[Aluminum and iron deposition in dialysis patients].
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Aluminum↗
Biomedical subjects
Satoshi Kurihara
Publications and source records attributed to Satoshi Kurihara.
[Risk management based on results of nationwide questionaire on medical accidents].
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Accident Prevention↗
Targeted deletion of apoptosis signal-regulating kinase 1 attenuates left ventricular remodeling.
Left ventricular remodeling that occurs after myocardial infarction (MI) and pressure overload is generally accepted as a determinant of the clinical course of heart failure. The molecular mechanism of this process, however, remains to be elucidated. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in stress-induced apoptosis. We used ASK1 knockout mice (ASK-/-) to test the hypothesis that ASK1 is involved in development of left ventricular remodeling. ASK-/- hearts showed no morphological or histological defects. Echocardiography and cardiac catheterization revealed normal global structure and function. Left ventricular structural and functional remodeling were determined 4 weeks after coronary artery ligation or thoracic transverse aortic constriction (TAC). ASK-/- had significantly smaller increases in left ventricular end-diastolic and end-systolic ventricular dimensions and smaller decreases in fractional shortening in both experimental models compared with WT mice. The number of terminal deoxynucleotidyl transferase biotin-dUDP nick end-labeling-positive myocytes after MI or TAC was decreased in ASK-/- compared with that in WT mice. Overexpression of a constitutively active mutant of ASK1 induced apoptosis in isolated rat neonatal cardiomyocytes, whereas neonatal ASK-/- cardiomyocytes were resistant to H2O2-induced apoptosis. An in vitro kinase assay showed increased ASK1 activity in heart after MI or TAC in WT mice. Thus, ASK1 plays an important role in regulating left ventricular remodeling by promoting apoptosis.
Animals↗
Long-term follow-up of polyurethane vascular grafts for hemoaccess bridge fistulas.
The new polyurethane vascular graft (PVG) has been reported to be better than the expanded polytetrafluoroethylene (PTFE) graft in terms of early access and prompt hemostasis, but long-term patency and safety of PVGs have not been investigated objectively. To evaluate late clinical outcome of the PVG, we compared the complication and patency rates of stretch PTFE grafts with those of PVGs implanted for hemodialysis vascular access. Subjects were 53 patients who received 58 arteriovenous grafts between October 1997 and July 2000. They were divided in a prospective fashion into two groups according to the type of implanted graft: PVG ( n = 30) or PTFE ( n = 28). The study group comprised 27 men and 31 women with a mean age of 61.7 +/- 10.9 years (range: 23-84 years). The average number of previous accesses was 5.1 +/- 3.1 (range: 0-12). There were no differences between the groups in term of age, sex, body surface area, etiology of renal disease, presence of diabetes, previous access procedures, anatomical positions of grafts, or mean follow-up period. Primary patency rates for the PVG and PTFE grafts were equivalent at 1 year (60.7% vs. 56.5%) and at 2 years (54.7% vs. 51.8%). Similarly, secondary patency rates for the two groups did not differ at 1 year (78.7% vs. 79.9%) or at 2 years (78.7% vs. 69.3%). These findings indicate that the PVG is an acceptable alternative to the PTFE graft for blood access.
Adult↗
Evaluation of blood supply to the parathyroid glands in secondary hyperparathyroidism compared with histopathology.
BACKGROUND: In chronic renal failure patients, the parathyroid glands progress from diffuse hyperplasia to nodular hyperplasia, and it is important to distinguish between these as the latter form is more aggressive. This progress can be confirmed histologically, but the present study aimed to determine whether the different types of hyperplasia could be distinguished by power-Doppler ultrasonography (US). METHODS: Twenty-one consecutive renal failure patients were scheduled to undergo parathyroidectomy (PTx). Of 70 resected parathyroid glands, 63 were assessed by pre-operative power-Doppler US, classified into four groups based on the flow signal pattern and then correlated with the post-operative histopathology. RESULTS: With power-Doppler US imaging, 60.0% of glands without a signal inside the gland were diagnosed as diffuse hyperplasia or diffuse hyperplasia with early nodularity. Of glands with in-gland signals, 83.7% were nodular or had a single nodule typical of nodular hyperplasia. Even when the focus was on parathyroid glands weighing <or=0.5 g, similar results were obtained. CONCLUSIONS: Power-Doppler US imaging is a useful method for determining the pathological features of parathyroid glands and is recommended for selecting the most suitable therapy.
Female↗
Cardiac-specific overexpression of a high Ca2+ affinity mutant of SERCA2a attenuates in vivo pressure overload cardiac hypertrophy.
In cardiomyocytes, calcium plays important roles as a signal in cardiac hypertrophy and contraction-relaxation cycling. Elevation of Ca2+ concentration in myoplasm is associated with the onset and progression of hypertrophy as well as the enhancement of contractility. The cardiac Ca2+ ATPase (SERCA2a) of the sarcoplasmic reticulum plays a dominant role in lowering cytoplasmic calcium levels during relaxation and is regulated by phospholamban (PLN). To examine whether the modulation of SERCA2a activity results in the attenuation of cardiac hypertrophy and enhancement of contractility, we generated transgenic mice (TG) overexpressing a high calcium affinity SERCA2a mutant (K397/400E), lacking a functional association with PLN. In the TG hearts, the apparent affinity of SERCA2a for Ca2+ significantly increased compared with their nontransgenic littermate controls. The TG showed increased contraction and relaxation, with increases in the amplitude of Ca2+ transient and rapid Ca2+ decay. Upon induction of pressure overload by transverse aortic constriction, the TG developed less cardiac hypertrophy than littermate controls did. The activation of Ca2+-sensitive protein kinase C by pressure overload was significantly attenuated in the TG hearts. Our findings indicate an association of SERCA2a activity with cardiac hypertrophy and thus a new therapeutic target for the prevention and treatment of cardiac hypertrophy.
Animals↗
Radial mass transfer of cross-bridges in a tetanized ferret heart muscle.
An X-ray diffraction experiment on ferret heart muscle was made to examine the relationship between tension and mass transfer from the thick to the thin filament associated with the interaction of cross-bridges with actin. A ferret papillary muscle was electrically stimulated for 8 s in the presence of 5 microM ryanodine to give a tetanus. At different extracellular Ca2+ concentrations (2-20 mM), a linear relationship was found between the tension and the mass transfer. It was concluded that a change in tension caused by altering the extracellular Ca2+ concentration is due to a change in the number of myosin heads bound to actin. This is in contrast to the results obtained on skinned preparations, which showed a markedly nonlinear relationship between the number of heads in the vicinity of the thin filaments and force. It was found that the tension per myosin head is similar in twitch and tetanus of cardiac muscle. Also, a similar fraction of myosin heads is recruited in tetanus of cardiac and skeletal muscles.
Aequorin↗
Bupivacaine attenuates contractility by decreasing sensitivity of myofilaments to Ca2+ in rat ventricular muscle.
BACKGROUND: Bupivacaine exhibits a cardiodepressant effect, the molecular mechanism(s) of which have yet to be fully understood. Bupivacaine may directly act on contractile proteins and thereby decrease myofibrillar Ca2+ sensitivity. METHODS: Rat ventricular muscle was used. First, the effect of bupivacaine was examined on tetanic contractions in isolated intact myocytes. Next, Triton X-100-treated ventricular trabeculae were used to investigate the effect of bupivacaine on the pCa (= -log [Ca2+ ])-tension relation as well as on maximal Ca2+ -activated tension. Furthermore, to test whether bupivacaine inhibits the pathway downstream from Ca2+ binding to troponin C, tension was elicited in the skinned preparations by lowering the Mg-adenosine triphosphate (MgATP) concentration in the absence of Ca2+. The effect of bupivacaine on the pMgATP (= -log [MgATP])-tension relation was examined. RESULTS: In myocytes, 3 microm bupivacaine significantly (P < 0.01) increased intracellular Ca2+ concentration required for 5% cell shortening from the resting cell length. In skinned preparations, bupivacaine shifted the pCa-tension relation to the lower pCa side; the midpoint of the pCa curve (pCa50) was significantly (P < 0.05) changed by 10 and 100 microm bupivacaine. A highly correlated linear relation (R = 0.81; P< 0.0005) was present between pCa50 and maximal Ca2+ -activated tension. Bupivacaine (10 and 100 microm) significantly (P < 0.05) shifted the midpoint of the pMgATP-tension relation to the higher pMgATP side. CONCLUSIONS: Bupivacaine decreases myofibrillar Ca2+ sensitivity in ventricular muscle, and this is coupled with the compound's inhibitory effect on the pathway beyond Ca2+ binding to troponin C, possibly on the actomyosin interaction. The current results may partly explain the overall cardiodepressant effect of bupivacaine in vivo.
Actin Cytoskeleton↗
Use of tetanus to investigate myofibrillar responsiveness to Ca(2+) in isolated mouse ventricular myocytes.
We used the relation between intracellular Ca(2+) concentration ([Ca(2+)](i)) and cell shortening during tetanus to evaluate the endogenous characteristics of Ca(2+) responsiveness of myofibrils in mouse ventricular myocytes. Enzymatically isolated myocytes were loaded with fura-2 AM (4 microM for 10 min), and the fura-2 fluorescence ratio at 340 and 380 nm excitation wave length [F(340)/F(380)] and cell length were measured simultaneously. Following treatment with thapsigargin (0.2 microM) (an inhibitor of the Ca(2+) pump of sarcoplasmic reticulum), myocytes were stimulated at 10 Hz for 10 s to produce a tetanic contraction and an instantaneous plot of the fluorescence ratio signal versus cell length (R-L trajectory) was constructed. An increase in the extracellular Ca(2+) concentration ([Ca(2+)](o)) from 0.5 to 2 mM extended the R-L trajectory without a substantial shift of the relation. The R-L trajectory was shifted rightward by the nonselective phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xantine (IBMX, 200 microM) (desensitization of the myofibrils to Ca(2+)), and shifted leftward by the Ca(2+) sensitizing thiadiazinone derivative, EMD-57033 (0.5 microM) (sensitization of the myofibrils to Ca(2+)). Beta-adrenergic stimulant, isoproterenol (5 nM), also shifted the R-L trajectory to the right, suggesting that the membrane receptor could be preserved. These results suggest that the R-L trajectory is a useful method to estimate the myofibrillar responsiveness to Ca(2+) in isolated mouse myocytes and can be applied to various mouse models of heart disease.
1-Methyl-3-isobutylxanthine↗
The mechanism of increasing Ca2+ responsiveness by alpha1-adrenoceptor stimulation in rat ventricular myocytes.
We investigated the mechanism of alpha(1)-adrenoceptor stimulation on the myofibrillar Ca(2+) responsiveness at steady-state in intact rat ventricular myocytes. We produced tetanus, and an instantaneous plot of [Ca(2+)](i) vs. cell length (Ca-L trajectory) was constructed to estimate the Ca(2+) responsiveness. An alpha(1)-agonist, phenylephrine, dose-dependently shifted the Ca-L trajectory to the left, corresponding to sensitization of the myofilaments. An alpha(1)-antagonist, prazosin, and inhibition of the Na/H exchange by ethylisopropylamiloride (EIPA) completely reversed the phenylephrine-induced shift. Phenylephrine increased pH(i) (DeltapH(i) = +0.1), which was reversed by prazosin and EIPA. Chelerythrine, an inhibitor of protein kinase C (PKC), completely blocked the effects of phenylephrine on Ca(2+) responsiveness and pH(i). When pH(i) was increased (DeltapH(i) = +0.1) without phenylephrine by changing pH(o), the Ca-L trajectory was shifted to the same extent as that observed with phenylephrine. We conclude that alpha(1)-adrenoceptor stimulation activates Na/H exchange through a PKC-mediated pathway and that an increase in pH(i) is mainly responsible for the increase in Ca(2+) responsiveness.
Adrenergic alpha-Agonists↗
[Therapeutic agents for hyperphosphatemia].
Hyperphosphatemia is one of the major causes of secondary hyperparathyroidism (II degrees HPT) in dialysis patients. Aluminum (Al) hydroxide was commonly used as a phosphate binder in Japan until the beginning of the 1990's, when it was replaced by calcium(Ca) compounds to eliminate undesirable side effects. Although Ca compounds are effective phosphate binders, the concomitant use of vitamin D derivatives can often result in hypercalcemia. For the reason, physicians today have been requesting phosphate binders that contain neither Al nor Ca. In this paper, we introduce several such phosphate binders. Sevelamer hydrocholoride (SH) is a new phosphate binder that contains neither Al nor Ca, and is not absorbed from the gastrointestinal tract. Several short-term clinical studies have established that SH is as efficient as calcium carbonate at lowering serum phosphorus (P) levels, with significant improvement in the Ca x P product and lipids metabolism. Furthermore, a long-term (52 weeks) study revealed that SH attenuated the progression of coronary and aortic calcification in hemodialysis (HD) patients. SH is considered a highly effective phosphate binder in protecting against the progression of II degrees HPT and cardiovascular death in HD patients.
English Abstract↗