Laparoscopic tension-free hernioplasty for lumbar hernia.

Lumbar hernia, a defect of the posterior abdominal wall, is a very rare condition. The repair of a posterior abdominal wall hernia by simply closing the hernia port with sutures may not be adequate, especially when the herniation is due to a weakness in the abdominal wall. Recently, a simple, logical method of tension-free repair has become a popular means for the treatment of various abdominal wall hernias. Previous studies have advocated the use of tension-free repair for lumbar hernia; the technique uses a mesh replacement and requires an extensive incision. Herein we present a case of superior lumbar hernia. Our technique consisted of a laparoscopic tension-free hernioplasty with the application of a Prolene mesh. This technique, which provides an excellent operative view, is safe, feasible, and minimally invasive. We conclude that laparoscopic tension-free repair should be the preferred option for the treatment of lumbar hernia.

Elevation of soluble thrombomodulin antigen levels in the serum and urine of streptozotocin-induced diabetes model rats.

The present study was designed to evaluate the serum thrombomodulin (TM) antigen levels, the TM content in several tissues, and vascular endothelium injury in a streptozotocin-induced diabetic mellitus model of rats with the basic observations concerning soluble serum TM antigen. The soluble TM antigen levels in the serum of 1-week-old Sprague-Dawley rats were 1028.7+/-56.8 ng/mL in the immunoassay using rabbit anti-rat TM IgG. The levels gradually decreased to about 400 ng/mL within 11 weeks during the development, and the levels in 11-week-old rats were preserved up to 31 weeks of age (experimental period). Identical patterns of five kinds of TM antigen subspecies (105, 52, 46, 31, and 28 kDa) in the serum were observed during normal development from 1 to 31 weeks in the Western blotting under reducing conditions. Soluble TM antigen levels in the serum and urine of the model rats were significantly increased to 1. 3 times the levels in the buffer-administrated control rats without an increase in the serum creatinine levels. In contrast to the TM antigen levels in the serum and urine, the TM content in several tissues including the lung, pancreas, kidney, and spleen of the model rats significantly decreased by 47% to 10% of those in the buffer-administrated control rats. Flattening of the longitudinal ridges in the endothelium, crevasse-like endothelial sloughing, platelet activation and aggregation, and/or leukocyte adherence on the endothelium were observed in the aorta of the model rats based on scanning electron microscopic observations, indicating endothelium injury. The present results indicate that the serum TM antigen levels increased with injury to the endothelium in the model, even when renal dysfunction was not present. It is suggested that increased TM antigen levels in diabetic patients could reflect endothelium injury as observed in this diabetic model experiment.

TJS-010, a new prescription of oriental medicine, enhances 8-OH-DPAT-induced effects in rats.

We evaluated the effect of TJS-010, a new prescription of oriental medicine, on hypothermia and flat body posture in rats, induced by activation of serotonin (5-HT)-1A receptors by (+/-)-8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT). Hypothermia was induced by 8-OH-DPAT in a dose and time-dependent manner. The hypothermia induced by 0.1 mg/kg 8-OH-DPAT was enhanced by 500 and 750 mg/kg of TJS-010. At the concentration of 0.1 mg/kg, 8-OH-DPAT also produced flat body posture in rats, and 750 mg/kg TJS-010 increased the flat body posture. These results suggest that TJS-010 facilitates the 5-HT-1A receptors in the central nervous system.

Cyclic GMP generation mediated by 5-HT-2 receptors via nitric oxide-dependent pathway and its effect on the desensitization of 5-HT-2 receptors in C6 glioma cells.

Serotonin (5-HT)-2 receptor-mediated cGMP generation was investigated in comparison with calcium (Ca2+) mobilization in C6 glioma cells. 5-HT enhanced cGMP generation, and risperidone and ketanserin potently blocked the response. These results indicate that 5-HT-2 receptors are responsible for the cGMP generation. 5-HT-induced cGMP production was completely abolished by BAPTA, an intracellular Ca2+ chelating agent, or NG-mono-methyl-L-arginine(NMMA), a nitric oxide synthase (NOS) inhibitor, suggesting that 5-HT-induced cGMP generation was through nitric oxide (NO)-dependent pathway. 5-HT (10 microM)-elicited Ca2+ mobilization and cGMP generation were reduced to 40 and 15% after pretreatment with 10 microM 5-HT for 4 hours. NMMA did not modify 5-HT-induced desensitization of either Ca2+ mobilization or cGMP generation, suggesting that NO pathway is independent of the desensitization. The present study has demonstrated the nature of 5-HT-2 receptor-mediated cGMP generation in C6 glioma cells.

Serotonin-induced platelet calcium mobilization is enhanced in mania.

The time-course of 5-HT-induced intracellular Ca2+ mobilization in platelets displays biphasic curves; a rapid peak occurs within 10 sec, followed by a prolonged plateau phase. In platelets of patients with affective disorders, many reports have suggested that there is an increase in the rapid peak in intracellular Ca2+ mobilization, but there is no report concerning the plateau phase in intracellular Ca2+ mobilization. We, then, assessed the time course of 5-HT-induced Ca2+ mobilization to compare untreated manic patients with euthymic bipolar disorders and normal subjects. Not only peak amplitude but also plateau phase were more significantly enhanced in the platelets of untreated manic patients than in those of normal controls. These results suggest that the serotonergic neural transmission by means of intracellular Ca2+ was enhanced by the prolonged plateau phase as well as by increased peak amplitude in platelets of mania. The enhanced rapid peak and plateau phase in untreated bipolar mania were restored to their control levels in treated euthymic bipolar disorders. These findings suggest that the reduction of the enhancement in Ca2+ mobilization might be related to either the effects of chronic treatment with lithium or the affective states of the patients.

Metabotropic glutamate receptor in C6BU-1 glioma cell has NMDA receptor-ion channel complex-like properties and interacts with serotonin2 receptor-stimulated signal transduction.

We found in cultured glioma (C6BU-1) cells that excitatory amino acids (EAAs) such as glutamate, N-methyl-D-aspartate (NMDA), aspartate, and metabotropic glutamate receptor agonist trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylate caused an increase in the inositol 1,4,5-trisphosphate formation and the intracellular Ca2+ concentration ([Ca2+]i) in the absence of extracellular Mg2+ and Ca2+. Pertussis toxin treatment abolished this glutamate-induced [Ca2+]i increase. Various antagonists against NMDA receptor-ion channel complex, such as Mg2+, D-2-amino-5-phosphonovalerate (D-APV), HA-966, and MK-801, also inhibited the increase in [Ca2+]i induced by glutamate. These results indicate that these metabotropic EAA receptors coupled to pertussis toxin-susceptible GTP-binding protein and phospholipase C system in C6BU-1 glioma cells have the pharmacological properties of NMDA receptor-ion channel complexes. We also found that in the presence of Mg2+ these metabotropic receptors resemble the NMDA receptor-ion channel complex interacted with 5-hydroxytryptamine2 (5-HT2) receptor signaling. EAAs inhibited 5-HT2 receptor-mediated intracellular Ca2+ mobilization and inositol 1,4,5-trisphosphate formation in a concentration-dependent manner. The inhibitory effect of glutamate was reversed by various NMDA receptor antagonists (D-APV, MK-801, phencyclidine, and HA-966), but L-APV failed to block the inhibitory effect of glutamate. The same result was observed in the absence of extracellular Ca2+. In addition, this inhibitory effect on 5-HT2 receptor-mediated signal transduction was abolished by treatment of C6BU-1 cells with pertussis toxin, whereas 5-HT2 receptor-mediated [Ca2+]i increase was not abolished by pertussis toxin treatment. We can, therefore, conclude that the inhibitory effect of glutamate is not a result of the influx of Ca2+ through the ion channel and that it operates via metabotropic glutamate receptors, having NMDA receptor-ion channel complex-like properties and being coupled with pertussis toxin-sensitive GTP-binding protein and phospholipase C.

[Experience in surgical management for active aortic valve endocarditis with periannular abscess--outcome of abscess cavity after patch closure].

Two patients with active aortic valve endocarditis and periannular abscess underwent surgical management. Both patients had bicuspid aortic valves. Involvement of the aortic annulus with the formation of the periannular abscess was found at one third circumference in the aortic annulus and extended to the sinuses of Valsalva. In one patient the periannular abscess ranged from the right side of the ostia of a left coronary artery to the right commissural region, and in another patient it existed at the left commissural region. the ostia of coronary arteries were separated from the inflammatory and necrotic tissue in both patients. The wall of periannular abscess could not be totally excised. Instead, debridement and transaortic patch closure of the abscess cavity were performed. In the former patient, partial resection of the aneurysmal wall of the abscess was performed and the remaining aortic wall was approximated with extra-luminal sutures supported by Teflon felt pledgets. However, in the latter patient, the plication of the abscess wall could not be performed. Prosthetic mechanical valve was implanted at the paraannular position by utilizing the patch. In the former patient it took a month and a half until the disappearance of the inflammatory reaction, and the echo free space could not be detected at the same place of the abscess cavity by the two-dimensional echocardiogram since early postoperative period. However, in the latter patient it took three months until the disappearance, and the echo free space had been existing at the same place for thirteen months after the operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Homologous desensitization of serotonin 5-HT2 receptor-stimulated intracellular calcium mobilization in C6BU-1 glioma cells via a mechanism involving a calmodulin pathway.

Serotonin 5-HT2 receptor-mediated intracellular Ca2+ mobilization was investigated in rat glioma C6BU-1 cells. The receptors became desensitized after previous exposure to 5-HT in a time- and concentration-dependent manner. The desensitization of 5-HT2 receptor-mediated intracellular signaling appeared to be homologous because previous exposure to 5-HT did not alter the response to other transmitters such as thrombin or isoproterenol and because previous exposure to thrombin or isoproterenol did not diminish the response to 5-HT. The desensitization induced by pretreatment with 5-HT was potently prevented by the naphthalenesulfonamide derivative W-7, a calmodulin antagonist, when it was cosupplied with 5-HT. Furthermore, the preventive effect of W-7 was greater than that of W-5, a weak analogue of W-7, and than that of H-7, a nonselective inhibitor of protein kinases. These results suggest that 5-HT2 receptor-mediated Ca2+ mobilization can be desensitized homologously after prolonged exposure to 5-HT in a calmodulin-dependent manner in rat glioma C6BU-1 cells.

Induction of L-lysine-2-oxoglutarate reductase by glucagon and glucocorticoid in developing and adult rats: in vivo and in vitro studies.

L-Lysine-2-oxoglutarate reductase (EC 1.5.1.8, NADP) in the liver of adult rats increased 4-5 times when the animals were treated with alloxan. In diabetic rats injection of insulin or adrenalectomy prevented the increase in enzyme activity. The activity of the similar enzyme in kidney was not changed by these treatments. The enzyme activity in primary cultured adult rat hepatocytes was also induced by addition of dexamethasone and glucagon together, and glucagon could be replaced by dibutyryl cyclic AMP. Insulin inhibited the induction. The hormonal induction was also inhibited by actinomycin D and by cycloheximide. During development of rats, fetal liver showed very low activity, but the activity appeared on day 1 after birth and then increased rapidly, reaching the adult level by day 5. The activity of the kidney enzyme increased more slowly and reached adult level 1 month after birth. Intra-uterine injection of glucagon caused precocious induction of the liver enzyme in fetuses. These results indicate that the activity of L-lysine-2-oxoglutarate reductase in the adult liver and in part in neonatal liver also, in controlled by both glucagon and glucocorticoid.

Insulin and glucagon as a new regulator system for tryptophan oxygenase activity demonstrated in primary cultured rat hepatocytes.

The basal activity of tryptophan 2,3-dioxygenase (EC-1.13.11.11) in primary cultured rat hepatocytes decreased during culture, but addition of either tryptophan (2.5 x 10(-3) M) or dexamethasone (1 x 10(-6) M) could prevent the decrease. Addition of both compounds caused severalfold induction of activity. Glucagon (1 x 10(-8) M) alone did not induce the activity, but its inductive effect in combination with tryptophan was similar to that of tryptophan plus dexamethasone. The effect of glucagon was additive with those of tryptophan and dexamethasone and hence the highest induction (7-fold) was achieved by addition of all three inducers. Glucagon could be replaced by dibutyryl cyclic AMP (1 x 10(-5) M). Insulin (1 x 10(-8) M) inhibited the inductions by glucagon and dexamethasone, but not that by tryptophan. Cycloheximide inhibited the inductions by all three inducers, but actinomycin D inhibited only the induction by dexamethasone. These results suggest that the three compounds have different mechanisms of induction of tryptophan oxygenase activity: tryptophan prevents enzyme inactivation, dexamethasone may stimulate enzyme synthesis at the level of transcription, and glucagon may enhance the synthesis at the translational level.

Biochemical functions of adult rat hepatocytes in primary culture.

Liver parenchymal cells from adult rats were isolated by treatment with collagenase and cultured as monolayers in Williams medium E with 10% fetal or calf serum. The additions of dexamethasone and insulin to the medium were essential for maintaining liver functions of the cells. These cells synthesized and secreted various serum proteins into the medium. Gluconeogenesis and glycogenolysis were enhanced by glucagon, and lipogenesis was stimulated by insulin. Many enzymes were also induced by various hormones. These activities were very low in freshly isolated cells, but were restored when the cells were cultured for a few days. Markers of plasma membranes, such as 5'-nucleotidase and insulin receptors, were reduced to half the normal levels on freshly isolated cells, but they were restored to the normal levels during culture of the cells without added hormones. Analysis of the profile of amino acids in the medium showed that freshly isolated cells were in a catabolic state of protein turnover and released branched chain amino acids into the medium, but that cultured cells consumed amino acids, not only for protein synthesis, but also for other metabolic processes, such as gluconeogenesis. These findings show that freshly isolated cells have impaired functions and are unsuitable for use in studies of liver metabolism, but that after culture for a few days the cells regain the activity of normal liver and hance become useful for studies of liver functions. Studies with these cells are simpler and give clear results than studies in vivo.

Isozyme patterns of branched-chain amino acid transaminase in human tissues and tumors.

The isozymes (enzymes I and III) of branched-chain amino acid transaminase (EC 2.6.1.42) from various human tissues were separated by DEAE-cellulose column chromatography. Their distributions were found to be considerably different from those in rat tissues reported before. In rats, all tissues examined contained enzyme I and in addition enzyme II was found in the liver and enzyme III in the brain, ovary, and placenta. In humans, however, enzyme II was not found in any tissues examined including the liver, and enzyme III was found in many other tissues besides brain, ovary, and placenta. All normal human tissues except the lung, ovary, and brain contain less enzyme III than enzyme I. Various human cancers of the liver, kidney, stomach, pancreas, and uterus showed significantly higher ratios of enzyme III to enzyme I than those of the corresponding normal tissues. Fetal liver and kidney also contained much higher concentrations of enzyme III than adult liver and kidney. These findings suggest that change of the isozyme pattern of this enzyme in cancer is similar in humans and rats, and that cancer tissues tend to express more immature phenotypes than normal tissues. Enzymes I and III of human tissues showed the same substrate specificities for valine, leucine, and isoleucine, and these amino acids competed for the active site of the enzyme. Thus the hereditary diseases, hypervalinemia and hyperisoleucine-leucinemia, may be due to genetic alteration of the enzyme protein, resulting in change of its substrate specificity.