Renal Dysfunction Phenotypes in Patients Undergoing Obesity Surgery

Obesity surgery candidates are at an increased risk of kidney injury, but pre-operative evaluation usually neglects kidney function assessment. This study aimed to identify renal dysfunction in candidates for bariatric surgery. To reduce the sources of bias, subjects with diabetes, prediabetes under metformin treatment, neoplastic or inflammatory diseases were excluded. Patients' (n = 192) average body mass index was 41.7 +/- 5.4 kg/m(2). Among these, 51% (n = 94) had creatinine clearance over 140 mL/min, 22.4% (n = 43) had proteinuria over 150 mg/day and 14.6% (n = 28) albuminuria over 30 mg/day. A creatinine clearance higher than 140 mL/min was associated with higher levels of proteinuria and albuminuria. Univariate analysis identified sex, glycated hemoglobin, uric acid, HDL and VLDL cholesterol as being associated with albuminuria, but not with proteinuria. On multivariate analysis, glycated hemoglobin and creatinine clearance as continuous variables were significantly associated with albuminuria. In summary, in our patient population prediabetes, lipid abnormalities and hyperuricemia were associated with albuminuria, but not with proteinuria, suggesting different disease mechanisms might be implicated. Data suggest that in obesity-associated kidney disease, tubulointerstitial injury precedes glomerulopathy. A significant proportion of obesity surgery candidates present clinically relevant albuminuria and proteinuria along with renal hyperfiltration, suggesting that routine pre-operative assessment of these parameters should be considered

Predicting cortical bone adaptation to axial loading in the mouse tibia

The development of predictive mathematical models can contribute to a deeper understanding of the specific stages of bone mechanobiology and the process by which bone adapts to mechanical forces. The objective of this work was to predict, with spatial accuracy, cortical bone adaptation to mechanical load, in order to better understand the mechanical cues that might be driving adaptation. The axial tibial loading model was used to trigger cortical bone adaptation in C57BL/6 mice and provide relevant biological and biomechanical information. A method for mapping cortical thickness in the mouse tibia diaphysis was developed, allowing for a thorough spatial description of where bone adaptation occurs. Poroelastic finite-element (FE) models were used to determine the structural response of the tibia upon axial loading and interstitial fluid velocity as the mechanical stimulus. FE models were coupled with mechanobiological governing equations, which accounted for non-static loads and assumed that bone responds instantly to local mechanical cues in an on–off manner. The presented formulation was able to simulate the areas of adaptation and accurately reproduce the distributions of cortical thickening observed in the experimental data with a statistically significant positive correlation (Kendall's τ rank coefficient τ = 0.51, p < 0.001). This work demonstrates that computational models can spatially predict cortical bone mechanoadaptation to a time variant stimulus. Such models could be used in the design of more efficient loading protocols and drug therapies that target the relevant physiological mechanisms

Light activated antimicrobial agents can inactivate oral malodour causing bacteria.

Oral malodour is a common condition which affects a large proportion of the population, resulting in social, emotional and psychological stress. Certain oral bacteria form a coating called a biofilm on the tongue dorsum and degrade organic compounds releasing volatile sulfur compounds that are malodourous. Current chemical treatments for oral malodour such as mouthwashes containing chlorhexidine or essential oils, are not sufficiently effective at reducing the bacterial load on the tongue. One potential alternative to current chemical treatments for oral malodour is the use of light activated antimicrobial agents (LAAAs), which display no toxicity or antimicrobial activity in the dark, but when exposed to light of a specific wavelength produce reactive oxygen species which induce damage to target cells in a process known as photodynamic inactivation. This study aimed to determine whether oral malodour causing bacteria were susceptible to lethal photosensitization. Five bacterial species that are causative agents of oral malodour were highly sensitive to lethal photosensitization and were efficiently killed by methylene blue in conjunction with 665 nm laser light. Between 4.5-5 log10 reductions in the number of viable bacteria were achieved with 20 µM methylene blue and 14.53 J cm(-2) laser light for Porphyromonas gingivalis, Prevotella intermedia, Peptostreptococcus anaerobius and Solobacterium moorei. The number of viable cells fell below the limit of detection in the case of Fusobacterium nucleatum. These findings demonstrate that methylene blue in combination with 665 nm laser light is effective at killing bacteria associated with oral malodour, suggesting photodynamic therapy could be a viable treatment option for oral malodour

Can the mitochondrial malondialdehyde content be an useful tool to distinguish ecological quality of Petromyzon marinus habitat?

The sea lamprey is an anadromous species that migrates twice during its life cycle between freshwater and seawater. Microphagous larvae generally spend 4–5 years burrowed in the substrate of rivers and streams before undergoing metamorphosis that ends with the beginning of the juvenile trophic migration. Once metamorphosis is complete, sea lamprey juvenile downstream migrants are fully tolerant to 35 PSU seawater. Pollution resulting from industrial effluents may disturb the seawater acclimatization causing oxidative damages, and ultimately may lead to a decrease of sea lamprey population. The aim of this study was to compare salt acclimation of sea lamprey juveniles captured in river basins with different levels of aquatic pollution, using mitochondrial glutathione and malondialdehyde of gills and liver as markers of physiological stress and cell damages. The results showed that juveniles from Lima basin exhibited the highest levels of mitochondrial malondialdehyde in gills, even though significant changes in the stress markers of mitochondrial gills of all animals subject to salt acclimation were not detected. In addition, an increase in the oxidative damages of hepatic mitochondria of macrophthalmia from Vouga basin suggests the occurrence of metabolic failures with the potential to disturb the capacity to adaptation to the marine environment

Hepatic mitochondrial content in malondialdehyde may be a marker of sea lamprey contact with atrazine

The atrazine attracts special attention as pollutant because of itspersistence in the aquatic environment. Although this herbicide has been studied in teleost, its toxicity in the sea lamprey, Petromyzon marinus is still poorly understood. Oxidative stress may occur if chemical pollutants contribute to block the capacity of mitochondria to generate ATP with continuous production of reactive oxygen species (ROS), disturbing the success of P. marinus seawater acclimation. So, the aim of this study was to evaluate how atrazine influences the malondialdehyde (MDA), glutathione (GSH) and glutathione disulfide (GSSG) contents of gills and liver mitochondria of juveniles from Lima river basin, Portugal during salt acclimation. Sampling occurred at the beginning of the P. marinus downstream migration. The sampled juveniles were transported alive to the laboratory and maintained in 200 l tanks with LSS 8 life support system. Two groups of 40 specimens were hold in tanks with 50 or 100 lg/l atrazine, during 30 days. The salinity was gradually increased from 0 to 35 psu,following a three step procedure during a 30 days period. The control group was maintained in freshwater without atrazine. Mitochondria obtained by centrifugation at 15000 g, 30 min, 4°C, of tissues homogenates prepared in 50 mM Tris-HCl pH 7.5 buffer were used in determination of ROS, MDA, GSH and GSSG by fluorescence. The statistical analysis were performed by ANOVA I and Duncan (p < 0.05), using SPSS 22 for Windows.The results showed that in P. marinus juveniles, no significant changes in the markers of oxidative stress and cell damages were detected in the mitochondrial gills. Nevertheless, in the animals exposed to 50 lg/l atrazine the content in glutathione and GSSG increased. A similar pattern of stress markers was detected in hepatic mitochondria. However, in the presence of atrazine, the MDA level of the mitochondria of liver increased threefold in the animals during salt acclimation. The high level of mitochondrial damages, detected in the hepatic mitochondria of macrophthalmia treated with atrazine, suggests that herbicide exposure caused metabolic failures which can disturb the adaptation of these specimens to the oceanic feeding phase. The hepatic mitochondrial MDA levels of P. marinus, may eventually detect sea lamprey contact with chlorine herbicides

Time spent with cats is never wasted: Lessons learned from feline acromegalic cardiomyopathy, a naturally occurring animal model of the human disease

<div><p>Background</p><p>In humans, acromegaly due to a pituitary somatotrophic adenoma is a recognized cause of increased left ventricular (LV) mass. Acromegalic cardiomyopathy is incompletely understood, and represents a major cause of morbidity and mortality. We describe the clinical, echocardiographic and histopathologic features of naturally occurring feline acromegalic cardiomyopathy, an emerging disease among domestic cats.</p><p>Methods</p><p>Cats with confirmed hypersomatotropism (IGF-1>1000ng/ml and pituitary mass; n = 67) were prospectively recruited, as were two control groups: diabetics (IGF-1<800ng/ml; n = 24) and healthy cats without known endocrinopathy or cardiovascular disease (n = 16). Echocardiography was performed in all cases, including after hypersomatotropism treatment where applicable. Additionally, tissue samples from deceased cats with hypersomatotropism, hypertrophic cardiomyopathy and age-matched controls (n = 21 each) were collected and systematically histopathologically reviewed and compared.</p><p>Results</p><p>By echocardiography, cats with hypersomatotropism had a greater maximum LV wall thickness (6.5mm, 4.1–10.1mm) than diabetic (5.9mm, 4.2–9.1mm; Mann Whitney, p<0.001) or control cats (5.2mm, 4.1–6.5mm; Mann Whitney, p<0.001). Left atrial diameter was also greater in cats with hypersomatotropism (16.6mm, 13.0–29.5mm) than in diabetic (15.4mm, 11.2–20.3mm; Mann Whitney, p<0.001) and control cats (14.0mm, 12.6–17.4mm; Mann Whitney, p<0.001). After hypophysectomy and normalization of IGF-1 concentration (n = 20), echocardiographic changes proved mostly reversible. As in humans, histopathology of the feline acromegalic heart was dominated by myocyte hypertrophy with interstitial fibrosis and minimal myofiber disarray.</p><p>Conclusions</p><p>These results demonstrate cats could be considered a naturally occurring model of acromegalic cardiomyopathy, and as such help elucidate mechanisms driving cardiovascular remodeling in this disease.</p></div

Ultraprecise single-molecule localization microscopy enables in situ distance measurements in intact cells

Single-molecule localization microscopy (SMLM) has the potential to quantify the diversity in spatial arrangements of molecules in intact cells. However, this requires that the single-molecule emitters are localized with ultrahigh precision irrespective of the sample format and the length of the data acquisition. We advance SMLM to enable direct distance measurements between molecules in intact cells on the scale between 1 and 20 nm. Our actively stabilized microscope combines three-dimensional real-time drift corrections and achieves a stabilization of <1 nm and localization precision of ∼1 nm. To demonstrate the biological applicability of the new microscope, we show a 4- to 7-nm difference in spatial separations between signaling T cell receptors and phosphatases (CD45) in active and resting T cells. In summary, by overcoming the major bottlenecks in SMLM imaging, it is possible to generate molecular images with nanometer accuracy and conduct distance measurements on the biological relevant length scales

ANÁLISE DO CONHECIMENTO DOS ACADÊMICOS DA UNIEVANGÉLICA SOBRE O FLÚOR

O  flúor  é  utilizado  na  prevenção  e  controle  da  doença  cárie, pois interfere no processo de desmineralização e remineralização dos dentes. O  conhecimento  sobre  os  métodos  de  utilização  do  flúor  e  seus  efeitos  é importante  para  toda  a  população  para  que  o  flúor  seja  utilizado  de  maneira adequada.

Improved methods for detection of β-galactosidase (lacZ) activity in hard tissue

The ß-galactosidase gene (lacZ) of Escherichia coli is widely used as a reporter gene. The expression of lacZ can be detected by enzyme-based histochemical staining using chromogenic substrates such as 5-bromo-4-chloro-3-indolyl-ß-D: -galactoside (X-gal). Because the enzymatic activity of lacZ is vulnerable to high temperatures and acid treatment for demineralization, detection of lacZ on paraffinized sections is difficult, especially for hard tissues, which require demineralization before sectioning in paraffin. To circumvent this problem, whole-mount X-gal staining before sectioning is performed. However, detection of lacZ activity in the center of larger portions of hard whole adult tissues is challenging. In this study, focusing on fixation procedures, we determined the conditions conducive to improved detection of lacZ activity in deeper areas of whole tissues. We used an annexin a5 (Anxa5)-lacZ reporter mouse model in which the Anxa5 expression in hard tissue is indicated by lacZ activity. We found that lacZ activity could be detected throughout the periodontal ligament of adult mice when fixed in 100% acetone, whereas it was not detected in the periodontal ligament around the root apex fixed in glutaraldehyde and paraformaldehyde. This staining could not be detected in wild-type mice. Acetone maintains the lacZ activity within 48 h of fixation at both 4°C and at room temperature. In conclusion, acetone is the optimal fixative to improve permeability for staining of lacZ activity in large volumes of adult hard tissues