General anesthesia is important for pharmacological studies in laboratory animals. Although a number of
transgenic animals have been reported, basic analyses concerning mouse ECG and heart rate variability (HRV) have
not been rigorously examined.
In the present study, we analyzed the effects of isoflurane as an inhalational anesthetic agent on ECG in C57BL6
mice, which have highly homogeneous genetic background. With 2% isoflurane anesthesia, the heart rate was
acceptable (～500 bpm). Interestingly, C57BL6 mice showed relatively large standard deviation (57.3 bpm).
Our data indicates that C57BL6 mice have various heart rates, although its genetic background is homogeneous.
Higher concentrations of isoflurane resulted in a decreased heart rate, in a dose-dependent manner, and resulted
in a marginal response to the sympathetic β-blocker, propranolol. Furthermore, we evaluated HRV as well as ECG
parameters in mice. Our results indicate the importance of selecting an anesthesia for pharmacological studies using
standard ECG parameters and HRV in C57BL6 mice. We provide basic ECG parameters from a large population of
C57BL6 mice, which are fundamental baseline data for cardiovascular physiology.
Objectives: The aim of this study is to investigate the effect of washed salvaged red blood cells on
hemostasis in open heart surgery using the cardiopulmonary bypass (CPB). Methods: Nine patients were enrolled in this study. The cell salvage system was used throughout the surgery. Three blood samples (1mL each) were obtained from each patient one hour after the CPB for the measurements consisting of control blood sample (Control group), 1.0ml of blood added with 0.2mL salvage blood (CS group) or 0.2mL normal saline (NS group). Test samples were evaluated using rotational thromboelastometry （ROTEM®）. Coagulation was triggered by ellagic acid. Results: No significant differences were observed in the clotting time among the three groups. Clot formation time in the CS group and NS group was prolonged significantly compared with Control group (Control, 138±51; CS, 103±28; NS, 135±48 sec). Amplitude of ROTEM® band at 10 minutes and maximum clot firmness in both the CS and NS group were significantly narrower than that of Control group. Conclusions: This ex-vivo study using ROTEM® suggested that the perioperative administration of washed salvaged red blood cells might have a potential to induce coagulopathy in cardiac surgery using the CPB.
We compared the effects of inhalation anesthesia (2% isoflurane), intraperitoneal injection of pentobarbital anesthesia (50 mg/kg), and a combination anesthetic consisting of medetomidine, midazolam and butorphanol (MMB) on electrocardiograms in mice. Using either isoflurane inhalation anesthesia or pentobarbital anesthesia, heart rate (HR) was in the acceptable range (ca. 450-500 bpm). In contrast, MMB anesthesia decreased HR
significantly. Importantly, MMB anesthesia responded minimally to propranolol (β-blocker), suggesting that MMB
anesthesia affects sympathetic tonus and is not suitable for evaluation of the cardiovascular or sympathetic system.
We confirmed that modified MMB, with a decreased dose of medetomidine from the original protocol (an α₂ agonist), was associated with a HR of 400 bpm and a diminished response to propranolol. Our present results illustrate the importance of using an appropriate form of anesthesia suitable for experimental pharmacological studies.
Background: We reported that enhanced phospholipase C (PLC)-δ1, which was detected in patients with
coronary spasm, caused coronary spasm in mice. We investigated the role of protein kinase C (PKC) in acetylcholine
(ACh)-induced Ca²⁺ influx under enhanced PLC-δ1 using human embryonic kidney (HEK)-293 cells. Methods and Results: Intracellular free Ca²⁺ concentration （[Ca²⁺]i） was measured by fura-2, and Ca²⁺ influx was evaluated by the increase in [Ca²⁺]i after addition of extracellular Ca²⁺. ACh-induced Ca²⁺ influx (nM) in HEK-293 cells was 21±2 in control HEK-293 cells, 52±6 in the cells with PLC-δ1 overexpression, and 75±9 in those with PLC-δ1 overexpression and PKC down-regulation (all p<0.05 among 3 groups). Ca²⁺ influx under treatment with nifedipine at 10⁻⁵M was 2.9±0.1 times higher in the cells with PLC-δ1 overexpression and 5.6±0.2 times higher in those with PLC-δ1 overexpression and PKC down-regulation compared with the control cells (all p<0.05 among 3 groups). Conclusions: ACh-induced Ca²⁺ influx was enhanced by PLC-δ1 overexpression, but was attenuated by PKC activation. PKC plays an important role in Ca²⁺ influx under enhanced PLC-δ1 in a negative feedback fashion.
Both pancreas head ductal carcinoma (PHDC) and distal bile duct carcinoma (DBDC) are located within
the pancreas head/intra-pancreatic bile duct region, and are the most aggressive malignancies with poor patient
prognosis. In the present study, we demonstrated clinicopathological features and patients prognosis of PHDC/DBDC. We examined total 87 surgically resected cases of PHDC (40 cases) and DBDC (47 cases). PHDC showed
frequent neural invasion (85.0%) and lymph node metastasis (77.5%), compared with DBDC (57.4% and 40.4%
respectively), resulting in the poorer prognosis (P=0.0219) than DBDC. In addition, PHDC expressed MUC2 (10.0%)
and MUC6 (25.0%) less frequently, compared with DBDC (36.2% and 55.3%, respectively). MUC5AC-negative PHDC
exhibited significantly poorer patient’s prognosis, compared with MUC5AC-positive PHDC (P=0.0111), MUC5ACpositive
DBDC (P=0.000162), and MUC5AC-negative DBDC (P=0.00416). In conclusion, MUC5AC-negative PHDC
showed significantly poor patient's prognosis.
Patients with chronic respiratory diseases have been found to develop malnutrition as a result of enhanced resting metabolic rate (RMR) associated with exacerbated ventilatory impairment. It is therefore necessary to measure each individual's required amount of energy in order to provide nutritional support. There are few reports regarding the RMR of patients with chronic respiratory diseases that have used indirect calorimetry. We investigated the association between body composition, pulmonary function, and dyspnea grade by measuring RMR using indirect calorimetry in 23 patients with chronic obstructive pulmonary disease (COPD) and 21 patients with interstitial pneumonia (IP). We found no increase in RMR in COPD patients without any decrease in weight or muscle mass and increase in RMR in IP patients. Fat mass was suggested to influence RMR in IP patients. Early nutritional
support for COPD patients in whom no reduction in body weight or muscle mass is seen may possibly prevent RMR
enhancement and malnutrition. RMR measurements using indirect calorimetry are an easy means of ascertaining the
amount of energy required for nutritional support, and are easy enough to use when evaluating the nutritional status
of patients with chronic respiratory diseases.
We conducted a preliminary comparative study of 32 carpal tunnel syndrome patients and a control group of 60 individuals matched for age, gender, height, and weight. Our aim is to determine a diagnostic cutoff score for a screening tool we had developed by carefully selecting questions based on the Japanese Society for Surgery of the Hand version of the Carpal Tunnel Syndrome Instrument (CTSI-JSSH). The results were analyzed by using a ROC curve and Youden's index, and the cutoff score was determined to be 7, indicating that subjects scoring ≥ 7 were positive for CTS. We then used this cutoff score to create a 2 × 2 contingency table to calculate the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value, and efficiency of the tool. The values obtained were the same as, or higher than, those in previous studies. The screening tool that we developed has the advantages of low cost and low risk; furthermore, it allows for quick self-assessment. Our next step will be to conduct a field survey using a large number of subjects to verify the usefulness of the tool.
Objectives: To elucidate the relationship between posture and oral function in the elderly and to verify
the effects of interventions aimed at improving posture on oral functions, particularly in the frail elderly. Methods: We evaluated postural conditions and oral and respiratory functions in 11 healthy elderly people living locally and 9 frail elderly persons using day-care services. The frail elderly were assigned to 2 groups. Interventions were performed for a total of 16 weeks in a crossover design; they comprised regular swallowing exercises and fall-prevention exercises aimed at improving posture and balance. Results: Postural conditions in the elderly were correlated with oral function and respiratory function. Intervention with either the aspiration-prevention exercises or the fall-prevention exercises significantly improved kyphotic posture in the frail elderly. Intervention with the fall-prevention exercises alone improved swallowing function and oral-related quality of life (QOL). Conclusions: To effectively improve oral function in the frail elderly, exercises helping to improve posture and balance should be added to swallowing exercises.
Chronic pancreatitis is histopathologically characterized by the progression of pancreatic fibrosis. Pancreatic stellate cells (PSCs) play a principal role in the development of pancreatic fibrosis. Tranilast suppresses collagen synthesis of fibroblasts derived from keloid hypertrophic scars and cell proliferation of fibroblasts. Hence, we hypothesize that tranilast suppresses fibrosis and is effective against pancreatic fibrosis. In this study, we examined the effect of tranilast on cell proliferation, activation, and collagen synthesis of cultured PSCs. Tranilast significantly inhibited the proliferation of PSCs when they were cultured with and without of platelet-derived growth factor (PDGF) and decreased the expression of alpha smooth muscle actin (α-SMA) in cultures with Transforming Growth Factor-β1 (TGF-β1) and PDGF. Tranilast did not cause a significant dose-dependent reduction in the amount of collagen in the medium. Neither did it significantly affect the expression of Col-1 mRNA compared to the control. Our results suggest that tranilast inhibits the development of pancreatic fibrosis, making it a potential therapeutic agents for chronic pancreatitis.
Objectives: We investigated the usefulness of “open-crotch underpants for single-arm manipulation” developed to facilitate toileting in stroke patients requiring help because of impaired standing balance. Methods: The subjects were stroke patients allocated to two groups (independent and dependent). The study
consisted of two parts. In Step 1, the degrees of crotch opening and exposure of the genital and anal area were
evaluated. In Step 2, after manipulating the underpants, subjects excreted and their underpants were visually
examined for soiling. In addition, subjects rated satisfaction with toileting. Results: The Step-1 results showed that subjects in both groups had a significantly larger opening after the crotch-opening task than before it, suggesting that there was sufficient exposure of the genital and anal area. The Step-2 experiments revealed no soiling of underpants through excretion. Satisfaction with toileting was significantly higher with unassisted toileting using the underpants than with assisted toileting. Conclusion: This study demonstrated the usefulness of these “open-crotch underpants for single-arm manipulation”, particularly for dependent hemiplegic patients.