In order to elucidate the role of macrophage in lipid-induced nephrotoxicity in diabetic nephropathy, we examined the effect of macrophage colony-stimulating factor (M-CSF) on the progression of renal lesions in hypercholesterolemic steptozotocin (STZ)-diabetic rats fed with high cholesterol chow. Hypercholesterolemia aggravated albuminuria in diabetic rats accompanied by infiltration of macrophages in glomeruli. Treatment with M-CSF suppressed simultaneously infiltration of glomerular macrophages and urinary albumin excretion in hypercholesterolemic diabetic rats. These results suggest that infiltration of glomerular macrophage has a primary role in lipid-induced nephrotoxicity in diabetic nephropathy, and M-CSF is involved in this process as a preventive factor.

Albuminuria↗

PubMedDate not supplied

Rat epididymal sperm motion changes induced by ethylene glycol monoethyl ether, sulfasalazine, and 2,5-hexandione.

Epididymal sperm was examined using the Hamilton-Thorne Sperm analyzer (HTM-IVOS, version 10.6) in male rats treated with known male reproductive toxicants that act by different mechanisms to detect effects on sperm motion. Three agents known to produce changes in sperm motion at high exposure levels were administered at lower levels. Ethylene glycol monoethyl ether (EGEE), sulfasalazine (SASP), and 2,5-hexandione (2,5-HD) were administered by oral gavage to adult male Sprague-Dawley rats at 250 or 500 mg/kg/day, at 300 or 600 mg/kg/day, or at 100 or 250 mg/kg/day, respectively. The males were treated with EGEE, SASP, and 2,5-HD for 35, 28, and 28 days, respectively. The males treated with EGEE and SASP were mated with untreated females to assess male fertility. All males were examined for body weight, testicular and epididymal weight, epididymal sperm count, and sperm motion. The sperm motion parameters included percentage of motile sperm, percentage of progressively motile sperm (progressive motility), curvilinear velocity (VCL), average path velocity (VAP), straight line velocity (VSL), amplitude of lateral head displacement (ALH), beat cross frequency (BCF), linearity (LIN), and straightness (STR). For the male rats treated with SASP, no treatment-related effects on percentages of motile sperm or sperm count were observed despite impaired male fertility. However, abnormal motion of epididymal sperm from the SASP treated males was detected by a significant reduction in mean progressive motility, VAP, and ALH, and an increase in BCF and STR. For the males treated with 2,5-HD for 4 weeks, most parameters generated by the HTM-IVOS indicated decreased sperm motion despite no remarkable changes in testicular weight, epididymal weight, or sperm count. In the EGEE-treated males at 250 mg/kg/day for 5 weeks, abnormal motion of epididymal sperm was detected by decreased progressive motility and increased BCF, although there were no treatment-related effects on testicular weight or male fertility. Progressive motility was decreased in all treated groups and the difference from the control value was of the greatest magnitude among the sperm motion parameters generated by the HTM-IVOS. Velocity parameters (VAP, VSL, VCL) responded sensitively to abnormal sperm motion in the SASP and 2,5-HD studies. In spite of decreased sperm motion, BCF values were significantly increased in all treated groups except the 7-week EGEE high-dose group, where there were no motile sperm to evaluate. ALH was significantly decreased in the treated groups in which remarkable effects on sperm motion were noted. There were no significant changes in ALH at the low-dose of EGEE at which only mild effects on sperm motion were observed. STR was increased for epididymal sperm from the males treated with SASP when compared with the controls. For the males treated with EGEE and 2,5-HD, however, STR was decreased when compared with the controls. There were no significant differences in LIN in any of the groups treated with SASP, in which remarkably reduced sperm motion was detected by the other parameters. In conclusion, among the parameters generated by the HTM-IVOS, progressive motility was significantly decreased in all treated groups and the most valuable for detecting slight changes in sperm motion induced by these three different target toxicants. Further investigation with a larger set of compounds is needed to evaluate which IVOS parameters are the most sensitive in detecting motion changes.

Animals↗

PubMedDate not supplied

Adult xanthogranulomatous intracranial lesion involving familial hypercholesterolemia.

A 35-year-old man was admitted because of loss of hearing in the left ear. The patient had been known to have familial hypercholesterolemia for at least 12 years. Computerized axial tomography of the brain showed a large tumor occupying in the left mastoid region. Surgical intervention revealed xanthogranuloma, histologically. Xanthogranuloma is classified as a kind of normocholesterolemic xanthomatoses. Hypercholesterolemia with adult xanthogranuloma (AXG) is extremely rare. Moreover intracranial involvement with AXG has been reported in only one previous case. We wish to report on the possibility of a new syndrome that has characteristics common to primary xanthomatoses, entities which have heretofore been considered etiologically distinct.

Adult↗

PubMedDate not supplied

Effect of arotinolol on insulin sensitivity in obese hypertensive patients.

Insulin sensitivity in terms of glucose disposal rate was determined by using the hyperinsulinemic euglycemic clamp technique in seven obese hypertensive patients and nine normotensive control subjects. The technique was used on all study subjects at baseline and on the hypertensive patients after 12 weeks of arotinolol treatment. Mean supine systolic blood pressure decreased from 155 +/- 3 mm Hg before treatment to 133 +/- 6 mm Hg after treatment (P < 0.02), and diastolic blood pressure decreased from 100 +/- 3 mm Hg before treatment to 86 +/- 3 mm Hg after treatment (P < 0.05). The mean dose of arotinolol was 10 mg/d, except for one patient who received 20 mg/d. The glucose disposal rate during the last 30 minutes of the glucose clamp procedure was not significantly affected by treatment with arotinolol. Compared with the hypertensive patients, the glucose disposal rate in the normotensive subjects was significantly increased, both before and after treatment (P < 0.01). The study results show that the obese hypertensive patients were insulin resistant and that treatment with arotinolol did not significantly affect insulin sensitivity.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Doxazosin improves insulin sensitivity in hypertensive patients.

Insulin sensitivity in terms of glucose disposal rate was measured by the hyperinsulinemic/euglycemic clamp technique in 10 hypertensive patients and 7 normotensive control subjects before and after 12 weeks of doxazosin therapy. Supine blood pressure fell significantly, from 150/98 mmHg before treatment to 136/90 mmHg after treatment (systolic P < 0.001/diastolic P < 0.01). The average dose of doxazosin at the end of the study was 3.3 +/- 0.4 mg/day. The glucose disposal rate during the last 30 minutes of the glucose clamp procedure was significantly increased, from 5.8 +/- 0.7 mg/kg/min before to 7.8 +/- 0.7 mg/kg/min after treatment (P < 0.02). Insulin sensitivity was 8.7 +/- 0.4 mg/kg/min in the normotensive subjects, which represented a significant difference when compared with that of the hypertensive subjects before treatment (P < 0.01). Steady-state serum insulin concentrations, as measured during the glucose clamp procedure, were 172 +/- 10.4 microU/ml before and 176 +/- 13.5 microU/ml after doxazosin treatment; these levels were significantly higher than the 137 +/- 7.0 microU/ml reading obtained in the normotensive subjects (P < 0.05). Study results show that hypertensive patients tend to be insulin resistant and that treatment with doxazosin improves insulin sensitivity.

Adult↗