In-vivo Calibration of Microdialysis Probe by Use of Endogenous Glucose as an Internal Recovery Marker: Measurement of Skin Distribution of Tranilast in Rats

To estimate the absolute concentration of substrates surrounding a microdialysis probe in-vivo, we developed a simple calibration method using endogenous glucose as an internal recovery marker and determined the skin distribution of tranilast (N-(3,4-dimethoxycinnamoyl)anthranic acid), an anti-allergic agent, in rats. This calibration method was based on the assumption that the concentration of glucose in the extracellular fluid of skin tissues is the same as that in plasma and that the in-vivo recovery ratio of glucose to tranilast by microdialysis is the same as that estimated in-vitro. Based on these assumptions, the dialysate concentrations of tranilast and glucose recovered from cutaneous microdialysis, glucose concentration in plasma, and in-vitro recovery ratio of tranilast to glucose by microdialysis were determined for the estimation of absolute unbound concentration of tranilast in the extracellular fluid of skin tissues. In an in-vitro study employing plasma containing tranilast, the unbound concentration of tranilast in plasma estimated from the dialysate concentration was just comparable with that determined by ultrafiltration methods. Also in an in-vivo study under steady-state plasma concentration of tranilast in rats, the estimated concentration of tranilast in the skin extracellular fluid was the same level as the unbound concentration of tranilast in plasma. Using the present calibration method, the skin distribution of tranilast administered into the intestinal loop or transdermally was continuously monitored in a quantitative manner.     

Adult Wilms'' tumor mimicking hemorrhagic renal cyst

A 36-year-old man presented with macroscopic hematuria associated with right flank pain. Examination of the patient revealed a cystic mass in the right kidney. Because the mass had increased in size, enucleation of the mass was performed. Histopathological findings revealed nephroblastoma, therefore, radical nephrectomy was performed. We believe the pathogenesis of the cystic formation to be a process in which a tumor that had developed in the pericalyceal region spontaneously ruptured, exuding urine into the perinephric space, forming a cystic mass. The patient is alive with no evidence of disease 24 months after the operation.     

Renal aminopyrine demethylation in several species determined by a sensitive radiometric method

Renal microsomal aminopyrine demethylation activities of several species were measured by a sensitive radiometric method using [dimethylamino-¹⁴C-]aminopyrine as a substrate and 2,4-dinitrophenylhydrazine as a trapping agent for the formaldehyde formed. The activity was highest in hamsters (0·75 nmol min⁻¹ mg⁻¹ protein) and that in rabbits, rats, mice, and guinea-pigs was 19·7, 7·0, 4·5 and 3·7%, respectively, of the hamster values. These species differences did not correlate with species differences in cytochrome P-450 content or in NADPH cytochrome c reductase activity. Aminopyrine demethylation activities in sliced renal tissues of several species were also compared. This activity was also found highest in hamsters (0·54 nmol min⁻¹ g⁻¹ wet tissue) and the activities in rabbits, rats, and guinea-pigs were 9·2, 1·8 and 2·5%, respectively, of the hamster values.     

SYSTEMIC LUPUS ERYTHEMATOSUS: A CASE-CONTROL EPIDEMIOLOGIC STUDY IN JAPAN

Background. Systemic lupus erythematosus (SLE) is designated by the Japanese government as one of the intractable diseases and all patients, who suffer from these diseases, are registered to get financial aid for treatment. Using newly registered SLE patients, a case-control study was conducted to evaluate potential risk factors. Methods. Two-hundred and eighty-two women SLE patients, newly registered to receive financial aid for treatment, and 292 randomly selected health examination participants at public health centers (controls) were surveyed from April 1988 through March 1990. By means of a self-administered questionnaire, data concerning demographic variables, smoking and drinking habits, past medical and reproductive history, and family history were collected. Results. Based on unconditional logistic regression analysis, the risk of SLE was significantly increased for current smokers (age-adjusted odds ratio (OR) = 2.31, 95% confidence interval (CI) (1.34–3.97). Alcohol and milk intake were inversely associated with risk. Family histories of asthma and collagen diseases, including SLE, were associated with significantly elevated risk of SLE (OR = 2.07, 95% ci 1.14–3.77; OR = 5.20, 95% CI 1.08–24.95, respectively). Regarding reproductive function, women with menarche at age 15 or later had significantly higher risk than those, who started menstruating before age 12 (OR = 3.82, 95% CI 1.66–8.81 for menarche at > 15 years and OR = 2.90, 95% a 1.14–7.39 for menarche at 16y). Conclusions. Our study suggests several risk factors, including smoking, family history, and reproductive history that may increase the risk of SLE.     

Proliferation and cytotoxicity of lectin-induced lymphokine-activated killer (LILAK) cells

More than 10(11) killer cells are needed for adoptive immunotherapy, but it is difficult to obtain so many from patients. Peripheral blood lymphocytes (PBL) treated with lectin and then with recombinant interleukin-2 (rIL-2) give many lectin-induced lymphokine-activated killer (LILAK) cells, studied here for proliferation, cytotoxicity, IL-2 receptors (IL-2R) and subsets. PBL obtained from hepatoma patients or healthy adults were incubated with phytohaemagglutinin (PHA) or concanavalin A (ConA) for 3 days and with rIL-2 for 4 days. Then the medium was replaced with fresh medium containing rIL-2 every 3 or 4 days, with the volume increased as cells proliferated. Cytotoxicity was expressed as the percentage lysis of target cells by 4 h 51Cr release. LILAK cells from healthy adults increased 120-fold in 2 weeks when incubated with ConA; the lymphokine-activated killer (LAK) cells increased 7-fold. The percentage of IL-2R+ cells increased more with ConA than with rIL-2 alone. ConA induced more suppressor T cells than PHA. LILAK cells obtained from patients by PHA treatment increased 180-fold in 2 weeks. Their cytotoxicity to Daudi cells was 1% before culture and 91% in 2 weeks; that of LAK cells was 60%. LILAK cells were cytotoxic to the tumour target cells, but not to allogeneic PBL. Adoptive immunotherapy may become more practical if many LILAK cells can be obtained at once by large-scale culture, such as by a hollow-fibre system.     

In-vitro Permeability to Salicylic Acid of Human,Rodent, and Shed Snake Skin

Abstract— In-vitro permeability to salicylic acid of human, rodent, and shed snake skin has been examined for the purpose of selecting model membranes for human skin corresponding to different anatomic sites, since a marked regional variation is suggested among the different sites. The greatest permeability to salicylic acid was observed in the scrotum, that of the sole was negligible. The cheek, neck, and inguinal skin seemed more permeable than the breast, back, thigh, lower leg, or foot skin. Shed snake and skin of hairless rat were found to show similar permeability to human breast and thigh skin. Wistar rat and nude mouse skin showed similar permeability to human cheek, neck, and inguinal skin.