Effect of chloroquine, methylene blue and artemether on red cell and hepatic antioxidant defence system in mice infected with Plasmodium yoelii nigeriensis

Reactive oxygen species are mediators of tissue injury and are involved in malaria infection. In this study, the status of red cell and hepatic oxidative stress and antioxidant defence indices were investigated during Plasmodium yoelii nigeriensis (P. yoelii) infection, and treatment with chloroquine (CQ), methylene blue (MB) or artemether (ART) in mice. P. yoelii infection caused a significant (p?<?0.05) increase in oxidative stress as evidenced by the elevated level of malondialdehyde. This was followed by a significant decrease (p?<?0.05) in hepatic antioxidant defence indices, viz. reduced glutathione (GSH) and glutathione-S-transferase (GST). Also, the red cell catalase activity was significantly (p?<?0.05) lower in malaria infection, while there was no significant difference (p?>?0.05) in the superoxide dismutase (SOD) activity of infected mice when compared to untreated normal. Treatment of infected mice with the three antimalarials showed that the drugs suppressed the parasitaemia in the order CQ?>?ART?>?MB. CQ, MB and ART treatment of infected mice caused a significant (p?<?0.05) increase in the levels of hepatic GSH and GST. Specifically, CQ, MB and ART increased the levels of hepatic GSH by 108, 124 and 98 %, respectively, at day 6. Also, ART treatment of infected mice significantly (p?<?0.05) elevated the red cell SOD level by 200 % at day 3. Taken together, the findings suggest that the antimalarial effect of CQ, MB and ART countered the P. yoelii-induced oxidative stress leading to the elevation of enzymatic and non-enzymatic antioxidants in the host system.     

Serum Growth Arrest-Specific Protein 6 Levels are a Reliable Biomarker of Disease Activity in Systemic Lupus Erythematosus

Purpose

Growth arrest-specific protein 6 (Gas6) has been suggested to be a biomarker of disease activity in patients with systemic lupus erthematosus (SLE). We investigated the clinical significance of this protein in Korean SLE.

Methods

Blood samples were collected from 150 SLE patients and 50 normal controls (NC). In addition, follow-up samples were collected from 50 SLE patients.

Results

Serum Gas6 levels of SLE patients (43.01?±?28.02 ng/mL) were higher than those of NC (20.15?±?9.23 ng/mL, p?<?0.001). When evaluated sensitivity and specificity of the Gas6 for diagnosing SLE using ROC curves, the sensitivity and specificity were 72.7 % and 84 % with a cut-off value of 25.3 ng/mL. In the ROC analysis of Gas6, anti-dsDNA antibody, ESR, complement 3 and complement 4 to identify patients with active lupus, area under the curve (AUC) of Gas6 was highest with 0.763. Serum Gas6 levels were significantly higher in the patients with serositis (70.04?±?30.85 ng/mL) and renal disorder (65.66 ±32.28 ng/mL) compared to those without (41.88?±?27.44 ng/mL, p?=?0.033, 40.3?±?26.33 ng/mL, p?=?0.001, respectively). Gas6 levels were correlated positively with anti-dsDNA antibody (r?=?0.199, p?=?0.015), ESR (r?=?0.204, p?=?0.013) and SLEDAI (r?=?0.512, p?<?0.001). In addition, serum Gas6 levels were correlated negatively with hemoglobin (r?=??0.165, p?=?0.043), lymphocyte count (r?=??0.165, p?=?0.043), complement 3 (r?=??0.343, p?<?0.001) and complement 4 (r?=??0.316, p?<?0.001). Furthermore, change in serum Gas6 levels was correlated with change in SLEDAI levels in the SLE patients that were followed up (r?=?0.524, p?<?0.001).

Conclusion

These results suggest that serum Gas6 can be a reliable clinical marker for monitoring disease activity and treatment response in SLE.     

Evaluation of sperm characteristics and plasma testosterone in the goldfish (Carassius auratus) during four consecutive seasons

The overall objective of the study was to investigate changes in quantitative parameters of goldfish (Carassius auratus) semen, testosterone (T), and gonadosomatic index (GSI) during the four seasons of the year (spring, summer, autumn, and winter). Simple environmental and hormonal treatments were used to induce out-of-season spawning in goldfish. The semen was taken from goldfish in different periods during the four seasons, and the characteristics of sperm and pH were analyzed. Plasma levels of T, GSI, and histological studies of the testes, as well as a range of indices of ovarian development, were measured. No significant differences were observed between volumes of semen which can be extracted per fish, in the four seasons (P?>?0.05). Significant differences were found between sperm motility at different seasons (P?<?0.05), as the maximum total duration of motility was observed in autumn (109.25?±?14.00 s). Sperm density showed a higher value during summer (57.30?±?10.41?spermatozoa (spz)?ml^?1) and winter (65.09?±?80.40 spz ml^?1) than values that were obtained from spring (48.00?±?7.08 spz ml^?1) and autumn (40.42?±?16.54?×?10⁹ spz ml^?1) (P?<?0.05). However, spermatocrit (in percent) was higher in winter (39.90?±?4.74) compared with other seasons (P?<?0.05). Values of pH were higher in autumn (7.87?±?0.05) and in winter (7.83?±?0.03) than values that were obtained from other seasons. The peaks of T and GSI during spermiation in spring (T, 21.08 ng/ml, and GSI?=?5.21 %) and in summer (T, 23.32 ng/ml, and GSI?=?6.10 %), when most gonadal development took place, were statistically significantly higher than the levels observed during autumn (T, 15.08 ng/ml, and GSI?=?3.21 %) and winter (T, 22.18 ng/ml, and GSI?=?2.78 %) (P?<?0.05). Our results provided the statistically significant evidence of seasonal variation in sperm characteristics, T and GSI, for goldfish. These findings may be used to: (1) optimize semen collection for hatchery production and (2) characterize the potential impact of seasons on sperm quality and plasma androgen levels.     

The association of urinary interferon-gamma inducible protein-10 (IP10/CXCL10) levels with kidney allograft rejection

Background

Interferon-gamma inducible protein-10 (IP-10/CXCL10) is a chemokine involved in the alloimmune response against kidney allograft. We aimed to investigate the association of urinary CXCL10 protein levels with rejection in renal transplant patients.

Methods

A total of 273 urine samples from (biopsy-proven) rejection and non-rejection patients and controls were included in this study. CXCL10 levels were analyzed for association with rejection.

Results

The data showed statistically significant differences in the CXCL10 levels between rejection vs. non-rejection (p?<?0.001). Among the rejection groups, statistically significant differences for CXCL10 levels were found between ACR vs. NAD (p?<?0.001), ACR vs. BLR (p?=?0.019) and AVR vs. NAD (p?=?0.009). Receiver Operating Characteristic (ROC) curve analysis of CXCL10 showed an area under the curve (AUC) of 0.74 with 72% sensitivity and 71% specificity at 27.5 pg/ml between rejection and non-rejection group. Kaplan–Meier curve analysis among different levels of CXCL10 showed a better rejection-free graft survival in patients with <100 pg/ml when compared to >200 pg/ml (38?±?6 vs. 12?±?1.0 weeks; log-rank p?<?0.001) and 100–200 pg/ml (38?±?6 vs. 22?±?9 weeks; log-rank p?=?0.442) concentration.

Conclusion

The results indicate significantly increased levels of CXCL10 protein in the urine at the time of allograft rejection. This association of urinary CXCL10 protein levels with rejection could provide an additional tool for the non-invasive monitoring of allograft rejection.

     

Decreased Proinflammatory Cytokines Production in Children with Complicated Parapneumonic Pleural Effusion after Intrapleural Fibrinolytic Treatment

Intrapleural fibrinolytic therapy (IFT) provides clinical benefit in the treatment of complicated pleural parapneumonic effusion (CPE). Whether IFT influences the proinflammatory cytokines production and fibrinlytic activity is currently unclear. Therefore, we collected pleural effusion samples from CPE patients with IFT (study group) and patients without IFT (control group). A membrane human inflammatory cytokines array kit was used to compare the difference of targeted cytokine production between these two groups. Enzyme-linked immunosorbent assay (ELISA) methods were used for quantitative analysis of targeted cytokines and fibrinolytic enzymes. The results showed there were no significant differences between the study (n = 16) and control (n = 14) groups in patients’ demographic data. After fibrinolytic therapy, the patients in the study group had significant lower plasminogen activator inhibitor (PAI) level (732.36?±?254.09 ng/mL vs 1,509.36?±?1,340.11 ng/mL, p?<?0.05) and higher urokinase plasminogen activator (u-PA) level (75.56?±?41.70 ng/mL vs 6.87?±?5.07 ng/mL, p?<?0.05) than they did before treatment. Moreover, the tissue inhibitors of metalloproteinase-2 (TIMP-2) (1,560.03?±?403.49 pg/mL vs 3,686.45?±?1,263.83 pg/mL, p?<?0.05) and inflammatory chemokine, regulated on activation normal T-cell expressed and secreted/chemokine (C-C motif) ligand 5 (RANTES), (293.58?±?212.93 pg/mL vs 749.27?±?53.79 pg/mL, p?<?0.05), were also significantly lower in the study group after fibrinolytic therapy, but not in the control group. In conclusion, intrapleural fibrinolytic treatment with urokinase could enhance fibrinolytic activity and decrease TIMP-2 and RANTES production.     

The effect of acute exercise with increasing workloads on inactive muscle blood flow and its heterogeneity in humans

The distribution of blood flow between active and inactive skeletal muscles has been sparsely studied in humans. Here we investigated non-exercising leg blood flow in six healthy young women during intermittent isometric one leg knee extension exercise with increasing workloads. Positron emission tomography was used to measure blood flow in hamstring muscles of the exercising leg, and whole thigh muscles as well as its knee extensor and hamstring compartment of the resting leg. Mean blood flow to the hamstrings of the exercising leg (5.8?±?2.6?ml/100?g/min during the highest exercise workload) and whole thigh muscle of the resting leg (7.1?±?3.8?ml/100?g/min) did not change significantly from rest (4.0?±?0.7 and 4.7?±?1.9?ml/100?g/min, respectively) to exercise, but flow heterogeneity increased substantially at increasing workloads. Importantly, during the highest exercise workload, mean blood flow in the knee extensors of the resting leg decreased (5.5?±?3.0?ml/100?g/min at rest and 3.4?±?2.0?ml/100?g/min during exercise, p?<?0.01) while flow heterogeneity increased (28?±?8% at rest and 83?±?26% during exercise, p?<?0.05). Conversely, in hamstring muscles of the resting leg blood flow increased from 3.9?±?1.0?ml/100?g/min at rest to 11.5?±?6.8?ml/100?g/min during exercise (p?<?0.05) while flow heterogeneity increased from 30?±?7 to 58?±?19% (p?<?0.05). In conclusion, while mean whole thigh muscle blood flow of the resting leg remains at resting level during one leg exercise of the contralateral leg, redistribution of blood flow between muscle parts occurs within the thigh. Based on previous studies, nervous constraints most probably act to cause this blood flow distribution.     

Antihyperglycaemic and antioxidant potentials of Cussonia arborea in alloxan-induced diabetic rats

This study was to evaluate the anti-hyperglycaemic potential of the methanolic stem bark extract of Cussonia arborea in alloxan-induced diabetic rat model. C. arborea extract was well tolerated by the rats at the highest dose of 3,200 mg/kg. The extract at the dose of 500 mg/kg body weight significantly (p?<?0.05) reduced the blood glucose levels of diabetic rats from 16.9?±?4.7 to 5.1?±?1.8 (72.4?±?2.9 % reduction) 6 h post-extract administration. Upon screening of the four fractions obtained after chromatographic techniques, fraction 2 showed the highest anti-hyperglycaemic activity (75.2?±?2.1 % reduction). Further phytochemical studies on fraction 2 revealed that it contains mainly saponin. Fraction 2 showed concentration-dependent antioxidant scavenging activity in 1,1-diphenyl-2-picrynyl phenyl hydrazyl photometric assay. The optimum percentage antioxidant activity was 55 % at the concentration of 400 μg/ml. Ferric reducing antioxidant power (FRAP) value (1.6 μm) of the fraction at 400 μg/ml was statistically comparable to that of 2 μm ascobic acid (reference standard).). It was concluded that the anti-hyperglycaemic property of the extract is attributable to fraction 2. The anti-hyperglycaemic activities of C. arborea could also be attributed to its antioxidant potentials.     

Preventive Effect of Chrysin on Bleomycin-Induced Lung Fibrosis in Rats

The aim of the current study is determination of protective effect of chrysin (CRS), a natural flavonoid, on cell injury produced by lung fibrosis induced with bleomycin (BLC) in rats. Twenty-eight female rats were assigned to four groups as follows: control group, CRS group; 50 mg/kg CRS was continued orally for 14 days, BLC group; a single intratracheal injection of BLC (2.5 mg/kg body weight in 0.25 ml phosphate buffered saline), BLC?+?CRS group; 50 mg/kg CRS was administered 1 day before the intratracheal BLC injection and continued for 14 days orally. All animals were sacrificed at day 14th after BLC administration. The semiquantitative assessment of histopathological consisting of lung inflammation and collagen deposition, tissue levels of thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reducted glutathione (GSH) were measured. BLC provoked histological changes consisting of alveolar congestion, increase connective tissue, infiltration, and the thickness of alveolar wall were detected significantly when compared to the control group (p?≤?0.0001). CRS supplementation significantly restored these histological damages (p?≤?0.0001). The level of tissue TBARS was increased with BLC (p?GPx, CAT, and GSH in the lung tissue compared to control group (p?p?相似文献   

Activity of ethanol and daptomycin lock on biofilm generated by an in vitro dynamic model using real subcutaneous injection ports

Vancomycin lock solution (LS) is recommended for the conservative treatment of subcutaneous injection port (SIP)-related infections, but may be associated with failure. We used an in vitro dynamic model of biofilm formation in an SIP, based on a continuous flow circulating via a real SIP, to assess the effectiveness of vancomycin (5 mg/ml), daptomycin (5 mg/ml) and ethanol 40 % LS in eradicating a pre-established Staphylococcus epidermidis biofilm. Heparin, Ringer’s lactate and enoxaparin sodium LS were used as controls. The logarithmic reductions of colony-forming units (CFU) were compared by Student’s t-test. After 24 h of exposure, the vancomycin LS did not exert a greater bactericidal effect than the heparin LS control (mean logarithmic reduction: 2.27?±?0.58 vs. 1.34?±?0.22, respectively, p?=?0.3). The mean logarithmic reduction was greater with daptomycin LS (5.45?±?0.14 vs. 0.39?±?0.12, p?<?0.01) and ethanol LS (6.79?±?1.03 vs. 1.43?±?0.54, p?=?0.02). Bacterial revival after exposure to 24 h of LS was assessed. The mean viable bacteria count was significantly higher for vancomycin LS (9.36?±?0.10 log₁₀CFU) and daptomycin LS (9.16?±?0.02 log₁₀CFU) than for ethanol LS (2.95?±?1.65 log₁₀CFU). Ethanol appeared to be the most attractive option to treat SIP-related infection, but its poor ability to entirely disrupt the biofilm structure may require its use in association with a dispersal agent to avoid renewal of the biofilm.     

Vitamin D deficiency affects the immunity against Mycobacterium tuberculosis infection in mice

The aim of the study is to investigate the immunological changes after stimulation with bacillus Calmette–Guerin (BCG) in mice with vitamin D deficiency. After weaning, mice were divided into the vitamin D-deficient group (?D group), the normal group (N group), and the vitamin D-supplemented group (+D group). Twelve-week-old mice were intraperitoneally injected with 0.5 mg/ml BCG (≥1.0 × 10⁶ CFU/mg) and maintained for 6 weeks. Spleen lymphocytes were isolated, and the percentages of CD4⁺ and CD8⁺ lymphocytes were determined by flow cytometry. IFN-γ levels, IL-10 levels, and the TB-PPD-specific antibody titer were determined by ELISA. The inter-group difference was analyzed using one-way ANOVA, and multiple comparisons were analyzed using the LSD test. The percentage of CD4⁺ cells was 27.1 ± 0.6 in the ?D group, 23.62 ± 0.42 in the N group, and 19.46 ± 0.32 in the +D group (P < 0.05). The percentage of CD8⁺ lymphocytes was 12.15 ± 0.61 in the ?D group, 8.7 ± 0.64 in the N group, and 7.12 ± 0.48 in the +D group (P < 0.05). The CD4⁺/CD8⁺ ratio was 2.23 ± 0.15 in the ?D group, 2.71 ± 0.21 in the N group, and 2.73 ± 0.31 in the +D group (P < 0.05). The plasma IFN-γ levels were 416.42 ± 16.42 pg/ml in the ?D group, 325.41 ± 11.16 pg/ml in the N group, and 276.26 ± 25.32 pg/ml in the +D group (P < 0.005). The plasma IL-10 levels were 16.45 ± 1.58 pg/ml in the ?D group, 24.31 ± 2.16 pg/ml in the N group, and 26.28 ± 0.42 pg/ml in the +D group (P < 0.005). The serum TB-PPD-specific antibody level was significantly higher in the ?D group than in the N and +D groups. Vitamin D deficiency affects the immunity against Mycobacterium tuberculosis infection in mice.     

Influence of formulation ratio of the plant components on the antimalarial properties of MAMA decoction

Mangifera indica, Alstonia boonei, Morinda lucida and Azadirachta indica (MAMA) decoction, commonly prepared and used in Nigeria from 1:1:1:1 ratio of Mangifera indica L. (Anacardiaceae), Alstonia boonei De Wild (Apocynaceae), Morinda lucida Benth (Rubiaceae), and Azadirachta indica A. Juss (Meliaceae) leaves, plus four new variants of this combination were subjected to three in vivo antimalarial test models using chloroquine-sensitive Plasmodium berghei berghei to determine the most active under each of the test models. Using the original formulation, MAMA (1:1:1:1) which gave ED₅₀ and ED₉₀ of 101.54?±?2.95 and 227.18?±?2.95, respectively, as reference for comparison, MAMA-1 (1:2:2:2), with 79.58?±?1.30 and 170.98?±?1.30, gave significantly (p?<?0.05) higher survival at 85 and 340 mg/kg when 80 % of the mice survived for 15.6 and 17.8 days, respectively, while MAMA-2 (2:1:2:2), with 83.57?±?1.93 and 164.23?±?1.93, gave comparable survival except at 170 mg/kg with 60 % survivors for 12 days. MAMA-1 and MAMA-2 were the best curative formulations with MAMA-1 giving additional prophylactic activity. MAMA-3 (2:2:2:1) with 98.70?±?0.91 and 220.17?±?0.91, gave comparable (p?>?0.05) survival at 85 mg/kg with 60 % survival for 13.2 days and significantly higher survival at 42.5 mg/kg for 17 days with 40 % survival. Both MAMA and MAMA-3 were the best chemosuppressive formulations plus additional curative activities. MAMA-4 (1:1:2:2), the best prophylactic formulation with 94.87?±?2.43 and 201.20?±?2.43 gave significantly higher (p?<?0.05) survival at all doses except at 21.25 mg/kg which gave 60 % survival up to 10 days. Thus, the antimalarial therapy desired, following appropriate diagnosis, whether prophylactic, chemosuppressive or curative would determine which of the MAMA decoction formulations to be prescribed. This phenomenon of formulary optimization may also be applied to other pharmacological activities.     

C-Reactive Protein Measurements as a Marker of the Severity of Chronic Obstructive Pulmonary Disease Exacerbations

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the lungs. Acute exacerbations of COPD (AE-COPD) are a result of infectious or non-infectious instances. In our study, we aimed to determine whether serum C-reactive protein (CRP) levels are predictive indicators for disease severity and prognosis in hospitalized patients with AE-COPD. A total of 64 patients (36 regular ward and 28 ICU patients) were included in the study. Cases were identified and classified according to the Global Initiative for COPD. The first CRP test levels at acceptance at the ward or intensive care unit were counted in the study. CRP levels of patients in intensive care were significantly higher than those of patients in the regular ward. Mean values of CRP were detected to be 6.28?±?6.53 mg/dl in the regular ward cases and 16.9?±?12.03 mg/dl in the ICU patients (p?<?0.01). The stage of COPD did not indicate a significant difference in terms of CRP values. Mean CRP values were found to be 16.02?±?6.95 mg/dl in mortal cases and 9.76?±?11.09 mg/dl in survivors (p?<?0.01). High CRP levels were considered as a prognostic parameter and indicator of severity of AE-COPD. Increased mortality risk was found to be associated with high CRP values.     

The protective effects of the methanolic root bark extract of <Emphasis Type="Italic">Afzelia africana</Emphasis> on conception and fetal development in diabetic female rats

This study was carried out to determine the protective effect of methanolic root bark extract of Afzelia africana on conception and fetal development in alloxan-induced diabetic female rats. Twenty-four female rats were used in this study and were assigned into four groups of six rats each using random sampling. Diabetes was induced in groups 1, 2, and 3 but not induced in group 4. Groups 1 and 2 were treated with 250 mg/kg of the extract and glibenclamide (2 mg/kg), respectively while groups 3 and 4 were treated with distilled water (10 ml/kg). From the study, there were significant increases (p?<?0.05) in both the mean crown-rump length and fetal weight (5.85?±?0.065) (6.02?±?0.085) in group 3 when compared with groups 1 (4.44?±?0.065) (4.87?±?0.075), 2 (4.54?±?0.070) (4.78?±?0.21), and 4 (4.53?±?0.08) (4.83?±?0.10), respectively. The mean crown-rump length and fetal weight of groups 1, 2, and 4 did not differ significantly (p?>?0.05) from one another. This shows that the extract (group 1) might have lowered the blood glucose level just as the standard drug (group 2) and prevented the transport of excess glucose from the mother through the placenta to the fetuses. There was a significant reduction (p?<?0.05) in the mean value of number of offspring or litter size in group 3 (2.75?±?0.25) when compared to groups 1 (6.50?±?0.87), 2 (6.54?±?0.79), and 4 (7.00?±?1.15). Also in group 3, there was a significant decrease (p?<?0.05) in the uterine weight (2.15?±?0.15) when compared to groups 1 (2.97?±?0.39), 2 (2.99?±?0.37), and 4 (3.17?±?0.17), respectively. From the above results, the extract had protective effect on conception and fetal development in diabetic females.     

White Blood Cell Subtypes after STEMI: Temporal Evolution, Association with Cardiovascular Magnetic Resonance��Derived Infarct Size and Impact on Outcome

The evolution of white blood cells after ST elevation myocardial infarction (STEMI) and their association with infarct size and major adverse cardiac events (MACE) remains unclear. Two hundred eleven patients underwent CMR after STEMI. Infarct mass (grams) was determined. Neutrophil, lymphocyte, and monocyte counts (×1,000 cells/ml) were measured upon arrival and at 12, 24, 48, 72, and 96 h. Patients with large infarctions (3rd tertile????28.5 g vs. 1st and 2nd tertiles?<?28.5 g) showed a larger neutrophil count at 12 h (14.8?±?4.8 vs. 11.4?±?3.3, p?<?0.0001) and an increased monocyte count (maximum at 24 h (0.65[0.50?C0.91] vs. 0.55[0.42?C0.71], p?=?0.004)) but no difference in lymphocyte count. Neutrophil count at 12 h independently predicted large infarctions (OR 1.14, 95%CI [1.04?C1.26], p?=?0.008). During follow-up (median 504 days), 25 MACE occurred. Neutrophil count at 96 h independently predicted MACE (HR 1.2, 95%CI [1.1?C1.4], p?=?0.003). Large infarctions show a marked neutrophil peak and an increasing monocyte count. Neutrophil count independently predicts large infarctions and MACE.     

Serum Levels of Calreticulin in Correlation with Disease Activity in Patients with Rheumatoid Arthritis

Objective

The aim of our study was to investigate the contribution of serum calreticulin (CRT) in the assessment of disease activity in rheumatoid arthritis (RA).

Methods

Serum CRT levels were measured by ELISA in 70 patients with established RA, 30 systemic lupus erythematosus (SLE), 25 other autoimmune diseases, 20 osteoarthritis (OA), and 35 of healthy controls (HC). Correlations of CRT serum levels with disease activity [Disease Activity Score for 28 joints (DAS28)], erythrocyte sedimentation rate(ESR) and C-reactive protein (CRP) were assessed. Serum CRT levels were also detected in RA patients whose RF, anti-CCP and anti- MCV antibodies were positive and negative.

Results

Serum CRT levels in RA patients (4.817?±?2.425 ng/ml) was significantly higher (P <0.05) compared with those in the serum of OA (3.574?±?0.942 ng/ml), SLE (4.013?±?1.536 ng/ml), other autoimmune diseases (3.882?±?0.837 ng/ml) and HC (3.726?±?0.627 ng/ml). Significant positive correlation of CRT with DAS28, ESR and CRP was found in RA patients. Furthermore, RA patients whose anti-CCP and anti-MCV antibodies were positive had higher levels of CRT (P?<?0.01).

Conclusion

Serum CRT levels were increased in patients with RA compared with those controls. Moreover, a significant correlation was observed between serum CRT levels and disease activity in RA. It might be used as a potential biomarker for clinical diagnosis and provide additional information regarding disease activity along with the traditional indices such as ESR and CRP.     

Serum Soluble Triggering Receptor on Myeloid Cells-1 (sTREM-1) is Elevated in Systemic Lupus Erythematosus but does not Distinguish Between Lupus Alone and Concurrent Infection

We sought to determine serum triggering receptor expressed on myeloid cell-1 (sTREM-1) level in a cohort of patients with systemic lupus erythematosus (SLE). Serum sTREM-1 level of 98 patients with SLE and 49 healthy controls was assayed by ELISA. Serum sTREM-1 level was significantly elevated in a cohort of 78 unselected consecutively recruited patients with SLE (mean 1.1?±?2.8 ρg/ml, median 0.02 ρg/ml) compared to that of the controls (mean 0.11?±?0.3 ρg/ml, median 0 ρg/ml; p?<?0.0001). We also determined serum sTREM-1 level of 20 SLE patients with a concurrent infection (mean 0.6?±?1.1 ρg/ml, median 0.12 ρg/ml) and found it not statistically significant compared with that of the patients without infection. Serum sTREM-1 level did not correlate with SLE disease activity. Our finding of elevated serum sTREM-1 level suggests an increased shedding of TREM-1 in SLE and a possible novel pathway of innate immune response in autoimmunity.     

Restorative effect of Dendrophthoe falcata (L.f.) Ettingsh on lipids,lipoproteins, and lipid-metabolizing enzymes in DMBA-induced mammary gland carcinogenesis in Wistar female rats

Lipid, lipoproteins, and lipid-metabolizing enzymes are associated with breast cancer risk. In this study, the potential of hydroalcoholic extract (HEDF) of Dendrophthoe falcata (L.f) Ettingsh (Loranthaceae) for the management of lipid metabolism on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma was investigated in Wistar female rats. Thirty female rats (55 days of age) were divided into five groups: control, DMBA (25 mg in 0.5 ml of olive oil by air pouch technique), DMBA?+?HEDF (250, 475, and 950 mg/kg). After 90 days of induction, HEDF was administered for 28 days by gastric intubations. The levels of lipids, lipid-metabolizing enzymes, and lipoproteins were analyzed in the plasma and liver of both control and experimental animals. Rats treated with DMBA showed an increase (p?<?0.05) in levels of phospholipids, triglycerides, free fatty acids, total cholesterol, and free cholesterol and a decrease (p?<?0.01) in levels of ester cholesterol in the plasma and liver. The levels of very low-density lipoprotein and low-density lipoprotein increased (p?<?0.01), while the levels of high-density lipoproteins decreased (p?<?0.001) in plasma. Moreover, there was a significant increase (p?<?0.001) in activities of total lipase, cholesterol ester hydrolase, cholesterol ester synthase but with a sharp decrease (p?<?0.01) in lecithin cholesterol-acyl transferase and lipoprotein lipase in animals with mammary cancer. HEDF treatment caused the activity of these alterations in biochemical parameters to return to almost normal control levels. Also, histopathological analysis of the breast tissue was analyzed by hematoxylin and eosin staining, and results revealed the cytoprotective role of HEDF against mammary carcinogenesis. The effects of HEDF were found to be dose dependent in nature.     

Oxidative stress levels are correlated with <Emphasis Type="Italic">P15</Emphasis> and <Emphasis Type="Italic">P16</Emphasis> gene promoter methylation in myelodysplastic syndrome patients

Oxidative stress and abnormal DNA methylation have been implicated in some types of cancer, namely in myelodysplastic syndromes (MDS). Since both mechanisms are observed in MDS patients, we analyzed the correlation of intracellular levels of peroxides, superoxide anion, and glutathione (GSH), as well as ratios of peroxides/GSH and superoxide/GSH, with the methylation status of P15 and P16 gene promoters in bone marrow leukocytes from MDS patients. Compared to controls, these patients had lower GSH content, higher peroxide levels, peroxides/GSH and superoxide/GSH ratios, as well as higher methylation frequency of P15 and P16 gene promoters. Moreover, patients with methylated P15 gene had higher oxidative stress levels than patients without methylation (peroxides: 460 ± 42 MIF vs 229 ± 25 MIF, p = 0.001; superoxide: 383 ± 48 MIF vs 243 ± 17 MIF, p = 0.022; peroxides/GSH: 2.50 ± 0.08 vs 1.04 ± 0.34, p < 0.001; superoxide/GSH: 1.76 ± 0.21 vs 1.31 ± 0.10, p = 0.007). Patients with methylated P16 and at least one methylated gene had higher peroxide levels as well as peroxides/GSH ratio than patients without methylation. Interestingly, oxidative stress levels allow the discrimination of patients without methylation from ones with methylated P15, methylated P16, or at least one methylated (P15 or P16) promoter. Taken together, these findings support the hypothesis that oxidative stress is correlated with P15 and P16 hypermethylation.     

The effect of self-licking behavior on pharmacokinetics of eprinomectin and clinical efficacy against Psoroptes cuniculi in topically administered rabbits

Ear mange mite Psoroptes cuniculi, one of the predominant parasites in rabbits, can cause considerable weight loss, low favorable fee conversion rates, and meningitis. The present experiment was to investigate the difference of plasma disposition and the variation of clinical efficacy under the effect of animal self-licking behavior in topically administered rabbits. Ten rabbits for pharmacokinetic study in two groups (the self-licking and the non-licking) were topically administered with 1 mg kg^?1 of eprinomectin. In the self-licking group, rabbits were allowed to self-lick freely, while, to prevent self-licking, each animal in the non-licking group was fitted with a pet collar. Compared to the non-licking group, self-licking behavior contributed to an extremely significant shorter half-life of absorption (14.85?±?2.79 h in licking group vs. 29.44?±?7.81 h in non-licking group, p?<?0.01) and an extremely significant higher C _max value for eprinomectin (21.95?±?5.36 h in licking group vs. 6.98?±?0.72 ng ml^?1 in non-licking group, p?<?0.01) in plasma disposition. An extremely significantly shorter mean residence time (50.72?±?3.45 h) in self-licking group was also determined compared with the value obtained in non-licking group (106.66?±?7.39 h; p?<?0.01). Clinical efficacy study of eprinomectin was examined in rabbits naturally infested with P. cuniculi which were randomly allocated in three groups: the self-licking, the non-licking, and control groups. All rabbits in the self-licking and the non-licking groups were treated with topical eprinomectin at a single dose of 2 mg kg^?1 (day 0). Topical eprinomection led to a complete parasitological recovery in both treated groups on day 14 and remained free of live mites and clinical lesions from day 21 to the end of the study period (day 35).     

Atrial functional and geometrical remodeling in highly trained male athletes: for better or worse?

Purpose

Highly trained athletes have an increased risk of atrial arrhythmias. Atrial geometrical and functional remodeling may be the underlying substrate. We analyze and relate atrial size, deformation and performance in professional handball players compared with non-sportive subjects.

Methods

24 Professional handball players and 20 non-sportive males were compared. All subjects underwent an echocardiographic study with evaluation of left (LA), right atrial (RA) dimensions and deformation by strain (Sa) and strain rate (SRa). Atrial performance was assessed from the atrial stroke volume (SV). With computational geometrical models, we studied the relation between atrial volumes, strains and SV and compared atrial working conditions. We estimated the functional reserve and a resulting average wall stress.

Results

LA and RA volumes were larger in athletes than in controls (35.2 ± 8.8 vs. 24.8 ± 4.3 ml/m², p < 0.01 and 29.0 ± 8.4 vs. 19.0 ± 5.1 ml/m², p < 0.01 respectively). LASa and RASa during active atrial contraction were decreased in athletes (?12.2 ± 2.0 vs. ?14.5 ± 2.1 %, p < 0.01 and ?12.1 ± 1.8 vs. ?14.2 ± 1.5 %, p < 0.01 respectively). LASV was similar between groups (6.6 ± 1.4 vs. 7.3 ± 1.1 ml, p = 0.19) and RASV was lower in athletes (6.2 ± 1.3 vs. 7.2 ± 1.1 ml, p < 0.01). Computational models showed that this different operational mode potentially increases performance reserve, but at the cost of higher atrial wall stress.

Conclusion

A proportion of athletes with enlarged LA and RA showed different atrial contractile performance, likely resulting in atria working at higher wall stress.