| 1. |
- Nordquist, Lina, 1977-
(författare)
-
Novel Approaches to Treatment and Prevention of Diabetic Nephropathy
- 2007
-
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.
|
|
| 2. |
|
|
| 3. |
- Sharma, Hari Shanker, et al.
(författare)
-
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
-
Ingår i: Journal of Nanoscience and Nanotechnology. - 1533-4880 .- 1533-4899. ; 9:8, s. 5073-5090
-
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.
|
|
