Hydrogen sulfide donor micelles protect cardiomyocytes from ischemic cell death.

Hydrogen sulfide, an important gaseous signaling molecule in the human body, is known to protect cardiomyocytes from ischemia, a condition characterized by insufficient oxygen supply to the cells. Here we show that a nanosized H2S donor micelle releases H2S intracellularly and prevents cardiomyocyte apoptosis in an in vitro ischemia model.

A comprehensive search for mutations in the PKD1 and PKD2 in Japanese subjects with autosomal dominant polycystic kidney disease.

To elucidate the genotypic and phenotypic characteristics of autosomal dominant polycystic kidney disease (ADPKD) in Japanese populations, we performed a comprehensive search for mutations in PKD1 and PKD2 in 180 Japanese ADPKD patients from 161 unrelated families. We identified 112 (89 PKD1 and 23 PKD2) mutations within 135 families. Patients with PKD2 mutations account for 23.6% of all Japanese ADPKD families in this study. Seventy-five out of the 112 mutations have not been reported previously. The estimated glomerular filtration rate (eGFR) decline was significantly faster in patients with PKD1 mutations than in those with PKD2 mutations (-3.25 and -2.08 ml min(-1) year(-1) for PKD1 and PKD2, respectively, p < 0.01). These results indicate that mutations within PKD1 and PKD2 can be linked to most of the cases of Japanese ADPKD, and the renal function decline was faster in patients with PKD1 mutations than in those with PKD2 mutations also in the Japanese ADPKD. We also found that PKD2 mutations were more frequent in Japanese ADPKD than that in European or American ADPKD.

Antihypertensive effect of a fixed-dose combination of losartan/hydrochlorothiazide in patients with uncontrolled hypertension: a multicenter study.

BACKGROUND: Achieving adequate blood pressure (BP) control often requires more than one antihypertensive agent. The purpose of this study was to determine whether a fixed-dose formulation of losartan (LOS) plus hydrochlorothiazide (HCTZ) (LOS/HCTZ) is effective in achieving a greater BP lowering in patients with uncontrolled hypertension. METHODS: The study was a prospective, multicenter, observational trial exploring the antihypertensive effect of a single tablet of LOS 50 mg/HCTZ 12.5 mg. A total of 228 patients whose BP had previously been treated with more than one antihypertensive agents without having achieved BP goal below 130/80 mmHg enrolled in the study. RESULTS: A significant decrease in systolic and diastolic BP was observed in both clinic and home measurement after switching from the previous treatment to LOS/HCTZ. There was a significant decrease in both B-type natriuretic peptide (BNP) and urinary albumin creatinine (Cr) excretion ratio (ACR), especially in patients with elevated values. In contrast, there was a significant increase in serum Cr concentration in conjunction with a decrease in estimated glomerular filtration rate (eGFR). Overall serum uric acid (UA) concentration increased, whereas in patients with hyperuricemia there was a significant reduction in this value. CONCLUSION: Switching to LOS/HCTZ provides a greater reduction in clinic and home BP in patients with uncontrolled hypertension. This combination therapy may lead to cardio-, reno protection and improve UA metabolism.

Clinical impact of a combined therapy of peritoneal dialysis and hemodialysis.

AIMS: Although peritoneal dialysis (PD) is recommended as the first-line treatment for end-stage renal disease, limitations exist to achieving good clinical status when the residual renal function (RRF) has declined. Combined therapy with PD and hemodialysis (HD) is the treatment of choice for patients who cannot control body fluid status and/or cannot obtain adequate solute removal by PD alone. The aim of this study was to evaluate the clinical efficacy of this combined therapy. METHODS: In this retrospective study, 53 patients on PD and diagnosed with underdialysis and/or overhydration with declining RRF were recruited. Parameters of volume control, uremic solute removal, anemia, and predictors for encapsulating peritoneal sclerosis (EPS) were compared before and 1 year after combined therapy. RESULTS: The patients' hydration status improved significantly with reductions in atrial natriuretic peptide and blood pressure. Serum creatinine and beta2 microglobulin also decreased significantly. The hemoglobin level increased remarkably from 8.2 ± 1.6 to 10.7 ± 1.2 g/dl (p < 0.01) and the reticulocyte count also increased significantly, even though at the same time the dose of recombinant human erythropoietin decreased significantly. The dialysate to plasma creatinine ratio obtained from the fast peritoneal equilibration test (PET) decreased significantly from 0.65 ± 0.11 to 0.59 ± 0.13, and the level of interleukin 6 in PET drainage also significantly decreased. Furthermore, serum C-reactive protein and fibrinogen decreased significantly. CONCLUSIONS: Combined therapy with PD and HD is an effective way to control fluid status and to correct inadequate solute removal, leading to improvement in inflammation, peritoneal function and anemia.

Serum beta2 microglobulin (beta2MG) level is a potential predictor for encapsulating peritoneal sclerosis (EPS) in peritoneal dialysis patients.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a serious complication in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD). The aim of this study was to find a predictor for EPS. METHODS: Patients with EPS who were detected by a historical cohort study using clinical data of 219 CAPD patients at our hospital. We recruited 25 patients with EPS who were compared with the patients without EPS who were matched for age and dialysis period as controls. Differences between the two groups (non-EPS group and EPS group) with respect to age, gender, primary disease, dialysis period, serum urea nitrogen, serum creatinine, beta2MG, CRP and PET (peritoneal equilibration test) category (determined by the peritoneal function testing) were analyzed. RESULTS: According to multiple regression analysis, a high beta2MG level was an independent risk factor for EPS (odds ratio 1.162, 95% confidence interval 1.026 - 1.317, p = 0.018). Other clinical markers did not show positive significance. A ROC (receiver operating characteristic) curve was prepared to evaluate the suitability of I(2)2MG measurement as a screening test. The sensitivity was 64% and the specificity was 80% when a beta2MG level of 37.0 mg/dl was taken as the cut-off value. The odds ratio for occurrence of EPS was 8.8 when beta2MG level was in the range of 35 - 40 mg/dl, 13.5 when I(2)2MG level was > 40 mg/dl and 1 when beta2MG level was < 30 mg/dl. CONCLUSION: These findings suggest that beta2MG is useful as a screening test for the onset of EPS, and that beta2MG and accumulation of middle-molecular uremic substances may be related to the pathophysiology of EPS.

Transient decreases in Bispectral Index without associated changes in the level of consciousness during photic stimulation in an epileptic patient.

This case report describes a patient with a history of epileptic seizures who showed unusual decreases in the Bispectral Index (BIS) attributable to the induction of abnormal slow electroencephalographic (EEG) waves by photic stimulation, without any associated decrease in his level of consciousness. After starting anticonvulsive therapy, photic stimulation no longer induced abnormal EEG activity nor decreased BIS values. These findings suggest that BIS values may not accurately reflect a patient's actual level of consciousness in the presence of epilepsy-related abnormal EEG activity and that the BIS monitor may be able to track such EEG changes.

Transition of mouse de novo methyltransferases expression from Dnmt3b to Dnmt3a during neural progenitor cell development.

Dnmt3a and Dnmt3b, which are known as functional de novo methyltransferases, are responsible for creating genomic methylation patterns during mammalian development. Recently, we have shown that specific expression of Dnmt3b in epiblast, embryonic ectoderm, hematopoietic progenitor cells and spermatogonia cells is followed by Dnmt3a expression (Watanabe D, Suetake I, Tada T, Tajima S (2002) Stage- and cell-specific expression of Dnmt3a and Dnmt3b during embryogenesis. Mech Dev 118:187-190; Watanabe D, Suetake I, Tajima S, Hanaoka K (2004) Expression of Dnmt3b in mouse hematopoietic progenitor cells and spermatogonia at specific stages. Gene Expr Patterns 5:43-49). In this study, we analyzed the expression of mouse de novo methyltransferases during development of the nervous systems. In the embryonic olfactory epithelium (OE), Dnmt3b was specifically expressed in Mash1 positive globose basal cells (i.e. transiently amplifying neural progenitor cells), while Dnmt3a was expressed in immature olfactory receptor neurons. Dnmt3b-positive cells were rarely observed in the adult OE, but were increased in regenerating OE with intranasal ZnSO(4) administration. Dnmt3b was also detected in the E8.5 neural plate, E10.5 spinal cord and retina cells, while Dnmt3a was expressed in postmitotic young neurons. Furthermore, Dnmt3b was specifically expressed in ES cells, while Dnmt3a was transiently expressed during neural cell differentiation of ES cells. Dnmt3b is specifically expressed in progenitor cells during hematopoiesis, spermatogenesis and neurogenesis, suggesting an important role in the initial steps of progenitor cell differentiation. Dnmt3a is expressed in postmitotic young neurons following the Dnmt3b expression. Dnmt3a may be required for the establishment of tissue-specific methylation patterns of the genome. The coordinated expression of de novo methyltransferases from Dnmt3b to Dnmt3a suggests conserved mechanisms of de novo methylation of the genome and different functions for Dnmt3b and Dnmt3a during progenitor cell development.

[Anesthesia for thoracic surgery in elderly patients].

Aging and advances in medical technology have lead to a rise in the number of patients of advanced age undergoing surgery. This is also observed in thoracic surgery. Aging itself is not a disease, but it is one of the risk factors of perioperative complications. Individual assessment of patients is required to ascertain the organ system capacity and functional reserve. The management of anesthesia is based on the characteristic changes in the elderly, related to physiology and pharmacokinetics, taking account of possible perioperative complications.

Is the ARX index a more sensitive indicator of anesthetic depth than the bispectral index during sevoflurane/nitrous oxide anesthesia?

BACKGROUND: During general anesthesia, hypnotic components have been monitored with electroencephalogram. The bispectral index is derived from a cortical electroencephalogram, but the A-line ARX index is the electroencephalographic response to auditory stimuli. The purpose of this study was to compare the changes of the A-line ARX index and the bispectral index during sevoflurane - nitrous oxide anesthesia. METHODS: One hundred females aged 30-60 years, and scheduled for partial mastectomy, were divided into two groups. Anesthesia was induced with sevoflurane 5% and nitrous oxide in oxygen for 3 min. A laryngeal mask airway was inserted, and anesthesia was maintained with sevoflurane 1-2% and nitrous oxide in oxygen. During surgery, the sevoflurane end-tidal concentration was kept at 0.5%, 1%, or 2% for 5 min before each measurement. Blood pressure, heart rate, and the A-line ARX index (n = 50), and the bispectral index (n = 50) were measured. RESULTS: Blood pressure and heart rate increased following laryngeal mask airway insertion and blood pressure decreased at 2% sevoflurane in both groups similarly. The A-line ARX index, but not the bispectral index, increased significantly by laryngeal mask airway insertion and skin incision. The A-line ARX index decreased at 2% sevoflurane compared with 0.5%, while the bispectral index remained unchanged. CONCLUSION: During sevoflurane-nitrous oxide anesthesia, the A-line ARX index might be a more sensitive indicator of anesthetic depth than the bispectral index.

Shear properties of the temporomandibular joint disc in relation to compressive and shear strain.

Shear stress can result in fatigue, damage, and irreversible deformation of the temporomandibular joint disc. Insight into the dynamic shear properties of the disc may give insight into the mechanism inducing tissue failure due to shear. We tested the hypothesis that the dynamic shear properties of the disc depend on the amount of shear and compressive strain. Twenty-four porcine discs were used for dynamic shear tests. The specimens were clamped between the plates of a loading apparatus under compressive strains of 5%, 10%, and 15%. Dynamic shear was applied to the specimen by a sinusoidal strain of, respectively, 0.5%, 1.0%, and 1.5%. Both the dynamic elasticity and viscosity were proportional to compressive strain and inversely proportional to shear strain. These shear characteristics suggest a significant role of compressive and shear strain on the internal friction of the disc.

The frictional coefficient of the temporomandibular joint and its dependency on the magnitude and duration of joint loading.

In synovial joints, friction between articular surfaces leads to shear stress within the cartilaginous tissue, which might result in tissue rupture and failure. Joint friction depends on synovial lubrication of the articular surfaces, which can be altered due to compressive loading. Therefore, we hypothesized that the frictional coefficient of the temporomandibular joint (TMJ) is affected by the magnitude and duration of loading. We tested this by measuring the frictional coefficient in 20 intact porcine TMJs using a pendulum-type friction tester. The mean frictional coefficient was 0.0145 (SD 0.0027) after a constant loading of 50 N during 5 sec. The frictional coefficient increased with the length of the preceding loading duration and exceeded 0.0220 (SD 0.0014) after 1 hr. Application of larger loading (80 N) resulted in significantly larger frictional coefficients. In conclusion, the frictional coefficient in the TMJ was proportional to the magnitude and duration of joint loading.

Usefulness of epidural anesthesia in gynecologic laparoscopic surgery for infertility in comparison to general anesthesia.

BACKGROUND: Although the advantages of epidural anesthesia in open surgery have been established, its usefulness in the setting of laparoscopic surgery remains to be studied. METHODS: Patients undergoing laparoscopic surgery for infertility were randomly administered epidural anesthesia (group A, n = 11) or general anesthesia (group B, n = 9). The operation was performed under 4 mmHg pneumoperitoneum and in the 20 degrees Trendelenburg position. Respiratory function tests using a spirometer and blood gas analysis were performed during the intra- or perioperative period. Pain status was evaluated with visual analog scale scoring. The number of postoperative recovery days needed to resume daily activities was obtained by a questionnaire. RESULTS: Respiratory rate, minute volume, P(a)CO2, % vital capacity (VC), and forced expiratory volume in 1 s (FEV1) % were virtually constant throughout the study period in group A, whereas %VC was decreased immediately after operation in group B (p < 0.05). Minute volume immediately after operation was significantly increased in group B compared with group A (p < 0.01), suggesting shallow respiration in women undergoing general anesthesia. Observed pain scores on abdominal pain, shoulder pain, and dyspnea were very low during operation in group A. Pain scores immediately and 3 h after operation were also minimal in group A, whereas abdominal pain scores at these points were significantly higher in group B than those in group A (both p < 0.01). The number of days required for a half reduction in wound pain, trotting, and full recuperation for group A were less than those for group B (p < 0.05). CONCLUSIONS: Epidural anesthesia, when used in laparoscopic surgery for infertility treatment, has advantages over general anesthesia in terms of analgesic effects, postoperative respiratory function, and a return to preoperative daily activities.

Cerebral ischaemia during cardiac surgery in children detected by combined monitoring of BIS and near-infrared spectroscopy.

BACKGROUND: Children frequently suffer transient cerebral ischaemia during cardiac surgery. We measured cerebral ischaemia in children during cardiac surgery by combining two methods of monitoring. METHODS: We studied 65 children aged between 5 months and 17 yr having surgery to correct non-cyanotic heart disease using hypothermic cardiopulmonary bypass (CPB). During surgery, we measured the Bispectral Index (BIS) and regional cerebral haemoglobin oxygen saturation (SrO2) with near-infrared spectroscopy (NIRS). Cerebral ischaemia was diagnosed if both SrO2 and BIS decreased abruptly when acute hypotension occurred. In each patient, the relationship between SrO2 and arterial blood pressure (AP) was indicated by a plot of mean SrO2 against simultaneous mean AP. RESULTS: We noted 72 episodes of cerebral ischaemia in 38 patients. Sixty-three ischaemic events were during CPB. Cerebral ischaemia was less frequent in older patients. Cerebral ischaemia was more common and more frequent in children under 4 yr old. Haematocrit during CPB was lower and SrO2 was more dependent on AP in children under 4 yr. CONCLUSIONS: Children less than 4 yr of age are more likely to have cerebral ischaemia caused by hypotension during cardiac surgery. Ineffective cerebral autoregulation and haemodilution during CPB may be responsible.

Load independence of temperature-dependent Ca2+ recirculation fraction in canine heart.

Intramyocardial Ca(2+) recirculation fraction (RF) critically determines the economy of excitation-contraction coupling. RF is obtainable from the exponential decay of the postextrasystolic potentiation of left ventricular (LV) contractility. We have shown that RF remains unchanged despite increasing LV volume (LVV) at normothermia, but decreases with increasing temperature at a constant LVV. However, it remains unknown whether the temperature-dependent RF was not due to the simultaneously changed peak LV pressure (LVP) at a constant LVV. We hypothesized that this temperature-dependent RF would be independent of the simultaneous change in LVP. We used nine excised, cross-circulated canine hearts and allowed their LVs to contract isovolumically. During stable regular beats at 500 msec intervals, we inserted an extrasystolic beat at 360 msec interval followed by the postextrasystolic beats (PESs) at 500 msec intervals. We equalized the temperature-dependent peak LVPs of the regular beats at 36 degrees C and 38 degrees C to the peak LVP level of the stable regular beat at 33 degrees C by adjusting LVV. We fitted the same equation: nEmax = a.exp[-(i - 1)/tau(e)] + b.exp[-(i - 1)/tau(s)]cos[pi(i - 1)] + 1, used before to the normalized Emax (maximum elastance) values of PESi (i = 1-6) relative to the regular beat Emax. RF given by exp(-1/tau(e)) decreased by 19% to 38 degrees C from 33 degrees C. The temperature coefficient (Q(10)) of 1/RF was significantly greater than 1.3. The present results indicated a similar temperature dependence of RF and its Q(10) to those we observed previously without equalizing peak LVP. Thus, the temperature-dependent RF is independent of ventricular loading conditions.

Detection of cerebral hypoperfusion with bispectral index during paediatric cardiac surgery.

BACKGROUND: The bispectral index (BIS) may indicate changes in cerebral activity when the cerebral circulation is affected by acute hypotension. METHODS: We measured BIS and cerebral haemoglobin saturation (Sr(O(2))) by near-infrared spectroscopy in 10 children undergoing cardiac surgery. RESULTS: We noted 14 episodes of simultaneous decreases in Sr(O(2)) and BIS during acute hypotension in five children. An acute decrease in BIS, which coincided with a decrease in Sr(O(2)) suggesting a reduction in cerebral blood flow, was associated with acute slowing of the raw EEG waveforms. CONCLUSIONS: Our findings suggest that an acute decrease in BIS during acute hypotension indicates cerebral hypoperfusion, and that cerebral hypoperfusion caused by hypotension may occur frequently during paediatric cardiac surgery.

Dynamic shear properties of the temporomandibular joint disc.

Shear stress might be an important factor associated with fatigue failure and damage of the temporomandibular joint disc. Little information, however, is available on the dynamic behavior of the disc in shear. Since the disc is an anisotropic and viscoelastic structure, in the present study the dependency of the dynamic shear behavior on the direction and frequency of loading was examined. Ten porcine discs were used for dynamic shear tests. Shear stress was applied in both anteroposterior (A-P test) and mediolateral (M-L test) directions. The dynamic moduli increased as the loading frequency increased. The dynamic elasticity was significantly larger in the A-P test than in the M-L test, although the dynamic viscosity was similar in both tests. The present results suggest that non-linearities, compression/shear coupling, and intrinsic viscoelasticity affect the shear material behavior of the disc, which might have important implications for the transmission of load in the temporomandibular joint.

Association of HLA-A*3303-B*4403-DRB1*1302 haplotype, but not of TNFA promoter and NKp30 polymorphism, with postherpetic neuralgia (PHN) in the Japanese population.

Herpes zoster is a common disease caused by reactivation of the varicella zoster virus (VZV). In a small number of herpes zoster patients, pain persists beyond 4 weeks or more after healing of vesicular eruptions; this condition is termed postherpetic neuralgia (PHN). Positive associations of human histocompatibility leukocyte antigens (HLA) class I antigens, A33 and B44, with PHN in the Japanese population have been reported. Our hypothesis is that susceptibility genes to PHN might exist in the HLA region and the study objective is to further examine possible associations of genes in HLA class I, II and III regions, HLA-A, -B, -DRB1, tumor necrosis factor alpha (TNFA) promoter, and a natural killer cell activating receptor, NKp30 polymorphisms with PHN. Although TNFA or NKp30 in the class III region had been considered as a candidate locus, we found no associations of TNFA promoter or NKp30 polymorphisms with PHN in this study. We demonstrated that HLA-A*3303, -B*4403 and -DRB1*1302 alleles were significantly associated with PHN (P = 0.0007 for A*3303, P = 0.001 for B*4403 and P = 0.001 for DRB1*1302). The frequency of the HLA-A*3303-B*4403-DRB1*1302 haplotype was also significantly higher in the PHN patients than in the healthy controls (P = 0.0039). Our results suggest that this haplotype might be related to the pathogenesis of PHN.

Biomechanical response of bovine temporomandibular joint disc to prolonged tensile stress.

This study was designed to evaluate the influence of prolonged tensile stress on the viscoelasticity of the temporomandibular joint (TMJ) disc. Twenty discs from 10, 3-year-old cattle were used. Tensile stress of 1.5 MPa was applied to specimens from the discs for 10, 20, 40 and 60 min. Following the prescribed period of tension for creep, the specimens were removed from the tension device and any recovery observed for 20 min. In all specimens, strain increased at the onset of stress application and reached almost steady conditions after 5 min. Although, the strain became slightly larger when the creep time was longer, no significant differences were found in the strains between any two tests with different periods of creep. The residual strain increased significantly with creep duration, and similarly the degree of recovery decreased significantly. In 10- and 20-min creep tests, the residual strains were 0.1 and 1.0%, the specimens in 40- and 60-min tests revealed irreversible changes in length. It was concluded that continuous loading for >40 min causes creep damage in bovine TMJ disc, and that prolonged sustained tension affects the recovery of joint homeostasis.