Edward J. Hinsman

Morphological characteristics of dendrite bundles in the lumbar spinal cord of the rat

The finding of motoneuron dendrites organized into small compact bundles in cats, monkeys and pigs suggested that a study of this phenomenon in rats should be undertaken. An analysis was performed with electron microscopy, light microscopy and Golgi methods. An extensive dendrite bundle organization was found in the sixth lumbar segment of the spinal cord. Two discrete bundles were localized bilaterally: a lateral bundle in the ventrolateral gray substance, and a medial bundle in the ventral funiculus. The lateral bundle was found to consist of longitudinally oriented dendrites, neurocytons, glial cells and capillaries. As many as 1678 closely packed dendrites were observed in the lateral bundle. The medial bundle contained dendrites directed across the midline and also longitudinally oriented dendrites. Neurocytons in the medial dendrite bundle were found singly or in clusters, and many radiating bundles of dendrites were observed projecting toward the lateral bundle. Golgi analysis confirmed that neurons in the lateral bundle had most of their dendrites oriented longitudinally. It was possible to trace several dendrites into the lateral bundle from dorsally and medially lying neurons. Electron microscopy substantiated the fact that the bundles were composed of dendrites. It also revealed numerous dendrodendritic and dendrosomatic contacts which were desmosomal in type as well as an abundance of small unidentified processes. Various functions which have been attributed to the dendrite bundles are discussed.

Species dependent gentamicin pharmacokinetics and nephrotoxicity in the young horse

Gentamicin pharmacokinetics and nephrotoxic potential were evaluated in twelve 2 to 3 month-old horses. Whereas recent evidence in our clinic indicated that young horses may be especially susceptible to gentamicin nephrotoxicity, young rabbits and rats are usually resistant. Gentamicin (4.5 mg/kg) was given by rapid intravenous injection. Serum gentamicin concentrations over a 13-hour period were fitted to an open, two-compartment, pharmacokinetic model. Subsequently, the same horses were divided into groups of 3 horses each. Each group received 0, 2.2, 4.4 or 8.8 mg gentamicin/kg, intramuscularly, every 12 hours for 15 days. Renal function was monitored. Peak and trough gentamicin concentrations were monitored daily. Renal sections were collected for histopathologic and electron microscopic examination. The (mean +/- SD) serum halflife was 194 +/- 37 minutes, total body clearance (ClB) was 1.65 +/- 0.79 mL/min/kg and volume of distribution at steady state (Vd(ss)) was 30.6 +/- 9.4 L/100 kg. Decreased renal function, as detected by elevated serum urea nitrogen or creatinine concentrations, was detected only in the two youngest foals (including animals in both the 4.4 and 8.8 mg/kg dose groups). The trough serum gentamicin concentrations of these 2 horses increased over time. These horses had the lowest ClB and Vd(ss) in the intravenous study. Morphologic changes were seen in kidneys of all treated horses and were similar to those occurring with gentamicin toxicity in other species. Our results support the clinical impression that very young horses may be more susceptible than adult horses, and adults of other species, to gentamicin nephrotoxicity.

Gentamicin pharmacokinetic changes in induced acute canine nephrotoxic glomerulonephritis.

Most clinical schemes used to adjust gentamicin dosage regimens in renal insufficiency assume that the volume of distribution remains constant. The purpose of this investigation was to determine the pharmacokinetic parameters of gentamicin (two-compartment open model) before and at two points during the acute phase of experimentally induced nephrotoxic (injection of anti-glomerular basement membrane antibody) glomerulonephritis in beagle dogs. Disease was verified by decreased 24-h creatinine clearance, increased 24-h urinary protein excretion, and characteristic immunofluorescent, light- and electron-microscopic lesions. After disease induction, the concentration of drug in serum at time zero (Cp0) was significantly decreased and the volume of the central compartment (Vc) and the volume of distribution (Vd(area)) were increased in all treated dogs. These findings suggest that the assumption of unchanged volume of distribution in acute glomerulonephritis could lead to a serious overestimation of serum drug concentration.

Single Dose Gentamicin Nephrotoxicity in the Dog: Early Functional and Ultrastructural Changes

A single dose (15mg/kg) of the aminoglycoside antibiotic gentamicin was administered intravenously to 4 purebred 5-month old beagles. Six 24-hour creatinine, urea, phosphate, sodium, and potassium clearances were performed, three before and three after gentamicin infusions, as were hematology and urinalysis. Animals were necropsied on the fourth day after drug infusion. Renal clearances tended to decrease. Light microscopy revealed no significant renal lesions, but transmission electron microscopy demonstrated increased cytosomes with myeloid figures (cytosegresomes) in the proximal tubule cells of treated dogs. These structures are characteristic markers of gentamicin. therapy. In addition, the proximal tubules of treated dogs contained single membrane limited vesicles with granular proteinaceous material; a structure not previously reported to be associated with aminoglycoside nephrotoxicity. The significance and relationship of these vesicles to the pathogenesis of gentamicin toxic nephropathy is not known. This study suggests that a single moderate dose of gentamicin is nephrotoxic in the beagle as judged by functional and morphological criteria.

Morphological and functional aspects of experimental gentamicin nephrotoxicity in young beagles and foals

A toxic nephropathy induced by gentamicin was investigated in young beagles and foals. Preliminary results indicated that a single 15 mg/kg dose of gentamicin administered to beagles produced subclinical functional and morphological changes in the kidney. Light histological lesions of aminoglycoside nephrotoxicosis were detected in all foals given gentamicin, suggesting an enhanced susceptibility of young horses to clinical renal dysfunction.

An inexpensive method for preparing freeze-dried sections of tissue for autoradiography

Abstract An inexpensive method is presented for preparing thin-section autoradiograms of diffusible substances by freeze-drying and osmium tetroxide vapor fixation of tissue. The unit can be easily constructed, occupies a minimum of space, and should be within the budget of most research laboratories. Both thin sections for light microscopy and ultrathin sections for electron microscopy can be prepared with the apparatus. Due to thinness of sections, the apparatus is best utilized for autoradiographic studies of tissue where there is a significant concentration of the isotope being studied.