piperidines and Amyloidosis

Topics: Amyloidosis; Humans; Piperidines; Pyrimidines; Skin Diseases

Topics: Adenine; Amyloidosis; Drug Tolerance; Humans; Immunoglobulin M; Piperidines; Pyrazoles; Pyrimidines; Survival Analysis; Treatment Outcome

Oxidative stress and amyloid deposition are tightly interconnected pathological features of Alzheimer disease. In this respect, both amyloid production and aggregation may be stimulated by oxidative stress and also the increase of pathogenic β-amyloid and its aggregated form lead to oxidative stress progression. Therefore, the search for potential drugs with both antioxidant and antiaggregation properties are of great interest.. In this study, we described the stereospecific synthesis of alkaloid securinine aminoderivatives.. We showed that the newly synthesized compounds possess antioxidant and metal-chelating properties. Indeed, we report that one compound has inhibitory effects towards μ-amyloid aggregation.. Based on these results, aminoderivatives of securinine scaffold are promising compounds for development of new drugs for the treatment of neurodegenerative diseases.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloidosis; Animals; Antioxidants; Azepines; Heterocyclic Compounds, Bridged-Ring; Humans; Lactones; Male; Oxidative Stress; Peptide Fragments; Piperidines; Rats

Deposition of islet amyloid has been associated with beta-cell death, thereby furthering diabetes progression. Several hypoglycemic agents, such as thiazolidinediones, biguanide and dipeptidyl peptidase-4 inhibitors, have been known to preserve beta-cell mass, possibly by direct inhibition of islet amyloid formation. The general objective of this study was to evaluate the impact of the major representatives of hypoglycemic agents on amyloid formation by using in vitro molecular screening approaches.. Ten prototypical representatives of hypoglycemic agents were evaluated for the inhibition of amyloid formation in vitro using thioflavin fluorescence assays, far-ultraviolet circular dichroism, photo-induced cross linking assays and cell viability assays.. Glyburide, repaglinide and troglitazone showed the highest potency in delaying and reducing fibril formation. Troglitazone, a thiazolidinedione, was the most effective agent abrogating amyloid fibril formation. Troglitazone affected the secondary structures of incubated human islet amyloid polypeptide (hIAPP). The circular dichroism spectra showed a delayed transition to the beta sheet conformation. A photo-induced cross-linking-based oligomerization assay demonstrated that repaglinide supressed the formation of hIAPP oligomers, whereas glyburide and troglitazone were ineffective in inhibiting oligomerization. Cell toxicity induced by hIAPP was reduced by all 3 compounds.. This study provides new insights that could potentially identify new therapeutic strategies to impede the progression of pancreatic amyloidosis in human patients with type 2 diabetes.

Topics: Amyloid; Amyloidosis; Animals; Carbamates; Cell Survival; Chromans; Circular Dichroism; Glyburide; Humans; Hypoglycemic Agents; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Piperidines; Protein Structure, Secondary; Rats; Thiazolidinediones; Troglitazone

To report a case of lower respiratory tract obstruction occurring in a patient with primary pulmonary amyloidosis and discuss anesthetic management.. A 53-yr-old man was referred to our institution for microlaryngoscopy and laser treatment of the larynx. He presented with a five-year history of primary laryngo-tracheo-bronchial amyloidosis and symptoms consistent with narrowing of the conducting airways. General anesthesia was induced with iv propofol 150 mg and remifentanil 50 microg. Mivacurium 20 mg provided muscle relaxation for endotracheal intubation. Following endotracheal intubation, the airway became obstructed and patient ventilation impossible. The endotracheal tube was removed and a Dedo laryngoscope inserted. Gas exchange was maintained using supraglottic jet ventilation via a distal port of the laryngoscope. Rigid bronchoscopy showed tissue partially obstructing the lumen of the lower trachea. This was removed and the airway appeared patent. At the end of the case, a further episode of lower airway obstruction occurred requiring reinsertion of the laryngoscope and resumption of jet ventilation. Extensive debridement through the bronchoscope was required before adequate ventilation could be restored. Some days later when the patient's condition deteriorated again and he required further debridement of the trachea and insertion of a tracheostomy, guide wires were positioned in the femoral vessels in the event that cardiopulmonary bypass was required for gas exchange.. Primary laryngo-tracheo-bronchial amyloidosis is a recurrent disease, requiring repetitive surgical procedures. Airway compromise can be a persistent problem. Awareness of this uncommon disease process and its presentation may serve to caution the anesthesiologist presented with this type of case.

Topics: Amyloidosis; Anesthesia, General; Anesthetics, Intravenous; Bronchial Diseases; High-Frequency Jet Ventilation; Humans; Intubation, Intratracheal; Isoquinolines; Laryngoscopy; Laryngostenosis; Lung Diseases; Male; Middle Aged; Mivacurium; Neuromuscular Nondepolarizing Agents; Piperidines; Propofol; Remifentanil; Reoperation; Respiratory Tract Diseases; Tracheal Stenosis

A case of chronic intestinal pseudoobstruction secondary to systemic amyloidosis in a patient with multiple myeloma is described. Gastrointestinal symptoms and indices of nutrition improved markedly after commencing treatment with cisapride, which may have been responsible for relatively prolonged survival compared with similar reported cases.

Topics: Amyloidosis; Cisapride; Female; Humans; Intestinal Diseases; Intestinal Pseudo-Obstruction; Middle Aged; Piperidines; Serotonin Antagonists; Stomach Diseases