Digital slide and virtual microscopy based routine and telepathology evaluation of routine gastrointestinal biopsy specimens.

AIMS: To evaluate a recently developed digital slide and virtual microscope system, and to compare this method with optical microscopy on routine gastrointestinal biopsy specimens in both local and remote access modes. METHODS: A fully computer controlled commercial microscope was used. The scanning program included object detection, autofocus, and image compression algorithms. The overall hard disk space for a gastric biopsy was between 30 and 50 MB and the scanning time was between 20 and 40 minutes. Haematoxylin and eosin stained routine gastric (61) and colon (42) biopsy specimens were selected, scanned, and evaluated by two specialists on an optical (OM) and virtual microscope (VM). RESULTS: The overall concordance of VM and OM with the consensus diagnosis was 95.1% and 97%, respectively. Clinically important concordance was 96.1% and 98% for VM and OM, respectively. The two methods showed concordance in 92% of cases and clinically important concordance in 94.1% of cases. The reasons for discordance were image quality (one case), interpretation difference (three cases), and insufficient clinical information (three cases). Remote evaluation of the digital slides through the Internet has the advantages of the previously used static and dynamic telepathology methods. CONCLUSIONS: Diagnostic concordance was found between OM and VM. The digital slide and the virtual microscope can be alternative techniques in the computerisation of the histology laboratory and in teleconsultation services after further evaluation of time and storage constraints.

[In vitro models for research on cell differentiation and malignant degeneration in the human prostate]. / Modeli in vitro dlia izucheniia differentisirovki i malignizatsii kletok predstatel'noi zhelezy cheloveka.

The methods are reviewed for obtaining monolayer epithelium cultures both in normal and hyperplastic or malignant prostate glands. Preparation of pure epithelial tissue cultures is dealt with in detail. The major prostate cell lines are described. Special attention is paid to the markers of differentiation and sensitivity to hormones in normal and tumour prostatic cells in vitro. Prospects for the use of prostatic cell cultures as models in oncology are outlined.

[The reproductive function of male rats in the late periods after x-ray irradiation]. / Reproduktivnaia funktsiia samtsov krys v otdalennye sroki posle rentgenovskogo oblucheniia.

Reproductive function in male rats was studied in 1, 3 and 6 months after X-ray irradiation of doses of 2 and 3 Gy. It has been established that long-term effects of irradiation at a dose of 3 Gy are manifested through decrease in spermatozoa content in the epididymis and reduction of nucleic acid and protein content in the testes. Fertility of male rats under study significantly lowered shortly after irradiation and full recovery of fecundating ability was observed 6 months later. The effect of irradiation with a dose of 2 Gy was less pronounced.

[Characteristics of the long-term effects of niphtholide on the functional state of the testes in animals]. / Osobennosti prodolzhitel'nogo vozdeistviia niftolidom na funktsional'noe sostoianie semennikov zhivotnykh.

Long-term application of non-steroid antiandrogen niphtholid (10 or 25 mg/kg daily for 8-9 months) exerts a stimulating effect on the functional state of testicles. This effect is more pronounced in rats, than in dogs and guinea pigs. In all these animals the drug antiandrogenic effect caused a decrease of the prostatic mass, while in rats--an increase of the adenohypophysis mass. The peculiarities of the niphtholid effect in various animals should be taken into account when evaluating and interpreting investigation results.

[Androgen status in rabbits after long-term administration of non-steroid androgen antagonist niftolid]. / Androgennyi status u krolikov v usloviiakh prodolzhitel'nogo vvedeniia nesteroidnogo antiandrogena niftolida.

Niphtholid (25 mg/kg/dl for 60 days) significantly increases the LH and testosterone blood levels but has no marked effect on ++androstenedione and testosterone-estradiol-binding globulin levels in Chinchilla++ mature rabbits. The concentration of latter was elevated against a background of low testosterone and androstenedione and high LH levels in the castrated rabbits. The obtained results show that niphtholid exerts a continuous stimulating and pronounced effect on the rabbit pituitary-gonadal axis and simultaneously prevents the manifestation of suppressing androgen effect on testosterone-estradiol-binding globulin contents in the organism.

[The correlation of the hormonal and clinical effects in patients with prostatic cancer undergoing niftolid treatment in combination with low doses of synestrol]. / Koreliatsiia hormonal'nykh ta klinichnykh efektiv u khvorykh na rak peredmikhurovoï zalozy pry likuvanni niftolidom u poiednanni z malymy dozamy synestrolu.

Effects were studied of niftolide in tablets, 0.25 g on a three-times daily basis in combination with low doses of sinestrol, 5 mg intramuscularly within 24 h, on tumor growth, blood plasma content of luteinizing hormone (LH), testosterone (T) and testosterone-estradiol-binding globulin (TEBG) in 46 patients with prostate gland carcinoma, including seven patients with metastases. After treatment for three months, plasma T level decreased by 63%, that of LH by 53% whereas TEBG increased twice as much. The treatments were administered for as long as 10 months, with estrogen therapy being tapered to a dose of 3 mg daily. The above treatment schedule resulted in stabilization or partial regression of tumor growth in as many as 94.9% cases; also deserving to be noticed was improvement in the outflow of urine and alleviation of the pain syndrome. The clinical effect is believed to be due to pharmacological blockade of androgenic receptors in the tumor and its metastases as well as to antigonadotropic activity of estrogen and striking lowering of blood plasma free T.

[Recovery of various parameters of the functional state of the reproductive system in thymectomized rats as affected by thymic membrane factor]. / Vosstanovlenie nekotorykh pokazatelei funktsional'nogo sostoianiia reproduktivnoi sistemy u timéktomirovannykh krys pod vliianiem membrannogo faktora timusa.

Ten-month-old male rats thymectomized in early post-puberty were ascertained to have lower plasma luteinizing and testicular hormones and higher testicular steroid dehydrogenase activity. Following 24 hours of administration of a thymocyte membrane structural agent, pituitary gonadotropic and gonadal androgenic functions became normal. There was no agreement between the hormonal parameters and the levels of nucleic acids in the testes and prostate.

[Biochemical bases of the antifertility action of the nonsteroidal antiandrogen niphtolid]. / Biokhimicheskie osnovy antifertil'nogo deistviia nesteroidnogo antiandrogena niftolida.

The study was made of biosynthesis and levels of nucleic acids and proteins in the head of epididymis as well as of the fertility of intact mature male rats under antiandrogenic exposure to nonsteroid antiandrogenic compound niphtolid. Niphtolid given per os in a dose of 25 micrograms/kg during 8 or 30 days decreased the mass of the organ and its concentrations of DNA, RNA and proteins. The above mentioned alterations seemed to be caused by inhibited inclusion of labeled precursors into biopolymers. A long-term intake of antiandrogen (10 micrograms/kg of body mass daily for a six-months period) was followed by developing transient infertility. The possibility to use niphtolid-like compounds both alone and in combination with antigonadotrophic drugs for fertility regulation is assumed.

[Antiandrogenic effects of hydroxyniftolide in male rats]. / Antiandrogennye éffekty gidroksiniftolida u samtsov krys.

Experiments on intact mature male Wistar rats showed the ability of hydroxyniftolide (4'-nitro-3'-trifluoromethyl-2-hydroxy-2-methylpropionylanilide), a hydroxylated antiandrogen derivative of niftolide, to inhibit the effects of male sex hormones in androgen target organs. At doses of 10 mg/kg and upwards administered intravenously or intramuscularly for 10 days, it stimulated the hypothalamohypophy-seogonadal system expressed in an increase in the activity of delta 5-steroid-3 beta-ol-dehydrogenase in the testicles and blood plasma testosterone concentration. Comparative studies on antiandrogenic properties of niftolide and hydroxyniftolide made it possible to show that the effect of the first agent was more noticeable with relation to the hypothalamic centers of gonadotropin secretion regulation whereas the effect of the second one was more noticeable in the accessory sex glands.

[Nucleic acid and protein biosynthesis in the accessory sex organs of rats during blockade of testosterone effect by androgen antagonist 4-nitro-3-trifluoromethylisobutyranilide]. / Biosintez nukleinovykh kislot i belka aktsessornykh polovykh organakh krys pri blokade deistviia testosterona antiandrogenom 4-nitro-3-triftormetilizobutiranilidom.

The influence of testosterone and antiandrogen 4-nitro-3-trifluoromethylisobutyranilide (4N3TFMIBA) on the content and biosynthesis of nucleic acids and the protein in the ventral prostate and the seminal vesicles of Wistar rats was studied under experimental conditions. As revealed, with the simultaneous administration of the androgen and its antagonist there was a fall in the organs under study of the RNA and protein content and a reduction of incorporation of labeled precursors into the DNA, RNA, and protein. Similar changes were seen after castration. A conclusion was drawn that the capacity to block the stimulating influence of testosterone on the nucleic acid and protein biosynthesis underlay "castration" effects of antiandrogen 4N3TFMIBA, this causing atrophy of the accessory genital apparatus.

[Nucleic acid and protein biosynthesis in the androgen-sensitive organs of intact male rats given the nonsteroid antiandrogen niftolide]. / Biosintez nukelinovykh kislot i belka v androgenchuvstvitel'nykh organakh intaktnykh samtsov krys v usloviiakh vvedeniia nesteroidnogo antiandrogena niftolida.

In experiments on adult male rats it was found that the oral injection of non-steroid antiandrogen 4-nitro-3-trifluoromethylisobutyranilide (niftolide) in a dose of 25 mg/kg during 8 or 30 days induces atrophy of the accessory genital glands and the levator ani muscle and a decrease in the nucleic acid and protein content. Niftolide "castration" effect is realized through its ability to inhibit biosynthesis of these compounds in androgen-sensitive organs. The antiandrogen dose used exerted a potent prolonged antiandrogenic action, despite its stimulating effect upon the hypothalamic-hypophyseal-gonadal system.

[Specific binding of androgens by the skin in hirsutism of ovarian genesis]. / Spetsificheskoe sviazyvanie androgenov kozhei pri girsutizme ovarial'nogo geneza.

The role of raised skin sensitivity to circulating androgens in the pathogenesis of hirsutism, determined by the syndrome of polycystic ovaries, was studied. A two-fold increase in the specific binding of 3H-methyltrienolone++ was noted in the cytosol fraction of the public skin of women suffering from hirsutism as compared to healthy women using saturation analysis. The specific binding of androgens indicated an increase in the content of androgen receptors of the skin in hirsutism.

[Interrelation of sex hormone-binding globulin and the androgen-estrogen balance in patients with hypercorticism]. / Vzaimosviaz' globulina, sviazyvaiushchego polovye gormony, i angrogeno-éstrogennogo balansa u bol'nykh s giperkortitsizmom.

The concentration of testosterone and estradiol in the blood plasma and the binding capacity of testosterone-estradiol binding globulin (TEBG) were studied in 30 women and 6 men with Icenko-Cushing's disease in the active phase and in 24 women with hormonally active adrenal tumors. In hypercorticism against a background of unchanged of lowered concentration of plasma estradiol there was a decrease in the concentration of testosterone and an increase in the testosterone-estradiol binding capacity (TEBC) in men and an increase in the concentration of testosterone and a decrease in TEBC in women. The authors have assumed that the testosterone/TEBC ratio reflects more accurately change in the dynamics of androgens than isolated concentrations of testosterone and TEBG, and recommended its determination for the assessment of the body androgenic saturation in disturbed function of the adrenal or sex glands.

[Antiandrogenic effects of 4-nitro-3-trifluoromethylisobutyrylanilide (niftolide) in prepubertal male rats during stimulation with exogenous gonadotropins]. / Antiandrogennye éffekty 4-nitro-3-triftormetilizobutiranilida (niftolida) u samtsov krys prepubertatnogo vozrasta v usloviiakh ékzogennoi gonadotropnoi stimuliatsii.

Nonsteroid antiandrogen 4-nitro-3-trifluoromethylisobutyranilide (10 mg/kg per os from the 26th to the 37th day after birth) decreased the weight of the accessory sex organs, and levator ani muscle. DNA, RNA, and protein content in the ventral prostate and the seminal vesicles, the thickness of the secretory cell epithelium of the ventral prostate under conditions of stimulation of prepubertal male rat gonads with human gonadotropin (100 Units/kg subcutaneously from the 21st to the 37th day after birth). The mentioned effects were observed against the background of hyperplasia and hypertrophy of Leidig's cells and increase of the activity of steroid-delta5-3beta-ol-dehydrogenase of the testes activity. A conclusion was made that niftolide was capable of preventing or delaying the development of some signs of premature sexual maturation.

[Diethylstilbestrol potentiation of the antiandrogenic effects of niftolide in the prostate]. / Potentsirovanie diétilstil'béstrolom antiandrogennykh éffektov niftolida v predstatel'noi zheleze.

In experiments on intact mature male Wistar rats it was shown that a combined administration of niftolide (2.5, 5 and 10 mg/kg) and diethylstilbestrol (10 and 50 mg/kg) produced a more pronounced antiprostatic effect than their separate administration.

[Radioimmunological and biochemical study of the reaction of the adenohypophysis, testes and adrenals in rats and guinea pigs to the administration of the antiandrogen, 4-nitro-3-trifluoromethylisobutyranilide]. / Radioimmunologicheskoe i biokhimicheskoe issledovanie reaktsii adenogipofiza, semennikov i nadpochechnikov krys i morskikh svinok na vvedenie antiandrogena 4-nitro-3-triftormetilizobutiranilida.

A study was made of the influence of antiandrogen 4'-nitro-3'-trifluorome-thylisobutyranilide (niftolide) on the content of the luteinizing hormone, testosterone and corticosterone in the rat blood plasma, the content of testosterone in the blood plasma and on the 17-OCS and 17-KS urinary excretion in guinea pigs. The data obtained pointed to a marked intensification of lutropin and testosterone secretion. The observed changes are explained by the capacity of niftolide to block the inhibitory influence of the androgens of the feed-back mechanism of the gonadotropin secretion control. It is suggested that niftolide can be used for the investigation of the functional condition of the hypothalamo-hypophysio-testicular system. Niftolide had no effect on the indices of the glucocorticoid activity of the adrenal glands in rats and guinea pigs.

Hypothalamo-hypophyseal-gonadal system in male rats and guinea pigs treated with the antiandrogen 4-nitro-3-trifluoromethylisobutyranilide.

Influence of the competitive testosterone antagonist 4-nitro-3-trifluoromethylisobutyranilide (NFBA) on the hypothalamo-hypophyseal-gonadal system in male Wistar rats and guinea pigs was studied. NFBA as well as nonlabelled testosterone diminished 3H-testosterone uptake in hypothalamus and hypophysis of castrated animals. Increase of plasma testosterone level was obtained after the antiandrogen treatment in a dose of 10 or 25 mg/kg per os during 3, 10 and 48 days. Maximal level of the hormone was noticed on the 10th day. The contents of 17-ketosteroids in testes had not changed, but the testosterone content and steroid-delta5-3beta-ol-dehydrogenase activity were high during the treatment period. After 10 days of NFBA administration increased plasma LH level was found. Increase in size and number of gonadotropocytes was revealed by histological and histochemical methods as well as Leydig cell hypertrophy. High plasma testosterone level and Leydig cell activation were obtained in guinea pigs as a result of NFBA subcutaneous injections in a dose of 10 mg/kg during 30 days. The suggestion is made that prolonged NFBA treatment produces changes in the testosterone metabolism. Short-term administration of NFBA may be used for the estimation of the hypothalamo-hypophyseal functional abilities.