PACAP and migraine headache: immunomodulation of neural circuits in autonomic ganglia and brain parenchyma.

The discovery that intravenous (IV) infusions of the neuropeptide PACAP-38 (pituitary adenylyl cyclase activating peptide-38) induced delayed migraine-like headaches in a large majority of migraine patients has resulted in considerable excitement in headache research. In addition to suggesting potential therapeutic targets for migraine, the finding provides an opportunity to better understand the pathological events from early events (aura) to the headache itself. Although PACAP-38 and the closely related peptide VIP (vasoactive intestinal peptide) are well-known as vasoactive molecules, the dilation of cranial blood vessels per se is no longer felt to underlie migraine headaches. Thus, more recent research has focused on other possible PACAP-mediated mechanisms, and has raised some important questions. For example, (1) are endogenous sources of PACAP (or VIP) involved in the triggering and/or propagation of migraine headaches?; (2) which receptor subtypes are involved in migraine pathophysiology?; (3) can we identify specific anatomical circuit(s) where PACAP signaling is involved in the features of migraine? The purpose of this review is to discuss the possibility, and supportive evidence, that PACAP acts to induce migraine-like symptoms not only by directly modulating nociceptive neural circuits, but also by indirectly regulating the production of inflammatory mediators. We focus here primarily on postulated extra-dural sites because potential mechanisms of PACAP action in the dura are discussed in detail elsewhere (see X, this edition)

Comparison of the diagnostic yield and outcomes between standard 8 h capsule endoscopy and the new 12 h capsule endoscopy for investigating small bowel pathology

AIM: To evaluate the completion rate and diagnostic yield of the PillCam SB2-ex in comparison to the PillCam SB2. METHODS: Two hundred cases using the 8-h PillCam SB2 were retrospectively compared to 200 cases using the 12 h PillCam SB2-ex at a tertiary academic center. Endoscopically placed capsules were excluded from the study. Demographic information, indications for capsule endoscopy, capsule type, study length, completion of exam, clinically significant findings, timestamp of most distant finding, and significant findings beyond 8 h were recorded. RESULTS: The 8 and 12 h capsule groups were well matched respectively for both age (70.90 +/- 14.19 vs 71.93 +/- 13.80, P = 0.46) and gender (45.5% vs 48% male, P = 0.69). The most common indications for the procedure in both groups were anemia and obscure gastrointestinal bleeding. PillCam SB2-ex had a significantly higher completion rate than PillCam SB2 (88% vs 79.5%, P = 0.03). Overall, the diagnostic yield was greater for the 8 h capsule (48.5% for SB2 vs 35% for SB2-ex, P = 0.01). In 4/70 (5.7%) of abnormal SB2-ex exams the clinically significant finding was noted in the small bowel beyond the 8 h mark. CONCLUSION: In our study, we found the PillCam SB2-ex to have a significantly increased completion rate, though without any improvement in diagnostic yield compared to the PillCam SB2

Medical Benefit Clubs.

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Acute respiratory diseases: a study on health inequalities

Apresentam-se as desigualdades em saúde valendo-se das doenças respiratórias agudas na infância na área de abrangência de um centro de saúde na cidade de São Paulo, Brasil, para subsidiar o planejamento local de ações de promoção da saúde. O trabalho se fundamentou em estudos ecológicos que utilizam a área geográfica como unidade de análise, permitindo a comparação de indicadores de saúde e sócio-econômicos mediante dados censitários. Foram construídos indicadores de "inserção social" e de "qualidade do domicílio", gerando o "índice potencial de exposição" que reflete as condições de risco para o adoecimento por agravos respiratórios. O tratamento estatístico incluiu o agrupamento pela técnica de cluster. Foram identificados quatro grupos sociais homogêneos nas condições de risco para as doenças respiratórias agudas. Os grupos III e IV - com as piores condições sócio-econômicas - mostraram diferenciais importantes em relação aos grupos I e II. Os diferenciais de mortes por pneumonia encontrados, sugerem iniqüidades em saúde. Os resultados permitiram a localização geográfica de maior e menor concentração das carências relativas às condições de vida e a comparação entre os setores censitários para o reconhecimento de necessidades distintas, que subsidiem propostas para a articulação intersetorial.This article discusses health inequalities based on acute childhood respiratory diseases in the coverage area of a health center in the city of São Paulo, Brazil, to help plan local health promotion activities. The work was based on ecological studies using the geographic area as the unit of analysis, allowing a comparison of health and socioeconomic indicators based on census data. Indicators were constructed for "social inclusion" and "housing quality", generating the "potential exposure index", which reflects the respiratory disease risk conditions. Statistical treatment included grouping according to the cluster technique. Four homogenous social groups were identified in terms of risk conditions for acute respiratory diseases. Groups III and IV, with the worst socioeconomic conditions, showed important differences in comparison to groups I and II. The differences in mortality from pneumonia suggest important health inequalities. The results allow the geographic localization of the highest and lowest concentration of needs in terms of living conditions and the comparison of census tracts for recognizing distinct needs, thus supporting proposals for inter-sector collaboration.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Measuring Red Blood Cell Velocity with a Keyhole Tracking Algorithm

A tracking algorithm is proposed to measure the velocity of red blood cells traveling through microvessels of tumors growing in skin flaps implanted on mice. The tracking is based on a keyhole model that describes the probable movement of a segmented cell between contiguous frames in a video sequence. When a history of movements exists, past, present and a predicted landing position define two regions of probability with a keyhole shape. This keyhole is used to de- termine if cells in contiguous frames should be linked to form tracks. Pre-processing segments cells from background and post-processing joins tracks and discards links that could have been formed due to noise or uncertainty. The algorithm pre- sents several advantages over traditional methods such as kymographs or particle image velocimetry: manual interven- tion is restricted to the thresholding, several vessels can be analyzed simultaneously, algorithm is robust to noise and a wealth of statistical measures can be obtained. Two tumors with different geometries were analyzed; average velocities were 211±136 [μm/s] (mean±std) with a range 15.9-797 [μm/s], and 89±62 [μm/s] with a range 5.5-300 [μm/s] respec- tively, which are consistent with previous results in the litera- ture

Oxo and Oxofree Rhenium(V) Complexes with N,O-donor Schiff Bases

The reaction between cis-[ReVO2I(PPh3)2] and H3duo (N-(2-hydroxybenzylidene)-5-amino-1,3-dimethyl uracil) led to the formation of the oxofree, imido compound, trans-[ReV(ddd)(Hduo)(PPh3)2]I (1) (H2ddd=5,6-diamino-1,3-dimethyluracil). An oxo complex, cis-[ReV(bcp)OCl2(PPh3)](2) [Hbcp = N-(2-hydroxybenzylidene)-benzothiazole] was isolated from the reaction of trans-[ReOVCl3(PPh3)2] with Hbcp. The crystal structures of the compounds were determined by single crystal X-ray diffraction.Keywords: Rhenium(V), imido, oxo, crystal structure, spectral characterizatio

Microflow of fluorescently labelled red blood cells in tumours expressing single isoforms of VEGF and their response to VEGF-R tyrosine kinase inhibition

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.In this work we studied the functional differences between the microcirculation of murine tumours that only express single isoforms of vascular endothelial growth factor-A (VEGF), VEGF120 and VEGF188, and the effect of VEGF receptor tyrosine kinase (VEGF-R TK) inhibition on their functional response to the vascular disrupting agent, combretastatin A-4 phosphate (CA-4-P). We used measurement of fluorescentlylabelled red blood cell (RBC) velocities in tumour microvessels to study this functional response. RBC velocity for control VEGF120-expressing tumours was over 50% slower than for control VEGF188-expressing tumours, which may be due to the immature and haemorrhagic vasculature of the VEGF120 tumour. After chronic treatment with a VEGF-R tyrosine kinase inhibitor, SU5416, RBC velocities in VEGF120 tumours were significantly increased compared to control VEGF120 tumours, and similar to velocities in both VEGF188 treatment groups. Control and SU5416 treated VEGF188 tumours were not different from each other. Treatment of VEGF120 tumours with SU5416 reduced their vascular response to CA-4-P to a similar level to the VEGF188 tumours. Differential expression of VEGF isoforms not only affected vascular function in untreated tumours but also impacted on response to a vascular disrupting drug, CA-4-P, alone and in combination with an anti-angiogenic approach involving VEGF-R TK inhibition. Analysis of RBC velocities is a useful tool in measuring functional responses to vascular targeted treatments.This study is funded by the Cancer Research UK