Enhanced effect of intra-arterial adriamycin administration in combination with degradable starch microspheres on an intra-arterial chemotherapy model of nude rats transplanted of human gastric cancer

Enhancement of the antitumor effects of adriamycin (ADR) by concomitant use of degradable starch microspheres (DSM) and pharmacokinetics of ADR in combination with DSM was investigated. An intra-arterial chemotherapy model of the nude rats transplanted of human gastric cancer xenografts (H-154) in the hind-limbs was used for this study. Drug was administered through a catheter inserted into the carotid artery with the tip in the common iliac artery. In the pharmacological study, increase of regional uptake of ADR and decrease of systemic distribution of ADR were recognized in some degree. DSM 30 mg/kg, which caused temporary arrest of blood flow in the tumor, had an only weak effect on tumor growth. ADR 3 mg/kg mixed with DSM 30 mg/kg was more effective than ADR 3 mg/kg solution. Furthermore, mixture of ADR 2 mg/kg and DSM 30 mg/kg had a greater effect on tumor growth than ADR 2 mg/kg following DSM 30 mg/kg. It seems that embolization by DSM, retention of ADR in regional tissues and cytotoxic effect of ADR have contributed to such a strong effect of ADR mixed with DSM.     

Differing time courses between Δlactate and mitochondrial respiration during coronary occlusion and after reperfusion in canine hearts

Summary The present study was designed to clarify whether or not a difference between arterial and venous lactate (lactate) levels is useful for evaluation of mitochondrial function in ischemia-reperfused myocardium. In the first experiment, 12 dogs were divided into 2 groups: 10-min occlusion of the left anterior descending coronary artery (LAD) followed by 10-min reperfusion, or 30-min occlusion followed by 40-min reperfusion, were performed. The lactate levels in the femoral artery and the great cardiac vein were measured enzymatically. Lactate was reversed immediately after occlusion. Ten min and 20 min were required for the recovery of lactate in the 10-min-occlusion with 10-min-reperfusion, and 30-min-occlusion with 40-min-reperfusion groups, respectively. In the second experiment, 36 dogs were divided into 6 groups: 10-min occlusion of LAD; 10-min occlusion with 10-min reperfusion; 30-min occlusion; and 30-min occlusion with 10-, 20-, or 40-min reperfusion were performed. Mitochondria from normal and occluded or reperfused areas were prepared, and the respiratory function of the mitochondria was measured polarographically. No significant decreases in the mitochondrial function were observed in the 10-min-occlusion, and 10-min-occlusion with 10-min-reperfusion groups. On the other hand, respiratory function of mitochondria was impaired by 30-min occlusion and was not improved by 10- or 20-min reperfusion. Significant recovery in the mitochondrial function was observed after 40-min reperfusion. That is, differing recovery time courses between lactate and the mitochondrial function were observed.     

Membrane-limited hepatic transport of the conjugative metabolites of 4-methylumbelliferone in rats

The hepatic transports of 4-methylumbelliferone (4-MU) and its conjugative metabolites, the glucuronide (4-MUG) and sulfate (4-MUS), were investigated in rats with various methods. The extraction ratio (E) was estimated with the multiple indicator dilution (MID) method using isolated perfused rat liver. The values of E for 4-MUG and 4-MUS were much lower (less than 0.2) than that for the parent compound, 4-MU (0.89). In addition, we examined the simulation of the outflow curves of conjugates based on the "distributed" model in which we varied the permeability between the blood and hepatocytes. When the permeability was much smaller relative to the hepatic blood flow, the simulated curve was superimposed on the dilution curve. These results suggest that the influx permeabilities of these conjugates are so low that little extraction occurs during the passage through the liver. Measuring the unidirectional uptake of these conjugates into the liver with the in vitro centrifugal filtration method using isolated hepatocytes, we determined the influx permeabilities (PSinf(total] for the total ligands. The value of PSinf(total) determined with the in vitro method was extrapolated to that per gram of liver, assuming 1 g of liver has 1.3 X 10(8) cells. The values of PSinf(total) for 4-MU, 4-MUG, and 4-MUS were 4.8, 0.06, and 0.11 mL/min/g liver, respectively. Thus, the influx permeabilities for 4-MUG and 4-MUS were much smaller than the hepatic blood flow (1.6 mL/min/g liver), confirming the results of MID method.     

Radial flap: a valuable fasciocutaneous flap for intra-oral reconstruction

The radial forearm flap, or the forearm flap, is called "Chinese flap" for its development of the chinese doctors, and is originally designed for the correction to the post-burn contraction of the face and neck. The radial forearm flap is one of the fasciocutaneous flap, supplied by the radial artery, and transferred as a single-stage reconstruction micro-surgically. In oral and maxillofacial region, the deltopectral flap (D-P flap) and the pectralis major myocutaneous flap (P-M-M-C flap) are mainly used for the reconstruction. These flaps, however, are sometimes too bulky and limited to transfer, and more require two-stage operations. On the other hand, as the forearm flap being thin and pliable, some doctors use this flap micro-surgically at single-stage free flap reconstruction. Before two years, we have begun to transfer the radial forearm flap for the intra-oral reconstruction. The operation method is as follows. Design and Elevation of the Radial Forearm Flap 1. Using the ultrasonic doppler flow meter, the radial artery and the subcutaneous forearm veins are marked on the skin. 2. The flap is designed 20% larger according to the pattern to be reconstructed, with the distal section of the radial artery as an axis on the forearm and the median vein of forearm inclusively. 3. Before the operation, Allen test must be performed in order to determine whether the hand will survive without a radial arterial in-put. 4. The operation is performed with a arm tourniquet. The margin of the flap are incised down to the deep fascia, isolating and preserving the proximal subcutaneous veins as required.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of the bare lymphocyte syndrome with clinical manifestations of diffuse panbronchiolitis

Touraine et al reported some cases lacking HLA-class I antigens on the cell surface of their lymphocytes as "Bare lymphocyte syndrome" (BLS). Recently we experienced a case of BLS the clinical features of which are very similar to those of diffuse panbronchiolitis (DPB). Namely, she had chronic pansinusitis, diffuse nodular shadows on her chest X-ray film, obstructive impairment of pulmonary function tests and continuous increase of cold hemagglutinin titer. The pathogenesis of DPB is not confirmed. However, this case and other cases with sino-bronchial syndrome suggest that patients with DPB may have some immunodeficiencies. In addition the immunosuppressive action of erythromycin and its effectiveness on DPB were interesting. From these points of view, we discussed the relationship between this case and DPB, and the pathogenesis of DPB.     

Diazepam reduces both arterial blood pressure and muscle sympathetic nerve activity in human

It is known that benzodiazepines have a hypotensive effect, but the mechanism has not been well elucidated yet. To clarify whether this effect is due to central or peripheral mechanism, we administered 5 mg of diazepam or saline intravenously to healthy volunteers and assessed the change in blood pressure, heart rate, muscle sympathetic nerve activity and heart rate variability. After diazepam administration, systolic and mean blood pressure decreased significantly. Muscle sympathetic nerve activity was also significantly reduced but heart rate did not change, whereas the variables of spectral analysis of heart rate variability did not show significant change. We concluded that the hypotensive effect of diazepam in human is mainly due to the central mechanism.     

Amino acid residues conferring the nucleotide binding properties of N-acetyl-D-glucosamine 2-epimerase (renin binding protein)

Our recent studies have demonstrated that the middle domain of N-acetyl-D-glucosamine (GlcNAc) 2-epimerase participates in the specificity for and binding of nucleotides. To identify the residue conferring nucleotide binding, amino acid substitutions were introduced in the human and rat GlcNAc 2-epimerases. The mutational analyses indicate that residue 171 of GlcNAc 2-epimerase is critical for the nucleotide binding of GlcNAc 2-epimerase.     

Case of minocycline-induced pneumonitis with bilateral pleural effusion]

A 51-year-old man was admitted to our hospital with fever, dry cough and dyspnea. He had taken minocycline for 11 days because of urinary tract infection. Chest X-ray on admission showed diffuse reticular shadows in bilateral lung fields with bilateral pleural effusion. Cessation of minocycline led to spontaneous improvement of symptoms and radiographic findings. The lymphocyte stimulation test for minocycline with peripheral blood and pleural effusion were negative. After provocation test with minocycline, he developed fever and dry cough and bilateral ground glass opacity appeared on his chest X-ray. He was diagnosed as minocycline-induced pneumonitis and recovered rapidly following corticosteroid therapy.     

Regional difference in the appearance of apoptotic cell death in the ligamentum flavum of the human cervical spine

Ossification or calcification of the ligamentum flavum (LF) is relatively common in the middle and lower cervical, thoracic, and lumbar spine but extremely rare in the upper cervical region. This clinical fact suggests that there exist local factors promoting or preventing ossification or calcification of LF. However, little is known about the differences in the ultrastructure and cellular alterations of the LF between the different spinal levels, even in the cervical spine. With electron microscopy, we examined samples of LF collected surgically from the upper and lower cervical spine regions; we then studied the apoptotic appearance of ligament cells using a preferential labeling method. We found direct evidence of apoptosis of ligament cells in the LF. Apoptosis was more apparent in the upper region samples than in the lower region samples. The spaces around the normal fibroblasts were filled with thick collagen fibrils, but the collagen fibrils disappeared around the apoptotic bodies and thin fibrils were formed. The difference of the level of apoptosis may correlate to the ultrastructual difference of LF, and our data will benefit further investigations seeking to clarify the mechanism of various pathological conditions in the human LF.     

Presynaptic dendrites and serial synapses in the intermediate and deep layers of the cat superior coliculus.

Presynaptic dendrites (PSDs) which participate in the serial synapses have frequently been found in the intermediate and deep layers of the cat superior colliculus. The PSDs are presynaptic to small dendritic shafts or spines with symmetrical membrane thikening, and postsynaptic to axon terminals with asymmetrical synaptic contact. Two types of the axon terminals are observed, both of which contain pleomorphic vesicles.