Yacon diet (Smallanthus sonchifolius, Asteraceae) improves hepatic insulin resistance via reducing Trb3 expression in Zucker fa/fa rats.

OBJECTIVE: Yacon is a perennial plant forming a clump of >20 big, edible underground tubers. Yacon, which originates from South America, has become increasingly popular in the Japanese diet for tubers have a lower caloric value and a high fiber content. Recent studies have suggested that yacon feeding ameliorates diabetes as indicated by reduced blood glucose. METHODS: We fed male Zucker fa/fa rats for 5 weeks with isocaloric normal chow diet containing from 6.5% control aroid or 6.5% yacon. Insulin sensitivity was evaluated by euglycemic-hyperinsulinemic clamp study. RESULTS: Body weight was comparable between yacon- and aroid-fed rats. In the basal state, yacon feeding had an effect to lower fasting glucose levels from 184.1±4.1 to 167.8±2.7 mg dl(-1) (P<0.01), as well as basal hepatic glucose output (HGO) from 9.9±0.4 to 7.4 ± 0.2 mg kg(-1) per min (P<0.01). During the clamp studies, the glucose infusion rate required to maintain euglycemia was increased by 12.3% in yacon-fed rat. The insulin suppression of HGO was also increased in yacon-fed rats compared with control rats (85.3±2.4% vs 77.0±3.0%; P<0.05), whereas the glucose disposal rate was not different between the two groups. Consistent with the clamp data, the insulin-stimulated phosphorylation of Akt was significantly enhanced in liver but not in skeletal muscle. Furthermore, tribbles 3 (Trb3) expression, which is a negative regulator of Akt activity, was markedly reduced in the liver of yacon-fed rats compared with control rats. CONCLUSION: These results indicate that the effect of yacon feeding to reduce blood glucose is likely due to its beneficial effects on hepatic insulin sensitivity in the insulin resistant state.

Current perception thresholds of patients with long-term administration of maprotiline.

The purpose of this study was to evaluate sensory nerve function using current perception thresholds (CPTs) in patients who were administrated maprotiline. Twelve patients with post-herpetic neuralgia and 20 control subjects were studied. The patients with post-herpetic neuralgia were given a daily dose of 60 mg of maprotiline and were maintained at the same dose for 6 months. Twenty control subjects were randomly selected from healthy volunteers. ACPT test was used for quantitative assessment of A beta, A sigma, and C fiber transmission, which are associated with pain, by three (2000, 250, and 5 Hz) different frequencies of electric stimulation. CPTs of 5, 250, and 2000 Hz in patients with post-herpetic neuralgia 2 months after administration of maprotiline were 141.7 +/- 17.3 for 5 Hz, 120.8 +/- 12.9 for 250 Hz, and 256.4 +/- 18.0 for 2000 Hz, which were significantly (P < 0.01) higher than those (67.0 +/- 9.1 for 5 Hz, 73.4 +/- 7.0 for 250 Hz, and 191.3 +/- 20.2 for 2000 Hz) before treatment and than those (35.3 +/- 15.8, 62.0 +/- 18.9, and 198.9 +/- 15.8) of control subjects. An increase in CPT for 5 Hz at 2 months after administration of maprotiline correlated (r = 0.71, p = 0.01) with a decrease in pain score. There were no correlations between an increase in CPT and changes in Hamilton Depression Scale (HAMD) values until 3 months after maprotiline treatment. However, we found that an increase in CPT for 5 Hz at 6 months after maprotiline treatment correlated (r = 0.68, p = 0.015) with a decrease in HAMD values. In conclusion, administration of 60 mg maprotiline significantly increased current perception thresholds at 2 months after the administration.

Plasma proinflammatory cytokine response to surgical stress in elderly patients.

We investigated the change of plasma cytokines concentrations in elderly patients during lower abdominal surgery. Plasma interleukin (IL-)6 concentrations (68.0+/-15.4 and 36.1+/-20.7 pg/ml) in elderly patients at 24 h and at 3 days after surgery were significantly higher than those (35.1+/-21.5 and 18.6+/-10.6 pg/ml) of young adults. Plasma IL-6 concentrations (92.3+/- 31.9 pg/ml) in elderly patients anesthetized with propofol and fentanyl were significantly higher at the end of the operation than that (57.9+/-36.7 pg/ml) of elderly patients anesthetized with sevoflurane and fentanyl. In conclusion, elderly patients have an increased and delayed IL-6 response to surgical trauma compared with young adults. Plasma IL-6 production after surgical trauma in elderly patients with total intravenous anesthesia with propofol was significantly higher than that in elderly patients with sevoflurane anesthesia.

Effect of epidural analgesia on postoperative paralytic ileus in chronic schizophrenia.

BACKGROUND AND OBJECTIVES: Postoperative paralytic ileus is frequently encountered in chronic schizophrenic patients who undergo abdominal surgery. We investigated whether epidural analgesia with local anesthetics minimizes postoperative ileus in schizophrenic patients who are treated long term with antipsychotic drugs. METHODS: We measured the VAS pain after surgery and the time that elapsed before the first passage of flatus and/or feces after the end of surgery in schizophrenic patients provided analgesia with systemic buprenorphine (group A) and schizophrenic patients receiving epidural analgesia with local anesthetics (group B). RESULTS: The frequency of patients who did not pass flatus and/or feces for more than 120 hours postoperatively was significantly higher in group A. Postoperative pain scores of group A at 8 and 24 hours after the end of anesthesia were 36.0 +/- 12.8 and 31.7 +/- 10.7 (0 to 100 mm scale), which were significantly higher than 25.4 +/- 13.2 and 20.5 +/- 9.4 scores in group B. CONCLUSIONS: Epidural analgesia with local anesthetics in chronic schizophrenic patients undergoing abdominal surgery minimizes postoperative ileus compared to patients receiving systemic buprenorphine.

Plasma cytokine response to surgical stress in schizophrenic patients.

Schizophrenic patients are reported to have immunological dysfunction, however, the immune response to surgery in schizophrenic patients remains unclear. We measured plasma interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) before, during and after colectomy, hemicolectomy and sigmoidectomy in 25 chronic schizophrenic patients (Group S) and 25 control patients (Group C) using ELISA assays. We could find no significant difference in the baseline plasma concentrations of IL-6, IL-8 and TNF-alpha between Group S and Group C. Plasma IL-6 concentrations (32.1 (30.3) and 15.8 (9.6) pg/ml) in Group S at the end of the operation and 24 h after surgery were significantly lower than 76.9 (37.1) and 35.1 (21.5) pg/ml of Group C. Plasma IL-8 concentration (6.1 (2.8)) in Group S at the end of the operation was significantly lower than 8.7 (4.2) pg/ml of Group C. There were no significant changes in plasma TNF-alpha concentration throughout the study period in either group. Plasma cortisol concentrations of schizophrenic patients during surgery were significantly lower than those of control patients. The plasma IL-6 concentrations correlated with plasma cortisol concentrations in either group. We conclude that proinflammatory cytokine response to abdominal surgery is inhibited in schizophrenic patients.

Effects of the aminopeptidase P inhibitor apstatin on bradykinin-induced inositol 1,4,5-triphosphate in neonatal rat cardiomyocytes.

We investigated the effect of apstatin (an aminopeptidase P inhibitor) on bradykinin-induced inositol 1,4,5-triphosphate (IP3) formation and glucose uptake in isolated neonatal rat cardiomyocytes. Apstatin enhanced bradykinin-induced IP3 formation in a dose-dependent manner. We found that 1 microM Hoe 140 (a bradykinin B2-receptor antagonist) significantly decreased the potentiation of bradykinin-induced IP3 production by 5 microM apstatin from 781.8+/-67.2 to 127.4+/-33.0 pmol/mg protein; 5 microM apstatin increased bradykinin-induced glucose uptake from 197.0+/-25.5 to 297.3+/-64.0 pmol/h per milligram of protein. The stimulation of glucose uptake with apstatin was blocked to 132.5+/-26.2 pmol/h per milligram of protein by 1 microM Hoe 140. We conclude that apstatin stimulates bradykinin-induced IP3 formation and glucose uptake by preventing the degradation of bradykinin.

Endocrine response to surgical stress in three patients over 100 yr.

PURPOSE: To report the change of plasma epinephrine, norepinephrine, cortisol, plasma renin activity, plasma aldosterone and plasma atrial natriuretic peptide during general anesthesia in three centenarian patients. CLINICAL FEATURES: Three patients aged 101, 101 and 102-yr, underwent a screw fixation of femoral fracture under general anesthesia. Plasma concentrations of epinephrine, norepinephrine, cortisol, renin activity, aldosterone and atrial natriuretic peptide were measured before the induction of anesthesia, 15 min after incision and 60 min after the end of surgery. Plasma epinephrine concentrations in the three patients increased from 419, 344 and 377 pg x ml(-1) before anesthesia to 688, 534 and 478 pg x ml(-1) 15 min after skin incision. Plasma norepinephrine concentrations increased markedly from 408, 513 and 606 pg x ml(-1) before anesthesia to 2950, 1864 and 1574 pg x ml(-1) 15 min after skin incision. The cortisol response to surgery was similar to that of young adults. Plasma aldosterone and renin activity was low throughout anesthesia. Plasma atrial natriuretic peptide increased from 353, 367 and 109 pg x ml(-1) before induction to 479, 487 and 168 pg x ml(-1) 15 min after skin incision. CONCLUSION: Plasma norepinephrine concentration in patients over 100 yr increased markedly during anesthesia, while plasma renin activity and aldosterone were lower.

Plasma inflammatory cytokine response to surgical trauma in chronic depressed patients.

We investigated inflammatory cytokine response in chronic depressed patients during abdominal surgery. Twenty-five major depressed patients (Group D) and twenty-five patients (Group C) as the control were studied. Plasma interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) concentrations were measured before and at 15 min after induction of anesthesia, the end of surgery, 24 h and 3 days after the operation. Plasma IL-6 concentrations in Group D at the end of the operation and 24 h after surgery were significantly lower than those of Group C. The plasma IL-6 concentration (87.1+/-55.3 pg/ml) of patients scoring more than 18 points in the Hamilton depression-rating score at the end of the operation was significantly higher than 57.5+/-76.7 pg/ml of patients scoring less than 18 points. Plasma IL-8 concentration (6.1+/-3.2 pg/ml) in Group D at the end of the operation was significantly lower than 8.7+/-4.2 pg/ml of Group C. We conclude that plasma IL-6 and IL-8 response to surgical trauma is inhibited in chronic depressed patients. The IL-6 response to surgical trauma is depending on the clinical state of depression.

Bradykinin-induced inositol 1,4,5-triphosphate in neonatal rat cardiomyocytes is activated by endotoxin.

We studied the effect of endotoxin on bradykinin-induced inositol 1,4,5-triphosphate (IP3) production and the relationship between IP3 and phospholipase A2 or thromboxane A2. When exposed with 0.1, 1.0, and 10 microg ml(-1) lipopolysaccharide (LPS) for short-term (60 min), 100 nmol L(-1) bradykinin-induced IP3 production was stimulated in a dose-dependent manner from 569.2+/-42.4 in absence of LPS to 714.3+/-52.8, 804.5+/-42.6, and 894.1+/-62.6 pmol mg protein(-1). Treatment of 100 micromol L(-1) ACA (a phospholipase A2 inhibitor) and 10 micromol L(-1) BM13.177 (a thromboxane A2 inhibitor) significantly decreased bradykinin-induced IP3 production and LPS (1.0 microg mL(-1)) modulation of bradykinin-induced IP3 formation from 804.5+/-42.6 to 217.4+/-12.7 and 208.6+/-17.1 pmol mg protein(-1), respectively. LPS modulation of bradykinin-induced IP3 production was significantly blocked by 1 micromol L(-1) TMB-8 (an intracellular Ca2+ antagonist) from 804.5+/-42.6 to 507.8+/-33.4 pmol mg protein(-1). LPS modulation of bradykinin-induced IP3 production was significantly inhibited from 804.5+/-42.6 to 397.4+/-30.3 pmol mg protein(-1) by treatment of 10 micromol L(-1) indomethacin. In conclusion, short-term administration of LPS stimulates bradykinin-induced IP3 formation through activation of phospholipase A2 and thromboxane A2 and the stimulation is associated with an elevation of intracellular Ca2+.

Current perception thresholds of epileptic patients treated with valproate.

We investigated the current perception threshold (CPT) of epileptic patients treated with valproate. The CPTs at frequencies of 5 Hz, 250 Hz and 2000 Hz in the control group of patients were 198.9 +/- 15.8, 62.0 +/- 18.9 and 35.3 +/- 15.8, respectively. The CPTs at 5 Hz, 250 Hz and 2000 Hz in the epileptic group of patients were 350.6 +/- 61.3, 338.6 +/- 64.3 and 193.2 +/- 21.1, respectively. The CPTs at 5 Hz, 250 Hz and 2000 Hz in the epileptic group were significantly higher than those of the control group. We measured the CPTs for 6 months after the administration of valproate in three patients with traumatic epilepsy. Their CPTs were higher than that of the epileptic group. The CPTs at 5 Hz, 250 Hz and 2000 Hz reached a maximum 4 weeks after the administration of valproate for two of these patients and in 6 weeks for the other patient. When the administration of valproate to a patient was stopped, CPTs decreased.

Inhibition of the cortisol response to surgical stress in chronically depressed patients.

STUDY OBJECTIVE: To evaluate whether the pituitary-adrenal and catecholamine response to surgical stress is modified in chronically depressed patients. DESIGN: Prospective, controlled study. PATIENTS: 25 ASA physical status I and II depressed patients taking chronic antidepressant therapy and 25 control patients undergoing orthopedic surgery of the extremities. INTERVENTIONS: All patients received anesthesia induction with thiopental 5 mg/kg and suxamethonium 1 mg/kg intravenously (IV) and were maintained with 1.5% to 2.0% isoflurane in nitrous oxide (70%) and oxygen (30%). MEASUREMENTS AND MAIN RESULTS: Plasma cortisol concentration (27.7 +/- 3.6 microg/dL) in chronic depressed patients at 60 minutes after the skin incision was not significantly higher than that (23.9 +/- 2.7 microg/dL) before the induction, although plasma cortisol concentration in the control group significantly increased. Plasma norepinephrine concentration at 60 min after the skin incision in depressed patients with more symptoms of depression was significantly higher than that of patients with less symptoms of depression. CONCLUSION: The cortisol response to surgical stress in depressed patients was inhibited and norepinephrine response to surgical stress was increased in depressed patients with more symptoms of depression.

Halothane and sevoflurane decrease norepinephrine-stimulated glucose transport in neonatal cardiomyocyte.

UNLABELLED: Catecholamine regulates myocardial glucose use. However, the effect of inhaled anesthetics on myocardial glucose transport stimulated by catecholamine is unclear. We studied the effect of halothane and sevoflurane on uptake of 2-deoxyglucose stimulated by norepinephrine in neonatal cardiomyocytes and the mechanism that modulates glucose transport. We studied the effects of halothane and sevoflurane on norepinephrine (NE)-stimulated glucose uptake and the effects of halothane and sevoflurane on glucose uptake stimulated by W7 (a calcium releasing agent), phorbol 12 myristate-13-acetate (a protein kinase C agonist), and LiCl. Sevoflurane decreased NE-stimulated glucose uptake from 63.7 +/- 7.0 to 41.2 +/- 3.7 pmol h(-1) mg protein(-1), and halothane also attenuated NE-stimulated glucose uptake to 37.8 +/- 5.7 pmol h(-1) mg protein(-1). W7 at 10 micromol/L increased glucose uptake from 16.4 +/- 1.4 to 41.2 +/- 3. 4 pmol h(-1) mg protein(-1). The stimulation was inhibited in the presence of 0.8 mmol/L sevoflurane and 0.58 mmol/L halothane to 23.9 +/- 3.7 and 25.6 +/- 3.6 pmol h(-1) mg protein(-1), respectively. Halothane and sevoflurane did not significantly affect the glucose uptake stimulated by 1 nmol/L insulin, 10 micromol/L PMA, or 10 mmol/L LiCl. We conclude that halothane and sevoflurane decrease NE-stimulated glucose uptake through decrease in intracellular calcium in cardiomyocytes. IMPLICATIONS: The effect of inhaled anesthetics on myocardial glucose uptake during administration of catecholamine is unclear. The myocardial glucose uptake is stimulated not only by catecholamine, but also by insulin, protein kinase C, and increase of intracellular calcium. We examined the effects of halothane and sevoflurane on glucose uptake.

Current perception thresholds and postoperative pain in schizophrenic patients.

BACKGROUND AND OBJECTIVES: Schizophrenic patients may have less sensitivity to pain; however, pain insensitivity in schizophrenia has not been adequately evaluated. We investigated current perception threshold (CPT) and postoperative pain intensity in patients with long-standing and treated schizophrenia and control patients. METHODS: We measured CPTs for 2,000 Hz, 250 Hz, and 5 Hz and postoperative pain intensity using a visual analogue scale (VAS) in 50 chronic schizophrenic patients who were on chronic phenothiazine derivatives (> 10 years) and for 25 control patients. RESULTS: CPTs for 2,000 Hz, 250 Hz, and 5 Hz in schizophrenic patients were 334.2 +/- 112.2, 303.9 +/- 117.1, and 165.0 +/- 72.3, respectively. CPTs for 2,000 Hz, 250 Hz, and 5 Hz in schizophrenic patients were significantly higher than those of control patients. VAS pain scores of schizophrenic patients were 4.0 +/- 1.7 at 2 hours post-operatively and 3.8 +/- 1.5 at 5 hours postoperatively, which were significantly (P < .05) lower than those (5.0 +/- 1.6 and 5.1 +/- 1.9) of the control group. CONCLUSIONS: Chronic schizophrenic patients have increased current perception threshold and lower VAS pain scores in postoperative pain compared with control patients.

Effects of angiotensin-converting enzyme inhibitors on glucose uptake.

We investigated the effect of angiotensin-converting enzyme inhibitors on glucose uptake regulation as well as the effect of bradykinin (BK) on glucose uptake and its regulation by using inhibitors of phospholipase C, BK B2 receptor, protein kinase C, phosphatidylinositol 3-kinase, tyrosine kinase, and intracellular Ca(2+). We measured 2-deoxyglucose uptake by using L(6) skeletal muscle cells. In the presence of 1 nmol/L of insulin, 1 micromol/L of enalaprilat enhanced insulin-induced glucose uptake from 89.2+/-8. 1 to 138.0+/-13.6 pmol/h per mg protein. The stimulation of glucose uptake with enalaprilat was blocked to 92.7+/-7.8 pmol/h per mg protein by 10 micromol/L HOE 140 (a BK B2 receptor antagonist). In the presence of 1 nmol/L of insulin, exposure to 10 micromol/L BK stimulated glucose uptake from 89.2+/-8.1 to 171.6+/-10.1 pmol/h per mg protein. However, in the absence of insulin, BK could not enhance glucose uptake. One hundred nanomoles per liter of tyrphostin A-23 and genistein, which are tyrosine kinase inhibitors, significantly decreased the BK-induced glucose uptake from 142.0+/-8.4 to 87.6+/-6. 4 and 85.2+/-7.3 pmol/h per mg protein, respectively. BK-induced glucose uptake was inhibited significantly by 10 micromol/L U73122 (a phospholipase C antagonist) from 142.0+/-8.4 to 95.7+/-9.5 pmol/h per mg protein. One and 20 micromol/L of TMB-8 (an intracellular calcium antagonist) significantly decreased BK-induced glucose uptake from 142.0+/-8.4 to 108.0+/-9.6 and 100.8+/-11.4 pmol/h per mg protein. Angiotensin-converting enzyme inhibitors enhanced insulin-induced glucose uptake via the BK B2 receptor. BK-stimulated glucose uptake is related to phospholipase C, tyrosine kinase, and an increase in intracellular calcium.

Sevoflurane stimulates inositol 1,4,5-trisphosphate in skeletal muscle.

UNLABELLED: Inositol 1,4,5-triphosphate (IP(3)) plays an important role in excitation-contraction coupling and malignant hyperthermia in skeletal muscle. We investigated whether sevoflurane affects IP(3) formation in L(6) skeletal muscle cells and studied the mechanisms that modulate IP(3). Sevoflurane stimulated IP(3) production from a basal level of 78.4 +/- 6.1 to 730.0 +/- 53.1 pmol. mg. protein(-1) in 2 mM of sevoflurane in a dose-dependent manner. A dose of 10 microM of U73122 (a phospholipase C antagonist) significantly decreased 0.8 mM of sevoflurane-stimulated IP(3) production from 387. 8 +/- 24.7 to 247.8 +/- 19.8 pmol. mg. protein(-1). A dose of 100 microM of (p-amylcinnamoyl) anthranilic acid (a PLA(2) antagonist) also significantly decreased sevoflurane-stimulated IP(3) production to 282.0 +/- 24.0 pmol. mg. protein(-1). Exposure to 1 microM of genistein and tyrphostin A23 (tyrosine kinase inhibitors) significantly decreased sevoflurane-stimulated IP(3) production to 241.0 +/- 35.3 and 267.4 +/- 32.9 pmol. mg. protein(-1). Sevoflurane-stimulated IP(3) production was significantly decreased by 10 microM of 8-(N,N-diethylamino) octyl-3,4-5-trimathoxybenzoate (an intracellular calcium antagonist) and 100 microM and 1 mM of guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS), a guanosine 5'triphosphate-binding protein inhibitor. Elevation of IP(3) production was significantly higher in halothane than in sevoflurane and isoflurane at the same concentration of 0.8 mM. We conclude that sevoflurane-stimulated IP(3) production involves phospholipase C, phospholipase A(2), tyrosine kinase, and guanosine 5'triphosphate-binding protein and the stimulation is associated with concentration of intracellular ionized calcium. IMPLICATIONS: Inhaled anesthetics increase intracellular ionized calcium in the skeletal muscle cell and the ionized calcium increase is partly released from the intracellular store by inositol 1,4,5-triphosphate (IP(3)) formation. IP(3) plays an important role in excitation-contraction coupling and malignant hyperthermia. We studied whether sevoflurane affects IP(3) formation and the mechanisms that modulate IP(3).

Insulin enhances the bradykinin response in L8 rat skeletal myoblasts.

Inhibitors of ACE/kininase II enhance insulin sensitivity, an action that is mediated in part by bradykinin (BK). We investigated whether insulin interacts with the BK receptor signaling to modulate the inositol 1,4,5-trisphosphate (IP3) response to BK in L8 rat skeletal myoblasts. Stimulation of the cultures with BK (10 nmol/l) for 15 s increased IP3 from a basal level of 75.2 +/- 7.6 to 200.2 +/- 15.7 pmol/mg protein. Treatment of the cultures with 1, 2, and 20 nmol/l of insulin for 90 min before adding BK increased IP3 formation by the same BK dose to 328.2 +/- 19, 434.5 +/- 18, and 460.8 +/-21.3 pmol/mg protein, respectively. When wortmannin was administered to inhibit phosphatidylinositol (PI) 3-kinases at lower concentration (1 nmol/l), it increased IP3 formation stimulated by BK only when insulin was present. At a higher concentration (100 nmol/l), wortmannin significantly enhanced BK-induced IP3 formation in the absence of insulin. Genistein and tyrphostin A-23, tyrosine kinase inhibitors, completely reversed the elevated IP3 formation by BK and insulin. The IP3 response to 10 nmol/l BK was 223.3 +/- 11.8 pmol/mg protein in the absence of insulin and 402.2 +/- 12.0 pmol/mg protein in the presence of 2 nmol/l insulin. However, when exposing the cultures to 1 nmol/l genistein or tyrphostin A-23, the IP3 response to BK in the presence of insulin decreased to 211.8 +/- 46.7 and 187.7 +/- 19.9 pmol/mg protein. Tyrphostin A-1, the inactive analog, was ineffective. Exposing the cells to 1 micromol/ 3,4,5-trimethoxybenzoic acid 8-[diethylamino]octyl ester, an intracellular Ca2+ antagonist, did not change the potentiation by insulin. But, exposing them to 0.1 micromol/l n-[6-aminohexyl]-5-chloro-1-naphthalene-sulfonamide, a calmodulin antagonist, resulted in enhanced IP3 response to BK alone to 292.2 +/- 18.5 pmol/mg protein and to BK in the presence of 1, 2, and 20 nmol/l insulin to 488 +/- 22.2, 625.5 +/- 11.6, and 665.2 +/- 15.9 pmol/mg protein, respectively. In conclusion, insulin potentiates BK-induced IP3 production in L8 rat skeletal myoblasts, and this action of insulin involves a tyrosine kinase. Inhibition of PI 3-kinases potentiated BK-induced IP3 formation in the presence of insulin. Calmodulin blocked the action of insulin. These results support a modulatory effect of insulin on the BK signaling system via a tyrosine kinase in L8 rat skeletal myoblasts that results in increased IP3 formation. Because BK release from skeletal muscle increases during contractions, this action of insulin is likely to play a role in the modulation of the excitation-contraction coupling process of the skeletal muscle.

[A case of recurrent breast cancer with carcinoma erysipeloides responding to sequential therapy with docetaxel (TXT) and doxifluridine (5'-DFUR) accompanied by leucovorin (LV)].

A left radical mastectomy was performed on a 53-year-old woman, diagnosed with left inflammatory breast cancer, after local arterial chemotherapy with cyclophosphamide (CPA), doxorubicin and 5-fluorouracil (5-FU). Adjuvant therapy was added with irradiation and ECF. Four months after the operation, a red eruption was detected on the left upper chest wall. The lesion was diagnosed by skin biopsy as a recurrent breast cancer with carcinoma erysipeloides. Tumor marker levels suggested the recurrent cancer was ECF resistant, so we changed the chemotherapy regime to a single dose of TXT. Although tumor marker levels and the skin eruptions improved at the beginning of the therapy, pleuritis carcinomatosa was found. We changed the regime again to a continuous dose of 5'-DFUR and LV for day 1 to 7. With this regime the clinical symptoms improved, and 2 courses of this modified FL therapy were carried out. After the therapy, the tumor seemed resistant to this modified FL therapy. Therefore, we tried a sequential therapy with TXT and the modified FL, which induced an improvement in clinical symptoms. Two years later, the patient died from the breast cancer. Therefore, we conclude that the sequential therapy may be beneficial in managing untreatable carcinoma erysipeloides of recurrent breast cancer.

[A case of unresectable gallbladder cancer responding to combination therapy with hyperthermia and local chemotherapy].

A 78-year-old woman was admitted to our hospital for the control of gallbladder cancer. A peritoneal metastasis, diagnosed as unresectable cancer, was detected during surgery in a previous hospital, and a biliary stent was introduced and gastrojejunostomy was performed. In our hospital she was treated weekly with local chemotherapy (PFL; cisplatin 2.5-5 mg/body ia, fluorouracil 300 mg/body ia, and calcium folinate 30 mg/body ia, via the common hepatic arterial port) at the time of hyperthermia. Hyperthermia was performed with a Thermox 500 (HEH-500 C) at the power of 500 watts for 45-60 minutes. To enhance the hyperthermia effect, mitomycin C 2-4 mg/body ia via the common hepatic arterial port and 500 ml of 7.5% glucose infusion were given. As a result of the combination therapy, the volume of the whole tumor was reduced to 60.9% on computed tomography, and diagnosed as PR. The serum level of CA19-9 decreased from 3,000 U/ml to 300 U/ml. The patient continued to receive the therapy for 1 year, and is now well. Therefore, we conclude that combination therapy with hyperthermia and local chemotherapy seems beneficial in managing unresectable advanced gallbladder cancer, especially for the elderly.

Effect of linear polarized light radiation on impaired mitochondrial oxidative phosphorylation in skeletal muscle.

PURPOSE: The aim of this study was to investigate the effect of linear polarized light radiation (LPLR) on mitochondrial oxidative phosphorylation impaired by hemorrhagic shock or Escherichia coli lipopolysaccharide (LPS) in skeletal muscle. METHODS: We studied the effect of LPLR on mitochondrial function of skeletal muscle by using a model of mitochondria impaired by hemorrhage or LPS. The oxygen uptake in states 3 and 4, the respiratory control ratio (RCR), and the adenosine diphosphate-to-oxygen ratio (ADP/O) were measured with a Clark oxygen electrode. RESULTS: Oxygen uptake in states 3 and 4, RCR, and ADP/O were significantly decreased by hemorrhage for 4 h and by LPS treatment for 12 h. Oxygen uptake in states 3 and 4 impaired by hemorrhage increased significantly from 40.1 +/- 3.2 to 60.1 +/- 5.4 nmol O(2).min(-1).mg protein(-1) after LPLR, and oxygen uptake in state 4 decreased significantly from 22.8 +/- 2.4 to 17.7 +/- 1.5 nmol O(2).min(-1).mg protein(-1) after LPLR. RCR and ADP/O were also significantly increased from 1.8 +/- 0.3 and 0.9 +/- 0.2 to 3.4 +/- 0.3 and 1.5 +/- 0.1, respectively, by LPLR. Oxygen uptake in states 3 and 4 impaired by LPS was improved from 46.6 +/- 5.1 and 21.0 +/- 1.9 to 53.8 +/- 6.2 and 17.9 +/- 2.3 nmol O(2).min(-1).mg protein(-1), respectively following LPLR. RCR and ADP/O were also elevated significantly from 2.2 +/- 0.2 and 0.9 +/- 0.2 to 3.0 +/- 0.3 and 1.4 +/- 0.2, respectively, after LPLR. CONCLUSION: LPLR improved mitochondrial oxidative phosphorylation of skeletal muscle impaired by hemorrhagic shock or E. coli LPS.