[Correcting effect of the locus coeruleus on ophthalmic hypertension of the hypothalamic genesis]. / Korrigiruiushchee vliianie sinego piatna mozga na oftal'mogipertenziiu gipotalamicheskogo geneza.

We studied the intraocular pressure and the humor aquosus volume changes after a chronic emotional stress produced by a prolonged electrical stimulation of the multiple ventromedial (VMHN) hypothalamic nuclei and the locus coeruleus. The VMHN stimulation caused an increase in the intraocular pressure and production of the humor aquosus, as well as a decrease in the outflow ratio. Stimulation of the locus coeruleus increased the intraocular pressure to a lesser extent. A combined effect of both types of stimulation normalised the intraocular pressure due to a decrease in the humor aquosus production, the outflow ratio remaining unchanged.

Endogenous regulation of a therapeutic transgene restores homeostasis in arthritic joints.

The treatment of chronic inflammatory diseases is complicated by their unpredictable, relapsing clinical course. Here, we describe a new strategy in which an inflammation-regulated therapeutic transgene is introduced into the joints to prevent recurrence of arthritis. To this end, we designed a recombinant adenoviral vector containing a two-component, inflammation-inducible promoter controlling the expression of human IL-10 (hIL-10) cDNA. When tested in vitro, this system had a low-level basal activity and was activated four to five orders of magnitude by various inflammatory stimuli, including TNF-alpha, IL-1 beta, IL-6, and LPS. When introduced in joints of rats with recurrent streptococcal cell wall-induced arthritis, the IL-10 transgene was induced in parallel with disease recurrence and effectively prevented the influx of inflammatory cells and the associated swelling of the joints. Levels of inflammation-inducible hIL-10 protein within the joints correlated closely with the severity of recurrence. An endogenously regulated therapeutic transgene can thus establish negative feedback and restore homeostasis in vivo while minimizing host exposure to the recombinant drug.

NF-kappaB activation provides the potential link between inflammation and hyperplasia in the arthritic joint.

The transcription factor NF-kappaB is a pivotal regulator of inflammatory responses. While the activation of NF-kappaB in the arthritic joint has been associated with rheumatoid arthritis (RA), its significance is poorly understood. Here, we examine the role of NF-kappaB in animal models of RA. We demonstrate that in vitro, NF-kappaB controlled expression of numerous inflammatory molecules in synoviocytes and protected cells against tumor necrosis factor alpha (TNFalpha) and Fas ligand (FasL) cytotoxicity. Similar to that observed in human RA, NF-kappaB was found to be activated in the synovium of rats with streptococcal cell wall (SCW)-induced arthritis. In vivo suppression of NF-kappaB by either proteasomal inhibitors or intraarticular adenoviral gene transfer of super-repressor IkappaBalpha profoundly enhanced apoptosis in the synovium of rats with SCW- and pristane-induced arthritis. This indicated that the activation of NF-kappaB protected the cells in the synovium against apoptosis and thus provided the potential link between inflammation and hyperplasia. Intraarticular administration of NF-kB decoys prevented the recurrence of SCW arthritis in treated joints. Unexpectedly, the severity of arthritis also was inhibited significantly in the contralateral, untreated joints, indicating beneficial systemic effects of local suppression of NF-kappaB. These results establish a mechanism regulating apoptosis in the arthritic joint and indicate the feasibility of therapeutic approaches to RA based on the specific suppression of NF-kappaB.

[Infectious complications in patients in the terminal stages of chronic renal insufficiency]. / Infektsionnye oslozhneniia u bol'nykh s terminal'noi stadiei khronicheskoi pochechnoi nedostatochnosti.

Characteristics of infectious complications were investigated in 112 patients at the terminal stage of renal insufficiency treated by programme hemodialysis. High frequency of sepsis (32.4 per cent), urinary tract infections (27.7 per cent), respiratory tract infections (26.4 per cent) and tuberculosis (5.6 per cent) was stated. The lethal outcomes of the infectious complications averaged 20.3 per cent.

[Lomefloxacin pharmacokinetics in patients in the terminal stage of chronic renal insufficiency, undergoing treatment with programmed hemodialysis]. / Farmakokinetika lomefloksatsina u bol'nykh v terminal'noi pochechnoi nedostatochnosti, nakhodiashchikhsia na lechenii programmnym gemodializom.

The most frequent complications in patients with the terminal stage of chronic renal insufficiency are infections of various severity. The problem of the antibacterial therapy choice is especially urgent because of a high frequency of antibiotic resistant strains and the necessity to correct the treatment regimens in regard to the severity of the renal failure. The pharmacokinetics of lomefloxacin, a new fluoroquinolone, was studied in the treatment of patients with the terminal stage of chronic renal insufficiency treated by programmed hemodialysis. Lomefloxacin was administered orally in a dose of 400 mg at an interval of 48 hours 24 hours prior to the hemodialysis application. There was observed a decrease in the maximum serum concentration of the drug by comparison to that in healthy persons which could be due to slow absorption of the drug and hyperhydration in the patients because of anuria. In the treatment of such patients it is necessary to provide high serum concentrations of lomefloxacin attainable by using higher single doses of the drug.

[Biochemical study of the A2F4 antigen associated with human pulmonary adenocarcinoma]. / Biokhimicheskoe izuchenie antigena A2F4, assotsiirovannogo s adenokartsinomoi legkogo cheloveka.

The tissue-specific antigen associated with human lung adenocarcinoma had been investigated using immunological and biochemical methods. The antigen, which represents a new tissue-specific marker, has a molecular weight of 400 kDa. Purification of the antigen was achieved by gel chromatography. Antibody binding to the antigen was studied using enzyme-linked immunoassay after preincubation with enzymes or treatment with periodate. The results obtained testify to the proteinaceous nature of the antigenic determinant and the glycoprotein nature of the antigen.

[Intensive therapy of DIC-syndrome in patients with acute renal insufficiency caused by long-term crush syndrome]. / Intensivnaia terapiia DVS-sindroma u bol'nykh s ostroi pochechnoi nedostatoch-nost'iu, obuslovlennoi sindromom dlitel'nogo sdavleniia.

Impairment of parenchymatous organs, primarily kidneys, responsible for their dysfunction in crush syndrome results in many respects from disseminated intravascular coagulation (DIC). It is also associated with hemorrhagic complications. It is demonstrated that treatment modalities aimed at arrest of DIC syndrome (plasmapheresis, heparin, dysaggregation drugs, transfusions of large amounts of fresh frozen plasma) stopped bleeding and septic shock in 12 patients with crush syndrome following the earthquake in Armenia (1988).

[The results of using pseudoplasmapheresis in bronchial asthma (a preliminary report)]. / Rezul'taty primeneniia lozhnogo plazmafereza pri bronkhial'noi astme (predvaritel'noe soobshchenie).

The authors provide the results of the treatment of 15 patients with infectious bronchial asthma by plasmapheresis (PA). All the patients received PA in accordance with the techniques developed by the authors. These techniques simulate standard procedures using a plasticized container and a refrigerator centrifuge. As a result of the studies carried out, it has been concluded that the clinical efficacy of false PA is similar to that of routine PA as regards the clinical manifestations of bronchial asthma. Apparently, the elimination effect and the effect of red blood cells plasma withdrawal are of no material importance in the mechanism by which PA influences bronchial asthma. The psychosomatic causes, effects of temporary blood loss, blood contact with polymeric materials, and the influence of temporary blood cooling may be under discussion.

[Relation between arterial hypertension and disorder of erythrocyte deformability in patients with chronic renal failure]. / O sviazi mezhdu arterial'noi gipertoniei i narusheniem deformiruemosti éritrotsitov u bol'nykh s khronicheskoi pochechnoi nedostatochnost'iu.

A total of 29 patients with chronic renal insufficiency (CRI) were investigated. Noticeable disorder of erythrocytic deformability (ED) was detected in half of them. The expression of arterial hypertension showed correlation with a degree of ED disorder. A possibility of the main role of ED disorder in the development and progression of arterial hypertension was discussed. ED disorder was found to correlate with a degree of expression of laboratory signs of the DIC-syndrome and was practically unassociated with the blood level of creatinine.

[Use of plasmapheresis in the nephrotic syndrome]. / Primenenie plazmafereza pri nefroticheskom sindrome.

Plasmapheresis efficacy was demonstrated in the treatment of the nephrotic syndrome as a manifestation of various types of glomerulonephritis. Plasmapheresis could be used independently for the treatment of the nephrotic syndrome. It was shown to be a method of choice in case of the impossibility of common therapy. Plasmapheresis was well tolerated by patients causing no complications.

[Correction of blood rheological disorders in patients with chronic kidney failure using heparin and antiaggregants]. / Korrektsiia gemoreologicheskikh narushenii u bol'nykh s khronicheskoi pochechnoi nedostatochnost'iu geparinom i dezagregantami.

The state of microcirculation and blood rheology was studied in 32 patients with chronic renal insufficiency. Improved microcirculation and the reduction of clinico-laboratory indices of the DIC-syndrome were noted against a background of heparin and antiaggregant therapy in patients on programmed hemodialysis as well as in patients receiving systemic conservative therapy. In both groups of patients blood pressure decreased in parallel with a decrease in the level of creatinine and urea; a tendency toward improved renal function was noted.