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At least 91 records · Page 5Linked to original sources
PubMed2006

Skeletal muscle apoptosis in experimental heart failure: the only link between inflammation and skeletal muscle wastage?

PURPOSE OF REVIEW: The purpose of this review is to enlighten the mechanisms of muscle wastage in experimental heart failure with attention to skeletal muscle apoptosis and the role of proinflammatory cytokines that trigger apoptosis. RECENT FINDINGS: Mechanisms leading to muscle wastage in chronic heart failure include cytokine-triggered skeletal muscle apoptosis, but also ubiquitin/proteasome and non-ubiquitin-dependent pathways. The regulation of fibre type involves the growth hormone/insulin-like growth factor 1/calcineurin/transcriptional coactivator PGC1 cascade. SUMMARY: Several mechanisms can lead to muscle wastage in heart failure. The imbalance between protein synthesis and degradation plays an important role. Protein degradation can occur through ubiquitin-dependent and non-ubiquitin-dependent pathways. Systems controlling ubiquitin/proteasome activation have been described. These are triggered by tumour necrosis factor alpha and growth hormone/insulin-like growth factor 1. However, an important role is played by apoptosis. In humans and experimental models of heart failure programmed cell death has been found in skeletal muscle and interstitial cells. Apoptosis is triggered by tumour necrosis factor alpha and in-vitro experiments have shown that it can be induced by its second messenger sphingosine. Apoptosis correlates with the severity of the heart failure syndrome. It involves activation of caspases 3 and 9 and mitochondrial cytochrome c release.

Animals↗
PubMed2006

Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on ubiquinone levels in rat skeletal muscle and heart: relationship to cytotoxicity and inhibitory activity for cholesterol synthesis in human skeletal muscle cells.

Although statins are prescribed as relatively safe and effective drugs for hypercholesterolemic patients, it has been reported that a significant side effect, myopathy, occurs infrequently during medication. Moreover, because statins decrease cardiac ubiquinone levels, the risk of cardiac dysfunction has been suggested. This study sought to evaluate and compare the cytotoxicity of statins (cerivastatin, pitavastatin, fluvastatin, simvastatin, atorvastatin and pravastatin) in cultured human skeletal muscle cells (HSkMCs) and the effects on ubiquinone levels in statin-treated rat skeletal muscle and heart. Cerivastatin, the most potent inhibitor of HMG-CoA reductase, showed the strongest cytotoxicity (over 10-fold) among the statins examined, while the effects of the others were in a similar range. In rat experiments, neither pitavastatin nor cerivastatin decreased ubiquinone levels in skeletal muscle, but both dose-dependently lowered ubiquinone levels in the heart. As the rates of reduction by pitavastatin (9.6% at 30 mg/kg) and cerivastatin (9.7% at 0.3 mg/kg) were almost equal, it was estimated that cerivastatin reduced ubiquinone levels in the rat heart approximately 100-fold more strongly than pitavastatin, based on the effective doses. We found that cerivastatin showed the most potent cytotoxicity in HSkMCs and strongly lowered ubiquinone levels in the rat heart.

Animals↗
PubMed2002

Initiation and termination of calcium sparks in skeletal muscle

Three main paths to derive the Ca2+ release flux underlying Ca2+ sparks are reviewed here: Some properties of release flux can be inferred from an examination of spark morphology. Others from model simulations, which generate sparks assuming an ion source within a cytoplasm-like medium. Finally, the release flux can be derived from the fluorescence transient by generalizing an algorithm developed earlier for global or whole cell signals. The transient and spatially limited nature of sparks adds many uncertainties to the process. These methods yield estimates between 1.4 and 30 pA, not clearly greater in skeletal than in cardiac muscle. At their low end, the estimates are consistent with generation of sparks by one or two ryanodine receptor channels, but the results are easier to explain if several channels, from as little as four to as many as 60, cooperate in their generation. How release flux determines spark shape and time course has been understood largely through simulations. The rise time of sparks corresponds to active release time. Both release flux and release time may vary among individual sparks, leading to their varied size and shape. Release flux turns off abruptly, therefore the decay of sparks is determined by Ca2+ removal and diffusion. Spatial width increases with release time (rise time). That its experimentally determined value is too large compared with simulations, remains the single most important question in the interpretation of shape. Sparks are not the sole form of local fluorescence transients. When channel opening drugs are present, or sometimes spontaneously, sparks may be prolonged by embers. If the release flux calculated during an ember corresponds to a single open channel, then the release underlying a spark must require many open channels. The continued examination of Ca2+ release flux appears to be an essential requisite for the interpretation of sparks and their place in calcium signaling.

Animals↗
PubMed1975

The significance of occult skeletal metastases, detected by skeletal scintigraphy, in patients with otherwise apparently 'early' mammary carcinoma.

Fifty patients with apparently 'early' mammary carcinoma on clinical, radiological and biochemical grounds had a skeletal scintigram carried out when they first presented. Twelve (24 per cent) of the patients had a positive scintigram. All these patients have developed metastatic disease in the first 5 years following mastectomy, and at least 9 (75 per cent), and probably 10 (83 per cent), have died from mammary carcinoma during this period. This compares with 10 (26 per cent) of the patients with a negative scintigram who have developed recurrent or metastatic disease, of whom 8 (21 per cent) have died from their disease. Five years following mastectomy none of the patients with a positive scintigram was alive and free from disease, compared with 25 (66 per cent) of the patients with a negative scintigram. It would appear that skeletal scintigraphy is the most sensitive method of detecting skeletal metastases and of staging breast carcinoma at the moment. Where practicable, this investigation should be carried out before embarking upon treatment for any particular patient, and this certaily should become part of any clinical trial comparing different therapeutic regimens. However, before some of the newer bone-seeking isotopes are used in this way, further studies are required to determine their false positive rate.

Bone Neoplasms↗
PubMed2003

Zoledronic acid delays the onset of skeletal-related events and progression of skeletal disease in patients with advanced renal cell carcinoma.

BACKGROUND: The objective of this study was to assess the efficacy and safety of zoledronic acid in patients with bone metastases secondary to renal cell carcinoma (RCC). METHODS: A retrospective subset analysis of patients with RCC enrolled in a multicenter, randomized, placebo-controlled study of zoledronic acid was performed. Patients were randomized to receive zoledronic acid (4 or 8 mg as a 15-minute infusion) or placebo with concomitant antineoplastic therapy every 3 weeks for 9 months. The primary efficacy analysis was the proportion of patients with one or more skeletal-related events (SREs), which were defined as pathologic fracture, spinal cord compression, radiation therapy, or surgery to bone. Secondary analyses included time to first SRE, skeletal morbidity rate (events per year), disease progression, and multiple event analysis. RESULTS: In this subset of 74 patients with RCC, zoledronic acid (4 mg) was found to significantly reduce the proportion of patients with an SRE (37% vs. 74% for placebo; P = 0.015). Similarly, zoledronic acid significantly reduced the mean skeletal morbidity rate (2.68 vs. 3.38 for placebo; P = 0.014) and extended the time to the first event (median not reached vs. 72 days for placebo; P = 0.006). A multiple event analysis demonstrated that the risk of developing an SRE was reduced by 61% compared with placebo (hazard ratio of 0.394; P = 0.008). The median time to progression of bone lesions was significantly longer for patients who were treated with zoledronic acid (P = 0.014 vs. placebo). Zoledronic acid appeared to be well tolerated; the most common adverse events in all treatment groups included bone pain, nausea, anemia, and emesis. CONCLUSIONS: Zoledronic acid (4 mg as a 15-minute infusion) demonstrated significant clinical benefit in patients with bone metastases from RCC, suggesting that further investigation of zoledronic acid in this patient population is warranted.

Aged↗
PubMed1976

The value of enzyme histochemical techniques in classifying fibre types of human skeletal muscle. 1. Adult skeletal muscles with no apparent disease of the neuromuscular system.

Fibre-type classification of human skeletal muscle into type I and type II fibres is mostly based on their slight or strong staining with the myosin adenosine triphosphatase reaction. In order to evaluate the reliability of this screening technique a combined histochemical and biochemical study was performed on normal and diseased skeletal muscle of human subjects. In the present investigation activities of enzymes which play a role in the aerobic and anaerobic pathways and which can characterize fibre type, were examined in muscle specimens, with no apparent disease of the neuromuscular system. Special attention is given to the maximal activities of phosphofructokinase and fructose-1,6-diphosphatase, the rate limiting enzymes for the regulation of the glycolysis and glyconeogenesis, respectively. A most important feature of the biochemical findings is the constancy of the activity ratios of the examined enzymes. From these results and from the histochemical results it can be concluded that in apparently normal adult human skeletal muscle the ATP-ase technique for type I and type II typing is reliable. For fibres with an intermediate intensity of staining with the myosin ATPase technique of typing it is also necessary to apply other enzyme histochemical techniques.

Adenosine Triphosphatases↗
PubMed1977

In vitro studies of skeletal muscle membranes. Effects of denervation on the macromolecular components of cation transport in red and white skeletal muscle.

The effects of denervation on the macromolecular components of active monovalent cation transport in skeletal muscle have been studied using purified sarcolemma membranes. A comparison of membrane activities of fast-twitch, slow-twitch, and mixed-fiber muscles was made to determine what role, if any, the motor nerve has in regulating this important aspect of muscle metabolism. A dramatic increase in the basal sarcolemmal Mg++ ATPase activity (three- to fourfold) was found for both major muscle types. An increase in the ouabain-inhibitable (Na+ + K+)-stimulated enzyme was also found, but the effect was substantially less (1.5- to twofold). [3H]-ouabain binding, as an index of glycoside receptor sites, also increased (two- to threefold) midway in the course of denervation. On the other hand, the phosphorylated intermediate activity, a functional component of the transport system, clearly decreased over the same time course and remained below control values for the remainder of the course. This resulted in a two- to threefold increase in the turnover number, suggesting that active transport of cations should increase dramatically with denervation. The membrane protein patterns on SDS gels were less obvious than the changes observed in the functional components. The major effects appeared after only one week and seemed to be restricted to high molecular weight membrane proteins, especially in the 100,000 to 250,000 daltons range. This effect was more prominent in slow-twitch membranes with an apparent semiquantitative decrease in stain at 240,000 daltons. In gels of membranes from fast-twitch muscles a decreased stain in the range of 100,000 to 110,000 daltons occurred, and this became more obvious with longer periods of denervation. The results suggest that considerable influence on the macromolecular components of active cation transport in skeletal muscle is exerted by the motor nerve. No appreciable difference was found in this effect when the two major types of skeletal muscle, fast-twitch and slow-twitch, were compared, suggesting that motor nerve regulation of this membrane property is qualitatively the same.

Adenosine Triphosphatases↗
PubMed1995

[The therapeutic effects after the dentoalveolar compensation of skeletal open bite in adults. The skeletal and dental parameters].

In the following study 20 adult skeletal open-bite patients were analysed after they had undergone dental compensation to camouflage the underlying skeletal discrepancy. The initial and final cephalometric records were analysed to determine the factors that led to the desired goal. The results showed no significant difference in the skeletal relationship. Molar intrusion was not recorded. The open-bite was correct mostly by reclining the upper incisors and by changing their position. Significant differences existed between the obtained results and the mechano-therapy employed. The geometrical model developed on the of the above makes it possible to predict and predetermine the targeted vertical dimension. Furthermore the results show extrusion of the front teeth as another dominant factor.

Adolescent↗
PubMed1987

Skeletal fixation versus skeletal relapse.

The use of skeletal fixation was evaluated for skeletal stability during the period of intermaxillary fixation following a modified sagittal split ramus osteotomy for mandibular prognathism. A combination of bilateral maxillary peralveolar wires and circummandibular wires in the canine region was used for the fixation. One group of patients with this method of fixation (S group) and a second group without the fixation (C group) were compared cephalometrically. Statistically significant differences existed in the amount and pattern of relapse; the fixation produced a significant effect on retention of the corrected chin position. As a consequence, downward and backward rotation of the distal fragment of the mandible and compensatory incisor extrusion were notably controlled. However, upward shift of the posterior end of the distal fragment occurred persistently even in the S group, causing considerable intrusion of the posterior teeth in comparison with the C group. This seems to indicate that tension, probably exerted by the pterygomasseteric sling, is important in postoperative skeletal instability.

Adolescent↗
PubMed2007

Effects of treatment with a combined maxillary protraction and chincap appliance in skeletal Class III patients with different vertical skeletal morphologies.

Several cephalometric studies and case reports have described the effects of treatment with a maxillary protraction appliance (MPA) and chincap appliance. The purpose of this investigation was to identify differences in the response to treatment with a combined MPA and chincap in skeletal Class III patients with different vertical skeletal morphologies: short- (low mandibular plane angle) and long- (high mandibular plane angle) face types. The cephalograms used in this study were of 42 Japanese girls at the beginning of treatment (T0, mean age 10.1 years) and at removal of the appliance (T1, mean age 11.5 years). The subjects were divided into two groups (short and long face) according to the inclination of the mandibular plane at T0. Total anterior face height, upper and lower face height, occlusal plane, and gonial angle were significantly larger in the long-face group at T0. In both groups, significant increases in SNA, maxillary size (A'-Ptm'), and ANB were noted during treatment. Compared with the long-face group, the short-face group showed greater forward displacement and size increment of the maxillary body, while there were no significant differences in changes in mandibular size or position between the two groups. These results indicate that the vertical dimensions of the craniofacial skeleton are important factors in the orthopaedic effects of a MPA and chincap and the prognosis for skeletal Class III patients.

Activator Appliances↗
PubMed1979

Divalent cation binding properties of slow skeletal muscle troponin in comparison with those of cardiac and fast skeletal muscle troponins.

1. New methods of preparing troponins from slow skeletal and cardiac muscle of the chicken have been developed. The electrophoretic mobilities of slow skeletal muscle troponin subunits were different from those of the corresponding fast skeletal muscle subunits. 2. A new method for determining the amount of divalent cations bound to troponin was developed. The principle of the method is to immobilize troponin by conjugating it with Sepharose 4B resin, thus making it readily sedimentable. 3. The numbers of Sr and Ca ions bound to slow muscle troponin at concentrations sufficient to produce maximum contraction were 1.73 and 1.36 mol per mol, respectively, being nearly equal to those of cardiac troponin but half of those of fast muscle troponin. 4. The concentrations of Sr and Ca ions giving half-maximal ion binding to slow muscle troponin (K50%) were 5.5 X 10(-6) M and 4.6 X 10(-7) M, respectively. 5. K50% for Sr of cardiac troponin was significantly higher than that of slow muscle troponin. Although K50% for Sr of cardiac troponin was the same as that of fast muscle troponin, cardiac troponin bound more Sr ions than fast muscle troponin at lower Sr ion concentrations. The mechanism underlying the high sensitivity of cardiac muscle contraction to Sr ions is discussed in comparison with that of slow muscle.

Animals↗
PubMed1996

Uranium skeletal dosimetry and distribution in young adult beagles: a guide for calculating uranium skeletal doses in humans.

Uranium isotopes were given via single intravenous injection into 22 young adult beagle dogs of both sexes to determine the metabolism of this element. Animals were given either 232U, 233U, 238U, or a combination of 232 (+) 233U. Calculations to assign a value of skeletal dose for each dog were performed using published radioactive properties of each uranium isotope and the metabolic data (including measured retention and skeletal distribution) derived from this study during a period of up to 2 y after injection. We believe that the procedures illustrated in this communication can serve as a useful pattern for estimating skeletal radiation doses to humans contaminated with 232U, 233U, or 238U.

Animals↗
PubMed2003

Skeletal scintigraphy in the multimodality assessment of young children with acute skeletal symptoms.

The authors review the scintigraphic manifestations of acute osteomyelitis, septic arthritis, transient synovitis, Legg-Calvé-Perthes disease, fractures of toddlers, and some systemic conditions that cause skeletal symptoms during childhood. They offer suggestions regarding incorporation of skeletal scintigraphy into a multimodality approach for assessing children with skeletal symptoms.

Arthritis, Infectious↗
PubMed2005

WISP3, the gene responsible for the human skeletal disease progressive pseudorheumatoid dysplasia, is not essential for skeletal function in mice.

In humans, loss-of-function mutations in WISP3 cause the autosomal recessive skeletal disease progressive pseudorheumatoid dysplasia (PPD) (Online Mendelian Inheritance in Man database number 208230). WISP3 encodes Wnt1-inducible signaling protein 3, a cysteine-rich, multidomain, secreted protein, whose paralogous CCN (connective tissue growth factor/cysteine-rich protein 61/nephroblastoma overexpressed) family members have been implicated in diverse biologic processes including skeletal, vascular, and neural development. To understand the role of WISP3 in the skeleton, we targeted the Wisp3 gene in mice by creating a mutant allele comparable to that which causes human disease. We also created transgenic mice that overexpress human WISP3 in cartilage. Surprisingly, homozygous Wisp3 mutant mice appear normal and do not recapitulate any of the morphological, radiographic, or histological abnormalities seen in patients with PPD. Mice that overexpress WISP3 are also normal. We conclude, that in contrast to humans, Wisp3 is not an essential participant during skeletal growth or homeostasis in mice.

Alleles↗
PubMed1983

Skeletal changes following growth hormone treatment in a child with combined hypopituitarism and a skeletal dysplasia.

A child with combined hypopituitarism and an undefined skeletal dysplasia is described. The hypopituitarism was manifested by post-natal growth failure, excessive sc fat, micropenis, and poor growth hormone response to provocative tests. Disproportionately short limbs, especially distally, and skeletal radiographs showing generalized brachydactyly, cone epiphyses of the phalanges and ossification defects in the proximal femoral metaphyses characterized the skeletal dysplasia. In contrast to the normal structure of the endochondral growth plate seen in hypopituitarism, the growth plate in this child was structurally abnormal; there was no differentiation of chondrocytes into hypertrophic and degenerative cells. Treatment with hGH for 8 months was associated with the appearance of chondrocyte differentiation, the restoration of growth plate structure to almost normal and a substantial increase in growth rate. There was no change in his disproportion or improvement in his radiographic abnormalities. These observations suggest that hGH may influence growth plate structure in certain instances and that this may be associated with increased linear growth.

Age Determination by Skeleton↗
PubMed1994

Time courses of changes in hepatic and skeletal muscle insulin action and GLUT4 protein in skeletal muscle after STZ injection.

To determine the relative time courses of changes in peripheral and hepatic insulin action and skeletal muscle GLUT4 protein levels after a streptozotocin (STZ) injection in rats, we performed hyperinsulinemic (14-18 nM), euglycemic (7.5 mM) clamps in control (n = 8) and diabetic rats at 1 (n = 7), 3 (n = 8), 7 (n = 8), and 14 (n = 6) days after intraperitoneal STZ (65 mg/kg). Basal plasma glucose concentrations increased from 8.1 +/- 0.2 mM in control rats to 23.5 +/- 1.2 mM 1 day after STZ (P < 0.01) and remained constant thereafter. Basal plasma insulin levels were approximately 35% of control levels in all STZ groups (P < 0.01). Insulin-stimulated whole-body glucose uptake decreased significantly as early as one day after STZ injection (P < 0.01), resulting predominantly from a decrease in whole-body glycolysis. Insulin action to suppress hepatic glucose output was normal on day 1 after STZ but impaired markedly on day 3 and thereafter (P < 0.01). Insulin-stimulated glucose uptake in individual skeletal muscles was not altered until day 7 after STZ, and the magnitudes of decreases in skeletal muscle insulin action on days 7 and 14 were not fully accounted for by the decreases in GLUT4 protein level measured from the same muscles. Our data indicate that there is a temporal hierarchy in the development of insulin resistance in STZ-induced diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Why should many skeletal scientists and clinicians learn the Utah paradigm of skeletal physiology?

Adding later facts and ideas to a universally accepted "1960 paradigm" of skeletal physiology led to the still-evolving "Utah paradigm". The ASBMR's William Neuman award in 2001 to one of the latter paradigm's architects (HMF) suggested that physiologists began to view it as a valid supplement to its predecessor. Nevertheless it diffused poorly among most SSCs (Skeletal Scientists and Clinicians, plus all others who work in any way on skeletal matters), even though success in the quest for knowledge and recognition by many of them could depend on learning that paradigm's insights. Those insights can help to minimize serious errors in some experimental designs and in interpreting some kinds of data. To explain how success in that quest could depend on the Utah paradigm requires explaining the nature of the above errors, some features of both paradigms, some implications of the newer one, and when that quest's success might not require knowing the Utah paradigm. A three-part message distilled from the past for present and future SSCs concludes the article. It took decades to understand such things and find effective ways to explain them, and both matters probably need improvement (to paraphrase Pogo, "We met the enemy and perhaps it was us more than them"). During those decades the author changed from an active SSC hunter-player to a spectator, known to some as a feisty eccentric old dinosaur (FEOD) (Note A). So here a voice from the past would speak to present and future SSCs.

Journal Article↗
PubMed2005

Morphologic skeletal asymmetry, with a Class III skeletal discrepancy, treated without surgical intervention.

Patient J.S., adult, female, presented with a morphologic skeletal asymmetry of the mandible resulting in a unilateral posterior crossbite, and a Class III skeletal discrepancy characterized by a hyperdivergent facial pattern (FMA, 30 degrees), retrognathic maxilla (SNA, 79 degrees), and compensating maxillary alveolar dental protrusion (1-NA, 7 mm). Maxillofacial surgery was declined. Orthodontic treatment, utilizing the Tweed-Merrifield edgewise technique, widened the maxillary dentition with a combination buccal crown torque and buccal root torque and with lingual crown torque in the mandibular posterior quadrant. Temporomandibular joint symptoms lessened and function improved with orthodontic treatment. The skeletal asymmetry improved and the patient was happy with the result, including her profile and her beautiful smile.

Adult↗