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1.
Musculoskelet Surg ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806854

RESUMEN

PURPOSE: In the 1960s, Harrington instrumentation (HRI) revolutionized the surgical treatment of adolescent idiopathic scoliosis (AIS). Despite the transition to more innovative techniques, concerns regarding its impact on sagittal alignment, associations with low back pain, and correction loss have consistently persisted. The aim of this meta-analysis is precisely to evaluate the clinical and radiological outcomes, as well as the complications of patients treated with HRI over an extended follow-up period. A systematic search of articles about AIS patients who underwent HRI and reported long-term outcomes (> 10 years) was conducted on electronic databases according to PRISMA guidelines. Data regarding radiographic and clinical outcomes were extracted and meta-analyses were performed. Eleven studies comprising 644 patients were included. The mean follow-up ranged from 10.8 to 51.7 years. Radiographic analysis revealed a decrease in the main curve Cobb angle from 60.6° to 38.3°, with a correction loss of - 9.49° between postoperative and last follow-up. Concerning sagittal parameters, preoperative thoracic kyphosis was 19.65° at last follow-up, and preoperative lumbar lordosis was 42.94°. Additional spine surgeries were required in 42% of patients. Clinical outcomes varied among studies, but overall, HRI patients showed comparable quality of life and function to controls, although a higher incidence of low back pain was reported. Patients who underwent HRI exhibited suboptimal correction of rib deformity and a flattened sagittal spinal alignment. However, they generally displayed favourable long-term functional outcomes. Despite the implant's tendency to reduce lumbar curvature, patients achieved good clinical outcomes and functional scores comparable to age-matched individuals, suggesting that disability is not an inevitable consequence of lumbar flattening.

2.
Indian J Orthop ; 58(6): 637-649, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38812868

RESUMEN

Background: The most effective injective treatment approach for sacroiliac joint (SIJ) pain remains unclear. Aim of this study was to quantify the safety and effectiveness of the available injective strategies to address SIJ pain. Methods: A systematic review and meta-analysis of the literature was conducted on PubMed, Scopus, and Embase databases from inception until January 2023. Inclusion criteria were studies written in English, comparative and non-comparative studies regardless of the minimum follow-up, and case series on SIJ injections. Safety and efficacy of the different injection therapies for the SIJ were quantified. A meta-analysis was conducted on the available data of the documented injective therapies. The "Checklist for Measuring Quality" by Downs and Black was used to assess the risk of bias and the quality of papers. Results: The literature search retrieved 43 papers (2431 patients): 16 retrospective case series, 2 retrospective comparative studies, 17 prospective case series, 3 prospective comparative studies, and 5 randomized controlled trials. Of the selected studies, 63% examined the effect of steroid injections, 16% of PRP injections, while 21% reported other heterogeneous treatments. The failure rate was 26% in steroid injections and 14% in PRP injections. The meta-analysis showed a statistically significant reduction in pain with the VAS score for both steroids and PRP: steroids improvement at mid-term 3.4 points (p < 0.05), at long-term 3.0 (p < 0.05), PRP improvement at mid-term 2.2 (p = 0.007), at long-term 2.3 points of the VAS pain scale (p = 0.02). Conclusions: Steroids are the most documented injective approach, with studies showing an overall safety and effectiveness. Still, the high number of failures underlined by some studies suggest the need for alternative procedures. Early PRP data showed promise, but the limitations of the current literature do not allow to clearly define the most suitable injective approach, and further studies are needed to identify the best injective treatment for SIJ patients.

3.
Musculoskelet Surg ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38805165

RESUMEN

Postoperative care of ankle fractures treated with open reduction and internal fixation (ORIF) is a debated topic. A meta-analysis of Randomized Controlled Trials was conducted with the aim of comparing early mobilization and weightbearing to traditional postoperative protocols. A systematic search of electronic databases was conducted according to the PRISMA guidelines. Only randomized clinical trials were included. Data about clinical outcome, time to return to work and complications were extracted and summarized. Meta-analyses were performed. Twenty studies for a total of 1328 patients were included. Early mobilization was compared to immobilization in 724 patients: the two groups did not significantly differ in terms of short- and long-term clinical outcome (p = 0.08 and p = 0.41, respectively). However, early mobilization resulted to be significantly associated with faster return to work (p = 0.047). Early weightbearing was compared to nonweightbearing in 1088 patients. While the clinical difference between the two groups was not significant at short term (p = 0.08), it was significant at long term (p = 0.002). No other significant differences, in particular regarding complications, were highlighted between different groups. Early motion, early weightbearing and traditional postoperative protocols are all safe strategies after ORIF for unstable ankle fractures. Early mobilization is significantly associated with faster return to work and early weightbearing improves long term clinical outcome.Level of evidence: I.

5.
Musculoskelet Surg ; 108(1): 47-61, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36877336

RESUMEN

To conduct a systematic review of the literature in order to establish if there is an overall adverse effect of accidental durotomy on the long-term patients' reported outcome after elective spine surgery. A systematic literature search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data about pre- and postoperative clinical outcomes of patients with accidental durotomy and patients without were extracted and analysed. After screening, eleven studies were included with a total of 80,541 patients. About 4112 of these patients (5.10%) had incidental dural tear. When comparing patients with dural tear to patients without, 9/11 authors found no patients' reported differences at last follow-up. One author found a slightly worse VAS back pain in dural tear patients, and another author found inferior SF-36 and ODI scores in dural tear patients (both below minimal clinically important difference). Accidental dural tear did not have a significant adverse effect on clinical outcome of elective spine surgery. More studies are needed to better demonstrate this result.


Asunto(s)
Procedimientos Ortopédicos , Columna Vertebral , Humanos , Columna Vertebral/cirugía , Procedimientos Ortopédicos/efectos adversos
6.
Musculoskelet Surg ; 108(1): 1-9, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37943411

RESUMEN

The purpose of this systematic review was to analyze the current use of adipose-derived mesenchymal stem cells (ADMSCs) and present the available evidence on their therapeutic potential in the treatment of ankle orthopedic issues, evaluating the applications and results. A literature search of PubMed, Google Scholar, EMBASE and Cochrane Library database was performed. The review was conducted following PRISMA guidelines. Risk of bias assessment was conducted through the Methodological Index for Non-Randomized Studies (MINORS) criteria. Initial search results yielded 4348 articles. A total of 8 articles were included in the review process. No clinical evidence has demonstrated the effectiveness of one isolation method over the other, but nonenzymatic mechanical method has more advantages. In all studies included significant clinical outcomes improvement were recorded in patients affected by osteochondral lesion and osteoarthritis of ankle. All studies performed a concomitant procedure. No serious complications were reported. ADMSC injection, especially through the nonenzymatic mechanical methods, looks to be simple and promising treatment for osteochondral lesions and osteoarthritis of the ankle, with no severe complications. The current scarcity of studies and their low-quality level preclude definitive conclusions presently. LEVEL OF EVIDENCE: III.


Asunto(s)
Osteoartritis , Astrágalo , Humanos , Tobillo , Articulación del Tobillo , Osteoartritis/terapia , Células Madre , Resultado del Tratamiento
7.
Phys Rev Lett ; 131(16): 162701, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37925687

RESUMEN

The ^{12}C/^{13}C ratio is a significant indicator of nucleosynthesis and mixing processes during hydrogen burning in stars. Its value mainly depends on the relative rates of the ^{12}C(p,γ)^{13}N and ^{13}C(p,γ)^{14}N reactions. Both reactions have been studied at the Laboratory for Underground Nuclear Astrophysics (LUNA) in Italy down to the lowest energies to date (E_{c.m.}=60 keV) reaching for the first time the high energy tail of hydrogen burning in the shell of giant stars. Our cross sections, obtained with both prompt γ-ray detection and activation measurements, are the most precise to date with overall systematic uncertainties of 7%-8%. Compared with most of the literature, our results are systematically lower, by 25% for the ^{12}C(p,γ)^{13}N reaction and by 30% for ^{13}C(p,γ)^{14}N. We provide the most precise value up to now of 3.6±0.4 in the 20-140 MK range for the lowest possible ^{12}C/^{13}C ratio that can be produced during H burning in giant stars.

8.
Musculoskelet Surg ; 2023 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-37338751

RESUMEN

The aim of the present study is to systematically review the current literature about diagnosis and treatment of acute inflammatory sacroiliitis in pregnant or post-partum women. A systematic search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data about clinical presentation, diagnosis methods and treatment strategies were retrieved from included studies and reported in a table. After screening, five studies on 34 women were included; they were all affected by acute inflammatory sacroiliitis. Clinical examination and magnetic resonance imaging were used to confirm diagnosis. In four studies, patients were treated with ultrasound-guided sacroiliac injections of steroids and local anesthetics, while one study used only manual mobilization. Clinical scores improved in all patients. Ultrasound-guided injections proved to be a safe and effective strategy for inflammatory sacroiliitis treatment during pregnancy or post-partum.

9.
Musculoskelet Surg ; 107(3): 337-343, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36376751

RESUMEN

PURPOSE: To describe a new surgical technique for osteochondral lesions of the ankle, using bone marrow concentrate on a scaffold and homologous bone graft positioned through a retrograde approach. Many surgical options for ankle osteochondral lesions have been described, and the ideal treatment is still debated. Bone marrow stimulating techniques are recommended for cystic lesions, with some concerns regarding the healing potential of the subchondral bone. In case of wide osteochondral defects, regenerative solutions are preferred but a massive chondral debridement is usually required. To overcome these problems, a novel technique is proposed. METHODS: The proposed technique was performed on patients affected by osteochondral lesions of the talus, either cysts with intact cartilage or wide osteochondral defects. A preoperative magnetic resonance imaging was obtained to localize the lesion. A 6-mm tarsal tunnel was retrogradely created toward the lesion, to allow a complete sub-endo-chondral debridement preserving the healthy cartilage. A hyaluronan scaffold soaked with a previously prepared bone marrow concentrate was retrogradely positioned under the cartilage surface and the tunnel was filled with homologous bone graft. Preoperative clinical scores and postoperative x-rays were registered. RESULTS: Four patients were treated using this technique. No intraoperative and postoperative complications occurred. Good bone remodeling was observed at 12-week postoperative x-rays. CONCLUSIONS: This technique combines the mini-invasiveness of retrograde drilling with the regenerative properties of biological scaffold soaked with bone marrow concentrate. Despite further research being needed, it seems a new viable solution to treat both subchondral cysts and large osteochondral defects of the ankle, whose management is still controversial.


Asunto(s)
Cartílago Articular , Astrágalo , Humanos , Tobillo , Artroscopía/métodos , Articulación del Tobillo/diagnóstico por imagen , Articulación del Tobillo/cirugía , Astrágalo/cirugía , Radiografía , Imagen por Resonancia Magnética , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/cirugía , Resultado del Tratamiento
11.
Musculoskelet Surg ; 107(3): 323-331, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36183053

RESUMEN

PURPOSE: The aim of the present study is to evaluate the results of our all posterior-one stage surgical technique for the reduction and fusion of high-grade high-dysplastic spondylolisthesis. METHODS: Patients over 11 years old with high-grade spondylolisthesis treated by reduction and circumferential fusion with a posterior-only approach were reviewed. Data about operative time, blood loss, length of stay, intra- and postoperative complications were collected. Meyerding grade (M), lumbar lordosis (LL), thoracic kyphosis (TK), pelvic incidence (PI), pelvic tilt (PT), lumbosacral angle (LSA), slip angle (SLIP), lumbar index (LI) and severity index were measured on preoperative and last follow-up. Sagittal vertical axis (SVA) was used to assess sagittal balance. RESULTS: Of the 14 included patients, L5-S1 arthrodesis was performed in 12 cases, and L4-S1 was performed in 2 cases. Average surgical time was 275 ± 65 min; average blood loss was 635 ± 375 mL. Average length of stay of was 3.9 ± 1.5 days. The SLIP angle improves from 33.8° ± 7.3° to 6.4° ± 2.5°, (p = 0.002); the lumbosacral angle improves from 68.8° ± 18.6° to 100.7° ± 13.2°, (p = 0.01); and the SVA decreased from 49.4 ± 22.1 mm to 34.4 ± 8.6 mm (p = 0.02). No significant changes were observed in PI, PT and SS. Thoracic kyphosis (TK) and lumbar lordosis (LL) did not change significantly. At last follow-up, no patient had surgical site infection or mechanical complications; no pseudoarthrosis was observed. No revision surgery was performed. CONCLUSION: Although technically demanding, reduction and fusion with one stage all posterior approach prove to be a safe and effective.


Asunto(s)
Cifosis , Lordosis , Fusión Vertebral , Espondilolistesis , Humanos , Niño , Espondilolistesis/diagnóstico por imagen , Espondilolistesis/cirugía , Lordosis/diagnóstico por imagen , Lordosis/cirugía , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Estudios Retrospectivos , Cifosis/diagnóstico por imagen , Cifosis/etiología , Cifosis/cirugía , Fusión Vertebral/métodos
12.
Musculoskelet Surg ; 2022 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-35947326

RESUMEN

Little evidences are available in the literature concerning the outcomes of total knee replacement (TKR) in poliomyelitis patients with severe knee deformities or degeneration. Encouraging results have been reported concerning the use of constrained implants, i.e., rotating hinge knee prosthesis (RHK), compared to less constrained ones. The purpose of this paper is to report our experience with rotating hinge total knee replacement, using only RHK prosthesis, to determine functional results, complications, and survival of TKR in poliomyelitis patients. We performed a retrospective chart review of 14 patients with a history of knee osteoarthritis following poliomyelitis that underwent primary TKR, for a total of 15 surgical procedure (one bilateral case). Preoperative and postoperative clinical measurements have been conducted for all patients using the Knee Society Score (KSS). Hip-knee angle, recurvatum knee angle, and Insall-Salvati index were evaluated with full weight-bearing panoramic view X-ray preoperatively and postoperatively. The 2-year postoperative clinical KSS significantly improved from the preoperative scores. The average clinical KSS improved from 32,9 (range 3-48) preoperatively to 77,4 (range 60-88) postoperatively (P value < 0.005). The average functional KSS improved from 32,5 (range 10-60) preoperatively to 59,4 (range 30-95) postoperatively (P value < 0.005). TKR is a successful treatment in improving knee function and patient's quality of life. Using constrained implants, especially rotating hinge implants in polio patients with a quadriceps muscle weakness, could be a good alternative to maintain a physiological kinematics and reducing the revision rate due to knee instability.

13.
Musculoskelet Surg ; 2022 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-35943693

RESUMEN

Pedicle screws is the current gold standard in spine surgery, achieving a solid tricolumnar fixation which is unreachable by wires and hooks. The freehand technique is the most widely adopted for pedicle screws placing. While freehand technique has been classically performed with manual tools, there has been a recent trend toward the use of power tools. However, placing a pedicle screw remains a technically demanding procedure with significant risk of complications. The aim of this article is to retrospectively evaluate safety and accuracy of free-hand power-assisted pedicle screw placement in a cohort of patients who underwent correction and fusion surgery for scoliosis (both idiopathic and non-idiopathic) in our department. A retrospective review of all patients with scoliosis who underwent surgery and received a postoperative CT scan in our department in a 9-year period was undertaken. Screw density, number and location of pedicle screws were measured using pre and postoperative full-length standing and lateral supine side-bending radiographs. Then, postoperative CT scan was used to assess the accuracy of screw placement according to Gertzbein-Robbins scale. Malpositioned screws were divided according to their displacement direction. Finally, intra and postoperative neurological complications and the need for revision of misplaced screws were recorded. A total of 205 patients were included, with a follow-up of 64.9 ± 38.67 months. All constructs were high density (average density 1.97 ± 0.04), and the average number of fusion levels was 13.72 ± 1.97. A total of 5522 screws were placed: 5308 (96.12%) were grade A, 141 (2.5%) grade B, 73 (1.32%) grade C. Neither grade D nor grade E trajectories were found. The absolute accuracy (grade A) rate was 96.12% (5308/5522) and the effective accuracy (within the safe zone, grade A + B) was 98.6% (5449/5522). Of the 73 misplaced screws (grade C), 59 were lateral (80.80%), 8 anterior (10.95%) and 6 medial (8.22%); 58 were in convexity, while 15 were in concavity (the difference was not statistically significant, p = 0.33). Intraoperatively, neither neurological nor vascular complications were recorded. Postoperatively, 4 screws needed revision (0.072% of the total): Power-assisted pedicle screw placing may be a safe an accurate technique in the scoliosis surgery, both of idiopathic and non-idiopathic etiology. Further, and higher quality, research is necessary in order to better assess the results of this relatively emerging technique.

14.
Phys Rev Lett ; 127(15): 152701, 2021 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-34677992

RESUMEN

One of the main neutron sources for the astrophysical s process is the reaction ^{13}C(α,n)^{16}O, taking place in thermally pulsing asymptotic giant branch stars at temperatures around 90 MK. To model the nucleosynthesis during this process the reaction cross section needs to be known in the 150-230 keV energy window (Gamow peak). At these sub-Coulomb energies, cross section direct measurements are severely affected by the low event rate, making us rely on input from indirect methods and extrapolations from higher-energy direct data. This leads to an uncertainty in the cross section at the relevant energies too high to reliably constrain the nuclear physics input to s-process calculations. We present the results from a new deep-underground measurement of ^{13}C(α,n)^{16}O, covering the energy range 230-300 keV, with drastically reduced uncertainties over previous measurements and for the first time providing data directly inside the s-process Gamow peak. Selected stellar models have been computed to estimate the impact of our revised reaction rate. For stars of nearly solar composition, we find sizeable variations of some isotopes, whose production is influenced by the activation of close-by branching points that are sensitive to the neutron density, in particular, the two radioactive nuclei ^{60}Fe and ^{205}Pb, as well as ^{152}Gd.

15.
Musculoskelet Surg ; 105(2): 117-123, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34050490

RESUMEN

Pedicle screws are the gold standard in spine surgery, allowing a solid tricolumnar fixation which is unmatched by hooks and wires. The freehand technique is the most widely adopted for pedicle screws placing. While freehand technique has been classically performed with manual tools, there has been a recent trend toward the use of power tools. The aim of this review is to summarize and expose potential risks and advantages of power pedicle screws placing. The literature showed that the use of power tools offers an acceptable safety profile, comparable to manual technique. With an adequate training, the power technique may speed up the screw placing, reduce the fluoroscopy time and the physical stress to the spine surgeon. Regarding differences in pull-out strength between power and manual techniques, the literature is still uncertain and inconsistent, both in clinical and preclinical studies. The choice between the use of power and manual freehand pedicle screws placing is still based on the surgeon's own preference.


Asunto(s)
Tornillos Pediculares , Fusión Vertebral , Cirugía Asistida por Computador , Hilos Ortopédicos , Fluoroscopía , Humanos
16.
Knee Surg Sports Traumatol Arthrosc ; 29(10): 3323-3329, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32740877

RESUMEN

PURPOSE: The purpose of this study is to analyse long-term unicompartmental knee arthroplasty (UKA) focusing on survivorship, causes of failure and revision strategy. METHODS: This study is a retrospective analysis of data from a regional arthroplasty registry for cases performed between 2000 and 2017. A total of 6453 UKAs were identified and the following information was analysed: demographic data, diagnosis leading to primary implant, survivorship, complication rate, causes of failure, revision strategies. UKA registry data were compared with total knee arthroplasty (TKA) registry data of 54,012 prostheses, which were implanted in the same time period. RESULTS: 6453 UKAs were included in the study: the vast majority of them (84.4%) were implanted due to primary osteoarthritis followed by deformity (7.1%) and necrosis of the condyle (5.1%). When compared to TKA, UKA showed lower perioperative complication rate (0.3% compared to 0.6%) but higher revision rate (18.2% at 15 years, compared to 6.2% for TKA). No correlation was found between diagnosis leading to primary implant and prosthesis survival. The most frequent cause of failure was total aseptic loosening (37.4%), followed by pain without loosening (19.8%). Of the 620 UKAs requiring revision, 485 were revised with a TKA and 61 of them required a re-revision; on the other hand, of the 35 cases where another UKA was implanted, 16 required a re-revision. CONCLUSION: UKA is associated with fewer perioperative complications but higher revision rates when compared to TKA. Its survivorship is not affected by the diagnosis leading to primary implant. Revision surgery of a failed UKA should be performed implanting a TKA, which is associated with a lower re-revision rate when compared to another UKA. LEVEL OF EVIDENCE: Level 3, therapeutic study.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Artroplastia de Reemplazo de Rodilla/efectos adversos , Humanos , Osteoartritis de la Rodilla/cirugía , Falla de Prótesis , Sistema de Registros , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento
17.
Nature ; 587(7833): 210-213, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33177669

RESUMEN

Light elements were produced in the first few minutes of the Universe through a sequence of nuclear reactions known as Big Bang nucleosynthesis (BBN)1,2. Among the light elements produced during BBN1,2, deuterium is an excellent indicator of cosmological parameters because its abundance is highly sensitive to the primordial baryon density and also depends on the number of neutrino species permeating the early Universe. Although astronomical observations of primordial deuterium abundance have reached percent accuracy3, theoretical predictions4-6 based on BBN are hampered by large uncertainties on the cross-section of the deuterium burning D(p,γ)3He reaction. Here we show that our improved cross-sections of this reaction lead to BBN estimates of the baryon density at the 1.6 percent level, in excellent agreement with a recent analysis of the cosmic microwave background7. Improved cross-section data were obtained by exploiting the negligible cosmic-ray background deep underground at the Laboratory for Underground Nuclear Astrophysics (LUNA) of the Laboratori Nazionali del Gran Sasso (Italy)8,9. We bombarded a high-purity deuterium gas target10 with an intense proton beam from the LUNA 400-kilovolt accelerator11 and detected the γ-rays from the nuclear reaction under study with a high-purity germanium detector. Our experimental results settle the most uncertain nuclear physics input to BBN calculations and substantially improve the reliability of using primordial abundances to probe the physics of the early Universe.

18.
Toxicol In Vitro ; 30(1 Pt B): 583-92, 2015 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-26562325

RESUMEN

The fetal basis of adult disease (FeBAD) theorizes that embryonic challenges initiate pathologies in adult life through epigenetic modification of gene expression. In addition, inheritance of H3K27 methylation marks, especially in vitro, is still controversial. Metals, such as Cd, are known to affect differentiation, DNA repair and epigenetic status in mES cells. We tested the premise that Cd exerts differential toxicity in mouse embryonic stem (mES) cells by targeting total histone protein (THP) production early in stem cell development, while affecting H3K27-mono-methylation (H3K27me(1)) in latter stages of differentiation. The inability of mES cells to recover from Cd insult at concentrations greater than IC50 indicates that maximum cytotoxicity occurs during initial hours of exposure. Moreover, as a measure of chromatin stability, low dose acute Cd exposure lowers THP production. The heritable effects of Cd exposure on cell proliferation, chromatin stability and transcription observed through several cell population doublings were detected only during alternate passages on days 3, 7, and 11, presumably due to slower maturation of histone methylation marks. These findings demonstrate a selective disruption of chromatin structure following acute Cd exposure, an effect not seen in developmentally mature cells. Hence, we present that acute Cd toxicity is cumulative and disrupts DNA repair, while concurrently affecting cell cycle progression, chromatin stability and transcriptional state in mES cells.


Asunto(s)
Cadmio/toxicidad , Histonas/metabolismo , Células Madre Embrionarias de Ratones/efectos de los fármacos , Animales , Ciclo Celular/efectos de los fármacos , Células Cultivadas , Cromatina/efectos de los fármacos , ADN/biosíntesis , Proteína Potenciadora del Homólogo Zeste 2 , Histona Demetilasas con Dominio de Jumonji/antagonistas & inhibidores , Ratones , Mitosis/efectos de los fármacos , Células Madre Embrionarias de Ratones/metabolismo , Complejo Represivo Polycomb 2/metabolismo
19.
Cell Biol Toxicol ; 18(2): 97-108, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12046694

RESUMEN

An in vitro study using human cultured cells was conducted to determine the reliability of fluorescence-based cell viability indicators with traditional in vitro cytotoxicity testing methods. Human lung epithelial carcinoma (A549) cells, and human embryonic skin (WS1) and lung (HFLI) fibroblasts were studied in culture to evaluate their potential to screen for cytotoxicity and to compare to previous protocols conducted in our laboratory. Confluent monolayers were incubated in the absence or presence of increasing concentrations of test chemicals for 24 h, and fluorescent-labeled probes were used to assess toxicity. Eight chemicals, including mercuric chloride, copper sulfate, sodium fluoride, thioridazine HCl, paraquat, amitriptyline-HCl, verapamil-HCl and chloroquine sulfate, were tested with each cell line using calcein-AM and Sytox. The data suggest that fluorescent probes are sensitive indicators of cytotoxicity and contribute to understanding the mechanisms for each chemical. In combination with previously published reports, the similarity of results among cell lines may be explained by the origin of the cell lines rather than by the diversity of the methods and indicators employed.


Asunto(s)
Pulmón/efectos de los fármacos , Piel/efectos de los fármacos , Pruebas de Toxicidad , Células Cultivadas , Fluorescencia , Humanos , Técnicas In Vitro , Pulmón/citología , Piel/citología , Células Tumorales Cultivadas
20.
Toxicol In Vitro ; 16(1): 33-9, 2002 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11812637

RESUMEN

This study was designed to evaluate the potential of an in vitro cell culture method for its ability to determine subacute cytotoxicity and to compare the cytotoxic concentrations with rodent LD(50)s and clinical human toxicity data. Human fetal lung fibroblasts (HFL1) were incubated in the absence or presence of increasing concentrations of test chemicals for 72 h, and cell proliferation was used as a marker for toxicity. Inhibitory concentrations were extrapolated from concentration-effect curves after linear regression analysis. Comparison of the cytotoxicity data from testing 50 chemicals, with available human lethal concentrations for the same chemicals, revealed that the 72-h experimental IC(50)s are as accurate predictors of human toxicity as equivalent toxic blood concentrations derived from rodent LD(50)s. In addition, our results demonstrate that subacute 72-h exposure of HFL1 cells more accurately predicts cytotoxicity than a 24-h mitochondrial assay previously conducted in our laboratory, although the experimental IC(50) values were not statistically different in the two assays. It is anticipated that this procedure, together with a related battery of tests, may supplement or replace currently used animal protocols to screen chemicals for human risk assessment.


Asunto(s)
Pulmón/efectos de los fármacos , Pruebas de Toxicidad/métodos , Xenobióticos/toxicidad , Alternativas a las Pruebas en Animales/métodos , Animales , División Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Dosificación Letal Mediana , Pulmón/citología , Pulmón/metabolismo , Ratas , Sales de Tetrazolio/metabolismo , Tiazoles/metabolismo
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