Wash‐out of the non‐heart‐beating donor liver: a matter of flush solution and temperature?

BACKGROUND AND AIMS: Ischemically damaged donor livers are prone to graft non-function. This can in part be explained by a suboptimal wash-out during procurement. An enriched machine perfusion (MP) preservation solution for livers, named Polysol, was developed. The aim of this study was to investigate the type of flush solution, temperature and anticoagulant content on the wash-out of the non-heart-beating donor (NHBD) rat liver. METHODS: Rat livers were flushed after 30 min warm ischemia. After excision, livers were reperfused at 37 degrees C, with analysis of damage and function, concerning (1) solutions (University of Wisconsin (UW), histidine-tryptophan-ketoglutarate (HTK) and Polysol); (2) temperature (4 degrees C, 18 degrees C and 37 degrees C); (3) addition of heparin and (4) wash-out followed by 24 h MP. RESULTS: (1) Reperfusion results were inferior in the UW group; (2) less damage and improved function were seen after wash-out using Polysol at 37 degrees C; (3) No effects were seen of the addition of heparin to Polysol; (4) MP after wash-out using HTK resulted in more liver damage and decreased liver function as compared with wash-out using Polysol. CONCLUSIONS: Polysol is applicable as a flush solution for the NHBD liver, resulting in equal to better wash-out as compared with UW and HTK. The best temperature for this NHBD wash-out is 37 degrees C.     

Bacterial cholangitis causing secondary sclerosing cholangitis: A case report

Background  

Although bacterial cholangitis is frequently mentioned as a cause of secondary sclerosing cholangitis, it appears to be extremely rare, with only one documented case ever reported.     

Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF

Recombinant human interleukin-5 (rhIL-5), in either liquid or semi- solid cultures, selectively induced eosinophil production from normal human bone marrow, with no activity on other cell lineages. The time course of eosinophil production induced by murine IL-5, rhIL-3, and rh granulocyte-macrophage colony stimulating factor (GMCSF) was similar to rhIL-5. The rate of eosinophil maturation in vitro was independent of the stimulating cytokine, mature eosinophils being produced after 4 to 5 weeks in liquid culture with each of these cytokines. The eosinophils produced in response to each cytokine were morphologically indistinguishable, and had the ultrastructural features of maturity except that the electron-dense material in the granules had not formed into crystalline cores. Neither rhIL-1 nor rhIL-6 alone, or in combination with rhIL-5 or rhIL-3, induced eosinophil differentiation or proliferation under the conditions used. rhIL-3 and rhGMCSF induced more eosinophil colonies than rhIL-5, rhIL-5 had an additive, not synergistic, effect on eosinophil colony production when combined with either rhIL-3 or rhGMCSF, suggesting that rhIL-5 stimulates a smaller and possibly different population of eosinophil progenitors. However, rhIL-5 induced the greatest eosinophil production in liquid cultures, suggesting that although it may act on a smaller population of precursors, it is able to stimulate more proliferative steps than either rhIL-3 or rhGMCSF.     

The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis

We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice.     

Multimodal Functional Neuroimaging by Simultaneous BOLD fMRI and Fiber-Optic Calcium Recordings and Optogenetic Control

Recent developments of optogenetic tools and fluorescence-based calcium recording techniques enable the manipulation and monitoring of neural circuits on a cellular level. Non-invasive imaging of brain networks, however, requires the application of methods such as blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), which is commonly used for functional neuroimaging. While BOLD fMRI provides brain-wide non-invasive reading of the hemodynamic response, it is only an indirect measure of neural activity. Direct observation of neural responses requires electrophysiological or optical methods. The latter can be combined with optogenetic control of neuronal circuits and are MRI compatible. Yet, simultaneous optical recordings are still limited to fiber-optic-based approaches. Here, we review the integration of optical recordings and optogenetic manipulation into fMRI experiments. As a practical example, we describe how BOLD fMRI in a 9.4-T small animal MR scanner can be combined with in vivo fiber-optic calcium recordings and optogenetic control in a multimodal setup. We present simultaneous BOLD fMRI and calcium recordings under optogenetic control in rat. We outline details about MR coil configuration, choice, and usage of opsins and chemically and genetically encoded calcium sensors, fiber implantation, appropriate light power for stimulation, and calcium signal detection, to provide a glimpse into challenges and opportunities of this multimodal molecular neuroimaging approach.     

Sympathetic Input to Multiple Cell Types in Mouse and Human Colon Produces Region-Specific Responses

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