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| 2. |
- Blom, Anna M, et al.
(författare)
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Increase of bikunin and alpha1-microglobulin concentrations in urine of rats during pregnancy is due to decreased tubular reabsorption
- 1997
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Ingår i: Biochimica et Biophysica Acta. - 0006-3002. ; 1361:2, s. 198-202
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Tidskriftsartikel (refereegranskat)abstract
- Bikunin and alpha1-microglobulin are two plasma proteins of about 25 kDa which are made in the liver from a common precursor. The concentration of bikunin in human urine has been shown to increase several fold during various conditions of stress. The mechanism behind this increase is unknown. We have studied pregnant rats and found that the bikunin and alpha1-microglobulin levels in their urine increased 3-fold towards the end of the pregnancy, whereas those of albumin and orosomucoid did not. There were no significant changes in either the bikunin/alpha1-microglobulin mRNA level or the concentrations of the two proteins in serum. These findings imply that the synthesis and the clearance rates of bikunin and alpha1-microglobulin are normal during pregnancy but that the tubular reabsorption of these proteins is decreased.
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| 3. |
- Johansson, Hugo, et al.
(författare)
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Herpes simplex type 1-induced Fc receptor binds to the Cgamma2-Cgamma3 interface region of IgG in the area that binds staphylococcal protein A
- 1989
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Ingår i: Immunology. - 0019-2805. ; 66:1, s. 8-13
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Tidskriftsartikel (refereegranskat)abstract
- The binding site of immunoglobulin G (IgG) to herpes simplex virus (HSV) type 1-induced Fc receptor was investigated using human IgG Fc intermediate (Fc(i)) fragments, fragment D of staphylococcal protein A (SPA) and chemically modified human IgG. Human IgG Fc(i) fragment composed of one Cgamma2 and two Cgamma3 domains, bound strongly to HSV-1-infected cells. Fragment D, a monovalent subunit of SPA, inhibited the binding of radiolabelled human IgG Fc fragments to the HSV Fc receptor. Reductively methylated human IgG reacted equally well to HSV-infected cells, as did chemically unmodified IgG in contrast to N-acetylimidazole-modified and diethylpyrocarbonate-modifed human IgG, which were unreactive. These results suggest a similar binding site on human IgG for SPA and the HSV-1 Fc receptor with involvement of the amino acid residues Tyr and His but not Lys. The similarities of binding sites on the IgG molecule for the HSV-1 Fc receptor and rheumatoid factors (RF) may be important for understanding the mechanism of RF production in rheumatoid arthritis or other disease states.
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| 4. |
- Nardella, F A, et al.
(författare)
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Fc epitopes for human rheumatoid factors and the relationships of rheumatoid factors to the Fc binding proteins of microorganisms
- 1988
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Ingår i: Scandinavian Journal of Rheumatology. Supplement. - : Informa UK Limited. - 1502-7740 .- 0300-9742 .- 1502-7732. ; 17:Suppl. 75, s. 190-198
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Tidskriftsartikel (refereegranskat)abstract
- Work from our laboratories has shown that the major antigenic determinants for rheumatoid factors (RFs) are in the C gamma 2-C gamma 3 interface region of IgG in the same area that binds staphylococcal protein A (SPA). Furthermore, the Fc binding proteins of groups A, C and G streptococci as well as the Fc binding proteins induced on cell surfaces by herpes simplex virus type I also bind to the same area of IgG. These binding site similarities between RFs and the microbial Fc binding proteins suggested conformational similarities between the RF antigen combining regions and the Fc binding regions of the microbial proteins. This hypothesis was supported by the observation that antibodies to SPA bind to the antigen combining regions of most RFs as well as to the Fc binding region of the T15 group A streptococcal Fc binding protein. These findings indicate that RFs bear the conformational internal image of these microbial proteins and suggest that RFs could arise as antibodies to the idiotypic determinants on antibodies to microbial Fc binding proteins. Alternatively, microbial Fc binding proteins could present IgG to the immune system in a way that renders specific areas of the C gamma 2-C gamma 3 interface region immunogenic. These relationships between RFs and microbial Fc binding proteins may prove to be important for our understanding of the generation of RFs in rheumatoid arthritis.
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| 5. |
- Nordquist, Lina, 1977-
(författare)
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Novel Approaches to Treatment and Prevention of Diabetic Nephropathy
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Several studies have reported beneficial effects of C-peptide supplementation in diabetic patients and animal models of insulinopenic diabetes. However, it is also established that good glycemic control is essential to minimize the risk of diabetes-induced complications. This thesis investigates potential mechanisms for the beneficial effect of C-peptide on glomerular hyperfiltration, and a novel, painless route of insulin administration. The results demonstrate that both C-peptide and its C-terminal penta-peptide sequence reduce the diabetes-induced glomerular hyperfiltration within an hour. The results also indicate that C-peptide possibly reduces diabetes-induced hyperfiltration via three different mechanisms: 1. Constriction of the afferent arteriole was demonstrated on isolated vessels from diabetic mice. 2. A net dilation of the efferent arteriole was evident in vivo. 3. Inhibition of the Na+/K+-ATPase was demonstrated in vivo in diabetic rats as well as in vitro on isolated proximal tubular cells from diabetic rats. All these mechanisms are known regulators of the net glomerular filtration pressure. The last part of this thesis demonstrates that intradermal administration with a newly developed patch-like microneedle device results in similar insulin concentration compared to standard subcutaneous delivery. These findings provide an insight for the beneficial effects of C-peptide on diabetic kidney function, and shows that this effect can be achieved by infusion of the C-terminal penta-peptide sequence alone. This thesis also presents a novel, painless alternative to insulin injections that is controllable, requires minimal training, and therefore presents several advantages compared to current standard therapy.
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| 6. |
- Roos, Magnus W., et al.
(författare)
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Functional evaluation of cerebral microembolization in the rat
- 2003
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Ingår i: Brain Research. - 0006-8993 .- 1872-6240. ; 961:1, s. 15-21
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the effects of cerebral microembolism on motor performance and risk assessment behavior in the rat. Cerebral infarcts were produced in rats by injecting small plastic beads into the left heart ventricle under short-acting anesthesia. The functional outcome was tested 24 h later by subjecting the animals to a series of consecutive behavioral tests. Thereafter, the rats were anesthetized and underwent magnetic resonance imaging. On average about seven infarcts per brain were found. The volume of the individual infarcts was largest in the hippocampus (mean=4.26 mm(3)) and smallest in the white matter (mean=0.83 mm(3)). Embolized animals performed spontaneous and evident locomotion. The activity was, however, significantly decreased compared to rats treated with vehicle. More specific tests for motor ability revealed reduced gait capacity and muscular strength. A significant relationship was found between behaviors reflecting motor ability and the total volume of infarcted tissue in the brain stem, cortex and cerebellum. Also the behavioral profile of risk and benefit assessment was found to be altered by the microembolization. It is concluded that the combination of the microembolization method and behavioral tests provides a valuable tool for further studies of the pathophysiology of, and potential treatment for, cerebral infarction.
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| 8. |
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| 9. |
- Sharma, Hari Shanker, et al.
(författare)
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Chronic Treatment with Nanoparticles Exacerbate Hyperthermia Induced Blood-Brain Barrier Breakdown, Cognitive Dysfunction and Brain Pathology in the Rat : Neuroprotective Effects of Nanowired-Antioxidant Compound H-290/51
- 2009
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Ingår i: Journal of Nanoscience and Nanotechnology. - 1533-4880 .- 1533-4899. ; 9:8, s. 5073-5090
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Tidskriftsartikel (refereegranskat)abstract
- The possibility that chronic exposure of nanoparticles may alter stress reaction and brain pathology following hyperthermia was examined in a rat model. Engineered nanoparticles from Ag or M Cu (approximate to 50-60 nm) were administered (30 mg/kg, i.p.) once daily for 1 week in young male rats. M On the 8th day these animals were subjected to 4 h heat stress at 38 degrees C in a BOD incubator. In these animals stress symptoms, blood-brain barrier (BBB) permeability, cognitive and motor functions and brain pathology were examined. Subjection of nanoparticle treated rats to heat stress showed exacerbation of stress symptoms i.e., hyperthermia, salivation and prostration and exhibited greater BBB disruption, brain edema formation, impairment of cognitive and motor functions M and brain damage compared to normal animals. This enhanced brain pathology in heat stress was most marked in animals that received Ag nanoparticles compared to Cu treatment. Treatment with antioxidant compound H-290/51 either 30 min or 60 min after heat stress did not alter hyperthermia M induce brain pathology in nanoparticle treated rats. Whereas, administration of nanowired-H-290/51 after 30 min or 60 min heat stress markedly attenuated BBB disruption, sensory motor function and brain pathology. These results suggest that chronic nanoparticles treatment exacerbate hyperthermia induced brain pathology that is significantly attenuated by nanowired but not normal H-290/51 compound. Taken together, our observations suggest that nano-wired drug delivery of H-290/51 is a promising approach to induce neuroprotection in hyperthermia induced brain pathology, not reported earlier.
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| 10. |
- Sharma, Hari Shanker, et al.
(författare)
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Neuroprotective effects of insulin like growth factor-1 on engineered metal nanoparticles Ag, Cu and Al induced blood-brain barrier breakdown, edema formation, oxidative stress, upregulation of neuronal nitric oxide synthase and brain pathology
- 2021
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Ingår i: Progress in Brain Research. - : Elsevier. - 0079-6123 .- 1875-7855. ; 266, s. 97-121, s. 97-121
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Tidskriftsartikel (refereegranskat)abstract
- Military personnel are vulnerable to environmental or industrial exposure of engineered nanoparticles (NPs) from metals. Long-term exposure of NPs from various sources affect sensory-motor or cognitive brain functions. Thus, a possibility exists that chronic exposure of NPs affect blood-brain barrier (BBB) breakdown and brain pathology by inducing oxidative stress and/or nitric oxide production. This hypothesis was examined in the rat intoxicated with Ag, Cu or Al (50–60 nm) nanoparticles (50 mg/kg, i.p. once daily) for 7 days. In these NPs treated rats the BBB permeability, brain edema, neuronal nitric oxide synthase (nNOS) immunoreactivity and brain oxidants levels, e.g., myeloperoxidase (MP), malondialdehyde (MD) and glutathione (GT) was examined on the 8th day. Cu and Ag but not Al nanoparticles increased the MP and MD levels by twofold in the brain although, GT showed 50% decline. At this time increase in brain water content and BBB breakdown to protein tracers were seen in areas exhibiting nNOS positive neurons and cell injuries. Pretreatment with insulin like growth factor-1 (IGF-1) in high doses (1 μg/kg, i.v. but not 0.5 μg/kg daily for 7 days) together with NPs significantly reduced the oxidative stress, nNOS upregulation, BBB breakdown, edema formation and cell injuries. These novel observations demonstrate that (i) NPs depending on their metal constituent (Cu, Ag but not Al) induce oxidative stress and nNOS expression leading to BBB disruption, brain edema and cell damage, and (ii) IGF-1 depending on doses exerts powerful neuroprotection against nanoneurotoxicity, not reported earlier.
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