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Biomedical subjects

J Prazma

Publications and source records attributed to J Prazma.

At least 73 records · Page 4Linked to original sources

Alteration of aminoglycoside antibiotic ototoxicity by hyper- and hypohydration.

The ototoxicities of tobramycin sulfate and gentamicin sulfate were investigated in guinea pigs under conditions of normal, increased, and decreased hydration. Increased hydration was associated with no decline in the amplitude of the cochlear microphonics, a lesser decline in the eighth nerve action potentials and lesser damage to the organ of Corti. Decreased hydration was associated with an increase in the threshold of the cochlear microphonics and the eighth nerve action potentials, a decline in the amplitude of the cochlear microphonics, a greater decline in the eighth nerve action potentials, and greater damage to the organ of Corti. Tobramycin sulfate was substantially less toxic than gentamicin sulfate with normal, increased and decreased hydration. These findings suggest the preferential use of tobramycin sulfate for patients with normal renal function, and especially patients with renal impairment.

Action Potentials↗

A correlation of the effects of normoxia, hyperoxia and anoxia on PO2 of endolymph and cochlear potentials.

Change in PO2 in endolymph, endocochlear potentials and cochlear microphonics have been tested in normoxia, hyperoxia and anoxia on 24 guinea pigs. The polarographic method and construction of oxygen-sensitive microelectrodes is described in detail. The normal level of PO2 in endolymph vaires between 20 and 30 mm Hg. One-minute anoxia induced by breathing 100% N2 caused a decline in PO2, EP and CM, but during recovery only PO2 returned with over-correction to the preexposure level. Hyperoxia evoked by breathing 100% oxygen failed to increase the cochlear potentials and the PO2 in the endolymph. This suggests that vasoconstriction most likely occurs proximal to the capillaries bed of the stria vascularis.

Animals↗

Carbonic anhydrase in the generation of cochlear potentials.

The experiments on 18 guinea pigs were divided into two groups and each group was arranged in such a way that the effect of hypercapnia (generated by breathing 10% CO2-90% O2) was investigated with and without inhibition of carbonic anhydrase by methazolamide, 25 mg/kg, in the first group and acetazolamide, 50 mg/kg, in the second group, administered intravenously. The endocochlear potentials (EP) and endocochlear PO2 were recorded by microelectrodes introduced into the scala media, and cochlear microphonics (CM) were monitored by a silver-wire electrode from the round window. In the first exposure to hypercapnia (20-40 min) EP increased about + 6 mV. At the same time CM decreased; the reason for this is not yet known. During the second period of hypercapnia (80-100 min) when carbonic anhydrase was inhibited with methazolamide and acetazolamide, EP did not elevate as during the first period when carbonic anhydrase was not inhibited. In this work, under specific conditions, it was observed for the first time that carbonic anhydrase affects the generation of EP.

Acetazolamide↗

Current-to-voltage convertor for measurement of oxygen.

A highly sensitive, miniature, inexpensive circuit for the measurement of PO2 in vivo has been described. The circuit is constructed from a current-to-voltage convertor, clamping circuit, differential amplifier, and reverse voltage and overvoltage protector. The design of the circuit allows us to apply voltage bias to the measuring electrode while grounding the preparation. The clamping circuit holds the selected bias voltage constant while the differential amplifier subtracts this bias potential from the PO2 signal yielding an output voltage that is proportional to the current sensed by the oxygen electrode. The circuit is protected from reverse voltage and overvoltage.

Electronics↗

Outer hair cell loss and alterations in glycogen due to tobramycin sulfate.

A total of 26 albino guinea pigs were treated with 200 mg/kg/day of tobramycin sulfate. Animals were killed at various intervals of up to three weeks after seven days treatment. Outer hair cell (OHC) loss of the organ of Corti was evaluated by surface preparation techniques, and glycogen was assessed with PATCO- and PAS-stained sections. We have concluded that permanent damage of OHCs is most prevalent in areas that normally have the least amount and the smallest granule size of glycogen. With treatment, these susceptible areas are the least responsive in terms of an early increase in glycogen production. Furthermore, by 21 days after seven days of treatment, these same areas will reveal an almost total loss of glycogen at a time when damage is maximal.

Animals↗

Ototoxicity of tobramycin sulfate.

Fifty-four healthy guinea pigs were studied histologically for evaluation of Tobramycin sulfate ototoxicity. They were treated with 50, 100, 150 and 200 mg/kg/day under different schedules. Loss of hair cells occurred when dosage of 1,200 mg/kg was reached. Animals receiving 700 mg/kg were without damage to the inner ear. Outer hair cell loss occurred first in the basal turn, spreading upward. Inner hair cell loss began in the apical turn, progressing downward. When a total dose of 1,400 mg/kg was reached by (two) different schedules the higher daily dose produced about twice the hair cell loss; therefore, the ototoxic effect depends on the total dose but even more on the increased blood concentration.

Animals↗

Electroanatomy of the lateral wall of the cochlea.

Metabolically, the most active membrane in the stria vascularis is the marginal cell membrane adjacent to the intermediate cells. It is probably at this site that K+ions are actively transported in and Cl minus ions are actively transported out by the Na+ in equilibrium K+, K+in equilibrium H+, and Cl minus ion pumps. Support for this hypothesis was derived from the work of other authors, from our own earlier results and the experimental results presented in this paper. Our experiments indicate that the marginal cells of the stria vascularis facing the endolymphatic space have a positive intracellular potential similar to the potential of the scala media, Therefore, the major portion of the active ion transport takes place on the intermediate cell side of the marginal cells. The pumping mechanisms, localized in this membrane, are responsible for the generation of the positive endocochlear potential (EP).

Animals↗

Ethacrynic acid. Effects on the cochlear potentials in normal and high blood oxygen.

The effect of ethacrynic acid (EA) at different blood O(2) saturations on cochlear potentials of guinea pigs was investigated. All 18 young healthy guinea pigs received 50 mg/kg/h of EA intravenously and were divided into three groups: first group, normal (90.00+/-6.30-86.17+/-4.83 mm Hg); second group, lower Po(2) (78.00+/-4.74-70.00+/-4.42 mm Hg); and third group, high Po(2) (174.40+/-13.41-179.00+/-26.15 mm Hg). The partial pressure of oxygen (Po(2)), the partial pressure of carbon dioxide (Pco(2)), and the pH of the blood were measured before EA administration and at the end of the experiment (3 h later) by drawing blood samples from the contralateral carotid artery. Cochlear potentials-endocochlear potential (EP), cochlear microphonics (CM), and action potentials (AP)-were recorded by standard methods from the first turn of the cochlea. Experimental data seem to indicate that elevation of the Po(2) to 174-179 mm Hg during relatively high doses of EA treatment prevents the declines in cochlear potentials which were observed in the first and second groups (normal and lower Po(2)), and preserves active ion transport which is responsible for the generation of cochlear potentials. These data suggest a means by which to reduce the ototoxic effect of EA and possibly indicates a method of treatment for hearing loss which developed after the administration of EA.

Action Potentials↗

Ototoxicity of cis-dichlorodiammine platinum (II) in guinea pigs.

Effects of cis-dichlorodiammine platinum (II), an agent that has potent antineoplastic activity, were studied in guinea pigs. With repeated administration of a daily dose of 1.5 mg/kg of cis-dichlorodiammine platinum, the cochlear microphonics were suppressed. Suppression of the cochlear microphonics was greater in the basal turn than in the third turn of the cochlea. There was a close correlation between loss of the cochlear hair cells and suppression of the cochlear microphonics. The endocochlear potential was decreased in the basal turn but remained unchanged in the upper turn of the cochlea. The sodium, potassium, and chloride concentrations in both endolymph and perilymph were not affected. Slight and moderate congestion and regeneration of tubular epithelium of kidney were observed in guinea pigs treated with cis-dichlorodiammine platinum.

Animals↗

Variation of endocochlear PO2 and cochlear potentials by breathing carbon dioxide.

The effect of carbon dioxide on oxygen dioxide tension in the endolymph was determined by the micropolarographic technique. Different concentrations (5% and 10% CO2) and different exposure times (3, 5, and 20 minutes) were investigated. The highest levels of PO2 in the endolymph (101.7, 93.9 and 69.5 mm Hg) were accomplished by respiration of 10% CO2, 90% O2, for 20, 5 and 3 minutes consecutively. The lowest PO2 increase, 50.7 mm Hg was observed after breathing 5% CO2, 90% O2 for 20 minutes. Extreme hypercapnia caused an increase of endocochlear potentials (EP) in all groups. In the second group EP increased from +79.3 to +84.9 and in all groups they had returned to the pretreatment level after CO2 discontinuation. These results support the theory that carbonic anhydrase participates in the generation of EP. At the same time that EP increased, cochlear microphonics declined and opposite after the breathing mixture was discontinued. The results permit the conclusion that high levels of PO2 in endolymph is achievable even with short periods of respiration with high CO2 mixture, and suggest the role of carbonic anhydrase during EP generation.

Action Potentials↗

Alteration of aminoglycoside antibiotic ototoxicity: effect of semistarvation.

The effect of semistarvation on the toxicity and ototoxicity of tobramycin sulfate (TO) and gentamicin sulfate (GE) was investigated in guinea pigs by electrophysiological and histopathological methods. The presented data has shown that the toxicity and ototoxicity of aminoglycoside antibiotics is substantially increased when guinea pigs were semistarved. Our results should also warn researchers using semistarvation in their conditioning experiments which investigate the toxicity of different chemicals. Toxicity was greater in GE- than TO-treated animals, which caused the GE-treated animals to die during treatment or shortly after treatment. Thus, TO should be preferentially used because it has been shown to be less toxic and ototoxic in normal and altered nutritional conditions.

Animals↗