To investigate the beneficial effects of cilnidipine, a calcium channel blocker that shows high selectivity for N-type receptors, on the progression of chronic renal insufficiency, we compared the efficacy of cilnidipine to that of benazepril, an angiotensin-converting enzyme (ACE) inhibitor with known renal protective effects, in a one-year trial evaluating hypertensive control, serum creatinine, and albuminuria in a cohort of patients. Given the seeming importance of the etiology of chronic renal insufficiency in determining drug efficacy, we limited our study to 20 patients with a single common condition, benign nephrosclerosis. The average age of the patients was 62+/-4 years old. The changes in systolic and diastolic blood pressure over the course of the study year revealed a similar reduction with cilnidipine and benazepril. Both cilnidipine and benazepril induced similar reductions in systolic and diastolic blood pressure over the course of the study year. The baseline levels of serum creatinine were 1.40+/-0.2 mg/dl and urinary excretion of albumin was 168+/-10 mg daily. The levels of serum creatinine were not significantly changed throughout the study in either group, although the levels of urinary excretion of albumin were significantly decreased in both groups. There were no significant differences in either of these values between the two groups. In conclusion, both cilnidipine and benazepril equally and effectively reduced blood pressure and albuminuria in hypertensive patients with benign nephrosclerosis in a one-year trial.
Hepatocytes isolated from F344 rats were transplanted into the spleens of congenic Nagase analbuminemic rats (NARs). The morphology and function of the transplanted hepatocytes were investigated after 18 months. The hepatocytes had formed nodules that occupied approximately 35% of the area of the splenic parenchyma on microscopic examination. Ultrastructural examination demonstrated that the organelles of the transplanted cells were indistinguishable from those of normal hepatocytes. The serum albumin level in NARs at 18 months after intrasplenic transplantation (HCTx) was about 3.6 % of that in normal rats. We confirmed that the hepatocytes in the spleen produced albumin and increased the serum albumin level in NARs with HCTx. The NAR model demonstrates the effect of HCTx and prolonged changes in the morphology of the hepatized spleen.
Nagase analbuminemic rats (NAR), which lack albumin synthesis in the liver, underwent intrasplenic hepatocyte transplantation (HCTx), and the long-term effects were studied using functional and morphological examinations. Hepatocytes were isolated from congenic ~44 rats with collagenase infusion, and 1 x 10 7 cells were llljected into the spleen of 3-month-old NAR (n = 10). ~erum albumin increased with time, reaching 53.9 mg/dl 4 months after HCTx, which was equivalent to 2.1% (maximum 4%) of serum albumin in normal rats. On the other hand, untreated NAR showed persistently low serum albumin levels (0.99 ± 0.23 mg/dl at 10 months).According to immunostaining with anti-rat albumin antib?dy at 16 months after HCTx, hepatocyte grafts occu-Pie~ 27-41% of the spleen area and weighed 120-420 mg, Whtch was equivalent to 0.8-2.9% of a whole liver. Our study demonstrated that grafted hepatocytes can grow in ~e spl.een with the ability to synthesize albumin. HCTx in . AR IS a new experimental system to monitor the func-t~on a~d survival of grafted heptocytes without sacrificing t e ~ntmals by measuring serum albumin levels. Certain mampulations to facilitate the growth of grafted hepatotes are necessary to achieve sufficient hepatic support in CTx.
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