Assessment of aquo-ethanolic extract of Camellia sinensis against Carbapenem Resistant Escherichia coli: In Vivo Trials in a Murine Model

The prevalence of Carbapenem Resistant Escherichia coli (CRE) has increased considerably during the last decade, which can be ascribed to relative scarcity of effective non toxic antimicrobial agents. The present study was conducted to evaluate the antimicrobial activity of aquo-ethanolic (1:1) extract of leaves of Camellia sinensis (PTRC-31911-A) against Carbapenem Resistant Escherichia coli at preclinical level using peritonitis infection model in Sprague Dawley rats. Efficacy analysis of PTRC-31911-A involved enumeration of CRE colonies in blood and urine samples of test animals for a period of 5 days from infection. A reduction in microbial count of biological fluids was considered as the primary endpoint of the selected murine model. Physical, biochemical, hematological and histological indices of toxicity were employed as secondary relative indicators of the induced disease. Physical manifestations of infected rats included significantly high body temperature (Temp_Infected = 103.18 °F, ∼5% increase) and noteworthy reduction in weight (Weight_Infected = 126.83 g, ∼15% decrease) as compared to control. Significant (P < 0.05) increase in total white blood cells, eosinophil and monocyte counts as well as a significant decrease (P < 0.05) in erythrocytes count, hematocrit volume, red blood cell distribution width and hemoglobin concentration were observed in the infected group as compared to the control group. Furthermore, noteworthy increase in liver and kidney function test parameters were observed in case of infected groups. All the hematological and biochemical parameters were found to be within optimum range in case of treatment group, indicating restoration of homeostasis. Histopathological studies also presented symptoms of hemorrhage and glomerular damage with structural distortion in glomerular capillary loops of infected groups, which were later recovered in treated groups, indicating the nephro-protective potential of PTRC-31911-A. The study clearly points out that Camellia sinensis extract (PTRC-31911-A; single dose of 5 mg/Kg bwt; oral, + 24 h) is highly effective against Carbapenem Resistant Escherichia coli owing mainly to the presence of flavonoids and polyphenolic compounds, identified by LCMS. Ongoing studies are expected to further unravel the mechanism of action and bioactivity determinants of this broad spectrum plant extract.     

Early targeted brain COOLing in the cardiac CATHeterisation laboratory following cardiac arrest (COOLCATH)

IntroductionTrials demonstrate significant clinical benefit in patients receiving therapeutic hypothermia (TH) after cardiac arrest. However, incidence of mortality and morbidity remains high in this patient group. Rapid targeted brain hypothermia induction, together with prompt correction of the underlying cause may improve outcomes in these patients. This study investigates the efficacy of Rhinochill^®, an intranasal cooling device over Blanketrol^®, a surface cooling device in inducing TH in cardiac arrest patients within the cardiac catheter laboratory.Methods70 patients were randomized to TH induction with either Rhinochill^® or Blanketrol^®. Primary outcome measures were time to reach tympanic ≤34 °C from randomisation as a surrogate for brain temperature and oesophageal ≤34 °C from randomisation as a measurement of core body temperature. Secondary outcomes included first hour temperature drop, length of stay in intensive care unit, hospital stay, neurological recovery and all-cause mortality at hospital discharge.ResultsThere was no difference in time to reach ≤34 °C between Rhinochill^® and Blanketrol^® (Tympanic ≤34 °C, 75 vs. 107 mins; p = 0.101; Oesophageal ≤34 °C, 85 vs. 115 mins; p = 0.151). Tympanic temperature dropped significantly with Rhinochill^® in the first hour (1.75 vs. 0.94 °C; p < 0.001). No difference was detected in any other secondary outcome measures. Catheter laboratory-based TH induction resulted in a survival to hospital discharge of 67.1%.ConclusionIn this study, Rhinochill^® was not found to be more efficient than Blanketrol^® for TH induction, although there was a non-significant trend in favour of Rhinochill^® that potentially warrants further investigation with a larger trial.     

Outcome and risk factors in children after traumatic cardiac arrest and successful resuscitation

IntroductionProspective collected data of the TraumaRegister DGU^® were analyzed to derive survival rates and predictors for non-survival in the children who had suffered traumatic cardiorespiratory arrest. Different time points of resuscitation efforts (only preclinical, in the emergency room (ER) or preclinical + ER) were analyzed in terms of mortality and neurological outcome.MethodsThe database of the TraumaRegister DGU^® comprising 122,742 patients from 1993 to 2013 was analyzed. The main focus of this survey was on the paediatric group defined by an age ≤14 years who could be compared to adults. Different statistical analysis (univariate and multivariate analysis, logistic regression) were performed with mortality as the target variable. Differences between the paedatric group and adults were analysed by Fisher's exact test.ResultsData after preclinical and/or ER resuscitation from 152 children and 1690 adults were analyzed. A good or moderate outcome (GOS 5 + 4) was found in 19.4% of the children's group compared to 12.4% of the adults (p = 0.02).Analysis of the GOS 5 + 4 subgroups after preclinical resuscitation only revealed that these outcomes were achieved by 19.4% of the paediatric group and 13.2% of the adults (p = 0.24), after ER-only resuscitation by 37.0% of the children and 19.6% of the adults (p = 0.046), and after preclinical and ER resuscitation by only 10.9% of the children compared to 2.5% of the adults (p = 0.006). Taking only survivors into account, 84.8% of the children and 62% of the adults had a GOS 4 + 5.The highest risk for mortality in the logistic regression model was associated with preclinical intubation, followed by GCS 3, blood transfusion and severe head injury with AIS ≥3 and ISS.ConclusionsCPR in children after severe trauma seems to yield a better outcome than in adults, and appears to be more justified than the current guidelines would imply. Resuscitation in the ER is associated with better neurological outcomes compared with resuscitation in a preclinical context or in both the preclinical phase and the ER. Our children's outcomes seem to be better than those in most of the earlier studies, and the data presented might support algorithms in the future especially for paediatric resuscitation.     

Improved cisplatin delivery in cervical cancer cells by utilizing folate-grafted non-aggregated gelatin nanoparticles

PurposeCisplatin is highly effective in the treatment of cervical cancer. However, in therapeutic doses, cisplatin induces several adverse effects due to undesirable tissue distribution. Therefore, it is worth targeting cisplatin in cervical cancer cells by implicating non-aggregated ligand-modified nanotherapeutics.Methods and resultsHere, we report the preparation of non-aggregated folic acid-conjugated gelatin nanoparticles of cisplatin (Cis-GNs-FA) by two-step desolvation method with mean particle size of 210.6 ± 9.6 nm and 140.5 ± 10.9 nm for Cis-GNs to improve the drug delivery in cervical cancer, HeLa cells. FTIR and DSC spectra confirmed the presence and stability of cisplatin in gelatin matrix. Furthermore, amorphization of cisplatin in nanoparticles was ascertained by PXRD. Drug release followed a first-order release kinetic at both pH ∼ 5.6 (cervical cancer pH) and pH ∼ 7.4. In addition, a significant (P < 0.05) decrease in IC₅₀ value (8.3 μM) and enhanced apoptosis were observed in HeLa cells treated with Cis-GNs-FA as compared to Cis-GNs (15.1 μM) and cisplatin solution (40.2 μM). In contrast, A549 lung cancer cells did not discriminate between Cis-GNs-FA and Cis-GNs due to the absence of folate receptors-α (FR-α). Consistently, higher cellular uptake, 80.54 ± 7.60% was promoted by Cis-GNs-FA significantly (two-way ANOVA, P < 0.05) greater than 51.68 ± 9.78%, by Cis-GNs. This was also illustrated by CLSM images, which indicated that Cis-GNs-FA preferably accumulated in the cytoplasm of HeLa cells nearby nucleus by following receptor-mediated endocytosis pathway as compared to Cis-GNs.ConclusionTherefore, Cis-GNs-FA warrants further in-depth in vitro and in vivo investigations to scale up the technology for clinical translation.     

The influence of post-rewarming temperature management on post-rewarming fever development after cardiac arrest

Aim of the studyWe evaluated the influence of post-rewarming temperature management (PRTM) on post-rewarming fever development and determined the association between the temperature in the immediate post-targeted temperature management (TTM) period and outcomes.MethodsThis retrospective observational study included consecutive adult cardiac arrest survivors treated with TTM from January 2008 to December 2013. Beginning in August 2010, our institution implemented a PRTM protocol involving continued use of temperature management device to maintain normothermia during the first 24 h after rewarming. The outcomes were in-hospital mortality and neurologic outcome at discharge. We evaluated the effect on clinical outcomes of post-rewarming fever defined at a temperature over 38 °C within 48 h after rewarming.ResultsOf 277 included patients, 55.2% underwent PRTM. The incidence of post-rewarming fever did not differ between the PRTM and no-PRTM groups (odds ratio [OR] 0.963, confidence interval [CI] 0.519, 1.787). Post-rewarming fever was associated with decreased in-hospital mortality (OR 0.243, CI 0.110, 0.534) and decreased rate of unfavorable neurologic outcome (OR 0.312, CI 0.182, 0.534). During 48 h following rewarming, mean temperature was 36.5 °C (36.2–36.8 °C), and peak temperature was 37.5 °C (36.8–38.1 °C). On multivariate analyses, lower mean temperature was associated with increased in-hospital mortality (OR 0.099, CI 0.037, 0.262) and unfavorable neurologic outcome (OR 0.071, CI 0.026, 0.193).ConclusionIt appeared that PRTM did not prevent post-rewarming fever development. Post-rewarming fever was associated with favorable outcomes while lower body temperature after rewarming was associated with unfavorable outcomes. Our results require further confirmation by larger prospective studies.     

Antidiabetic,antihyperlipidemic and anti-inflammatory effects of tilianin in streptozotocin-nicotinamide diabetic rats

Flavonoids from medicinal plants have been used in traditional medicine to treat a variety of prevalent diseases. Flavones activate the signaling pathways promoting fuel metabolism and insulin sensitizing in hepatocytes and adipocytes, which suggests that flavones may have the potential to exert in vivo antidiabetic and antihyperlipidemic effects. Thus, the aim of the current study was to determine the antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in diabetic rats. Also, to understand the mechanism involved using in vitro 3T3-L1 cells and tissues from experimental animals treated with test samples through molecular profile studies.Non insulin-dependent diabetic mellitus (NIDDM) rats were treated over a short period (for 10 days) with 60 mg/Kg/day of tilianin. After treatment, a biochemical blood profile was determined. Also, adipose and thoracic aortic tissues were used to determine pro-inflammatory profile, adiponectin and adhesion molecules by real-time PCR. In 3T3-L1 cells pretreated with tilianin (10 μM), PPARα, PPARγ, GLUT4, FATP-1 and ACSL-1 mRNA expression were measured. In order to explain the potential PPARα interaction with tilianin, a docking study with PPARα was carried out. Thus, intragastric administration of tilianin and metformin induced a decrease in plasma glucose (GLU) in diabetic rats on day 6, and remained significantly lower until the end of the treatment; also blood triacylglycerides (TAG) and cholesterol (CHOL) (p < 0.05) were diminished. Moreover, IL-1β and IL-18 expression was significantly decreased in adipose tissue (p < 0.05); meanwhile adiponectin was significantly overexpressed (p < 0.05). Besides, ICAM-1 expression was significantly reduced in aortic tissue (p < 0.05). In 3T3-L1 cells it was found that tilianin increased PPARα and ACSL1 mRNA levels (p < 0.05). Finally, tilianin docking studies with PPARα showed polar interactions with Glu269, Tyr314, His 440 and Tyr464 residues. In conclusion, short-term tilianin treatment might exert its antidiabetic and antihyperlipidemic effect by modulating a pro-inflammatory profile, and increasing adiponectin expression. In addition, our results suggest the possible interaction of tilianin with PPARα.     

CD26 a cancer stem cell marker and therapeutic target

Cancer stem cells (CSCs) comprise a tumor subpopulation responsible for tumor maintenance, resistance to chemotherapy, recurrence and metastasis. The identification of this cell group is very important, but there is still no consensus on its characterization. Several CSC markers have been described, like CD133, CD24, CD44 and ALDH1, but more research to identify new markers to facilitate the identification of CSC in a heterogeneous tumoral mass is required. Thus, this article describes the CD26 expression as a CSC marker and the role that it plays in different types of cancer. CD26 expression correlates with some characteristics of CSCs, like the formation of spheres in vitro, formation of new tumors, and resistance to chemotherapy. CD26 is therefore suggested as an auxiliary marker for CSC in different types of cancer, and as a potential therapeutic target.     

Stealth lipid coated aquasomes bearing recombinant human interferon-α-2b offered prolonged release and enhanced cytotoxicity in ovarian cancer cells

PurposeIn present investigation, recombinant human interferon-α-2b (rhINF-α-2b) loaded aquasomes were prepared, optimized and overlaid with PEGylated phospholipid to offer prolong release and high therapeutic index against ovarian cancer, SKOV3 cells.Methods and resultsCentral Composite Design (CCD) and Response Surface Methodology (RSM) were employed to calculate the optimized conditions, 1:3 core to coat ratio, sonication power of 12.5 W and time of about 55 min for preparation of aquasomes. Consequently, rhINF-α-2b-Py-5-P-Aq.somes exhibited higher protein loading capacity and retained structural conformations of rhINF-α-2b, as compared to rhINF-α-2b-Cellob-Aq.somes, rhINF-α-2b-Tre-Aq.somes and rhINF-α-2b-Core (CaHPO₄). Further, optimized rhINF-α-2b-Py-5-P-Aq.somes was superimposed with phospholipid-PEG₂₀₀₀ to prolong the release pattern of rhINF-α-2b from aquasomes. The rhINF-α-2b-core (CaHPO₄) released 97.3% of protein in 1 h, while 95.3% of rhINF-α-2b was released by rhINF-α-2b-Tre-Aq.somes in 4 h. Concurrently, rhINF-α-2b-Cellob-Aq.somes and rhINF-α-2b-Py-5-P-Aq.somes released 96.2% and 97.8% of rhINF-α-2b respectively in 6 and 8 h. Ultimately, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG₂₀₀₀ displayed evidence of its prolonged release pattern and released 98.1% of rhINF-α-2b in 336 h. FT–IR and XRD substantiated the involvement of vigorous intermolecular hydrogen bonding and amorphous geometry in rhINF-α-2b-Py-5-P-Aq.somes. In last, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG₂₀₀₀ exhibited the ∼ 4.55, 1.92, 2.3, 2.8, and 3.84 fold reductions in IC₅₀ as compared to free rhINF-α-2b, rhINF-α-2b-Py-5-P-Aq.somes, rhINF-α-2b-Cellob-Aq.somes, rhINF-α-2b-Tre-Aq.somes and rhINF-α-2b-Core (CaHPO₄), respectively.ConclusionTherefore, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG₂₀₀₀ warrant further in depth in vitro and in vivo antitumor study to scale up the technology for clinical intervention.     

Qi deficiency is associated with depression in chronic hemodialysis patients

ObjectiveDepression is a common bio-psycho-social problem in hemodialysis (HD) patients. Traditional Chinese medicine has been used for symptom management in patients with depression. Identification of the specific constitution in traditional Chinese medicine is critical for personalized care. However, the association between depression and specific constitution in HD patients is unknown.MethodsWe conducted a cross-sectional study in all chronic HD patients (HD for more than 3 months) at China Medical University Hospital in Taiwan. The depression symptom severity was determined using the Beck Depression Inventory II (BDI-II). Clinical patterns in Chinese medicine were determined using the Constitution in Chinese Medicine Questionnaire. The association between constitution and depression was analyzed using logistic regression.ResultsWe recruited 467 chronic hemodialysis patients, including 219 females and 248 males, with a mean age of 63 ± 12 years. The mean duration of HD was 5.8 years. The mean score for the BDI-II was 11 (interquartile range 8–14). The major constitution was Yang-deficiency (43.7%) among these chronic HD patients. Qi-deficiency was correlated with a duration of HD of more than 5.8 years (p = 0.04). Qi-deficiency [odds ratio (OR): 4.05, 95% confidence interval (CI): 1.69–9.72, p < 0.01] was also associated with depression in logistic regression with adjustments for confounders, including calcium, phosphorus and hemoglobin levels.ConclusionQi-deficiency constitution in Chinese medicine is associated with depression in chronic HD patients. Further studies are needed to determine whether treating Qi-deficiency integrating Chinese medicine treatment can improve patients’ depression symptoms.     

Changes in treatments and outcomes among elderly patients with out-of-hospital cardiac arrest between 2002 and 2012: A post hoc analysis of the SOS-KANTO 2002 and 2012

BackgroundLittle is known about recent changes in pre- and in-hospital treatments and outcomes for elderly patients with out-of-hospital cardiac arrest (OHCA).MethodsWe compared data collected for the SOS-KANTO study in 2002 and 2012. We included patients aged ≥65 years who experienced OHCA of cardiac aetiology. The primary endpoint was favourable neurological outcomes 1 month after cardiac arrest.ResultsA total of 8,964 (2002 vs. 2012: 3,544 vs. 5,420) patients were eligible for the current analysis. The proportion of pre-hospital return of spontaneous circulation (ROSC) increased significantly (3.8 vs. 5.6%, p < 0.001). Among patients achieving ROSC, the proportion of advanced in-hospital treatments (i.e. extracorporeal membrane oxygenation, therapeutic hypothermia, and/or percutaneous coronary angiogram/intervention) provided increased significantly in 2012 (1.2 vs. 5.5%, p < 0.001; 2.6 vs. 15.1%, p < 0.001; 4.9 vs. 16.5%, p < 0.001; respectively). The proportion of favourable neurological outcomes at 1 month increased significantly in 2012 (1.6 vs. 2.7%, p = 0.001). A logistic regression analysis that did not consider advanced in-hospital treatments showed a significantly higher rate of favourable neurological outcomes in the 2012 group than that in the 2002 group (OR, 2.2; 95% CI, 1.4–3.5). However, this difference was no longer observed in the second regression model that accounted for advanced in-hospital treatments (OR, 1.6; 95% CI, 0.9–2.9).ConclusionThere was an increased proportion of aggressive treatment, both pre- and in-hospital, for elderly patients with cardiogenic OHCA in the Kanto area, Japan. Favourable neurological outcomes improved significantly over 10 years.     

Pseudomonas aeruginosa injection enhanced antitumor cytotoxicity of cytokine-induced killer cells derived from cord blood

Cord blood (CB) is becoming an extensive source of cytokine-induced killer cells. It had been used in several clinical settings and proven to be efficacious and safe. Therefore, we investigated the possibility of combining CIK cells derived from cord blood (CB-CIK) and Pseudomonas aeruginosa injection (PA-MSHA) in order to enhance the cytotoxicity of CB-CIK cells against tumors. Compared with the CB-CIK cells, the PA-MSHA-treated CB-CIK cells demonstrated with increased proliferation rates, higher expression of activated cell surface marker CD28 and lower expression of inhibited cell surface markers PD-1 and CTLA-4. Furthermore, PA-MSHA-treated CB-CIK cells exhibited more effectively for secreting pro-inflammatory cytokine such as IFN-γ and expressing high levels of TLR2, TLR4 and TLR6. The expression of CD107a was higher in the CD3⁺CD56⁺ subset of PA-MSHA-treated CB-CIK cells. Our results indicate that the PA-MSHA-treated CB-CIK cells exhibited a more potent in cytotoxic activity against tumor cells. Thus, PA-MSHA enhanced the antitumor ability of CB-CIK cells.     

Prognostic values of gray matter to white matter ratios on early brain computed tomography in adult comatose patients after out-of-hospital cardiac arrest of cardiac etiology

Aim of the studyPrevious studies found that the gray matter to white matter ratio (GWR) on brain computed tomography (CT) could be used to predict poor outcomes in cardiac arrest survivors. However, these studies have included cardiac arrests of both cardiac and non-cardiac etiologies. We sought to evaluate if the GWR on brain CT can help to predict poor outcomes after out-of-hospital cardiac arrest (OHCA) of cardiac etiology.MethodsUsing a multicenter retrospective registry of adult cardiac arrest survivors treated with therapeutic hypothermia, we identified survivors of OHCA of cardiac etiology who underwent brain CT within 24 h after successful resuscitation. Gray and white matter attenuations were measured, and the GWRs were calculated as in previous studies. The prognostic values of the GWRs were analyzed, and a logistic regression analysis was performed to determine the contribution of the GWR in predicting poor outcomes (Cerebral Performance Category 3–5).Resultsof 283 included patients, 140 had good outcomes and 143 had poor outcomes. Although the GWRs could predict poor outcomes with statistical significance, the sensitivities were remarkably low (3.5% to 5.6%) at cutoff values with 100% specificity. No significant difference in predictive performance was found between the primary predictive model, containing independent poor outcome predictors, and the primary predictive model combined with the GWR.ConclusionIn a cohort of comatose adults after OHCA of cardiac etiology, the GWR demonstrated poor predictive performance and was not helpful in predicting poor outcomes.     

Erdheim-Chester Disease: Characteristics and Management

Erdheim-Chester disease is a rare CD68⁺, CD1a⁻ non-Langerhans cell histiocytosis with multiorgan involvement. The etiology of Erdheim-Chester disease is unclear; there are no known associated infectious or hereditary genetic abnormalities. However, somatic BRAF mutations have recently been identified in these patients. Historically, the literature regarding the management of Erdheim-Chester disease consisted of case reports and small case series with anecdotal therapeutic responses to agents including, but not limited to, cytotoxic chemotherapy, bone marrow transplantation, cladribine, corticosteroids, IFN-α, the BCR-ABL/KIT inhibitor imatinib mesylate, the IL-1 receptor antagonist anakinra, the TNF-inhibitor infliximab, and recently the BRAF inhibitor vemurafenib. We performed a search of the literature using PubMed with the terms Erdheim Chester disease, without date limitations, including case reports, case series, original articles, and previous review articles. In the absence of large-scale studies, experience-based management prevails. The present review details our approach to the management of patients with Erdheim-Chester disease.     

Antineutrophil Cytoplasmic Antibody-Associated Renal Vasculitis Treated With Autologous Mesenchymal Stromal Cells: Evaluation of the Contribution of Immune-Mediated Mechanisms

We report the first case of renal antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis treated with autologous mesenchymal stromal cells (MSCs). A 73-year-old man was admitted to the hospital for malaise, weight loss, and oliguria. His serum creatinine level was 2.7 mg/dL but it rapidly increased to 7.8 mg/dL; urinalysis showed proteinuria and hematuria, and the ANCA to myeloperoxidase with a perinuclear pattern (pANCA) titer was high (132 IU/mL). Renal biopsy showed necrotizing crescentic glomerulonephritis. Standard immunosuppressive therapy (cyclophosphamide and corticosteroids) was ineffective. Rituximab therapy was started, but it was discontinued after the third dose to minimize the risk of systemic spread of a severe oral Candida infection and to prevent superinfections that were facilitated by leukopenia. The patient received autologous MSCs, 1.5 × 10⁶ cells/kg body weight, intravenously. After 7 days, his serum creatinine level decreased to 2.2 mg/dL, pANCA titer decreased to 75 IU/mL, and urinalysis findings normalized. Eight months later, he received a second MSC infusion because his serum creatinine level increased. In 1 week, his creatinine level decreased to 1.9 mg/dL and his pANCA titer decreased to 14 IU/mL. Immunosuppressive therapy was subsequently withdrawn. At the last follow-up visit, 12 months after the second MSC infusion, the patient remained in clinical remission without any therapy. Infusion of MSCs induced expansion of the T-lymphocyte subset expressing a regulatory T-cell phenotype (CD4⁺CD25⁺Foxp3⁺) and a notable reduction in interferon-γ, interleukin 6, and tumor necrosis factor serum levels.     

Self-assembled betulinic acid protects doxorubicin induced apoptosis followed by reduction of ROS–TNF-α–caspase-3 activity

Doxorubicin (DOX) is a well-known drug used to treat a wide range of solid tumor and hematological malignancies, but the use of this drug is now restricted owing to its severe side effects, including normal cellular toxicity. This study was conducted to evaluate the potency of self-assembled betulinic acid (SA-BA) against DOX induced chemotherapeutic toxicity in human peripheral blood lymphocytes (PBLs). The isolated betulinic acid from the bark of Ziziphus jujuba tree was purified by column chromatography and characterized by FT–IR, XRD, ¹H NMR and self-assembly property was investigated by SEM imaging. DOX treatment produced significant reduction of viability of PBLs mainly by lowering cellular anti-oxidant pool and elevating the reactive oxygen species level. Pre-treatment with SA-BA followed by DOX exposure for 24 h protected the PBLs from DOX induced oxidative stress. Potent anti-apoptotic role of SA-BA was also confirmed by FACS analysis and western blot assay. Severe inflammation is one of the major concerns in DOX treatment. We found that pre-treatment with SA-BA on PBLs significantly protected the PBLs from DOX induced inflammation. Thus, our finding confirms that SA-BA can be used to ameliorate the cytotoxic effects of DOX, which can be a helpful strategy during DOX mediated chemotherapy in cancer patients.     

Reference Fitness Values in the Untrained Spinal Cord Injury Population

ObjectiveEstablish reference values of cardiorespiratory fitness applicable to the general, untrained spinal cord injury (SCI) population.DesignData were retroactively obtained from 12 studies (May 2004 to May 2012).SettingAn institution-affiliated applied physiology research laboratory.ParticipantsA total of 153 men and 26 women (age, 18–55y) with chronic SCI (N=179) were included. Participants were not involved in training activities for 1 or more months before testing and were able to complete a progressive resistance exercise test to determine peak oxygen consumption (Vo₂peak).InterventionsNot applicable.Main Outcome MeasurePercentile ranking (poor<20%; fair; 20%–40%; average, 40%–60%; good, 60%–80%; excellent, 80%–100%) used to establish reference values.ResultsReference cardiorespiratory fitness values based on functional classification as paraplegic or tetraplegic were established (paraplegic: median, 16.0mL·kg⁻¹·min⁻¹; range, 1.4–35.2mL·kg⁻¹·min⁻¹; tetraplegic: median, 8.8mL·kg⁻¹·min⁻¹; range, 1.5–21.5mL·kg⁻¹·min⁻¹) for untrained men and women. For the primary outcome measure (Vo₂peak), persons with paraplegia had significantly higher values than did persons with tetraplegia (P<.001). Although men had higher values than did women, these differences did not reach significance (P=.256). Regression analysis revealed that motor level of injury was associated with 22.3% of the variability in Vo₂peak (P<.001), and an additional 8.7% was associated with body mass index (P<.001). No other measure accounted for additional significant variability.ConclusionsEstablished reference fitness values will allow investigators/clinicians to stratify the relative fitness of subjects/patients from the general SCI population. Key determinants are motor level of injury and body habitus, yet most variability in aerobic capacity is not associated with standard measures of SCI status or demographic characteristics.     

Diagnosis and Management of Benign,Atypical, and Indeterminate Breast Lesions Detected on Core Needle Biopsy

Imaging abnormalities detected by mammographic screening often lead to diagnostic evaluations, with suspicious abnormalities subjected to image-guided core needle biopsy (CNB) to exclude malignancy. Most CNBs reveal benign pathological alterations, termed benign breast disease (BBD). Adoption of CNB presents challenges with pathologic classification of breast abnormalities and management of patients with benign or atypical histological findings. Patient management and counseling after CNB diagnosis of BBD depends on postbiopsy determination of radiologic-pathologic concordancy. Communication between radiologists and pathologists is crucial in patient management. Management is dependent on the histological type of BBD. Patients with concordant pathologic imaging results can be reassured of benign biopsy findings and advised about the future risk of developing breast cancer. Surgical consultation is advised for patients with discordant findings, symptomatic patients, and high-risk lesions. This review highlights benign breast lesions that are encountered on CNB and summarizes management strategies. For this review, we conducted a search of PubMed, with no date limitations, and used the following search terms (or a combination of terms): atypical ductal hyperplasia, atypical hyperplasia, atypical lobular hyperplasia, benign breast disease, cellular fibroepithelial lesions, columnar cell lesions, complex sclerosing lesion, core needle biopsy, fibroadenomas, flat epithelial atypia, lobular carcinoma in situ, lobular neoplasia, mucocele-like lesions, phyllodes tumor, pseudoangiomatous stromal hyperplasia, radial scar, and vascular lesions. The selection of references included in this review was based on study relevance and quality. We used additional articles culled from the bibliographies of retrieved articles to examine the published evidence for risk factors of BBD.     

Increased sensitivity of human lung adenocarcinoma cells to cisplatin associated with downregulated contactin-1

Contactin-1 (CNTN-1), a glycosyl phosphatidylinositol anchor neural cell adhesion molecule (ACAM), is thought to function not only in nervous system development but also in the invasion and metastasis of several tumours. To investigate whether CNTN-1 is involved in multidrug resistance (MDR) in lung adenocarcinoma, CNTN-1 expression was compared between MDR human lung adenocarcinoma A549/cisplatin (A549/DDP) cells and its progenitor A549 cells. The comparison showed that CNTN-1 expression in A549/DDP cells was significantly higher than in A549 cells both at the mRNA level and the protein level. In order to confirm the physiological function of the abnormal expression, lentivirus-mediated short hairpin RNA (shRNA) was used to silence CNTN-1. Cell cytotoxicity assay and cell apoptosis assay revealed that silencing CNTN-1 both in A549 cells and in A549/DDP cells not only rendered cells more sensitive to cisplatin than the negative control, but also increased the cisplatin-induced apoptosis. Metastasis and invasion assays demonstrated that CNTN-1 knockdown reduced metastasis and invasion but did not affect A549 or A549/DDP cell proliferation. To investigate whether the abnormal expression of CNTN-1 is associated with characteristics of patients with non-small cell lung cancer (NSCLC), immunohistochemistry was used to detect CNTN-1 expression in 143 tissue samples from NSCLC patients and the results showed that the degree of CNTN-1 expression positively correlated with lymphatic invasion in patients with lung adenocarcinoma who received adjuvant cisplatin- or carboplatin-based treatment after surgery. Thus, we concluded that CNTN-1 is closely related with MDR of lung adenocarcinoma. Additionally, CNTN-1 is a novel marker to predict chemotherapeutic efficacy of patients with lung adenocarcinoma, especially with regard to cisplatin- or carboplatin-based regimens.