The role of interpersonal synchrony in forming impressions of autistic and non-autistic adults.

When people meet, they almost instantaneously form an impression of each other. First impressions of character traits and rapport are less favourable when people with autism spectrum condition (ASC) are judged compared to non-autistic people. Little is known about the behavioural differences that drive these altered impressions. In the present study, we investigated the influence of interpersonal synchrony on impression formation of autistic and non-autistic people. Specifically, we used lagged cross-correlations to assess how much each interactant's motion energy, a measure which can be determined from video recordings, influenced the other interactant's motion energy. In short, silent clips of dyadic conversations, we asked non-autistic participants to rate their impression of one of the two interactants, which was solely based on the outlines of both interactants. We expected that the amount of leading of the target interactant, their diagnostic status as well as the interaction of these factors would influence impression formation. We found that while the amount of leading had a positive effect on the impressions of non-autistic interactants, this was not true for interactants with ASC. This suggests that interpersonal synchrony of motion energy is one driver of less favourable impressions of autistic compared to non-autistic people.

Reduced nonverbal interpersonal synchrony in autism spectrum disorder independent of partner diagnosis: a motion energy study.

BACKGROUND: One of the main diagnostic features of individuals with autism spectrum disorders is nonverbal behaviour difficulties during naturalistic social interactions. The 'Interactional Heterogeneity Hypothesis' of ASD proposes that the degree to which individuals share a common ground substantially influences their ability to achieve smooth social interactions. METHODS: To test this hypothesis, we filmed 29 autistic and 29 matched typically developed adults engaged in several conversational tasks. Windowed cross-lagged correlations were computed using the time series of motion energy of both individuals in a dyad. These coefficients were then compared across the three dyad types that were homo- or heterogenous with respect to diagnosis: pairs of two autistic individuals, two typically developed individuals or pairs of one autistic and one typically developed person. RESULTS: We found that all dyad types achieved above-chance interpersonal synchrony, but that synchrony was more expressed in typical dyads compared to both autistic and mixed dyads. LIMITATIONS: The method presented here provides only one, albeit objective and robust, approach to explore synchrony. The methodological choices as well as the lack of consideration for other communication modalities may limit our interpretation of the findings. Moreover, the sample size is small with respect to exploring associations between synchrony and various outcome and social skill measures. CONCLUSIONS: The present results do not provide support for the Interactional Heterogeneity Hypothesis given that autistic individuals do not coordinate better when interacting with another autistic individual, compared to when interacting with a typical individual.

Flap warming improves intraoperative indocyanine green angiography (ICGA) assessment of perfusion. An experimental study.

BACKGROUND: Indocyanine green angiography (ICGA) is slowly replacing conventional methods of evaluating perfusion during flap surgery. Microcirculatory changes during flap elevation create a marked state of hypoperfusion intraoperatively leading to ICGA underestimation of tissue viability and consequent resection of viable tissue. We propose a novel method of flap warming to induce maximum vasodilation before performing ICGA to increase accuracy in assessing perfusion. METHODS: Submental flaps harvested on a single perforator were created in 8 pigs. ICG angiography was performed in the intraoperative phase (ICGA-C), after inducing maximum vasodilatation by warming the flap at 42 °C (ICGA-W) and at 24H postoperative (ICGA-24). By setting a fluorescence threshold of 33% as indicative of necrosis, the flap surface deemed viable by ICGA was measured for ICGAC, ICGAW and ICGA24. The results were then compared to the actual flap survival observed clinically at 7 days. RESULTS: The mean of ICG-C predicted flap survival (FS-C = 49.17%) is 12.97% lower than the mean of actual flap survival on postoperative day 7 (FS = 62.14%). The mean difference between ICG-W and ICG-24 predicted flap survival (FS-W and FS-24) and actual flap survival in the postoperative day 7 (FS) is lower, 3.13% and 2.15%, respectively. Average perfusion recovery over 24 h was 10.83% (FS-24-FS-C). CONCLUSIONS: Conventional intraoperative ICGA underestimated perfusion in all cases. Warming the flap intraoperatively and achieving maximum vasodilation mitigates the effects of vasoconstriction and mimics the microcirculatory environment encountered at 24 h. Performing angiography after induced vasodilation improves ICGA assessment of flap perfusion.

Resistant Cytomegalovirus Infection in Solid-organ Transplantation: Single-center Experience, Literature Review of Risk Factors, and Proposed Preventive Strategies.

BACKGROUND: Cytomegalovirus (CMV) infection causes morbidity and mortality in solid-organ transplant recipients. Drug-resistant CMV is an emerging problem with poor survival outcomes and limited therapeutic options. In this study we comprehensively address the issue of drug resistance in CMV when compared with standard therapies, such as ganciclovir (GCV) and foscarnet. METHODS: We conducted a retrospective review of adult patients diagnosed with CMV after solid-organ transplant at our center between 2013 and 2017, and identified 7 resistant CMV cases. To study risk factors in the published literature, we performed an extensive database search. RESULTS: All patients had documented UL97 mutations, and 3 patients harbored both UL97 and UL54 mutations. For cases with increasing viral load or failure to achieve clinical improvement despite optimal therapy, genetic resistance testing was carried out. Patients received GCV and foscarnet combination therapy. As an adjunct, CMV immunoglobulin, cidofovir, and leflunomide were added. Risk factors, including donor+/recipient- serostatus, persistent high viral replication, prolonged therapeutic GCV exposure (>2.5 months), and allograft rejection, were assessed. CONCLUSION: Patients at risk, especially those with D+/R- serostatus, should be judiciously monitored for resistance. Prolonged intravenous GCV exposure increases the risk for development of drug resistance. Therefore, precise guidelines are required for prevention of long-term GCV/VGCV exposure. Investigation regarding interferon-gamma release assay and adoptive transfer of T cells in diagnosed CMV patients is warranted to improve future prophylactic and management strategies against CMV, with a potential to reduce the requirement for available toxic antiviral drugs.

Abdominal Wall Reconstruction after Flap Surgery and the Effect on the Immune System.

BACKGROUND: The aim of our study was to investigate the impact of abdominal wall reconstruction surgery on tissue anatomy and to explore how flap surgery influences the patient's immune status. METHODS: Experimental abdominal wall defects were created in 8 Sus scrofa (swine) animal models. The animals were divided into two groups: 4 swine were euthanized one month after surgery for the biopsies retrieval purpose and the other 4 swine were kept alive and the collection of blood samples has been done 6 months after surgery. In order to evaluate the relative gene expression in operated-on animal cohorts we compared them with samples from 4 healthy swine used as controls. RESULTS: The inflammatory process was present in all types of repairs. Collagen I deposition was higher in the flap repairs. The expression level for the genes related to immune response after 6 months from surgery was relatively similar to the control group except minor alteration registered in the case of two swine models. CONCLUSION: Our findings indicate a less pronounced proinflammatory response to surgical trauma in animal models after flap surgery. The postoperative levels of the inflammatory cytokines did not show significant differences after abdominal wall reconstruction using flap surgery.

Microparticles of healthy origins improve endothelial progenitor cell dysfunction via microRNA transfer in an atherosclerotic hamster model.

AIM: In this study, we aimed: (i) to obtain and functionally characterize the cultures of late endothelial progenitor cells (EPCs) from the animal blood; (ii) to investigate the potential beneficial effects of circulating microparticles (MPs) of healthy origins on EPC dysfunctionality in atherosclerosis as well as involved mechanisms. METHODS: Late EPCs were obtained and expanded in culture from peripheral blood isolated from two animal groups: hypertensive-hyperlipidaemic (HH) and control (C) hamsters. In parallel experiments, late EPC cultures from HH were incubated with MPs from C group. RESULTS: The results showed that late EPCs display endothelial cell phenotype: (i) have ability to uptake 1,1-dioctadecyl-3,3,3,3 tetramethylindocarbocyanine-labelled acetylated low-density lipoprotein and Ulex europaeus agglutinin lectin-1; (ii) express CD34, CD133, KDR, CD144, vWF, Tie-2. Late EPCs from HH exhibited different morphological and functional characteristics compared to control: (i) are smaller and irregular in shape; (ii) present decreased endothelial surface marker expression; (iii) display reduced proliferation, migration and adhesion; (iv) lose ability to organize themselves into tubular structures and integrate into vascular network; (v) have diminished function of inward rectifier potassium channels. The incubation of late EPCs with MPs improved EPC functionality by miR-10a, miR-21, miR-126, miR-146a, miR-223 transfer and IGF-1 expression activation; the kinetic study of MP incorporation into EPCs demonstrated MP uptake by EPCs followed by the miRNA transfer. CONCLUSION: The data reveal that late EPCs from atherosclerotic model exhibit distinctive features and are dysfunctional, and their function recovery can be supported by MP ability to transfer miRNAs. These findings bring a new light on the vascular repair in atherosclerosis.

Lack of TAFI increases brain damage and microparticle generation after thrombolytic therapy in ischemic stroke.

BACKGROUND: Thrombin-activatable fibrinolysis inhibitor (TAFI) plays an important role in coagulation and fibrinolysis. Whereas TAFI deficiency may lead to a haemorrhagic tendency, data from TAFI knockout mice (TAFI-/-) are controversial and no differences have been reported in these animals after ischemic stroke. There are also no data regarding the role of circulating microparticles (MPs) in TAFI-/-. OBJECTIVES: to examine the effect of tPA on the rate of intracranial haemorrhage (ICH) and on MPs generated in a model of ischemic stroke in TAFI-/- mice. METHODS: Thrombin was injected into the middle cerebral artery (MCA) to analyse the effect of tPA (10mg/Kg) on the infarct size and haemorrhage in the absence of TAFI. Immunofluorescence for Fluoro-Jade C was performed on frozen brain slides to analyse neuronal degeneration after ischemia. MPs were isolated from mouse blood and their concentrations calculated by flow cytometry. RESULTS: Compared with saline, tPA significantly increased the infarct size in TAFI-/- mice (p<0.05). Although plasma fibrinolytic activity (fibrin plate assay) was higher in these animals, no macroscopic or microscopic ICH was detected. A positive signal for apoptosis and degenerating neurons was observed in the infarct area, being significantly higher in tPA treated TAFI-/- mice (p<0.05). Interestingly, higher numbers of MPs were found in TAFI-/- plasma as compared to wild type, after stroke (p<0.05). CONCLUSIONS: TAFI deficiency results in increased brain damage in a model of thrombolysis after ischemic stroke, which was not associated with bleeding but with neuronal degeneration and MP production.

Effect of VEGFR, PDGFR and PI3K/mTOR Targeting in Glioblastoma.

Resistance to targeted therapy is a well known obstacle in cancer therapy. The cross-talk between several growth factor receptors generates redundancy in their intracellular pathways that usually mediates resistance to receptor targeted therapy. Simultaneous inactivation of two or more growth factor receptors has been suggested to prevent the cross-talk between their signaling pathways and to better eliminate malignant cells. Here we found that targeted therapy against these receptors induced moderate cell death in glioblastoma cells. More important, dual PDGFR and VEGFR inactivation induced more pronounceable cell death compared to inactivation of each receptor alone but failed to induce synergistic cell death in glioblastoma. PI3K/mTOR dual targeting has been identified as an efficient therapeutic approach in several malignant diseases, including glioblastoma. Therefore, we also investigated the PI3K/mTOR pathways inhibition effect in glioblastoma cells. Our results showed that inactivation of PI3K/mTOR pathways were more efficient than PDGFR or VEGFR single targeting or their dual inhibition.

The Effect of Human Mesenchymal Stem Cells-Conditioned Media on Glioblastoma Cells Viability In Vitro.

A novel target for cancer treatment is based on the effects of non-tumor cells, including hMSCs on tumor growth. However, the results are controversial: some studies showed that hMSCs inhibit tumor progression, while others found they promote tumor cell proliferation. In this study, we analyse the effect of human mesenchymal cells derived from umbilical cord tissue (hUC-MSCs) and bone-marrow- mesenchymal stem cells (hBM-MSCs) on glioblastoma cells viability in vitro. GB cell cultures were established from fresh sample tissues provided by "Bagdasar-Arseni" Hospital, Bucharest, from consented GB patients. hUC-MSCs, HUC-1 and HUC-2 cell lines, were established from human umbilical cord tissue collected after delivery from natural term births at the Emergency Hospital of Craiova, Romania. hBM-MSCs cell line was purchased from Life Technologies. Conditioned media (CM) from MSCs was used to treat GB cells for 24, 48, 72 and 96 hours. To determine GB cell viability was used MTT cell proliferation assay. Statistical analyses were performed using Students t-test. hUC-MSCs CM displayed the potential to be cytotoxic to GB cells, while the treatment with hBM-MSCs CM significantly stimulated GB cell growth 24 hours after the treatment and showed minor growth cell inhibition 48, 72 and 96 hours after the treatment. This report proved that hUC-MSCsCM inhibited GB cell proliferation, while little inhibitory effect was exerted by hBM-MSCs CM.

Dupuytren contracture recurrence project: reaching consensus on a definition of recurrence.

The aim of this study was to determine a definition of recurrence of Dupuytren disease that could be utilized for the comparison of the results independently from the treatment used. 24 hand surgeons from 17 countries met in an international consensus conference. The participants used the Delphi method to evaluate a series of statements: (1) the need for defining recurrence, (2) the concept of recurrence applied to the Tubiana staging system, (3) the concept of recurrence applied to each single treated joint, and (4) the concept of recurrence applied to the finger ray. For each item, the possible answer was given on a scale of 1-5: 1=maximum disagreement; 2=disagreement; 3=agreement; 4=strong agreement; 5=absolute agreement. There was consensus on disagreement if 1 and 2 comprised at least 66% of the recorded answers and consensus on agreement if 3, 4 and 5 comprised at least 66% of the recorded answers. If a threshold of 66% was not reached, the related statement was considered "not defined". A need for a definition of recurrence was established. The presence of nodules or cords without finger contracture was not considered an indication of recurrence. The Tubiana staging system was considered inappropriate for reporting recurrence. Recurrence was best determined by the measurement of a specific joint, rather than a total ray. Time 0 occurred between 6 weeks and 3 months. Recurrence was defined as a PED of more than 20° for at least one of treated joint, in the presence of a palpable cord, compared to the result obtained at time 0. This study determined the need for a standard definition of recurrence and reached consensus on that definition, which we should become the standard for the reporting of recurrence. If utilized in subsequent publications, this will allow surgeons to compare different techniques and make is easier to help patients make an informed choice.

Neural correlates of "social gaze" processing in high-functioning autism under systematic variation of gaze duration.

Direct gaze is a salient nonverbal signal for social interest and the intention to communicate. In particular, the duration of another's direct gaze can modulate our perception of the social meaning of gaze cues. However, both poor eye contact and deficits in social cognitive processing of gaze are specific diagnostic features of autism. Therefore, investigating neural mechanisms of gaze may provide key insights into the neural mechanisms related to autistic symptoms. Employing functional magnetic resonance imaging (fMRI) and a parametric design, we investigated the neural correlates of the influence of gaze direction and gaze duration on person perception in individuals with high-functioning autism (HFA) and a matched control group. For this purpose, dynamically animated faces of virtual characters, displaying averted or direct gaze of different durations (1 s, 2.5 s and 4 s) were evaluated on a four-point likeability scale. Behavioral results revealed that HFA participants showed no significant difference in likeability ratings depending on gaze duration, while the control group rated the virtual characters as increasingly likeable with increasing gaze duration. On the neural level, direct gaze and increasing direct gaze duration recruit regions of the social neural network (SNN) in control participants, indicating the processing of social salience and a perceived communicative intent. In participants with HFA however, regions of the social neural network were more engaged by averted and decreasing amounts of gaze, while the neural response for processing direct gaze in HFA was not suggestive of any social information processing.

Circulating microparticles and endothelial progenitor cells in atherosclerosis: pharmacological effects of irbesartan.

AIMS: This study aimed to (i) employ our newly designed model, the hypertensive-hypercholesterolemic hamster (HH), in order to find out whether a correlation exists between circulating microparticles (MPs), endothelial progenitor cells (EPCs) and their contribution to vascular dysfunction and (ii) to assess the effect of irbesartan treatment on HH animals (HHI). METHODS AND RESULTS: The results showed that compared with the control (C) group, HH displayed: (i) a significant increase in plasma cholesterol and triglyceride concentration, and an augmentation of systolic and diastolic arterial blood pressure, and of heart rate; (ii) a marked elevation of MPs and a significant decrease in EPCs; (iii) structural modifications of the arterial wall correlated with altered protein expression of MMP2, MMP9, MMP12, TIMP1, TIMP2 and collagen type I and III; (iv) a considerably altered reactivity of the arterial wall closely correlated with MPs and EPC adherence; and (v) an inflammatory process characterized by augmented expression of P-Selectin, E-Selectin, von Willebrand factor, tissue factor, IL-6, MCP-1 and RANTES. Additionally, the experiments showed the potential of irbesartan to correct all altered parameters in HH and to mobilize EPCs by NO, chemokines and adhesion molecule-dependent mechanisms. CONCLUSIONS: Hypertension associated with hypercholesterolemia is accompanied by structural modifications and expression of pro-inflammatory molecules by the vessel wall, the alteration of vascular tone, enhanced release of MPs and reduced EPCs; the ratio between the latter two may be considered as a marker of vascular dysfunction. Irbesartan, which exhibits a pharmacological control on the levels of MPs and EPCs, has the potential to restore homeostasis of the arterial wall.

[Expectations concerning psychotherapy of high-functioning adults with autism spectrum disorders]. / Erwartungen an eine Psychotherapie von hochfunktionalen erwachsenen Personen mit einer Autismus-Spektrum-Störung.

BACKGROUND: In recent years there has been a strong increase in psychiatric diagnoses belonging to the autism spectrum in adulthood. For this diagnostic group of patients, often characterised by normal or above-average intelligence, i.e, high-functioning autism or Asperger syndrome, only few adequate psychotherapeutic treatment options exist. In order to develop a disorder-specific psychotherapeutic group training in a demand-oriented manner, we surveyed adults with autism spectrum disorders (ASD) concerning their needs and expectations relating to psychotherapy. METHODS: A two-step analysis of needs was carried out: First, after a set of open questions written descriptions of 33 individuals with ASD were analysed using the qualitative content analysis according to Mayring. The resulting category system provided the basis for the closed questionnaire EPAS ("Expectations Psychotherapy Autism Spectrum"). In a second step, 64 individuals with ASD were assessed by EPAS to confirm the relevance of the qualitatively derived dimensions. RESULTS: Both the results of the qualitative and the quantitative analysis confirmed the initial hypothesis that adults with ASD expressed problems associated with disorder-specific core symptoms. Moreover, the quantitative analysis demonstrated that in addition to deficits in social competence and identity formation, the lack of stress management skills represents a crucial load factor. Also, the therapist-associated variables were reported to play an important role for the patients. DISCUSSION: The analysis of needs indicates that psychotherapy for adults with ASD should focus on the training and development of social-communicative skills. Furthermore, dealing with stress in everyday situations and identity formation after diagnosis should also be considered. Psychotherapists can refer to well-established techniques from cognitive behavioural therapy, which are known to be effective in the identified fields and should have sufficient disorder-specific knowledge, not least in order to prevent misunderstandings within the therapeutic working relationship.

Platelet activation in hypertension associated with hypercholesterolemia: effects of irbesartan.

AIM: The aim of this study was to determine the effect of simultaneous hypertension and hypercholesterolemia on platelet activation, nitric oxide (NO) production and oxidative stress, and to evaluate the role of irbesartan, an angiotensin II type 1 receptor antagonist. METHODS: Golden Syrian hamsters were divided into three groups: controls, C (fed a standard diet); hypertensive-hypercholesterolemic, HH (fed a diet enriched in 3% cholesterol, 15% butter and 8% NaCl, for 4 months); and hypertensive-hypercholesterolemic treated with irbesartan, HHI (fed as HH group, plus irbesartan 10 mg kg(-1) per day, for 4 months). RESULTS: Compared with the C group, platelets isolated from the HH group showed: morphological modifications; increased integrin ß3 exposure and protein expression of P-selectin, FAK, PI3K, Akt and Src; reduced eNOS protein expression and NO production; higher generation of ROS, mostly produced by NADPH-oxidase, cyclooxygenase-1 (COX-1) and 12-lipoxygenase; and enhanced NAD(P)H oxidase activity and protein expression of gp91phox and p22phox subunits, 12-lipoxygenase, COX-1, cPLA(2) and PKC. Compared with the HH group, the treatment with irbesartan (HHI group) significantly attenuates the changes in all the molecules tested, reduces platelet aggregation, and improves intraplatelet redox balance. CONCLUSIONS: Experimental hypertension associated with hypercholesterolemia produces major changes in morphology, signaling mechanisms and oxidative stress in blood platelets. These changes were significantly diminished by irbesartan administration, which functions as an antioxidant on platelets.

IL-17 in cutaneous lupus erythematosus.

BACKGROUND: Lupus erythematosus (LE) is a heterogeneous disease with broad clinical spectrum from cutaneous to visceral and systemic inflammation. IL-17 isoforms (IL-17A and IL-17F) are proinflammatory cytokines with unclear implications in lupus erythematosus pathogenesis. In this study we focused upon IL-17 in normal and modified lupus skin with a correlative study between local and serological expression. MATERIAL AND METHODS: 89 subjects were recruited and divided in 5 groups-10 patients with psoriasis (disease control group), 13 healthy controls, 26 with discoid chronic lupus (DLE), 23 with systemic lupus erythematosus (SLE) and 17 with subacute lupus erythematosus (SCLE). Blood samples and skin punched-biopsy specimens were performed. Serum IL-17A, IL-17F, and IL-23 concentrations were determined by ELISA. Skin IL-17A and CD4 expression were evaluated by immunohistochemistry. RESULTS: Immunohistochemical expression of IL-17A was higher in DLE, SCLE and SLE patients than in negative control subjects (all p<0.05). Serum IL-17A concentrations were higher in DLE and SLE patients than in negative controls (p<0.05). Serum IL-17A levels were similar in SCLE and negative controls (p>0.05). Serum IL-17F concentrations were higher in DLE, SCLE and SLE patients than in healthy controls (all p<0.05). In DLE, SCLE, SLE patients and healthy controls we observed comparable levels of IL-23 (p>0.05). Serum anti Ro antibodies correlate with IL-17A+ lymphocytes from SCLE lesion and SLE normal skin (all p<0.05). CONCLUSION: IL-17 isoforms (IL-17A and IL-17F) are implicated in SLE but also in DLE and SCLE immunopathogenesis.

Atomic force microscopy study regarding the influence of etching on affected and sclerotic dentine.

UNLABELLED: Aim of study is to compare the effect of etching with ortho-phosphoric acid on sound dentine, affected dentine and sclerotic dentine through AFM analysis. MATERIAL AND METHODS: The group study included 30 extracted third molars, 20 with acute and chronic carious lesions and 10 intact teeth. Teeth were sectioned in long axe to prepare sections with carious lesions surrounded by sound dentine. The sound teeth were sectioned to a depth of dentine comparable with carious lesions depth. The sections were etched with 37% ortho-phosphoric acid. The surface roughness was determined initially and after etching using AFM analysis. The results were expressed as relative variation of squared roughness. RESULTS: The values of relative roughness indices were between 2.78 and 3 for sclerotic dentine, 3.18 and 3.26 for sound dentine, 3.32 and 3.38 for affected dentine. The highest values of roughness index were recorded for the affected dentine samples. Significant statistically values were recorded when comparing relative roughness indices for sclerotic dentine with relative roughness indices for affected dentine and sound dentine. CONCLUSIONS: clerotic dentine has significant higher resistance to the action of ortho-phosphoric acid than affected dentine and sound dentine. The lowest resistance to the action of etching agent was recorded for the affected dentine.

Chronic venous insufficiency is associated with elevated level of circulating microparticles.

BACKGROUND: Chronic venous insufficiency (CVI) results when the veins in the legs no longer pump blood back to the heart effectively. Microparticles (MPs) are small membrane vesicles released by several circulating and vascular cells upon activation or apoptosis. OBJECTIVES: The purpose of this study was to assess the subpopulations of circulating endothelial (EMPs) and platelet microparticles (PMPs) in CVI, and to disclose their contribution in mediating dysfunction of human peripheral venules. PATIENTS AND METHODS: Human peripheral venules were explanted during leg surgery on patients with CVI and on control subjects (C); concurrently, blood samples were collected and circulating MPs isolated. The techniques used were: flow cytometry, fluorescence and electron microscopy, myograph technique and western-blotting technique. RESULTS: The results showed that compared with controls, patients with CVI had: (i) a marked elevation of circulating EMPs and PMPs; (ii) a structural modification of the venous wall consisting of activation of endothelial and smooth muscle cells, an abundance of intermediary filaments and synthesis of hyperplasic-multilayered basal lamina; (iii) a significantly altered reactivity of the venous wall, closely associated with EMPs and PMPs adherence; (iv) altered contractile response to noradrenaline, acetylcholine, 5-hydroxytryptamine and KCl, and an impeded relaxation in response to sodium nitroprusside; and (iv) a substantially increased protein expression of tissue factor (TF) and of P-Selectin both in the venular vascular wall and on the surface of EMPs and PMPs. CONCLUSIONS: The findings indicate that CVI is accompanied by an enhanced release of EMPs and PMPs that contribute to altered dysfunctional response of the venous wall.

Nebivolol induces a hyperpolarizing effect on smooth muscle cells in the mouse renal artery by activation of beta-2-adrenoceptors.

Nebivolol is a highly selective beta(1)-adrenoceptor antagonist with vasodilator properties involving the vascular endothelium, but its effect on the smooth muscle cells (SMC) is still unclear. In this paper, we tested the effect of nebivolol on renal artery smooth muscle cells and investigated the cellular mechanism involved. To this purpose, the denuded renal arteries isolated from mice were studied in vitro using the myograph and the nitric oxide (NO) sensor techniques, while the SMC in culture were analyzed by the patch-clamp technique. The myograph technique was used to assay the vasodilator effect of nebivolol on the arterial muscular layer, and to establish the optimal dose of the drug to be tested on single SMC by the patch-clamp technique. Using both the myograph and the patch-clamp techniques, we examined the potential contribution of beta(2)-adrenoceptors and Ca(2+)-activated K(+) channels to the nebivolol-induced effects, by exposing the denuded arteries and SMC cultures to specific inhibitors such as butoxamine (100 micromol/l), tetraethylammonium (TEA, 1 mmol/l), and iberiotoxin (100 nmol/l). The direct measurement of NO using the NO sensor enabled us to evaluate if nebivolol induces/or not the release of NO in denuded renal arteries. The results of this study show that nebivolol exerts vasodilator effects on the SMC in the denuded renal arteries and the maximal response is achieved at a concentration of 50 micromol/l. Nebivolol effects involve binding to the beta(2)-adrenoceptors and the subsequent activation of Ca(2+)-activated K(+) channels in SMC, with no contribution of NO. Taken together, the study brings new insights into the mechanism underlying the nebivolol-induced arterial vasodilation.

Female pelvi-abdominal multilocular recurrent fluid collection of uncertain aetiology.

UNLABELLED: Recurrent pelvi-abdominal multilocular fluid collections in female patients may be of various aetiology: infections, haemorrhage, benign or malignant tumours. PURPOSE: Diagnosis of such fluid collections is complex, imaging examinations (ultrasonography, computed tomography, MRI) and biochemical, cytological and histological examinations must be included. Some cases, however, are difficult to diagnose, and their treatment is uncertain. MATERIALS AND METHODS: We present the case of a 22-year-old unmarried female patient with minor symptoms, not correlated with a pelvi-peritoneal fluid collection extending into the infra-mesocolic space, revealed by ultrasonography and MRI. The aetiology was uncertain after biological examinations and cytology. The disease course was recurrent during 14 months, under anti-inflammatory treatment and surgical intervention with removal of the fluid (2.5 l), resection of the right ovary (histological examination revealed small ovarian mucinous cysts) and excision of a fibroma of the right utero-sacral ligament. Follow-up sonography was the chosen method for repeated diagnostic and therapeutic echo-guided punctures. Finally, after immuno-stimulating treatment, we observed almost complete remission of the peritoneal fluid collection. RESULTS: This paper reveals significant discordances between the clinical appearance and the presence of a large peritoneal fluid collection, between locally recurrent appearance and cytological and histopathological "benign" results, between positive intradermal reaction to tuberculin and negative culture of B. Koch from aspirate. There were concordances between immune electrophoresis and some cytological elements and between three dimensional and panoramic SieScape ultrasonography and MRI. We must, however, note the superiority of MRI in the designation of anatomical findings and analysis of the histological structure. CONCLUSION: The importance of this case is derived from the atypical clinical appearance and course, with uncertain aetiology after complex imaging, biological and surgical explorations.