Use of Sorbsan, a calcium alginate fiber dressing, as a drug reservoir in iontophoretic transdermal delivery.
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Administration, Cutaneous↗
Biomedical subjects
Y Ikuta
Publications and source records attributed to Y Ikuta.
Plasma transforming growth factor-beta 1 concentrations in patients with chronic viral hepatitis.
Transforming growth factor (TGF)-beta 1 is an important cytokine involved in the pathobiology of tissue fibrosis through its stimulation of the production of, and inhibition of the degradation of, extracellular matrix proteins. We examined the clinical usefulness of plasma TGF-beta 1 concentration as a marker of fibrogenesis in patients with chronic viral hepatitis. Thirty-five patients, 11 with minimal chronic hepatitis, 14 with mild chronic hepatitis and 10 with moderate chronic hepatitis and 20 healthy subjects were studied. Transforming growth factor-beta 1 concentrations in platelet-poor plasma were measured with a TGF-beta 1 enzyme-linked immunosorbent assay system kit after acid-ethanol extraction. Plasma TGF-beta 1 levels were significantly elevated in patients with mild and moderate chronic hepatitis, but not in those with minimal chronic hepatitis, compared with the levels in the controls. Plasma TGF-beta 1 levels were increased in parallel with the histological degree of necroinflammation and of liver fibrosis. Plasma TGF-beta 1 levels were positively correlated with blood levels of procollagen type III N-peptide, and 7S fragment and central triple-helix of type IV collagen. These results suggest that plasma TGF-beta 1 level is a useful marker in assessing the situation of liver active fibrogenesis in patients with chronic viral hepatitis.
Biomarkers↗
Topical delivery of keloid therapeutic drug, tranilast, by combined use of oleic acid and propylene glycol as a penetration enhancer: evaluation by skin microdialysis in rats.
Topical delivery of tranilast (N-(3,4-dimethoxycinnamoyl)anthranic acid), an inhibitor of collagen synthesis and a therapeutic drug for keloid and hypertrophic scar, was examined, in rats, with oleic acid alone or a combination of oleic acid and propylene glycol as penetration enhancer. Evaluation was by measurement of the concentration of tranilast in plasma and in the dialysate from skin microdialysis. When tranilast at a dose of 1.5 mg was applied topically as an ethanol solution containing 5% polyvinylpyrrolidone on a dorsal skin surface (2.25 cm2), the maximum concentration of tranilast in skin dialysate was approximately 2 microM. When 10 or 20% oleic acid was added to the same ethanol solution the maximum concentration of tranilast in the dialysate increased to 10-20 microM, and this value was further increased to 60 microM by the addition of a combination of oleic acid (10 or 20%) and propylene glycol (10%) to the solution. With the combination of oleic acid and propylene glycol the area under the plot of the concentration of tranilast in skin dialysate against time between 0 and 4 h (AUC0-4) was more than 400-fold that after intravenous administration. The transdermal bioavailability of tranilast as assessed by the AUC0-4 of tranilast in plasma, was 0.2% of the dose applied in the ethanol solution, 3-5% of that applied in the ethanol solution containing oleic acid, and 14-16% of that applied in the ethanol solution containing both oleic acid and propylene glycol. These results suggest that the topical delivery of tranilast with an absorption enhancer such as a mixture of oleic acid and propylene glycol might be a more effective medication than oral administration of tranilast for the treatment of keloid and hypertrophic scar.
Animals↗
Post-prandial serum hyaluronan concentration in patients with chronic liver disease.
Serum hyaluronan measurement is an option for diagnosing cirrhosis and assessing liver fibrosis, but it is of little use in the diagnosis of chronic hepatitis and compensated liver cirrhosis. It is generally known that intake of food results in elevation of the serum hyaluronan concentration. This work was designed to determine whether a change in the serum hyaluronan concentration after eating might reflect the hepatic sinusoidal endothelial cell impairment in chronic liver diseases. The chronological measurement of serum hyaluronan concentration after eating was performed after an overnight fast in 31 patients with chronic hepatitis, 31 cirrhotic patients, and 8 healthy subjects. The hyaluronan concentration in the loading test increased with the severity of the liver disease in the patients with chronic hepatitis, being significantly higher in the patients with moderate or a higher grade of necroinflammation than in those with a minimal grade, and also significantly higher in patients with stage 3 fibrosis than in those with stage 2 or less. The elevation of the concentration after eating in patients with liver cirrhosis was marked and the range did not overlap with that in patients with chronic hepatitis. Even in 14 patients with compensated liver cirrhosis whose hyaluronan concentration pre-prandially was less than 200 ng/ml, the range of the post-prandial peak concentration did not overlap with that in the chronic hepatitis patients. These results suggest that the evaluation of post-prandial serum hyaluronan concentration is potentially useful for assessing the grading of necroinflammation and staging of fibrosis in patients with chronic hepatitis, as well as for diagnosing compensated liver cirrhosis.
Biomarkers↗
Molecular weight of hyaluronate in the serum of patients with chronic liver disease.
Hyaluronate in tissue and lymph is known to be heterogenous and to show a wide range of molecular weights (10(4) to 10(7) Da). Serum hyaluronate concentrations are increased under various pathophysiological conditions such as liver disease, post-gastrectomy, and after the ingestion of food. To clarify whether the chromatographic patterns of hyaluronate in serum from patients with chronic liver disease are different under these conditions, we subjected sera to chromatography using a Sephacryl S 400 HR column. The chromatograms revealed that the hyaluronate in serum was eluted as a single peak at the position corresponding to the molecular weight of blue dextran, the molecular weight being more than 2 x 10(6) Da. The patterns of the chromatogram were similar among the patients with liver disease and the healthy subject although the heights of the peaks were different. Ingestion of food and a history of gastrectomy for gastric cancer did not influence the elution patterns of serum hyaluronate. These results indicate that hyaluronate in serum has molecular weight of more than 2 x 10(6) Da, and that its elution patterns are not influenced by pathophysiological factors, such as the severity of liver disease, or history of gastrectomy or by food intake in patients with chronic liver disease.
Adult↗
Influence of distal nerve segment volume on nerve regeneration in silicone tubes.
The influence of a volume of a distal nerve segment upon nerve regeneration in an 8-mm gap created within a silicone tube was examined. The rats were randomly divided into four groups. Each group had 5 mm, 1 mm, or a half volume of 1-mm nerve segment (a nerve piece of 1 mm transected longitudinally) inserted into the distal end of a silicone tube of 11 mm. The empty group without a nerve segment was used as control. Diameters of regenerated cylindrical structure between the nerve ends in the silicone tube were measured under an operation microscope and myelinated axon diameter, myelinated axon density, myelin sheath width, and ratio of myelinated axon area to total cross sectional area were measured using the transverse sections at the midpoint of the silicone tube at 6 weeks after surgery. Although there was a significant difference in all of those parameters between the control group and any of the remaining three groups, no significant difference was found between any pair of these three groups. The results of this study indicated that the degree of nerve regeneration does not correlate with the volume of a distal nerve segment and even a very small piece can play an important role in supporting regenerating nerve beyond a definitive gap.
Animals↗
Histological and biomechanical observations of the rabbit patellar tendon after removal of its central one-third.
Using 35 Japanese white rabbits, a study was made of tissue regeneration and the mechanical properties of the patellar tendon after removal of its central one-third. After removal of the central one-third of the patellar tendon on one side, in experiment 1 the strength of the entire patellar tendon including the regenerated tissue was compared with that of the patellar tendon on the opposite side with the central one-third removed at the time of killing, and in experiment 2 the strength of only the regenerated tissue was compared with that of the patellar tendon on the opposite side with two-thirds of the medial and lateral sides removed at the time of death. In experiment 1, the maximum load showed no significant difference between the operated side and the control. In one half of the cases, the strength of the operated side including the regenerated tissue was weak, suggesting weakening of the patellar tendon on the residual bilateral sides. In experiment 2, the maximum load of the regenerated tissue was significantly lower than that of the control, the former being 25% of the latter even at 6 months. Histologically, the characteristics of the cells and collagen fibers gradually approached those of normal tissue, but the crimp pattern of the collagen fibers and fibrils was evidently smaller than that of the control. These results indicate that regenerated tissue was still mechanically weak and immature at 6 months.
Animals↗
Rotational acetabular osteotomies: a rabbit model.
We investigated the morphological changes in the articular cartilage after rotational acetabular osteotomy in 16 adolescent rabbits. Radiological and histological studies were conducted at 12 and 24 weeks postoperatively. The radiological evaluations at 12 and 24 weeks showed significantly increased femoral head coverage. No cases of osteonecrosis of the acetabulum or femoral head nor narrowing of the joint space was observed. The histology of the articular cartilage at 12 weeks postoperatively showed cloning and hypercellularity of the chondrocytes in the medial portion of the acetabular roof, indicating remodelling due to the increased weight-bearing stress caused by the osteotomy. The histology at 24 weeks postoperatively showed less cloning of the chondrocytes, indicating that the remodelling process in the articular cartilage induced by this procedure was almost complete at 24 weeks. Degeneration of the articular cartilage was not observed within 24 weeks of the operation.
Acetabulum↗
Tissue inhibitor of metalloproteinase-1 in the liver of patients with chronic liver disease.
BACKGROUND/AIMS: Tissue inhibitor of metalloproteinase (TIMP)-1 is an important regulator of matrix metalloproteinase activity. To clarify the changes in TIMP-1 in diseased livers, we measured TIMP-1 concentrations in liver tissue samples from patients with chronic liver disease. The relationship between serum and liver levels of TIMP-1 was also examined in some patients. METHODS: The subjects were 68 patients who underwent liver biopsy. The liver TIMP-1 concentration was measured using an enzyme immunoassay after the extraction of TIMP-1 with 2 M guanidine. RESULTS: As compared with the controls (n=10), the liver TIMP-1 level was increased 2.2-fold in the 24 chronic active hepatitis 2A patients, 2.9-fold in the 10 chronic active hepatitis 2B patients and 4.1-fold in the six liver cirrhosis patients, but no significant increase was observed among the 18 chronic persistent hepatitis patients. The liver TIMP-1 levels were closely correlated with the histological degrees of periportal necrosis, portal inflammation, and liver fibrosis. When the localization of TIMP-1 was examined immunohistochemically, TIMP-1 was stained mainly in hepatocytes, and the intensity was stronger in the livers of chronic active hepatitis and liver cirrhosis patients than in those of the chronic persistent hepatitis patients. The serum TIMP-1 and liver TIMP-1 levels were significantly correlated, indicating that serum TIMP-1 could reflect the change of liver TIMP-1 in patients with chronic liver disease. CONCLUSION: Liver TIMP-1 concentration increases with progression of the liver disease, when the degradation of extracellular matrix proteins is decreased, resulting in the development of liver fibrosis.
Adult↗
Skin vasomotor reflex induced by laryngoscopy: comparison of the McCoy and Macintosh blades.
We studied 22 female patients (ASA I or II) to investigate if laryngoscopy and intubation induced the skin vasomotor reflex (SVmR), and to compare the effects of the McCoy and Macintosh blades on the SVmR. Anaesthesia was induced with fentanyl, midazolam, vecuronium and nitrous oxide. In 11 patients, the vocal cords were seen for 3 s with the McCoy blade. Two minutes later, laryngoscopy was performed with the Macintosh blade and the trachea was intubated. In the other 11 patients, the first and second laryngoscopies, respectively, were performed with the Macintosh and McCoy blades. Laryngoscopy alone and intubation with laryngoscopy significantly reduced skin blood flow in the ring finger of all patients (P < 0.01), indicating that both procedures provoked the SVmR. The magnitude of the SVmR and haemodynamic changes did not differ significantly between the two groups.
Adult↗
Treatment of keloid and hypertrophic scars by iontophoretic transdermal delivery of tranilast.
The feasibility of iontophoretic transdermal delivery of tranilast (N-(3,4-dimethoxycinnamoyl) anthranilic acid) for the treatment of keloid and hypertrophic scars was evaluated in hairless rats and humans. A drug electrode containing tranilast 1.5 ml (8 mg/ml in ethanol/water (8/2, v/v) mixture) was placed on the dorsal skin surface of anaesthetised rats or the affected parts of patients, and connected to the negative pole; an electric current (0.5-4 mA for rats, 2 mA for people) was pulsed through at one minute intervals. Tranilast was effectively delivered transdermally iontophoretically into the restricted skin tissues of hairless rats and the affected parts of four patients with hypertrophic scars with no skin damage. In four other patients tranilast given iontophoretically for a period of 30 minutes a week reduced the patients' complaints of pain and itching after only one or two treatments although there were some variations among patients. These results indicate that the transdermal iontophoretic delivery of tranilast is a useful treatment for keloid and hypertrophic scars, particularly for relieving pain and itching, and is more beneficial than tranilast given orally.
Administration, Cutaneous↗
Autoantibodies to red cells associated with metallosis--a case report.
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Anemia, Hemolytic, Autoimmune↗
Changes in the permeability and histologic findings of rabbit menisci after immobilization.
The knees of mature rabbits were immobilized for 2 to 8 weeks by a long leg cast to examine adverse effects on the meniscus. Some joints were remobilized for 1 to 4 weeks after an immobilization period of either 6 or 8 weeks. Horseradish peroxidase was injected into knee joints, and the degree of permeation into the meniscus was visualized with diaminobenzidine tetrahydrochloride. Menisci were examined histologically by light and transmission electron microscopic study. Injected horseradish peroxidase permeated all areas of the meniscus in nonimmobilized joints. However, permeability of horseradish peroxidase gradually decreased with increasing time of immobilization and was restricted to the superficial layer of the meniscus in the 8-week immobilization group. Degenerative changes in the deep layers of the meniscus were noted in the 6-week immobilization group: 8 weeks of immobilization induced additional degenerative changes. Although permeability of horseradish peroxidase gradually recovered with remobilization, the degenerative changes remained in the deep meniscal layer in the 8-week immobilization group, even after 4 weeks of remobilization. These results clearly show that long-term immobilization of the knee joint causes adverse changes in the meniscus.
Animals↗
[A case of advanced colon cancer with marked response to combination chemotherapy with 5-FU, low dose CDDP, and leucovorin].
We encountered an elderly patient with advanced colon cancer who responded marked by to combination chemotherapy with 5-fluorouracil (5-FU), low-dose cisplatin (CDDP), and leucovorin (LV). The 86-year-old man was admitted for advanced transverse colon cancer with liver and lung metastasis. Combination chemotherapy with 5-FU, low dose CDDP, and LV was given for a total of 12 weeks. After this chemotherapeutic regimen, diagnostic CT scan revealed the metastatic lesions had disappeared, and a pathological analysis of primary tumor confirmed that the patient had achieved a complete remission (CR). During chemotherapy, there was no severe side effect, apart from mild nausea (WHO: Grade 1). The patient is presently enjoying a good general condition and has been rehabilitated for discharge.
Adenocarcinoma↗
[An anesthesia machine malfunction due to dew condensation produced by abnormally high humidity in the electronically-controlled panel].
We present a case of anesthesia machine (NAR-KOMED 2CTM; N2C) malfunction caused by dew condensation. N2C is electronically controlled by an alarm-panel using the remote display. Abnormally high humidity in the operating room made dew condensation in the alarm-panel resulting in an electronic short circuit. Of great importance may be the damp proof improvement on medical equipment including anesthesia machines which have electronic circuits.
Anesthesiology↗
Characterization of tissue inhibitor of metalloproteinases-1 in plasma from patients with chronic liver disease.
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Chromatography, Gel↗
Augmented meniscal healing with free synovial autografts: an organ culture model.
We examined whether or not free synovial autografts can augment the healing of lesions artificially created in the human knee meniscus in an organ culture model. The effectiveness of free synovial autografts was also compared with that of fibrin glue (Tisseel). In the control group, the accumulation of cellular components increased at the edge of a 4-mm meniscal defect following culture, although no cells were found to invade the defect. In the fibrin glue group, an increased migration of cells into fibrin glue packed into the defect was observed until 4 weeks following cultivation. However, newly formed collagen produced by the cells in the fibrin glue was minimal even 4 weeks after cultivation. In contrast, in the synovial group, newly formed collagen production, as well as cellular proliferation, increased in the grafted synovium with time after cultivation. By 4 weeks, the gap between the edge of the defect and the grafted synovium was bridged by newly formed collagen tissue, indicating improved histologic repair. Our results suggest that free autogenous synovial tissue grafts in meniscal lesions are superior to fibrin glue, and that interpositional synovial autografts to augment repair of meniscal tears in the avascular zone may be clinically useful.
Adolescent↗
Comparison of serum 7S fragment of type IV collagen and serum central triple-helix of type IV collagen for assessment of liver fibrosis in patients with chronic viral liver disease.
BACKGROUND/AIMS: A competitive radioimmunoassay for serum 7S fragment of type IV collagen (7S collagen) using a polyclonal antibody against 7S collagen and a sandwich enzyme immunoassay for serum central triple-helix of type IV collagen (IV collagen) using two monoclonal antibodies against the pepsin-solubilized type IV collagen may be used as diagnostic aids for liver fibrosis in clinical medicine. We compared the clinical usefulness for assessing liver fibrosis of serum 7S collagen and IV collagen tests in chronic viral liver diseases, and also examined the elution pattern of 7S collagen- and IV collagen-related antigens in serum by gel filtration analysis. METHODS: Serum 7S collagen and IV collagen levels were assayed in 151 patients with chronic viral liver disease and 30 healthy control subjects. RESULTS: Gel filtration on the Sephacryl S400HR column revealed that the 7S collagen antigenicity in serum was heterogeneous, whereas the IV collagen antigen in serum was uniform in size. Serum levels of 7S collagen and IV collagen showed increases closely correlated with the severity of liver disease. The abnormal percentage of 7S collagen in three patient groups was similar to that of IV collagen in the corresponding groups. Serum 7S collagen and IV collagen levels were strongly correlated with the histological degree of liver fibrosis; the correlation coefficients were r = +0.675 for 7S collagen and r = +0.665 for IV collagen. When we assessed the ability of each test to detect cirrhosis with a receiver operating curve, the serum 7S collagen test was a slightly better marker than the serum IV collagen test. For the detection of cirrhosis, serum 7S collagen was 83% sensitive and 88% specific at a cutoff value of 9 ng/ml, and serum IV collagen was 80% sensitive and 81% specific at a cutoff value of 160 ng/ml. CONCLUSIONS: These findings suggested that serum 7S collagen and IV collagen tests are similarly useful for assessing liver fibrosis in patients with chronic viral liver disease, although the former is slightly better for diagnosing cirrhosis than the latter.
Adult↗