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Objectives: We evaluated a prospective cohort of 150 patients under observation in our centre for lacunar strokes. The purpose of this study was to evaluate the outcome at time of discharge and 6 months after lacunar stroke, as well as the correlation with cardiovascular risk factors and selected biochemical parameters already evaluated on admission. Focus was to identify possible prognostic factors, which might be targeted through appropriate intervention concentrating on reduction in the incidence and impact of early clinical deterioration. Methods: 150 patients with a lacunar stroke were included in the present study. A clinical 6‐month follow‐up was available for 98.7% of the patients. Infarcts were classified by size, shape and location. Results: The most important predictors of high NIHSS score at time of discharge resulted NIHSS on admission (P < .001), leukocytosis (P = .013), in‐hospital infections (P = .016) and size of lacunae (P = .005). Similarly, the most important predictors of poor outcome 6 months later were NIHSS on admission (P = .01), leukocytosis (P = .014), elevated CRP (P = .019), in addition to pre‐admission Rankin (P < .001). Conclusion: Although infections are not causatively related to lacunar strokes, their prompt recognition and early treatment, control of inflammatory markers and fever are most important in influencing functional outcome in lacunar stroke. [ABSTRACT FROM AUTHOR]

We developed an in vitro contact through-feet blood brain barrier (BBB) model built using type IV collagen, rat astrocytes, and human umbilical vein endothelial cells (HUVECs) cocultured through Transwell porous polycarbonate membrane. The contact between astrocytes and HUVECs was demonstrated by electron microscopy: astrocytes endfeet pass through the 8.0 μm pores inducing HUVECs to assume a cerebral phenotype. Using this model we evaluated transmigration of melanoma cells from two different patients (M1 and M2) selected among seven melanoma primary cultures. M2 cells showed a statistically significant higher capability to pass across the in vitro BBB model, compared to M1. Expression of adhesion molecules was evaluated by flow cytometry: a statistically significant increased expression of MCAM, αvβ3, and CD49b was detected in M1. PCR array data showed that M2 had a higher expression of several matrix metalloproteinase proteins (MMPs) compared to M1. Specifically, data suggest that MMP2 and MMP9 could be directly involved in BBB permeability and that brain invasion by melanoma cells could be related to the overexpression of many MMPs. Future studies will be necessary to deepen the mechanisms of central nervous system invasion. [ABSTRACT FROM AUTHOR]

Despite the continuous description of new conditions pre-disposing for cerebral venous thrombosis (CVT), no apparent cause is found in about 30% of cases. Hyperhomocysteinemia (hyper-Hcy) is an established risk factor for deep venous thrombosis and stroke but has not been clearly associated with increased risk of CVT. We assessed the prevalence of hyper-Hcy and other thrombophilic risk factors in a population of 26 consecutive patients with non-pyogenic CVT, by review of a prospectively maintained database. The prevalences of hyper-Hcy and prothrombin G20210A, factor V G1691A and methylenetetrahydrofolate reductase (MTHFR) C677T mutations in these patients were compared with those in 100 healthy controls and 100 patients with cerebroarterial disease. The prevalence of hyper-Hcy was greater in patients with CVT (10/26, 38.5%) than healthy controls (13/100; OR 4.18, 95% CI 1.58–11.16) and comparable with that in patients with cerebroarterial disease (42/100). No significant differences were found in the prevalences of prothrombin or MTHFR mutation. No factor V mutation was found. Our findings indicate that hyper-Hcy is associated with an increased risk of CVT. Additional prospective cohort studies on large series of patients are required to clarify the time relationship between hyper-Hcy and the thrombotic event. [ABSTRACT FROM AUTHOR]

The association of primary sclerosing cholangitis (PSC) to HLA class II genes was studied by comparing patients from five different European populations. Deduced HLA-DRB1, DQA1, DQB1 haplotypes of 256 PSC patients from England, Italy, Norway, Spain and Sweden were compared to those observed in 764 ethnically-matched controls. Increased frequencies of the DRB1*03, DQA1*0501, DQB1*02 (RR=3.0, P<0.00001) and the DRB1*13, DQA1*0103, DQB1*0603 haplotypes (RR=2.4, P<0.0001) were observed in all five patient groups. A total of 16% of the PSC patients were homozygous for the DRB1*03, DQA1*0501, DQB1*02 haplotype compared to 1% of the controls (RR=20, P<0.0001). The DRB1*04, DQA1*03, DQB1*0302 haplotype was significantly reduced in frequency(RR=0.4, P<0.00001). Among Norwegian, Swedish and British patients that did not carry neither the DRB1*03, DQA1*0501, DQB1*02 nor the DRB1*13, DQA1*0103, DQB1*0603 haplotype, an increased frequency of the DRB1*15, DQA1*0102, DQB1*0602 haplotype was observed (RR=2.0, P<0.0001). Thus, PSC was found to be positively associated to three different HLA class II haplotypes (i.e. the DRB1*03, DQA1*0501, DQB1*02, the DRB1*15, DQA1*0102, DQB1*0602 and the DRB1*13, DQA1*0103, DQB1*0603 haplotypes) and negatively associated to one HLA class II haplotype (i.e. the DRB1*04, DQB1*0302 haplotype). [ABSTRACT FROM AUTHOR]

The ability of human brain endothelial cells to produce mRNA for interleukin-10, and release IL-10 in culture supernatants after in vitro stimulation with LPS, TNF-α and γ-IFN was assessed and compared to that of astrocytes, peripheral blood mononuclear cells and human umbilical vein endothelial cells. IL-1β and β2-microglobulin release were also analysed. IL-10 and TNF-α mRNA presence was investigated in normal brain as well as in three plaques from two multiple sclerosis patients. While increased IL-1β and β2-microglobulin release in the supernatants of stimulated cells could be detected in all the studied cell lineages, IL-10 mRNA and protein release was only seen in LPS-stimulated PBMNCs. Similarly, mRNA for IL-10 was not detected in CNS tissues, while TNF-α was present in all plaques. The lack of production of significant amounts of IL-10 by astrocytes and human brain endothelial cells suggests that these cells may not be the primary source of in vivo IL-10-mediated down-regulation of immune reactions within the central nervous system. [ABSTRACT FROM AUTHOR]

Current leukaemia therapy focuses on increasing chemotherapy efficacy. Mesenchymal stromal cells (MSCs) have been proposed for carrying and delivery drugs to improve killing of cancer cells. We have shown that MSCs loaded with Paclitaxel (PTX) acquire a potent anti-tumour activity. We investigated the effect of human MSCs (hMSCs) and mouse SR4987 loaded with PTX (hMSCsPTX and SR4987PTX) on MOLT-4 and L1210, two leukaemia cell (LCs) lines of human and mouse origin, respectively. SR4987PTX and hMSCsPTX showed strong anti-LC activity. hMSCsPTX, co-injected with MOLT-4 cells or intra-tumour injected into established subcutaneous MOLT-4 nodules, strongly inhibited growth and angiogenesis. In BDF1-mice-bearing L1210, the intraperitoneal administration of SR4987PTX doubled mouse survival time. In vitro, both hMSCs and hMSCsPTX released chemotactic factors, bound and formed rosettes with LCs. In ultrastructural analysis of rosettes, hMSCsPTX showed no morphological alterations while the attached LCs were apoptotic and necrotic. hMSCs and hMSCsPTX released molecules that reduced LC adhesion to microvascular endothelium (hMECs) and down-modulated ICAM1 and VCAM1 on hMECs. Priming hMSCs with PTX is a simple procedure that does not require any genetic cell manipulation. Once the effectiveness of hMSCsPTX on established cancers in mice is proven, this procedure could be proposed for leukaemia therapy in humans., (© 2013 Blackwell Publishing Ltd.)