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41.
Lonomia achelous caterpillar, Lepidoptera distributed along some South American countries, induces a hemorrhagic syndrome in people who come into contact with its bristles. A clinical characteristic in these patients is that fresh healed wounds are re-opened and bleed. In order to explain this symptomatology, we evaluated the effect of Lonomin V (a protein isolated from L. achelous hemolymph), on some functional properties of fibronectin, which in turn plays an important role in the hemostasis. The effect of Lonomin V on fibronectin was studied by SDS-PAGE in reduced condition, binding to gelatin and heparin, crosslinking to fibrin and platelet adhesion. Formation of degradation products of 120, 66, 50, 40 and 29 kDa, some of which retain affinity to heparin and gelatin were observed; however, the fibronectin degradation fragments presented a significant decrease of crosslinking capacity to fibrin and platelet adhesion, suggesting that the proteolysis of fibronectin by Lonomin V induces changes in its crosslinking sites and on platelet receptors. These findings might partially explain the wound dehiscence observed in the patients. Due to its effect on adhesive proteins with concomitant impairment of some functional properties, Lonomin V might be useful for cellular adhesion studies involved in hemostasis such as platelet adhesion.  相似文献   
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It has been shown that a single exposure to amphetamine is sufficient to induce long‐term behavioral, neurochemical, and neuroendocrine sensitization in rats. Dopaminergic neurotransmission in the nucleus accumbens and the caudate‐putamen plays a critical role in the addictive properties of drugs of abuse. Angiotensin (Ang) II receptors are found on the soma and terminals of mesolimbic dopaminergic neurons and it has been shown that Ang II acting through its AT1 receptors facilitates dopamine release. The hypothesis was tested that Ang II AT1 receptors are involved in the neuroadaptative changes induced by a single exposure to amphetamine and that such changes are related to the development of behavioral and neurochemical sensitization. For this purpose, the study examined the expression of amphetamine‐enhanced (0.5 mg kg−1 i.p.) locomotor activity in animals pretreated with candesartan, an AT1 blocker, (3 mg kg−1 p.o × 5 days), 3 weeks after an amphetamine injection (5 mg kg−1 i.p.). Dopaminergic hyperreactivity was tested by measuring the 3H‐DA release in vitro from caudate‐putamen and nucleus accumbens slices, induced by K+ stimulus. It was confirmed the behavioral sensitization in the two‐injection protocol and candesartan pretreatment attenuate this response. It was also found that AT1 blockade pretreatment did not affect the locomotor response to dopamine agonists. In respect to the neurochemical sensitization tested using ex vivo 3H‐DA release experiments it was found that AT1 receptor pretreatment blunted the enhanced response induced by K+ stimulus. The results support the idea that the development of neuroadaptive changes induced by amphetamine involves brain AT1 Ang II receptor activation. Synapse, 2011. © 2010 Wiley‐Liss, Inc.  相似文献   
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Lifestyle interventions addressing diet, exercise‐training, sleep hygiene, and/or tobacco/alcohol cessation are recommended in the management of obstructive sleep apnoea (OSA). Yet their effectiveness on this condition still requires further research. This systematic review and meta‐analysis was aimed at establishing (a) the effectiveness of lifestyle interventions on apnoea‐hypopnoea index (AHI), oxygen desaturation index (ODI), excessive daytime sleepiness (EDS), and secondary OSA measures among adults, and (b) which intervention characteristics may drive the greatest improvements. A systematic search of studies was conducted using CINAHL, ProQuest, Psicodoc, Scopus, and Web of Science, from inception to April 2018. Standardized mean differences were calculated using the inverse variance method and random‐effects models. The meta‐analyses of 13 randomized controlled trials and 22 uncontrolled before‐and‐after studies (1420 participants) revealed significant reductions on AHI (d = ?0.61 and ?0.46, respectively), ODI (d = ?0.61 and ?0.46) and EDS (d = ?0.41 and ?0.49). Secondary OSA outcomes were also improved after interventions. However, effectiveness of interventions differed depending on their components, OSA severity, and gender. Thus, until future research further supports the differential effectiveness among lifestyle interventions on OSA, those addressing weight loss through diet and exercise‐training may be the most effective treatments for male patients with moderate‐severe OSA.  相似文献   
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Background

We recently showed PAM50 gene expression data can be represented by five quantitative, orthogonal, multi-gene breast tumor traits. These novel tumor ‘dimensions’ were superior to categorical intrinsic subtypes for clustering in high-risk breast cancer pedigrees, indicating potential to represent underlying genetic susceptibilities and biological pathways. Here we explore the prognostic and predictive utility of these dimensions in a sub-study of GEICAM/9906, a Phase III randomized prospective clinical trial of paclitaxel in breast cancer.

Methods

Tumor dimensions, PC1–PC5, were calculated using pre-defined coefficients. Univariable and multivariable Cox proportional hazards (PH) models for disease-free survival (DFS) were used to identify associations between quantitative dimensions and prognosis or response to the addition of paclitaxel. Results were illustrated using Kaplan–Meier curves.

Results

Dimensions PC1 and PC5 were associated with DFS (Cox PH p = 6.7 (times) 10−7 and p = 0.036), remaining significant after correction for standard clinical–pathological prognostic characteristics. Both dimensions were selected in the optimal multivariable model, together with nodal status and tumor size (Cox PH p = 1.4 (times) 10−12). Interactions with treatment were identified for PC3 and PC4. Response to paclitaxel was restricted to tumors with low PC3 and PC4 (log-rank p = 0.0021). Women with tumors high for PC3 or PC4 showed no survival advantage.

Conclusions

Our proof-of-concept application of quantitative dimensions illustrated novel findings and clinical utility beyond standard clinical–pathological characteristics and categorical intrinsic subtypes for prognosis and predicting chemotherapy response. Consideration of expression data as quantitative tumor dimensions offers new potential to identify clinically important patient subsets in clinical trials and advance precision medicine.

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Chlorpromazine is known to produce both systemic phototoxic and photoallergic reactions. However, it may also cause photoallergic contact dermatitis and, albeit exceptionally, allergic contact dermatitis (ACD). We present a series of photoallergic contact dermatitis and ACD to chlorpromazine diagnosed at a tertiary centre cutaneous allergy unit between 1980 and 2019.  相似文献   
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