Search results for " neuropathies"
showing 10 items of 54 documents
The serum protease network—one key to understand complex regional pain syndrome pathophysiology
2019
Complex regional pain syndrome (CRPS) develops after fracture. The acute CRPS phenotype resembles exaggerated inflammation, which is explained by local and systemic activation of a proinflammatory network including peptides and cytokines. Epidemiologic data suggest that inactivation of the peptidase angiotensin-converting enzyme in patients treated for hypertension increases the odds to develop CRPS. This hint leads us to investigate the serum protease network activity in patients with CRPS vs respective controls. For this purpose, we developed a dabsyl-bradykinin (DBK)-based assay and used it to investigate patients with CRPS, as well as healthy and pain (painful diabetic neuropathy [dPNP]…
Therapy of ATTR Cardiac Amyloidosis: Current Indications
2023
Transthyretin cardiac amyloidosis is a restrictive cardiomyopathy caused by extracellular deposition in the heart of amyloid fibrils derived from plasma transthyretin (ATTR), either in its hereditary (ATTRh) or acquired (ATTRwt) forms. Cardiac amyloidosis has a very poor prognosis if therapy is not started promptly. Therefore, it is very important to recognize cardiac amyloidosis early in order to immediately start a treatment capable of modifying the prognosis. Treatment of cardiac amyloidosis is not easy, often requiring a multidisciplinary team. New RNA-interfering drugs (such as patisiran) have been devised and are effective in the treatment of ATTRh amyloidosis. Tafamidis (a stabilizer…
Familial Amyloid Polyneuropathy
2013
Familial amyloid polyneuropathy (FAP; also known as familiar amyloidosis and hereditary amyloidosis) is an autosomal dominant inherited disease due to mutations of the transthyretin (TTR) gene coding for the corresponding protein, consisting of 127 amino acids. The gene is located on chromosome 18q. More than 100 different mutations are known. Other mutant precursor proteins produced in the liver, such as apolipoprotein I and II, lysozyme and fibrinogen Aα, may be of etiological importance as well. Amyloidogenic mutations of the TTR gene lead to decreased stability of the corresponding protein and subsequently to extracellular deposition of amyloid in several tissues (peripheral and autonom…
Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3.
2014
Many neurodegenerative disorders present with sensory loss. In the group of hereditary sensory and autonomic neuropathies loss of nociception is one of the disease hallmarks. To determine underlying factors of sensory neurodegeneration we performed whole-exome sequencing in affected individuals with the disorder. In a family with sensory neuropathy with loss of pain perception and destruction of the pedal skeleton we report a missense mutation in a highly conserved amino acid residue of atlastin GTPase 3 (ATL3), an endoplasmic reticulum-shaping GTPase. The same mutation (p.Tyr192Cys) was identified in a second family with similar clinical outcome by screening a large cohort of 115 patients …
Experimental diabetic neuropathy: role of oxidative stress and mechanisms involved.
1998
Oxidative stress has been related to the development of diabetic neuropathy. Experimental diabetes (alloxan injection to mice) promotes early biochemical changes in peripheral nervous tissue, e.g., decrease in Na,K-ATPase activity and glutathione (GSH) peroxidase (GSHPx) activity. The former decrease can be reverted by inhibiting protein kinase C (PKC), since it has been reported that PKC is activated in these experimental conditions. Here we present data demonstrating that the inhibition of PKC, as early as 4 days after alloxan administration, is not able to return to normal values GSHPx activity in sciatic nerve of diabetic mice. Thus, it would fit with our previous proposal of the possib…
Alpha 1 adrenoceptor expression in skin, nerves and blood vessels of patients with painful diabetic neuropathy
2021
Abstract Diabetic neuropathy (dNP) patients often suffer from severe neuropathic pain. It was suggested that alpha-1 adrenoceptor (α1-AR) hyperresponsiveness contributes to pain in dNP. The aim of our study was to quantify α1-AR expression using immunohistochemistry in skin biopsies of nine patients with painful diabetic neuropathy compared to 10 healthy controls. Additionally, the association between α1-AR expression and activation with spontaneous and sympathetically maintained pain (SMP) induced by intradermal injection of the α1-agonist phenylephrine was investigated. For control purposes the α2-agonist clonidine was injected in a different session. We found that dermal nerve density wa…
Polymer-doxycycline conjugates as fibril disrupters: an approach towards the treatment of a rare amyloidotic disease.
2014
The term amyloidosis describes neurological diseases where an abnormal protein is misfolded and accumulated as deposits in organs and tissues, known as amyloid, disrupting their normal function. In the most common familial amyloid polyneuropathy (FAP), transthyretin (TTR) displays this role primarily affecting the peripheral nervous system (PNS). Advanced stages of this inherited rare amyloidosis, present as fibril deposits that are responsible for disease progression. In order to stop disease progression, herein we designed an efficient family of nanoconjugates as fibril disrupters. These polymer conjugates are based on doxycycline (doxy), already in phase II trials for Alzheimer's disease…
Derivatives of Erythropoietin That Are Tissue Protective But Not Erythropoietic
2004
Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype–selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyeli…
Elevated serum leptin concentrations in type 2 diabetic patients with microalbuminuria and macroalbuminuria
1999
Leptin levels are elevated in end-stage renal disease, suggesting an impairment of renal leptin degradation. The present study aimed to determine whether leptin levels are also elevated in patients with earlier stages of renal disease, ie, microalbuminuric and macroalbuminuric nephropathy. A total of 60 subjects were assigned to two study groups. Group A contained 10 type 2 diabetics with macroalbuminuria, 10 type 2 diabetics with normoalbuminuria, and 10 healthy control subjects. Group B contained 10 type 2 diabetics with microalbuminuria, 10 type 2 diabetics with normoalbuminuria, and 10 healthy controls. The subgroups of both study groups were matched for sex and body fatness. In group A…
Effectiveness of Duloxetine Compared With Pregabalin and Gabapentin in Diabetic Peripheral Neuropathic Pain
2013
This study aimed to compare the effectiveness of duloxetine (DLX) and the anticonvulsants pregabalin (PGB) and gabapentin (GBP) for the treatment of diabetic peripheral neuropathic pain (DPNP) in routine clinical care.Data from a 6-month, noninterventional study involving 2575 patients in whom treatment of DPNP was initiated with or changed to DLX, PGB, or GBP (n=1523) were analyzed post hoc; patients treated with other medications or combinations were excluded from this analysis. Propensity scoring was used to compare patient groups, assessing Brief Pain Inventory (BPI), Clinical and Patient Global Impression (CGI/PGI), the Hospital Anxiety and Depression Scale (HADS), the Sheehan Disabili…