ABSTRACT
Cilnidipine, an L-/N-type calcium channel blocker, dilates the efferent glomerular arterioles in an experimental model and shows a renoprotective effect, but its clinical benefits and safety have not yet been assessed in type II diabetics with albuminuria. The objective of this trial was to evaluate the effect of reducing albuminuria in type II diabetic patients with a combination therapy consisting of valsartan plus cilnidipine versus monotherapy with valsartan. An open-label, randomized controlled trial was conducted from April 2002 to October 2003 in 87 Japanese patients aged 31-90 years with type II diabetes showing albuminuria (urinary albumin/creatinine ratio: 10-300 mg/g). The patients were randomized to receive either valsartan (n=41) or valsartan plus cilnidipine (n=46) once daily for 1 year. The primary end point was the percent change in the albumin/creatinine ratio. The secondary end points were the progression/regression of albuminuria, blood pressure (BP), renal function, and safety. After 1 year, the albumin/creatinine ratio was found to have decreased more markedly in the valsartan plus cilnidipine group than in the valsartan group (reduction rate -44+/-11% (s.e.) versus -9+/-7% (s.e.); P=0.014 by analysis of covariance). Although a significant reduction was observed in the systolic and diastolic BP of both groups from baseline to 1 year (P<0.0001, respectively), there was no significant difference in the change in the BP between the two groups (systolic BP, P=0.066; diastolic BP, P=0.391). There were also no significant differences in the side effects between the two groups. Cilnidipine was thus found to show an additive effect with valsartan and thereby caused a reduction in albuminuria in type II diabetics.
Subject(s)
Albuminuria/drug therapy , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Calcium Channel Blockers/therapeutic use , Diabetes Mellitus, Type 2/complications , Dihydropyridines/therapeutic use , Tetrazoles/therapeutic use , Valine/analogs & derivatives , Aged , Albuminuria/etiology , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Treatment Outcome , Valine/therapeutic use , ValsartanABSTRACT
BACKGROUND: There is as yet no definite consensus on the predictive value of the various lipid profiles and fibrinolytic parameters that became available in clinical use recently for coronary artery disease. METHODS: Levels of lipoprotein(a), high-density lipoprotein cholesterol (HDL-C), remnant-like particles cholesterol (RLP-C), tissue plasminogen activator (TPA), TPA inhibitor, antithrombin III, and protein C were measured in 124 patients who underwent diagnostic coronary angiograms. RESULTS: Of these patients, 37 had no significant stenoses (group N) and 87 had significant stenoses (group S). There were no significant differences in patient characteristics between the two groups. HDL-C was significantly lower (p = 0.0071 ) and RLP-C was significantly higher (p = 0.0022) in group S. When a product and a ratio of each of two factors were calculated, RLP-C/HDL-C was demonstrated to be a highly significant predictor for coronary artery stenoses (p < 0.0001). There were also significant increases in RLP-C/HDL-C levels with increasing number of vessels involved (r = 0.359, p < 0.0001 ). CONCLUSION: Our present study disclosed the predictive value of RLP-C/HDL-C ratio as a new indicator of coronary artery disease.
Subject(s)
Cholesterol, HDL/blood , Cholesterol/blood , Coronary Disease/diagnosis , Fibrinolysis/physiology , Lipoprotein(a)/blood , Adult , Aged , Aged, 80 and over , Antithrombin III/metabolism , Coronary Angiography , Coronary Disease/blood , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Protein C/metabolism , Risk Factors , Tissue Plasminogen Activator/bloodABSTRACT
A 55-year-old man had rhabdomyolysis and myocardial damage induced by palytoxin. Weakness and myalgia of four extremities occurred five hours after eating a fish. Rhabdomyolysis developed and the serum creatine phosphokinase (CK) was elevated to 40,000 IU/l on the 3rd day. Gastric lavage with activated charcoal and forced mannitol-alkaline diuresis therapy were performed. The patient recovered with no complication such as renal failure. In this case, palytoxin was suggested to induce myocardial damage which was demonstrated by an elevation of the myosin light chain level and a change in electrocardiogram.
Subject(s)
Acrylamides/poisoning , Cardiomyopathies/chemically induced , Cnidarian Venoms/poisoning , Fishes , Rhabdomyolysis/chemically induced , Animals , Cardiomyopathies/blood , Cardiomyopathies/therapy , Creatine Kinase/blood , Diuretics, Osmotic/therapeutic use , Electrocardiography , Follow-Up Studies , Foodborne Diseases/etiology , Gastric Lavage , Humans , Male , Middle Aged , Myosin Light Chains/blood , Rhabdomyolysis/blood , Rhabdomyolysis/therapyABSTRACT
Calsequestrin (CS) is a Ca(2+)-storing protein present in the sarcoplasmic reticulum (SR) of muscle cells. Calreticulin (CR) is a functional homologue of CS in the endoplasmic reticulum (ER) of non-muscle cells. During skeletal muscle differentiation, the major Ca(2+)-storing protein switches from CR to CS. To study the regulation of CS and CR expression in cardiomyocytes and the morphological maturation of Ca(2+)-storing sites in the SR, we examined rat hearts at various developmental stages and cultured adult cardiomyocytes by Western blotting and immunocytochemical analyses. CR was expressed in 14-day-old fetal rat cardiomyocytes, but disappeared gradually by 1 week after birth. CR reappeared in dedifferentiated adult cardiomyocytes in long-term culture. On Western blots, the concentration of CS in the heart did not change during development. Immunostaining for CS in fetal or neonatal rat cardiomyocytes revealed as scattered dots. CS-positive structures increased with development, and the regular striated distribution of CS at Z lines was completed around 3 weeks after birth. These results indicated that (1) CR expression is downregulated during cardiac differentiation and upregulated during dedifferentiation, and (2) maturation of SR involves the organization of CS-positive structure after birth.
Subject(s)
Calcium-Binding Proteins/metabolism , Calsequestrin/metabolism , Endoplasmic Reticulum/metabolism , Myocardium/metabolism , Ribonucleoproteins/metabolism , Sarcoplasmic Reticulum/metabolism , Animals , Calreticulin , Cell Differentiation , Cells, Cultured , Heart/embryology , Male , Myocardium/ultrastructure , Rabbits , Rats , Rats, WistarABSTRACT
A major Ca(2+)-storing protein in endoplasmic reticulum (ER) of non-muscle cells is calreticulin (CR), which is considered to be functionally homologous to calsequestrin. Calsequestrin is a Ca(2+)-binding protein in sarcoplasmic reticulum (SR) of striated muscle, which stores Ca2+ during muscle relaxation. In order to investigate the expression and distribution of calsequestrin and calreticulin during skeletal muscle differentiation, cultured chick embryonic skeletal muscles were observed by immunofluorescence using anti-calsequestrin, anti-calreticulin, anti-desmin, and anti-sarcomeric myosin antibodies and rhodamine-phalloidin. Within 6 hours in culture, myoblasts started to express desmin. Desmin-positive cells demonstrated the reticular staining of calreticulin, as did desmin-negative cells. Around fusion, calsequestrin and sarcomeric myosin started to appear in desmin-positive cells. The expression of calsequestrin slightly preceded that of sarcomeric myosin. As the myotubes matured, the fluorescent dots of calsequestrin increased and spread to the cell periphery along the myofibrils, while the reticular pattern of calreticulin gradually disappeared. Double labeling showed that calsequestrin colocalized with calreticulin. In mature myotubes, anti-calsequestrin staining demonstrated many dots along myofibrils, whereas calreticulin was barely seen except at the perinuclear region. These results suggest that the expression of calsequestrin and calreticulin are switched during skeletal muscle differentiation.
Subject(s)
Calsequestrin/metabolism , Gene Expression Regulation, Developmental , Muscles/cytology , Animals , Calcium-Binding Proteins/metabolism , Calreticulin , Calsequestrin/genetics , Cell Differentiation , Cells, Cultured , Chick Embryo , Endoplasmic Reticulum/metabolism , Microscopy, Fluorescence , Myofibrils/metabolism , Ribonucleoproteins/metabolism , Sarcoplasmic Reticulum/metabolism , Stem Cells/metabolismABSTRACT
We encountered a 52-year-old man with Takayasu's disease (pulseless disease) and severe respiratory failure due to recurrent pulmonary hemorrhage. Angiography revealed occlusion of multiple branches of the pulmonary artery, which were filled via collateral circulation from the coronary, intercostal, and intermammary arteries. This is a rare case that causes massive pulmonary bleeding and respiratory failure in Takayasu's arteritis.