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1.
J Family Med Prim Care ; 12(9): 2042-2046, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38024925

RESUMO

Introduction: PICU admission of a child may cause anxiety and stress among the caregivers. The criteria for admission to a PICU are terrifying and may legitimately cause parents to fear that their child may pass away or suffer a serious disability. They may be overburdened with stress and anxiety of illness and compliment medical information while trying to maintain a balance with other family demands. They must learn coping mechanisms and use resources to stay stable when they face challenges. Evidence on the coping mechanisms used by primary caregivers to control their stress and anxiety is scarce so this study assessed the anxiety and coping mechanism among the primary caregivers of children admitted in PICU. Materials and Methods: A cross-sectional study was conducted among 143 primary caregivers by using convenience sampling technique at PICU, AIIMS, Jodhpur, from April 31, 2021, to January 20, 2022. The participants were enrolled after obtaining informed consent and were interviewed by the researcher. Results: Study findings revealed that primary caregivers had 38% severe anxiety, 54% moderate anxiety, and 8% mild anxiety. They used emotion-focused coping (43.5%) followed by problem focused coping (37.2%) and avoidant coping (19.3%). Also, there was a significant association found between anxiety of primary caregivers and gender of the child (P = 0.012). Conclusion: Anxiety and stress are one of the expected psychological problems faced by caregivers of children admitted in PICU. Healthcare workers must make concerted attempts to support caregivers adaptive coping mechanisms, so they can retain a sense of balance.

2.
J Biochem Mol Toxicol ; 37(3): e23283, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36541368

RESUMO

Multiwalled carbon nanotubes (MWCNTs) have been used in biomedical applications due to their ability to enter the cells. Carboxylic functionalization of MWCNT (MWCNT-COOH) is used to mitigate the toxicity of MWCNTs. Our study focuses on comparing the toxicity of MWCNT and MWCNT-COOH on the neuronal cells, LN18. Concentrations of 5, 10, 20, and 40 µg ml-1 were used for the study, and cytotoxicity was determined at 0, 1, 3, 6, 12, 24, and 48 h of incubation. Cell viability was assessed by Trypan Blue, MTT, and Live dead cell assays, and the oxidative stress produced was determined by reactive oxygen species (ROS) and Lipid peroxidation assays. MWCNT-COOH showed higher cell viability than MWCNT for 20 and 40 µg ml-1 at 24 and 48 h. This was also visually observed in the live dead cell imaging. However, at 48 h, the morphology of the cells appeared more stretched for all the concentrations of MWCNT and MWCNT-COOH in comparison to the control. A significant amount of ROS production can also be observed at the same concentration and time. Viability and oxidative stress results together revealed that MWCNT-COOH is less toxic when compared to MWCNT at longer incubation periods and higher concentrations. However, otherwise, the effect of both are comparable. A concentration of 5-10 µg ml-1 is ideal while using MWCNT and MWCNT-COOH as the toxicity is negligible. These findings can further be extended to various functionalizations of MWCNT for wider applications.


Assuntos
Citotoxinas , Nanotubos de Carbono , Neurônios , Linhagem Celular Tumoral , Humanos , Nanotubos de Carbono/toxicidade , Espécies Reativas de Oxigênio/análise , Citotoxinas/toxicidade , Neurônios/efeitos dos fármacos , Estresse Oxidativo , Sobrevivência Celular/efeitos dos fármacos
3.
J Phys Chem Lett ; 13(18): 4125-4132, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35506614

RESUMO

Supported noble metals offer key advantages over homogeneous catalysts for in vivo applications of parahydrogen-based hyperpolarization. However, their performance is compromised by randomization of parahydrogen spin order resulting from rapid hydrogen adatom diffusion. The diffusion on Pt surfaces can be suppressed by introduction of Sn to form Pt-Sn intermetallic phases. Herein, an unprecedented pairwise selectivity of 19.7 ± 1.1% in the heterogeneous hydrogenation of propyne using silica encapsulated Pt-Sn intermetallic nanoparticles is reported. This high level of selectivity exceeds that of all supported metal catalysts by at least a factor of 3. Moreover, the pairwise selectivity for alkyne hydrogenation is about 2 times higher than for alkene hydrogenation, an observation attributed to the higher coverage of the former and its effect on diffusion. Lastly, PtSn@mSiO2 nanoparticles exhibited improved coking resistance, and any loss of activity is shown to be fully reversible through high-temperature oxidation-reduction cycling.


Assuntos
Nanopartículas , Platina , Hidrogenação , Espectroscopia de Ressonância Magnética , Dióxido de Silício , Estanho
4.
Pharmaceutics ; 14(4)2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35456529

RESUMO

The ability to predict formulation behaviour at production scale during formulation design can reduce the time to market and decrease product development costs. However, it is challenging to extrapolate compaction settings for direct compression formulations between tablet press models during scale-up and transfer from R&D to commercial production. The aim of this study was to develop statistical process models to predict tablet tensile strength, porosity and disintegration time from compaction parameters (pre-compression and main compression force, and press speed), for three formulations, with differing deformation characteristics (plastic, brittle and elastic), on three tablet press models (one pilot-scale tablet press (KG RoTab) and two production-scale presses (Fette 1200i and GEA Modul P)). The deformation characteristics of yield pressure and elastic recovery were determined for the model placebo formulations investigated. To facilitate comparison of dwell time settings between tablet press models, the design of experiments (DoE) approach was 9 individual 16-run response surface DoEs (3 formulation × 3 press models), whose results were combined to create a polynomial regression model for each tablet property. These models predicted tablet tensile strength, porosity and disintegration time and enabled the construction of design spaces to produce tablets with specified target properties, for each formulation on each press. The models were successfully validated. This modelling approach provides an understanding of the compaction behaviour of formulations with varying deformation behaviour on development and commercial tablet press models. This understanding can be applied to inform achievable production rates at a commercial scale, during the formulation development.

5.
J Educ Health Promot ; 11: 24, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281390

RESUMO

BACKGROUND: The corona virus disease-2019 (COVID-19) infection is a current public health crisis, and it is challenging to the world health-care system. As there is no treatment, prevention is the crucial importance to break the chain of transmission of infection and prevent fatality among the high-risk populations. The aim of the study was to assess the Expressed COVID-19 preventive practices among health-care workers (HCWs) and the public visiting tertiary care hospital, AIIMS, Jodhpur. METHODOLOGY: A cross-sectional study was conducted among 406 HCWs and 238 public, recruited by convenient sampling technique. A validated and pretested self-structured practice questionnaire used to collect the data regarding COVID-19 preventive practice. The data were collected through online Google Forms and interview techniques and analyzed by software SPSS 26 version. RESULTS: Majority of 87.7% HCWs and 76.5% public always followed practice of hand wash with soap and water and sanitize for 20 s. Majority of 79.6% HCWs and 49.2% public maintain social distance in public place. Gender (χ 2 = 18.806 P ≤ 0.001) and education (χ 2 = 43.270 P ≤ 0.001) among HCWs and in public demographic variable income (χ 2 = 21.102 P = 0.002), religion (χ 2 = 13.302 P = 0.006) and source of information (χ 2 = 17.030 P = 0.026) was significantly associated with level of COVID-19 preventive practice. CONCLUSION: The study showed moderate level of COVID-19 preventive practice among HCWs and public. Based on this result, an effective IEC intervention programs can be designed to educate public and HCWs and follow a safe COVID-19 preventive practice.

6.
Wirel Pers Commun ; 124(3): 2261-2270, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35035106

RESUMO

Corona Virus continues to harms its effects on the people lives across the globe. The screening of infected persons has to be identified is a vital step because it is a fast and low-cost way. Certain above mentioned things can be recognized by chest X-ray images that plays a significant role and also used for examining in detection of CORONA VIRUS(COVID-19). Here radiological chest X-rays are easily available with low cost only. In this survey paper, Convolutional Neural Network(CNN) based solution that will benefit in detection of the Covid-19 positive patients using radiography chest X-Ray images. To test the efficiency of the solution, using data sets of publicly available X-Ray images of Corona virus positive cases and negative cases. Images of positive Corona Virus patients and pictures of healthy person images are divided into testing images and trainable images. The solution which are providing the good results with classification accuracy within the test set-up. Then GUI based application supports for medical examination areas. This GUI application can be used on any computer and performed by any medical examiner or technician to determine Corona Virus positive patients using radiography X-ray images. The result will be precisely obtaining the Covid-19 Patient analysis through the chest X-ray images and also results may be retrieve within a few seconds.

7.
Pharmaceutics ; 13(7)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34371725

RESUMO

Optimizing processing conditions to achieve a critical quality attribute (CQA) is an integral part of pharmaceutical quality by design (QbD). It identifies combinations of material and processing parameters ensuring that processing conditions achieve a targeted CQA. Optimum processing conditions are formulation and equipment-dependent. Therefore, it is challenging to translate a process design between formulations, pilot-scale and production-scale equipment. In this study, an empirical model was developed to determine optimum processing conditions for direct compression formulations with varying flow properties, across pilot- and production-scale tablet presses. The CQA of interest was tablet weight variability, expressed as percentage relative standard deviation. An experimental design was executed for three model placebo blends with varying flow properties. These blends were compacted on one pilot-scale and two production-scale presses. The process model developed enabled the optimization of processing parameters for each formulation, on each press, with respect to a target tablet weight variability of <1%RSD. The model developed was successfully validated using data for additional placebo and active formulations. Validation formulations were benchmarked to formulations used for model development, employing permeability index values to indicate blend flow.

8.
Nanoscale ; 12(15): 8519-8524, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32242595

RESUMO

The molecular basis for the high cis-alkene selectivity over intermetallic PtSn for alkyne semi-hydrogenation is demonstrated. Unlike the universal assumption that the bimetallic surface is saturated with atomic hydrogen, molecular hydrogen has a higher barrier for dissociative adsorption on intermetallic PtSn due to the deficiency of Pt three-fold sites. The resulting molecular behavior of adsorbed hydrogen on intermetallic PtSn nanoparticles leads to pairwise-hydrogenation of three alkynes to the corresponding cis-alkenes, satisfying both high stereoselectivity and high chemoselectivity.

9.
Nanoscale ; 11(12): 5336-5345, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30843547

RESUMO

The outstanding catalytic activity and chemical selectivity of intermetallic compounds make them excellent candidates for heterogeneous catalysis. However, the kinetics of their formation at the nanoscale is poorly understood or characterized, and precise control of their size, shape and composition during synthesis remains challenging. Here, using well-defined Pt nanoparticles (5 nm and 14 nm) encapsulated in mesoporous silica, we study the transformation kinetics from monometallic Pt to intermetallic PtSn at different temperatures by a series of time-evolution X-ray diffraction studies. Observations indicate an initial transformation stage mediated by Pt surface-controlled intermixing kinetics, followed by a second stage with distinct transformation kinetics corresponding to a Ginstling-Brounstein (G-B) type bulk diffusion mode. Moreover, the activation barrier for both surface intermixing and diffusion stages is obtained through the development of appropriate kinetic models for the analysis of experimental data. Our density-functional-theory (DFT) calculations provide further insights into the atomistic-level processes and associated energetics underlying surface-controlled intermixing.

10.
Mol Pharm ; 15(1): 31-39, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-28926716

RESUMO

The ability of broadband acoustic resonance dissolution spectroscopy (BARDS) to assess the wettability of powder blends is investigated. BARDS is a novel analytical technology developed on the basis of the change in acoustic phenomena observed when material is added into a solvent under resonance. Addition of solid material to the solvent results in the introduction of gas (air) into the solvent, changing the compressibility of the solvent system, and reducing the velocity of sound in the solvent. As a material is wetted and dissolved, the gas is released from the solvent and resonance frequency is altered. The main purpose of this work is to demonstrate the ability of BARDS to assess differences in the wetting behavior of tablet excipients (microcrystalline cellulose (MCC) and magnesium stearate (MgSt)) and a model drug (metoclopramide hydrochloride) as single component powders and multicomponent powder blends. BARDS acoustic responses showed a prolonged release of gas for the powdered blends with lubricant compared to unlubricated blends. As the elimination of gas from the solvent was assumed to follow first order elimination kinetics, a compressible gas elimination rate constant was calculated from the log plots of the gas volume profiles. The gas elimination rate constant was used as a parameter to compare the release of gas from the powder introduced to the solvent and hence the powder wetting behavior. A lower gas elimination rate constant was measured for lubricated blends compared to nonlubricated blends, suggesting the prolonged hydration of lubricated blends. Standard wetting techniques such as contact angle measurements and wetting time analysis were also used to analyze the blends and confirmed differences in wetting behavior determined by BARDS. The study results demonstrate the capability of BARDS as a rapid, analytical tool to determine the wetting behavior of the pharmaceutical powder blends and the potential of BARDS as a process analytical technology (PAT) tool.


Assuntos
Pós/química , Análise Espectral/métodos , Ácidos Esteáricos/química , Molhabilidade
11.
Jt Comm J Qual Patient Saf ; 43(3): 138-145, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28334592

RESUMO

BACKGROUND: The metric "Unplanned returns to operating room (ROR)" is being tracked in surgical quality dashboards; 70% of unplanned RORs may be related to surgical complications. With increasing regionalization of trauma and complex surgical care at tertiary care academic centers, it is unclear if a simple ROR metric is a valid assessment of surgical quality at such centers. METHOD: A real-time electronic tool was used to identify all RORs-planned and unplanned-in a high-volume, high-complexity academic surgical practice at Mayo Clinic-Rochester within 45 days of the index operation. Analysis by ROR type and indication was performed. RESULTS: During the analysis period (June 2014-February 2015) 44,031 operations were performed, with 5,552 subsequent RORs (13%). Of all RORs, 51% (n = 2,818) were planned staged returns, 29% (n = 1,589) were unrelated, 15% (n = 830) were unplanned and 6% (n = 315) were planned because of previous complications. Overall, unplanned reoperations were uncommon (n = 830, 2% of all operations). The most common indications for unplanned RORs included "other" (32%, n = 266), bleeding related (24%, n = 198) and wound complications (20%, n = 166). CONCLUSION: In a high-volume, high-complexity academic surgical practice, RORs occurred after 13% of cases. Unplanned returns were infrequent and usually were associated with complications; most RORs were planned staged or unrelated returns. A simple ROR metric that does not consider planned/unrelated returns is likely not a valid surgical quality measure. Electronic tools designed specifically to identify in real-time RORs, associated indication, and clinical validation should provide more reliable data for public reporting and quality improvement efforts.


Assuntos
Sistemas de Informação/organização & administração , Período Perioperatório , Melhoria de Qualidade/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Atenção Terciária à Saúde/estatística & dados numéricos , Centros Médicos Acadêmicos , Documentação , Humanos , Salas Cirúrgicas/organização & administração , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco
12.
Nanoscale ; 7(40): 16721-8, 2015 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-26399612

RESUMO

Metal nanostructures have attracted great attention in various fields due to their tunable properties through precisely tailored sizes, compositions and structures. Using mesoporous silica (mSiO2) as the inorganic capping agent and encapsulated Pt nanoparticles as the seeds, we developed a robust seeded growth method to prepare uniform bimetallic nanoparticles encapsulated in mesoporous silica shells (PtM@mSiO2, M = Pd, Rh, Ni and Cu). Unexpectedly, we found that the inorganic silica shell is able to accommodate an eight-fold volume increase in the metallic core by reducing its thickness. The bimetallic nanoparticles encapsulated in mesoporous silica shells showed enhanced catalytic properties and thermal stabilities compared with those prepared with organic capping agents. This inorganic capping strategy could find a broad application in the synthesis of versatile bimetallic nanostructures with exceptional structural control and enhanced catalytic properties.

13.
Environ Monit Assess ; 187(1): 4080, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25416966

RESUMO

The ancient scientific Sanskrit texts of Ayurveda (science of longevity) deal with waters, plants, and animals in relation to human health. Based on the studies mentioned in Ayurveda and modern literature, biological responses of grazing animals in Mangampeta barite mining area in Kadapa District, Andhra Pradesh, were studied. A non-mineralized Tirupati area in Chittoor District, Andhra Pradesh, was selected for the purpose of comparison. In these areas, certain animal products of selected grazing animals were studied if they could be used as tools in mineral exploration. Samples of dung, urine, and milk from cow, bullock, she-buffalo, he-buffalo, sheep, and goat were collected from these two areas during winter and summer seasons. Goat dung was found to have lowest moisture content and highest organic matter while goat urine contained highest amounts of organic matter and ash content. All these animal products were analyzed for 11 trace elements. The concentration of trace elements released through dung, urine, and milk widely varied in different animal species with seasonal variations. The elemental concentration was higher in dung and lower in urine, when compared to that of milk. The concentration of all elements in dung, urine, and milk of all animals, in both the areas, was higher in winter than that in summer. Dung represents the metabolic process of the whole animal and reflects the dietary conditions whether fed on natural or inorganic supplement. It can be inferred that dung, urine, and milk of any animal can be used as tools in mineral exploration during winter, while during summer, only dung can be useful. The dung of goat when compared to that of the other cattle serves as a better tool in environmental studies as goat depends almost entirely on natural vegetation without human interference.


Assuntos
Monitoramento Ambiental/métodos , Poluentes Ambientais/análise , Fezes/química , Herbivoria , Mineração , Animais , Sulfato de Bário , Bovinos , Dieta , Ciências da Terra , Poluentes Ambientais/metabolismo , Feminino , Humanos , Índia , Masculino , Leite/química , Plantas , Estações do Ano , Ovinos , Oligoelementos/análise
14.
ChemSusChem ; 6(10): 1915-22, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24039118

RESUMO

We report the synthesis, structural characterization, thermal stability study, and regeneration of nanostructured catalysts made of 2.9 nm Pt nanoparticles sandwiched between a 180 nm SiO2 core and a mesoporous SiO2 shell. The SiO2 shell consists of 2.5 nm channels that are aligned perpendicular to the surface of the SiO2 core. The nanostructure mimics Pt nanoparticles that sit in mesoporous SiO2 wells (Pt@MSWs). By using synchrotron-based small-angle X-ray scattering, we were able to prove the ordered structure of the aligned mesoporous shell. By using high-temperature cyclohexane dehydrogenation as a model reaction, we found that the Pt@MSWs of different well depths showed stable activity at 500 °C after the induction period. Conversely, a control catalyst, SiO2 -sphere-supported Pt nanoparticles without a mesoporous SiO2 shell (Pt/SiO2 ), was deactivated. We deliberately deactivated the Pt@MSWs catalyst with a 50 nm deep well by using carbon deposition induced by a low H2 /cyclohexane ratio. The deactivated Pt@MSWs catalyst was regenerated by calcination at 500 °C with 20 % O2 balanced with He. After the regeneration treatments, the activity of the Pt@MSWs catalyst was fully restored. Our results suggest that the nanostructured catalysts-Pt nanoparticles confined inside mesoporous SiO2 wells-are stable and regenerable for treatments and reactions that require high temperatures.


Assuntos
Nanopartículas Metálicas/química , Platina/química , Dióxido de Silício/química , Temperatura , Catálise , Cicloexanos/química , Etilenos/química , Hidrogenação , Porosidade
15.
Environ Monit Assess ; 185(12): 10431-40, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23892716

RESUMO

Biogeochemical characteristics of the cattle are dealt based on the observations made in Ayurveda in the light of modern scientific developments in applied environmental geochemistry. The biogeochemical characteristics of certain important ecological components and animal products of the stall-fed animals were studied. For this purpose, a dairy farm of Tirumala-Tirupati Devasthanams, a religious organization in Tirupati, Chittoor District, Andhra Pradesh was selected. This study is intended to trace out the trace element interactions in the ecological components (soil, water, fodder, feed) of the stall-fed animals and their output components viz. dung, urine and milk. Physical, physico-chemical properties and certain trace elements were determined for composite samples of ecological components and dung, urine, and milk of stall-fed animals. The variations in the distribution of pH and EC of urine and milk reflect the variations in their physico-chemical or hydro-chemical properties. As mentioned in Ayurveda, not only the properties of milk but also the properties of dung and urine reflect their diet and conditions of their habitat. Even though the diet is the same, the cows of different breeds yield milk of variable physical, physico-chemical properties and trace element composition which can be attributed to their body colour, substantiating Ayurveda.


Assuntos
Indústria de Laticínios , Monitoramento Ambiental , Poluentes Ambientais/análise , Oligoelementos/análise , Ração Animal/análise , Animais , Poluentes Ambientais/metabolismo , Índia , Leite/metabolismo , Solo/química
16.
J Am Chem Soc ; 135(26): 9592-5, 2013 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-23758405

RESUMO

The enhanced stability and modified electronic structure of intermetallic compounds provide discovery of superior catalysts for chemical conversions with high activity, selectivity, and stability. We find that the intermetallic NaAu2 is an active catalyst for CO oxidation at low temperatures. From density functional theory calculations, a reaction mechanism is suggested to explain the observed low reaction barrier of CO oxidation by NaAu2, in which a CO molecule reacts directly with an adsorbed O2 to form an OOCO* intermediate. The presence of surface Na increases the binding energy of O2 and decreases the energy barrier of the transition states.


Assuntos
Ligas/química , Monóxido de Carbono/química , Ouro/química , Sódio/química , Temperatura , Adsorção , Catálise , Oxirredução , Oxigênio/química , Teoria Quântica , Propriedades de Superfície
17.
J Dent Child (Chic) ; 79(2): 46-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22828756

RESUMO

PURPOSE: The purpose of this study was to volumetrically analyze the efficacy of root canal fillings in primary teeth using spiral computed tomography (CT). METHODS: Root canals in 30 primary maxillary and mandibular molars were instrumented with K files to size 30, and the volumes of the canals were then measured using spiral CT. The teeth were randomly divided into 3 groups of 10 each, and 18 of the canals in each group were evaluated with spiral CT after obturation with zinc oxide eugenol paste, Metapex and Vitapex. The filled volume in each canal was mea- sured using spiral CT, and the percentage of obturated volume (POV) was calculated. The pre- and post-mean canal volume values within each group and the POV of the 3 groups were statistically analyzed using one-way analysis of variance and paired t tests. RESULTS: Filler voids were seen in all groups, but there was a statistically significant difference (P <.001) in the calculated POV. Vitapex showed 95% POV compared to Metapex (88%) and ZOE (84%). CONCLUSION: Voids were seen in all 3 filling materials. Vitapex showed the maximum percentage of obturated volume among the 3 groups.


Assuntos
Dente Molar/diagnóstico por imagem , Dente Molar/cirurgia , Materiais Restauradores do Canal Radicular/uso terapêutico , Obturação do Canal Radicular/métodos , Tomografia Computadorizada Espiral , Dente Decíduo/diagnóstico por imagem , Dente Decíduo/cirurgia , Análise de Variância , Hidróxido de Cálcio , Criança , Cavidade Pulpar/diagnóstico por imagem , Humanos , Técnicas In Vitro , Distribuição Aleatória , Óleos de Silicone , Silicones , Cimento de Óxido de Zinco e Eugenol
18.
Am J Pathol ; 174(5): 1827-36, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19342370

RESUMO

Podocytopenia characterizes many forms of glomerular disease, preceding the development of glomerulosclerosis. While detachment of viable podocytes from the underlying glomerular basement membrane is an important mechanism of podocyte loss, the underlying factors involved remain unclear. Secreted protein acidic and rich in cysteine (SPARC), a matricellular protein with counteradhesive properties, is normally expressed at low levels by the podocyte but is markedly increased following podocyte injury. Accordingly, we elucidate the role of SPARC in mediating experimental crescentic glomerulonephritis by inducing passive nephrotoxic nephritis in SPARC(+/+) and SPARC(-/-) mice. By days 4, 7, and 21 following disease induction, podocyte number is better preserved, glomerulosclerosis is ameliorated, and proteinuria is reduced in SPARC(-/-) mice as compared with SPARC(+/+) littermates. Moreover, the preserved podocyte number in SPARC(-/-) mice correlates with reduced urinary levels of both nephrin and podocin. To establish a causal role for SPARC in mediating detachment, cultured SPARC(+/+) and SPARC(-/-) podocytes were subjected to mechanical strain as well as trypsin digestion, and detachment assays were performed. While podocytes lacking SPARC were more resistant to stretch-induced detachment, stable re-expression of SPARC restored detachment rates to levels comparable with SPARC(+/+) podocytes. Taken together, this study proves that SPARC plays a causal role in mediating podocyte detachment and accelerating glomerulosclerosis in experimental crescentic glomerulonephritis.


Assuntos
Modelos Animais de Doenças , Glomerulonefrite/fisiopatologia , Osteonectina/fisiologia , Animais , Células Cultivadas , Progressão da Doença , Immunoblotting , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Podócitos/metabolismo , Podócitos/patologia
19.
Nephrol Dial Transplant ; 24(2): 404-12, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18820279

RESUMO

BACKGROUND: Clinical studies suggest that statins reduce proteinuria and slow the decline in kidney function in chronic kidney disease. Given a rich literature identifying podocyte apoptosis as an early step in the pathophysiological progression to proteinuria and glomerulosclerosis, we hypothesized that rosuvastatin protects podocytes from undergoing apoptosis. Regarding a potential mechanism, our lab has shown that the cell cycle protein, p21, has a prosurvial role in podocytes and there is literature showing statins upregulate p21 in other renal cells. Therefore, we queried whether rosuvastatin is prosurvival in podocytes through a p21-dependent pathway. METHODS: Two independent apoptotic triggers, puromycin aminonucleoside (PA) and adriamycin (ADR), were used to induce apoptosis in p21 +/+ and p21 -/- conditionally immortalized mouse podocytes with or without pre-exposure to rosuvastatin. Apoptosis was measured by two methods: Hoechst 33342 staining and fluorescence-activated cell sorting (FACS). To establish a role for p21, p21 levels were measured by western blotting following rosuvastatin exposure and p21 was stably transduced into p21 -/- mouse podocytes. RESULTS: Rosuvastatin protects against ADR- and PA-induced apoptosis in podocytes. Further, exposure to rosuvastatin increases p21 levels in podocytes in vitro. ADR induces apoptosis in p21 -/- mouse podocytes, but rosuvastatin's protective effect is not seen in the absence of p21. Reconstituting p21 in p21 -/- podocytes restores rosuvastatin's prosurvival effect. CONCLUSION: Rosuvastatin is prosurvival in injured podocytes. Rosuvastatin exerts its protective effect through a p21-dependent antiapoptotic pathway. These findings suggest that statins decrease proteinuria by protecting against podocyte apoptosis and subsequent podocyte depopulation.


Assuntos
Apoptose/efeitos dos fármacos , Fluorbenzenos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Podócitos/citologia , Podócitos/efeitos dos fármacos , Pirimidinas/farmacologia , Sulfonamidas/farmacologia , Animais , Apoptose/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/deficiência , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Doxorrubicina/toxicidade , Humanos , Camundongos , Camundongos Knockout , Podócitos/metabolismo , Proteinúria/prevenção & controle , Puromicina Aminonucleosídeo/toxicidade , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Rosuvastatina Cálcica , Transdução Genética
20.
Am J Physiol Renal Physiol ; 296(2): F213-29, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18784259

RESUMO

Glomerular diseases remain the leading cause of chronic and end-stage kidney disease. Significant advances in our understanding of human glomerular diseases have been enabled by the development and better characterization of animal models. Diseases of the glomerular epithelial cells (podocytes) account for the majority of proteinuric diseases. Rodents have been extensively used experimentally to better define mechanisms of disease induction and progression, as well as to identify potential targets and therapies. The development of podocyte-specific genetically modified mice has energized the research field to better understand which animal models are appropriate to study acquired podocyte diseases. In this review we discuss inducible experimental models of acquired nondiabetic podocyte diseases in rodents, namely, passive Heymann nephritis, puromycin aminonucleoside nephrosis, adriamycin nephrosis, liopolysaccharide, crescentic glomerulonephritis, and protein overload nephropathy models. Details are given on the model backgrounds, how to induce each model, the interpretations of the data, and the benefits and shortcomings of each. Genetic rodent models of podocyte injury are excluded.


Assuntos
Modelos Animais de Doenças , Nefropatias/patologia , Podócitos/patologia , Animais , Camundongos , Ratos
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