Psoriasis and drugs: influence of tetracyclines on the course of psoriasis

Patients with psoriasis vulgaris (462) were studied by questionnaire to find the effect on psoriasis of drug therapy for intercurrent diseases or focal infections. Of 462 patients with psoriasis, in 76 (16.45%) the disease became more severe during drug therapy. Of these, 19 worsened after administration of tetracyclines, and in five psoriasis was precipitated after therapy with drugs of the tetracycline family. We suggest that tetracyclines should be avoided in patients with psoriasis and in healthy persons with a genetic predisposition (positive family history, human leukocyte antigens B13, B17, B27).     

Transport and signaling through the phosphate-binding site of the yeast Pho84 phosphate transceptor

A novel concept in eukaryotic signal transduction is the use of nutrient transporters and closely related proteins as nutrient sensors. The action mechanism of these “transceptors” is unclear. The Pho84 phosphate transceptor in yeast transports phosphate and mediates rapid phosphate activation of the protein kinase A (PKA) pathway during growth induction. We have now identified several phosphate-containing compounds that act as nontransported signaling agonists of Pho84. This indicates that signaling does not require complete transport of the substrate. For the nontransported agonist glycerol-3-phosphate (Gly3P), we show that it is transported by two other carriers, Git1 and Pho91, without triggering signaling. Gly3P is a competitive inhibitor of transport through Pho84, indicating direct interaction with its phosphate-binding site. We also identified phosphonoacetic acid as a competitive inhibitor of transport without agonist function for signaling. This indicates that binding of a compound into the phosphate-binding site of Pho84 is not enough to trigger signaling. Apparently, signaling requires a specific conformational change that may be part of, but does not require, the complete transport cycle. Using Substituted Cysteine Accessibility Method (SCAM) we identified Phe¹⁶⁰ in TMD IV and Val³⁹² in TMD VIII as residues exposed with their side chain into the phosphate-binding site of Pho84. Inhibition of both transport and signaling by covalent modification of Pho84^F160C or Pho84^V392C showed that the same binding site is used for transport of phosphate and for signaling with both phosphate and Gly3P. Our results provide to the best of our knowledge the first insight into the molecular mechanism of a phosphate transceptor.     

Synthesis and effect of biguanide derivatives on biochemiluminescence and level of reduced glutathione in rat blood serum and brain under ischemia-reperfusion conditions

We have studied the effect of the newly synthesized biguanides N-[amino(imino)methyl]morpholine-4-carboximidamide (I) and N-[amino(imino)methyl]piperidine-1-carboximidamide (II) on biochemiluminescence (BCL) parameters including (i) lightsum (S) and maximum flash intensity (I _max), which characterize the level of free-radical processes, and (ii) the slope of the BCL kinetic curve (tan α₂), which characterizes general antioxidant activity, and on the reduced glutathione level in rats brain and blood serum under post-ischemic reperfusion conditions. It was found that the investigated parameters, which increased in response to the development of oxidative stress with brain pathology, changed toward normalization under the influence of the biguanides. A dose-dependent action of these substances has been established. The administration of I and II in 25 and 50 mg/kg led to the most pronounced decrease in the BCL parameters and reduced glutathione concentration while 12.5 and 75 mg/kg doses did not lead to significant changes in the studied parameters. The results show that biguanides introduced in certain doses can decrease the free-radical oxidation level and produce a neuroprotective effect.     

Effect of mesodiencephalic modulation on small intestinal mucosa after massive blood loss in rats

Effect of mesodiencephalic modulation on small intestinal mucosa was studied in rats subjected to massive blood loss. Massive blood loss induced structural changes in intestinal epitheliocytes typical of tissue hypoxia: intraintestinal edema, mitochondrial alterations, and microcirculation disturbances. A single session of mesodiencephalic stimulation carried out 60 min after massive blood loss produced a pronounced adaptive effect, restored disturbed structure of the intestinal villi, and induced compensatory hypertrophy of the mitochondria. This suggests that mesodiencephalic modulation promotes normalization of intracellular energy metabolism, improves the absorption capacity of bordered enterocytes, and restores the disturbed intestinal barrier.     

Electrophysiological effects of ethacizine in experimental myocardial infarction and stimulation of sympathetic heart innervation

The electrophysiological effect of ethacizine, an antiarrhythmic agent of class IC, was studied in dogs with experimental myocardial infarction under the beta-adrenergic stimulation conditions. It was found that ethacizine (i) slows down the atrioventricular conduction and the AV-node conduction; (ii) increases the time of the sinus node function recovery; and (iii) increases the effective atrioventricular refractory periods. Under the conditions of isoproterenol-induced stimulation of the beta-adrenergic structures, some of the ethacizine effects (e.g., increased refractoriness) completely disappeared and the other (slowed down conduction) decreased. As the stimulation frequency was increased, the effect of ethacizine upon the conduction exhibited a decrease. Upon the isoproterenol injection, dependence of the QRS complex on the forced rhythm frequency disappeared.     

Surgical treatment of multiple primary neoplasms

Comparison of two groups of patients with polyneoplasia was carried out: in group 1 surgeries were performed simultaneously, in group 2--at different time. Choice of surgical technique seems to depend on the time between detection of the tumors. When polyneoplasias were revealed at the same time, surgeries were performed simultaneously. These operations were conducted more often when the tumors were localized in organs accessible by one surgical approach. When multiple synchronous tumors located in various anatomic regions consecutive operations were performed more often. The stage of the tumor does not influence the choice of time of operation for the first and second tumor. Simultaneous operations are preferable for young patients without concomitant diseases.     

Evaluation of immunity in children from rural localities and the levels of trace elements in environmental objects

Immunity was evaluated in 890 schoolchildren living in rural localities of the Central and Western lands of the Orenburg Region. There was a correlation between the immunological parameters of the examinees and the levels of trace elements in environmental objects. The children's immunity showed unilateral changes in the studied parameters as compared with the regional standards. The closest correlation was found between the absolute count of T lymphocytes, stab neutrophils, the levels of IgA, IgM in children and the content of I, Sr, Mn, Cr in cereals and vegetables, as well as between the levels of IL-2 and alpha-TNF and the blood concentrations of Cu, Fe, Cr, Ni, Co in the examined children. The immunological changes may result from the imbalance of trace elements in the studied environmental objects and biological substrates.     

Clinical picture and differential diagnosis of anterior granulomatous uveitis

Nineteen patients with anterior endogenous granulomatous uveitis were examined. Tuberculous and sarcoidosal anterior uveites run by and large similarly, but have some differences. Valid etiological diagnosis of granulomatous uveites requires a complex approach with consideration of extraocular manifestations.     

Model of normal prepubertal growth

Overheating may cause terminal apnoea and cot death. Rectal temperature and breathing patterns were examined in normal infants at home during the first 6 months of life. Twenty one infants had continuous overnight rectal temperature and breathing recordings for 429 nights (mean 20.4 nights, range 7-30) spaced over the first six months of life. Periods when breathing was 'regular' were directly marked on single night records. Sleep state was determined from respiratory variables. 'Regular' breathing was a reliable marker of 'quiet' sleep (specificity 93%). The duration of 'quiet' sleep increased from 6 to 22 minutes from two weeks to three months of age and then remained static, as did the proportion of sleep spent in the quiet phase (9% to 34%). Rectal temperature fell during 66% of quiet sleep and usually rose during rapid eye movement (REM) sleep. The drop in rectal temperature was maximal at the start of quiet sleep, whereas the maximum rise during REM sleep was reached after 10 to 15 minutes. Oscillations in rectal temperature are associated with changes in sleep and breathing state. The maturation of rectal temperature patterns during the first six months of life are closely related to a maturation of sleep state and breathing patterns.