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1.
Small ; 19(34): e2300104, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37186509

RESUMO

Gossypol is a chemotherapeutic drug that can inhibit the anti-apoptotic protein Bcl-2, but the existing gossypol-related nanocarriers cannot well solve the problem of chemotherapy resistance. Based on the observation that gossypol becomes black upon Fe3+ coordination, it is hypothesized that encasing gossypol in glyceryl monooleate (GMO) and making it coordinate cobalt ferrite will not only improve its photothermal conversion efficiency (PCE) but also help it enter tumor cells. As the drug loading content and drug encapsulation efficiency of gossypol are 10.67% (w/w) and 96.20%, the PCE of cobalt ferrite rises from 14.71% to 36.00%. The synergistic therapeutic effect finally induces tumor apoptosis with a tumor inhibition rate of 96.56%, which is 2.99 and 1.47 times higher than chemotherapy or photothermal therapy (PTT) alone. PTT generated by the GMO nanocarriers under the irradiation of 808 nm laser can weaken tumor hypoxia, thereby assisting gossypol to inhibit Bcl-2. In addition, the efficacy of nanocarriers is also evaluated through T2 -weighted magnetic resonance imaging. Observations of gossypol-induced apoptosis in tissue slices provide definitive proof of chemotherapy sensitization, indicating that such coordination nanocarriers can be used as an effective preclinical agent to enhance chemotherapy.


Assuntos
Cobalto , Gossipol , Neoplasias , Humanos , Apoptose , Linhagem Celular Tumoral , Cobalto/farmacologia , Cobalto/uso terapêutico , Gossipol/farmacologia , Gossipol/uso terapêutico , Neoplasias/tratamento farmacológico
2.
Spine Deform ; 11(4): 815-823, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36920741

RESUMO

PURPOSE: To evaluate the effectiveness of vancomycin prophylaxis on spinal implant metal types. METHODS: 42 rabbits underwent posterior, single-level instrumentation at L5-L6 with stainless steel (n = 18), cobalt chrome (n = 12), or titanium (n = 12) wire. All implants were inoculated with 1 × 106 colony forming units (CFU) of methicillin-resistant S. Aureus (MRSA). In the intrawound vancomycin subgroup (n = 18, 6 from each metal type), 40 mg of vancomycin powder was placed in the wound. In the IV vancomycin subgroup (n = 6, all stainless steel), 15 mg/kg of IV vancomycin was given preoperatively. Local soft tissue and implants were harvested 1-week postoperatively and separately cultured. RESULTS: Intrawound vancomycin significantly reduced the rate of soft tissue infection (44.4% vs 100%) and implant infection (27.8% vs 100%) (p < 0.001). Within the intrawound vancomycin subgroup, cobalt chrome implants were associated with higher median soft tissue MRSA growth (130 CFU) than stainless steel (0 CFU) or titanium (0 CFU) (p = 0.02). Cobalt chrome implants were also more likely to develop soft tissue MRSA infection (83.3%) as compared to stainless steel (16.7%) or titanium (33.3%) (p = 0.04). Median soft tissue MRSA growth among stainless steel implants without prophylaxis, with IV vancomycin, and with vancomycin powder was 1.18 × 107, 195, and 0 CFU, respectively. The rate of soft tissue MRSA infection without prophylaxis, with IV vancomycin, and with vancomycin powder was 100, 66.7, and 16.7%, respectively (p = 0.015). CONCLUSION: Intrawound vancomycin is more effective than IV vancomycin and effectively reduces the risk of infection, but is less effective in cobalt chrome implants due to residual soft tissue infection.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Relacionadas à Prótese , Infecções dos Tecidos Moles , Doenças da Coluna Vertebral , Animais , Coelhos , Vancomicina/uso terapêutico , Antibacterianos/uso terapêutico , Titânio , Infecções dos Tecidos Moles/tratamento farmacológico , Pós/uso terapêutico , Aço Inoxidável , Cobalto/uso terapêutico
3.
J Neurol ; 269(11): 5798-5811, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35900586

RESUMO

Parkinson's disease (PD) is an ageing disorder with deterioration of dopamine neurons which leads to motor complications like tremor, stiffness, slow movement and postural disturbances. In PD, both genetics as well as environmental factors both play a major role in causing the pathogenesis. Though there are surfeit of risk factors involved in PD occurrence, till now there is lack of an exact causative agent as a risk for PD with confirmative findings. The role of heavy metals reported to be a significant factor in PD pathogenesis. Heavy metal functions in cell maintenance but growing pieces of evidences reported to cause dyshomeostasis with increased PD rate. Metals disturb the molecular processes and results in oxidative stress, DNA damage, mitochondrial dysfunction, and apoptosis. The present review elucidates the role of cobalt, nickel, mercury, chromium, thallium metals in α-synuclein aggregation and its involvement in blood brain barrier flux. Also, the review explains the plausible role of aforementioned metals with a mechanistic approach and therapeutic recommendations in PD.


Assuntos
Mercúrio , Metais Pesados , Doença de Parkinson , Cromo/uso terapêutico , Cobalto/uso terapêutico , Humanos , Mercúrio/uso terapêutico , Metais Pesados/toxicidade , Níquel/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Tálio/uso terapêutico , alfa-Sinucleína
4.
J Alzheimers Dis ; 87(4): 1503-1516, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35527546

RESUMO

BACKGROUND: Acetylcholinesterase (AChE) regulates the transmission of neural messages by hydrolyzing acetylcholine in synaptic spaces. OBJECTIVE: The effects of many AChE inhibitors have been evaluated in the treatment of Alzheimer's disease, but the present study examined a synthetic complex containing cobalt (SC) for the first time in the field of enzyme activity to evaluate enzyme inhibitory function. METHODS: Ellman's test was applied. AChE function was assessed in the presence of SC through docking and molecular dynamics analyses. The second structure of AChE was studied through circular dichroism (CD) spectroscopy. RESULTS: Several enzymatic methods were utilized for the kinetics of AChE, which indicated the non-Michaelis and positive homotropic behavior of AChE in the absence of inhibitors (Hill coefficient = 1.33). However, the existence of inhibitors did not eliminate this homotropic state, and even AChE had a more sigmoidal shape than the galantamine at the presence of SC. Based on the CD spectroscopy results, AChE structure changed in the existence of inhibitors and substrates. Bioinformatics analysis revealed SC bonding to the channel of active site AChE. The number of hydrogen bonds was such that the flexibility of the enzyme protein structure due to inhibitor binding reduced AChE function. CONCLUSION: The results reflected that AChE exhibited a non-Michaelis and positive homotropic behavior, leading to a more inhibitory effect on the SC than the galantamine. The positive homotropic behavior of AChE was intensified due to the alteration in AChE protein structure by binding SC to hydrophobic region in the active site pathway and impressing Trp84.


Assuntos
Doença de Alzheimer , Galantamina , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Cobalto/farmacologia , Cobalto/uso terapêutico , Galantamina/farmacologia , Galantamina/uso terapêutico , Humanos , Simulação de Acoplamento Molecular
5.
ACS Appl Mater Interfaces ; 13(10): 11683-11695, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33656325

RESUMO

Glucose oxidase (GOx) is regarded as an ideal endogenous natural enzyme for tumor starvation therapy and photothermal therapy (PTT) is a promising strategy for the ablation of primary tumor. In this work, Cu-doped cobalt oxide and porous carbon nanocomposites (CuCo(O)@PCNs) were synthesized from double-layered ZIF-8@ZIF-67 and GOx was loaded in the porous carbon to form a CuCo(O)/GOx@PCNs hybrid nanozyme. CuCo(O) was characterized as the Cu0.3Co2.7O4 phase through X-ray diffraction analysis and it can react with H2O2 to generate O2 and alleviate tumor hypoxia, resulting in the recovered enzymatic activity of GOx and the enhanced starvation therapy. The porous nanocarbon can ablate the primary tumor because of its high photothermal conversion efficiency of 40.04%. The three-in-one functions of oxygen supply, glucose consumption, and photothermal conversion were realized in the ZIFs-derived CuCo(O)/GOx@PCNs nanozyme and the starvation therapy effect was improved by PTT and oxygen supplement. Furthermore, the inhibition effect of CuCo(O)/GOx@PCNs on metastatic tumor is similar to combined therapy of the nanozyme and the immune checkpoint-blocking antibody, α-PD-1. The related antitumor immune mechanism was studied through the analysis of immune-related proinflammatory cytokines and the activated T cells. This work may provide new ideas for the development and application of the ZIFs-derived hybrid nanozyme in tumor therapy and the CuCo(O)/GOx@PCNs nanozyme may be a promising alternative to immune checkpoint inhibitors.


Assuntos
Carbono/uso terapêutico , Cobalto/uso terapêutico , Cobre/uso terapêutico , Glucose Oxidase/uso terapêutico , Imidazóis/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Neoplasias/terapia , Óxidos/uso terapêutico , Animais , Linhagem Celular Tumoral , Humanos , Imunoterapia , Camundongos , Terapia Fototérmica , Hipóxia Tumoral
6.
Adv Mater ; 32(45): e2003712, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33002227

RESUMO

Nanoparticle-based magnetic hyperthermia is a well-known thermal therapy platform studied to treat solid tumors, but its use for monotherapy is limited due to incomplete tumor eradication at hyperthermia temperature (45 °C). It is often combined with chemotherapy for obtaining a more effective therapeutic outcome. Cubic-shaped cobalt ferrite nanoparticles (Co-Fe NCs) serve as magnetic hyperthermia agents and as a cytotoxic agent due to the known cobalt ion toxicity, allowing the achievement of both heat and cytotoxic effects from a single platform. In addition to this advantage, Co-Fe NCs have the unique ability to form growing chains under an alternating magnetic field (AMF). This unique chain formation, along with the mild hyperthermia and intrinsic cobalt toxicity, leads to complete tumor regression and improved overall survival in an in vivo murine xenograft model, all under clinically approved AMF conditions. Numerical calculations identify magnetic anisotropy as the main Co-Fe NCs' feature to generate such chain formations. This novel combination therapy can improve the effects of magnetic hyperthermia, inaugurating investigation of mechanical behaviors of nanoparticles under AMF, as a new avenue for cancer therapy.


Assuntos
Cobalto/química , Cobalto/uso terapêutico , Compostos Férricos/química , Compostos Férricos/uso terapêutico , Nanopartículas/química , Animais , Linhagem Celular Tumoral , Cobalto/efeitos adversos , Compostos Férricos/efeitos adversos , Humanos , Hipertermia Induzida , Campos Magnéticos , Camundongos , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Nanotechnology ; 31(30): 305706, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32235044

RESUMO

Novel supported inorganic metal nano-complexes of Ag(I) and Co(II) derived from 4-amino-N-(4-methylpyrimidin-2-yl) benzene sulfonamide (SulMer) were synthesized using olive leaf extract as a reducing agent with grinding and microwave methods. The prepared samples were denoted as Comp1-6. The surface morphologies of the synthesized nanomaterials were analyzed using C, H, N, S analysis, Fourier-transform infrared spectroscopy, UV- visible spectroscopy, proton and carbon nuclear magnetic resonance, scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, and x-ray powder diffraction (XRD) analysis. The data revealed that all the synthesized complexes exhibited a 1:1 metal-to-ligand ratio with a coordination number of 4 or 6. The mean particle size of the nanomaterial samples was 25-35 nm. The XRD patterns indicated a crystalline nature for the complexes. The supported inorganic metal nano-complexes displayed good activity in the adsorptive removal of Direct Red 81 (DR-81) from aqueous solutions. In addition, the effect of the supported metal nano-complexes on the immune system was studied as well as how these anti-inflammatory compounds could be used to treat many autoimmune diseases, most notably rheumatoid arthritis. An experimental model for arthritis can be induced using complete Freund's adjuvant. It was shown that the supported complex offers several advantages such stability, eco-friendliness, simple experimental conditions, short reaction times, and easy work- up.


Assuntos
Anti-Inflamatórios/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Cobalto/administração & dosagem , Adjuvante de Freund/efeitos adversos , Prata/administração & dosagem , Adsorção , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/induzido quimicamente , Compostos Azo/química , Cobalto/química , Cobalto/uso terapêutico , Modelos Animais de Doenças , Feminino , Nanopartículas Metálicas/química , Nanotubos de Carbono/química , Olea/química , Tamanho da Partícula , Folhas de Planta/química , Ratos , Prata/química , Prata/uso terapêutico
8.
Med Phys ; 47(4): 1807-1812, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32056218

RESUMO

PURPOSE: Tattoo fiducials are commonly used in radiotherapy patient alignment, and recent studies have examined the use of UV-excited luminescent tattoo ink as a cosmetic substitute to make these visible under UV illumination. The goal of this study was to show how luminescent tattoo inks could be excited with MV radiation and imaged during beam delivery for direct visualization of field position. METHODS: A survey of nine UV-sensitive tattoo inks with various emission spectra were investigated using both UV and MV excitation. Images of liquid solutions were collected under MV excitation using an intensified-CMOS imager. Solid skin-simulating phantoms were imaged with both surface-painted ink and in situ tattooing during dose delivery by both a clinical linear accelerator and cobalt-60 source. RESULTS: The UV inks have peak fluorescence emission ranging from approximately 440 to 600 nm with lifetimes near 11-16 µs. The luminescence intensity is approximately 6x higher during the x-ray pulse than after the pulse, however, the signal-to-noise is only approximately twice as large. Spatial resolution for imaging was achieved at 1.6 mm accuracy in a skin test phantom. Optical filtering allows for continuous imaging using a cobalt source and provides a mechanism to discriminate ink colors using a monochromatic image sensor. CONCLUSIONS: This study demonstrates how low-cost inks can be used as fiducial markers and imaged both using time-gated and continuous modes during MV dose delivery. Phantom studies demonstrate the potential application of real-time field verification. Further studies are required to understand if this technique could be used as a tool for radiation dosimetry.


Assuntos
Cobalto/uso terapêutico , Tinta , Luminescência , Aceleradores de Partículas , Radioterapia Guiada por Imagem/métodos , Tatuagem , Marcadores Fiduciais , Imagens de Fantasmas , Raios Ultravioleta
9.
Brain Res ; 1732: 146684, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32001242

RESUMO

BACKGROUND: Calcium signaling is described as a relevant factor in synchronization of neurons and increased excitability in epileptogenesis. Aim of the present investigations was to test the antiepileptic effect of the classical inorganic calcium channel blockers cobalt (Co2+), manganese (Mn2+) and magnesium (Mg2+). METHODS: Experiments were carried out on hippocampal slices of guinea pigs. Epileptiform field potentials (EFP) were elicited by adding bicuculline (10 µmol/l) to the artificial cerebrospinal fluid (CSF). Kalium was elevated from normal (4 mmol/l) to 8 mmol/l. Co2+ (CoCl2; 2, 1, 0.5 and 0.1 mmol/l), Mn2+ (MnCl2; 2, 1, 0.5 and 0.1 mmol/l) and Mg2+ (MgCl2; 8, 6, 5, 4 and 2 mmol/l) were added to the superfusate. RESULTS: Concentrations of 2, 1 and 0.5 mmol/l Co2+, 2 and 1 mmol/l Mn2+ and 8 respectively 6 mmol/l Mg2+ were able to suppress EFP sufficient in a dose dependent manner. In concentrations of 0.1 mmol/l Co2+, 0.5 mmol/l and 0.1 mmol/l Mn2+ and 5 respectively 4 and 2 mmol/l Mg2+ suppression was incomplete. With washout of the inorganic calcium channel blockers the EFP reappeared. DISCUSSION: All tree inorganic calcium channel blockers were able to suppress EFP in a dosage dependent and reversible manner. Weak reappearance of EFP after washout of Co2+ might be due to additional cytotoxic effects. The following mechanisms may contribute: i) blockade of voltage-activated calcium channels in the postsynaptic membrane, ii) changes in the activation of voltage-dependent sodium channels, iii) blockade of synaptic transmission.


Assuntos
Cobalto/uso terapêutico , Epilepsia/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Magnésio/uso terapêutico , Manganês/uso terapêutico , Neurônios/efeitos dos fármacos , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Bicuculina/farmacologia , Cobalto/farmacologia , Convulsivantes/farmacologia , Cobaias , Magnésio/farmacologia , Manganês/farmacologia
10.
Chem Res Toxicol ; 33(2): 333-342, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-31599574

RESUMO

There is presently no antidote available to treat azide poisoning. Here, the Schiff-base compound Co(II)-2,12-dimethyl-3,7,11,17-tetraazabicyclo-[11.3.1]heptadeca-1(17)2,11,13,15-pentaenyl dibromide (Co(II)N4[11.3.1]) is investigated to determine if it has the capability to antagonize azide toxicity through a decorporation mechanism. The stopped-flow kinetics of azide binding to Co(II)N4[11.3.1] in the absence of oxygen exhibited three experimentally observable phases: I (fast); II (intermediate); and III (slow). The intermediate phase II accounted for ∼70% of the overall absorbance changes, representing the major process observed, with second-order rate constants of 29 (±4) M-1 s-1 at 25 °C and 70 (±10) M-1 s-1 at 37 °C. The data demonstrated pH independence of the reaction around neutrality, suggesting the unprotonated azide anion to be the attacking species. The binding of azide to Co(II)N4[11.3.1] appears to have a complicated mechanism leading to less than ideal antidotal capability; nonetheless, this cobalt complex does protect against azide intoxication. Administration of Co(II)N4[11.3.1] at 5 min post sodium azide injection (ip) to mice resulted in a substantial decrease of righting-recovery times, 12 (±4) min, compared to controls, 40 (±8) min. In addition, only two out of seven mice "knocked down" when the antidote was administered compared to the controls given toxicant only (100% knockdown).


Assuntos
Antídotos/farmacologia , Antídotos/uso terapêutico , Cobalto/farmacologia , Complexos de Coordenação/farmacologia , Bases de Schiff/farmacologia , Azida Sódica/antagonistas & inibidores , Azida Sódica/envenenamento , Animais , Antídotos/administração & dosagem , Antídotos/química , Cobalto/administração & dosagem , Cobalto/química , Cobalto/uso terapêutico , Complexos de Coordenação/administração & dosagem , Complexos de Coordenação/química , Complexos de Coordenação/uso terapêutico , Espectroscopia de Ressonância de Spin Eletrônica , Concentração de Íons de Hidrogênio , Injeções Intraperitoneais , Masculino , Camundongos , Bases de Schiff/administração & dosagem , Bases de Schiff/química , Bases de Schiff/uso terapêutico , Azida Sódica/administração & dosagem , Taxa de Sobrevida
11.
J Photochem Photobiol B ; 192: 141-146, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30735955

RESUMO

Multidrug resistance (MDR) in bacteria is a major concern these days. One of the reasons is the mutation in efflux pump that prevents the retention of antibiotics and drugs in the bacterial cell. The current work is a step to overcome MDR in bacteria via inhibition of efflux pump and further photoinhibition by thiolated chitosan coated cobalt doped zinc oxide nanoparticles (Co-ZnO) in visible light. Co-ZnO were synthesized in a size range of 40-60 nm. Antibacterial activity of the Co-ZnO against methicillin resistant Staphylococcus aureus (MRSA) was found 100% at a concentration of 10 µg/ml upon activation in sunlight for 15 min. Interestingly, it was found that cobalt as a dopant was able to increase the photodynamic and photothermal activity of Co-ZnO, as in dark conditions, there was only 3-5% of inhibition at 10 µg/ml of nanoparticle concentration. Upon excitation in light, these nanoparticles were able to generate reactive oxygen species (ROS) with a quantum yield of 0.23 ±â€¯0.034. The nanoparticles were also generating heat, Because of the magnetic nature, thus helping in more killing. Thiolated chitosan further helped in blocking the efflux pump of MRSA. The current nanoparticles were also found biocompatible on human red blood cells (LD50 = 214 µg/ml). These data suggest that the MRSA killing ability was facilitated through efflux inhibition and oxidative stress upon excitation in visible light hence, were in accordance with previous findings.


Assuntos
Cobalto/química , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Fotólise , Óxido de Zinco/farmacologia , Proteínas de Bactérias , Cobalto/uso terapêutico , Eritrócitos , Humanos , Luz , Nanopartículas/uso terapêutico , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Óxido de Zinco/uso terapêutico
12.
Biomater Sci ; 7(4): 1554-1564, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30681674

RESUMO

The renoprotective effects of hypoxia inducible-factor (HIF) activators have been demonstrated by improving renal hypoxia in chronic kidney disease. Cobalt chloride is one of the most widely used HIF activators in biomedicine; however, poor kidney targeting and undesirable side effects greatly limit its clinical applications. Here, we report a novel stimuli-responsive drug release nanoplatform in which glutathione (GSH)-modified Au nanoparticles (GLAuNPs) and Co2+ self-assemble into nanoassemblies (GLAuNPs-Co) through coordination interactions between empty orbitals of Co2+ and lone pairs of GSH. The GLAuNPs, when used as a drug carrier, demonstrated high drug loading capacity and pH-triggered drug release after assembling with Co2+. The acidic environment of lysosomes in renal fibrosis tissues could disassemble GLAuNPs-Co and release Co2+. Moreover, encapsulation of the Co2+ ions in the GLAuNPs greatly lowered the cytotoxicity of Co2+ in kidney tubule cells. Tissue fluorescence imaging showed that GLAuNPs-Co specifically accumulated in the kidneys, especially in the renal proximal tubules. After GLAuNPs-Co was intraperitoneally injected into ureter-obstructed mice, significant attenuation of interstitial fibrosis was exhibited. The beneficial effects can be mainly ascribed to miR-29c expression restored by HIF-α activation. These findings revealed that GLAuNPs-Co have pH-responsive drug release and renal targeting capabilities; thus, they are a promising drug delivery platform for treating kidney disease.


Assuntos
Cobalto/uso terapêutico , Fibrose/tratamento farmacológico , Ouro/química , Nefropatias/tratamento farmacológico , Nanopartículas Metálicas/química , Animais , Células Cultivadas , Cobalto/química , Cobalto/farmacologia , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Imagem Óptica , Ratos
13.
N Z Vet J ; 67(2): 105-108, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30557526

RESUMO

AIMS: To investigate the production responses and cost-benefit of administering a controlled-release anthelmintic capsule (CRC) to pregnant yearling ewes prior to lambing. METHODS: Yearling ewes from two commercial sheep flocks (A, n=489; B, n=248) in the North Island of New Zealand were enrolled in the study. Prior to lambing, CRC containing albendazole and abamectin were administered to half the ewes while the other half remained untreated. Ewe liveweights and body condition scores were measured prior to lambing, at weaning and, for Flock B, prior to subsequent mating. Lambs were matched to dams shortly after birth and the weight and number of lamb weaned per ewe were determined. A cost-benefit analysis was undertaken for Flock B considering the increased weight of lamb weaned per ewe, and the weight of ewes at the next mating and the benefit in terms of lambs born. RESULTS: The mean weight at weaning of treated ewes was greater for treated than untreated ewes by 2.76 (95% CI 0.64-4.88) kg in Flock A (p<0.001) and 2.35 (95% CI -0.41-5.12) kg in Flock B (p=0.003); the weight of lamb weaned per ewe was greater for treated than untreated ewes by 1.43 (95% CI -0.71 to -3.49) kg in Flock A (p=0.041) and 3.97 (95% CI 1.59-6.37) kg in Flock B (p<0.001), and ewe liveweight prior to subsequent mating was greater for treated than untreated ewes in Flock B by 4.60 (95% CI 3.6-5.6) kg (p<0.001). There was no difference in the percentage of lambs reared to weaning between treated and untreated ewes in either flock (p>0.8). The overall cost-benefit of treatment for Flock B was NZ$9.44 per treated ewe. CONCLUSIONS AND CLINICAL RELEVANCE: Pre-lambing CRC administration to yearling ewes resulted in increased ewe weaning weights and weight of lamb weaned in both the flocks studied. There was an economic benefit in the one flock where this was assessed.


Assuntos
Albendazol/uso terapêutico , Cobalto/uso terapêutico , Helmintíase Animal/prevenção & controle , Ivermectina/análogos & derivados , Selênio/uso terapêutico , Doenças dos Ovinos/prevenção & controle , Albendazol/administração & dosagem , Albendazol/economia , Animais , Anti-Helmínticos/economia , Anti-Helmínticos/uso terapêutico , Cobalto/administração & dosagem , Cobalto/economia , Análise Custo-Benefício , Preparações de Ação Retardada , Feminino , Helmintíase Animal/economia , Ivermectina/administração & dosagem , Ivermectina/economia , Ivermectina/uso terapêutico , Nova Zelândia/epidemiologia , Gravidez , Selênio/administração & dosagem , Selênio/economia , Ovinos , Doenças dos Ovinos/economia , Doenças dos Ovinos/epidemiologia
14.
Int J Med Sci ; 15(13): 1423-1432, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30443161

RESUMO

Peripheral nerve injury is known to activate the hypoxia-inducible factor-1α (HIF-1α) pathway as one of pro-regenerative transcriptional programs, which could stimulate multiple injury-induced gene expression and contribute to axon regeneration and functional recovery. However, the role of HIF-1α in peripheral nerve regeneration remains to be fully elucidated. In this study, rats were divided into three groups and treated with sham surgery, surgery with cobalt chloride (CoCl2) and surgery with saline, respectively. Sciatic functional index, morphologic evaluations of muscle fibers, and never conduction velocity were performed to measure the functional recovery at 12 weeks postoperatively. In addition, the effects of CoCl2 on the expression of HIF-1α, glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were determined at mRNA levels; as well as HIF-1α, the dual leucine zipper kinase (DLK), the c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), BDNF and NGF were measured at protein level at 4 weeks postoperatively. Systemic administration of CoCl2 (15 mg/kg/day intraperitoneally) significantly promoted functional recovery of rats with sciatic nerve transection injury. This study demonstrated in rats treated with CoCl2, the expression of HIF-1α, GDNF, BDNF and NGF was significantly increased at mRNA level, while HIF-1α, DLK, p-JNK, BDNF and NGF was significantly increased at protein level.


Assuntos
Cobalto/uso terapêutico , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Animais , Feminino , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Regeneração Nervosa/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/lesões
15.
Nanomedicine (Lond) ; 13(10): 1221-1238, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29882719

RESUMO

Magnetic nanoparticles (MNPs) are very attractive especially for biomedical applications, among which, iron oxide nanoparticles have received substantial attention in the past decade due to the elemental composition that makes them biocompatible and degradable. However recently, other magnetic nanomaterials such as spinel ferrites that can provide improved magnetic properties such as coercivity and anisotropy without compromising on inherent advantages of iron oxide nanoparticles are being researched for better applicability of MNPs. Among various spinel ferrites, cobalt ferrite (CoFe2O4) nanoparticles (NPs) are one of the most explored MNPs. Therefore, the intention of this article is to provide a comprehensive review of CoFe2O4 NPs and their inherent properties that make them exceptional candidates, different synthesis methods that influence their properties, and applications of CoFe2O4 NPs and their relevant applications that have been considered in biotechnology and bioengineering.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Cobalto/uso terapêutico , Compostos Férricos/uso terapêutico , Nanopartículas de Magnetita/uso terapêutico , Anisotropia , Materiais Biocompatíveis/química , Cobalto/química , Compostos Férricos/química , Humanos , Nanopartículas de Magnetita/química , Nanotecnologia/tendências
16.
Med Phys ; 45(1): 429-437, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29171060

RESUMO

PURPOSE: Experimental dosimetry of high-dose-rate (HDR) 192 Ir brachytherapy (BT) sources is complicated due to high dose and dose-rate gradients, and softening of photon energy spectrum with depth. A single crystal synthetic diamond detector microDiamond (PTW 60019, Freiburg, Germany) has a small active volume, high sensitivity, direct readout, and nearly water-equivalent active volume. The purpose of this study was to evaluate the suitability of microDiamond detectors for the determination of absorbed dose to water around HDR 192 Ir BT sources. Three microDiamond detectors were used, allowing for the comparison of their properties. METHODS: In-phantom measurements were performed using microSelectron and VariSource iX HDR 192 Ir BT treatment units. Their treatment planning systems (TPSs), Oncentra (v. 4.3) and BrachyVision (v. 13.6), respectively, were used to create irradiation plans for a cubic PMMA phantom with the microDiamond positioned at one of three source-to-detector distances (SDDs) (1.5, 2.5, and 5.5 cm) at a time. The source was stepped in increments of 0.5 cm over a total length of 6 cm to yield absorbed dose of 2 Gy at the nominal reference-point of the detector. Detectors were calibrated in 60 Co beam in terms of absorbed dose to water, and Monte Carlo (MC) calculated beam quality correction factors were applied to account for absorbed-dose energy dependence. Phantom correction factors were applied to account for differences in dimensions between the measurement phantom and a water phantom used for absorbed dose calculations made with a TPS. The same measurements were made with all three of the detectors. Additionally, dose-rate dependence and stability of the detectors were evaluated in 60 Co beam. RESULTS: The percentage differences between experimentally determined and TPS-calculated absorbed doses to water were from -1.3% to +2.9%. The values agreed to within experimental uncertainties, which were from 1.9% to 4.3% (k = 2) depending on the detector, SDD and treatment delivery unit. No dose-rate or intrinsic energy dependence corrections were applied. All microDiamonds were comparable in terms of preirradiation dose, stability of the readings and energy response, and showed a good agreement. CONCLUSIONS: The results indicate that the microDiamond is potentially suitable for the determination of absorbed dose to water around HDR 192 Ir BT sources and may be used for independent verification of TPS's calculations, as well as for QA measurements of HDR 192 Ir BT treatment delivery units at clinical sites.


Assuntos
Braquiterapia/instrumentação , Radioisótopos de Irídio/uso terapêutico , Dosímetros de Radiação , Radiometria/instrumentação , Calibragem , Cobalto/uso terapêutico , Simulação por Computador , Método de Monte Carlo , Imagens de Fantasmas , Doses de Radiação , Água
17.
J Interv Cardiol ; 31(2): 170-176, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29166699

RESUMO

BACKGROUNDS: New-generation bioresorbable polymer-everolimus eluting stents (BP-EES) are available. This study aimed to compare the clinical outcomes for BP-EES compared to more established stent designs, namely the platinum chromium-EES (PtCr-EES) and cobalt chrome-EES(CoCr-EES) in patients with the end-stage chronic kidney disease (CKD) including hemodialysis (HD). METHODS: One-hundred-forty-one consecutive stents (BP-EES [n = 44], PtCr-EES [n = 45], and CoCr-EES [n = 52]) were implanted in 104 patients with CKD. All patients underwent a follow-up coronary angiography at 12 months after implantation. End-stage CKD was defined as an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 , or the need for HD. The following outcome variables were compared among the three stent groups after implantation and the 12-month follow-up: target lesion revascularization (TLR), stent thrombosis (ST), and major adverse cardiac event (MACE). Minimal stent diameter (MSD) and %diameter-stenosis (%DS) were measured using quantitative coronary angiography. RESULTS: The overall rate of TLR and MACE was 14.6% and 30.8%, respectively, with no incidence of ST. Immediately after implantation, the MSD (P = 0.22) and %DS (P = 0.42) were equivalent among the three groups. However, at the 12-month follow-up, a tendency towards higher TLR was observed for the BP-EES group (22.7%) compared with the PtCr-EES (8.8%) and CoCr-EES (9.6%) groups (P = 0.07). Late loss in lumen diameter was also significantly greater for the BP-EES (0.51 ± 0.64 mm) group than either the PtCr-EES (0.20 ± 0.61 mm) and CoCr-EES (0.25 ± 0.70 mm) groups (P = 0.03). CONCLUSIONS: BP-EES might increase the risk of in-stent restenosis in patients with end-stage of CKD or the need for HD.


Assuntos
Cromo/uso terapêutico , Cobalto/uso terapêutico , Doença da Artéria Coronariana , Reestenose Coronária , Vasos Coronários , Everolimo/uso terapêutico , Falência Renal Crônica , Intervenção Coronária Percutânea/efeitos adversos , Platina/uso terapêutico , Implantes Absorvíveis/normas , Idoso , Angiografia Coronária/métodos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/diagnóstico , Reestenose Coronária/epidemiologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Stents Farmacológicos/normas , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Diálise Renal/métodos , Fatores de Risco , Oligoelementos/uso terapêutico , Resultado do Tratamento
18.
Arq. bras. med. vet. zootec. (Online) ; 69(6): 1683-1692, nov.-dez. 2017. tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-911302

RESUMO

The quality of products derived from eggs depends on the quality of the raw material source and the industrial production. The contamination by fungi and bacteria can occur after exposure of the product in the retail market. The objective of this study was to evaluate the microbiological quality of 60 samples of derivated egg products and evaluate the effects of gamma radiation of cobalt-60, using the dose of 5 and 10 kGy, for decontamination of products collected in the retail market in the São Paulo city. The bacterial count was performed by the most probable number (MPN) and the fungal counts by serial dilution after plating surface. It was observed a decrease in the humidity and water activity (Aw) values of irradiated whole egg powder and white egg powder samples (p<0.05), but there was no significant change in the pH of the same samples irradiated with 5 and 10 kGy (p>0.05). In the powdered yolk the values of pH and Aw presented a significant difference (p<0.05), but no significant difference in the humidity values of 5 and 10 kGy irradiated samples (p>0.05). Effective microbial sterilization of all products occurred at the dose of 10 kGy.(AU)


A qualidade dos produtos derivados de ovos depende da qualidade da matéria-prima e da produção industrial. A contaminação por fungos e bactérias pode ocorrer após a exposição do produto no mercado varejista. O objetivo deste estudo foi avaliar a qualidade microbiológica de 60 amostras de derivados de ovos e avaliar os efeitos da radiação gama de cobalto-60, utilizando-se as doses de 5 e 10 kGy, para descontaminação dos produtos coletados no mercado varejista da cidade de São Paulo. A contagem bacteriana foi realizada pelo número mais provável (MPN), e as contagens fúngicas por diluição seriada em plaqueamento de superfície. Foi observada uma diminuição dos valores da umidade e da atividade de água (Aa) das amostras irradiadas de ovo integral em pó e clara em pó (p<0,05), mas sem alteração significativa do pH nas mesmas amostras irradiadas com 5 e 10 kGy (p>0,05). Em gema em pó, observou-se diferença significativa (p<0,05) nos valores de pH e Aa, mas não houve mudança expressiva nos valores de umidade nas amostras irradiadas com 5 e 10 kGy (p>0,05). A esterilização microbiana eficaz de todos os produtos ocorreu com a dose de 10 kGy.(AU)


Assuntos
Ovos/microbiologia , Ovos/efeitos da radiação , Raios gama/uso terapêutico , Esterilização/métodos , Cobalto/uso terapêutico , Fungos/efeitos da radiação
19.
Sci Rep ; 7(1): 4257, 2017 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-28652596

RESUMO

We demonstrate the effectiveness of out-of-plane magnetized magnetic microdiscs for cancer treatment through mechanical cell disruption under an applied rotating magnetic field. The magnetic particles are synthetic antiferromagnets formed from a repeated motif of ultrathin CoFeB/Pt layers. In-vitro studies on glioma cells are used to compare the efficiency of the CoFeB/Pt microdiscs with Py vortex microdiscs. It is found that the CoFeB/Pt microdiscs are able to damage 62 ± 3% of cancer cells compared with 12 ± 2% after applying a 10 kOe rotating field for one minute. The torques applied by each type of particle are measured and are shown to match values predicted by a simple Stoner-Wohlfarth anisotropy model, giving maximum values of 20 fNm for the CoFeB/Pt and 75 fNm for the Py vortex particles. The symmetry of the anisotropy is argued to be more important than the magnitude of the torque in causing effective cell destruction in these experiments. This work shows how future magnetic particles can be successfully designed for applications requiring control of applied torques.


Assuntos
Anisotropia , Glioma/terapia , Campos Magnéticos , Torção Mecânica , Linhagem Celular Tumoral , Cobalto/química , Cobalto/uso terapêutico , Glioma/patologia , Humanos , Ferro/química , Ferro/uso terapêutico
20.
World Neurosurg ; 103: 404-409, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28427980

RESUMO

BACKGROUND: The use of titanium alloy (Ti) rods is frequently associated with rod fracture after spinal fixation. To address this issue, cobalt chrome (CoCr) rods, which are advantageous because of their greater strength and resistance to fatigue relative to Ti rods, have been introduced. The purpose of the present study was to compare radiographic outcomes after the use of Ti versus CoCr rods in a matched cohort of patients undergoing posterior spinal fusion for treatment of spinal instability. METHODS: We retrospectively reviewed data from patients who had undergone spinal fusion involving more than 3 levels at a single institution between 2004 and 2015. Patients were matched for age, diagnosis, 3-column osteotomy, levels fused, and T score. Fifty patients with Ti rods were identified and appropriately matched to 50 consecutive patients with CoCr rods. RESULTS: The distributions of age at surgery, sex, diagnosis, 3-column osteotomy, levels fused, number of patients with previous surgical procedures, and T score did not significantly differ between the 2 groups. However, there were significant differences in length of follow-up (CoCr, 25.0 vs. Ti, 28.5 months; P < 0.001), fusion rate (CoCr, 45 [90%] vs. Ti, 33 [66%]; P = 0.004), occurrence of rod breakage (CoCr, 0 vs. T, 8 [16%]; P = 0.006), and junctional kyphosis (CoCr, 24 [46%] vs. Ti, 9 [18%]; P = 0.003). CONCLUSIONS: Our findings indicate that the use of CoCr rods is effective in ensuring stability of the posterior spinal construct and accomplishment of spinal fusion. Furthermore, our results indicate that junctional kyphosis may occur more frequently in CoCr systems than in Ti systems.


Assuntos
Ligas de Cromo/uso terapêutico , Cobalto/uso terapêutico , Cifose/etiologia , Fusão Vertebral/instrumentação , Titânio/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fixadores Internos , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/cirurgia , Cifose/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Doenças da Coluna Vertebral/diagnóstico por imagem , Doenças da Coluna Vertebral/cirurgia , Resultado do Tratamento , Adulto Jovem
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