A meta-analysis on the effects of incarceration-based opioid substitution treatment.

Objective: Opioid substitution treatment (OST) is a common treatment for individuals who use opioids; however, empirical evidence on the effects of OST during incarceration is scarce. Our aim was to conduct a meta-analysis on the effects of incarceration-based OST on substance use, treatment engagement post-release and re-incarceration. Method: We searched for studies on individuals who were incarcerated and treated with OST, compared to a comparison group. Studies were only included if they reported data post-release. Results: N = 15 studies met the inclusion criteria. We found less opioid use, less other drug use, higher treatment engagement post-release and less re-incarceration among treated individuals compared to the comparison group. Moderator analyses showed some influence of length of follow-up period and study quality. Conclusions: Incarceration-based OST reduces drug use, re-incarceration and leads to higher treatment engagement after release. More research is needed on the effects of incarceration-based OST on secondary outcomes (e.g. health and social integration) and on factors that moderate these effects.

[(section sign) 115 b SGB V threatens outpatient treatment for inguinal hernia. Analysis of outcome and economics]. / Das Aus für die minimal-invasive Leistenhernienversorgung durch (section sign) 115 b SGB V. Eine Analyse zu Patientenoutcome und Okonomie.

BACKGROUND: Current German legislation ( (section sign) 115 b SGB V) allows groin hernia inpatient treatment only under particular circumstances. That allows the operative technique of first choice for outpatient groin hernia repair to be determined by basic market principles. The aim of this paper was to study the feasibility of outpatient minimally invasive hernia surgery with regard to complication rates, patient satisfaction, and economic considerations. METHODS: For 1 year, a total of 571 patients with inguinal hernias (131 male, eight female, mean age 46 years, all ASA I) were treated at two surgical centers. Twenty-four percent (139/571) underwent outpatient total extraperitoneal repair (TEP). Complication rates were recorded. Patient satisfaction with the procedure was evaluated by a standard questionnaire. Cost calculations were compared with revenues according to the EBM2000plus. RESULTS: Of the patients, 96.4% were discharged on the day of operation without subsequent rehospitalization, 84% had no fears of complications at home, 54% went back to work in less than 14 days, and 88.7% were willing to undergo TEP a second time if necessary. Calculated average total cost of euro 709 exceeded the revenue of euro 565 by 20%. CONCLUSION: For a carefully selected group, outpatient TEP is patient-friendly and safe. Despite these advantages, it still remains economically unattractive to hospital management because of the 20% cover shortage. Improvements in the current legislation are urgently desired.

Thrombomodulin-dependent protein C activation is required for mitochondrial function and myelination in the central nervous system.

Essentials The role of protein C (PC) activation in experimental autoimmune encephalitis (EAE) is unknown. PC activation is required for mitochondrial function in the central nervous system. Impaired PC activation aggravates EAE, which can be compensated for by soluble thrombomodulin. Protection of myelin by activated PC or solulin is partially independent of immune-modulation. SUMMARY: Background Studies with human samples and in rodents established a function of coagulation proteases in neuro-inflammatory demyelinating diseases (e.g. in multiple sclerosis [MS] and experimental autoimmune encephalitis [EAE]). Surprisingly, approaches to increase activated protein C (aPC) plasma levels as well as antibody-mediated inhibition of PC/aPC ameliorated EAE in mice. Hence, the role of aPC generation in demyelinating diseases and potential mechanisms involved remain controversial. Furthermore, it is not known whether loss of aPC has pathological consequences at baseline (e.g. in the absence of disease). Objective To explore the role of thrombomodulin (TM)-dependent aPC generation at baseline and in immunological and non-immunological demyelinating disease models. Methods Myelination and reactive oxygen species (ROS) generation were evaluated in mice with genetically reduced TM-mediated protein C activation (TMPro/Pro ) and in wild-type (WT) mice under control conditions or following induction of EAE. Non-immunological demyelination was analyzed in the cuprizone-diet model. Results Impaired TM-dependent aPC generation already disturbs myelination and mitochondrial function at baseline. This basal phenotype is linked with increased mitochondrial ROS and aggravates EAE. Reducing mitochondrial ROS (p66Shc deficiency), restoring aPC plasma levels or injecting soluble TM (solulin) ameliorates EAE in TMPro/Pro mice. Soluble TM additionally conveyed protection in WT-EAE mice. Furthermore, soluble TM dampened demyelination in the cuprizone-diet model, demonstrating that its myelin-protective effect is partially independent of an immune-driven process. Conclusion These results uncover a novel physiological function of TM-dependent aPC generation within the CNS. Loss of TM-dependent aPC generation causes a neurological defect in healthy mice and aggravates EAE, which can be therapeutically corrected.

Peptide mimics of SNARE transmembrane segments drive membrane fusion depending on their conformational plasticity.

SNARE proteins are essential for different types of intracellular membrane fusion. Whereas interaction between their cytoplasmic domains is held responsible for establishing membrane proximity, the role of the transmembrane segments in the fusion process is currently not clear. Here, we used an in vitro approach based on lipid mixing and electron microscopy to examine a potential fusogenic activity of the transmembrane segments. We show that the presence of synthetic peptides representing the transmembrane segments of the presynaptic soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) synaptobrevin II (also referred to as VAMP II) or syntaxin 1A, but not of an unrelated control peptide, in liposomal membranes drives their fusion. Liposome aggregation by millimolar Ca(2+) concentrations strongly potentiated the effect of the peptides; this indicates that juxtaposition of the bilayers favours their fusion in the absence of the cytoplasmic SNARE domains. Peptide-driven fusion is reminiscent of natural membrane fusion, since it was suppressed by lysolipid and involved both bilayer leaflets. This suggests transient presence of a hemifusion intermediate followed by complete membrane merger. Structural studies of the peptides in lipid bilayers performed by Fourier transform infrared spectroscopy indicated mixtures of alpha-helical and beta-sheet conformations. In isotropic solution, circular dichroism spectroscopy showed the peptides to exist in a concentration-dependent equilibrium of alpha-helical and beta-sheet structures. Interestingly, the fusogenic activity decreased with increasing stability of the alpha-helical solution structure for a panel of variant peptides. Thus, structural plasticity of transmembrane segments may be important for SNARE protein function at a late step in membrane fusion.

Neuroepithelial cells downregulate their plasma membrane polarity prior to neural tube closure and neurogenesis.

Cell differentiation often involves changes in cell polarity. In this study we show that neuroepithelial cells, the progenitors of all neurons and macroglial cells of the vertebrate central nervous system, downregulate the polarized delivery to the apical and basolateral plasma membrane domains during development. Upon infection of the neuroepithelium of mouse embryos with fowl plague virus (FPV), polarized delivery of the viral envelope hemagglutinin, an apical marker, occurred at the neural plate stage (E8), but was downregulated at the open neural tube stage (E9). Upon infection with vesicular stomatitis virus, the viral envelope G protein, a basolateral marker, showed an unpolarized delivery not only at the open neural tube stage, but already at the neural plate stage. These results show that a progressive downregulation of plasma membrane polarity of neuroepithelial cells precedes neural tube closure and the onset of neurogenesis.

Alteration of the cytoskeleton of mammalian cells cultured in vitro by Clostridium botulinum C2 toxin and C3 ADP-ribosyltransferase.

The effects of Clostridium botulinum C3 ADP-ribosyltransferase and of Clostridium botulinum C2 toxin were studied on the cytoskeleton of rat hepatoma FAO and human glioma U333 cells. After treatment of these cells for 24 to 48 h with C3 (3-30 micrograms/ml), the actin microfilaments disappeared, and the intermediate filament network was found to collapse, while microtubules remained intact. Similar alterations of the cytoskeletal filaments without affecting microtubules were induced by the actin-ADP-ribosylating C2 toxin. In FAO cells, C3 caused the rounding up of cells. Concomitantly, cytosolic 22 to 24 kDa proteins were ADP-ribosylated in a guanine nucleotide-dependent manner. Rounding up of cells and ADP-ribosylation of proteins in intact cells were observed at similar concentration of the transferase. These data suggest a role of the protein substrates of C3 in the regulation of the cytoskeletal integrity.

[The initial clinical experiences with a dynamic FLASH-2D sequence in tumors of the head and neck area]. / Erste klinische Erfahrungen mit einer dynamischen FLASH-2D-Sequenz bei Tumoren im Kopf- und Halsbereich.

28 patients with clinically confirmed head and neck tumours were examined by MRI. The results of a dynamic FLASH-2D sequence and a Gd-DTPA enhanced T1-weighted sequence were analysed and retrospectively compared with surgery and pathological findings. The extent of tumours was clearly defined by the dynamic technique in 21 cases. Furthermore, it was found to be superior for the purpose of demonstrating contrast behaviour and concerning T-classification. Here the dynamic FLASH-2D sequence proved to be an important supplement for preoperative diagnosis.

Home ranges and satellite tactics of male green swordtails (Xiphophorus helleri) in nature.

Dominance relationships were studied between marked or otherwise individually recognizable male green swordtails in a creek at Lake Catemaco and in a tributary of the Rio Atoyac (Veracruz, Mexico). The Atoyac population is unique because of a high degree of polymorphism, including both macromelanophore spotting and a micromelanophore tailspot pattern. During the dry season males living in the same area maintained a linear social hierarchy for periods of many days. The subordinate males settled down either in the same home ranges or in home ranges largely overlapping with that of dominant males. Although dominant males untiringly chased the subordinate males away, they returned persistently and achieved the status of non-tolerated satellites. Females were less stationary and presumably passed through many male home ranges during their feeding activities. The data clearly demonstrate that green swordtails live in complex social systems in which male-male competition and probably also female mate choice are likely to be essential factors for individual reproductive success.

[Brain metastases of lung cancer: diagnostic accuracy of positron emission tomography with fluorodeoxyglucose (FDG-PET)]. / Diagnostische Aussagekraft der Positronen-Emissions-Tomographie (PET) bei zerebralen Metastasen von Bronchialkarzinomen.

The value of FDG-PET in oncology is currently investigated in clinical studies. There is only limited information on the usefulness of FDG-PET in the evaluation of distant metastases of lung cancer. The purpose of the present prospective investigation was to determine the diagnostic accuracy of FDG-PET in the detection of brain metastases of lung cancer. After intravenous injection of 220 +/- 50 MBq F-18-deoxyglucose PET acquisition was carried out using an ECAT ART scanner (CTI Siemens). Images were reconstructed using a filtered backprojection with a Hanning filter. PET data were analyzed by visual interpretation of coronal, sagittal and transversal slices. PET scans were interpreted by two experienced nuclear medicine physicians without prior knowledge of the results of other imaging studies or clinical data. Between March 1997 and July 1998 whole-body PET was performed in 417 patients with suspected lung cancer. 402 patients were used for statistical analysis. Based on conventional brain imaging with CT (occasionally MRI), brain metastases were suspected in 17 patients (prevalence 4.2%). For FDG-PET alone, sensitivity was 82% (14/17) and specificity 38% (14/37). Therefore, diagnostic accuracy of FDG-PET in detection of brain metastases was 93.5%. The low specificity of FDG-PET can be explained by reduced tracer uptake mainly due to brain infarction or vascular encephalopathy in this group of elderly patients. Our results indicate that due to its low specificity FDG-PET is not useful for the evaluation of brain metastases in the primary staging of patients with lung cancer.

Mitochondrial translocation of oxidized cofilin induces caspase-independent necrotic-like programmed cell death of T cells.

Oxidative stress leads to T-cell hyporesponsiveness or death. The actin-binding protein cofilin is oxidized during oxidative stress, which provokes a stiff actin cytoskeleton and T-cell hyporesponsiveness. Here, we show that long-term oxidative stress leads to translocation of cofilin into the mitochondria and necrotic-like programmed cell death (PCD) in human T cells. Notably, cofilin mutants that functionally mimic oxidation by a single mutation at oxidation-sensitive cysteins (Cys-39 or Cys-80) predominately localize within the mitochondria. The expression of these mutants alone ultimately leads to necrotic-like PCD in T cells. Accordingly, cofilin knockdown partially protects T cells from the fatal effects of long-term oxidative stress. Thus, we introduce the oxidation and mitochondrial localization of cofilin as the checkpoint for necrotic-like PCD upon oxidative stress as it occurs, for example, in tumor environments.

[WHO air quality guidelines and their significance for determining maximum allowable concentration values]. / Luftqualitätsleitlinien der WHO und ihre Bedeutung für die Festlegung der MIK-Werte.

A survey of the air quality guidelines for 28 pollutants published by the WHO is given. The principles of the deducation of the guidelines are explained. For comparison the foundamentals of the establishment of MIK-values (Maximum Allowable Immission Concentration) of the Soviet Union and the GDR are pointed out.

[International trends in the study of room air quality and conclusions for East Germany]. / Internationale Tendenzen bei der Untersuchung der Raumluftqualität und Schlussfolgerungen für die DDR.

The international literature is analyzed in order to recognize recent developments in the field of investigations of indoor air quality. Special attention is paid to the papers of the 4th International Conference on Indoor Air Quality and Climate, held in Berlin (West) August 1987. It is noticed that a certain emphasis is put on the investigation of volatile organic compounds and of radon and their effects on human health. General conclusions are drawn for the research on these problems in the GDR.

[The toxicity of a prometryne/simazine combination in the lactation stage of rats]. / Untersuchungen zur Toxizität einer Prometryn/Simazin-Kombination in der Laktationsphase bei Ratten.

The postnatal effect of a combination of Prometryne and Simazine was analyzed in rats. Lactating rats were administered from 5 through 10 d pp. The effect on rat pups were characterized by reflex development, behavioural toxicological tests, and selected biochemical investigations. Distinct effects were observed on body weight, neuro-muscular maturation, and somatic development. There were also significant differences in the content of C-reactive protein and the number of white blood cells.

Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells.

Using a new mAb raised against the mouse neuroepithelium, we have identified and cDNA-cloned prominin, an 858-amino acid-containing, 115-kDa glycoprotein. Prominin is a novel plasma membrane protein with an N-terminal extracellular domain, five transmembrane segments flanking two short cytoplasmic loops and two large glycosylated extracellular domains, and a cytoplasmic C-terminal domain. DNA sequences from Caenorhabditis elegans predict the existence of a protein with the same features, suggesting that prominin is conserved between vertebrates and invertebrates. Prominin is found not only in the neuroepithelium but also in various other epithelia of the mouse embryo. In the adult mouse, prominin has been detected in the brain ependymal layer, and in kidney tubules. In these epithelia, prominin is specific to the apical surface, where it is selectively associated with microvilli and microvilli-related structures. Remarkably, upon expression in CHO cells, prominin is preferentially localized to plasma membrane protrusions such as filopodia, lamellipodia, and microspikes. These observations imply that prominin contains information to be targeted to, and/or retained in, plasma membrane protrusions rather than the planar cell surface. Moreover, our results show that the mechanisms underlying targeting of membrane proteins to microvilli of epithelial cells and to plasma membrane protrusions of non-epithelial cells are highly related.

Noncytolytic terminal complement complexes may serve as calcium gates to elicit leukotriene B4 generation in human polymorphonuclear leukocytes.

Complement effects on human polymorphonuclear leukocytes (PMN) have generally been ascribed to the anaphylatoxin C5a, which induces degranulation, superoxide anion generation, migration, and cell aggregation via interaction with membrane receptors. We here report that complement activation on the surface of antibody-sensitized human PMN provokes generation of the potent lipid mediator leukotriene B4 (LTB4) in strict dependence on complement component C8, but in the absence of detectable C9. The kinetics of LT generation are rapid, comparable with those observed after challenge with the calcium-ionophore A23187. LTB4 release is a distinct event that is dissociable from cytotoxicity as assessed by lactate dehydrogenase (LDH) release (dependent on C9) and from superoxide generation (independent of C8 and C9). It is dose dependent on extracellular calcium and is not observed in the absence of calcium. It is inhibited by substances interfering with calcium-calmodulin function (trifluoperazine and W7), but not by blockers of physiologic calcium channels (nimodipine, verapamil, and D 888). Addition of purified C8 to cells bearing C5b-7 induces a severalfold increase in their passive permeability to 45calcium. Sieving experiments with the use of marker molecules of different sizes collectively indicate the existence of small hydrophilic channels consisting exclusively or predominantly of C5b-8 complexes, which allow passive transmembrane flux of small molecules with Mr less than 200. Thus, noncytolytic terminal complement complexes may serve as a biological bypass gate for calcium in PMN membranes, triggering the arachidonic acid cascade with generation of LTB4 at doses well below the threshold required to invoke overt cell damage.

Neurosecretory vesicles can be hybrids of synaptic vesicles and secretory granules.

We have investigated the relationship of the so-called small dense core vesicle (SDCV), the major catecholamine-containing neurosecretory vesicle of sympathetic neurons, to synaptic vesicles containing classic neurotransmitters and secretory granules containing neuropeptides. SDCVs contain membrane proteins characteristic of synaptic vesicles such as synaptophysin and synaptoporin. However, SDCVs also contain membrane proteins characteristic of certain secretory granules like the vesicular monoamine transporter and the membrane-bound form of dopamine beta-hydroxylase. In neurites of sympathetic neurons, synaptophysin and dopamine beta-hydroxylase are found in distinct vesicles, consistent with their transport from the trans-Golgi network to the site of SDCV formation in constitutive secretory vesicles and secretory granules, respectively. Hence, SDCVs constitute a distinct type of neurosecretory vesicle that is a hybrid of the synaptic vesicle and the secretory granule membranes and that originates from the contribution of both the constitutive and the regulated pathway of protein secretion.

Loss of occludin and functional tight junctions, but not ZO-1, during neural tube closure--remodeling of the neuroepithelium prior to neurogenesis.

Neuroepithelial cells can generate nonepithelial cells, the neurons. Here we have investigated, for chick and mouse embryos, the epithelial character of neuroepithelial cells in the context of neurogenesis by examining the presence of molecular components of tight junctions during the transition from the neural plate to the neural tube. Immunoreactivity for occludin, a transmembrane protein specific to tight junctions, was detected at the apical end of the lateral membrane of neuroepithelial cells throughout the chick neural plate. During neural tube closure, occludin disappeared from all neuroepithelial cells. Correspondingly, the addition of horseradish peroxidase to the apical side of the neuroepithelium by injection into the amniotic cavity of mouse embryos revealed the presence of functional tight junctions in the neural plate (Embryonic Day 8), but not the neural tube (Embryonic Day 9). In contrast to occludin, expression of ZO-1, a peripheral membrane protein of tight junctions, increased from the neural plate to the neural tube stage, also being confined to the apical end of the lateral neuroepithelial cell membrane. This localization coincided with that of N-cadherin, whose expression increased concomitantly with the disappearance of occludin. We propose that the loss of tight junctions from neuroepithelial cells reflects an overall decrease in their epithelial nature, which precedes the generation of neurons.

Mex67p, a novel factor for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores.

An essential cellular factor for nuclear mRNA export called Mex67p which has homologous proteins in human and Caenorhabditis elegans was identified through its genetic interaction with nucleoporin Nup85p. In the thermosensitive mex67-5 mutant, poly(A)+ RNA accumulates in intranuclear foci shortly after shift to the restrictive temperature, but NLS-mediated nuclear protein import is not inhibited. In vivo, Mex67p tagged with green fluorescent protein (GFP) is found at the nuclear pores, but mutant mex67-5-GFP accumulates in the cytoplasm. Upon purification of poly(A)+ RNA derived from of UV-irradiated yeast cells, Mex67p, but not nucleoporins Nup85p and Nup57p, was crosslinked to mRNA. In a two-hybrid screen, a putative RNA-binding protein with RNP consensus motifs was found to interact with the Mex67p carboxy-terminal domain. Thus, Mex67p is likely to participate directly in the export of mRNA from the nucleus to the cytoplasm.

Structural and functional implications of tau hyperphosphorylation: information from phosphorylation-mimicking mutated tau proteins.

Abnormal tau-immunoreactive filaments are a hallmark of tauopathies, including Alzheimer's disease (AD). A higher phosphorylation ("hyperphosphorylation") state of tau protein may represent a critical event. To determine the potential role of tau hyperphosphorylation in these disorders, mutated tau proteins were produced where serine/threonine residues known to be highly phosphorylated in tau filaments isolated from AD patients were substituted for glutamate to simulate a paired helical filament (PHF)-like tau hyperphosphorylation. We demonstrate that, like hyperphosphorylation, glutamate substitutions induce compact structure elements and SDS-resistant conformational domains in tau protein. Hyperphosphorylation-mimicking glutamate-mutated tau proteins display a complete functional loss in its ability to promote microtubule nucleation which can partially be overcome by addition of the osmolyte trimethylamine N-oxide (TMAO), which is similar to phosphorylated tau. In addition, glutamate-mutated tau proteins fail to interact with the dominant brain protein phosphatase 2A isoform ABalphaC, and exhibit a reduced ability to assemble into filaments. Interestingly, wild-type tau and phosphorylation-mimicking tau similarly bind to microtubules when added alone, but the mutated tau is almost completely displaced from the microtubule surface by equimolar concentrations of wild-type tau. The data indicate that glutamate-mutated tau proteins provide a useful model for analyzing the functional consequences of tau hyperphosphorylation. They suggest that several mechanisms contribute to the abnormal tau accumulation observed during tauopathies, in particular a selective displacement of hyperphosphorylated tau from microtubules, a functional loss in promoting microtubule nucleation, and a failure to interact with phosphatases.