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Calcium carbonate (CaCO3) is abundant on Earth, is a major component of marine biominerals and thus of sedimentary and metamorphic rocks and it plays a major role in the global carbon cycle by storing atmospheric CO2 into solid biominerals. Six crystalline polymorphs of CaCO3 are known—3 anhydrous: calcite, aragonite, vaterite, and 3 hydrated: ikaite (CaCO3·6H2O), monohydrocalcite (CaCO3·1H2O, MHC), and calcium carbonate hemihydrate (CaCO3·½H2O, CCHH). CCHH was recently discovered and characterized, but exclusively as a synthetic material, not as a naturally occurring mineral. Here, analyzing 200 million spectra with Myriad Mapping (MM) of nanoscale mineral phases, we find CCHH and MHC, along with amorphous precursors, on freshly deposited coral skeleton and nacre surfaces, but not on sea urchin spines. Thus, biomineralization pathways are more complex and diverse than previously understood, opening new questions on isotopes and climate. Crystalline precursors are more accessible than amorphous ones to other spectroscopies and diffraction, in natural and bio-inspired materials.A new carbonate phase calcium carbonate hemihydrate was recently discovered and characterized, but exclusively as a synthetic material. Here the authors find that it exists in nature, albeit transiently, on the surface of growing nacre and coral skeletons, and show that 2 amorphous and 2 metastable crystalline nano-minerals form before biominerals settle into their stable crystals. [ABSTRACT FROM AUTHOR]

Modern disease-modifying therapies (DMTs) in multiple sclerosis (MS) have variable modes of action and selectively suppress or modulate the immune system. In this review, we summarize the predicted and intended as well as unwanted adverse effects on leukocytes in peripheral blood as a result of treatment with DMTs for MS. We link changes in laboratory tests to the possible therapeutic risks that include secondary autoimmunity, infections, and impaired response to vaccinations. Profound knowledge of the intended effects on leukocyte counts, in particular lymphocytes, explained by the mode of action, and adverse effects which may require additional laboratory and clinical vigilance or even drug discontinuation, is needed when prescribing DMTs to treat patients with MS. [ABSTRACT FROM AUTHOR]

We report on the effect of different coatings (dextran, chitosan, polyethylene glycol, carboxy-silane, and silica) in the toxicity elicited by superparamagnetic iron oxide nanoparticles (SPIONs) in the developing zebrafish (Danio rerio). Animals were exposed to nanoparticle concentrations ranging from 0.125 to 8.0 mM of Fe during the first 5 days after fertilization. Embryotoxicity parameters (survival, hatching rate, and the incidence of anatomical malformations) and behavioral patterns (locomotion during the exploration of a new environment, thigmotaxis, and the escape response to an aversive stimulus) were evaluated. Exposed embryos hatched between 48 and 72 hpf, as expected for the species, but tendencies of either acceleration or delay were observed, depending on the nanoparticle coating. Malformations in exposed and control groups were similar, independent of the coating. Mortality rates were also not significantly affected by exposure to most of the coated SPIONs, except for animals treated with chitosan-coated nanoparticles, which induced 100% mortality at concentrations higher than 2 mM. A similar trend was observed in the behavioral parameters, in which significant adverse effects were mostly caused by chitosan-coated nanoparticles even at low concentrations. The higher toxicity observed for chitosan-coated particles raises concern and deserves further mechanistic investigations, considering the ample use of this compound in pharmaceutical and biomedical applications. [ABSTRACT FROM AUTHOR]

Palm wine, the most commonly consumed traditional alcoholic beverage in Western Africa, harbours a complex microbiota and metabolites, which plays a crucial role in the overall quality and value of the product. In the present study, a combined metagenomic and metabolomic approach was applied to describe the microbial community structure and metabolites profile of fermented saps from three palm species (Elaeis guineensis, Raphia hookeri, Borassus aethiopum) in Côte d'Ivoire. Lactobacillaceae (47%), Leuconostocaceae (16%) and Acetobacteriaceae (28%) were the most abundant bacteria and Saccharomyces cerevisiae (87%) the predominant yeasts in these beverages. The microbial community structure of Raphia wine was distinctly different from the others. Multivariate analysis based on the metabolites profile clearly separated the three palm wine types. The main differentiating metabolites were putatively identified as gevotroline hydrochloride, sesartemin and methylisocitrate in Elaeis wine; derivative of homoserine, mitoxantrone in Raphia wine; pyrimidine nucleotide sugars (UDP-D-galacturonate) and myo-Inositol derivatives in Borassus wine. The enriched presence of gevotroline (an antipsychotic agent) and mitoxantrone (an anticancer drug) in palm wine supports its therapeutic potential. This work provides a valuable insight into the microbiology and biochemistry of palm wines and a rationale for selecting functional microorganisms for potential biotechnology applications. [ABSTRACT FROM AUTHOR]

Purpose: Standardized added metabolic activity (SAM) is a PET parameter for assessing the total metabolic load of malignant processes, avoiding partial volume effects and lesion segmentation. The potential role of this parameter in the assessment of response to chemotherapy and bevacizumab was tested in patients with metastatic colorectal cancer with potentially resectable liver metastases (mCRC). Methods: F-FDG PET/CT was performed in 18 mCRC patients with liver metastases before treatment and after five cycles of FOLFOX/FOLFIRI and bevacizumab. Of the 18 patients, 16 subsequently underwent resection of liver metastases. Baseline and follow-up SUV, and SAM as well as reduction in SUV (∆SUV) and SAM (∆SAM) of all liver metastases were correlated with morphological response, and progression-free and overall survival (PFS and OS). Results: A significant reduction in metabolic activity of the liver metastases was seen after chemotherapy with a median ∆SUV of 25.3 % and ∆SAM of 94.5 % ( p = 0.033 and 0.003). Median baseline SUV and SAM values were significantly different between morphological responders and nonresponders (3.8 vs. 7.2, p = 0.021; and 34 vs. 211, p = 0.002, respectively), but neither baseline PET parameters nor morphological response was correlated with PFS or OS. Follow-up SUV and SAM as well as ∆SAM were found to be prognostic factors. The median PFS and OS in the patient group with a high follow-up SUV were 10.4 months and 32 months, compared to a median PFS of 14.7 months and a median OS which had not been reached in the group with a low follow-up SUV ( p = 0.01 and 0.003, respectively). The patient group with a high follow-up SAM and a low ∆SAM had a median PFS and OS of 9.4 months and 32 months, whereas the other group had a median PFS of 14.7 months and a median OS which had not been reached ( p = 0.002 for both PFS and OS). Conclusion: F-FDG PET imaging is a useful tool to assess treatment response and predict clinical outcome in patients with mCRC who undergo chemotherapy before liver metastasectomy. Follow-up SUV, follow-up SAM and ∆SAM were found to be significant prognostic factors for PFS and OS. [ABSTRACT FROM AUTHOR]

Adipocytes hypertrophy is the main cause of obesity and its affliction such as type 2 diabetes (T2D). Since superparamagnetic iron oxide nanoparticles (SPIONs) are used for a wide range of biomedical/medical applications, we aimed to study the effect of SPIONs on 22 and 29 risk genes (Based on gene wide association studies) for obesity and T2D in human adipocytes. The mRNA expression of lipid and glucose metabolism genes was changed upon the treatment of human primary adipocytes with SPIONs. mRNA of GULP1, SLC30A8, NEGR1, SEC16B, MTCH2, MAF, MC4R, and TMEM195 were severely induced, whereas INSIG2, NAMPT, MTMR9, PFKP, KCTD15, LPL and GNPDA2 were down-regulated upon SPIONs stimulation. Since SEC16B gene assist the phagocytosis of apoptotic cells and this gene were highly expressed upon SPIONs treatment in adipocytes, it is logic to assume that SPIONs may play a crucial role in this direction, which requires more consideration in the future. [ABSTRACT FROM AUTHOR]

Blood pressure (BP) is conventionally measured by cuff at the brachial artery as an indication of pressure experienced by the organs. However, individual variation in pulse pressure amplification means that brachial cuff BP may be a poor representation of true central BP. Estimation of central BP is now possible using non-invasive methods that are amenable for widespread use. This paper reviews the evidence regarding the potential value of central BP in hypertension management. The major lines of evidence that support the use of central BP as a clinical tool include the: (1) major discrepancies in central BP among people with similar brachial BP; (2) independent relationship of central BP with end-organ damage; (3) independent relationship of central BP with cardiovascular (CV) events and mortality; (4) differential central and brachial BP responses to antihypertensive medications and; (5) improvements in end-organ damage after therapy more strongly relate to central than brachial BP. Despite all this, important evidence gaps relating to clinical use of central BP need fulfilling. These include the lack of central BP reference values and randomized, controlled studies to determine if: (1) central BP can help with diagnostic/therapeutic decisions and; (2) CV outcome is improved by targeting therapy towards lowering central BP levels. Additional challenges such as standardization of central BP methods, and understanding which patients are most likely to benefit from central BP monitoring also need to be determined. Overall, the future for central BP as a worthwhile clinical instrument appears positive, but there is much to be done. [ABSTRACT FROM AUTHOR]

Background:The purpose of this study was to assess the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography computed tomography (FDG-PET/CT) for evaluation of response to chemotherapy and bevacizumab and for prediction of progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC) with potentially resectable liver lesions.Methods:A total of 19 mCRC patients were treated with FOLFOX/FOLFIRI and bevacizumab followed by surgery. Dynamic contrast-enhanced magnetic resonance imaging and FDG-PET/CT were performed before treatment and after cycle 5. PET results were quantified by calculating maximum standardised uptake value (SUVmax) whereas area under the enhancement curve (AUC), initial AUC (iAUC) and the endothelial transfer constant (Ktrans) were used to quantify DCE-MRI. Pathological analysis of the resection specimen was performed, including measurement of microvessel density (MVD) and proliferation index.Results:Both AUC and iAUC were significantly decreased following bevacizumab therapy (median change of 22% (P=0.002) and 40% (P=0.001) for AUC and iAUC, respectively). Progression-free survival benefit was shown for patients with >40% reduction in Ktrans (P=0.019). In the group of radiological responders, the median baseline SUVmax was 3.77 (IQR: 2.88-5.60) compared with 7.20 (IQR: 4.67-8.73) in nonresponders (P=0.021). A higher follow-up SUVmax was correlated with worse PFS (P=0.012). Median MVD was 10.9. Progression-free survival was significantly shorter in patients with an MVD greater than 10, compared with patients with lower MVD (10 months compared with 16 months, P=0.016).Conclusion:High relative decrease in Ktrans, low follow-up SUVmax and low MVD are favourable prognostic factors for mCRC patients treated with bevacizumab before surgery. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) and schizophrenia (SCZ) are two common neurodevelopmental syndromes that result from the combined effects of environmental and genetic factors. We set out to test the hypothesis that rare variants in many different genes, including de novo variants, could predispose to these conditions in a fraction of cases. In addition, for both disorders, males are either more significantly or more severely affected than females, which may be explained in part by X-linked genetic factors. Therefore, we directly sequenced 111 X-linked synaptic genes in individuals with ASD (n=142; 122 males and 20 females) or SCZ (n=143; 95 males and 48 females). We identified >200 non-synonymous variants, with an excess of rare damaging variants, which suggest the presence of disease-causing mutations. Truncating mutations in genes encoding the calcium-related protein IL1RAPL1 (already described in Piton et al. Hum Mol Genet 2008) and the monoamine degradation enzyme monoamine oxidase B were found in ASD and SCZ, respectively. Moreover, several promising non-synonymous rare variants were identified in genes encoding proteins involved in regulation of neurite outgrowth and other various synaptic functions (MECP2, TM4SF2/TSPAN7, PPP1R3F, PSMD10, MCF2, SLITRK2, GPRASP2, and OPHN1). [ABSTRACT FROM AUTHOR]

Lentiviral vectors are effective tools for gene transfer and integrate variable numbers of proviral DNA copies in variable proportions of cells. The levels of transduction of a cellular population may therefore depend upon experimental parameters affecting the frequency and/or the distribution of vector integration events in this population. Such analysis would require measuring vector copy numbers (VCN) in individual cells. To evaluate the transduction of hematopoietic progenitor cells at the single-cell level, we measured VCN in individual colony-forming cell (CFC) units, using an adapted quantitative PCR (Q-PCR) method. The feasibility, reproducibility and sensitivity of this approach were tested with characterized cell lines carrying known numbers of vector integration. The method was validated by correlating data in CFC with gene expression or with calculated values, and was found to slightly underestimate VCN. In spite of this, such Q-PCR on CFC was useful to compare transduction levels with different infection protocols and different vectors. Increasing the vector concentration and re-iterating the infection were two different strategies that improved transduction by increasing the frequency of transduced progenitor cells. Repeated infection also augmented the number of integrated copies and the magnitude of this effect seemed to depend on the vector preparation. Thus, the distribution of VCN in hematopoietic colonies may depend upon experimental conditions including features of vectors. This should be carefully evaluated in the context of ex vivo hematopoietic gene therapy studies. [ABSTRACT FROM AUTHOR]

The NMR diffusometry technique, based on the measurement of the diffusion coefficient of a ligand in the absence and in the presence of its macromolecular partner, was used to study the affinity for human serum albumin (HSA) of four gadolinium complexes, potential or already used magnetic resonance imaging contrast agents. Diamagnetic lanthanum(III) ion or europium(III) ion, which has the advantage of shifting the NMR signals far away from those of the macromolecule, was used to avoid the excessive broadening of the NMR signals induced by the gadolinium(III) ion. Titration experiments, in which the HSA concentration was kept constant and the concentration of the europium or lanthanum chelate was varied, were performed to evaluate the association constant and the number of binding sites. Some additional information about the kinetics of the exchange between the free and the bound chelate was also obtained. Competition experiments with ibuprofen and salicylate, which are ligands with a known affinity for the macromolecule and for which the binding site is known, were also performed to get information about the binding site of the contrast agents. [ABSTRACT FROM AUTHOR]

We have previously shown that patients with renal fibromuscular dysplasia (FMD) have asymptomatic carotid lesions and that familial forms may occur. The objective of this study was to test whether carotid lesions could be detected in relatives of familial cases. High-resolution echotracking of the carotid artery was performed in 47 relatives of 13 cases from six families. This non-invasive investigation led to a semiquantitative arterial score that was compared with that obtained for 47 controls matched for age and sex and that for 125 sporadic cases. Familial resemblance was tested by using a generalized estimating equation approach taking into account the clustering of scores in families. As expected, FMD cases had a significantly higher score than controls (4.02 vs 2.52, P<10−5). Familial cases were not significantly different from sporadic cases. Of interest, the 47 apparently healthy relatives of familial cases had also a high carotid score (4.17), very significantly higher than that of controls (2.52, P<10−5) even though lower than the corresponding index FMD cases (4.81, P=0.01). Segregation analysis showed that 52% of the descendants of subjects with a score >4 had a score >4, a proportion consistent with autosomal-dominant transmission of the trait. Altogether these results strengthen the hypothesis of renal FMD being a systemic arterial disease and argue for a familial resemblance that may be due to a major genetic effect. The carotid score obtained by high-resolution echotracking may provide a non-invasive surrogate marker for renal FMD of potential value for use in linkage strategies on large pedigrees.Journal of Human Hypertension (2007) 21, 393–400. doi:10.1038/sj.jhh.1002156; published online 1 March 2007 [ABSTRACT FROM AUTHOR]

We collected paraffin-embedded myelocytomatoses induced by subgroup J avian leukosis virus (ALV-J) in French poultry from 1992 to 2000. We used nested PCR to obtain the U3 LTR and the E element sequences that encompass putative binding sites for transcription factors. We observed minor mutations in the U3 sequences that rarely affected transcription factor binding sites, thus preserving the transcriptional potential of the U3 LTR. However, we observed a large variability in the E element sequences from both field and experimental tumor samples. This variability involved genomic rearrangements and various deletions that most often occurred between two direct repeat sequences. Moreover, in seven DNA samples of the 22 field tumors analyzed, we observed two different sequences for the E element region, suggesting that proviral genomes of two different sizes may be simultaneously present in a tumor. Even though most of the E element sequences were mutated or rearranged, all myelocytomatosis samples always exhibited one E element sequence containing at least one putative C/EBP binding site that was unaffected and still potentially functional. [ABSTRACT FROM AUTHOR]

Genetic diversity between French European brown hare syndrome (EBHS) viruses since the disease appeared has been evaluated. Nucleotide sequencing of the partial capsid protein genes of 169 EBHS viruses collected from various parts of France between 1989 and 2003, three reference strains, and a Greek EBHSV collected in 2002 revealed a maximum nucleotide divergence of 11.7%, indicating a high level of conservation between viruses. Two major groups were identified. The first group contained EBHS viruses collected since 1989 from different parts of France, the reference strains, and all of the viruses located in the far north of France. In this group, three genogroups were clearly identified as mainly related to their geographic origin. The distribution of the viruses suggests that the early viruses have not disappeared and have slowly evolved in their area of origin. The second group, supported by a significant bootstrap value, contained the Greek EBHSV with the French EBHS viruses collected between 1999 and 2003 from regions of southern France. It constitutes a newly identified genogroup. Our results demonstrate strong differences in genetic evolution between EBHSV and rabbit haemorrhagic disease virus, with persistence of the earlier EBHS viruses and interaction between the geographical and temporal distributions. [ABSTRACT FROM AUTHOR]

It is now well established that genetic factors play an important role in the pathogenesis of autism disorder and converging lines of evidence suggest the implication of the X chromosome. Using a sample of subjects diagnosed with autism spectrum disorders, exclusively composed of males from French-Canadian (FC) origin, we tested markers covering the entire X chromosome using a family-based association study. Our initial analysis revealed the presence of association at two loci: DXS6789 (P=0.026) and DXS8043 (P=0.0101). In a second step, we added support to the association at DXS8043 using additional markers, additional subjects and a haplotype-based analysis (best obtained P-value=0.00001). These results provide support for the existence of a locus on the X chromosome that predisposes the FC to autism spectrum disorders.Molecular Psychiatry (2006) 11, 206–213. doi:10.1038/sj.mp.4001756; published online 1 November 2005 [ABSTRACT FROM AUTHOR]

Wiskott-Aldrich syndrome (WAS) is an immune deficiency with thrombopenia resulting from mutations in the WASP gene. This gene normally encodes the Wiskott-Aldrich syndrome protein (WASP), a major cytoskeletal regulator expressed in hematopoietic cells. Gene therapy is a promising option for the treatment of WAS, requiring that clinically applicable WASP gene transfer vectors demonstrate efficacy in preclinical studies. Here, we describe a self-inactivating HIV-1-derived lentiviral vector encoding human WASP and show that it effectively transduced bone marrow progenitor cells of WASP knockout (WKO) mice. Transplantation of these transduced cells into lethally irradiated WKO recipients led to stable expression of WASP and correction of immune, inflammatory and cytoskeletal defects. Splenic T-cell proliferation was restored, podosomes were reinstated on bone-marrow-derived dendritic cells and colon inflammation was reduced. This shows for the first time (a) that cytoskeletal defects can be corrected in WKO mice, (b) that human WASP is biologically active in mice and (c) that a lentiviral vector is effective to express human WASP in vivo over several months. These data support further development of such lentiviral vectors for the gene therapy of WAS.Gene Therapy (2005) 12, 597-606. doi:10.1038/sj.gt.3302440 Published online 16 December 2004 [ABSTRACT FROM AUTHOR]

Summary. The first molecular epidemiological study of Rabbit haemorrhagic disease virus undertaken in France between 1988 and 1995, identified three genogroups, two of which (G1, G2) disappeared quickly. We used immunocapture-RT-PCR and sequencing to analyse 104 new RHDV isolates collected between 1993 and 2000. One isolate was obtained in 2000 from a French overseas territory, the Reunion Island. The nucleotide sequences of these isolates were aligned with those of some French RHDV isolates representative of the three genogroups previously identified, of some reference strains and German and American RHDV antigenic variants. Despite the low degree of nucleotide sequence variation, three new genogroups (G4 to G6) were identified with significant bootstrap values. Two of these genogroups (G4 and G5) were related to the year in which the RHDV isolates were collected. Genogroup G4 emerged from genogroup G3, which has now disappeared. Genogroup G5 is a new independent group. The genogroup G6 contained an isolate collected in mainland France in 1999 and the isolate collected from the Reunion Island, as well as German and American RHDV variants. Multiple sequence alignments of the VP60 gene and antigenic analysis with monoclonal antibodies demonstrated that these French isolates are two new isolates of the RHDV variant. [ABSTRACT FROM AUTHOR]

Summary. Rabbit hemorrhagic disease virus (RHDV) and European brown hare syndrome virus (EBHSV) are caliciviruses that produce severe symptoms and are lethal to rabbits and hares. The folding of the capsid protein was studied by determination of the antigenic pattern of chimeric capsid proteins, composed of regions from RHDV and EBHSV capsid proteins. The anti-RHDV monoclonal antibody (MAb) E3, which is known to bind an external conformational epitope, recognized the RHDV C-terminal region. The anti-RHDV MAb A47, which binds a buried epitope, recognized the RHDV N-terminal region. Using a pGEX expression library, we more precisely mapped the MAb A47 epitope on a 31 residues length peptide, between residue 129 and 160 of the VP60, confirming its location in the N-terminal part of the protein. These results demonstrate that the C-terminal part of the protein is accessible to the exterior whereas the N-terminal domain of the protein constitutes the internal shell domain of the particle. With the aim of using virus-like particles (VLPs) of RHDV as epitope carriers or DNA transfer vectors, we produced in the baculovirus system three proteins, ΔN1, ΔN2 and ΔN3, truncated at the N terminus. The ΔN1 protein assembled into VLPs, demonstrating that the first 42 amino acid residues are not essential for capsid assembly. In contrast, ΔN2, from which the first 75 residues were missing, was unable to form VLPs. The small particles obtained with the ΔN3 protein lacking residues 31 to 93, located in the immunodominant region of the RHDV capsid protein, indicate that up to 62 amino acid residues can be eliminated without preventing assembly. [ABSTRACT FROM AUTHOR]

Abstract The arteries and veins of the left vagus (VN) and left recurrent laryngeal (RLN) nerves from the thoracic inlet to the subaortic region are described following vascular casting with red colored latex in 6 adult fresh non-embalmed cadavers. In all specimens the anterior bronchoesophageal artery supplied at least one vessel to the VN and RLN in the subaortic region. For the RLN other arterial sources were arteries arising from the aortic arch in 1 specimen, the subclavian artery in 3 specimens, the first intercostal artery in 1 specimen, and the inferior thyroid artery in all specimens. For the VN other arterial sources were arteries arising from the aortic arch in 2 specimens and the inferior thyroid artery in 1 specimen. For both the VN and RLN the veins were located under the pleura and directed towards the internal thoracic vein anteriorly and the thoracic intercostal veins posteriorly. In conclusion, the inferior thyroid artery at the thoracic inlet for the RLN and the anterior bronchoesophageal artery are the more consistent vessels supplying the VN and RLN. Vascular damage occurring during mediastinal lymph node excision to the VN and RLN, especially in the subaortic region, may explain postoperative vocal fold paralysis. [ABSTRACT FROM AUTHOR]

MP-2269, the Gd(III) complex of 4-pcntylbicyclo[2.2.2] octane-l-carboxyl-di-L-aspartyl-lysinc-derived-DTPA, is a small Gd-agent that binds non-covalently to scrum albumin in vivo to assume the enhanced relaxivities associated with macromolecular agents, (due in part to increased rotational correlation time, τR). To further explore the fundamental parameters that govern the dynamics of water proton relaxation enhancement by this prototypical albumin-binding agent, the rotational correlation time (τR) for the deuterated La(III) analog of MP-2269 has been independently measured in the presence and absence of 4% albumin using2H-NMR approaches. The diamagnetic La(III) analog of MP-2269 was deuterated at the α-position of the carbonyl groups.2H-NMR studies were conducted at 7.05T (46 MHz) and 310°K on a Bruker NMR spectrometer. Spectral deconvolution permitted calculation of transverse relaxation rates, 1/T2, from the NMR linewidths and subsequently, τR. The results yielded a τR of the albumin bound complex of ∼ 8 ns. This value is intermediate between those earlier estimated by17O-NMR (∼ 1 ns) and1H-NMRD (∼ 20–50 ns) and significantly shorter than that of albumin. The2H-NMR study results also indicate that the exchange between free and albumin-bound forms of the La(III) analog is slow (exchange lifetimes > 1 ms). This slow exchange does not affect the water residence lifetimes (τM 140-280 ns). [ABSTRACT FROM AUTHOR]

The aim of the present study was to examine the effect of cigarette smoking in healthy non-smokers on blood pressure and forearm haemodynamics after acute oral administration of non-selective β-adrenoceptor blockers with and without intrinsic sympathomimetic activity, viz. pindolol 15 mg and propranolol 80 mg. A preliminary study was done to compare cigarette smoking and sham smoking to evaluate the time-course of the haemodynamic effects of cigarette smoking. The second experiment was then carried out in the same six volunteers, according to a double-blind randomized placebo-controlled crossover design, to evaluate the possible effect of pre-treatment with β-adrenoceptor blockers on blood pressure, heart rate and forearm haemodynamics (forearm blood flow, brachial artery diameter and brachio-radial pulse-wave velocity) measured at baseline, during smoking and every five minutes up to 1 h afterwards. No major difference from placebo in blood pressure or forearm haemodynamics was found and pre-treatment with beta-blockers did not prevent the acute vascular effects of cigarette smoking. [ABSTRACT FROM AUTHOR]