Association between early manifestations of infection or sepsis and prognosis in a high complexity hospital in the city of Medellín.

OBJECTIVE: To identify the first symptoms and signs of patients with suspected infection or sepsis and their association with the composite outcome of admission to the Intensive Care Unit (ICU) or mortality. DESIGN: Prospective cohort study between June 2019 and March 2020. SETTING: Hospital Universitario San Vicente Fundación, Colombia. PATIENTS: Over 18 years of age with suspicion or confirmation of sepsis, which required hospitalization. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Symptoms and signs associated with infection, with their time of evolution, specified in the study. RESULTS: From 1005 eligible patients, 261 were included. After multivariable adjustment with a logistic regression model, the main factors for ICU admission or mortality were heart rate (OR 1.04 with 95% CI 1.04-3.7), respiratory rate (OR 1.19 with 95% CI 1.0-1.4) and capillary refill time (OR 3.4 with 95% CI 1.9-6.1). CONCLUSIONS: Heart rate, respiratory rate, and capillary refill may behave as early predictors of ICU admission and mortality in cases of sepsis.

SKELETAL MUSCLE SENSITIVITY TO WASTING INDUCED BY UROTHELIAL CARCINOMA.

BACKGROUND: Skeletal muscle wasting is a common phenotypic feature of several types of cancer, and it is associated with functional impairment, respiratory complications, and fatigue. However, equivocal evidence remains regarding the impact of cancer-induced muscle wasting on the different fiber types. AIM: The aim of this study was to investigate the impact of urothelial carcinoma induced in mice on the histomorphometric features and collagen deposition in different skeletal muscles. MATERIALS AND METHODS: Thirteen ICR (CD1) male mice were randomly assigned into two groups: exposed to 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in drinking water for 12 weeks, plus 8 weeks of tap water (BBN, n = 8) or with access to tap water for 20 weeks (CONT, n = 5). Tibialis anterior, soleus, and diaphragm muscles were collected from all animals. For cross-sectional area and myonuclear domain analysis, muscle sections were stained with hematoxylin and eosin, and for collagen deposition assessment, muscle sections were stained with picrosirius red. RESULTS: All animals from the BBN group developed urothelial preneoplastic and neoplastic lesions, and the tibialis anterior from these animals presented a reduced cross-sectional area (p < 0.001), with a decreased proportion of fibers with a higher cross-sectional area, increased collagen deposition (p = 0.017), and higher myonuclear domain (p = 0.031). BBN mice also showed a higher myonuclear domain in the diaphragm (p = 0.015). CONCLUSION: Urothelial carcinoma induced muscle wasting of the tibialis anterior, expressed by a decreased cross-sectional area, higher infiltration of fibrotic tissue, and increased myonuclear domain, which also increased in the diaphragm, suggesting that fast glycolytic muscle fibers are more susceptible to be affected by cancer development.

Creatine supplementation exacerbates ethanol-induced hepatic damage in mice.

OBJECTIVE: The aim of this study was to investigate the effects of creatine supplementation on early stages of ethanol-induced hepatic damage. METHODS: Male Swiss mice were divided into three groups (n = 12/group): control (C), ethanol (E), and ethanol supplemented with creatine (EC). The control group received a diet containing 15.8% of total calories from proteins, 46.3% from carbohydrates, and 37.9% from lipids. The ethanol and ethanol and creatine groups received diets containing 15.8% of total calories from proteins, 16.2% from carbohydrates, and 34.5% from lipids; the remaining calories were obtained from the addition of 5% of 95% ethanol. Creatine (1%; weight/vol) was added to the diet of EC mice. After 14 and 28 d, six animals from each group were sacrificed, generating subdivisions in each group: C14 and C28, E14 and E28, EC14 and EC28. After sacrifice, the liver was removed, weighed, and prepared for histologic, biochemical, and molecular analysis, and blood was collected. RESULTS: Ethanol intake induced mild cell degeneration, liver damage, oxidative lesions, and inflammation. Surprisingly, ethanol intake combined with creatine exacerbated cell degeneration and fat accumulation, hepatic expression of genes related to ethanol metabolism, oxidative stress and inflammation, and promoted oxidative stress and elevated plasma alanine aminotransferase (P < 0.05). CONCLUSION: Creatine supplementation associated with ethanol is able to interfere in the alcohol metabolism and oxidative stress and to exacerbate ethanol-induced hepatic damage. These new findings are opposite to those observed in several studies where protective effects of creatine in a wide variety of injury models, including non-alcoholic fatty liver disease, were described.

Aged rats are more vulnerable than adolescents to "ecstasy"-induced toxicity.

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a widespread drug of abuse with known neurotoxic properties. The present study aimed to evaluate the differential toxic effects of MDMA in adolescent and aged Wistar rats, using doses pharmacologically comparable to humans. Adolescent (post-natal day 40) (3 × 5 mg/kg, 2 h apart) and aged (mean 20 months old) (2 × 5 mg/kg, 2 h apart) rats received MDMA intraperitoneally. Animals were killed 7 days later, and the frontal cortex, hippocampus, striatum and cerebellum brain areas were dissected, and heart, liver and kidneys were collected. MDMA caused hyperthermia in both treated groups, but aged rats had a more dramatic temperature elevation. MDMA promoted serotonergic neurotoxicity only in the hippocampus of aged, but not in the adolescents' brain, and did not change the levels of dopamine or serotonin metabolite in the striatum of both groups. Differential responses according to age were also seen regarding brain p-Tau levels, a hallmark of a degenerative brain, since only aged animals had significant increases. MDMA evoked brain oxidative stress in the hippocampus and striatum of aged, and in the hippocampus, frontal cortex, and striatum brain areas of adolescents according to protein carbonylation, but only decreased GSH levels in the hippocampus of aged animals. The brain maturational stage seems crucial for MDMA-evoked serotonergic neurotoxicity. Aged animals were more susceptible to MDMA-induced tissue damage in the heart and kidneys, and both ages had an increase in liver fibrotic tissue content. In conclusion, age is a determinant factor for the toxic events promoted by "ecstasy". This work demonstrated special susceptibility of aged hippocampus to MDMA neurotoxicity, as well as impressive damage to the heart and kidney tissue following "ecstasy".

Long-term exercise training prevents mammary tumorigenesis-induced muscle wasting in rats through the regulation of TWEAK signalling.

AIM: Exercise training has been suggested as a non-pharmacological approach to prevent skeletal muscle wasting and improve muscle function in cancer cachexia. However, little is known about the molecular mechanisms underlying such beneficial effect. In this study, we aimed to, firstly, examine the contribution of TWEAK signalling to cancer-induced skeletal muscle wasting and, secondly, evaluate whether long-term exercise alters TWEAK signalling and prevents muscle wasting. METHODS: Female Sprague-Dawley rats were randomly assigned to control and exercise groups. Fifteen animals from each group were exposed to N-Methyl-N-nitrosourea carcinogen. Animals in exercise groups were submitted to moderate treadmill exercise for 35 weeks. After the experimental period, animals were killed and gastrocnemius muscles were harvested for morphological and biochemical analysis. RESULTS: We verified that exercise training prevented tumour-induced TWEAK/NF-κB signalling in skeletal muscle with a beneficial impact in fibre cross-sectional area and metabolism. Indeed, 35 weeks of exercise training promoted the upregulation of PGC-1α and oxidative phosphorylation complexes. This exercise-induced muscle remodelling in tumour-bearing animals was associated with less malignant mammary lesions. CONCLUSION: Data support the benefits of an active lifestyle for the prevention of muscle wasting secondary to breast cancer, highlighting TWEAK/NF- κB signalling as a potential therapeutic target for the preservation of muscle mass.

Effects of doxorubicin administration on bone strength and quality in sedentary and physically active Wistar rats.

Doxorubicin (DOX) is used in pediatric cancer treatment. This study assessed the effects of 7 weeks of DOX and 10-week recovery on bone quality and biomechanical properties in sedentary and exercised Wistar rats. DOX decreases femur diaphysis radial growth and biomechanical properties. Some of these DOX effects were aggravated by exercise. INTRODUCTION: Bone growth in pre-pubertal years critically influences adult fracture risk. DOX is widely used in the treatment of pediatric cancers, but there is limited evidence on its potential negative effects on bone growth. Exercise improves bone growth in children, but there is no evidence if it protects against DOX-induced bone toxicity. This study investigates the early and intermediate effects of a 7-week course of DOX on bone histomorphometry and strength in sedentary and exercised growing animal models. METHODS: Sixty-eight male Wistar rats (8 weeks) were treated with DOX (2 mg kg-1) or vehicle for 7 weeks and afterward housed in standard cages or in cages with a running wheel and killed 2 or 10 weeks after last DOX administration. Femurs and blood were collected for assaying geometry, trabecular microarchitecture (histology), biomechanical properties (three-point bending and shearing of the femoral neck), bone calcium content and density (atomic absorption spectroscopy), and bone turnover markers (ELISA). RESULTS: DOX treatment reduced the femur diaphysis radial growth, with DOX-treated animals having a lower tissue area, cortical area, cortical thickness, and moment of inertia. DOX also decreased distal femur trabecular bone volume and trabecular number and increased trabecular separation. Femur diaphysis stiffness and maximum load were also reduced in past DOX-treated animals. Exercise was shown to worsen the effects of past DOX treatment on the femur diaphysis mechanical properties. CONCLUSION: DOX negatively affects bone geometry, trabecular microarchitecture, and femur mechanical properties in growing Wistar rats. Exercise further aggravates the detrimental effects of past DOX treatment on bone mechanical properties.

Urinary Incontinence and Levels of Regular Physical Exercise in Young Women.

The purpose of this study was to determine the influence of different levels of regular physical exercise on the frequency of urinary incontinence in young nulliparous women from the northern region of Portugal. Participants (n=386) self-reported demographic variables, frequency, and time spent practicing organized exercise per week, as well as completed the International Consultation on Incontinence Questionnaire-Short Form. The level of exercise was calculated based on the time (in minutes) usually spent per week in organized exercise. 19.9% of Portuguese nulliparous women reported incontinence symptoms. Considering the distribution of urinary incontinence among the different quartiles of organized exercise, women from the 4(th)quartile (those who train for competitive purposes) demonstrated highest relative frequency (p=0.000) and a 2.53 greater relative risk to develop (95% CIs,1.3-2.7) incontinence compared to women from the 1(st) quartile (inactive). Women who practice exercise for recreational purposes (2(nd) and 3(rd) quartiles) did not show significant differences in the urinary incontinence prevalence and relative risk of developing it compared to women from the 1(st) quartile. The results showed that women participating in organized exercise involving high volume training for competition are potentially at risk of developing urinary incontinence, although organized exercise undertaken without the intent to compete seems to be safe for maintaining urinary continence.

The interrelation between aPKC and glucose uptake in the skeletal muscle during contraction and insulin stimulation.

Contraction and insulin increase glucose uptake in skeletal muscle. While the insulin pathway, better characterized, requires activation of phosphoinositide 3-kinase (PI3K) and atypical protein kinase (aPKC), muscle contraction seems to share insulin-activated components to increase glucose uptake. This study aimed to investigate the interrelation between the pathway involved in glucose uptake evoked by insulin and muscle contraction. Isolated muscle of rats was treated with solvent (control), insulin, wortmannin (PI3K inhibitor) and the combination of insulin plus wortmannin. After treatment, muscles were electrically stimulated (contracted) or remained at rest. Glucose transporter 4 (GLUT4) localization, glucose uptake and phospho-aPKC (aPKC activated form) were assessed. Muscle contraction and insulin increased glucose uptake in all conditions when compared with controls not stimulating an effect that was accompanied by an increase in GLUT4 and of phospho-aPKC at the muscle membrane. Contracted muscles treated with insulin did not show additive effects on glucose uptake or aPKC activity compared with the response when these stimuli were applied alone. Inhibition of PI3K blocked insulin effect on glucose uptake and aPKC but not in the contractile response. Thus, muscle contraction seems to stimulate aPKC and glucose uptake independently of PI3K. Therefore, aPKC may be a convergence point and a rate limit step in the pathway by which, insulin and contraction, increase glucose uptake in skeletal muscle.

Cardiac regeneration and cellular therapy: is there a benefit of exercise?

Cardiovascular diseases (CVD) are a global epidemic in developed countries. Cumulative evidence suggests that myocyte formation is preserved during postnatal life, in adulthood or senescence, suggesting the existence of a growth reserve of the heart throughout lifespan. Several medical therapeutic approaches to CVD have considerably improved the clinical outcome for patients. Intense interest has been focused on regenerative medicine as an emerging strategy for CVD. Cellular therapeutic approaches have been proposed for enhancing survival and propagation of stem cells in myocardium, leading to cardiac cellular repair. Strong epidemiological and clinical data exists concerning the impact of regular physical exercise on cardiovascular health. Several mechanisms of acute and chronic exercise-induced cardiovascular adaptations to exercise have been presented, considering primary and secondary prevention of CVD. In this context, exercise-related improvements in the function and regeneration of the cardiovascular system may be associated with the exercise-induced activation, mobilization, differentiation, and homing of stem and progenitor cells. In this review several topics will be addressed concerning the relation between exercise, recruitment and biological activity of blood-circulating progenitor cells and resident cardiac stem cells. We hypothesize that exercise-induced stem cell activation may enhance overall heart function and improve the efficacy of cardiac cellular therapeutic protocols.

Overweight, obesity, physical activity, cardiorespiratory and muscular fitness in a Portuguese sample of high school adolescents.

AIM: The aim of this paper was to describe overweight, obesity, physical activity, cardiorespiratory and muscular fitness levels in school adolescents, aged between 12 to 17 years. METHODS: Cross-sectional study that took place in Castelo Branco district, Portugal. Height, weight, body mass index, waist circumference and percentage of fat mass by bioelectric impedance were measured. Physical activity was assessed by the Adapted Version to Portuguese Population of Weekly Activity Checklist (AVPPWAC); 20-metre shuttle run test (SRT) was performed to determine cardiorespiratory fitness level. Muscular fitness was determined with curl-ups, back-arch and push-ups. 924 adolescents were analyzed. RESULTS: According to BMI International Obesity Task Force reference values, male's overweight values showed a prevalence of 23.5% and 21.4% for females. For obesity values, males showed a prevalence of 5.4% and 3.4% for females. According to WC reference values, male's overweight values showed a prevalence of 67.4% and 74.3% for females. For obesity values, males showed a prevalence of 30.1% and 36.2% for females. According to %FM reference values, male's overweight values showed a prevalence of 13.8% and 20.2% for females. For obesity values, males showed a prevalence of 4.4% and 28.4% for females. The percentage of subjects with low PA level or below of the P25 was 25.9% for males and 26.3% for females. According to body mass status group, the PA decreases as adiposity increases. Males and females exhibited very low cardiorespiratory fitness based on SRT (males mean =47.65±22.75 rounds) and muscular fitness based on push-ups (males mean =14.66±10.36 repetitions; females mean =8.11±7.22 repetitions); curl-ups (males mean =41.35±23.76 repetitions; females mean =33.87±21.78 repetitions); and back arch (males mean =26.24±5.02 cm; females mean =26.37±5.28 cm) exhibited good values in accordance to the optimal zone for muscular fitness. CONCLUSION: There is a high prevalence of overweight and central adiposity in this population, with low physical activity and fitness levels. This profile may result in adverse health outcomes.

GNAS A-1121G variant is associated with improved diastolic dysfunction in response to exercise training in heart failure patients.

ß1-adrenergic receptors (ADRB1) and Gαs proteins (GNAS) play important roles in the regulation of cardiac function. The present study sought to investigate whether ADRB1 Arg389Gly (rs1801253), GNAS -1211 G/A (rs6123837) and GNAS 2291 C/T (rs6026584) variants are associated with left ventricular function and exercise tolerance in heart failure patients. 61 heart failure patients completed a 6-month exercise-training programme. Left ventricular ejection fraction (LVEF), mitral inflow velocities (deceleration time, and E/A ratio) and exercise tolerance (METs) were assessed at baseline and following exercise training. There were no associations between the studied variants and LVEF or E/A ratio measured at baseline and after exercise training. Deceleration time of early mitral flow was higher at baseline in GNAS -1211G allele carriers compared with -1211A allele homozygotes (P<0.05). Exercise training attenuated deceleration time in -1211G allele carriers (P<0.05) but not in -1211A allele homozygotes. Moreover, ADRB1 389Gly homozygotes had a greater training-induced increase in exercise tolerance than 389Arg homozygotes (P=0.04). This study shows that the functional GNAS -1121 G/A polymorphism is associated with diastolic function at baseline and in response to exercise training in heart failure patients. Furthermore, our data suggest that ADRB1 Arg389Gly polymorphism may influence exercise tolerance.

Relevance of the sterilization-induced effects on the properties of different hydroxyapatite nanoparticles and assessment of the osteoblastic cell response.

Hydroxyapatite (Hap) is a calcium phosphate with a chemical formula that closely resembles that of the mineral constituents found in hard tissues, thereby explaining its natural biocompatibility and wide biomedical use. Nanostructured Hap materials appear to present a good performance in bone tissue applications because of their ability to mimic the dimensions of bone components. However, bone cell response to individual nanoparticles and/or nanoparticle aggregates lost from these materials is largely unknown and shows great variability. This work addresses the preparation and characterization of two different Hap nanoparticles and their interaction with osteoblastic cells. Hap particles were produced by a wet chemical synthesis (WCS) at 37°C and by hydrothermal synthesis (HS) at 180°C. As the ultimate in vivo applications require a sterilization step, the synthesized particles were characterized 'as prepared' and after sterilization (autoclaving, 120°C, 20 min). WCS and HS particles differ in their morphological (size and shape) and physicochemical properties. The sterilization modified markedly the shape, size and aggregation state of WCS nanoparticles. Both particles were readily internalized by osteoblastic cells by endocytosis, and showed a low intracellular dissolution rate. Concentrations of WCS and HS particles less than 500 µg ml(-1) did not affect cell proliferation, F-actin cytoskeleton organization and apoptosis rate and increased the gene expression of alkaline phosphatase and BMP-2. The two particles presented some differences in the elicited cell response. In conclusion, WCS and HS particles might exhibit an interesting profile for bone tissue applications. Results suggest the relevance of a proper particle characterization, and the interest of an individual nanoparticle targeted research.

[Classification of disposable medical plastics and search for alternatives without polyvinyl chloride in the Hospital Virgen de las Nieves (Granada, Spain)]. / Clasificación de materiales plásticos sanitarios desechables y búsqueda de alternativas sin policloruro de vinilo en el Hospital Virgen de las Nieves.

OBJECTIVES: To identify and classify disposable hospital products containing polyvinyl chloride (PVC), including the search and evaluation of cost-effective sustainable alternative products free of PVC. METHODS: A descriptive observational analysis was performed, after classifying the latest research in major databases, and disposable products that could contain PVC. These were divided into 5 groups: cannulas, catheters, tubes, bags, and equipment, purchased in the period 2008-2009, differentiating between the technical and economic assessment of the materials. RESULTS: In the analysis of the composition of 492 articles selected, 234 (47.5%) contained PVC, and 19.4% were considered PVC-free alternatives, with only 11.3% of these being economically viable. CONCLUSIONS: This study highlights the advantages of the classification of PVC products, by showing that safe and efficient alternatives exist for some product lines that are consistent with patient safety and quality in the work by doctors.

Physical inactivity is a major contributor to ovariectomy-induced sarcopenia.

Since the mechanism(s) underlying menopause-related sarcopenia remain unknown we aimed to investigate the role of physical inactivity in its etiology. Ovariectomized and sham-operated rats were allocated into 2 experimental groups: (1) sedentary-standard housing; and (2) exercise-housed with running wheel. After a 9-month experimental period, soleus muscle structure and biochemical properties were analyzed. No differences existed in muscle fibre size or ultrastructure between sedentary sham and ovariectomized animals housed in standard conditions. In the exercise groups, average daily running distance was 10-fold less in ovariectomized compared to sham-animals. Further, in exercised animals, soleus fibre size was smaller in ovariectomized compared to sham-animals. Nonetheless, compared to both sedentary groups, muscle fibre size was larger in the exercised ovariectomized animals. Our results indicate that ovariectomy-induced sarcopenia is not due to the loss of ovarian hormones per se, but is largely due to physical inactivity.

The effect of age on glucose uptake and GLUT1 and GLUT4 expression in rat skeletal muscle.

During the life span, phenotypic and structural modifications on skeletal muscle contribute to a reduction on glucose uptake either in basal state or triggered by insulin, but the underlying mechanisms for this decline are not entirely identified. A reduction in the expression of skeletal muscle glucose transporters (GLUTs), glucose transporter type 1 (GLUT1) and glucose transporter type 4 (GLUT4), has been associated to such phenomena, but unlike the case of insulin, only few studies have addressed the effect of age on muscle-contraction-induced glucose uptake. The aim of the study was to investigate the influence of age on GLUT1 and GLUT4 expression in skeletal muscle and its relation to the glucose uptake induced by muscle contraction. For this purpose, soleus muscle from Wistar rats aged 4, 10, 22 and 42 weeks were isolated and electrically stimulated (30 min, 10 Hz, 20 V, 0.2 ms). After stimulation, glucose uptake and GLUT1 and GLUT4 expression and localisation were evaluated. Muscle contraction caused an increase in glucose uptake in all studied groups. In addition, the absolute rates of glucose uptake were negatively correlated with age. The expression of GLUT4 was lower in older animals, whereas no relation between age and GLUT1 expression was found. Immunohistochemistry confirmed the ontogenic effect on GLUT4 expression and suggested an age-related modification on GLUT1 distribution within the muscle fibres; for instance, this protein seems to be present mainly out of the sarcoplasm. The present findings demonstrate that the ability of muscle contraction to increase glucose uptake is not influenced by age, whereas glucose uptake under basal conditions decreases with age.

Exercise training increases interleukin-10 after an acute myocardial infarction: a randomised clinical trial.

The present study assessed the effects of exercise training on biomarkers of inflammation in postinfarction patients. This single-centre prospective randomized controlled trial encompassed 42 patients after the first myocardial infarction divided into exercise-training (n=22) or usual care (n=20) groups. Complete randomization was performed by choosing one of 2 sealed envelopes. The exercise-training group participated in an 8-week programme comprising 3 aerobic exercise sessions per week. The control group received usual care. The main measures were changes in circulating levels of C-reactive protein, interleukin (IL)-6 and -10, soluble vascular cell adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1 (ICAM-1), anthropometrics, dietary intake, daily physical activity, and cardiorespiratory fitness. 4 patients terminated the study prematurely, leaving 38 for the statistical analysis (exercise-training, n=20; control group, n=18). In comparison to control group, exercise-training group improved IL-10 levels [1.7(7.0) vs. - 0.3(2.4) pg/mL, P<0.05], daily moderate-intensity physical activity (12.9±21.3 vs. - 0.7±13.4 min, P<0.05), and cardiorespiratory fitness (3.0±3.5 vs. 0.3±4.1 ml/min/kg, P<0.05). Additionally, the change in VCAM-1 and ICAM-1 levels was significantly higher in the control group (respectively, 26.6±112.1 vs. 94.1±90.0 ng/mL and 7.3±41.0 vs. 35.0±39 ng/mL, P<0.05). In conclusion, exercise training improved the inflammatory profile in post myocardial infarction patients by enhancing the anti-inflammatory cytokine IL-10.

Antioxidant properties and associated mechanisms of salicylates.

The pharmacological action of salicylates has been historically related to their ability to inhibit cyclooxygenases, thereby blocking the synthesis of prostaglandins and thromboxane A2. On the other hand, several studies have suggested that salicylates have a multitude of cyclooxygenase-independent actions specially related with their antioxidant properties, which might contribute to the overall salutary effects of these compounds. Although salicylates are well-known antioxidants through their ability to scavenge hydroxyl radical, their antioxidant mechanisms of action have not been fully compiled and characterized. In this context, several mechanisms of action have been suggested, namely i) scavenging of hydroxyl radical and chelation of transition metals; ii) upregulation of nitric oxide; iii) increased synthesis of lipoxins; iv) inhibition of neutrophil oxidative burst; v) inhibition of NF-κB and AP-1 protein kinases; and vii) inhibiton of lectin-like oxidized LDL receptor-1. The newly discovered acetyl salicylic acid-triggered lipoxins probably play a key role in the maintenance of the oxidative stress balance. Furthermore, salicylates have shown to protect low-density lipoprotein from oxidation and elicit an inhibitory effect on the expression of lectin-like receptors on endothelial cells. This review aims to provide an overview of the various proposed antioxidant mechanisms of salicylates.

Lifelong sedentary behaviour and femur structure.

The aim of the present study was to analyze the lifelong differences of femur structure in sedentary and physically active animal models. Thirty male C57BL/6 mice, 2 months old, were either: i) housed in cages with running wheel (AA; n=10), ii) housed in cages without running wheel (AS; n=10), iii) or sacrificed without intervention (Y; n=10). AA and AS animals were sacrificed after 23 months of housing. Right femur structure was analyzed in all animals by histomorphometry. Significant differences in several microarchitectural parameters of cancellous and cortical bone were identified between Y mice and both groups of aged mice, as well as between AA and AS groups. Lifelong physically active mice had significantly higher cancellous bone surface (Cn.BS) and trabecular number (Tb.N) and decreased trabecular separation (Tb.Sp) at both epiphyses when compared to AS animals. No differences were observed between Y and AA groups regarding osteocyte number (N.Ot) despite its significant reduction in AS animals, suggesting that age alone was not a cause for decreases in N.Ot. Our results suggest that the reduced bone quality observed in the elderly is not only a consequence of age but also of lack of physical activity since sedentary behaviour significantly aggravated the degenerative age-related bone differences.

Collection of biological samples in forensic toxicology.

Forensic toxicology is the study and practice of the application of toxicology to the purposes of the law. The relevance of any finding is determined, in the first instance, by the nature and integrity of the specimen(s) submitted for analysis. This means that there are several specific challenges to select and collect specimens for ante-mortem and post-mortem toxicology investigation. Post-mortem specimens may be numerous and can endow some special difficulties compared to clinical specimens, namely those resulting from autolytic and putrefactive changes. Storage stability is also an important issue to be considered during the pre-analytic phase, since its consideration should facilitate the assessment of sample quality and the analytical result obtained from that sample. The knowledge on degradation mechanisms and methods to increase storage stability may enable the forensic toxicologist to circumvent possible difficulties. Therefore, advantages and limitations of specimen preservation procedures are thoroughfully discussed in this review. Presently, harmonized protocols for sampling in suspected intoxications would have obvious utility. In the present article an overview is given on sampling procedures for routinely collected specimens as well as on alternative specimens that may provide additional information on the route and timing of exposure to a specific xenobiotic. Last, but not least, a discussion on possible bias that can influence the interpretation of toxicological results is provided. This comprehensive review article is intented as a significant help for forensic toxicologists to accomplish their frequently overwhelming mission.