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Benjamin Storek Nina M Harder Michaela S Banck Cheng Wang Douglas M McCarty William GM Janssen John H Morrison Christopher E Walsh Andreas S Beutler 《Molecular pain》2006,2(1):1-11
Background
Intrathecal (IT) gene transfer is an attractive approach for targeting spinal mechanisms of nociception but the duration of gene expression achieved by reported methods is short (up to two weeks) impairing their utility in the chronic pain setting. The overall goal of this study was to develop IT gene transfer yielding true long-term transgene expression defined as ≥ 3 mo following a single vector administration. We defined "IT" administration as atraumatic injection into the lumbar cerebrospinal fluid (CSF) modeling a lumbar puncture. Our studies focused on recombinant adeno-associated virus (rAAV), one of the most promising vector types for clinical use.Results
Conventional single stranded rAAV2 vectors performed poorly after IT delivery in rats. Pseudotyping of rAAV with capsids of serotypes 1, 3, and 5 was tested alone or in combination with a modification of the inverted terminal repeat. The former alters vector tropism and the latter allows packaging of self-complementary rAAV (sc-rAAV) vectors. Combining both types of modification led to the identification of sc-rAAV2/l as a vector that performed superiorly in the IT space. IT delivery of 3 × 10e9 sc-rAAV2/l particles per animal led to stable expression of enhanced green fluorescent protein (EGFP) for ≥ 3 mo detectable by Western blotting, quantitative PCR, and in a blinded study by confocal microscopy. Expression was strongest in the cauda equina and the lower sections of the spinal cord and only minimal in the forebrain. Microscopic examination of the SC fixed in situ with intact nerve roots and meninges revealed strong EGFP fluorescence in the nerve roots.Conclusion
sc-rAAVl mediates stable IT transgene expression for ≥ 3 mo. Our findings support the underlying hypothesis that IT target cells for gene transfer lack the machinery for efficient conversion of the single-stranded rAAV genome into double-stranded DNA and favor uptake of serotype 1 vectors over 2. Experiments presented here will provide a rational basis for utilizing IT rAAV gene transfer in basic and translational studies on chronic pain. 相似文献82.
Giulio Galla Gianni Barcaccia Angelo Ramina Silvio Collani Fiammetta Alagna Luciana Baldoni Nicolò GM Cultrera Federico Martinelli Luca Sebastiani Pietro Tonutti 《BMC plant biology》2009,9(1):128-17
Background
Olea europaea L. is a traditional tree crop of the Mediterranean basin with a worldwide economical high impact. Differently from other fruit tree species, little is known about the physiological and molecular basis of the olive fruit development and a few sequences of genes and gene products are available for olive in public databases. This study deals with the identification of large sets of differentially expressed genes in developing olive fruits and the subsequent computational annotation by means of different software. 相似文献83.
Ralf Janssen Martine Le Gouar Matthias Pechmann Francis Poulin Renata Bolognesi Evelyn E Schwager Corinna Hopfen John K Colbourne Graham E Budd Susan J Brown Nikola-Michael Prpic Carolin Kosiol Michel Vervoort Wim GM Damen Guillaume Balavoine Alistair P McGregor 《BMC evolutionary biology》2010,10(1):1-21
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Foliar elemental composition of European forest tree species associated with evolutionary traits and present environmental and competitive conditions 下载免费PDF全文
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Fish populations in Albasini and Nandoni dams are negatively affected by extensive netting practices. This observation was made by the authors following a number of fish health assessment surveys related to aquatic pollution in the Luvuvhu River catchment. A comparison between the number and size of fish collected over a period of ten years indicated decreases in the average size and a consistent low number of fish, despite similar extensive sampling efforts. Unregulated netting is a common practice in both dams. This may become a serious problem as fish from these two dams are an important source of protein for the local communities. The purpose of this note is to report that gillnets are illegally used in the system and on the effect this could have on the fish population. The authors suggest educational and awareness initiatives to inform local communities about the importance of utilising fish in a sustainable manner to ensure the livelihood of generations to come. 相似文献
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Opstelten W Van Wijck AJ Van Essen GA Buskens E Bak AA Kalkman CJ Verheij TJ Moons KG 《BMC anesthesiology》2004,4(1):2-7
BACKGROUND: Postherpetic neuralgia (PHN) is by far the most common complication of herpes zoster (HZ) and one of the most intractable pain disorders. Since PHN is seen most often in the elderly, the number of patients with this disorder is expected to increase in our ageing society. PHN may last for months to years and has a high impact on the quality of life. The results of PHN treatment are rather disappointing. Epidural injection of local anaesthetics and steroids in the acute phase of HZ is a promising therapy for the prevention of PHN. Since randomised trials on the effectiveness of this intervention are lacking, the PINE (Prevention by epidural Injection of postherpetic Neuralgia in the Elderly) study was set up. The PINE study compares the effectiveness and cost-effectiveness of a single epidural injection of local anaesthetics and steroids during the acute phase of HZ with that of care-as-usual (i.e. antivirals and analgesics) in preventing PHN in elderly patients. METHODS / DESIGN: The PINE study is an open, multicenter clinical trial in which 550 elderly (age >/= 50 yr.) patients who consult their general practitioner in the acute phase of HZ (rash < 7 days) are randomised to one of the treatment groups. The primary clinical endpoint is the presence of HZ-related pain one month after the onset of the rash. Secondary endpoints include duration and severity of pain, re-interventions aiming to treat the existing pain, side effects, quality of life, and cost-effectiveness. CONCLUSION: The PINE study is aimed to quantify the (cost-) effectiveness of a single epidural injection during the acute phase of HZ on the prevention of PHN. 相似文献
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Esther Reefman Marcelus CJM de Jong Hilde Kuiper Marcel F Jonkman Pieter C Limburg Cees GM Kallenberg Marc Bijl 《Arthritis research & therapy》2007,8(6):R156
Apoptotic cells are thought to play an essential role in the pathogenesis of systemic lupus erythematosus (SLE). We hypothesise
that delayed or altered clearance of apoptotic cells after UV irradiation will lead to inflammation in the skin of SLE patients.
Fifteen SLE patients and 13 controls were irradiated with two minimal erythemal doses (MEDs) of ultraviolet B light (UVB).
Subsequently, skin biopsies were analysed (immuno)histologically, over 10 days, for numbers of apoptotic cells, T cells, macrophages,
and deposition of immunoglobulin and complement. Additionally, to compare results with cutaneous lesions of SLE patients,
20 biopsies of lupus erythematosus (LE) skin lesions were analysed morphologically for apoptotic cells and infiltrate. Clearance
rate of apoptotic cells after irradiation did not differ between patients and controls. Influx of macrophages in dermal and
epidermal layers was significantly increased in patients compared with controls. Five out of 15 patients developed a dermal
infiltrate that was associated with increased epidermal influx of T cells and macrophages but not with numbers of apoptotic
cells or epidermal deposition of immunoglobulins. Macrophages were ingesting multiple apoptotic bodies. Inflammatory lesions
in these patients were localised near accumulations of apoptotic keratinocytes similar as was seen in the majority of LE skin
lesions. In vivo clearance rate of apoptotic cells is comparable between SLE patients and controls. However, the presence of inflammatory
lesions in the vicinity of apoptotic cells, as observed both in UVB-induced and in LE skin lesions in SLE patients, suggests
that these lesions result from an inflammatory clearance of apoptotic cells. 相似文献
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