D1 dopamine receptor activation reduces extracellular glutamate and GABA concentrations in the medial prefrontal cortex

The present study examined effect of administration of a selective D1 dopamine receptor agonist, SKF38393 on extracellular concentrations of glutamate (Glu) and gamma-aminobutyric acid (GABA) in mPFC, by using in vivo microdialysis. Perfusion with SKF38393 via a dialysis probe reduced concentrations of both Glu and GABA dose-relatedly, and these effects were prevented by co-perfusion with a D1 dopamine receptor antagonist, SCH23390 (40 microM). These results suggested that the dopaminergic hyperactivity may lead to the hypofunction of glutamatergic and GABAergic systems in mPFC via D1 dopamine receptor stimulation.     

Autologous blood transfusion in patients with hepatocellular carcinoma undergoing hepatectomy

BACKGROUND: Homologous blood transfusion (HBT) has the risk of an immunosuppressive effect and may adversely affect the prognosis of patients with carcinomas. Autologous blood transfusion (ABT) has not yet become a standard procedure in gastroenteric cancer surgery. We investigated the usefulness and problems of ABT combined with the use of recombinant human erythropoietin (rh-EPO). METHODS: An evaluation of autologous blood transfusion (ABT) combined with recombinant human erythropoietin (rh-EPO) treatment was conducted in 46 patients with hepatocellular carcinoma undergoing hepatectomy. Preoperative autologous blood donation (ABD) was accomplished for 25 of the 46 patients. The preoperative changes in hemoglobin and hematocrit in relation to route of administration of erythropoietin were studied. In addition, intraoperative blood requirements and the postoperative complications for patients who predonated were compared with those of patients who underwent surgery without autologous predonation. RESULTS: The proportion of patients not requiring additional homologous blood transfusions (HBT) during operation was significantly higher in the ABD group than in the non-ABD group (88% versus 38%). The incidence of postoperative complications was significantly higher in patients receiving HBT than in nontransfused patients and in those receiving ABT. CONCLUSIONS: Preoperative autologous blood donation in combination with rh-EPO therapy markedly reduced the requirement for homologous blood transfusion during surgery in patients with hepatocellular carcinoma having hepatectomy.     

Compensatory renal hypertrophy and changes of renal function following nephrectomy

We studied the changes in the serum creatinine level and the volume of the remaining kidney following nephrectomy using contrast-enhanced compounded tomogram (CT) scans. Twenty-five patients undergoing nephrectomy for renal cell carcinoma without obvious disease in the remaining kidney were carefully followed for a period of at least two years at our hospital. Twelve patients received follow-up CT scans each year after nephrectomy. The ellipsoid volume of the kidney was calculated by measuring the 3-dimensional size on CT scans. The mean relative volume (%) of the remaining kidney increased up to year 3 postoperatively, and the final mean relative volume at varying periods from years 2 to 7 was 120%. Kidneys that were smaller prior to nephrectomy showed a tendency to have a larger final relative volume after nephrectomy, although there was no significant correlation between the kidney volume prior to nephrectomy and at final measurement. The mean serum creatinine level was significantly increased at one year after nephrectomy, but it decreased significantly over time. Therefore, both compensatory renal hypertrophy and improved renal function seemed to be established within several years after nephrectomy. However, the improvement of serum creatinine was delayed compared with the increase of kidney volume. That is, renal plasma flow might be increased early by compensatory renal hypertrophy, followed within a few years by an increase in glomerular filtration and a decrease of serum creatinine.     

Morbidity and mortality after 94 extrapleural pneumonectomies for empyema

BACKGROUND: Extrapleural pneumonectomy is still indicated in some patients with empyema. We examined morbidity and mortality after this high-risk operation. METHODS: Between 1979 and 1998, 94 (92 chronic, 2 postsurgical) patients with empyema underwent extrapleural pneumonectomy. There were 79 men and 15 women (mean age, 59 years). Eighty-eight patients had a history of tuberculosis, and 53 had undergone a therapeutic pneumothorax. The right side was operated on in 50 patients and left in 44. RESULTS: Operative mortality was 8.5%. Fifteen major complications (1 esophageal perforation, 9 empyemas, and 5 bronchopleural fistulas) occurred in 13 patients. Eight patients required reexploration for hemorrhage. Reexploration was a risk factor for empyema. Bronchopleural fistulas occurred only on the right side. Eighty-nine percent of the 86 operative survivors were free of empyemas at 5 years. Overall 5-year survival was 83%, and survival was better in patients without than in those with empyema. CONCLUSIONS: Extrapleural pneumonectomy for empyema has acceptable morbidity and mortality. Postoperative empyema affects prognosis. Covering a bronchial stump with muscle is recommended, especially when the operation is performed on the right side.     

Clinical efficacy of heparin-bonded bypass circuits related to cytokine responses in children

BACKGROUND: Cardiopulmonary bypass (CPB) induces numerous systemic reactions. This study examined the efficacy of heparin-bonded CPB circuits on inflammatory responses and postoperative status in children. METHODS: Thirty-four infants undergoing elective cardiac surgery were randomly divided into two groups: a heparin-bonded CPB group (n = 17) and a non-heparin-bonded group (n = 17). Plasma levels of the inflammatory cytokines were measured before, during, and after CPB, and postoperative status was determined by examining the respiratory index, blood loss, and the post- and preoperative body weight percent ratio. RESULTS: Significant differences in tumor necrosis factor-alpha, interleukin-6, and interleukin-8 patterns were observed during and after CPB between the two groups (p < 0.01, p < 0.01, p < 0.05, respectively). All cytokines measured were significantly lower in the heparin-bonded group just after CPB (p < 0.05). There were no differences in duration of intubation, intensive care unit or hospital stay, or postoperative blood loss, but the respiratory index 3 hours after CPB and body weight percent ratio 24 and 48 hours after CPB were significantly reduced in the bonded group (p < 0.05, p < 0.01, p < 0.05, respectively). CONCLUSIONS: Our findings suggest that heparin bonding of the bypass circuits affects early postoperative status and reduces cytokine responses in pediatric cardiac surgery.     

Redo without transfusion in a patient with idiopathic thrombocytopenic purpura

Mitral valve replacement was able to be carried out at redo operation requiring neither allogeneic platelet nor blood transfusion in a patient with idiopathic thrombocytopenic purpura, by means of preoperative high-dose intravenous gamma-globulin, autologous blood predonation, use of a centrifugal pump, heparin-coated extracorporeal circuits, and simultaneous splenectomy.     

Biological basis of anxiety disorders and serotonergic anxiolytics]

Selective serotonin reuptake inhibitors (SSRIs) have wide indications for the treatment of anxiety disorders, including panic disorder, generalized anxiety disorder, posttraumatic stress disorder, obsessive-compulsive disorder and social anxiety disorder in addition to depression. Until recently, no animal model has been available for screening the anxiolytic effect of SSRIs and studying its mechanism of action. We have investigated the relationship between serotonin neurotransmission and anxiety using conditioned fear stress (CFS), an animal model of anxiety. CFS increased serotonin neurotransmission in the medial prefrontal cortex and amygdala. In behavioral pharmacological studies, SSRIs, serotonin1A agonists and monoamine oxidase inhibitors, which are assumed to facilitate serotonin neurotransmission, decreased conditioned freezing, an index of anxiety or fear, in CFS. In vivo microdialysis studies showed that serotonin neurotransmission in the medial prefrontal cortex increased after recovery from the freezing behavior. Microinjection of SSRI to the basolateral nucleus of the amygdala reduced conditioned freezing, indicating that the amygdala is one of target brain sites of anxiolytic action of SSRIs. Furthermore, CFS-induced c-Fos expression in the basolateral nucleus of the amygdala was reduced by SSRI pretreatment. Taken together, recent studies indicate that facilitation of brain serotonin neurotransmission decreases anxiety in agreement with the clinical evidence.     

Differences in gut integrity following abdominal surgery according to the magnitude of the surgical stress

BACKGROUND: An increase in serum diamine oxidase (DAO) activity reflects intestinal mucosal damage. This was used to estimate the effect of surgical stress after elective abdominal surgery on gut integrity. METHODS: Patients with gastrointestinal tract cancers were placed in either group T (transthoracic esophagectomy for esophageal cancer, n = 9) or group L (laparotomy, n = 10). The serum DAO activity was measured pre-operatively, and on postoperative days 1, 3, and 8. RESULTS: Transthoracic esophagectomy was associated with a more extensive stress than the operations in group L, as measured by the intra-operative blood loss, the amount of blood transfused, and the operative time (P = 0.007, P = 0.0002, P = 0.0011, respectively). Following surgery, the serum DAO activity was decreased markedly in all patients in group T. In contrast, the activity was unchanged in group L (P = 0.04). CONCLUSIONS: The severity of the surgical insult plays a significant role in the decrease in serum DAO activity. These results suggest that surgical stress influences gut integrity following elective abdominal surgery.     

A novel compound RS-0466 reverses beta-amyloid-induced cytotoxicity through the Akt signaling pathway in vitro

In order to determine whether 5-[bis(carboxymethyl) amino]-2-carboxy4-cyano-3-thiopheneacetic acid distrontium salt (S12911-2) inhibits bone resorption by acting on the differentiation and/or function of osteoclasts, its effects were assessed on the 1,25-dihydroxyvitamin D(3)-induced expression of carbonic anhydrase II and vitronectin receptor in chicken bone marrow cells, and on the resorbing activity of authentic rat osteoclasts cultured on bone slices. S12911-2 dose-dependently inhibited, after a 6-day exposure, the expression of carbonic anhydrase II and vitronectin receptor in stimulated osteoclasts (46% and 40%, respectively, at 10(-3) M Sr(2+), P<0.05). A pre-incubation of bone slices with S12911-2 induced a dose-dependent inhibition of bone resorbing activity from 32% at 10(-4) M Sr(2+) to 66% at 10(-3) M Sr(2+) (P<0.05 in each case). A continuous incubation (10(-3) M Sr(2+)) induced a greater inhibition of bone resorbing activity (73%, P<0.05). The inhibition of bone resorption obtained specifically with S12911-2 is related to an inhibition of the differentiation and resorbing activity of the osteoclasts.