Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease in the elderly. Progressive accumulation of insoluble isoforms of amyloid-β peptide (Aβ) and tau protein are the major neuropathologic hallmarks, and the loss of cholinergic pathways underlies cognitive deficits in patients. Recently, glial involvement has gained interest regarding its effect on preservation and impairment of brain integrity. The limbic system, including temporal lobe regions and the olfactory bulb, is particularly affected in the early stages. In the early 1980s, the reduced expression of the somatostatin neuropeptide was described in AD. However, over the last three decades, research on somatostatin in Alzheimer’s disease has been scarce in humans. Therefore, the aim of this study was to stereologically quantify the expression of somatostatin in the human hippocampus and olfactory bulb and analyze its spatial distribution with respect to that of Aβ and au neuropathologic proteins and astroglia. The results indicate that somatostatin-expressing cells are reduced by 50% in the hippocampus but are preserved in the olfactory bulb. Interestingly, the coexpression of somatostatin with the Aβ peptide is very common but not with the tau protein. Finally, the coexpression of somatostatin with astrocytes is rare, although their spatial distribution is very similar. Altogether, we can conclude that somatostatin expression is highly reduced in the human hippocampus, but not the olfactory bulb, and may play a role in Alzheimer’s disease pathogenesis. 相似文献
In this field trial, a protocol for the treatment of retained fetal membranes (RFM) without any intrauterine therapy was compared with 3 protocols based on the intrauterine use of antibiotic pills (AP), the manual removal (MR) of the fetal membranes, or the combination of both (PR). The study was conducted on 5 commercial dairy farms in Germany. Cows with RFM for at least 24 h after calving were assigned to 1 of 4 treatment groups. Cows of all groups with a rectal temperature ≥ 39.5°C received a systemic antibiotic treatment with ceftiofur (1 mg/kg per d) for 3 to 5 consecutive days. In case of continued fever after 5 treatments, cows received a different antibiotic as an escape therapy. In the reference group (REF; n = 131), cows did not receive any additional treatment. All cows in group AP (n = 119) received intrauterine treatment with antibiotic pills consisting of 1,000 mg of ampicillin and 1,000 mg of cloxacillin for 3 consecutive days. In group MR (n = 121), an attempt was made to remove the fetal membranes manually, but uterine pills were not administered. In group PR (n = 130), an attempt was made to remove the fetal membranes manually and all cows received a local antibiotic treatment as in group AP. All cows received 2 doses of 25 mg of PGF2α: one dose between 18 and 24 d and another between 32 and 38 d postpartum. Statistical analyses were performed using binary logistic regression models and survival analyses with group REF as reference. Of all animals, 79.8% had a body temperature of ≥ 39.5°C at least once within 10 d postpartum and were treated with ceftiofur. Occurrence of fever within 10 d postpartum was significantly lower in groups AP and PR compared with reference group REF, but was not different between groups MR and REF. Risk of receiving an escape therapy in case of fever after 5 treatments with ceftiofur did not differ among groups. Reproductive performance measures did not differ significantly between group REF and any of the comparison groups. Compared with a treatment protocol based only on systemic treatment with antibiotics for cows with a fever, neither intrauterine antibiotics nor manual removal of fetal membranes alone or in combination reduced proportions of cows needing an escape therapy nor did those treatments improve reproductive measures in the current lactation. Systemic treatment alone based on elevated rectal temperature was effective and reduced use of antibiotics compared with therapies that included intrauterine antibiotics. 相似文献
Summary: Hydrotalcite‐catalyzed polycondensation of BHET was studied by thermogravimetry to elucidate the kinetics. The reaction was found to follow second‐order kinetics with respect to hydroxyl end groups. The overall activation energy of the polycondensation was found to decrease with increasing catalyst concentration before it leveled out to the value of 93 kJ · mol−1 at high catalyst concentration. This is a result of the uncatalyzed reaction that takes place parallel to the catalyzed one. The activation energy of the uncatalyzed path was found to be 156 kJ · mol−1. IR spectroscopy and XRD showed that the monomer intercalates between the layers of hydrotalcite at the beginning of the reaction enabling the complexation of oxygen‐containing functional groups with the hydroxide groups of the catalyst. Based on these findings a polycondensation mechanism is proposed. One end group of the monomer is activated in the form of alkoxide that counterbalances the positive charge of the hydrotalcite layer. This alkoxide group attacks an ester carbonyl group fixed close to it, generating a new ester bond and a glycoxide species. The role of hydrotalcite is to activate the reactants, rendering the attacking hydroxyl group more nucleophilic and the ester carbonyl group more electrophilic, and at the same time fixing the reactant together in a favorable geometry.
Intercalation of BHET in the gallery of HT layers in a twisted alkoxide form. 相似文献
Current views of the role of beta-amyloid (Abeta) peptide fibrils range from regarding them as the cause of Alzheimer's pathology to having a protective function. In the last few years, it has also been suggested that soluble oligomers might be the most important toxic species. In all cases, the study of the conformational properties of Abeta peptides in soluble form constitutes a basic approach to the design of molecules with "antiamyloid" activity. We have experimentally investigated the conformational path that can lead the Abeta-(1-42) peptide from the native state, which is represented by an alpha helix embedded in the membrane, to the final state in the amyloid fibrils, which is characterized by beta-sheet structures. The conformational steps were monitored by using CD and NMR spectroscopy in media of varying polarities. This was achieved by changing the composition of water and hexafluoroisopropanol (HFIP). In the presence of HFIP, beta conformations can be observed in solutions that have very high water content (up to 99 % water; v/v). These can be turned back to alpha helices simply by adding the appropriate amount of HFIP. The transition of Abeta-(1-42) from alpha to beta conformations occurs when the amount of water is higher than 80 % (v/v). The NMR structure solved in HFIP/H2O with high water content showed that, on going from very apolar to polar environments, the long N-terminal helix is essentially retained, whereas the shorter C-terminal helix is lost. The complete conformational path was investigated in detail with the aid of molecular-dynamics simulations in explicit solvent, which led to the localization of residues that might seed beta conformations. The structures obtained might help to find regions that are more affected by environmental conditions in vivo. This could in turn aid the design of molecules able to inhibit fibril deposition or revert oligomerization processes. 相似文献
Microencapsulated paraffin based phase change material (PCM) have been incorporated into Poly(methyl-methacrylate) (PMMA)
matrix in order to enhance the thermo-mechanical properties. Calorimetric and mechanical analyses are carried out and the
thermo regulating potential of PMMA/PCM composites is investigated. Results indicate that the PCM phase has a negligible effect
on the glass transition temperature of the PMMA matrix, and the thermal regulating capability spans around body temperature
absorbing or releasing a thermal energy up to 30 J/g. One of the effect of the PCM phase into the cement is the reduction
of the peak temperature developed during the exothermal reaction. 相似文献
Although it is well known that damage to neurons results in release of substances that inhibit axonal growth, release of chemical signals from damaged axons that attract axon growth cones has not been observed. In this study, a 532 nm 12 ns laser was focused to a diffraction-limited spot to produce site-specific damage to single goldfish axons in vitro. The axons underwent a localized decrease in thickness (‘thinning’) within seconds. Analysis by fluorescence and transmission electron microscopy indicated that there was no gross rupture of the cell membrane. Mitochondrial transport along the axonal cytoskeleton immediately stopped at the damage site, but recovered over several minutes. Within seconds of damage nearby growth cones extended filopodia towards the injury and were often observed to contact the damaged site. Turning of the growth cone towards the injured axon also was observed. Repair of the laser-induced damage was evidenced by recovery of the axon thickness as well as restoration of mitochondrial movement. We describe a new process of growth cone response to damaged axons. This has been possible through the interface of optics (laser subcellular surgery), fluorescence and electron microscopy, and a goldfish retinal ganglion cell culture model. 相似文献