[In vitro antituberculous activity of levofloxacin].
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Biomedical subjects
Publications and source records attributed to Y Kitano.
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The combination of some new quinolone antibacterials with 4-biphenylacetic acid (BPAA) functionally inhibits the gamma-amino-butyric acid (GABA) receptors and thereby induces clonic convulsions. We examined the effects of ofloxacin and its optical isomers on this quinolone-induced neurotoxicity. Norfloxacin at 10(-5) M alone or at 10(-7) M in combination with BPAA (10(-4) M) inhibited [3H]muscimol binding to rat brain synaptic membranes. Ofloxacin and its optical isomers did not affect muscimol binding by themselves. While they slightly reduced muscimol binding at 10(-4) M in combination with BPAA, the inhibitory activity of the l-isomer levofloxacin (DR-3355) on muscimol binding was slightly, but significantly, weaker than that of the d-isomer DR-3354 and ofloxacin. Intracisternal injection of norfloxacin (5 micrograms), ofloxacin, levofloxacin or DR-3354 (50 micrograms each) induced clonic convulsions in mice. The incidence of these convulsions was enhanced by the combination with BPAA (50 micrograms). The epileptogenic activity of levofloxacin was also weaker than that of DR-3354 or ofloxacin when quinolones were given alone or in combination with BPAA. These results suggest that epileptogenic activity of quinolones is closely related to the inhibitory potency in GABA receptor binding and that levofloxacin may have lower neurotoxicity than ofloxacin and DR-3354.
A 74-year-old woman with erythropoietic protoporphyria (EPP) with hepatic dysfunction is reported. She had been photosensitive for two years prior to admission. Physical examination revealed hepatosplenomegaly and erosions on her face. Moderate increases in serum bilirubin and biliary tract enzymes were noted. Histology of the biopsied liver revealed moderate fibrosis and dilatation of bile canaliculi containing orange pigment. Marked increases in protoporphyrin in erythrocytes and feces were noted. The patient died of hepatic failure a year and a half after admission with maximum serum bilirubin of 34 mg/dl. This patient seems to be the oldest among reported EPP cases with liver dysfunction.
The general pharmacological properties of a novel cognition-enhancing agent, nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, DM-9384, CAS 77191-36-7) were investigated, and the following results were obtained. 1. Central nervous system: Nefiracetam showed depressant activities (such as ataxia) on general behavior (mice), and inhibited spontaneous locomotor activity, rota-rod and traction performances (mice) and polysynaptic potential of the spinal reflex (rats), and potentiated pentobarbital anesthesia (mice). The drug inhibited electroshock-induced seizure at relatively low doses, but did not affect chemoshock-induced seizure (mice). Nefiracetam failed to show analgesic activity in the tail pinch test, but inhibited the acetic acid-induced writhing syndrome (mice). An inhibitory pattern in the electroencephalogram was observed (cats). Nefiracetam had little or no effect on body temperature (rats). 2. Respiratory and cardiovascular systems: Nefiracetam induced transient decreases in blood pressure, left ventricular pressure and LV dp/dt max at higher doses (dogs). 3. Autonomic nervous system: Nefiracetam had no influence on pupil size (rabbits). The drug induced no significant effect on the pressor response to norepinephrine or depressor response to acetylcholine, but inhibited the contractile response of the nictitating membrane to preganglionic cervical sympathetic nerve stimulation at the highest dose (dogs). 4. Gastrointestinal system: Nefiracetam inhibited gastrointestinal propulsion (mice), gastric emptying rate and gastric secretion (rats) at higher doses. Nefiracetam produced no apparent damage in the gastric mucosa, and had no effect on bile secretion (rats). 5. Isolated smooth muscle: Nefiracetam had no effect on the resting tonus of isolated ileum, whereas it inhibited the contractile response to acetylcholine, histamine, serotonin, nicotine and BaCl2 at higher concentrations (guinea pigs). Nefiracetam had no effect on the resting tonus or the serotonin-induced contraction of stomach fundus (rats). The drug had no effect on the resting tonus or the norepinephrine-induced contraction of vas deferens, but tended to inhibit the contraction induced by nerve stimulation (guinea pigs). Nefiracetam had little or no effect on the resting tonus or oxytocin-induced contraction of virgin uterus, or on spontaneous contraction of pregnant uterus (rats). Nefiracetam did not affect the resting tonus of trachea, whereas it inhibited isoproterenol-induced relaxation at the highest concentration (guinea pigs). Nefiracetam had no chronotropic effect in isolated atria, but showed a slight negative inotropic effect at the highest concentration (guinea pigs). 6. Miscellaneous: Nefiracetam slightly decreased urinary volume, whereas it did not affect urinary electrolyte excretion (rats).(ABSTRACT TRUNCATED AT 400 WORDS)
We report the effect of 18-month ciclosporin (CS) treatment in 19 children with steroid-dependent frequently relapsing nephrotic syndrome. CS was started at 3-5 mg/kg per day after remission with steroid therapy, was adjusted to maintain a trough blood level of between 200 and 600 ng/ml and was administered for 6 months (high-dose CS). Then, the dosage of CS was decreased and 2.5 mg/kg per day was administered for the subsequent 12 months (low-dose CS). Only 2 patients had relapses during the initial 6 months of CS therapy. Eight patients had infrequent relapses, 4 had frequent relapses and 7 had no relapses during the 12 months of low-dose CS. Not only did continuation of CS at a lower dosage decrease the relapse rate, it also reduced steroid toxicity, allowed increased growth in 16 of the 19 patients and also decreased obesity scores in 12 of these patients. All of the side-effects that occurred during the 18-month period of CS treatment were reversible and none was serious enough to necessitate discontinuation of therapy. Our 18-month CS treatment was helpful in preventing relapses and reducing steroid toxicity in children with steroid-dependent frequently relapsing nephrotic syndrome.
Thymolipoma, a rare benign mediastinal tumor, was found in a 6-year-old boy. Computed tomography scans, magnetic resonance imaging, and angiography of internal thoracic artery confirmed the diagnosis before surgery.
A 27-year-old mother was diagnosed by prenatal ultrasonography as having triplets at gestational age 32 weeks. Following cesarean section at 37 weeks, a pair of female babies were noted for the first time to be joined by a common pelvis with three lower limbs. They had separate upper gastrointestinal tracts, which joined in the distal ileum, leading to a common colon, rectum, and a single anus. Each twin had a functioning kidney, with a single ureter leading to a common bladder. A common urethra originating from the bladder neck ran into the urogenital sinus of one baby. Prior to the surgical separation, placement of four tissue expanders and 20 pneumoperitoneums were performed, in order to stretch the parietes for easier approximation of the wound edges. At 13 months of age, separation was performed, requiring 17 hours. The skin and musculature from the conjoined third leg was used as a fillet for abdominal wall closure in each patient. One infant was given the distal half of the colon and an entire anus with a temporary jejunostomy, and the right half of the bladder with the urethra. The other infant was given the proximal half of the colon with a permanent colostomy, and the left half of the bladder with permanent cystostomy using appendiceal pedicle graft (Mitrofanoff's procedure). This is the 10th case of surgical separation in ischiopagus tripus twins reported in the literature, and the seventh successful separation with both patients alive.
We have investigated alterations in Epstein-Barr virus antigen specific cytotoxic T-lymphocyte (EBV-CTL) activity during human pregnancy. EBV-CTL activity was determined by a modified EBV induced B-cell focus regression assay and was expressed in terms of a regression index (IR50), i.e. the initial cell concentration required to achieve a 50%-incidence of regression in EBV-infected cell culture. Increased values of IR50 indicate the suppression of EBV-CTL activity. In 113 human female T-cell leukemia type-I (HTLV-I) non-carriers, the IR50 values (mean +/- S.E.) in non-pregnant, pregnant (the first trimester, second trimester and third trimester of pregnancy) and puerperal women were 10.6 +/- 1.4, 16.1 +/- 1.1 (20.1 +/- 2.0, 14.8 +/- 2.0, 14.6 +/- 1.6), and 12.1 +/- 1.9 respectively. Among HTLV-I carriers, the IR50 values (mean +/- S.E.) were likewise 34.6 +/- 8.0, 87.4 +/- 5.2 (101.7 +/- 6.3, 88.3 +/- 8.4 and 79.5 +/- 9.2) and 39.2 +/- 7.1 respectively. This data demonstrate: 1) EBV-CTL activity was suppressed during pregnancy (P < 0.05), especially in the first trimester (P = 0.0003). 2). In HTLV-I carriers, this suppression was shown in the first trimester (P = 0.0002), in the second trimester (P = 0.0002) and in the third trimester of pregnancy (P = 0.0014) and 3). One month after delivery, this suppression had returned to the non-pregnant level in both HTLV-I non-carriers and HTLV-I carriers. Pregnancy therefore has a suppressive effect on antigen specific cytotoxic T-lymphocyte activity and this effect is amplified in HTLV-I carriers.
We have made a skin equivalent constructed of fibroblasts embedded in a type I collagen, with an overlying stratified keratinocyte epithelium to examine formation of the basement membrane. We assessed the influence of the existence and species of fibroblasts in the collagen gel. Cultured human keratinocytes were well attached to the dermal equivalent. Plating efficiency was not clearly different among several types of gel. On the control and mouse fibroblast gel, sheet formation was delayed and epithelial stratification on the human fibroblast gel was more remarkable than on the control gel. On the human fibroblast gel, we observed the expression of basement membrane components (bulbous phemphigoid antigen, laminin, type IV collagen and fibronectin) between the sheet of cultured keratinocytes and the human fibroblast gel earlier than those on the control gel and mouse fibroblast gel. Type VIII collagen was not observed in any of the models at 4 weeks.
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Recombinant human granulocyte colony-stimulating factor (rhG-CSF) induced cutaneous eruptions in two cases of acute myelogenous leukemia. In both cases, the eruptions appeared during rhG-CSF therapy for neutropenia induced by the remission-induction chemotherapy and disappeared rapidly after the discontinuance of rhG-CSF therapy. Histopathology of those eruptions revealed dermal cell infiltrations consisting of some neutrophils and atypical cells. It was interesting that, although there were no leukemic cells in the peripheral blood or bone marrow, eruptions containing many leukemic cells appeared. The mechanism of the appearance of these eruptions was unclear, but it was considered that a few leukemic cells might have responded to rhG-CSF and proliferated in the skin.
BACKGROUND: Ras p21, a ras oncogene product, plays an important role in tumorigenesis, proliferation, and differentiation in various tissues and cells. METHODS: Using a monoclonal antibody raised against ras p21 (RASK 4), localization of ras p21 in normal epidermis and involved epidermis of various skin diseases was examined immunohistologically. RESULTS: Ras p21 was not present in basal cells of normal epidermis or basaloid cells of basal cell epithelioma but was found almost evenly in the cytoplasm of squamous cells and granular cells. This suggests that ras p21 is concerned with differentiation of epidermal cells. The mode of distribution of ras p21 differed from one cell to another in epidermal cells that turned to malignancy. The distribution was uneven and irregular in the tumorous region on the whole. CONCLUSIONS: This result might possibly represent abnormal differentiation of epidermal cells that turned to malignancy, deviating from the regular mode of the distribution of ras p21, which is necessary for normal differentiation.
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The reaction of dihydroxo(1R,2R-cyclohexanediamine)platinum(II) with 2,4-dioxopentanoic acid gave a water-soluble complex, (1R,2R-cyclohexanediamine-N,N')[2-hydroxy-4-oxo-2-pentenoato (2-)-O2] platinum(II). The structure of the complex was determined by X-ray crystal analysis. The data indicated a chelation of the acetylacetonato part of 2,4-dioxo-pentanoic acid to platinum(II). The complex showed moderate antitumor activity against murine leukemia L1210 in mice (T/C = 195% at a dose of 200 mg/kg) and high activity against cisplatin-resistant L1210 leukemia (T/C = 275% at a dose of 25 mg/kg).
Central effects of intravenously (i.v.)-administered iohexol were compared with those of iopamidol in a series of tests. Mannitol was used as a reference. As assayed by the primary screening test based on Irwin's method, i.v. administration of mannitol resulted in a score of 0 in ddY mice and a score of 0.6 in ICR mice in the startle response. These results were not different from the data of both iohexol and iopamidol. Iopamidol at a dose of 1750 mgI/kg produced an inhibitory effect on the spontaneous locomotor activity. Iohexol at a dose of 7000 mgI/kg potentiated the duration of thiopental-induced narcosis. Hypothermia was caused by high doses of both iohexol and iopamidol. Electric stimulus increased the mortality of mice pretreated with high doses of iohexol and iopamidol. Both drugs had no notable activities in the anticonvulsant, electroencephalic, muscle relaxant and antinociceptive tests. These results indicate that both iohexol and iopamidol do not necessarily possess a similar pharmacological action. Judging from the LD50 of approximately 15000 mgI/kg for both drugs, they seem unlikely to have a specific pharmacological action on the central nervous system.
Patients with atopic dermatitis (AD) were treated with diode low reactive level laser therapy (LLLT), and the following results were obtained. 1) Itchy sensation decreased in 79 of 112 cases (71%) after this therapy. 2) Skin eruptions improved in 69 of 112 cases (62%). 3) There were no side effects during and after LLLT. 4) Major histocompatibility complex (MHC) class II antigen and inter-cellular adhesion molecule (ICAM)-1 expression on epidermal cells decreased after the therapy. 5) The number of CD1 positive epidermal dendritic cells did not significantly change before and after LLLT.