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PubMed1993

Phantom studies in osteoporosis.

Differences in measurement results of bone densitometry are an obvious disadvantage of this method. The differences are mainly due to the calibration procedures for bone densitometry systems employed by the manufacturers, the software algorithms for defining the region of interest or edge detection, and the physiological inhomogeneity of body composition. Whereas intra-unit variation of reproducibility is acceptable, inter-unit variation may reach up to 20%. This paper discusses the problems of designing measurement phantoms and underlines the need for standardisation of phantoms for calibration, cross-calibration, and quality control in bone densitometry. A general phantom used for cross-calibration should handle all parameters influencing measurement of bone minerals to yielded dynamic reference values. One has to note that densitometry systems do not measure the absolute bone mineral content but a model-related equivalent of the calibration material.

Absorptiometry, Photon↗
PubMed2004

A prospective clinical practice intervention to improve osteoporosis management following distal forearm fracture.

Secondary prevention of osteoporosis after fracture is underutilized, despite cost-effective therapies. This clinical practice intervention aimed to improve osteoporosis care of the postfracture patient. Residents of Olmsted County, Minnesota, USA, > or = age 45 who sustained a moderate trauma distal forearm fracture were identified, and participants received educational materials, referral for bone densitometry and physician consultation to address osteoporosis in January 1999 through October 2000. Osteoporosis educational materials were provided to patients at the time of recruitment, and primary care physicians provided osteoporosis practice guidelines. Outcomes included: completion of bone densitometry, acceptance of interventions at the first postfracture primary care physician visit, and adherence to advice at 6 months. There were 105 patients identified (80% women), but only 58 agreed to participate (88% women). Women with lower T-scores (< -1.5) had an 89% initial treatment rate, and 67% were adherent to treatment at 6 months. All women with normal bone density (T-score above -1.5) were advised by their primary care physicians about antiresorptive treatment, and 100% adhered to these recommendations, even though they were not eligible for such treatment based on the National Osteoporosis Foundation (NOF) guidelines. None of the men accepted the treatments offered, despite T-scores that fell at or below the NOF treatment threshold. Bone densitometry and consultation improved osteoporosis interventions after index fracture from a 16% baseline rate in the population (1993-1997) to a 45% overall rate for the study population. In summary, while referral for bone densitometry and discussion by a physician about postfracture osteoporosis preventive treatments did increase treatment rate, the majority of patients at highest risk did not accept interventions. Further initiatives are needed to overcome both system and patient barriers.

Absorptiometry, Photon↗
PubMed1999

Evaluation of the simple calculated osteoporosis risk estimation (SCORE) in older Caucasian women: the Rancho Bernardo study.

Osteoporosis is a major health problem in older women. A risk assessment tool, the Simple Calculated Osteoporosis Risk Estimation (SCORE), has been developed to identify postmenopausal women likely to have low bone mass who should be referred for bone densitometry. The objective of this study was to calculate the sensitivity, specificity and predictive values of SCORE in a community-dwelling sample of older women. A total of 1013 postmenopausal Caucasian women aged 44-98 years provided a standard medical history including history of osteoporotic fractures and medication use. Bone mineral density (BMD) was measured at the femoral neck using dual-energy X-ray absorptiometry. In accordance with the SCORE protocol, low BMD was defined as 2 or more standard deviations below the mean BMD in healthy young women. Among these older women (mean age = 72.5 years), 67% had low BMD. Using the recommended SCORE cutpoint of 6, the sensitivity of SCORE was 98% but the specificity was only 12.5%. The positive predictive value (PPV) and negative predictive value (NPV) were 69% and 75%, respectively, meaning that all but 5.5% of the women would be recommended for bone densitometry. Increasing the cutpoint of 11, based on ethnicity and the receiver operating characteristic (ROC) curve, reduced sensitivity to 80% but improved specificity to 46%. The PPV and NPV were 75% and 53%, respectively, meaning that bone scans would not be recommended for 28% of the women. However, 13% of the women with low BMD would be missed. Analyses restricted to women <74 years of age reduced the rate of recommended bone densitometry but increased the number of women with low BMD who would be missed. We conclude that SCORE has limited value as a method for appropriately referring older ambulatory women for bone densitometry.

Absorptiometry, Photon↗
PubMed1998

Prediction of femoral fracture load using automated finite element modeling.

Hip fracture is an important cause of morbidity and mortality among the elderly. Current methods of assessing a patient's risk of hip fracture involve local estimates of bone density (densitometry), and are limited by their inability to account for the complex structural features of the femur. In an effort to improve clinical and research tools for assessing hip fracture risk, this study investigated whether automatically generated, computed tomographic (CT) scan-based finite element (FE) models can be used to estimate femoral fracture load in vitro. Eighteen pairs of femora were examined under two loading conditions one similar to loading during the stance phase of gait, and one simulating impact from a fall. The femora were then mechanically tested to failure and regression analyses between measured fracture load and FE-predicted fracture load were performed. For comparison, densitometry measures were also examined. Significant relationships were found between measured fracture load and FE-predicted fracture load (r = 0.87, stance; r = 0.95, fall; r = 0.97, stance and fall data pooled) and between measured fracture load and densitometry data (r = 0.78, stance; r = 0.91, fall). These results indicate that this sophisticated technique, which is still early in its development, can achieve precision comparable to that of densitometry and can predict femoral fracture load to within -40% to +60% with 95% confidence. Therefore, clinical use of this approach, which would require additional X-ray exposure and expenditure for a CT scan, is not justified at this point. Even so, the potential advantages of this CT/FE technique support further research in this area.

Accidental Falls↗
PubMed2002

[Diagnosing osteoporosis in primary care in Spain (ABOPAP 2000 study)].

OBJECTIVE: To discover how osteoporosis is tackled in Spanish primary care before the publication of the semFYC osteoporosis guide. DESIGN: Self-filled questionnaire for primary care doctors sent out by commercial mail (in blocks per province). SETTING: Five thousand family medicine clinics in Spain.Participants. Doctors working in primary care.Measurements. Level of activity relating to osteoporosis in daily consultations (identification of risk factors, screening, who conducts diagnosis and follow-up, level of access to densitometry and specialist) and identification data (province, type of work centre and number of consultations per day). MAIN RESULTS: 414 replies embracing reformed and non-reformed centres from the entire country, with different case overloads. 32.3% stated that osteoporosis treatment was viewed as a preventive activity in their centre and only 35.5% systematically asked for family history of osteoporosis. Osteoporosis screening was high in determined situations (82.9% in vertebral compression, 78.3% in hip fracture) and deficient in others (59.6% in glucocorticoid treatment, 46.6% in colles fractures, 36% in chronic nephropathy, 29.2% in thinness, 17.1% in chronic hepatopathy and 11.8% in treatment for epilepsy or with lithium). 73.9% could not request bone densitometry and 64.3% thought that access to other care levels was complicated. 51.9% said they continued to monitor osteoporosis. The impossibility of requesting densitometry or difficult access conditioned the screening level. There were differences in access according to autonomous communities, with Catalonia having best access to Densitometry (75%), followed by the communities of Madrid, Valencia and Euskadi (30%). CONCLUSIONS: Diagnosis of osteoporosis in primary care is deficient and is partly conditioned by difficulty in access to diagnostic tests and the lack of systematic screening.

Humans↗
PubMed2001

Diagnostic yield of computed tomography and densitometric measurements of the lung in thoracoscopically-defined idiopathic spontaneous pneumothorax.

In the present study, the diagnostic yield of high resolution computed tomography (HRCT) is evaluated in patients with thoracoscopically-verified idiopathic spontaneous pneumothorax (SP). Visual assessment as well as densitometry of lung parenchyma was performed. In eight of the 20 prospectively-evaluated SP patients, emphysema-like (EL) changes such as blebs and bullae could be detected. The SP patients with EL changes were significantly older and were more heavy smokers. Spirometrically-controlled CT lung densitometry showed no differences between the patient group with or without these EL changes. Comparing the densitometric measurements of the patient group with a healthy control group no significant differences in densitometry between both groups were found. In conclusion, this study confirms that HRCT is a reliable method of detecting blebs and bullae in patients with spontaneous pneumothorax. Furthermore CT lung densitometry revealed no parenchymal abnormalities or signs of air trapping in patients with spontaneous pneumothorax.

Adult↗
PubMed1990

Assessment of fat-free mass in teen-agers: use of TOBEC methodology.

The accuracy of total-body electrical conductivity (TOBEC) for body composition assessment was examined in 50 teen-agers (33 males and 17 females) aged 11-19 y. Body composition measures included densitometry, hydrometry, bone mineral density of the one-third distal radius, and TOBEC. Fat-free mass (FFM) was calculated by using one-, two-, and three-compartment models: densitometry, FFMd; densitometry and hydrometry, FFMdw; and densitometry, hydrometry, and bone mineral density, FFMdwb. Correlations between TOBEC variables and the three calculations of FFM were highly significant (r = 0.88-0.95; P less than 0.01). No significant differences were observed (ANOVA) between the TOBEC estimate of FFM (FFMT) and FFMd, FFMdw, and FFMdwb. Similar results were observed when the data were analyzed by gender. The TOBEC estimate of FFM was equivalent to the estimates of FFM derived from one-, two-, and three-component models. Its ease of measurement and its prediction accuracy (R2 = 0.933; SEE = 2.45 kg) in teen-agers make it a preferred technique for body composition assessment.

Adipose Tissue↗
PubMedDate not supplied

Difference in global hepatic enhancement assessed by dynamic CT in normal subjects and patients with hepatic metastases.

PURPOSE: Our goal was to determine if there are differences in liver densitometry parameters using helical CT between normal subjects and subjects with liver metastases. METHOD: One-hundred fifty subjects (64 with normal livers and 86 with CT-visible hepatic metastases) underwent dual phase helical scanning of the liver. Images were obtained in the "arterial" (early) and "venous" (late) phases of hepatic enhancement. Densitometry measurements were obtained from the liver (distinct from obvious lesions or vessels) and aorta at 25, 40, 75, and 90 s. Enhancement values at the same time points were calculated in 73 subjects in whom noncontrast images of the liver were available. A peak liver densitometry value was also determined. Several ratios were determined for each time point: the liver/aortic ratio (L/A), liver/liver peak ratio (L/P), liver enhancement/aortic enhancement ratio (LE/AE), and liver enhancement/liver peak enhancement ratio (LE/LPE). The degree of tumor burden in the hepatic metastatic group was assessed in each case. RESULTS: Values for L/A, L/P, LE/AE, and LE/LPE at 25 and 40 s were significantly (p < 0.05) higher in the liver metastases group than the normal liver group. Enhancement ratios were even more elevated in breast cancer, which can have hypervascular metastases. These CT parameters did not show significant differences when analyzed according to the degree of hepatic metastatic tumor burden. All densitometry parameters and ratios obtained at 75 and 90 s were not significantly different between the two groups. CONCLUSION: In the early phase of bolus intravenous contrast agent administration, the visually normal portion of the liver parenchyma in patients with hepatic metastases enhances to a greater degree than the liver in normal subjects. This may reflect generalized increased hepatic arterial flow in tumor-bearing livers and has the potential to increase the sensitivity of CT for detection of hepatic metastases.

Absorptiometry, Photon↗
PubMed2003

Regional expression of cyclooxygenase isoforms in the rat kidney in complete unilateral ureteral obstruction.

PURPOSE: The cyclooxygenase (COX) pathway is activated in unilateral ureteral obstruction (UUO), contributing to renal hemodynamic alterations in different regions of the kidney. After the release of 24-hour UUO cortical vasoconstriction occurs but medullary hyperemia is seen. We examined the expression of the 2 COX isoforms COX-1 and COX-2 in different regions of the kidney in rats subjected to UUO. MATERIALS AND METHODS: Clearance experiments were performed after ureteral obstruction release in rats with 24-hour UUO or sham operated rats. COX-1 and COX-2 expression in the cortex and medulla were examined by Western blot analysis and immunohistochemistry. RESULTS: After UUO release the glomerular filtration rate and renal plasma flow were markedly lower in post-obstructed kidneys than in contralateral kidneys or in kidneys in sham operated rats (p <0.001). Western blot analysis showed that COX-2/beta-actin in the cortex of the obstructed kidney was 0.28 +/- 0.02 densitometry units, significantly lower than 0.67 +/- 0.12 densitometry units in the contralateral unobstructed kidney. In contrast, COX-2/beta-actin in the outer and inner medullae of the obstructed kidney was 7.85 +/- 1.09 and 2.51 +/- 0.14 densitometry units, significantly greater than 3.03 +/- 0.22 and 0.66 +/- 0.14 densitometry units, respectively, in the contralateral unobstructed kidney. The expression of COX-1/beta-actin in the obstructed kidney was similar to that in the contralateral unobstructed kidney in the cortex and medulla. CONCLUSIONS: Renal COX-2 expression is markedly altered in UUO. Decreased cortical expression of COX-2 and markedly increased expression in the medulla may contribute to disparate regional hemodynamic alterations in UUO.

Animals↗
PubMed1996

Ultrasound Densitometric Analysis: Comparison Between an Online Digital Acquisition Acoustic Program and an Offline Analog Program.

Videodensitometric analysis of myocardial contrast echocardiography is traditionally performed off line. Recently, an online contrast ultrasound analysis system, Acoustic Densitometry (Hewlett-Packard), was introduced. We compared pixel intensities acquired with Acoustic Densitometry to pixel intensities derived from videodensitometry. A tissue phantom was imaged in phase I using three transducer frequencies (2.5, 3.5, and 5.0 MHz). In phase II, an in vitro flowing tube model with various concentrations of Albunex(R) was imaged at two flow rates, 0.6 and 1.2 m/sec, and at two transducer frequencies, 2.5 and 3.5 MHz. The relationship between pixel intensities yielded by the two systems for identical ultrasound signals was determined with linear regression. Intensities derived with Acoustic Densitometry strongly correlated with those derived from the offline videodensitometry system. The intensities were related by a predictive multiplicative factor based on display characteristics of the two systems. These results suggest that semiquantitative, online perfusion analysis with Acoustic Densitometry is as sensitive as analysis offline with videodensitometry. (ECHOCARDIOGRAPHY, Volume 13, September 1996)

Journal Article↗
PubMed2004

Influence of calibration on densitometric studies of emphysema progression using computed tomography.

The fundamental importance of calibration for any measuring device is indisputable, but computed tomography (CT) calibration in longitudinal lung densitometry studies is largely unexplored. Although the validity of CT as a measure of emphysema has been confirmed in cross-sectional studies, there are limited data on long-term reproducibility, and this is critically important for validating its use as an outcome measure in therapeutic trials. A general understanding of the strengths and pitfalls of CT densitometry is critical for physicians reviewing the published literature using this methodology. In our study of 57 patients with alpha-1 antitrypsin deficiency (phenotype PiZ), progression of voxel index determined from three successive annual scans acquired with a fully calibrated scanner was intimately associated with changes in CT air densitometry, sampled from patient images. Images were therefore reanalyzed, using a correction technique validated in phantom studies that adjusted for changes in measured air density, and the reliability of the voxel index as a measure of emphysema progression was improved. Comparison of adjusted voxel index thresholds indicated the optimum threshold was -950 Hounsfield units. Internal air calibration is therefore critical in longitudinal and multicenter lung densitometry studies of emphysema and incorporation of a correction factor is essential for quantitative image analysis.

Absorptiometry, Photon↗
PubMed1998

Diagnosis of osteoporosis in clinical practice.

Measurement of bone mineral density is the basis of the diagnosis of osteoporosis. The risk of fracture increases with decreasing bone mineral density, which can be measured using several different techniques. Dual energy x-ray absorptiometry is the most commonly used technique today. A further facility of the new bone densitometry technology is the option for vertebral morphometry. There are errors of accuracy in all bone densitometry techniques and also in the interpretation of the data they provide. Ultrasound of bone may provide new measures of bone fragility. Broadband ultrasound attenuation of the calcaneus predicts the risk of hip fracture in elderly women almost or equally as well as bone densitometry. Ultrasound does not expose to radiation and the equipment is portable. However, bone ultrasound cannot replace bone densitometry. Biochemical bone markers do not differentiate osteoporotic patients from healthy adults. However, they can be useful in deciding on interventions and in monitoring the efficacy of treatment. Their predictive value in individuals suffers from large variability. Biochemistry is widely used in the differential diagnosis of secondary osteoporosis. Suspicion of osteomalacia or an invasive process in the bone marrow are the most common indications for bone biopsy. Finally, although history and physical examination are insufficient in diagnosing primary osteoporosis, they are important in targeting other investigations to exclude secondary forms of osteoporosis.

Absorptiometry, Photon↗
PubMed2001

Regional expression of inducible nitric oxide synthase in the kidney in dogs with unilateral ureteral obstruction.

PURPOSE: In the early stage of unilateral ureteral obstruction total renal blood flow increases but medullary blood flow decreases, exacerbating medullary tissue hypoxia. We examined the expression of inducible nitric oxide synthase, a product of a hypoxia sensitive gene, in the cortex and medulla in dogs with unilateral ureteral obstruction for 21 hours. MATERIALS AND METHODS: Hemodynamic and clearance experiments were performed after release of ureteral obstruction in 6 dogs with unilateral ureteral obstruction, followed by Western blot analysis of nitric oxide synthase and immunohistochemistry. RESULTS: Ureteral obstruction raised mean ureteral pressure plus or minus standard error to 35.0 +/- 7.2 mm. Hg. In dogs with unilateral ureteral obstruction mean renal blood flow was 116 +/- 10 ml. per minute, lower than the 213 +/- 22 ml. per minute in sham operated dogs (p <0.01). After unilateral ureteral obstruction release the mean glomerular filtration rate was 9.5 +/- 2.1 ml. per minute, lower than the 27.3 +/- 1.8 ml. per minute in the contralateral unobstructed kidney (p <0.01). Western blot analysis showed that mean nitric oxide synthase/beta-actin in the cortex of the obstructed kidney was 0.04 +/- 0.01 densitometry units, lower than 0.11 +/- 0.02 densitometry units in the unobstructed contralateral kidney (p <0.05). In contrast, mean nitric oxide synthase/beta-actin in the medulla of the obstructed kidney was 1.29 +/- 0.33 densitometry units, greater than the 0.34 +/- 0.03 densitometry units in the unobstructed kidney (p <0.05). Immunohistochemistry revealed that the increased expression of nitric oxide synthase protein was localized to the endothelium of the vasa recta. CONCLUSIONS: Unilateral ureteral obstruction enhances nitric oxide synthase expression in the medulla but not in the cortex. This increased expression in the medulla may be the result of increased medullary hypoxia in unilateral ureteral obstruction, possibly contributing to medullary hyperemia after unilateral ureteral obstruction release.

Animals↗
PubMedDate not supplied

[Digital computerized absorptiometry in the diagnosis of osteoporosis in a group of the severely mentally retarded].

BACKGROUND: The loss of bone mass after a certain age is a physiological fact that, in certain circumstances, is capable of inducing osteoporosis. In the diagnostic strategies for this condition, densitometry is a well-accepted technique now widely used. On patients with severe mental retardation, a number of circumstances come into play and may foster a greater frequency of osteoporosis. GOAL AND SCOPE OF STUDY: The goal of the study is to identify the bone mineral density values in a group of severe mentally retarded individuals using a digital densitometry technique in order to compare these with the general population and investigate the possible influence on these values of certain clinical variables and therapeutic regimens. VOLUNTEERS: One hundred and ninety-two patients of both sexes and treated at an institution devoted to the study and care of severely mentally retarded individuals. ACTIONS TAKEN: In all cases, the bone mineral density value has been obtained by means of digital densitometry using a compact desktop system using dual X-ray absorption measurement technology The data obtained have been contrasted with sex, age, degree of mobility and anti-epilepsy or sedative medication. RESULTS: In the population under study, the bone mineral density is significantly lower than that of the general population: 25% present osteopenia and 22% osteoporosis. These results are associated with the fact that they move little and are regularly taking phenobarbital medication. The population with Down's syndrome is also seen to be a group at risk. CONCLUSIONS: Osteoporosis is frequent among severe mentally retarded patients. The greatest risk is associated with insufficient mobility, Down's syndrome and regular medication with phenobarbital. Digital densitometry is a simple procedure that may be useful to identify the true dimension of this problem and the efficacy of the various preventive or curative procedures put forward.

Absorptiometry, Photon↗
PubMed2004

[Different forms of clinical presentation of an autosomal dominant hypophosphatemic rickets caused by a FGF23 mutation in one family].

In this report we describe different forms of clinical presentation of an autosomal dominant hypophosphatemic rickets (ADHR) in 4 members of the same family as well as the treatment used in these patients and their response to it. Patient No 1: a 60 year old female who consulted for bone pain: Bone densitometry showed osteoporosis. Laboratory assays showed hypophosphatemia with low renal phosphate threshold, high total alkaline phosphatase, normal intact PTH and normal serum calcium. With neutral phosphate and calcitriol, the biochemical parameters normalized and bone densitometry improved significantly in less than a year. Patient No 2 her grand daughter consulted at 1 year and 8 months of age for growth retardation (height at percentile 3) and genu varum. Laboratory assays showed low serum phosphate and high total alkaline phosphatase; thickening and irregular epiphyseal borders of the wrists were observed radiologically. She began treatment with calcitriol and phosphorus with normalization of laboratory parameters and increase in growth (height increasing to percentile 50 after 20 months of therapy). Patient No 3: mother of patient No 2, she had no clinical manifestations and normal densitometry but presented low serum phosphate (1.9 mg/dl) that normalized with neutral phosphate therapy. Patient No 4: he was the youngest son of Patient No 1, who had had hypophosphatemic rickets, by age 5; his serum phosphate normalized without treatment At age 29, he presented normal serum phosphate and bone densitometry. Genomic DNA analysis performed in patient No 3, showed missense mutation with substitution of arginine at position 179 for glutamine. The family was catalogued as having autosomal dominant hypophosphatemic rickets/osteomalacia.

Adult↗
PubMed2001

Diagnosis and treatment of osteoporosis in Brazil.

The definition of Osteoporosis as proposed by WHO is widely accepted amongst Brazilian physicians. The main diagnostic tool in Brazil is Bone Densitometry (DXA). Both public and private health insurance systems reimburse the densitometry test. DXA have been used also for monitoring changes in BMD. Biochemical markers and peripheral methods of bone assessment are not widely used in Brazil. Estrogens, Vitamin D and its metabolites, Salmon Calcitonin, Ipriflavone, Tibolone, Etidronate, Alendronate, Raloxifene and Risendronate are currently available for treating osteoporosis. Since 1995, Brazilian Society of Clinical Densitometry have been educating Bone Densitometry Professionals and all clinicians in order to improve their ability to turn DXA results into adequate clinical decisions.

Journal Article↗
PubMed2006

[Tumor necrosis factor alpha-induced expression and activity of alveolar macrophages matrix metalloproteinase-9 in chronic obstructive pulmonary disease].

OBJECTIVE: To explore the expression and activity of matrix metalloproteinase-9 (MMP-9) from alveolar macrophages (AMs) induced by tumor necrosis factor-alpha (TNFalpha) in patients with chronic obstructive pulmonary disease (COPD), and therefore to study the possible mechanisms. METHODS: AMs were collected from bronchoalveolar lavage fluid from patients with COPD, and then were stimulated for 24 h with TNFalpha at concentrations of 0.1 ng/ml, 1 ng/ml, 5 ng/ml, 10 ng/ml, and 20 ng/ml, respectively. The gene expression level of MMP-9 induced by TNFalpha was detected by semi-quantitative RT-PCR, and MMP-9 activity was measured by zymography. NF-kappaB activity was detected by electrophoretic mobility shift assay. RESULTS: In unstimulated AMs, the densitometry unit rate of MMP-9 mRNA to beta-actin mRNA was 0.1826 +/- 0.0084. When AMs were stimulated by TNFalpha at concentrations of 0.1 ng/ml, 1 ng/ml, 5 ng/ml, 10 ng/ml, and 20 ng/ml, the densitometry unit rates of MMP-9 mRNA to beta-actin mRNA were 0.4279 +/- 0.0204, 0.5431 +/- 0.0058, 0.6185 +/- 0.0208, 0.6859 +/- 0.0080, and 0.7784 +/- 0.0208, respectively. In unstimulated AMs, the densitometry unit of active MMP-9 was 10 227 +/- 738, but when AMs were stimulated by TNFalpha at concentrations of 0.1 ng/ml, 1 ng/ml, 5 ng/ml, 10 ng/ml, and 20 ng/ml, the densitometry units of active MMP-9 were 40,528 +/- 974, 113,741 +/- 4547, 190,696 +/- 4032, 309,505 +/- 7639, and 427,305 +/- 9145, respectively. NF-kappaB activity was significantly elevated after AMs were stimulated by TNFalpha at the concentration of 10 ng/ml (P < 0.05). CONCLUSIONS: The expression and activity of MMP-9 can be induced by TNFalpha, and the induction was possibly related with the NF-kappaB-mediated signal transduction pathway.

Bronchoalveolar Lavage Fluid↗
PubMed1986

Anthracycline effects on actin and actin-containing thin filaments in cultured neonatal rat myocardial cells.

Adriamycin (ADR, Doxorubicin) effects on actin and other proteins in cultured neonatal rat cardiac myocytes were investigated. Heart cells were exposed to ADR in doses of 10(-8) M to 10(-5) M for 24 hours. Cells were harvested in 2 mM of Tris buffer containing Triton X-100, homogenized and centrifuged in a microfuge. Parallel dishes of cultured cardiac myocytes were washed in buffered saline and were fixed at 4 degrees C in Karnovsky's fixative. The supernatant solutions were dialyzed and then incubated with pancreatic DNAase I to quantify actin by enzyme inhibition. In parallel studies, both cell supernatant solutions and pellets were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis and the stained polypeptide bands were quantified by densitometry. Results showed that heart cells exposed to 10(-6) M of ADR for 24 hours had unpolymerized actin levels reduced to 7.7 micrograms/10(6) cells (as measured by DNAase I inhibition or by sodium dodecyl sulfate polyacrylamide gel electrophoresis along with densitometry) compared to 11.0 micrograms/10(6) cells in untreated culture heart cells. When ADR concentration was 10(-7) or 10(-8) M, unpolymerized actin levels were similar to the levels of untreated heart cells. Protein content of extract solutions of untreated and ADR-treated myocytes were 1.2 mg/ml and 0.8 mg/ml, respectively. Gel densitometry of electrophoretograms showed actin to account for 12 to 16% of total density of bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Comparative densitometry of ADR-treated cells treated with 10(-6) M of ADR show depolymerized actin to account for 77% of total actin. Ultrastructural results show a large clear cytoplasmic zone of disorganized 12 to 14-nm filaments in cultured myocytes exposed to 10(-6) M ADR. Little change in myocyte ultrastructure was seen at 10(-7) M or 10(-8) M ADR exposure. Data support ADR as a cellular disruptor with toxic effects on cardiac cytoplasmic and contractile proteins and filaments. This ADR effect on heart cells in culture is dose-related.

Actins↗