The effects of acetyl-L-carnitine and sorbinil on peripheral nerve structure, chemistry, and function in experimental diabetes.

Nerve conduction velocity (NCV) increased with age in nondiabetic male Wistar rats for the first 26 weeks of life. The NCV of animals made hyperglycemic at age 6 weeks by administration of streptozotocin (STZ) also increases, but at a slower rate. Animals with 4 weeks of hyperglycemia and reduced NCV treated with an aldose reductase inhibitor (sorbinil) or a short-chain acyl-carnitine (acetyl-L-carnitine [ALC]) daily for 16 weeks showed an improvement in NCV.

The effect of hyperglycemia on nerve conduction and structure is age dependent.

The nerve conduction velocity (NCV) of nondiabetic male Wistar rats continues to increase until approximately 26 weeks of age. Rats made hyperglycemic at 6 weeks of age manifest reduced NCV by 10 weeks of age and show morphological differences in the sciatic tibial nerve after 5 months of hyperglycemia when compared with age-matched controls. Fiber diameter, myelin width, and the number of large myelinated fibers were decreased in the tibial nerves of the hyperglycemic animals.

Acetyl-L-carnitine corrects the altered peripheral nerve function of experimental diabetes.

Acetyl-L-carnitine (ALC) has been shown to facilitate the repair of transected sciatic nerves. The effect of ALC (50 mg/kg/d) on the diminished nerve conduction velocity (NCV) of rats with streptozotocin (STZ)-induced hyperglycemia of 3 weeks' duration was evaluated. The aldose reductase inhibitor, sorbinil, which is reported to normalize the impaired NCV associated with experimental diabetes, was used as a positive control.

Acetyl-L-carnitine corrects electroretinographic deficits in experimental diabetes.

Acetyl-L-carnitine reduces the latencies of electroretinogram oscillatory potentials in healthy humans. The effect of acetyl-L-carnitine (50 mg.kg-1.

Measurements of tissue sorbitol in diabetes mellitus: enzyme method versus gas-liquid chromatography.

Two methods are commonly used to measure sorbitol in mammalian tissues. The first uses sorbitol dehydrogenase for a coupled enzymatic reaction; unfortunately, other polyols are also substrates for this enzyme. The second uses gas-liquid chromatography (GLC) for separation of polyols and mass quantitation of sorbitol.

Altered neuroexcitability in experimental diabetic neuropathy: effect of acetyl-L-carnitine.

Sciatic nerve conduction velocity (NCV) is reduced in rats made hyperglycaemic with streptozotocin (STZ). This neurophysiological dysfunction has been associated with increased nerve sorbitol and reduced nerve inositol. Treatment of STZ diabetic rats with aldose reductase inhibitors (ARIs) which reduce sorbitol and increase inositol in the nerve results in normalization of NCVs.

Improvement in peripheral nerve function after one year of Sorbinil.

The effect of 250 mg day-1 of the aldose reductase inhibitor, Sorbinil, upon peripheral nerve function was assessed in 23 adult diabetics with clinical neuropathy. Sorbinil was given for 4 weeks to 10 subjects, while 13 received placebo in this double-blind study. Open label treatment with Sorbinil was then continued for 52 weeks in 10 of the 23 subjects.

Nonosmotic diabetic cataracts.

It has been suggested that sugar cataracts associated with diabetes mellitus result from the accumulation of excess sorbitol within lens fibrils. Swelling of lens fibrils occurs when water moves in to maintain osmotic balance; the excess water causes disruption of fibrils and cataract formation. Other studies have indicated that more than sorbitol-induced osmotic stress is involved.

Multiparametric analysis of peripheral blood in the normal pediatric population by flow cytometry.

Lymphocyte subset analysis was performed on 114 healthy children and 84 healthy adults. Samples were prepared by a whole blood lysis technique and analyzed by flow cytometry. The percentage and total number of CD3+, CD4+, CD8+, and CD19+ lymphocytes were calculated for each of six age groups.

Cone electroretinograms and visual acuities of diabetic patients on sorbinil treatment.

Photopic, 30-Hz, and foveal electroretinograms were measured in 19 diabetic patients in an experimental study of the effects of short-term Sorbinil (an aldose-reductase inhibitor) on retinal function. Patients were assigned in double-blind fashion to Sorbinil (250 mg/day) or placebo groups and were tested at the outset and after four weeks of therapy. Comparisons (t-test) between the Sorbinil and placebo groups failed to show significant effects of treatment on electroretinograms, although there was a significant correlation within the Sorbinil group between foveal recordings and red cell sorbitol at the end of treatment.

Effects of ketotifen on the responsiveness of peripheral blood lymphocyte beta-adrenergic receptors.

The effects of ketotifen therapy on the responsiveness of lymphocyte beta-adrenergic receptors was evaluated by measuring cyclic AMP elevations caused by isoproterenol in cells isolated from patients treated with ketotifen for more than 1 year. Binding of 3H-dihydroalprenolol to beta-receptors was also evaluated. The isoproterenol-induced rise in cyclic AMP relative to each individual's baseline level was greater in patients on current ketotifen therapy than in other asthmatic patients or non-asthmatic subjects.

Hematuria and hypercalciuria in children with diabetes mellitus.

Hematuria of unknown origin occurs in 30% of patients with diabetic nephropathy. In nondiabetic persons, hematuria may be caused by hypercalciuria with or without nephrolithiasis. Eight children with type I diabetes mellitus, hematuria, and hypercalciuria were observed in our clinic during a 1-year period.

Comparison of insulin levels after injection by jet stream and disposable insulin syringe.

Intermediate-acting biosynthetic human (NPH) insulin was administered by disposable insulin syringe into the right upper thigh of nine insulin-dependent diabetic youths. Seven days later, the same amount and type of NPH insulin was given in the same anatomic site with a Medi-Jector II, which delivers insulin as a jet stream. Blood was collected before insulin injection and at hourly intervals subsequently for the measurement of glucose and insulin.

Factors influencing acquired subgottic stenosis in infants.

A prospective study of factors that might contribute to the development of acquired subglottic stenosis was undertaken in newborn infants with endotracheal tubes in place for 7 days or more. Duration of intubation, the number of endotracheal tubes inserted, the duration of mechanical ventilation, the presence of post-extubation stridor, and the size of the endotracheal tube in relation to gestational age significantly correlated with the development of subglottic stenosis. Patients at risk for significant subglottic stenosis were those with post-extubation stridor and those with tubes in place for 25 days or longer.

Hypercalciuria, hyperphosphaturia, and growth retardation in children with diabetes mellitus.

The role of hypercalciuria and hyperphosphaturia in the growth retardation of children with diabetes mellitus was investigated in 157 children with diabetes whose mean height was less than that of 37 nondiabetic siblings of similar age (P less than .025). Hyperglycemia, hypercalciuria, and hyperphosphaturia were assessed coincident with the height measurement of each child in a cross-sectional survey.

Depression of hepatic mixed-function oxidase activity by B. pertussis in splenectomized and athymic nude mice.

Administration of Bordetella pertussis (B. pertussis), Corynebacterium parvum (C. parvum), and several other immunoactive substances is known to cause a marked decrease in the activity of the hepatic microsomal mixed-function oxidase system.

Endotoxin depression of hepatic mixed function oxidase system in C3H/HeJ and C3H/HeN mice.

The effect of endotoxin to depress the hepatic drug-metabolizing enzyme activity has been studied in the C3H/HeJ and C3H/HeN strains of mice. The C3H/HeJ mouse strain is generally considered to be unresponsive to the biological effects of endotoxin. However, injection of these mice with 0.