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Biomedical subjects

A Pataki

Publications and source records attributed to A Pataki.

10 recordsLinked to original sources

Quantitative radiographic diagnosis of osteo-arthritis of the knee-joint in the C57BL mouse.

Comparative histopathological and radiographic investigations in the C57BL mouse model of spontaneous osteo-arthritis of the knee-joint indicate that there is a relation between quantitative radiographic diagnosis and semiquantitative histopathological diagnosis. Statistical analysis based on a set of quantitative radiographic parameters of the mouse knee-joint shows that the greater part of the radiographic information reflecting the histopathological degree of the osteo-arthritis is contained in the projection areas of the lateral and medial meniscus: progression of the osteo-arthritic process is accompanied with enlargement of the menisci. On the basis of these observations, a radiography score for the osteo-arthritis has been constructed, which consists of a weighted sum of the - suitably transformed - projection areas of the lateral and medial meniscus. In addition to the size of the menisci, the width of the joint space is also a useful quantitative parameter of osteo-arthritis of the mouse knee-joint.

Animals

Spontaneous osteo-arthritis of the knee-joint in C57BL mice receiving chronic oral treatment with NSAID's or prednisone.

In a statistically planned study based on quantitative radiography, treatment for 25-26 weeks with the 2 NSAIDs, diclofenac sodium, or indomethacin (both 0.5 and 1.5 mg/kg p.o. daily), or prednisone (6 mg/kg p.o.) had no influence on the progression of spontaneous osteo-arthritis of the knee-joint of the C57BL mouse, by comparison with placebo-treated controls.

Animals

Electrophysiological studies with a 2,3-benzodiazepine muscle relaxant: GYKI 52466.

The effects of GYKI 52466, a new 2,3-benzodiazepine with muscle relaxant and anticonvulsant properties, were investigated and compared to those of midazolam in electrophysiological experiments. The effects of the drugs on the reflex potentials evoked by afferent nerve stimulation and recorded from the spinal roots in unanesthetized spinal cats were studied. GYKI 52466 exerted a strong inhibitory effect on the monosynaptic as well as the polysynaptic ventral root reflexes, while the dorsal root responses decreased slightly. In contrast, midazolam markedly enhanced the dorsal root responses, did not modify the monosynaptic reflex and partially inhibited the polysynaptic reflex. The spontaneous firing of cerebellar Purkinje cells was depressed by midazolam, but not by GYKI 52466. These results suggest strongly that, contrary to the classical 1,4-benzodiazepines, potentiation of the GABA-A receptor-mediated inhibition does not play a significant role in the pharmacological actions of GYKI 52466.

Animals

Arthritis induced by continuous infusion of hr-interleukin-1 alpha into the rabbit knee-joint.

Continuous infusion of 200 ng/day hrIL-1 alpha for 14 days into knee-joints of rabbits leads to a severe arthritis of low aggressivity. This arthritis shows simultaneously characteristics of acute (serous and fibrinous exudation, polymorph infiltration, etc.) as well as chronic (synovial cell proliferation and fibrosis, pannus formation, cartilage and bone erosion, etc.) inflammation. The arthritis was associated with a distinct loss of metachromasia of the articular cartilage. These results indicate that IL-1 might play an important role in the induction and maintenance of arthritis.

Animals

Micropreparation techniques in quantitative histochemistry - density gradient centrifugation, manual microdissection and laser microbeam preparation of tissue.

Each quantitative histochemical problem needs its specific method for tissue preparation. In this connection two of the most important preparation methods, density gradient centrifugation and microdissection of freeze-dried tissue slices, are described. Density gradient centrifugation is a very effective procedure for preparative separation of cell particles such as cell nuclei. The details of the preparation of glial and neuronal cell nuclei are described. The in vitro phosphorylation of histone in the chromatin in relation to age is given as a practical example of the quantitative histochemical application to a preparation of cell nuclei. Other techniques of tissue preparation are the manual tissue microdissection according to Lowry and the Laser microbeam preparation. Advantages and disadvantages of both methods are compared. It is shown, that the introduction of Laser microbeam dissection technique, as alternative to manual microdissection, add new dimensions to Lowry's ultramicrochemical methods. One has greater freedom in the choice of the sample size and the number of samples dissected from the same slice. Furthermore, the need for a well-trained person for the preparation is eliminated. The preparation is also considerably less time consuming and easier to perform than the manual free hand preparation. Two quantitative histochemical methods used for the investigation of microdissected tissue samples are described: the gas-chromatography-massfragmentography (GC/MS)-method for determination of transmitters and its metabolites as well as the enzymatic cycling technique of Lowry. The GC/MS-method is explained with an example of noradrenaline and dopamine determination. The enzymatic cycling technique is demonstrated in combination with the Oil-Well-Technique for determination of the NADP-cycle.

Cell Fractionation

Enzyme histochemistry of rat folic acid nephropathy.

One hour after a single i.v. dose of 250 mg/kg folic acid, the straight portion of distal tubules in the outer medulla of rat kidneys showed a distinct reduction in succinate dehydrogenase, NADH2-diaphorase, glutamate dehydrogenase, cytochrome oxydase, Na+/K+-ATPase, and acid phosphatase activity. In contrast, the proximal tubules exhibited only a reduction in glutamate dehydrogenase and alkaline phosphatase activity. At this time the straight portion of the distal tubules, whose enzyme activity had changed, showed partly regressive epithelial changes. 24 hours after folic acid administration an even greater reduction in enzyme activity had occurred in the straight portion of distal tubules; these structures also became dilated. The adjacent collecting tubules and the corresponding proximal tubules were also severely dilated, the proximal tubules showing a loss in enzyme acitivities similar to those observed in the distal tubules. 48 hours after folic acid administration the changes largely resembled those observed after 24 hours, but were more pronounced. At this time a tubular regeneration was observed. 72 hours after folic administration extensive normalization of the histological and histochemical changes had occured. It is postulated that a disturbance of the hairpin counter-current mechanism occurs as a result of a direct, concentration-dependent effect of folic acid on the enzymes of the energy supplying metabolism. A dilation in the region of the loop of Henle and the collecting tubules occurs subsequently.

Acid Phosphatase

The relevance of drug-induced organ pigmentation in animals.

Postmortem examination of animals from long-term safety evaluation studies often reveals pigment deposition in tissues. A review of several such observations is given and the possible chemical backgrounds of their origin are described, in an attempt to aid the determination of relevance in individual cases. It is suggested that one may be fairly broad-minded in the interpretation of the relevance of such pigments, especially if they are found only in one species, and have no influence on the function of the organs involved. A final answer comes only after administration of the particular drug to man, although he is normally dosed at all events one should not overvalue the relevance of pigmentation found in long-term animal studies.

Animals

The automation of microspectrophotometry of tissue sections.

A system for quantitative microspectrophotometry with automatic data acquisition is described. It is relatively simple and less expensive than presently-available equipment. Fitted with the appropriate software, the system permits various types of probe selection, with both selection and measurement made under individual optimal conditions.

Computers

Histochemical study of monoamine oxidase latency in the liver of the rat.

In a histochemical test system with adrenaline as substrate and nitroblue tetrazolium (NBT) as electron acceptor, an increase of NBT reduction in rat liver sections was found microspectrophotometrically following short hypotonic treatment. Investigations with iproniazide, a monoamine oxidase inhibitor, and non-enzymatic NBT reduction showed that the increased formazan formation was related to the presence of monoamine oxidase. It is suggested that the reason for the observed increase of formazan formation is due to increased permeability of the inner mitochondrial membrane to NBT. Consequently, the increase of monoamine oxidase observed in the histochemical test system does not represent mobilization of a latent activity, but rather complete assessment of activity that is normally present.

Animals

[Relevance of enzyme histochemistry of rat thyroid gland].

High doses of aniline analgesics produced increased lipofuscin accumulation in rats thyroid glands after 18 week's treatment. To assess the significance of this change histochemical, biochemical and functional tests have been performed. Increased benzidineperoxidase, decreased acid phosphatase and unchanged leucyl-beta-naphtylamidase activities have been found histochemically and partly confirmed by biochemical methods. 131I-uptake was unchanged and PBI-levels decreased. The selection of appropriate histochemical methods in combination with additional techniques is stressed.

Acetaminophen