Decreased tolerance to acoustic stress in late postresuscitation period in Krushinsky-Molodkina rats

The effect of circulation arrest on the development of stress-induced injuries was studied in Krushinsky—Molodkina rats genetically predisposed to audiogenic seizure. Resuscitated rats were subjected to acoustic stress 1.5 month after circulation arrest. The severity of neurological disorders and the frequency and severity of intracranial hemorrhages increased, while excitability of the central nervous system remained unchanged during stress. Thus, the resistance to stress considerably decreased in rats survived a short-term circulatory arrest due to dysfunction of the autonomic nervous regulation of hemodynamics rather than enhanced excitability of the central nervous system. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 17–19, June, 2000     

The Effects of Rituximab on Lipids,Arterial Stiffness and Carotid Intima-Media Thickness in Rheumatoid Arthritis

The aim of the study was to examine lipid profiles, arterial stiffness (AS), carotid intima-media thickness (cIMT), in 55 women with RA without overt cardiovascular disease (СVD) treated with rituximab (RTX).The following parameters were recorded before and 24 weeks after RTX therapy (2 infusions of 500 or 1,000 mg RTX intravenously, fortnightly): plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, DAS 28-ESR, serum C-reactive protein (CRP), RF IgM, AS (SI - stiffness index, RI – reflection index) by digital volume pulse contour analysis (Micro Medical, UK), and common cIMT by high-resolution B-mode carotid ultrasound. Based on the European League Against Rheumatism (EULAR) criteria, patients were divided into two groups: 1) moderate/good response to RTX therapy after 24 weeks (41 patients, 75%), 2) no response to RTX therapy (14 patients, 25%). Effective RTX therapy resulted in 9% increase in TC, 23% increase in HDL-C and 14% decrease in atherogenic index, 57% decrease in SI and 24% decrease in RI. We observed a 9% decrease of cIMTmax at 24 weeks. The improvement of cardiovascular parameters was accompanied by statistically significant decreases of CRP, ESR, RF IgM and DAS 28 in group 1 (P < 0.05). There were not significant changes in lipid profile, AS parameters, and cIMT in group 2. Two infusions of RTX in case of moderate/good EULAR effect of therapy exerted favorable effects on lipid profile, AS and cIMT in women with RA without overt CVD.     

Novel therapeutic compound tuftsin–phosphorylcholine attenuates collagen‐induced arthritis

Treatment with helminthes and helminthes ova improved the clinical symptoms of several autoimmune diseases in patients and in animal models. Phosphorylcholine (PC) proved to be the immunomodulatory molecule. We aimed to decipher the tolerogenic potential of tuftsin–PC (TPC), a novel helminth‐based compound in collagen‐induced arthritis (CIA) a mouse model of rheumatoid arthritis (RA). CIA DBA/1 mice were treated with TPC subcutaneously (5 µg/0.1 ml) or orally (250 µg/0.1 ml), starting prior to disease induction. The control groups were treated with PBS. Collagen antibodies were tested by enzyme‐linked immunosorbent assay (ELISA), cytokine protein levels by ELISA kits and regulatory T (T_reg) and regulatory B (B_reg) cell phenotypes by fluorescence‐activated cell sorter (FACS). TPC‐treated mice had a significantly lower arthritis score of 1.5 in comparison with control mice 11.8 (P < 0.0001) in both subcutaneous and orally treated groups at day 31. Moreover, histology analysis demonstrated highly inflamed joints in control mice, whereas TPC‐treated mice maintained normal joint structure. Furthermore, TPC decreased the titres of circulating collagen II antibodies in mice sera (P < 0.0001), enhanced expression of IL‐10 (P < 0.0001) and inhibited production of tumour necrosis factor (TNF)‐α, interleukin (IL)?17 and IL‐1β (P < 0.0001). TPC significantly expanded the CD4⁺CD25⁺ forkhead box protein 3 (FoxP3⁺) T_reg cells and CD19⁺IL‐10⁺CD5^highCD1d^highT cell immunoglobulin mucin‐1 (TIM‐1⁺) B_reg cell phenotypes (P < 0.0001) in treated mice. Our data indicate that treatment with TPC attenuates CIA in mice demonstrated by low arthritic score and normal joints histology. TPC treatment reduced proinflammatory cytokines and increased anti‐inflammatory cytokine expression, as well as expansion of T_reg and B_reg cells. Our results may lead to a new approach for a natural therapy for early rheumatoid arthritis onset.     

Tuftsin–phosphorylcholine (TPC) equally effective to methylprednisolone in ameliorating lupus nephritis in a mice model

The role of helminth treatment in autoimmune diseases is growing constantly. Systemic lupus erythematosus (SLE) is a multi‐system autoimmune disease with challenging treatment options. Tuftsin–phosphorylcholine (TPC) is a novel helminth‐based compound that modulates the host immune network. This study was conducted to evaluate the potential value of TPC in ameliorating lupus nephritis in a murine model and specifically to compare the efficacy of TPC to the existing first‐line therapy for SLE: corticosteroids (methylprednisolone). Lupus‐prone NZBxW/F₁mice were treated with TPC (5 µg/mouse), methylprednisolone (MP; 5 mg/body weight) or phosphate‐buffered saline (PBS) (control) three times per week once glomerulonephritis, defined as proteinuria of grade > 100 mg/dl, was established. Levels of anti‐dsDNA autoantibodies were evaluated by enzyme‐linked immunosorbent assay (ELISA), splenic cytokines were measured in vitro and the kidney microscopy was analysed following staining. TPC and MP treatments improved lupus nephritis significantly and prolonged survival in NZBxW/F₁ mice. TPC‐treated mice showed a significantly decreased level of proteinuria (P < 0·001) and anti‐dsDNA antibodies (P < 0·001) compared to PBS‐treated mice. Moreover, TPC and MP inhibited the production of the proinflammatory cytokines interferon IFN‐γ, interleukin IL‐1β and IL‐6 (P < 0·001) and enhanced expression of the anti‐inflammatory cytokine IL‐10 (P < 0·001). Finally, microscopy analysis of the kidneys demonstrated that TPC‐treated mice maintained normal structure equally to MP‐treated mice. These data indicate that the small molecule named TPC hinders lupus development in genetically lupus‐prone mice equally to methylprednisolone in most of the cases. Hence, TCP may be employed as a therapeutic potential for lupus nephritis.     

Effects of temporal lobe epilepsy on retrograde memory

PURPOSE: In a previous investigation (Lah et al., 2004), we found deficits in retrograde memory in patients who had undergone temporal lobectomy (TL). In this study, we set out to determine whether such deficits are present before surgery in patients with temporal lobe epilepsy (TLE). METHODS: Memory for public and autobiographic facts and events was assessed in patients with focal left-sided (n=15) or right-sided (n=14) TLE and healthy control subjects (n=15). The impact of epilepsy and underlying cognitive deficits on retrograde memory also was examined. RESULTS: Patients with left TLE demonstrated retrograde memory deficits across domains. Patients with right TLE showed defective recall only in the autobiographic domain. Young age at onset (younger than 14 years) was associated with greater difficulties in recall of famous events, and patients receiving polytherapy had significantly reduced recall of autobiographic events compared with those receiving monotherapy. In most cases, deficient memory for the past was associated with impairments in other cognitive skills, especially language abilities. CONCLUSIONS: In unoperated-on patients with TLE, we found deficits in retrograde memory that were similar to those seen after TL, with the pattern of deficits being influenced by side of lesion, anticonvulsant medication, and word-finding deficits. Unlike patients tested after right TL, patients with right TLE did not have difficulty recalling details of famous events, which raises the possibility that right TL results in a decline in this aspect of retrograde memory.     

Toxico-genetic risk factors for adolescents living in a large industrial city

Cytogenetic study of adolescents in a large industrial city (n = 211) and donors (n = 41) showed an increase in the number of chromosomal aberrations per 100 lymphocytes in urban adolescents from 1.58 +/- 0.41 in 1992 to 4.53 +/- 0.48 in 1996. A significant increase in the spontaneous level of aberrations (2.02 +/- 0.21) was observed starting from 1993. Time course of the number of chromosomal aberrations and components of the environment (radiation background, chemical pollution of potable water, foodstuffs, and atmospheric air) in the city of Kemerovo in 1992-1996 are compared. According to the data of analysis of correlations, the most significant genotoxicants are nitrogen oxide (II), methanol, and benz(a)pyrene.     

The effect of smoking on the long-term outcome of closure of perforated gastric and duodenal ulcer]

Examined were 164 patients at the long-term period after closure of a perforative ulcer of the stomach and duodenum. The negative effect of smoking on acid production and protective barrier of gastroduodenal mucosa leading to worsened healing of an ulcer closed and its recurrence in 50% of the patients operated on has been established. It was noted that in smokers, irrespective of a number of the cigarettes being smoked, an excellent and good long-term result was observed 2.5 times less often, and a poor one--3 times more often than in non-smokers.