Effect of hydration status on cerebral blood flow and cerebrospinal fluid lactic acidosis in rabbits with experimental meningitis

The effects of hydration status on cerebral blood flow (CBF) and development of cerebrospinal fluid (CSF) lactic acidosis were evaluated in rabbits with experimental pneumococcal meningitis. As loss of cerebrovascular autoregulation has been previously demonstrated in this model, we reasoned that compromise of intravascular volume might severely affect cerebral perfusion. Furthermore, as acute exacerbation of the inflammatory response in the subarachnoid space has been observed after antibiotic therapy, animals were studied not only while meningitis evolved, but also 4-6 h after treatment with antibiotics to determine whether there would also be an effect on CBF. To produce different levels of hydration, animals were given either 50 ml/kg per 24 h of normal saline ("low fluid") or 150 ml/kg 24 h ("high fluid"). After 16 h of infection, rabbits that were given the lower fluid regimen had lower mean arterial blood pressure (MABP), lower CBF, and higher CSF lactate compared with animals that received the higher fluid regimen. In the first 4-6 h after antibiotic administration, low fluid rabbits had a significant decrease in MABP and CBF compared with, and a significantly greater increase in CSF lactate concentration than, high fluid rabbits. This study suggests that intravascular volume status may be a critical variable in determining CBF and therefore the degree of cerebral ischemia in meningitis.

Effect of sibling competition and male carotenoid supply on offspring condition and oxidative stress

Early developmental conditions have major implications for an individual's fitness. In species where offspring are born simultaneously, the level of sibling competition for food access is intense. In birds, high sibling competition may subject nestlings to decreased growth rate as a result of limited food and increased levels of oxidative stress through high metabolic activity induced by begging behaviors. We manipulated the level of sibling competition in a natural population of great tits and assessed the consequences for nestling body condition and resistance to oxidative stress. In a full factorial design, we both augmented brood size to increase sibling competition and supplemented the male parents with physiological doses of carotenoids thereby doubling the natural carotenoid intake, aiming at increasing the males' investment in current reproduction and thereby decreasing sibling competition. Nestling body mass was reduced by the brood enlargement and enhanced by the carotenoid supplementation of fathers. Nestling resistance to oxidative stress, measured as total antioxidant defenses in whole blood, was not influenced by the treatments. Because nestlings experience high metabolic activities, an absence of an effect of sibling competition on free radicals production seems unlikely. Nestling body mass decreased and resistance to oxidative stress tended to increase with initial brood size, and hence these correlational effects suggest a trade-off between morphological growth and development of the antioxidant system. However, the result of the experimental treatment did not support this trade-off hypothesis. Alternatively, it suggests that nestling developed compensatory mechanisms that were not detected by our antioxidant capacity measure.

The effect of brief electrical and manual acupuncture stimulation on mechanical experimental pain

Although manual and electrical stimulation are frequently used in acupuncture analgesia, studies comparing both stimulation modalities are contradictory. This blinded, placebo-controlled cross-over study investigates effects of brief manual and electrical acupuncture stimulation on pressure pain detection thresholds (PPDT) compared with nonpenetrating sham acupuncture (NPSA).

Effect of tumor size and tumor-to-liver contrast of hypovascular liver tumors on the diagnostic performance of hepatic CT imaging

To assess the effect of tumor size and tumor-to-liver contrast of simulated hypovascular liver tumors on the diagnostic accuracy of hepatic computed tomography (CT).

Effect of low doses and high homeopathic potencies in normal and cancerous human lymphocytes: an in vitro isopathic study

OBJECTIVES: Biologic effects of high homeopathic potencies can be studied in cell cultures using cell lines or primary cells. We hypothesized that primary cells would be more apt to respond to high potencies than cell lines, especially cancer cell lines. We set out to investigate the effects of low doses and high homeopathic potencies of cadmium chloride, respectively, in an intoxication model with human primary lymphocytes compared to a human leukemia cell line (Jurkat). DESIGN: Cells were pretreated with either low concentrations (nM-microM) or high potencies (pool 15-20c) of cadmium for 120 hours, following which they were exposed to a toxic treatment with a range of cadmium concentrations (8-80 microM) during 24 hours. Cell viability was eventually assessed by use of the MTS/PES assay. Controls included a vehicle (NaCl 0.9%) for the low concentrations of cadmium or water 15-20c for cadmium 15-20c. A total of 34 experiments were conducted, 23 with low concentrations and 11 with high potencies of cadmium. Data were analyzed by analysis of variance. RESULTS: Pretreatment with low concentrations or high potencies of cadmium significantly increased cell viability in primary lymphocytes after toxic challenge, compared to control cells (mean effect +/- standard error = 19% +/- 0.9% for low concentrations respectively 8% +/- 0.6% for high potencies of cadmium; p < 0.001 in both cases). The pretreatment effect of low doses was significant also in cancerous lymphocytes (4% +/- 0.5%; p < 0.001), albeit weaker than in normal lymphocytes. However, high homeopathic potencies had no effect on cancerous lymphocytes (1% +/- 1.9%; p = 0.45). CONCLUSIONS: High homeopathic potencies exhibit a biologic effect on cell cultures of normal primary lymphocytes. Cancerous lymphocytes (Jurkat), having lost the ability to respond to regulatory signals, seem to be fairly unresponsive to high homeopathic potencies.

Effect of endotoxin, dobutamine and dopamine on muscle mitochondrial respiration in vitro

INTRODUCTION: Mitochondrial respiration is impaired during endotoxemia. While catecholamines are frequently used in sepsis, their effects on mitochondrial function are controversial. We assessed effects of dobutamine and dopamine endotoxin on isolated muscle mitochondria. MATERIALS AND METHODS: Sternocleidomastoid muscle mitochondria were isolated from six anesthetized pigs. Each sample was divided into six different groups. Three groups were incubated with endotoxin, three with vehicle. After 1 h, dopamine and dobutamine at final concentrations of 100 microM were added to the vehicle and endotoxin groups. After 2 h, state 3 and 4 respiration rates were determined for all mitochondrial complexes. Oxygen consumption was determined with a Clark-type electrode. RESULTS: Endotoxin increased glutamate-dependent state 4 respiration from 9.3 +/- 3.6 to 31.9 +/- 9.1 (P = 0.001) without affecting state 3 respiration. This reduced the efficiency of mitochondrial respiration (RCR; state 3/state 4, 9.9 +/- 1.9 versus 3.6 +/- 0.6; P < 0.001). The other complexes were unaffected. Catecholamine partially restored the endotoxin-induced increase in complex I state 4 respiration rate (31.9 +/- 9.1 versus 17.1 +/- 6.4 and 20.1 +/- 12.2) after dopamine and dobutamine, respectively (P = 0.007), and enhanced the ADP:O ratio (P = 0.033). CONCLUSIONS: Dopamine and dobutamine enhanced the efficiency of mitochondrial respiration after short-term endotoxin exposure.

Differential effect of pioglitazone (PGZ) and rosiglitazone (RGZ) on postprandial glucose and lipid metabolism in patients with type 2 diabetes mellitus: a prospective, randomized crossover study

Postprandial metabolism is impaired in patients with type 2 diabetes (T2Dm). Two thiazolidinediones pioglitazone (PGZ) and rosiglitazone (RGZ) have similar effects on glycaemic control but differ in their effects on fasting lipids. This study investigated the effects of RGZ and PGZ on postprandial metabolism in a prospective, randomized crossover trial.

Influence of pulmonary status and diabetes mellitus on aortic neck dilatation following endovascular repair of abdominal aortic aneurysms: a EUROSTAR report

PURPOSE: To elucidate the association of impaired pulmonary status (IPS) and diabetes mellitus (DM) with clinical outcome and the incidences of aortic neck dilatation and type I endoleak after elective endovascular infrarenal aortic aneurysm repair (EVAR). METHODS: In 164 European institutions participating in the EUROSTAR registry, 6383 patients (5985 men; mean age 72.4+/-7.6 years) underwent EVAR. Patients were divided into patients without versus with IPS or with/without DM. Clinical assessment and contrast-enhanced computed tomography (CT) were performed at 1, 3, 6, 12, 18, and 24 months and annually thereafter. Cumulative endpoint analysis comprised death, aortic rupture, type I endoleak, endovascular reintervention, and surgical conversion. RESULTS: Prevalence of IPS was 2733/6383 (43%) and prevalence of DM was 810/6383 (13%). Mean follow-up was 21.1+/-18.4 months. Thirty-day mortality, AAA rupture, and conversion rates did not differ between patients with versus without IPS and between patients with versus without DM. All-cause and AAA-related mortality, respectively, were significantly higher in patients with IPS compared to patients with normal pulmonary status (31.0% versus 19.0%, p<0.0001 and 6.8% versus 3.3%, p = 0.0057) throughout follow-up. In multivariate analysis adjusted for smoking, age, gender, comorbidities, fitness for open repair, co-existing common iliac aneurysm, neck and aneurysm size, arterial angulations, aneurysm classification, endograft oversizing >or=15%, and type of stent-graft, the presence of IPS was not associated with significantly higher rates of aortic neck dilatation (30.6% versus 38.0%, p>0.05) and did not influence cumulative rates of type I endoleak, endovascular reintervention, or conversion to open surgery (p>0.05). Similarly, the presence of DM did not influence the above-mentioned study endpoints. CONCLUSION: In contrast to observations regarding the natural course of AAAs, impaired pulmonary status does not negatively influence aortic neck dilatation, while the presence of diabetes does not protect from these dismal events after EVAR.

Effect of interferon-beta and atorvastatin on Th1/Th2 cytokines in multiple sclerosis

Beneficial effects by both interferon-beta and statin treatment in patients with multiple sclerosis (MS) may be linked to interference with the Th1/Th2 cytokine balance. We determined patterns of Th1/Th2 cytokines (interleukin (IL)-1beta, IL-2, IL-6, IL-12p70, tumor-necrosis factor (TNF)-alpha and interferon-gamma, and IL-4, IL-5 and IL-10, respectively) in the serum of patients with relapsing-remitting MS treated with 250microg interferon-beta 1b or with interferon-beta plus 40mg atorvastatin. In treatment naïve patients with MS, a trend for lower TNF-alpha serum levels compared to controls was detected (P=0.08). Interferon-beta treatment increased TNF-alpha levels, while a trend for lowering of IL-5 serum levels was found (P=0.07). Addition of atorvastatin raised IL-12p70 serum levels (P<0.05). Mean levels of two Th2 cytokines (IL-4, IL-10) showed a non-significant increase after addition of atorvastatin. We conclude that interferon-beta and atorvastatin exert divergent action on Th1/Th2 serum cytokines levels in MS. Supplemental atorvastatin might promote a Th1-type response by raising IL-12p70. Further studies are required to support a Th2 cytokine shift by atorvastatin in patients with MS.

The moderating effect of personal mastery and the relations between stress and Plasminogen Activator Inhibitor-1 (PAI-1) antigen

OBJECTIVE: This study tested whether feelings of personal control over one's life circumstances (i.e., personal mastery) would attenuate the relations between stress (i.e., negative life events and caregiving distress) and Plasminogen Activator Inhibitor (PAI)-1 antigen, an inhibitor of fibrinolysis implicated in the development of cardiovascular disease. DESIGN: Seventy-one spousal dementia caregivers were assessed for plasma levels of PAI-1 antigen, negative life events, caregiver distress, and feelings of personal mastery. Regression analysis was used to determine if personal mastery moderated the relations between stress (i.e., life stress and caregiving distress) and PAI-1 antigen levels. MAIN OUTCOME MEASURE: Plasminogen activator inhibitor (PAI)-1 antigen in plasma. RESULTS: After controlling for other factors associated with PAI-1 antigen levels, negative life events were positively associated with plasma PAI-1 antigen concentrations in participants low in personal mastery (beta = .31; p = .050) but not in individuals high in personal mastery (beta = .22; p = .184). The moderating effect of mastery on the relations between caregiving distress and PAI-1 antigen did not reach statistical significance (p = .091). CONCLUSIONS: These data suggest that mastery may protect individuals from some of the alterations in hemostatic factors that have been linked to cardiovascular risk.