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1.
Arthroscopy ; 37(6): 1883-1889, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33529783

RESUMO

PURPOSE: The purpose of this double-blind, randomized, controlled trial was to evaluate the use of intravenous (IV) tranexamic acid (TXA) in patients undergoing primary bone-patellar tendon-bone (BPTB) anterior cruciate ligament reconstruction (ACLR) regarding postoperative hemarthrosis, pain, opioid consumption, and quadriceps atrophy and activation. METHODS: A controlled, randomized, double-blind trial was conducted in 110 patients who underwent ACLR with BPTB autograft. Patients were equally randomized to the control and experimental groups. The experimental group received two 1-g boluses of IV TXA, one prior to tourniquet inflation and one prior to wound closure; the control group did not receive TXA. If a clinically significant hemarthrosis was evident, the knee was aspirated and the volume of blood (in milliliters) was recorded. Additionally, we recorded perioperative blood loss (in milliliters); visual analog scale scores on postoperative days 1, 4, and 7 and at postoperative weeks 1, 6, and 12; postoperative opioid consumption on postoperative days 1, 4, and 7; range of motion (ROM) and ability to perform a straight leg raise at postoperative weeks 1, 6, and 12; and preoperative and postoperative thigh circumference ratio. RESULTS: There was no significant difference in perioperative blood loss between the TXA and control groups (32.5 mL vs 35.6 mL, P = .47). In the TXA group, 23 knees were aspirated; in the control group, 26 knees were aspirated (P = .56). No significant difference in postoperative hemarthrosis volume was seen in patients who received IV TXA versus those who did not (26.7 mL vs 37.3 mL, P = .12). There was no significant difference in visual analog scale scores between the 2 groups (P = .15); in addition, there was no difference in postoperative opioid consumption (P = .33). No significant difference in ROM, ability to perform a straight leg raise, or postoperative thigh circumference ratio was observed (P > .05 for all). CONCLUSIONS: IV TXA in patients who undergo ACLR with BPTB autograft does not significantly impact perioperative blood loss, postoperative hemarthrosis, or postoperative pain levels. Additionally, no significant differences were seen in early postoperative recovery regarding ROM or quadriceps reactivation. LEVEL OF EVIDENCE: Level I, randomized controlled trial.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Ligamento Patelar , Ácido Tranexâmico , Lesões do Ligamento Cruzado Anterior/cirurgia , Autoenxertos , Enxerto Osso-Tendão Patelar-Osso , Hemartrose , Humanos , Dor Pós-Operatória/tratamento farmacológico
2.
J Environ Manage ; 279: 111502, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33160741

RESUMO

Development of on-site treatment strategies for PFAS-containing investigation derived waste (IDW) will decrease the potential for secondary release following off-site disposal, lower disposal costs, and promote more effective long-term management of PFAS-laden waste. Herein, we report the application of a simple, drop-in treatment that utilizes one of two PFAS sorbents: bituminous granular activated carbon (GAC) or strong base anion exchange resin (IX) and a small circulation pump to adsorb and concentrate PFAS impacted mass from liquid IDW collected from two sites with disparate water chemistries and synthetic IDW amended with PFAS-containing aqueous film forming foam (AFFF). Bench scale intermittent circulation experiments revealed that bituminous granular activated carbon (GAC, 0.5 mg/mL) removed up to 97.0 ± 1.4% and 96.4 ± 0.5% of PFOS and PFOA, respectively, in both site-derived IDW sources. Improved performance was observed in experimental treatments containing a strong base anion exchange resin (IX, 0.5 mg/mL), where up to 99.4 ± 0.1% and 96.7 ± 0.2% of PFOS and PFOA were removed, respectively. High chloride concentrations (20 g/L) reduced removal of short chain perfluorocarboxylates (PFBA and PFHxA) using GAC or IX, but high salt concentrations had negligible effects on the removal of PFOA, PFBS, PFHxS, or PFOS. Excellent scalability was observed in mesoscale experiments, where the majority of amended PFAS mass was removed from synthetic IDW within five days of vessel circulation using two different PFAS-capture configurations. Combined PFOS and PFOA concentrations were reduced to levels below 0.07 µg/L using either GAC or IX for both configurations. Results generated in this study support the application of this approach as an economical strategy for potential waste volume reduction in IDW destined for off-site disposal.


Assuntos
Fluorocarbonos , Poluentes Químicos da Água , Purificação da Água , Carvão Vegetal , Fluorocarbonos/análise , Água , Poluentes Químicos da Água/análise
3.
Environ Sci Technol ; 54(24): 15768-15777, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33270425

RESUMO

Transport of poly- and perfluoroalkyl substances (PFAS) at aqueous film-forming foam (AFFF)-impacted sites is limited by various processes that can retain PFAS mass within the source area. This study used concentration data obtained via a high-resolution sampling and analytical protocol to estimate the PFAS mass distribution in source and downgradient areas of a former firefighter training area. The total PFAS mass present at the site was approximately 222 kg, with 106 kg as perfluoroalkyl acids (PFAAs) and 116 kg as polyfluorinated precursors. Zwitterionic and cationic PFAS represented 83% of the total precursor mass and were found primarily in the source and up/side-gradient areas (75%), likely due to preferential hydrophobic partitioning, electrostatic interactions, and diffusion into lower-permeability soils. Based on the release history and the high percentage of total PFAS mass represented by precursors (primarily electrochemical fluorination-derived compounds), the estimated conversion rate of precursors to PFAAs was less than 2% annually. Eighty-two percent of the total PFAS mass was encountered in lower-permeability soils, which limited the potential for advection and transformation. This contributed to a 99% decrease in the mass discharge rate at the far-downgradient plume (0.048 kg/yr compared to the near-source area (3.6 kg/yr)). The results provide field-scale evidence of the importance of these PFAS retention processes at sites where AFFF has been released.


Assuntos
Fluorocarbonos , Poluentes Químicos da Água , Cátions , Fluorocarbonos/análise , Solo , Água , Poluentes Químicos da Água/análise
4.
J Ind Microbiol Biotechnol ; 47(9-10): 889-895, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33026637

RESUMO

A simple potentiostat was constructed as a strategy to enhance solvent production in a mediatorless and oxygen-exposed fermentation inoculated with the aerotolerant strain Clostridium sp. C10. Elevated n-butanol and acetone titers were recorded in all fermentations with either glucose or xylose in the presence of electrodes poised at + 500 mV (+ 814 mV vs SHE) relative to cells plus substrate only controls. Respective butanol titers and volumetric butanol productivities in studies performed with 30 g/L glucose or 30 g/L xylose were 1.67 and 2.27 times and 1.90 and 6.13 times greater in the presence of electrodes compared to controls. Glucose and xylose utilization in the presence of electrodes was 61 and 125% greater than no-electrode controls, respectively. Increasing substrate concentrations to 60 g/L decreased the butanol yields relative to the studies performed at 30 g/L. These data suggest that it may be more efficient to alter reactor reduction potential than increase substrate concentration for solvent output during industrial fermentations, which favors higher yield with few additional inputs.


Assuntos
Clostridium , Fermentação , Glucose , Xilose , 1-Butanol , Acetona , Butanóis , Clostridium/metabolismo , Eletrodos , Etanol , Solventes
5.
Biotechnol Bioeng ; 115(3): 577-585, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29131314

RESUMO

Reports suggest that ferric iron and electron shuttling molecules will select for Fe3+ -reducer dominated microbial biomass. We investigated the influence of the redox mediators anthraquinone-2,6-disulfonate (AQDS) and riboflavin using xylose as the sole fermentation substrate, with or without ferric iron. Electron shuttling to insoluble ferrihydrite enhanced solventogenesis, acidogenesis, hydrogen production, and xylose consumption, relative to the cells plus xylose controls in fermentations inoculated with woodland marsh sediment, wetwood disease, or raw septic liquid, over multiple transfers in 15-day batch fermentations. 16S rRNA gene based community analyses indicated that ferrihydrite alone, and AQDS/riboflavin plus ferrihydrite, immediately shifted native heterogeneous communities to those predominantly belonging to the Clostdridiales, rather than stimulating Fe3+ respiring populations. Data were similar irrespective of the inoculum source, suggesting that Fe3+ and/or electron shuttling compounds select for rapid proliferation of fermentative genera when fermentable substrates are present, and increases the extent of xylose consumption and solvent production.


Assuntos
Biomassa , Reatores Biológicos/microbiologia , Clostridiales/crescimento & desenvolvimento , Compostos Férricos/metabolismo , Hidrogênio/metabolismo , Xilose/metabolismo
6.
Appl Microbiol Biotechnol ; 102(20): 8707-8715, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30109398

RESUMO

Xylose is the second most abundant sugar derived from lignocellulose; it is considered less desirable than glucose for fermentation, and strategies that specifically increase xylose utilization in wild type or engineered cells are goals for biofuel production. Issues arise with xylose utilization because of carbohydrate catabolite repression, which is the preferential utilization of glucose relative to xylose in fermentations with both pure and mixed cultures. Taken together the low substrate utilization rates and solvent yields with xylose compared to glucose, many industrial fermentations ignore the xylolytic portion of the reaction in lieu of methods to maintain high glucose. This is shortsighted given the massive potential for xylose generation from a number of sustainable biomass feedstocks, based on utilization of the hemicellulose fraction(s) that enter pretreatment. A number of strategies have been developed in recent years to address xylose utilization and solvent production from xylose in systems with just xylose, or in systems with mixtures of glucose plus xylose, which are more typical of pretreated lignocellulose. The approaches vary in terms of complexity, stability, and ease of introduction to existing fermentation infrastructure (i.e., so-called drop-in fermentation strategies). Some approaches can be considered traditional engineering approaches (e.g., change the reaction conditions), while others are more subtle cellular approaches to eliminate the impacts of catabolite repression. Finally, genetic engineering has been used to increase xylose utilization, although this can be considered a relatively nascent approach compared to manipulations completed to date for glucose utilization.


Assuntos
Bactérias/metabolismo , Microbiologia Industrial , Solventes/metabolismo , Xilose/metabolismo , Bactérias/genética , Biocombustíveis/análise , Fermentação , Engenharia Genética
7.
J Arthroplasty ; 33(1): 6-9, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28870744

RESUMO

BACKGROUND: The frequency of total joint arthroplasties (TJAs) performed in ambulatory surgery centers (ASCs) is increasing. However, not all TJA patients are healthy enough to safely undergo these procedures in an ambulatory setting. We examined the percentage of arthroplasty patients who would be eligible to have the procedure performed in a free-standing ASC and the distribution of comorbidities making patients ASC-ineligible. METHODS: We reviewed the charts of 3444 patients undergoing TJA and assigned ASC eligibility based on American Society of Anesthesiologists (ASA) status, a set of exclusion criteria, and any existing comorbidities. RESULTS: Overall, 70.03% of all patients undergoing TJA were eligible for ASC. Of the ASA class 3 patients who did not meet any exclusion criteria but had systemic disease (51.11% of all ASA class 3 patients), 53.69% were deemed ASC-eligible because of sufficiently low severity of comorbidities. The most frequent reasons for ineligibility were body mass index >40 kg/m2 (32.66% of ineligible patients), severity of comorbidities (28.00%), and untreated obstructive sleep apnea (25.19%). CONCLUSION: A large proportion of TJA patients were found to be eligible for surgery in an ASC, including over one-third of ASA class 3 patients. ASC performed TJA provides an opportunity for increased patient satisfaction and decreased costs, selecting the right candidates for the ambulatory setting is critical to maintain patient safety and avoid postoperative complications.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/normas , Artroplastia de Substituição/estatística & dados numéricos , Idoso , Procedimentos Cirúrgicos Ambulatórios/estatística & dados numéricos , Artroplastia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Apneia Obstrutiva do Sono
8.
Appl Microbiol Biotechnol ; 101(21): 8053-8061, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28963627

RESUMO

Xylose is the second most abundant sugar derived from lignocellulose; it is considered less desirable than glucose for fermentation, and strategies that specifically increase xylose utilization in wild-type cells are goals for biofuel production. Xylose consumption, butanol production, and hydrogen production increased in both Clostridium beijerinckii and a novel solventogenic bacterium (strain DC-1) when anthraquinone-2,6,-disulfonate (AQDS) or riboflavin were used as redox mediators to transfer electrons to poorly crystalline Fe(OH)3 as an extracellular electron sink. Strain DC-1 was most closely related to Rhizobiales bacterium Mfc52 based on 95% 16S rRNA gene sequence similarity, which demonstrates that this response is not limited to a single genus of xylose-fermenting bacteria. Xylose utilization and butanol production were negligible in control incubations containing cells plus 3% (w/v) xylose alone during a 10-day batch fermentation, for both strains tested (n-butanol titers of 0.05 g L-1). Micromolar concentrations of AQDS and riboflavin were added as electron shuttling compounds with poorly crystalline Fe(OH)3 as an insoluble electron acceptor, and respective n-butanol titers increased to 6.35 and 7.46 g L-1. Increases in xylose consumption for the iron treatments were relatively high, from less than 0.49 g L-1 (xylose alone, no iron or electron shuttling molecules) to 25.98 and 29.15 g L-1 for the AQDS and riboflavin treatments, respectively. Hydrogen production was also 3.68 times greater for the AQDS treatment and 5.27 greater for the riboflavin treatment relative to controls. Strain DC-1 data were similar, again indicating that the effects are not specific to the genus Clostridium.


Assuntos
Butanóis/metabolismo , Clostridium beijerinckii/metabolismo , Transporte de Elétrons , Compostos Férricos/metabolismo , Rhizobiaceae/metabolismo , Xilose/metabolismo , Antraquinonas/metabolismo , Análise por Conglomerados , Meios de Cultura/química , Citosol/química , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Fermentação , Filogenia , RNA Ribossômico 16S/genética , Rhizobiaceae/classificação , Rhizobiaceae/genética , Riboflavina/metabolismo , Análise de Sequência de DNA , Açúcares/análise
9.
Tohoku J Exp Med ; 242(4): 273-279, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28781337

RESUMO

Cardiovascular morbidity is the leading cause of death in dialysis patients and many risk factors have been involved in its pathogenesis. Genetic susceptibility may be of importance including polymorphism for matrix metalloproteinase 3 (MMP3), which is an enzyme that catalyzes the degradation of collagen, proteoglycans, fibronectin, laminine and elastin. The MMP3 gene promoter contains an insertion/deletion polymorphism characterised by an array of 5 or 6 adenosine residues (5A/6A) at -1612 position. Literature data show that the 5A or 6A allele of the MMP3 gene shows different risk for cardiovascular and overall outcome in general population. The aim was to analyze the -1612 5A/6A promoter polymorphism in a group of hemodialysis patients and to correlate the findings with cardiovascular morbidity and 7-year all-cause and cardiovascular mortality. This study included 196 patients on hemodialysis for longer than six months at University Medical Center Zvezdara. The leading causes of end stage renal disease were hypertension and diabetes mellitus. Venous blood was collected on midweek dialysis session and genotype analysis was performed by using polymerase chain reaction-restriction fragment length polymorphism method. Among the 198 hemodialysis patients, there were 142 (72%) 5A/6A heterozygotes, 12 (6%) 5A/5A homozygotes, and 44 (22%) 6A/6A homozygotes. These data are consistent with Hardy-Weinberg equilibrium. After 7-year follow-up, the 5A homozygotes showed the lowest all-cause and cardiovascular survival, while the 6A homozygotes showed the highest cardiovascular survival. The 5A allele of the MMP3-gene promoter polymorphism is a potential risk factor in the poor outcome of hemodialysis patients.


Assuntos
Alelos , Predisposição Genética para Doença , Metaloproteinase 3 da Matriz/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Diálise Renal , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Morbidade , Fatores de Risco , Resultado do Tratamento
11.
Curr Microbiol ; 68(6): 743-50, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24522483

RESUMO

A fermentative, non-spore forming, motile, rod-shaped bacterium, designated strain MJ1(T), was isolated from an RDX contaminated aquifer at a live-fire training site in Northwest NJ, United States. On the basis of 16S rRNA gene sequencing and DNA base composition, strain MJ1(T) was assigned to the Firmicutes. The DNA G+C content was 42.8 mol%. Fermentative growth was supported by glucose and citrate in a defined basal medium. The bacterium is a strict anaerobe that grows between at pH 6.0 and pH 8.0 and 18 and 37 °C. The culture did not grow with hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) as the electron acceptor or mineralize RDX under these conditions. However, MJ1(T) transformed RDX into MNX, methylenedinitramine, formaldehyde, formate, ammonium, nitrous oxide, and nitrate. The nearest phylogenetic relative with a validly published name was Desulfotomaculum guttoideum (95 % similarity). However, MJ1(T) was also related to Clostridium celerecrescens DSM 5628 (95 %), Clostridium indolis DSM 755 (94 %), and Clostridium sphenoides DSM 632 (94 %). DNA:DNA hybridization with these strains was between 6.7 and 58.7 percent. The dominant cellular fatty acids (greater than 5 % of the total, which was 99.0 % recovery) were 16:0 fatty acid methyl ester (FAME) (32.12 %), 18:1cis 11 dimethyl acetal (DMA) (16.47 %), 16:1cis 9 DMA (10.28 %), 16:1cis 9 FAME (8.10 %), and 18:1cis 9 DMA (5.36 %). On the basis of morphological, physiological, and phylogenetic data, Clostridium geopurificans is proposed as a new species in genus Clostridium, with strain MJ1(T) as the type strain.


Assuntos
Clostridium/classificação , Clostridium/fisiologia , Substâncias Explosivas/metabolismo , Triazinas/metabolismo , Anaerobiose , Técnicas de Tipagem Bacteriana , Composição de Bases , Clostridium/genética , Clostridium/isolamento & purificação , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Microbiologia Ambiental , Ácidos Graxos/análise , Fermentação , Microscopia Eletrônica de Varredura , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Oxirredução , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Estados Unidos
12.
Curr Microbiol ; 68(4): 510-7, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24343174

RESUMO

A Gram-negative, rod-shaped bacterium was isolated from a mixed culture that degraded tert-butyl alcohol (TBA) in a granular-activated carbon (GAC) sample from a Biological-GAC reactor. Strain YZ2(T) was assigned to the Betaproteobacteria within the family Comamonadaceae based on 16S rRNA gene similarities. The nearest phylogenetic relative (95.0 % similarity) with a valid name was Hydrogenophaga taeniospiralis. The DNA G+C content was 66.4 mol%. DNA:DNA hybridization indicated that the level of relatedness to members of the genus Hydrogenophaga ranged from 1.1 to 10.8 %. The dominant cellular fatty acids were: 18:1 w7c (75 %), 16:0 (4.9 %), 17:0 (3.85 %), 18:0 (2.93 %), 11 methyl 18:1 w7c (2.69 %), Summed Feature 2 (2.27 %), and 18:0 3OH (1.35 %). The primary substrate used was TBA, which is a fuel oxygenate and groundwater contaminant. YZ2(T) was non-motile, without apparent flagella. It is a psychrotolerant, facultative aerobe that grew between pH 6.5 and 9.5, and 4 and 30 °C. The culture grew on and mineralized TBA at 4 °C, which is the first report of psychrotolerant TBA degradation. Hydrogen was used as an alternative electron donor. The culture also grew well in defined freshwater medium with ethanol, butanol, hydroxy isobutyric acid, acetate, pyruvate, citrate, lactate, isopropanol, and benzoic acid as electron donors. Nitrate was reduced with hydrogen as the sole electron donor. On the basis of morphological, physiological, and chemotaxonomic data, a new species, Hydrogenophaga carboriunda is proposed, with YZ2(T) as the type strain.


Assuntos
Comamonadaceae/metabolismo , Aerobiose , Comamonadaceae/química , Comamonadaceae/genética , Microbiologia Ambiental , Microbiologia Industrial , Fenótipo , Filogenia , terc-Butil Álcool/metabolismo
13.
Nephron Clin Pract ; 124(1-2): 94-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24192666

RESUMO

BACKGROUND/AIMS: Compared to all other complications, literature data about vascular access aneurysm (VAA) are the scarcest. The aim of this cross-sectional study was to evaluate the prevalence of arteriovenous fistula (AVF) aneurysms and to confirm the risk factors for their appearance. METHODS: The presence, number and morphological characteristics of AVF aneurysms were confirmed, and according to the score of AVF aneurysm (the sum of the length and width in cm), patients were classified into group 1 (score ≤12) and group 2 (score >12). Analysis included the last data from the medical records including vascular calcifications score. RESULTS: Out of 181 patients, 150 with native fistula were included in this study. Aneurysmatic changes were detected in 90 (60%) patients, and the majority had two or more aneurysms. VAA were more frequent in patients with adult polycystic kidney disease (ADPKD) than in other diagnostic categories. By using forward stepwise logistic regression, we confirmed that patients on high-flux hemodialysis (HD) had 5.3-fold higher risk, and patients with diabetes mellitus had 5.8-fold less risk for developing AVF aneurysm. While vascular calcification score did not influence the incidence of VAA, higher PWV had significant negative influence on formation of AVF aneurysm (OR 1.25, 95% CI 1.003-1.56, p = 0.047). By ROC curve analysis, it was determined that patients who were longer than 5.7 years on HD had greater risk for developing VAA (area = 0.741, p = 0.000). CONCLUSION: This single-center study confirmed the very high prevalence of VAA (60%). Aneurysms were more frequent in patients with ADPKD and in those who had longer dialysis vintage on high-flux membranes with higher blood flow rate.


Assuntos
Aneurisma/epidemiologia , Derivação Arteriovenosa Cirúrgica/estatística & dados numéricos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Diálise Renal/estatística & dados numéricos , Distribuição por Idade , Causalidade , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Sérvia/epidemiologia , Distribuição por Sexo , Resultado do Tratamento
14.
Eur J Drug Metab Pharmacokinet ; 38(1): 69-76, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22618469

RESUMO

This study presents application of a new linear and nonlinear fractional derivative two compartmental model to the evaluation of individual pharmacokinetics. In the model, the integer order derivatives are replaced by derivatives of real order. A specific nonlinear function is used for the fit improvement of a fractional derivative two compartmental model with the mass balance conservation. The agreement of the values predicted by the proposed model with the values obtained through experiments with bumetanide tablets in human volunteers is shown to be good. Thus, pharmacokinetics of bumetanide can be described well by a linear or a nonlinear two compartmental model with fractional derivatives of the same order proposed here. Parameters in the model are determined by the least squares method and the particle swarm optimization numerical procedure is used. The results show that the linear fractional order two compartmental model for bumetanide is useful improvement of the classical (integer order) two compartmental model and that the nonlinear fractional order model is useful improvement of the linear model in a great number of volunteers.


Assuntos
Bumetanida/farmacocinética , Diuréticos/farmacocinética , Modelos Lineares , Modelos Biológicos , Dinâmica não Linear , Administração Oral , Bumetanida/administração & dosagem , Diuréticos/administração & dosagem , Humanos , Análise dos Mínimos Quadrados , Comprimidos
15.
Biomed Pharmacother ; 167: 115528, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37738800

RESUMO

We examined whether combinig diclofenac and metformin in doses equivalent to human doses would synergize their anticancer activity on fibrosarcoma inoculated to hamsters and in vitro. Rescue experiment was performed to examine whether the prosurvival NF-κB stimulation by mebendazole can reverse anticancer effects of the treatment. BHK-21/C13 cell culture was subcutaneously inoculated to Syrian golden hamsters randomly divided into groups (6 animals per group): 1) untreated control; treated daily with 2) diclofenac; 3) metformin; 4) combinations of diclofenac and metformin at various doses; 5) combination of diclofenac, metformin and mebendazole; 6) mebendazole. Dose response curves were made for diclofenac and metformin combination. Tumor growth kinetics, biophysical, pathological, histological and immunohistochemical characteristics of excised tumors and hamster organs as well as biochemical and hematological blood tests were compared among the groups. Single treatments had no anticancer effects. Diclofenac (60 mg/kg/day) exhibited significant (P < 0.05) synergistic inhibitory effect with metformin (500 mg/kg/day) on all tumor growth parameters, without toxicity and influence on biochemical and hematological blood tests. The same results were obtained with double doses of diclofenac and metformin combination. The addition of mebendazole to the diclofenac and metformin combination rescued tumor expansion. Furthermore, diclofenac with metformin demonstrated antiproliferative effects in hamster fibrosarcoma BHK-21/C13, human lung carcinoma A549 (CCL-185), colon carcinoma HT-29 (HTB-38) and cervical carcinoma HeLa (CCL-2) cell cultures, with markedly lower cytotoxicity in the normal fetal lung MRC-5 cells. In conclusion, diclofenac and metformin combination may be recommended for potential use in oncology, due to synergistic anticancer effect in doses achievable in humans.

16.
Eur J Drug Metab Pharmacokinet ; 37(4): 301-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22527972

RESUMO

The aim of this study is to investigate the protective effect of fullerenol C60(OH)24 in various doses, on lipid peroxidation of rat's kidneys, testes and lungs after application of doxorubicin. The experiment was performed on healthy male Wistar rats. The animals were randomly divided into five experimental groups and treated with saline (0.9 % NaCl i.v.), doxorubicin alone (10 mg/kg i.v.), combination of doxorubicin/fullerenol (50 and 100 mg/kg fullerenol, respectively, 30 min before the introduction of doxorubicin) and fullerenol alone (100 mg/kg), respectively. Animals were killed on the 2nd and 14th day after treatment. Products of lipid peroxidation and thiobarbituric acid are determined spectrophotometrically from the crude homogenate fraction of the kidney, testis and lung tissues of the rats. Fullerenol, applied as a pre-treatment of doxorubicin, significantly reduced or completely prevented the appearance of doxorubicin toxicity in kidneys and testes, in both tested doses. A dose of 100 mg/kg i.p. exhibited a better protective effect. When fullerenol was applied alone, at a dose of 100 mg/kg i.p, it did not significantly affect the intensity of lipid peroxidation in all tested organs.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Doxorrubicina/toxicidade , Fulerenos/farmacologia , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/metabolismo , Testículo/metabolismo , Animais , Masculino , Ratos , Ratos Wistar
17.
J Contam Hydrol ; 247: 103986, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35279484

RESUMO

Two of the most important retention processes for per- and polyfluoroalkyl substances (PFAS) in groundwater likely are sorption and matrix diffusion. The objective of this study was to model concentration and mass discharge of one PFAS, perfluorooctane sulfonate (PFOS), with matrix diffusion processes incorporated using data from a highly chemically- and geologically-characterized site. When matrix diffusion is incorporated into the REMChlor-MD model for PFOS at this research site, it easily reproduces the field data for three key metrics (concentration, mass discharge, and total mass). However, the no-matrix diffusion model produced a much poorer match. Additionally, after about 40 years of groundwater transport, field data and the REMChlor-MD model both showed the majority (80%) of the measured PFOS mass that exited the source zones was located in downgradient low permeability zones due to matrix diffusion. As such, most of the PFOS mass is not available to immediately migrate downgradient via advection in the more permeable sands at this site, which has important implications for monitored natural attenuation (MNA). Plume expansion over the next 50 years is forecasted to be limited, from a 350-m plume length in 2017 to 550 m in 2070, as matrix diffusion will attenuate groundwater plumes by slowing their expansion. This phenomenon is important for constituents that do not degrade, such as PFOS, compared to those susceptible to degradation. Overall, this work shows that matrix diffusion is a relevant process in environmental PFAS persistence and slows the rate of plume expansion over time.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Água Subterrânea , Difusão
18.
Eur J Drug Metab Pharmacokinet ; 36(3): 183-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21553340

RESUMO

Blood loss during cesarean section was calculated based on post-operative decrement of hemoglobin (Hb) and hematocrit (Hct) level. The model used for pregnant women was previously validated for non-pregnant women who underwent gynecological surgery. 1,068 pregnant women who underwent cesarean section and 517 women who underwent gynecological surgery were included in the study. Regression lines between collected (x) and calculated (y) blood loss in pregnant women (y = 0.164 + 0.602x) and non-pregnant (y = 0.255 + 0.750x) women were statistically parallel. This study confirmed the applicability of one-compartmental model based on the drop in Hb levels for blood loss calculations for both gynecological surgery and cesarean section. Improved methods for calculating blood loss, V after cesarean section as V = [0.0115 × body weight (kg) × ln (preoperative Hb/postoperative Hb)] + [0.1905 × height³ (m) × ln (preoperative Hb/postoperative Hb)] + 0.3158 and after gynecological surgery V = [0.004 × body weight (kg) × ln (preoperative Hb/postoperative Hb)] + [0.4624 × height ³(m) × ln (preoperative Hb/postoperative Hb)] + 0.0472 were suggested.


Assuntos
Biometria , Perda Sanguínea Cirúrgica , Cesárea , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hemoglobinas/análise , Humanos , Pessoa de Meia-Idade , Gravidez , Análise de Regressão
19.
Eur J Drug Metab Pharmacokinet ; 36(2): 103-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21327754

RESUMO

Blood loss can be measured directly and indirectly. The latter reflects blood loss through the assessment of hemoglobin level. Thus aim of this study was to determine the applicability of the drop in hemoglobin levels blood loss calculation when transfused blood volume is taken into account on the patients who underwent aneurysmectomy and to estimate whether this model is applicable on geriatric population. In this study, 14 patients were included and their blood loss was calculated based on hemoglobin concentration. Linear correlation (y = 0.18467 + 1.19315·x) with high correlation coefficient (r = 0.90809) was found between calculated and collected blood loss only if transfused blood volume was taken into account. The coefficient of the regression slope for the blood volume measured during surgery and the calculated blood loss in eight patients ≤65 years (y = 0.90866 + 0.86296·x) and six patients >65 years (y = 0.0299 + 1.32707·x) did not show any significant difference. The applicability of the indirect measurement of surgical blood loss, when transfused blood volume was taken into account, was demonstrated in both populations, in the age of 65 and less and in the age over 65 years after aneurysmectomy.


Assuntos
Aneurisma/patologia , Aneurisma/cirurgia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Transfusão de Sangue , Volume Sanguíneo/fisiologia , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Idoso , Algoritmos , Aneurisma Roto/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Eritrócitos/metabolismo , Hematócrito , Hemoglobinas/análise , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Estudos Prospectivos
20.
Eur J Drug Metab Pharmacokinet ; 36(4): 189-96, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21805207

RESUMO

This study presents a new nonlinear two compartmental model and its application to the evaluation of valproic acid (VPA) pharmacokinetics in human volunteers after oral administration. We have used literature VPA concentrations. In the model, the integer order derivatives are replaced by derivatives of real order often called fractional order derivatives. Physically that means that the history (memory) of a biological process, realized as a transfer from one compartment to another, is taken into account with the mass balance conservation observed. Our contribution is the analysis of a specific nonlinear two compartmental model with the application in evaluation of VPA pharmacokinetics. The agreement of the values predicted by the proposed model with the values obtained through experiments is shown to be good. Thus, pharmacokinetics of VPA after oral application can be described well by a nonlinear two compartmental model with fractional derivatives of the same order proposed here. Parameters in the model are determined by the least-squares method and the particle swarm optimization (PSO) numerical procedure is used. The results show that the nonlinear fractional order two compartmental model for VPA pharmacokinetics is superior in comparison to the classical (integer order) linear two compartmental model and to the linear fractional order two compartmental model.


Assuntos
Modelos Biológicos , Ácido Valproico/farmacocinética , Simulação por Computador , Humanos , Dinâmica não Linear
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