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The role of the free radicals in aging has been in center of research for long years. It is assumed that with advancing age, damaging effects of oxygen free radicals might be accumulated in the organisms on all components, especially on the DNA and the mitochondria. In addition, because of the decreased efficiency of the antioxidant systems, the oxidative mechanisms prevail in numerous age-dependent diseases, such as the arterio -sclerosis, Parkinson and Alzheimer diseases. The present study was aimed at revealing an eventual correlation between the free radical levels and the psychophysical health state of an ultraoctagenarian East-Sicilian population living in institutes or at home. Our study population consisted of 125 ultraoctagenarian subjects, 62 of them were institutionalized and 63 living outside the institutes. The free radical effects were measured by using the free radical analytical system (FRAS) assessing the derivatives of reactive oxygen metabolites(D-ROMs). The results are expressed in units of Caratelli (U-CARR). The psycho-physical state of the subjects was estimated by means of the mini mental state examination(MMSE), geriatric depression scale (GDS), activities of daily living (ADL) and instrumental activities of daily living (IADL). The nutritional state and the physical activity of the subjects were evaluated through the mini nutritional assessment (MNA) and the physical performance test (PPT). All studied parameters underwent a correlation analysis of Pearson. Statistically significant negative correlation was found between the free radical levels and the cognitive performance (p < 0.0001), as well as the levels of autonomy and autosufficiency,the physical activity in the total population (p < 0.01). These correlations were even more expressed in the institutionalized subjects. Statistically significant positive correlation seems to exist between the free radical levels and the nutritional status (p < 0.001). These studies revealed some important differences between the institutionalized and noninstitutionalized population. The levels of oxygen free radicals were higher in the former group, indicating a stronger oxidative stress, influencing the psychophysical state of the elderly subjects. This may have negative consequences on the quality and duration of the life. It is difficult to define the exact role of free radicals in the determination of aging pattern,but they may be considered without any doubt as true "markers" of an enhanced oxidative stress, accompanying a non-successful aging process.

Objective: This study evaluated whether prostacyclin is a necessary mediator of inflammation in graded bacteremia or is sufficient alone in pathophysiologic concentrations to cause the pulmonary derangement of bacteremic shock. Design: Experimental. Setting: Laboratory. Subjects: Twenty-three anesthetized adult swine. Intervensions: Swine were studied in four groups for 4 hrs: a) an anesthesia control group (n = 6); b) a septic control group (n = 6), in which 10 10 /mL Aeromonas hydrophila was infused intravenously at 0.2 mL.kg -1 .hr -1 and increased to 4.0 mL.kg -1 .hr -1 over 3 hrs; c) a prostacyclin infusion group (n = 6), which received prostacyclin infusion to match septic control plasma concentrationsclm without bacteremia; and d) an antiprostacyclin antibody group (n = 5), which received continuous Aeromonas hydrophila infusion plus antiprostacyclin antibody infusion. Measurements and Main Results: Pulmonary hemodynamics, arterial blood gases, and plasma concentrations of arachidonate metabolites were measured hourly over a 4-hr period. In the septic control group and antiprostacyclin antibody group, elevated pulmonary vascular resistance index and pulmonary artery pressure with decreased PaO 2 , as well as lower pH, were documented after 1 and 3 hrs of graded bacteremia compared with the anesthesia control group and prostacyclin infusion group (p < .05). Thromboxane B 2 concentration increased significantly in all groups during septic shock. In the antiprostacyclin antibody group, leukotriene B 4 increased immediately after starting antiprostacyclin antibody infusion and reached significance at 3 hrs compared with the septic control group (p

Objective : To determine whether or not platelet activating factor (PAF) is a necessary mediator of cardiovascular dysfunction during graded bacteremia, and to identify PAF interactions with eicosanoids and tumor necrosis factor-alpha (TNF-α). Methods : Seventeen anesthetized, hemodynamically monitored adult swine were studied for 4 hours in three groups. Group 1 (ANES, n = 5) were anesthesia controls ; group 2 (septic control, SC, n = 6) received intravenous Aeromonas hydrophila (109/mL) at rates incrementally increased from 0.2 to 4.0 mL/kg/h; group 3 (WEB, n = 6) received the PAF receptor antagonist WEB 2086, 3.0 mg/kg intravenously, then A. hydrophila. Cardiopulmonary parameters and plasma thromboxane B 2 (TXB 2 ), prostaglandin 6-keto F 1 α (PGI 2 ), leukotriene B 4 (LTB 4 ), leukotrienes C 4 D 4 E 4 (LTC 4 D 4 E 4 ), and TNF-α were measured hourly. Statistical analysis was carried out using two-way analysis of variance (ANOVA) for repeated measurements, Dunnett's t test, and Student's t test, where appropriate. Statistical significance was determined at the 95% confidence interval. Values are presented as the mean ± SEM. Results : Pulmonary arterial pressure, pulmonary capillary wedge pressure, central venous pressure heart rate, Vo 2 and o 2 ER decreased significantly after WEB 2086 infusion, compared with SC, and mean arterial pressure, systemic vascular resistance index, stroke volume index, and left ventricular stroke work index increased. Arterial pH decreased significantly in SC animals, but was maintained at normal levels during bacteremia in the WEB group. Differences between WEB and SC for cardiac index, pulmonary vascular resistance index, right ventricular stroke work index, Pao 2 , Sao 2 , and Pco 2 , were not significant. The addition of WEB 2086 significantly decreased plasma levels of TXB 2 , PGI 2 , LTB 4 , and TNF-α compared with the SC group. LTC 4 D 4 E 4 was decreased in WEB compared with SC animals, in which LTC 4 D 4 E 4 increased during graded bacteremia. Conclusions : PAF is necessary to the development of systemic vasodilation and hypotension, pulmonary hypertension, decreased stroke volume, metabolic acidosis, and increased oxygen uptake during graded bacteremia. PAF-induced eicosanoid and cytokine release may be involved.

The osteoporosis is a systemic disease of multicausal etiopathogenesis. A progressive bone loss and qualitative alterations in the macro- and micro-architecture of the remaining bones, resulting in a loss of strength of bones to such an extent that even very modest traumas will cause fractures characterize it. Three forms are defined (i) postmenopausal appearing after the menopause, (ii) senile appearing with advancing age, and (iii) the idiopathic forms. Severe osteoporosis is declared when the patients suffer vertebral or femoral fractures without any trauma during a treatment with anti-reabsorptive medicines of at least 1-year. The treatment of osteoporosis is based on various categories of pharmaca, such as bisphosphonates, selective estrogen receptor modulators (SERMs), diaminobutyric acid (DABA), parathyroid hormone (PTH), estrogens and non-hormonal drugs. The teriparatide, the recombinant human (rh)PTH(1-34), is identical in amino acid sequence until the 34th (N-terminal) amino acid of the endogenous, human PTH. It is produced in E. coli using the recombinant DNA technology. It is a pharmacon having a strong trophic-anabolic action on the bone tissue, assuring both the inhibition of the bone loss, and the formation of new bones of good quality. It acts as a stimulant of the osteoblast functions, and at the same time, increases the absorption of calcium from the intestine, and also the renal reabsorption of calcium, and decreases the excretion of phosphates in the kidney. This study summarizes our own experience with the use of rhPTH(1-34) in the treatment of senile patients with severe osteoporosis. Our sample consisted of 40 elderly women of the mean age of 78+/-5 years, having severe osteoporosis. They displayed a columnar T-score>-3.5 and femoral T-score>-2.5, had been under antireabsorptive treatment since at least 12 months. In particular, 15 patients were treated with Alendronate (70 mg/week), 10 of them with Risedronate (35 mg/week), and 15 of them with Raloxifene (60 mg/day). These patients in our study were treated for 1 year with 20 microg/day of rhPTH (1-34), injected subcutaneously, and supplemented also with a daily dose of 1g of calcium and 800 IU of Vitamin D, per os. At start of this treatment (time t(0)), after 6 months (time t(6)) and after 12 months (time t(12)) patients underwent a bone mineral density (BMD) analysis (Dexa-Lunar-DPX-P) on the lumbar vertebral column, (L1-L4 zone), as well as a femoral BMD. We applied also quality of life (QoL) questionnaire of the European Foundation for Osteoporosis (QUALEFFO), and evaluated also the use of non-steroidal anti-inflammatory drugs (NSAIDs). Our final considerations are that the teriparatide therapy increases significantly the bone mass density, expressed in terms of T-Score, reduces the occurrence of new fractures, improves the QoL, and decreases also the consumption of NSAIDs.

The identification of risk factors for osteoporosis has been an essential step towards the understanding of the onset of the disease as well as of the osteoporosis-related fractures due to bone fragility. The present study has been aimed at assessing whether a correlation may exist between the increment in bone mass, consequent to an antiresorption therapy, and the reduction in the incidence of fractures. Moreover, the possibility that such a reduction might result from the action of other factors, such as the changes in bone microstructure, has been investigated. A total of 2,000 osteoporotic women (mean age: 68 +/- 9 years) were enrolled in the study and divided at random into 4 treatment groups. Each group received one of the following treatments: Alendronate 10 mg/daily (1,000 patients), Clodronate 100 mg/weekly i.m. (800 patients), Risedronate 5 mg/dailt (100 patients), and Raloxifene 60 mg/daily (100 patients). Clinical evaluation was based on bone mineral density (BMD) assay on lumbar vertebrae (L1-L4) by means of a DEXA (Lunar DPX) mineralometer, as well as on the incidence of fractures following both 12- and 24-month treatment periods. The results showed an overlapping pattern in patients treated with Alendronate or Risedronate, namely a significant increment in BMD after a 24-month treatment period, whereas such an increment in BMD was less evident in patients receiving either Clodronate or Risedronate after a 24-month treatment period. In addition, a total of 18 osteoporosis-related fractures were observed during the entire study period; 10 out of 18 fractures occurred in the Alendronate treated group, whereas the remaining 8 fractures were observed in the Clodronate treated group. Fourteen fractures were detected in patients over 80-year old, whereas the remaining 4 occurred in patients aged from 70 to 79 years and appeared to be independent of both the T-score assigned and the BMD increment obtained as a result of the therapy. Such findings suggest that the plain monitoring of BMD appears not to be adequate to anticipate clearly the danger of the probable onset of additional fractures, while the higher incidence of fractures in patients over 80-year old evidences that "old age" has to be considered the most serious risk factor for osteoporosis, since it is also the real responsible factor for changes taking place in bone microstructure.

This survey covered 60 post-menopausal women with osteoporosis. The patients were divided into three equal groups, and each group was treated with one of the three so-called anti-resorptive drugs, namely alendronate (10 mg/day) risedronate (5 mg/day) and raloxifene (60 mg/day) for 12 months. The Elisa technique was used to measure circulating IL-18 and MMP-9. Lumbar bone mineral density (BMD) levels were determined by using dexa mineralometry (Lunar DPX) at baseline and after 12 months of treatment. The results showed comparable responses of the patients treated with alendronate or risedronate, being a significant increase in BMD, an increase in circulating IL-18, and only slight modifications in circulating MMP-9 levels. After 12 months of treatment with raloxifene, there were minimal, non-significant increases in BMD, slight modifications in IL-18 levels, and a significant reduction in circulating MMP-9 levels. The conclusions can be drawn that all three drugs, albeit through different mechanisms, can be considered valid treatments for post-menopausal osteoporosis. Although measurements of circulating IL-8 and MMP-9 levels allowed us to differentiate the effects of the three drugs used, as of today, they have no real role in the diagnosis and/or follow-up of osteoporosis.

This study evaluated whether or not prostacyclin (PGI2) was necessary or sufficient by itself in a pathophysiologic concentration to mediate the cardiovascular dysfunction of septic shock. Anesthetized adult swine received anesthesia only (ANESTHESIA CONTROL, n = 6); graded Aeromonas hydrophila, 10(10)/mL, infusion at 0.2 mL/kg/h that increased to 4.0 mL/kg/h over 3 h (SEPTIC SHOCK CONTROL, n = 6); pathophysiologic prostacyclin infusion to match septic shock control plasma levels without bacteremia (PGI2 INFUSION, n = 6), or graded Aeromonas hydrophila plus anti-prostacyclin antibody infusion (ANTI-PGI2-Ab INFUSION, n = 5). This graded porcine bacteremia model was 100% lethal after 4 h. Cardiovascular hemodynamics, arterial blood gases, and plasma levels of arachidonate metabolites were measured at baseline and hourly over a 4-h period. The results showed that PGI2 was not a necessary mediator of impaired cardiovascular hemodynamics in graded bacteremia, as anti-PGI2 antibody infusion did not improve the cardiac index, systemic vascular resistance, or peripheral oxygen balance in septic animals. Also, PGI2 was not sufficient alone to cause the cardiovascular dysfunction of sepsis, as pathophysiologic infusion of PGI2 did not reproduce such changes in normal animals. PGI2 blockade during bacteremia significantly increased LTC4D4E4, and LTB4 whereas PGI2 infusion suppressed LTC4D4E4 concentration, suggesting that endogenous PGI2 may blunt leukotriene release during septic shock. These results indicate a complex dynamic equilibrium among prostacyclin and leukotrienes in septic shock.

Gut ischemia has been implicated in the pathogenesis of necrotizing enterocolitis. Cyclosporine A and rapamycin, both potent novel immunosuppressants which act on signal transduction pathways in CD4+ T-cells, could potentially modulate immune/inflammatory cellular reactions involved in tissue ischemia/reperfusion injury. We hypothesized that cyclosporine A and rapamycin would preserve mucosal cell function and attenuate inflammatory T-cell-mediated cellular changes associated with small bowel ischemic injury. Forty Sprague-Dawley rats underwent 60 min of gut ischemia by vascular occlusion of the superior mesenteric vessels. Animals were randomized to four groups (n = 10): cyclosporine A (CSA, 5 mg/kg/day SQ), rapamycin (RAP, 2 mg/kg/day SQ), cyclosporine A and rapamycin (CR), and vehicle given to controls (CON). Following 1 hr of reperfusion, small bowel was harvested for xanthine oxidase (XO, units/mg protein) and maltase (MALT, mM substrate degraded/min/g protein) assays. Blood was obtained from the portal vein for tumor necrosis factor-alpha (TNF-alpha, pg/ml) assay. The results of the study are presented below (mean +/- SEM, *, P0.05 versus controls). (Table in text) The results indicate that cyclosporine and rapamycin each play a significant role in attenuating ischemia/reperfusion injury in the gut. These data suggest that there are cytoprotective and anti-inflammatory mechanisms of these drugs independent of T-cell signal transduction that provide some protective effect in small bowel ischemia. Furthermore, T-cell-mediated immune mechanisms may not be associated with the adverse effects of small bowel ischemia/reperfusion injury. Additional investigation will be necessary in order to define the role of T-cell-mediated immune injury in the gut and how this relates to the beneficial effect of immunosuppression in small bowel mucosal ischemic injury.

Purpose: Gut ischemia has been implicated in the pathogenesis of necrotizing enterocolitis. Cyclosporine A (CSA), a potent immunosuppressant, attenuates immune/inflammatory cellular reactions. CSA also might be useful for inhibiting cellular immune responses involved in tissue ischemia/reperfusion injury. The authors hypothesized that CSA would attenuate inflammatory cellular changes associated with gut ischemic injury and that these effects could be quantified by computerized morphometry. Methods: Twenty Sprague-Dawley rats underwent 60 minutes of gut ischemia by vascular occlusion of the superior mesenteric vessels. After 1 hour of reperfusion, the ischemic small bowel was harvested for histopathological examination and computerized morphometry, as well as xanthine oxidase (XO, U/mg protein) and maltase (MALT, mmol/L substrate degraded/min/mg protein) assays. CSA (5 mg/kg/d subcutaneously) was given to experimental animals (CSA, n=10) for 5 days before ischemia, and vehicle was given to controls (CON, n=10). The computer morphometric parameters studied were: surface index (SI, mucosal surface length per linear unit of intestine), average villous thickness (AVT), and average villous height (AVH). Results: Results are provided in Table 1. Conclusion: The results of this study show that CSA may play a role in attenuating ischemia/reperfusion injury in the gut. Enzymatic analysis showed a beneficial role in the preservation of mucosal cell function after gut ischemia/reperfusion injury, as demonstrated by an elevated maltose level. Computerized morphometry demonstrated significant differences in all parameters in the experimental group, showing that CSA does confer gut mucosal protection during ischemia.

Histopathologic alterations in the intestinal mucosa after ischemic injury have been extensively described in the literature, but these descriptions have primarily been qualitative in nature. The purpose of this study was twofold: (1) to establish parameters obtained by computerized digital image analysis that would be useful in identifying ischemic injury, and (2) to use these parameters to identify the critical period of intestinal ischemia producing measurable histopathologic change. Seventy male Sprague-Dawley rats weighing 80 to 150 g underwent various times of gut ischemic injury by vascular occlusion of the superior mesenteric artery and vein with a microaneurysm clamp. The clamp times were 0, 1, 20, 30, 40, 50, 60, 70, 80, and 90 minutes. Histological sections of the terminal ileum were quantitatively analyzed using Jandel Scientific's computerized morphometric image analysis system. Parameters studied were surface index (SI, surface length per linear unit of mucosa), average villous thickness (AVT), average villous height (AVH), and the number of villous cells/100 μm length (VC). Ischemic times of 1, 20, 30, and 40 minutes produced no measurable injury as compared with baseline ( P [40 minutes versus baseline] = SI, .60; AVT, .84; AVH, .93; VC, .09). At 50 minutes, SI and AVH showed a measurable change from baseline ( P [50 minutes versus baseline] = SI, .01; AVH, .02). Sixty minutes of ischemic time produced measurable change in all parameters ( P [60 minutes versus baseline] = SI, .007; AVT, .001; AVH, .002; VC, .007). Ischemic times beyond 60 minutes produced significant changes from baseline, but were not measurably different from that of 60 minutes ( P [90 minutes versus 60 minutes] = SI, .15; AVT, .89; AVH, .43; VC, .18). Interestingly, when each histological parameter was analyzed over time, the earliest measurable changes were noted in the SI and AVH between 40 and 50 minutes of ischemia. During this time period, there was a reduction in surface index ( P = .03) and average villous height ( P = .005) with a concomitant increase in the Chiu score ( P = .02). These results suggest that the critical period of ischemia producing significant histopathologic change without irreversible death lies within 40 to 50 minutes. Furthermore, morphometric analysis can be used with reliability in quantitatively evaluating the degree of gut ischemic injury, allowing a more objective and reproducible measurement of ischemic change.

Laparoscopy is used increasingly in managing critically ill patients. Carbon dioxide (CO 2 ) pneumoperitoneum is used during these procedures. The increased intra-abdominal pressure of CO 2 pneumoperitoneum, however, can affect cardiopulmonary performance adversely. Recently, gasless abdominal wall distention has been introduced as an alternative to CO 2 pneumoperitoneum. The purpose of this study was to compare the hemodynamic effects of gasless abdominal distention (GAD) with those of CO 2 pneumoperitoneum during mechanical ventilation with positive end-expiratory pressure (PEEP). Six anesthetized, paralyzed, mechanically ventilated adult swine were monitored with pulmonary artery and arterial catheters at incremental values of PEEP (0-20 cm H 2 O, by 5, Control) and then allowed to return to baseline hemodynamic status at 0 cm H 2 O PEEP. The animals were then randomly assigned to receive either CO 2 pneumoperitoneum at 15 mm Hg intra-abdominal pressure (PNEUMO) or GAD (equal to anterior abdominal wall displacement of CO 2 ) and PEEP was reapplied. The animals were allowed to return to hemodynamic baseline and PEEP was reapplied with the alternate method of abdominal wall distention. A complete hemodynamic profile and arterial/mixed venous blood gas measurements were monitored at each value of PEEP. With GAD, central venous pressure (CVP), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), and P a CO 2 were significantly reduced, compared to PNEUMO, and P a O 2 was increased. Cardiac index -was higher in GAD versus PNEUMO at baseline, but was lower for GAD at PEEP levels above 10 cm H 2 O. These results indicate that in its net effect, GAD does not exacerbate the adverse hemodynamic effects of PEEP. This technique may be a favorable alternative to CO 2 pneumoperitoneum in the critically ill ventilated patient when there is concern over PAP, CVP, PCWP, and P a O 2 /P a CO 2

To ensure the validity of their national standards, National Metrology Institutes, NMIs, participate regularly in international comparisons. In the area of neutron metrology, Section III of the Consultative Committee for Ionizing Radiation is in charge of the organization of these comparisons. From September 2011 to October 2012, the eleventh key comparison, named CCRI(III)-K11, took place at the AMANDE facility of the LNE-IRSN, in France. Participants from nine NMIs came with their own primary reference instruments, or instruments traceable to primary standards, with the aim of determining the neutron fluence, at 1 m distance from the target in vacuum, per monitor count at four monoenergetic neutron fields: 27 keV, 565 keV, 2.5 MeV and 17 MeV. The key comparison reference values (KCRV) were evaluated as the weighted mean values of the results provided by seven participants. The uncertainties of each KCRV are between 0.9 % and 1.7 %. The degree of equivalence (DoE), defined as the deviation of the result reported by the laboratories for each energy from the corresponding KCRV, and the associated expanded uncertainty are also reported and discussed.