Cyclosporine A (CSA), a lipophilic cyclic undecapeptide, is not accumulated evently in all tissues and has a high affinity to several tissues such as lymphoid organs, liver, and kidneys. From this point of view, it is reasonable to assume that the amount of CSA uptake would be correlated with the extent of cell injury. On the other hand, verapamil, a Ca2+ channel blocker, bas been shown to ameliorate CSA nephrotoxicity. Since proximal tubule is the major site of drug transport and CSA uptake and its interaction with verapamil in isolated human renal proximal tubular cells. The CSA uptake rapidly increased over the first 5 min and then achieved almost steady-state after 10 min at all concentrations (0.5-10 uM). Kinetic analysis yielded that the Km and Vmax values of CSA were 5.6 uM and 86.2 p mol/mg cell protein/min, respectively. And Ca2+ depletion in media enhanced CSA uptake significantly but verapamil reduced it. These results suggest that the Ca2+ channels and CSA transporting sites on cell membrane are closely associated and that Ca2+ and CSA might be taken up competitively by proximal tubular cells.
Humans

Nephrotoxicity is the most common dose-limiting factor of cyclosporine A (CSA) in clinical usage. But the mechanism of CSA-induced nephrotoxicity still remains unresolved. Many authors insisted that CSA induced renal proximal tubular cell injury is due to the secondary effects following hemodynamic changes or endothelial cell damage, instead of direct toxicity by CSA. To find out that CSA has a direct toxicity to the proximal tubular cells, the author used primary cultures of human proximal tubular cells to eliminate the hemodynamic or endothelial influences that could be produced in in vivo model. In the present study, the viability against CSA was tested by the neutral red assay method with modulation of Ca2+ amount in incubating media and observed electron microscopically. The viability test showed direct toxic effect of CSA on human proximal tubular cells and this was enhanced by Ca2+ depletion in incubating media. Morphologically noted are accumulation of lipid droplets and polyribosomal dispersion, which may be association with inhibition of cellular synthetic activity. These results suggest the toxixity is a direct effect of cyclosporine and that toxic mechanism may be due to inhibition of cellular synthetic activity. And this experiment also showed that primary cultures of human renal proximal tubular cells can be a good in in vivo model for investigating CSA nephrotoxicity.
Humans

No abstract available.

No abstract available.
Breast Feeding* ; Breast*

No abstract available.
Humans ; Infant, Newborn ; Infant, Premature* ; Milk*

No abstract available.
Humans ; Infant* ; Pregnancy*

No abstract available.
Biopsy* ; Biopsy, Fine-Needle*

An epidemiologic investigation was conducted to identify the source of infection and the mode of transmission of typhoid fever outbreak occurred in Ohchun middle and high schools located in Young il Gun, Kyungpook Province from May 21 to Jun 4, 1994. Four out of 13 hospitalized students in three general hospitals in Pohang City were culture positive typhoid fever (Salmonella typhi Group D). Review of the in and outpatient logbooks of the three general hospitals in Pohang City, county health center and local clinics in the vicinity of the Ohchun middle and high schools suggested that the outbreak was confined to the schools. Drinking water source of the schools was two underground water pumps that had no treatment facilities; one in northern end and the other in southern end of the main school building. However, the southern water pump was closed on April 28, 1994 because a recent test for the water revealed E-coli suggesting a possible fecal contamination. Two hundred twenty students stated that they had experienced symptoms related to typhoid fever since April l, 1994 in a self administered questionaire survey of all of the 2, 226 students. Personal interviews with these 220 students were performed to confirm the clinical history together with a rectal swab culture for typhoid fever and Widal test. A total of 39 patients were detected; 15 confirmed cases (culture-positive) and 24 suspected cases (symptom positive with equal to or greater than 1:160 titer of Salmonella O-antibody or 1:320 titer of H-antibody titer in Widal test). The epidemic curve showed a unimodal curve with a peak on the second week(17 May, 1994) and tailed down to the 5th week (22 28 May, 1994). The overall incidence rate of typhoid fever was 1.8 per 100 students; 1.5 (1.6 for male, 1.5 for female) in the middle school and 2. 4 (6. 2 for male, 0. 4 for female) in the high school. When contrasted with the students who did not drink water at all in the school, the relative risks of incidence rate of typhoid fever for the students who drank the underground water of the school, both underground water and water brought from home, or water brought from home only were 55.5, 19.0, and 3.0 respectively. Three classes which had especially high incidence rates of typhoid fever were located in the southern part of the main school building, where the contaminated underground water pump is located. These findings suggested that the source of infection was the contaminated underground water of the school. Both of the two underground water pumps were closed permanently and the public running water was supplied to the schools.
Drinking Water ; Groundwater ; Gyeongsangbuk-do* ; Hospitals, General ; Humans ; Incidence ; Male ; Outpatients ; Running ; Salmonella ; Typhoid Fever* ; Water

Echocardiographic examination was performed before, immediately after, 4-6 months after and 10-12 months after mitral valve replacement(MVR) surgery in 46 patients with mitral valve disease(8 patients with mitral regurgitation, 24 patients with mitral stenosis and 14 patients with mitral stenosufficiency) to evaluate the effects of mitral valve replacement on dimension of left atrium and left ventricle, volume of left ventricle, ejection fraction(EF) and fractional shortening(FS) of left ventricle. The results are as follows : 1) The endsystolic dimension(ESD), enddiastolic dimension(EDD), endsystolic volume(ESV) and enddiastolic volume(EDV) decreased significantly after operation in patients with mitral stenoinsufficiency(MSR), the ESD, EDD, ESV and EDV increased significantly after the operation, but returned to preoperative value 10-12 months after the operation. 2) The EF and FS of left ventrcle after MVR were significantly lower than preoperative value throughout the postoperative period in patients with MR. However in patients with MS or MSR, there were no significant postoperative changes in EF and FS, except transient depression in the patients with MS at the immediate postoperative period. 3) In all patients with mitral valve disease, the left atrial dimension and the ratio of domension of left atrium to the dimension of aorta decreased significantly after MVR. From above results, it is suggested that surgery should be considered seriously for the patients with MR before the ESD, EDD and ESV increase maekedly, even if the EF anf FS are in normal range and the symptoms are not severe, to prevent irreversible depression of myocardial function. It seems that serial echocardiographic examination is very helpful in this respect.
Aorta ; Atrial Natriuretic Factor ; Depression ; Echocardiography* ; Heart Atria ; Heart Ventricles ; Humans ; Mitral Valve Insufficiency ; Mitral Valve Stenosis ; Mitral Valve* ; Postoperative Period ; Reference Values

No abstract available.
Panniculitis, Peritoneal*