LPS alters pattern of sickness behavior but does not affect glutathione level in aged male rats

Behavioral symptoms of sickness, such as fever and motor activity are a coordinated set of changes that develop during infection. The aim of study was to compare the sickness behaviour (SB) in healthy old and young rats treated with pyrogenic dose of endotoxin and to check their glutathione level. Before experimentation male Wistar rats were selected according to standard body mass, motor activity, and white blood cells count. Intraperitoneal injection of lipopolysaccharide (LPS) from E. coli was used to provoke SB. The level of liver glutathione, interleukin (IL) -6, deep body temperature (Tb) and motor activity were measured. Glutathione level in old and young rats did not differ significantly. In both young and old rats LPS administration provoked fever (the mean value of Tb was 38.06 ± 0.01 °C in old rats, and 38.19 ± 0.06 °C in young rats). LPS injection affected night-time activity in both groups (12 h averages were 1.56 ± 0.40 counts in old LPS-treated rats vs 2.74 ± 0.53 counts in not-treated old rats and 3.44 ± 0.60 counts for young LPS-treated vs 4.28 ± 0.57 counts for young not-treated rats). The injection of LPS provoked an elevation of plasma IL-6 concentration (from values below the lowest detectable standard in not-treated groups of animals to 6322.82 ± 537.00 pg/mL in old LPS-treated rats and 7415.62 ± 451.88 pg/mL in young LPS-treated rats). Based on these data, we conclude that good health of aged rats prevents decrease in the glutathione level. Old rats are still able to develop SB in response to pyrogenic dose of LPS, although its components have changed pattern compared to young animals.     

Penicillin tolerance in multiply drug-resistant natural isolates of Streptococcus pneumoniae

Five of six multiply drug-resistant clinical isolates of Streptococcus pneumoniae from South Africa demonstrated penicillin tolerance. In contrast to the common wild-type strains of pneumococci, treatment of the tolerant strains with penicillin above the minimum inhibitory concentration did not induce cell wall degradation, lysis, or leakage of intracellular components, and the rate of loss of viability was reduced compared with that of nontolerant strains. While these South African strains contained lower specific activity of autolytic enzyme than did nontolerant strains, the residual autolytic activity (15%-26% of the nontolerant wild type) was much more than that found in lysis-defective laboratory mutants of pneumococci (less than or equal to 1%); the rate of penicillin-induced lysis did not correlate with the specific activity of residual autolysin. Also, in contrast to the complete lysis resistance of lysis-defective mutants to all lytic agents, the tolerant South African strains were resistant primarily to lysis by beta-lactam antibiotics but could still be lysed by other cell wall inhibitors (e.g., cycloserine) and detergents. The penicillin resistance and penicillin tolerance traits could be separated by genetic transformation. We suggest that the drug-specific tolerance of the South African pneumococcal strains is related to some alteration in the control of autolysin activity.     

Vasoactive intestinal peptide induces the synthesis of the cholesterol side-chain cleavage enzyme complex in cultured rat ovarian granulosa cells.

Vasoactive intestinal peptide (VIP) has been identified in ovarian nerves and stimulates steroid secretion from immature ovaries. To gain insight into its mechanism of action, the effect of VIP on the synthesis of the cholesterol side-chain cleavage enzyme complex was studied in ovarian granulosa cells from immature estrogen-primed rats. The cells were cultured for 48 hr in serum-free medium; the proteins were labeled with [35S]methionine; and the synthesis of cytochrome P-450, iron-sulfur protein, and NADPH:iron-sulfur protein reductase was evaluated by electrophoretic analysis after immunoisolation with polyclonal antibodies directed against the bovine adrenal enzymes. VIP at concentrations ranging from 0.001 to 1 microM stimulated 3- to 5-fold the synthesis of cytochrome P-450 and iron-sulfur protein. Peptide NH2-terminal histidine, COOH-terminal isoleucine, which has greater than 50% sequence homology of VIP, stimulated the synthesis of both proteins at approximately 50% of VIP effectiveness. Secretin, another member of the glucagon-secretin family of peptides, which has only 30% sequence homology to VIP, was without effect. Similar results were observed with the NADPH:iron-sulfur protein reductase. VIP-induced synthesis of the cholesterol side-chain cleavage enzyme complex was accompanied by a dose-related increase in cAMP accumulation and progestin formation. It is concluded that VIP regulates the synthesis of the ovarian cholesterol side-chain cleavage enzyme complex, which catalyzes the rate-limiting reaction in progesterone biosynthesis, and that the VIP effect is at least partially mediated through cAMP. It is suggested that a stimulatory action of VIP on the synthesis of ovarian progesterone may contribute to regulating the functional development of the ovary.     

Attempt to eliminate health inequalities in Poland arising at the time of political and economic transformation: Polish 400 Cities Project.

AIM: Epidemiological data show that citizens of small towns and villages have presented worse trends in cardiovascular mortality during the political, social and economic transformation in Poland during past 15 years than citizens of large towns. To try to eliminate these inequalities the Polish 400 Cities Project (P400CP), a large educational and interventional project, was prepared. The project consists of two arms: medical and social interventions. MATERIAL AND METHODS: The main aim of the medical screening intervention in P400CP is to increase detection and control of cardiovascular risk factors in inhabitants of 418 small cities (<8000 inhabitants) and surrounding villages, particularly in men and people of lower education. In 2003 and 2004 the P400CP covered 123 cities. All together, 36 696 subjects aged between 18 and 98 years were examined. In all participants, blood pressure (BP), anthropometric measurements, laboratory tests and questionnaire interviews were performed. The social arm of P400CP is one of multi-level educational intervention. Modern techniques of social psychology and marketing were involved to increase participation in interventions. RESULTS: Only 12.5% of all subjects had normal BP, cholesterol (<190 mg/dl) and glucose (<100 mg/dl in whole capillary blood) levels. During the first screening visit 65.5% of all examined subjects had BP>/=140 mmHg or >/=90 mmHg. The fasting glucose level was increased in 19% of women and 26% of men. Almost two-third of all subjects had a total cholesterol level above the norm. CONCLUSIONS: The prevalence of cardiovascular risk factors in participants of the screening programme P400CP in small towns in Poland was very high. High prevalence and low control of risk factors in participants of the P400CP confirm the decision to target this programme at citizens of small towns and villages.     

Hemorrhagic stroke in a patient requiring long-term anticoagulant treatment

Hemorrhagic stroke is a frequent cause of morbidity and mortality in Poland. It results from disruption of intracranial vessel wall continuity. We report a case of 66-years-old man with prosthetic aortic valve after three ischemic strokes treated with acenocoumarol who was admitted to hospital with vertigo and motoric aphasia. Computed tomography confirmed a hemorrhagic stroke related to anticoagulant treatment. We discussed the principles of management and therapeutic options in patients requiring long-term anticoagulation suffering from severe hemorrhagic complications.     

Percutaneous peripheral interventions in patients with non-ST elevation acute coronary syndromes performed by interventional cardiologists: rationale and results

BACKGROUND: The coexistence of peripheral artery disease (PAD) and multilevel atherosclerosis increases death and stroke rates in patients with coronary artery disease (CAD). Due to many comorbidities these patients are often treated conservatively without revascularisation. AIM: To investigate whether complex percutaneous cardiovascular interventions for CAD and PAD may improve prognosis and long-term outcome in this group of patients. METHODS: We studied consecutive patients treated for symptomatic CAD who also had chronic PAD. The primary cause of hospital admission for all our patients was non-ST elevation acute coronary syndrome (NSTE ACS). All percutaneous peripheral interventions were performed during one hospital stay (index hospitalisation). Major adverse cardio- and cerebrovascular events (MACCE) during follow-up were defined as follows: death (cardiac and non-cardiac), myocardial infarction (MI), urgent revascularisation (surgical or repeat PCI, peripheral percutaneous intervention), stroke/TIA or amputation. RESULTS: We performed 109 interventions in 78 consecutive patients with chronic peripheral artery stenoses and occlusions. The average age was 61.5+/-8.6 years and the majority were males (80%). Preinterventional angiography showed occlusions that involved the common iliac artery in 28 (36%) patients, the external iliac artery in 16 (21%) patients, internal iliac artery in 2 (3%) patients, and superficial femoral artery in 63 (81%) patients. Stenting was performed in half of the patients with a mean stent length of 69.6+/-50.3 mm. An average number of 1.24+/-0.55 stents was used for each lesion. During a mean follow-up of 18 months (range 4 to 42), there were 4 deaths, 3 MIs, 13 repeated percutaneous peripheral interventions due to restenosis in previously treated peripheral lesions, two urgent coronary interventions, two ischaemic strokes, two TIAs and one amputation. The combined follow--up MACCE end-point occurred in 32% of patients. CONCLUSIONS: Patients with concomitant CAD and PAD could safely undergo percutaneous cardiovascular and peripheral interventions. Multilevel intervention is associated with a promising long-term follow-up.     

Lack of association of interleukin-18 gene polymorphisms with susceptibility of Japanese populations to Graves' disease or Graves' ophthalmopathy.

OBJECTIVE: To investigate whether polymorphisms of interleukin (IL)-18 gene confer susceptibility to Graves' disease (GD) and Graves' ophthalmopathy (GO). DESIGN: We performed a case control study on polymorphisms of IL-18 gene in Japanese patients with GD (n = 435), and healthy control subjects without antithyroid autoantibodies or family history of autoimmune disorders (n = 255). The C-4675G, C-607A, and G-137C polymorphisms in the promoter region and A105C (exon 5) polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using restriction enzymes, sequence-specific PCR, and PCR-direct sequencing methods. RESULTS: None of the polymorphisms in the IL-18 gene were associated with development of Graves' disease. The CC genotype and C allele frequencies of IL-18 gene G-137C polymorphism tended to be greater in patients with ophthalmopathy than in patients without evident ophthalmopathy. However, the differences were not statistically significant. Although there were three major haplotypes, none of the haplotypes were statistically associated with susceptibility to GD or ophthalmopathy. CONCLUSIONS: These results suggest that IL-18 gene polymorphisms are not major genetic factors for susceptibility to GD in a Japanese population. Further studies with adequate sized data set in the subset analyses for GO are needed.