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1.
Musculoskelet Surg ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806854

RESUMO

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.
Musculoskelet Surg ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805165

RESUMO

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.

4.
Musculoskelet Surg ; 108(1): 47-61, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36877336

RESUMO

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.


Assuntos
Procedimentos Ortopédicos , Coluna Vertebral , Humanos , Coluna Vertebral/cirurgia , Procedimentos Ortopédicos/efeitos adversos
5.
Musculoskelet Surg ; 108(1): 1-9, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37943411

RESUMO

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.


Assuntos
Osteoartrite , Tálus , Humanos , Tornozelo , Articulação do Tornozelo , Osteoartrite/terapia , Células-Tronco , Resultado do Tratamento
6.
Musculoskelet Surg ; 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37338751

RESUMO

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.

7.
Musculoskelet Surg ; 107(3): 337-343, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36376751

RESUMO

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.


Assuntos
Cartilagem Articular , Tálus , Humanos , Tornozelo , Artroscopia/métodos , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Tálus/cirurgia , Radiografia , Imageamento por Ressonância Magnética , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/cirurgia , Resultado do Tratamento
9.
Musculoskelet Surg ; 107(3): 323-331, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36183053

RESUMO

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.


Assuntos
Cifose , Lordose , Fusão Vertebral , Espondilolistese , Humanos , Criança , Espondilolistese/diagnóstico por imagem , Espondilolistese/cirurgia , Lordose/diagnóstico por imagem , Lordose/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Cifose/diagnóstico por imagem , Cifose/etiologia , Cifose/cirurgia , Fusão Vertebral/métodos
10.
Musculoskelet Surg ; 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35947326

RESUMO

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.

11.
Musculoskelet Surg ; 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35943693

RESUMO

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.

12.
Musculoskelet Surg ; 105(2): 117-123, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34050490

RESUMO

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.


Assuntos
Parafusos Pediculares , Fusão Vertebral , Cirurgia Assistida por Computador , Fios Ortopédicos , Fluoroscopia , Humanos
13.
Knee Surg Sports Traumatol Arthrosc ; 29(10): 3323-3329, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32740877

RESUMO

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.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Artroplastia do Joelho/efeitos adversos , Humanos , Osteoartrite do Joelho/cirurgia , Falha de Prótese , Sistema de Registros , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
14.
Toxicol In Vitro ; 30(1 Pt B): 583-92, 2015 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-26562325

RESUMO

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.


Assuntos
Cádmio/toxicidade , Histonas/metabolismo , Células-Tronco Embrionárias Murinas/efeitos dos fármacos , Animais , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Cromatina/efeitos dos fármacos , DNA/biossíntese , Proteína Potenciadora do Homólogo 2 de Zeste , Histona Desmetilases com o Domínio Jumonji/antagonistas & inibidores , Camundongos , Mitose/efeitos dos fármacos , Células-Tronco Embrionárias Murinas/metabolismo , Complexo Repressor Polycomb 2/metabolismo
15.
Cell Biol Toxicol ; 18(2): 97-108, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12046694

RESUMO

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.


Assuntos
Pulmão/efeitos dos fármacos , Pele/efeitos dos fármacos , Testes de Toxicidade , Células Cultivadas , Fluorescência , Humanos , Técnicas In Vitro , Pulmão/citologia , Pele/citologia , Células Tumorais Cultivadas
17.
Arch. med. res ; 24(2): 189-92, jun. 1993. ilus, tab
Artigo em Inglês | LILACS | ID: lil-177000

RESUMO

In order to investigate the presence of secondary amyloidosis in patients with rheumatoid artritis (RA), we performed and abdominal subcutaneous fat biopsy with a truc-cut needle in 50 patients. The tissue was stained with Congo red and was observed with polarized light microscopy. We found amyloid deposits in 78 percent of our patientas. We randomly selected ten patients with a positive biopsy and a second procedure was performed. Tissues were studied with electron microscopy. We found unbranced fibrils characteristic of amyloid in all of them. We found a direct correlation with rheumatoid factor titers: the more intense the amyloid deposit, the higher the rheumatoid factor titers (p< 0.001). We did not find any correlation betwen amyloid deposits and clinical manifestations of disease. Amyloid deposits in RA are more frequent than previously thought, and their clinical importance remains to be determined


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Amiloidose/diagnóstico , Artrite Reumatoide/fisiopatologia
18.
Arch Biochem Biophys ; 276(1): 125-31, 1990 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2297219

RESUMO

The objective of this work was to characterize basal degradation of newly synthesized collagen in human fetal lung fibroblasts. Analysis of 22 separate determinations showed that in cells incubated under normal conditions, the level of intracellular degradation was normally distributed with a mean of 15.2% and a standard deviation of 2.6%. Within each experiment, however, the uncertainty (standard deviation) in determining degradation was very small, usually less than 1.5%. Consideration of the large variation between experiments and the ability of our analytic technique to detect small, but "statistically significant," differences between groups within the same experiment led us to formulate two criteria for determining whether degradation measured in cultures exposed to some agent differs in a "biologically significant" way from degradation measured in control cultures. These criteria were used to evaluate the effects of the following proteinase inhibitors on basal degradation: NH4Cl, which increases the pH of subcellular compartments that are normally acidic; and leupeptin and Na-p-tosyl-L-lysine chloromethyl ketone (TLCK), which are inhibitors of lysosomal cathepsins (B and L) that degrade collagen. NH4Cl (16 mM) lowered degradation to an extent that was both statistically and biologically significant, but neither leupeptin nor TLCK affected degradation. The effect of NH4Cl on degradation was independent of its inhibitory effects on production of collagen, protein, and ATP. These results suggest that basal degradation occurs in, or beyond, an acidic (i.e., NH4Cl-sensitive) but nonlysosomal compartment of the cell, and that NH4Cl inhibits processing within, or transport to, that compartment. This is the first report of an agent that inhibits basal degradation of newly synthesized collagen in soft tissue fibroblasts.


Assuntos
Cloreto de Amônio/farmacologia , Colágeno/metabolismo , Pulmão/metabolismo , Trifosfato de Adenosina/metabolismo , Células Cultivadas , Colágeno/biossíntese , Feto , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Cinética , Leupeptinas/farmacologia , Tosilina Clorometil Cetona/farmacologia
19.
Arch Biochem Biophys ; 270(1): 294-301, 1989 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2494943

RESUMO

Amino acid substitutions in collagen that impair folding of the triple helix result in significant increases in intracellular degradation of newly synthesized collagen. We have studied the effects of agents that cause other kinds of defects in collagen: hydroxynorvaline, a threonine analog that interferes with association of pro-alpha chains; and puromycin, an antibiotic that causes premature release of nascent polypeptides. cis-Hydroxyproline and cycloheximide, whose effects on collagen synthesis and degradation have already been studied and reported, were employed as reference compounds. Human fetal lung fibroblasts were used in these experiments. All the agents inhibited total protein production, and all except cycloheximide inhibited percentage collagen production. Intracellular collagen degradation was increased in cultures exposed to puromycin, hydroxynorvaline, and cis-hydroxyproline, but not in cultures exposed to cycloheximide. These results suggest that pro-alpha chains that were either unassociated (due to hydroxynorvaline) or shortened (due to puromycin) were recognized as abnormal and degraded to the same extent as chains that contained cis-hydroxyproline. However, the increases in degradation could not account completely for the decreases in collagen production (except when cis-hydroxyproline was used at low concentrations). These findings indicate that, in addition to rendering newly synthesized procollagen molecules or partial polypeptide chains more susceptible to intracellular degradation, puromycin, hydroxynorvaline, and cis-hydroxyproline significantly inhibited collagen synthesis.


Assuntos
Colágeno/biossíntese , Membranas Intracelulares/metabolismo , Pulmão/metabolismo , Puromicina/farmacologia , Treonina/análogos & derivados , Linhagem Celular , Colágeno/metabolismo , Cicloeximida/farmacologia , Relação Dose-Resposta a Droga , Feto/metabolismo , Fibroblastos/metabolismo , Humanos , Hidroxiprolina/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/embriologia , Matemática , Treonina/farmacologia
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