Thalidomide attenuates mammary cancer associated-inflammation,angiogenesis and tumor growth in mice

Thalidomide has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on key components (blood vessel formation, inflammatory cell recruitment/activation, cytokine production) of 4T1 mammary tumor in mice. In addition, tumor growth and lung metastasis were evaluated. 4T1 cells were injected subcutaneously into Balb/c mice. After tumor engraftment (5 days), thalidomide (150 mg/kg) was administered to the treated group for 7 days. Tumors of control (saline) and treated groups were sized regularly, removed 12 days after inoculation and processed for biochemical and immunohistological parameters to assess neovascularization, inflammation and proliferative activity. Daily oral dose of thalidomide was able to reduce in 46% the tumor volume. The number of metastasis in the lungs was less in the thalidomide-treated group compared with the control animals. Assessment of tumor vascularization revealed a significant decrease in blood vessels formation by thalidomide. Likewise, the expression of FGF-1 showed weaker cytoplasmic positivity in the group treated with thalidomide compared with the control group. The levels of two cytokines, VEGF (pro-angiogenic) and TNF-α (pro-inflammatory) were decreased in tumor samples of thalidomide-treated group compared with the control group. Accumulation of neutrophils or macrophages in the 4T1 tumor measured by the activities of inflammatory enzymes, myeloperoxidase (MPO) for neutrophils and N-acetyl-β-D-glucosaminidase (NAG) for macrophages was inhibited by the treatment. By targeting key components of 4T1 tumor simultaneously, thalidomide was effective in attenuating tumor growth and metastasis. This approach, suppression of inflammation and angiogenesis may provide further insights for both prevention and treatment of cancer.     

Inducible nitric oxide synthase inhibition attenuates lung tissue responsiveness and remodeling in a model of chronic pulmonary inflammation in guinea pigs

We evaluated the influence of iNOS-derived NO on the mechanics, inflammatory, and remodeling process in peripheral lung parenchyma of guinea pigs with chronic pulmonary allergic inflammation. Animals treated or not with 1400 W were submitted to seven exposures of ovalbumin in increasing doses. Seventy-two hours after the 7th inhalation, lung strips were suspended in a Krebs organ bath, and tissue resistance and elastance measured at baseline and after ovalbumin challenge. The strips were submitted to histopathological measurements. The ovalbumin-exposed animals showed increased maximal responses of resistance and elastance (p < 0.05), eosinophils counting (p < 0.001), iNOS-positive cells (p < 0.001), collagen and elastic fiber deposition (p < 0.05), actin density (p < 0.05) and 8-iso-PGF2α expression (p < 0.001) in alveolar septa compared to saline-exposed ones. Ovalbumin-exposed animals treated with 1400 W had a significant reduction in lung functional and histopathological findings (p < 0.05). We showed that iNOS-specific inhibition attenuates lung parenchyma constriction, inflammation, and remodeling, suggesting NO-participation in the modulation of the oxidative stress pathway.     

Coincident chronic inflammatory demyelinating polyneuropathy and focal segmental glomerulosclerosis: a common autoimmunity?

A 40-year-old male developed swallowing difficulties, loss of strength, and imbalance. On admission, the patient exhibited bifacial, extremity weakness, ataxia, impaired sensation, and areflexia. Electrophysiology and nerve biopsy suggested demyelination. Spinal fluid revealed increased protein content. Plasmapheresis showed benefit, but neuropathy relapsed. At second recurrence, urine analysis showed heavy proteinuria. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS). Methylprednisolone and oral cyclophosphamide were given. Long-term steroids and immunoglobulin showed steady benefit. Concurrence of chronic inflammatory demyelinating polyneuropathy and FSGS suggests synergistic cellular and humoral autoimmune mechanisms related to either cross-reactivity within antigenic targets or mimicry between neural and renal epitopes.     

Quantitative magnetization transfer and myelin water imaging of the evolution of acute multiple sclerosis lesions

Quantitative magnetization transfer imaging provides in vivo estimates of liquid and semisolid constituents of tissue, while estimates of the liquid subpopulations, including myelin water, can be obtained from multicomponent T₂ analysis. Both methods have been suggested to provide improved myelin specificity compared to conventional MRI. The goal of this study was to investigate the sensitivity of each technique to the progression of acute, gadolinium‐enhancing regions of multiple sclerosis. Magnetization transfer and T₂ relaxometry data were acquired longitudinally over the course of 1 year in five relapsing‐remitting multiple sclerosis patients and in five healthy controls. Parametric maps were analyzed in enhancing lesions and normal‐appearing white matter regions. Quantitative magnetization transfer parameters in lesions were most abnormal at the time of enhancement and followed a pattern of recovery over subsequent months. Lesion myelin water fraction was abnormal but did not show a significant trend over time. Quantitative magnetization transfer was able to track the degree and timing of the partial recovery in enhancing multiple sclerosis lesions in a small group of patients, while the recovery was not detected in myelin water estimates, possibly due to their large variability. Our data suggest the recovery is characterized by quick resolution of inflammation and a slower remyelination process. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Low Doses of Tetracycline Trigger the E. coli Growth: A Case of Hormetic Response

Hormesis is a biphasic dose-response relationship, occurring when low concentrations of toxic agents elicit apparent improvements. In this work, the ability of sub-inhibitory concentrations of Tetracycline to induce hormetic response in a model organism was investigated. To this aim a reference strain of Escherichia coli, MG1655, was exposed to six decreasing doses of Tetracycline (between 0.12 and 0.00375 μg/ml), much lower than the Minimal Inhibitory Concentration (4 μg/ml). An hormetic increase was observed at the intermediate concentrations (0.015-0.03 μg/ml) of the tested range. The Colony Forming Unit number, indeed, rose up to 141% and 121% as compared to the control. At the highest (0.12 μg/ml) and lowest (0.00375 μg/ml) concentrations a slight decrease in CFU number was found. Results demonstrated that, in Escherichia coli, low concentrations of Tetracycline bias the bacterial numerical increase through a hormetic response; the dose-response curve describing this numerical increase is an U-inverted curve. Furthermore, these data confirm that hormesis is common to many - if not all - living systems, including bacteria; they underline the relevance of a deepened knowledge of both the effects and the possible consequences of exposure to low doses of contaminants.     

Flexural strength of glass fibre‐reinforced posts bonded to dual‐cure composite resin cements

Davis P, Melo LSD, Foxton RM, Sherriff M, Pilecki P, Mannocci F, Watson TF. Flexural strength of glass fibre‐reinforced posts bonded to dual‐cure composite resin cements. Eur J Oral Sci 2010; 118: 197–201. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci The aims of this study were to evaluate the flexural strength of two different types of glass fibre‐reinforced posts bonded to dual‐cure composite resin cements. Forty glass methacrylate‐based fibre posts (GC Fiber Post) and 20 glass fibre inter‐polymerizing network posts (everStick POST) were divided into three groups. Group 1 contained 20 GC posts that were bonded to a dual‐cure composite cement (UnifilCore). Group 2 contained 20 Stick Tech posts that had adhesive applied (Scotchbond Multipurpose resin) and were bonded to a dual‐cure composite resin cement (RelyX Unicem). Group 3 contained 20 GC posts that were pretreated with a silane‐coupling agent before being treated with resin and composite, as in group 1. A 4‐point bend test was carried out to failure on all of the groups. Failure modes were determined using scanning electron microscopy. Pretreatment of the post surface with the silane‐coupling agent did not increase the flexural strength. The flexural strength of the Stick Tech post was significantly lower than the flexural strength of the GC post. The mode of failure for the GC Posts was adhesive, whereas the Stick Tech posts failed cohesively. Different flexural strengths and failure modes were observed among the two fibre post–resin systems.     

Different digestion enzymes used for human pancreatic islet isolation: A mixed treatment comparison (MTC) meta-analysis

Collagenases are critical reagents determining yield and quality of isolated human pancreatic islets and may affect islet transplantation outcome. Some islet transplantation centers have compared 2 or more collagenase blends; however, the results regarding differences in quantity and quality of islets are conflicting. Thus, for the first time, a mixed treatment comparison (MTC) meta-analysis was carried out to compile data about the effect of different collagenases used for human pancreas digestion on islet yield, purity, viability and stimulation index (SI). Pubmed, Embase and Cochrane libraries were searched. Of 755 articles retrieved, a total of 15 articles fulfilled the eligibility criteria and were included in the MTC meta-analysis. Our results revealed that Vitacyte and Liberase MTF were associated with a small increase in islet yield (islet equivalent number/g pancreas) when compared with Sevac enzyme [standardized mean difference (95% credible interval – CrI) = −2.19 (−4.25 to −0.21) and −2.28 (−4.49 to −0.23), respectively]. However, all other enzyme comparisons did not show any significant difference regarding islet yield. Purity and viability percentages were not significantly different among any of the analyzed digestion enzymes. Interestingly, Vitacyte and Serva NB1 were associated with increased SI when compared with Liberase MTF enzyme [unstandardized weighted mean difference (95% CrI) = −1.69 (−2.87 to −0.51) and −1.07 (−1.79 to −0.39), respectively]. In conclusion, our MTC meta-analysis suggests that the digestion enzymes currently being used for islet isolation works with similar efficiency regarding islet yield, purity and viability; however, Vitacyte and Serva NB1 enzymes seem to be associated with an improved SI as compared with Liberase MTF.