Prolonged response of multicentric reticulohistiocytosis to low dose methotrexate

We describe a case of multicentric reticulohistiocytosis complicated by central retinal vein thrombosis and trigeminal neuropathy. A variety of treatment modalities were tried in this patient. Both skin disease and arthritis responded to low dose methotrexate over 8 years of followup. Graduated compression gloves produced an excellent cosmetic improvement in the disfiguring skin lesions.     

Studies of small GTPase Rab7 association with endosomes of cells expressing normal and mutant forms of epidermal growth factor receptors

A study was made of an association of small GTPase Rab7, commonly considered as a marker of late endosomes, with endosomal compartments of cells expressing EGF receptor with different ability to be sorted for degradative pathway. It was found that in cells HER14, expressing normal EGF receptor, Rab7 was associated with both early and late endosomes and the extent of association correlated with the number of EGF-receptor complexes in the specific endosomal fraction. Cels with a receptor, lacking major sites of autophosphorylation by deletion of 126 C-terminal residues (CD126), demonstrated a low efficiency of EGF-receptor sorting to late endosomes and decreased association dynamics with Rab7. Interaction of Rab7 with endosomes of cells expressing kinase negative receptors (K721) was found to be minimal. At the same time, in cells Cd126 and K721 with a low sorting efficiency Rab7 was mainly associated with early endosomes. These data favor Rab7 involvement in mediating early-to-late endosomal transition.     

The characteristics of the technical instrumental support for the osteosynthesis of femoral neck fractures using the Seppo fixator

Operative treatment of fractures of the femur neck is the method of choice. The authors prefer the A. Seppo construction out of great number of fixtures but it is difficult to introduce and remove this fixture due to its complexity. To make the procedure of such interventions easier the authors propose a marking device, a screwdriver and a device allowing the fixture's curvature to be regulated. The modification of the technique and using a specially developed extractor is explained by difficulties in removing the fixture by common methods. The variant of the improved instrumental tooling proposed by the authors makes the operation more handy and practicable.     

Specific strategies in the treatment of young and middle-age patients with spontaneous intracerebral hemorrhage

The paper is based on the analysis of 235 young and middle-age patients with non-traumatic cerebral hemorrhage. Tactics of treatment is determined for each group depending on bleeding localization in accordance with World Health Organization's classification (1981). Operative treatment is recommended for lateral site of hematomas of 25 cm3 and more signs of media structures dislocation of 5 mm and more. With the development of hypertension-hydrocephal syndrome surgical intervention is directed at its elimination and where possible at hematoma's ablation. The amount of operative interventions is limited in case of medial and mixed variants of hemorrhages especially when bleedings affect mesencephal structures. In conditions of a neurosurgical clinic a pharmacotherapy is used as an independent one, as a preparation for surgical treatment as well as during operation and in postoperative period.     

The effect of an original analog of the C-terminal fragment of vasopressin on the behavior of white rats

Ethinylestradiol (EE) has evident paradoxical effects on cancer risk for human breast and hepatic cancer which parallel in some respects its effects on estrogen-induced neoplasms in the hamster kidney and liver. EE has been shown to be only weakly carcinogenic in the hamster kidney, but the most potent carcinogenic estrogen in the hamster liver following prolonged treatment. Unexpectedly, when EE and potent carcinogenic estrogens, such as diethylstilbestrol (DES), 17beta-estradiol (E2) and Moxestrol (MOX), are administered concomitantly, estrogen-induced carcinogenesis in the kidney is completely prevented. In studying this novel finding, we found that, compared with E2 exposure alone, EE at 0.05 and 1.0 nM significantly (P < 0.001) inhibited the rise in proliferation of cultured primary hamster proximal renal tubular (PRT) cells in the presence of E2 (1.0 nM). Consistent with these findings, combined EE + DES treatment for 5.0 months reduced hamster kidney c-myc, c-fos and c-jun RNA expression to 43, 37 and 52%, respectively, compared with levels observed after DES treatment alone. Interestingly, TAM + DES treatment for the same period also resulted in the same low level of RNA expression of these proto-oncogenes. c-MYC, c-FOS and c-JUN protein products were comparably reduced after either EE + DES or TAM + DES treatment. It appears that c-fos expression and c-FOS protein levels in the hamster kidney were more responsive to TAM inhibition. These data demonstrate that EE possesses unique anti-tumorigenic properties in vivo in the hamster kidney. Additionally, the observed anti-estrogen-like effect of EE on cell proliferation of cultured PRT cells suggests that EE may interfere critically with estrogen receptor (ER)-mediated mitogenic pathway(s) affected by potent carcinogenic estrogens, thus preventing subsequent gene dysregulation and, hence, tumor development. Based on competition studies, the differential binding of EE to hamster kidney ER relative to that of the other estrogens (E2, DES, MOX) appears not to contribute to the prevention of estrogen carcinogenesis at this organ site by EE.     

The participation of the serotoninergic system in regulating the activity of the central glutamatergic/aspartatergic and GABA-ergic synapses

Selective lesion of the serotoninergic system diminished the synaptic uptake of 3H-L-glutamic acid and 3H-DL-aspartic acid, as well as the Na+(-dependent) binding of 3H-L-glutamic acid in the cortex and the brain stem. The data obtained suggest an ability of the serotoninergic system to modify presynaptic processes in amino-acidergic neurons of the CNS.     

Alphoidless centromere of a familial unstable inverted Y chromosome

In 1984 the Dental Attitude Questionnaire (DAQ), an instrument for assessing various aspects of a person's attitude toward oral health care, was presented by STOCKWELL & BANTING. The DAQ consists of six content scales, Cynicism, Health Concern, Motivation, Oral Function, Social Aesthetic and Susceptibility, and two validity scales, Halo and Infrequency. A Dutch translation was presented in 1986 by HOOGSTRATEN & BROERS. In order to replicate the factor analysis on the original DAQ as reported by STOCKWELL & BANTING, the present study was undertaken. The results show a change in factor structure from a three factor solution to a two factor solution. A confirmatory factor analysis shows that the original three factor structure of the DAQ is not present in the data collected with the translated version. To account for this change, some possible reasons are discussed.     

Synthesis and in vitro activity of some epimeric 20 alpha-hydroxy, 20-oxime and aziridine pregnene derivatives as inhibitors of human 17 alpha-hydroxylase/C17,20-lyase and 5 alpha-reductase

Some epimeric 20-hydroxy, 20-oxime, 16 alpha, 17 alpha-, 17,20- and 20,21-aziridine derivatives of progesterone were synthesized and evaluated as inhibitors of human 17 alpha-hydroxylase/C17,20-lyase (P450(17) alpha) and 5 alpha-reductase (5 alpha-R). The reduction of 16-dehydropregenolone acetate (3a) was reinvestigated. NaBH4 in the presence of CeCl3 gave better stereo-selectivity for 20 beta-ol [20 alpha/20 beta-OH (4 alpha/4 beta) = 1/2.7] than LTBAH or the Meerwein-Pondroff method reported; reduction with Zn in HOAc formed exclusively 20 alpha-ol (4 alpha b). The 20 alpha- and 20 beta-hydroxy-4,16-pregnadien-3-one (9 alpha) and (9 beta) were synthesized from the alcohols 4 alpha b and 4 beta b. Several 20-oxime pregnadienes and 16 alpha, 17 alpha-, 17,20- and 20,21-aziridinyl-5-pregnene derivatives were also synthesized. LiAlH4 reduction of the 16-en-20-oxime (12b) yielded 20 (R)-(13a) and 20(S)-17 alpha,20-aziridine (13b) and 20(R)-17 beta,20-aziridine (14a). Several compounds inhibited the human P450(17) alpha with greater potency than ketoconzole. The 5 alpha-R enzyme assay showed that while (9 alpha) did not have any activity, (9 beta) and (3b) were potent 5 alpha-reductase (IC50 = 21 and 31 nM) inhibitors with activities similar to finasteride. The 20-oximes (17a) and (17b) were potent dual inhibitors for both 5 alpha-R (IC50 = 63 and 115 nM, compared to 33 nM for finasteride) and P450(17) alpha (IC50 = 43 and 25 nM, compared to 78 nM for ketoconazole).     

Pharmacological correction of lipid peroxidation during hypoxia and possibility to enhance human resistance to high altitude by using preparations of the metabolic type of action

In simulating acute hypoxic hypoxia with the participation of male volunteers, the authors investigated the antihypoxic and antioxidative activity of metabolic drugs (jakton, amtizole succinate, nootropil, probucol, and a mixture which consists of jakton, amtizole succinate, and probucol). The pharmaceuticals were shown to have heterodirectional effects on lipid peroxidative processes. Drugs having a pronounced antioxidative activity (such as probucol and the mixture) promotes oxygen utilization during hypoxia and posthypoxic reoxygenation chiefly by the oxygenase pathway. This rearrangement of oxygen utilization processes caused an increase in human high-altitude resistance. The use of the above drugs is a promising trend in the development of an adaptative response to hypoxia in persons engaged in hazardous jobs.