2.66-20.03) respectively. EA>8.85 was associated with a increased AMI risk (OR: 5.3 CI 95% 1.98-14.5). These results reinforces the view that in young AMI patients increased Fbg and TG may promote the development of ischaemic events not only through its known mechanism but also by altering rheological blood behaviour, mainly increasing EA.