Enhanced protein synthesis in the ipsilateral substantia nigra following middle cerebral artery occlusion in the rat

Following focal cerebral ischemia, neuronal cell death is detected in remote areas of the brain, including the ipsilateral thalamus and substantia nigra (SN), as well as in the ischemic core. We have investigated protein synthesis in the remote areas of rats exposed to focal ischemia using autoradiography. The proximal portion of the left middle cerebral artery (MCA) was permanently occluded, and at various periods (6 h, 2, 4 and 7 days and 2 and 4 weeks following ischemia) animals received a single dose of l-[2,3-³H]valine (6.7 mCi/kg). Brain sections containing the thalamus and SN were processed for autoradiography. In the ipsilateral cerebral cortex and striatum, marked impairment of protein synthesis was observed and was never completely recovered during the experiment. No changes in protein synthesis in the ipsilateral thalamus were detected during the experiment. However, a change in protein synthesis was demonstrated in the ipsilateral SN. At 2 days after MCA occlusion, incorporation of [³H]valine into the whole zona reticulata of the ipsilateral SN was slightly enhanced and the increase became evident at 4 days after ischemia. Increased incorporation of [³H]valine began to be localized in the lateral portion of the zona reticulata after 7 days and continued up to 4 weeks following ischemia. Enhanced protein synthesis during the early stage (2 and 4 days after ischemia) may be due to the activated function of the neurons in the zona reticulata and that during the late stage (7 days and 2 and 4 weeks) after ischemia to astroglial proliferation Received: 22 July 1997 / Revised, accepted: 13 November 1997     

Uterine rupture in a case with Ehlers-Danlos syndrome type IV--anesthetic considerations

The anesthetic management of a patient with Ehlers-Danlos syndrome (EDS) type IV, who suffered a ruptured uterus following delivery at 37 weeks of gestation was described. During laparotomy, massive blood loss occurred and blood was replaced through the catheter introducer sheath in the internal jugular vein. The woman with EDS type IV carries a risk of excessive bleeding during labour.     

Mechanical stretching force promotes collagen synthesis by cultured cells from human ligamentum flavum via transforming growth factor-beta1.

Although mechanical stress as a result of spinal instability is known to cause hypertrophy of the ligamentum flavum resulting in degenerative spinal canal stenosis, the mechanism of the ligament hypertrophy is not well understood. In the present study, we investigated the effect of mechanical stretching force on collagen synthesis and transforming growth factor-beta1 (TGF-beta1) production using ligament cells isolated from human ligamentum flavum in vitro. Ligamentum flavum cells (LFCs) were isolated from human ligamentum flavum obtained from patients who underwent lumbar spine surgery. The LFCs were subjected to a mechanical stretching force using a commercially available stretching device that physically deformed the cells. Collagen synthesis and TGF-beta1 production levels in the LFCs were then examined. Notable increases were observed in the gene expressions of collagen types I, III, and V in LFCs subjected to mechanical stretching force. The increase in collagen gene expression of LFCs was inhibited in the presence of anti-TGF-beta1 antibodies. Production of TGF-beta1 by the LFCs also increased significantly by the mechanical stretching force. Exogenous application of TGF-beta1 was confirmed to increase collagen synthesis of the LFCs. This data indicated that mechanical stretching force can promote TGF-beta1 production by LFCs, resulting in hypertrophy of the ligament.     

Two receptor systems are involved in the plasma clearance of tissue-type plasminogen activator (t-PA) in vivo.

Tissue-type plasminogen activator (t-PA) is a serine protease, catalyzing the initial step in the fibrinolytic process. Intravenously administered t-PA is rapidly cleared from the circulation by the liver. Two distinct clearance mechanisms, which are mediated by the low density lipoprotein receptor-related protein (LRP) on liver parenchymal cells and by the mannose receptor on liver endothelial cells, have been described. Using competitors and inhibitors of the receptors, we investigated the role of LRP and carbohydrate receptors in t-PA clearance in vivo. To inhibit LRP, the 39-kD protein, which is a potent inhibitor of LRP activity, was overexpressed in the liver of mice using an adenoviral gene transfer technique. Expression of the 39-kD protein resulted in a sustained plasma concentration and an increase in the plasma half-life of 125I-t-PA from less than 1 min to 4-5 min. Blockade of the mannose receptor by intravenous administration of ovalbumin also prolonged the plasma half-life of 125I-t-PA to 3-4 min. The same degree of inhibition of t-PA clearance was also observed after administration of an inhibitor of the fucose receptor, fucosyl-BSA. However, under the conditions established for the complete blockade of the mannose receptor, no additional inhibition of t-PA clearance was observed using fucosyl-BSA, suggesting little or no role for the fucose receptor in the clearance of t-PA. Furthermore, a dramatic increase of the plasma half-life of 125I-t-PA (>> 20 min) was observed in mice overexpressing 39-kD protein and administered ovalbumin +/- fucosyl-BSA. Our results clearly demonstrate that two independent receptor systems, LRP and the mannose receptor, are involved in the hepatic clearance of t-PA.     

Nested amplification protocol for the detection of Mycobacterium tuberculosis

Several methods for rapid diagnosis of tuberculosis have been devised through DNA amplification. However, the chemically strong cell wall of the species, the presumptively low numbers of organisms and their uneven distribution in clinical samples, and the lack of a "gold standard" for diagnosing tuberculosis, have hindered the routine clinical use of this method. In a pediatric patient group, these factors are more perplexing. To circumvent these problems, we made use of nested amplification and developed a standard protocol for extracting DNA from various forms of clinical samples which were suitable to our clinical laboratory. It is our impression that the overall sensitivity, including technical bias accompanying this method, is equal to, or at least greater than, that of culture. Most notably, the rapidity in obtaining results and the simplicity in handling, storage and transfer of samples are the principal advantages of this method.     

Duration of action of supplemental doses of vecuronium is related to the duration after the initial dose

Vecuronium was administered in an initial dose of 0.1 0.3mg·kg^–1 and in supplemental doses of 0.03mg·kg^–1 or 0.05mg·kg^–1 in 74 patients (ASA class 1 or 2) scheduled for abdominal surgery. The duration of the neuromuscular blockade provided by vecuronium after both the initial and supplemental doses was determined using the evoked integrated electromyographic device. A statistically significant positive correlation (correlation coefficient: 0.83 0.91) was found between the duration of action of the initial dose and that of the first to fourth supplemental doses.The regression lines of each of the first four supplemental doses to the initial dose were very similar to each other. These results suggest that, since the duration of action of supplemental doses of vecuronium was prolonged in patients showing a long duration of action of the initial dose, it would be wise to avoid blind adherence to a predetermined schedule for supplemental administration. Rather, anesthesiologists should take into account the patients response to the initial dose and then decide the most appropriate timing for supplemental doses. Moreover, since vecuronium shows little cumulative effect even after 4 supplemental administrations in clinical-range doses, it can be concluded that vecuronium can be safely used in a wide dose range.(Otagiri T, Narita M, Nishizawa M, et al.: Duration of action of supplemental doses of vecuronium is related to the duration after the initial dose. J Anesth 6: 138–144, 1992)