Caveolin-3 is Up-Regulated in the Physiological Left Ventricular Hypertrophy Induced by Voluntary Exercise Training in Rats

Various substances have been introduced in relation with cardiac hypertrophy almost always with controversy in their roles in signal transduction. Those controversies may attribute to the diversity of cardiac hypertrophy. We previously showed that calcineurin was activated in physiological left ventricular hypertrophy (LVH) induced by voluntary exercise training, but not in decompensated pressure-overload LVH. In the current study, we advanced our search for the differences between the voluntary exercise-induced LVH and the pressure-overload LVH into several other hypertrophy-related substances including caveolin. Wistar rats were assigned to one of the following three groups: 10 weeks of voluntary exercise (EX), sedentary regimen (SED), and 4 weeks of ascending aortic constriction (AC). The EX rats voluntarily ran 1.6 ± 1.1 km/day in the specially manufactured cages resulting in LVH (24 % increase in left ventricular weight per body weight ratio). Myocardial tissue homogenate of the EX rats revealed different characteristics in signal transduction of hypertrophy from that of the AC. The EX rats had normal sarcoplasmic reticulum (SR) Ca²⁺ATPase mRNA level and normal myosin heavy chain isozyme pattern assessed by RNA protection assay, while AC rats had decreased SR Ca²⁺ATPase mRNA level and increased beta myosin heavy chain mRNA level. Myocardial caveolin-3 protein levels assessed by Western blotting increased in the EX rats but decreased in the AC rats. The voluntary exercise-induced LVH differed in signal transduction from the decompensated pressure-overload LVH. Caveolin-3 was induced in the voluntary exercise-induced LVH, while it was decreased in the decompensated pressure-overload LVH.Key Words: Exercise, hypertrophy, signal transduction     

Cerebral blood flow and vasodilatory capacity in anemia secondary to chronic renal failure

BACKGROUND: Our previous study reported that cerebral oxygen extraction fraction (OEF) increased in hemodialysis patients with anemia. The increased OEF suggests that the cerebral vasodilatory capacity might be impaired in these patients. To clarify this issue, we measured the CO2 response in patients with anemia secondary to chronic renal failure (CRF) using positron emission tomography (PET). METHODS: Ten anemic patients with CRF (6 females and 4 males) and 6 age-matched normal controls were studied. The underlying diseases of CRF were glomerulonephritis in 8 patients, systemic lupus erythematosus (SLE) in one patient, and hypertension in one patient; in this cohort, 5 patients were on hemodialysis treatment and the remaining 5 patients were in a pre-hemodialysis state. The cerebral blood flow (CBF) was measured by the O-15 H2O bolus injection method with each patient in a resting state and during 5% CO2 inhalation. The CO2 response was estimated as the percentage change of CBF per 1 mm Hg change of PaCO2. RESULTS: The CO2 response was significantly attenuated in anemic patients with CRF in comparison to the normal controls, and it inversely correlated with the severity of anemia. There was no significant difference in the CO2 response between the hemodialysis and pre-hemodialysis patients. The CO2 response significantly correlated with CBF and the cerebral metabolic rate for oxygen (CMRO2) at rest, however, it did not correlate with OEF and cerebral blood volume (CBV). CONCLUSIONS: The present study revealed the existence of a reduced cerebral vasodilatory capacity in anemic patients with CRF, suggesting that chronic hypoxic brain damage might play a role in the impaired cerebrovascular response to CO2.     

A comparison of the INVOS 4100 and the NIRO 300 near-infrared spectrophotometers

We determined whether two different devices for measuring near-infrared spectroscopy (NIRS)---the INVOS 4100 and the NIRO 300---produce similar cerebral oxygenation data during the CO(2) challenge test. Nineteen patients anesthetized with sevoflurane, 67% nitrous oxide in oxygen, and fentanyl were studied. A series of measurements of regional cerebral oxygen saturation (rSO(2)), measured by the INVOS 4100, and tissue oxygen index (TOI), measured by the NIRO 300, were performed in the following conditions: 1) normocapnia (PaCO(2), 35--45 mm Hg); 2) hypocapnia (PaCO(2), 25--35 mm Hg); 3) normocapnia; and 4) hypercapnia (PaCO(2), 45--55 mm Hg). Hemodynamic variables, including arterial blood gases and cerebral blood flow velocity, were measured at the same time with transcranial Doppler. The values and percentage changes of rSO(2) and TOI were compared by using regression analysis and Bland and Altman analysis. The rSO(2) showed a significant positive correlation with TOI (r = 0.58, P < 0.01). The percentage change of rSO(2) also showed a significant positive correlation with the percentage change of TOI during the CO(2) challenge (r = 0.85, P < 0.01). Bland and Altman analysis revealed a bias of -0.5% with 2 SD of 15.6% when comparing the rSO(2) value with the TOI value, and it showed a bias of -3.4% with 2 SD of 15.2% when comparing the percentage change of rSO(2) with the percentage change of TOI, indicating unacceptable disagreement of these data. These results indicate that cerebral oxygen saturation and its relative change during the CO(2) challenge may vary depending on the type of NIRS used. Because the measurement technique and algorithm were different in each device, we should carefully consider the clinical application of the values produced by NIRS. IMPLICATIONS: Near-infrared spectroscopy (NIRS) has been proposed as a noninvasive clinical method for assessing cerebral oxygenation. The acceptable reliability and validity of NIRS values have not been established despite their widespread use. The INVOS 4100 and the NIRO 300 can display cerebral oxygen saturation as regional cerebral oxygen saturation and tissue oxygenation index, but they produce differing results.     

Laparoscopic radical nephrectomy in ACDK-associated renal cell carcinoma accompanied by duplicated IVC: a case report

A 59-year-old male patent who had undergone chronic dialysis for 13 years presented with gross hematuria. Radiological examinations showed a cystic renal tumor in the left kidney, multiple renal cysts due to acquired cystic disease of the kidney (ACDK), and a duplicated inferior vena cava (IVC). Although we suspected that the branches of the left IVC might be anormalous with regard to number and location, we could not obtain information about the left renal vein by 3-dimensional computed tomography because of the decreased blood flow in the end-stage kidney. Laparoscopic radical nephrectomy was performed using a transperitoneal approach. We first identified the left IVC and then exposed its surface widely so that we could identify the veins draining into it. We identified and divided two renal veins and also identified an adrenal vein and a gonadal vein draining directly into the left IVC. The enlarged kidney with multiple renal cysts was removed in a purely laparoscopic procedure.     

New parameter of flexion after posterior stabilized total knee arthroplasty: posterior condylar offset ratio on X-ray photographs

In cruciate-retaining (CR) type TKA, the increase in posterior condylar offset (PCO) is considered to be correlated to flexion angle acquired postoperatively according to the article reported by Bellemans (J Bone Joint Surg Br 84:50–53, 2002). However, the significance of PCO seems to differ according to the size of joints. We therefore have defined a new parameter of posterior condylar offset ratio (PCOR) on the lateral view of plain X-ray photographs and studied the relationship between PCOR and postoperative flexion status in posterior-stabilized (PS) type TKA. Flexion status includes two parameters, such as postoperative flexion angle (FA) and flexion achievement rate (AR). The subjects of this study were 160 knees (16 males and 144 females, average 75 years.) with PS type TKA for osteoarthritic knees between 1999 and 2003 at our institution, more than at least 1 year postoperative follow-up. In the study of FA, patients with FA of less than 100° were divided into Group L (n = 28), patients with FA of 130° and greater were divided into Group H (n = 58). In the study of AR, patients with AR of less than 100% were divided into Group P (n = 46), patients with AR of 120% and greater were divided into Group G (n = 22). PCOR was statistically compared in each group, respectively. In FA, PCOR in Group L (0.385) was significantly lower (P = 0.027) than that in Group H (0.428). In AR, PCOR in Group P (0.376) was significantly lower (P = 0.0018) than that in Group G (0.456). We have concluded, though there are many factors influencing the range of movement after TKA, our newly defined PCOR could possibly serve as a parameter of postoperative flexion status of PS type TKA on plain X-ray photographs. No benefits or funds were received in support of the study.     

Comparison of maxillary stability after Le Fort I osteotomy for occlusal cant correction surgery and maxillary advanced surgery.

OBJECTIVE: To compare postoperative maxillary stability following Le Fort I osteotomy for the correction of occlusal cant as compared with conventional Le Fort I osteotomy for maxillary advancement. STUDY DESIGN: The subjects were 40 Japanese adults with jaw deformities. Of these, 20 underwent a Le Fort I osteotomy and intraoral vertical ramus osteotomy (IVRO) to correct asymmetric skeletal morphology and inclined occlusal cant. The other 20 patients underwent a Le Fort I osteotomy and sagittal split ramus osteotomy (SSRO) to advance the maxilla. Lateral and posteroanterior cephalograms were taken postoperatively and assessed statistically. Thereafter, the 2 groups were followed for time-course changes. RESULTS: There was no significant difference between the 2 groups with regard to time-course changes during the immediate postoperative period. CONCLUSION: This suggests that maxillary stability after Le Fort I osteotomy for cant correction does not differ from that after Le Fort I osteotomy for maxillary advancement.     

Evaluation of upper lip hypoesthesia with a trigeminal somatosensory-evoked potential following Le Fort I osteotomy in combination with mandibular osteotomy.

PURPOSE: The purpose of this study was to objectively evaluate hypoesthesia of the upper lip following Le Fort I osteotomy in combination with mandibular osteotomy with trigeminal somatosensory evoked potential (TSEP). SUBJECTS AND METHODS: The subjects consisted of 25 patients with mandibular prognathism with maxillary retrognathism mandibular prognathism with or without asymmetry, who underwent Le Fort I osteotomy in combination with sagittal split ramus osteotomy (SSRO) or intraoral vertical ramus osteotomy (IVRO).Trigeminal nerve hypoesthesia at the region of the upper lip was assessed bilaterally by the TSEP method. The electrodes were placed exactly above the highest point of the vermilion border and on the mucosa of the upper lip. An electroencephalograph recording system (Neuropack Sigma; Nihon Koden Corp., Tokyo, Japan) was used to analyze the potentials. Each patient was evaluated preoperatively and then postoperatively at 1 week, 2 weeks, 1 month, 3 months, 6 months, and 1 year. RESULTS: The average measurable period and standard deviation of TSEP of the upper lip was 7.8 +/- 10.7 weeks following Le Fort I osteotomy, TSEP of the lower lip was 4.6 +/- 9.2 weeks in the patients who underwent SSRO with Le Fort I osteotomy, and 1.2 +/- 0.4 weeks in the patients who underwent IVRO with Le Fort I osteotomy. CONCLUSION: This study objectively proved that hypoesthesia could appear in the upper lips following Le Fort I osteotomy with TSEP. The measurable period for the upper lip following Le Fort I osteotomy tended to be longer than that for the lower lip in the patients who underwent SSRO and IVRO with Le Fort I osteotomy.     

Impact of polysol, a newly developed preservation solution, on cold storage of steatotic rat livers.

Chronic shortage of donor organs has led to acceptance of steatotic livers as grafts, although there is a higher risk of primary graft dysfunction. We herein report the beneficial impact of Polysol, a newly developed preservation solution, on cold storage of steatotic rat livers. Dietary hepatic steatosis was induced in Wistar rats by 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. Fatty livers were retrieved, flushed and then stored at 4 degrees C for 24 hours with either HTK or Polysol. Functional integrity of the grafts was evaluated by isolated reperfusion with oxygenated Krebs-Henseleit buffer at 37 degrees C for 45 minutes in both groups. Polysol preservation resulted in significant reductions of not only parenchymal (AST (IU/L); 6728+/-824 in HTK vs. 3107+/-718 in Polysol; P < 0.001) but also mitochondrial (GLDH (IU/L); 3189+/-773 vs. 1282+/-365; P < 0.01) enzyme release throughout reperfusion. Moreover, PVP (16.9+/-2.7 vs. 7.8+/-1.5 mmHg; P < 0.05), hepatic O2 consumption (0.291+/-0.047 vs. 1.056+/-0.053 micromol/g liver/min; P < 0.001), tissue ATP content (0.695+/-0.086 vs. 1.340+/-0.157 micromol/g dry-liver; P < 0.005), bile production (0.79+/-0.11 vs. 4.08+/-0.66 microL/g liver/45-min; P < 0.001), malondialdehyde into the perfusate (1.922+/-0.198 vs. 0.573+/-0.094 nmol/L; P < 0.0001) and wet/dry-weight ratio of the liver tissues (5.20+/-0.31 vs. 3.85+/-0.15; P < 0.005) were all better preserved by Polysol. In line with these benefits, electron microscopy revealed that Polysol preservation substantially suppressed deleterious mitochondrial alterations in steatotic livers. In conclusion, cold storage using Polysol resulted in significantly better integrity and function of steatotic livers. Polysol, therefore, may be a new alternative especially for "marginal" organs.     

Tacrolimus as prophylaxis for acute graft-versus-host disease in reduced intensity cord blood transplantation for adult patients with advanced hematologic diseases

BACKGROUND: Myeloablative cord blood transplantation (CBT) for adult patients offers a 90% chance of engraftment with a 50% rate of transplant-related mortality, mostly attributable to infection. We have demonstrated the feasibility of reduced-intensity CBT (RI-CBT) for adult patients, in which cyclosporine was used for acute graft-versus-host disease (GVHD) prophylaxis. Transplantation-related mortality (TRM) was 27% within 100 days. Therefore our objective was to evaluate the feasibility of RI-CBT with tacrolimus as GVHD prophylaxis for adult patients with hematologic malignancies. METHODS: Thirty-four patients with a median age of 56.5 years (range; 22-68) with hematologic diseases underwent RI-CBT at Toranomon Hospital between November 2003 and September 2004. Preparative regimen comprised fludarabine 25 mg/m2 on days -7 to -3, melphalan 80 mg/m2 on day -2, and 4 Gy total body irradiation on day -1. GVHD prophylaxis was continuous intravenous infusion of tacrolimus 0.03 mg/kg, starting on day -1. RESULTS: Thirty-one patients achieved neutrophil engraftment at a median of day 20. Median infused total cell dose was 2.4 x 10E7/kg (range; 1.6-4.8). Thirty-two patients achieved complete donor chimerism at day 60. Grade II-IV acute GVHD occurred in 45% of patients, with a median onset of day 26. Primary disease recurred in five patients, and TRM within 100 days was 12%. Estimated 1-year overall survival was 70%. CONCLUSION: This study demonstrated the possible improvement in transplant-related mortality by tacrolimus as GVHD prophylaxis in adult RI-CBT recipients.     

MAGI-2 orchestrates the localization of backbone proteins in the slit diaphragm of podocytes

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