Red blood cell deformability in patients with claudication after pain-free treadmill training.

OBJECTIVES: To assess the effect of pain-free treadmill training on red blood cell deformability and walking distance in patients with claudication. DESIGN: Randomized-controlled trial of exercise training. SETTING: Patients were recruited from the primary care, vascular outpatient clinic. PATIENTS: A total of 60 patients with peripheral arterial occlusive disease (stage II according to Leriche-Fontaine) were randomized into the treadmill program or a control group. Fifty-five patients completed the study (27 in the exercising group and 28 in the control group). INTERVENTIONS: Patients in the exercising group were walking on the treadmill 3 times a week for 3 months. Each session consisted of 1 hour repetitive walking [performed to 85% of the pain-free walking time (PFWT)] was supervised by a qualified physiotherapist. MAIN OUTCOME MEASUREMENTS: Changes in erythrocyte deformability and treadmill walking performance (PFWT, maximal walking time) were assessed in both groups before the study and after 3 months. RESULTS: After 3 months of treadmill training, red blood cell deformability in the exercising group significantly increased (P<0.01). No significant changes were seen in the erythrocyte deformability in the control group. PFWT was prolonged by 102% from 191+/-34 to 386+/-60 seconds (P<0.01), and maximal walking time increased by 49% from 438+/-62 to 656+/-79 seconds (P<0.01) in the exercising group, whereas these changes were insignificant in the control group. CONCLUSIONS: A significant improvement of walking ability over 3 months of pain-free treadmill training is associated with a significant increase in red cell deformability in patients with claudication.     

When the standards aren't standard: Evidence-based medicine in the Russian context

This paper examines the uses of evidence-based medicine (EBM) in post-Soviet Russia through the use of semi-structured interviews. It asks what it means to talk about practicing evidence-based medicine in a setting where the context of practice presents considerable barriers to the implementation of EBM principles. Drawing on interviews with Russian physicians, medical students and users of the healthcare system, the paper argues that in post-Soviet Russia EBM serves as a strategic discourse for segments of the medical profession. With the collapse of the U.S.S.R. the healthcare system has been going through a period of crisis, and Russian physicians are finding that they have to redefine their professional identity with respect to the domestic and the international context and have to seek new sources for legitimating their professional position. The western origins of EBM endow this rhetoric with considerable power in the Russian context and render it a very useful tool in the project of redefinition.     

Knee joint proprioception evaluation with own construction device]

Proprioception is a term covering together joint position sense, kinesthesia and integration of these stimuli in the central nervous system which is needed to keep homeosthasis of joints during motion. The aim of this study is to present authors originally created measuring device working according to the principles of Barrett, aiming at evaluation of proprioception of the knee. The construction of this device is based on the Summer chair, model UPR-01B, working in connection with Bosh goniometer DWM-40L measuring angles with a precision of 0,1 degree. The device presented in this study fulfills all criteria required for this kind of apparatus and may be an alternative to other constructs produced commercially and available on the market.     

Protective effect of tissue ferritins in experimental Escherichia coli infection of mice in vivo.

The effect of ferritins from horse (FH) and bovine (FB) spleen and murine liver (FM) on the survival rate of CFW mice lethally infected with Escherichia coli (strain 8440-78 K 80/B) was evaluated. Ferritins given intravenously 24 h before intravenous inoculation of bacteria, protected mice most effectively from death due to infection. The effect was dose dependent. At 500 micrograms of ferritin per mouse, the maximum survival rates were 86% (FH), 81% (FM) and 79% (FB), while only 5% of the control mice survived up to the 30th day. The survival rates of animals injected with bovine serum albumin (BSA) and heat-inactivated FB were 8 and 25%, respectively. Intraperitoneal injection of FB was as effective as intravenous in enhancing the resistance of mice against bacteria. These data provide evidence for the beneficial role of tissue ferritins in nonspecific antibacterial resistance.     

ReProComet: a new in vitro method to assess DNA damage in mammalian sperm.

The increasing request of chemical safety assessment demands for the validation of alternative methods to reduce the resort to animal experimentation. Methods that evaluate reproductive toxicity are among those requiring the largest use of animals. Presently, no validated in vitro alternative exists for the assessment of reproductive toxicity. Mammalian sperm are sensitive targets of DNA-reactive chemicals, which form premutagenic adducts. Here, we propose a new method based on comet assay to detect DNA damage induced by potential germ cell mutagens in bull sperm available from assisted reproduction practices. In somatic cells, chemical-induced adducts can be revealed by comet assay that detects DNA breaks produced during adduct repair. Mature sperm, however, are devoid of repair enzymes, and adducts are processed only after fertilization. For this reason, comet assay is not sensitive to detect DNA lesions induced in sperm by most chemicals. To overcome such limitation, we developed a modified comet assay based on the addition of a protein extract from HeLa cells to agarose-embedded sperm on microscopic slides. To test the method, sperm were treated in vitro with methyl methanesulfonate (MMS) or melphalan (MLP) and comet assay was conducted both with and without protein supplementation. No effect of MMS or MLP was detected without protein supplementation; on the contrary, a clear-cut dose-dependent effect was measured after addition of the cell extract. These results represent a proof of concept of a novel in vitro mutagenicity test on sperm that could offer a promising approach to complement previously validated in vivo germ cell genotoxicity assays.     

Thyrotrophin-Releasing Hormone Raises Cytosolic Free Calcium Concentration in Human Adenomatous Somatotrophs and Corticotrophs; Comparison with in vivo Responsiveness to Thyrotrophin-Releasing Hormone in Patients with Acromegaly or Cushing's Disease

The effect of thyrotrophin-releasing hormone (TRH) on intracellular free Ca²⁺ concentration, [Ca²⁺)i, was investigated with the fluorescent dye fura-2 in cell suspensions obtained from 13 human growth hormone-secreting adenomas and 6 adrenocorticotrophin-secreting adenomas. Preoperatively, 9 out of 13 acromegalic patients showed a positive growth hormone response to TRH administration while none of the 6 patients with Cushing's disease had a plasma adrenocorticotrophin increase after TRH injection. In all the growth hormone-secreting adenomas the addition of TRH (100 nM) caused a significant rise in [Ca²⁺]i (from a resting level of 133±40 (±SD) to a value of 284±119 nM at 100 nM TRH, n = 42; P<0.001). The transient induced by TRH was found to have a dual origin, one due to Ca²⁺ mobilization from intracellular stores which was maintained in presence of EGTA (3mM) and verapamil (10 μM) and a plateau phase due to Ca²⁺ influx from the extracellular media. Somatostatin (0.1 μM) lowered both resting [Ca²⁺]i and TRH-induced transients. The effect of gonadotrophin-releasing hormone on [Ca²⁺]i was evaluated on cell suspensions obtained from 6 growth hormone-secreting adenomas. Gonadotrophin-releasing hormone (100 nM) caused a marked rise in [Ca²⁺]i (from 179±25 to 283±15nM) on the cell suspension obtained from the only in vivo responsive adenoma while it was ineffective in the remaining 5. Although TRH was ineffective in modifying plasma adrenocorticotrophin levels in all patients with Cushing's disease, in 5 out of 6 tumors the addition of 100 nM TRH caused a significant rise in [Ca²⁺]i (from 102.5 ± 36 to 163±66 nM, n = 22; P < 0.005). However, the effect of TRH on [Ca²⁺]i was significantly lower than that caused by arginine vasopressin, a physiological stimulator of adrenocorticotrophin release ([Ca²⁺]i values; 145±78 nM at 100 nM TRH versus 300±140 at 10 nM arginine vasopressin, n = 15; P<0.05). Moreover, the effect of arginine vasopressin on [Ca²⁺]i was detectable at concentrations as low as 0.1 nM while TRH was effective at concentrations higher than 1 nM. By contrast, gonadotrophin-releasing hormone was ineffective in increasing [Ca²]i in all the adrenocorticotrophin-secreting adenomas studied. Collectively, these data indicate that sensitivity to TRH is present in almost all the growth hormone- and adrenocorticotrophin-secreting adenomas independently of the responsiveness of the individual patients to the peptide.     

Stimulation of corticosterone secretion by the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the rat

The selective 5-HT1A receptor agonist 8-OH-DPAT increased serum corticosterone concentration in rats in a dose-dependent manner. The synthetic corticoid dexamethasone lowered the serum corticosterone level and abolished its rise induced by 8-OH-DPAT. The corticosterone response to 8-OH-DPAT was also antagonized by spiperone, (+/-)- and (-)-pindolol and (+/-)-propranolol, all of which have been shown to have a high affinity for 5-HT1A receptors, though in most cases no complete blockade was found. A partial antagonism of the response was also observed after flumazenil, a benzodiazepine antagonist. On the other hand, the 5-HT1B receptor antagonist 21009, the 5-HT2 receptor antagonists ketanserin and pirenperone, the 5-HT3 receptor antagonist ICS 205-930, the alpha 2-adrenoceptor antagonists yohimbine and idazoxan, the beta-adrenoceptor blocker with no affinity to 5-HT1 receptors, atenolol, the dopaminergic antagonist pimozide, the histamine receptor blocker chloropyramine and the opiate receptor antagonist naloxone did not affect the hormonal response to 8-OH-DPAT. The 8-OH-DPAT-induced corticosterone secretion was not affected either in rats pretreated with p-chlorophenylalanine (PCPA, an inhibitor of tryptophan hydroxylase) or p-chloroamphetamine (PCA, a drug-inducing lesion of serotonergic nerve terminals). It is concluded that 8-OH-DPAT-induced increase in serum corticosterone concentration results from its action at a site different than the adrenal cortex and is mediated by postsynaptic 5-HT1A receptors, whereas other subtypes (5-HT1B, 5-HT2, 5-HT3) of 5-HT receptors do not participate in this response.(ABSTRACT TRUNCATED AT 250 WORDS)