We studied the effects of cilostazol, an antiplatelet and vasodilating agent, on axonal transport
patterns of cytoskeletal proteins in the motor fibers of sciatic nerve of streptozotocin-induced diabetic rats. Proteins labeled with L-[35S]methionine in 6-mm consecutive segments of the nerve were analyzed electrophoretically following fractionation into Triton-soluble and-insoluble subpopulations. Transport rates of proteins (particularly neurofilaments) in slow component a were reduced by 50% 2 weeks after labeling (4 weeks after streptozotocin). An apparent reduction of tubulin and actin was observed at later intervals after induction of diabetes. Actin transported in slow component b was also impaired, though to a lesser extent than in component a. Cilostazol prevented transport impairment of both slow components a and b without affecting hyperglycemia or reduction in body weight gain. These results suggest that in sciatic motor fibers early defects in slowly transported proteins are more marked in slow component a, and that impairment may be caused primarily by hemodynamic abnormalities.

Anti-restenosis Trials.

Reference: Curr Interv Cardiol Rep 2000 Nov;2(4):326-331.

The high frequency of restenosis after percutaneous coronary angioplasty is still a major clinical
problem. It occurs in 30% to 60% of patients and limits the long-term success of angioplasty. Many
clinical trials have been conducted to resolve this problem, using a wide range of pharmacologic
agents such as antiplatelet agents, anticoagulation drugs, lipid-lowering drugs, angiotensin-converting enzyme inhibitors, anti-inflammatory drugs, and antiproliferative drugs. Thus far, no effective drug has been reported, with the exception of probucol, which unfortunately is not approved by the US Food and Drug Administration because it prolongs the QT time, and possibly trapidil and cilostazol, two agents that are currently being tested in larger trials. Stent implantation has significantly reduced the frequency of restenosis in patients with 1) short lesions in large coronary arteries, (> 3.0 mm), 2) native coronary restenosis lesions, 3) venous bypass graft obstructions, 4) chronic total occlusions, and 5) acute myocardial infarction in patients referred for primary percutaneous intervention. A significant problem is the occurrence of in-stent restenosis because it is associated with a high recurrence of restenosis, after repeat coronary intervention irrespective of the technique or device used. Brachytherapy may limit this problem. The high restenosis rate occurring in long lesions and in small vessels still remains an unresolved issue.

The Potential of Cilostazol in Interventional Cardiology.

Reference: Curr Interv Cardiol rep 2000;2(2):143-148.

Cilostazol, an antiplatelet agent developed in Japan, has been demonstrated to have the potential to reduce restenosis after percutaneous transluminal coronary angioplasty (PTCA). Unlike conventional antiplatelet agents, cilostazol has several favorable properties in reducing restenosis. Besides the vasodilatory effect, cilostazol directly inhibits smooth muscle proliferation and may enhance reendothelialization after PTCA. Although the magnitude of prevention of restenosis may differ with the PTCA device used, cilostazol appears quite promising as a pharmacologic treatment adjunct to PTCA.

Effect of the antiplatelet drug dilazep dihydrochloride on urinary podocytes in patients in the early stage of diabetic nephropathy.

Reference: Diabetes Care 2000 23(8):1168-71.

OBJECTIVE: To determine whether the antiplatelet drug dilazep dihydrochloride affects the number ofurinary podocytes in diabetic patients with microalbuminuria. 

RESEARCH DESIGN AND METHODS:Fifty patients with type 2 diabetes and microalbuminuria (30 men and 20 women, mean age 48.6 years) and 30 age-matched control subjects (18 men and 12 women, mean age 49.2 years) were included in the study. No patients showed serum creatinine levels in excess of 2.0 mg/dl. Urinary podocytes were examined by immunofluorescence microscopy with monoclonal antibodies against podocalyxin. 

RESULTS: Urinary podocytes were detected in 18 of the 50 microalbuminuric diabetic
patients (mean, 1.3 cells/ml). Urinary podocytes were not detected in the remaining 32 patients or in
the 30 healthy control subjects. Diabetic patients positive for urinary podocytes were divided into 2
treatment groups: a dilazep dihydrochloride treatment group (300 mg/day; n = 9, group A) and a
placebo group (n = 9, group B). Treatments were continued for 6 months. In group A,
microalbuminuria decreased significantly from 146 +/- 42 to 86 +/- 28 microg/min (P < 0.01) and
urinary podocytes also decreased from 1.3 +/- 0.8 to 0.4 +/- 0.2 cells/ml (P < 0.01). However, in
group B, microalbuminuria and urinary podocytes changed little over the study period.

CONCLUSIONS: Podocyte injury may occur in patients with early diabetic nephropathy, and dilazep
dihydrochloride may be useful for preventing glomerular injury