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- Sundkvist, Göran, et al.
(författare)
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Sorbitol and myo-inositol levels and morphology of sural nerve in relation to peripheral nerve function and clinical neuropathy in men with diabetic, impaired, and normal glucose tolerance
- 2000
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 17:4, s. 259-268
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Sorbitol and myo-inositol levels and morphology of sural nerve were compared with nerve function and clinical neuropathy in men with diabetic, impaired (IGT), and normal glucose tolerance. Methods: After neurography of sural nerve and determinations of sensory thresholds for vibration, warm and cold on the foot, whole nerve sural nerve biopsy was performed in 10 men with Type 1 diabetes mellitus, 10 with IGT, and 10 with normal glucose tolerance. Polyol levels were assessed by gas-liquid chromatography/mass spectrometry. Results: Sural nerve amplitudes were significantly lower and sorbitol levels significantly higher in diabetic patients (median (interquartile range)) (3.7 (3.5) μV and 643 (412) pmol/mg protein, respectively) both compared with IGT (11.3 (10.6) μV; P = 0.04 and 286 (83) pmol/mg protein; P = 0.0032, respectively) and normally glucose tolerant (10.0 (11.6); P = 0.0142 and 296 (250) pmol/mg protein; P = 0.0191, respectively) subjects. There were no differences in nerve morphology between the three groups. Nerve myo-inositol levels correlated, however, positively with cluster density (r(s) = 0.56; P = 0.0054). In diabetic and IGT subjects, sural nerve amplitudes (2.6 (3.8) vs. 12.1 (10.6) μV; P = 0.0246) and myelinated nerve fibre density (MNFD; 4076 (1091) vs. 5219 (668) nerve fibres/mm2; P = 0.0021) were significantly lower in nine subjects with clinical neuropathy than in 10 without. Conclusions: Nerve degeneration (i.e. MNFD) correlated with clinical neuropathy but not with glucose tolerance status whereas nerve myo-inositol levels positively correlated with signs of nerve regeneration (i.e. increased cluster density).
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| 2. |
- Mohseni, Simin, 1959-
(författare)
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Hypoglycaemic neuropathy : Experimental studies in diabetic rats treated witn insulin implants
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Insulin dependent diabetes mellitus is a metabolic disease that causes secondary complications such as peripheral neuropathy. it is generally believed that diabetic neuropathy is due to chronic hyperglycaemia. In order to understand the pathophysiology of diabetic neuropathy many workers have examined nerves from diabetic rats. While most workers say that animals with high blood glucose levels develop neuropathy, some investigators report that the peripheral nerves are normal in hyperglycaemic rats. Hypoglycaemia may also cause neuropathy. The general aim of the present study is to examine the long-term relation between glycaemia and peripheral neuropathy in diabetic BB/Wor rats. This necessitated establishment of a treatment regime allowing long-term survival of these sick animals.We found that maintenance of diabetic BB/Wor rats on an eu/hyperglycaemic or an eu-/hypoglycaemic regime with insulin implants worked well for our purpose.Unexpectedly, light and electron microscopic examination of plantar nerves in eu-/hyperglycaemic diabetic rats showed a normal picture. But, nerves from eu-/hypoglycemic rats showed severe qualitative changes, interpreted as axonal de- and regeneration. The total number of axons was subnormal and the myelinated fibres were shifted towards smaller diameters. Hence, eu-/hypoglycaemic diabetic BB/Wor rats but not eu-/hyperglycaemic animals, develop a neuropathy in their plantar nerves.The immunohistochemical occurrence of epidermal protein gene product 9.5 immunoreactive axon profiles was normal in heel skin biopsies from eu/hypoglycaemic rats, but many profiles were short and thin. The content of the neuropeptide calcitonin gene-related peptide in skin biopsies was subnormal. The occurrence of end plate axon terminals labeled with antibodies against the vesicular acetylcholine transporter protein was subnormal in sections from a plantar muscle of eu-/hypoglycaemic rats. Moreover, the end plate axon terminals were abnormally small. Hence, the hypoglycaemic neuropathy seen in plantar nerve trunks of diabetic BB/Wor rats treated with insulin implants is accompanied by mild alterations in the epidermal innervation of plantar skin and a more obviously abnormal nerve terminal pattern in plantar muscle.Electron microscopic examination of L5 dorsal roots from eu/hypoglycaemic rats showed a normal morphology and normal numbers of axons. In L5 ventral roots the picture varied: in 2 rats it was normal and 3 rats showed signs of axonal degeneration. The L5 dorsal root ganglion and the L5 ventral horn showed a normal picture. Hence, eu-/hypoglycaemia affects ventral root axons but not dorsal root axons. Moreover, the degree of ventral root pathology is variable and sensory and motor neuron perikarya are not affected.
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| 3. |
- Nasizadeh, Sima, et al.
(författare)
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Proteasomal degradation of a trypanosomal ornithine decarboxylase
- 2003
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Ingår i: Cellular Physiology and Biochemistry. - : S. Karger AG. - 1015-8987 .- 1421-9778. ; 13:5, s. 321-328
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Tidskriftsartikel (refereegranskat)abstract
- Mammalian ornithine decarboxylase (ODC), which catalyses the first step in polyamine biosynthesis, has a very fast turnover. It is degraded by the 26S proteasome in an ubiquitin-independent process and the degradation is stimulated by polyamines in a feedback control of the enzyme. Interestingly, there is a major difference in the metabolic stability between ODCs from various trypanosomatids. Trypanosoma brucei and Leishmania donovani both contain stable ODCs, whereas Crithidia fasciculata has an ODC with a rapid turnover. In spite of the difference in stability there is a high degree of sequence homology between C. fasciculata ODC and L. donovani ODC. In the present study we demonstrate that C. fasciculata ODC is rapidly degraded also in mammalian systems like CHO cells and rabbit reticulocyte lysate, suggesting that the degradation signals of the enzyme are recognised by the mammalian systems. L. donovani ODC, on the other hand, is degraded very slowly in the same systems. The degradation of C. fasciculata ODC in the mammalian systems is markedly reduced by inhibition of the 26S proteasome. However, unlike mammalian ODC, C. fasciculata ODC is not downregulated by polyamines. Thus, the turnover of C. fasciculata ODC and L. donovani ODC in the mammalian systems reflects the degradation of the enzyme in the parasites, making such systems potentially useful as complements to parasitic knockout models for further analysis of the mechanisms involved in the rapid degradation of C. fasciculata ODC. Copyright (C) 2003 S. Karger AG, Basel.
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