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1.
Eur J Neurosci ; 47(11): 1353-1374, 2018 06.
Article in English | MEDLINE | ID: mdl-29770521

ABSTRACT

Activation of neuronal nicotinic acetylcholine receptors (nAChRs) by nicotine is reported to protect brain neurons from glutamate excitotoxicity. We inquired whether a similar phenomenon can occur in the rat isolated spinal cord (or spinal slice culture) challenged by a transient (1 hr) application of kainate (a powerful glutamate receptor agonist) to induce excitotoxicity mimicking spinal injury in vitro. We recorded spinal reflexes and fictive locomotion generated by the locomotor central pattern generator before and 24 hr after applying kainate. We also monitored network activity with Ca2+ imaging and counted neurons and glia with immunohistochemical methods. In control conditions, nicotine (1 µM; 4 hr) depressed reflexes and fictive locomotion with slow recovery and no apparent neurotoxicity at 24 hr although synchronous Ca2+ transients appeared in slice cultures. Kainate nearly halved neuron numbers (while sparing glia), decreased reflexes and Ca2+ transients, and suppressed fictive locomotion. When nicotine was applied (4 hr) after washout of kainate, fictive locomotor cycles appeared 24 hr later though with low periodicity, and significant protection of neurons, including motoneurons, was observed. Nicotine applied together with kainate and maintained for further 4 hr yielded better neuroprotection, improved fictive locomotion expression and reversed the depression of Ca2+ transients. nAChR antagonists did not intensify kainate neurotoxicity and inhibited the neuroprotective effects of nicotine. These data suggest that nicotine was efficacious to limit histological and functional excitotoxic damage probably because it activated and then desensitized nAChRs on excitatory and inhibitory network neurons to prevent triggering intracellular cell death pathways.


Subject(s)
Central Pattern Generators/drug effects , Excitatory Amino Acid Agonists/pharmacology , Motor Neurons/drug effects , Neuroprotective Agents/pharmacology , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Reflex/drug effects , Spinal Cord/drug effects , Spinal Injuries/prevention & control , Animals , Disease Models, Animal , Kainic Acid/pharmacology , Neuroprotective Agents/administration & dosage , Nicotine/administration & dosage , Nicotinic Agonists/administration & dosage , Nicotinic Antagonists/pharmacology , Rats , Rats, Wistar , Spinal Injuries/chemically induced
3.
Acta Myol ; 31(1): 16-20, 2012 May.
Article in English | MEDLINE | ID: mdl-22655512

ABSTRACT

Deflazacort is the most commonly prescribed corticosteroid for the treatment of Duchenne muscular dystrophy in Canada. We review the long-term experience with deflazacort treatment at two centers in Canada; Montreal and Toronto. Deflazacort has benefitted both cohorts by prolonged ambulation, preserved cardiac and respiratory function, less scoliosis and improved survival. Common side effects in both cohorts include weight gain, decreased height and cataract formation. The Canadian experience supports the use of deflazacort in treating boys with Duchenne muscular dystrophy.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Immunosuppressive Agents/therapeutic use , Muscular Dystrophy, Duchenne/drug therapy , Pregnenediones/therapeutic use , Adolescent , Adrenal Cortex Hormones/adverse effects , Body Height/drug effects , Bone Density/drug effects , Canada , Cataract/chemically induced , Child , Fractures, Bone/chemically induced , Humans , Immunosuppressive Agents/adverse effects , Male , Muscle Strength/physiology , Muscular Dystrophy, Duchenne/physiopathology , Pregnenediones/adverse effects , Spinal Injuries/chemically induced , Spine/pathology , Walking/physiology , Weight Gain
4.
CMAJ ; 179(4): 319-26, 2008 Aug 12.
Article in English | MEDLINE | ID: mdl-18695179

ABSTRACT

BACKGROUND: The use of proton pump inhibitors has been associated with an increased risk of hip fracture. We sought to further explore the relation between duration of exposure to proton pump inhibitors and osteoporosis-related fractures. METHODS: We used administrative claims data to identify patients with a fracture of the hip, vertebra or wrist between April 1996 and March 2004. Cases were each matched with 3 controls based on age, sex and comorbidities. We calculated adjusted odds ratios (OR) for the risk of hip fracture and all osteoporosis-related fractures for durations of proton pump inhibitor exposure ranging from 1 or more years to more than 7 years. RESULTS: We matched 15 792 cases of osteoporosis-related fractures with 47 289 controls. We did not detect a significant association between the overall risk of an osteoportic fracture and the use of proton pump inhibitors for durations of 6 years or less. However, exposure of 7 or more years was associated with increased risk of an osteoporosis-related fracture (adjusted OR 1.92, 95% confidence interval [CI] 1.16-3.18, p = 0.011). We also found an increased risk of hip fracture after 5 or more years of exposure (adjusted OR 1.62, 95% CI 1.02-2.58, p = 0.04), with even higher risk after 7 or more years exposure (adjusted OR 4.55, 95% CI 1.68-12.29, p = 0.002). INTERPRETATION: Use of proton pump inhibitors for 7 or more years is associated with a significantly increased risk of an osteoporosis-related fracture. There is an increased risk of hip fracture after 5 or more years exposure. Further study is required to determine the clinical importance of this finding and to determine the value of osteoprotective medications for patients with long-term use of proton pump inhibitors.


Subject(s)
Fractures, Bone/chemically induced , Hip Fractures/chemically induced , Proton Pump Inhibitors/adverse effects , Spinal Injuries/chemically induced , Wrist Injuries/chemically induced , Aged , Aged, 80 and over , Case-Control Studies , Confidence Intervals , Diagnosis-Related Groups , Dose-Response Relationship, Drug , Female , Fractures, Bone/epidemiology , Fractures, Bone/etiology , Hip Fractures/etiology , Humans , Male , Manitoba/epidemiology , Middle Aged , Osteoporosis/complications , Spinal Injuries/etiology , Wrist Injuries/etiology
5.
Rev Rhum Mal Osteoartic ; 58(11): 803-8, 1991 Nov 30.
Article in French | MEDLINE | ID: mdl-1780657

ABSTRACT

Osteocondensation of the spine and stress fractures of the appendicular bones are observed under treatment with sodium fluoride or after long-term drinking of Vichy Saint-Yorre spring water. Five patients with a mean total dose of fluoride intake of 24.7 g (9-66) were studied with MR imaging. Two of them had a diffuse osteocondensation; MRI showed a low signal intensity in the vertebrae on T1 and T2-weighted images. MRI was performed in an asymptomatic patient who was being treated with sodium fluoride for 16 months; it revealed a heterogenous low signal intensity in the pelvis and femoral metaphysis. Two patients experienced stress fractures; MRI demonstrated a linear area of very low signal intensity surrounded by an area of decreased signal intensity on T1-weighted images and high signal intensity on T2-weighted images. MRI of fluorosis shows a non specific low signal intensity linked to a densifying image on the standard radiograph or an area of high technetium-99m intake on bone scan.


Subject(s)
Fluoride Poisoning/complications , Fractures, Stress/chemically induced , Fractures, Stress/diagnosis , Spinal Injuries/chemically induced , Spinal Injuries/diagnosis , Aged , Aged, 80 and over , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged
6.
Geburtshilfe Frauenheilkd ; 50(1): 61-3, 1990 Jan.
Article in German | MEDLINE | ID: mdl-2311907

ABSTRACT

Multiple vertebral compression fractures occurred in the 33rd week of pregnancy in a breast-feeding mother receiving heparin (20,000-25,000 units/die over 5 months), for deep vein thrombosis. Osteoporosis under heparin therapy is a rare complication and this diagnosis was not made despite obvious clinical signs. It follows from this observation, that heparin therapy should be substituted by oral anticoagulant therapy and discontinued directly after delivery.


Subject(s)
Heparin/adverse effects , Osteoporosis/chemically induced , Pregnancy Complications, Cardiovascular/drug therapy , Puerperal Disorders/drug therapy , Thrombophlebitis/drug therapy , Adult , Breast Feeding , Female , Fractures, Spontaneous/chemically induced , Heparin/administration & dosage , Humans , Postphlebitic Syndrome/etiology , Pregnancy , Puerperal Disorders/etiology , Spinal Injuries/chemically induced
8.
JAMA ; 241(22): 2417-8, 1979 Jun 01.
Article in English | MEDLINE | ID: mdl-439319

ABSTRACT

A 27-year-old woman received heparin sodium for 152 days because of antepartum iliofemoral thrombophlebitis. At the end of this time, spinal osteoporosis and multiple vertebral fractures became clinically evident and were attributed to the prolonged administration of heparin. Previously reported cases of "heparin osteoporosis" were reviewed. The significance of the daily dose of heparin and the duration of therapy are reemphasized. This therapeutic complication and the management of antepartum iliofemoral thrombophlebitis are discussed. Prolonged administration of heparin in daily doses exceeding 10,000 units is potentially hazardous.


Subject(s)
Fractures, Spontaneous/chemically induced , Osteoporosis/chemically induced , Pregnancy Complications, Cardiovascular , Spinal Injuries/chemically induced , Adult , Female , Heparin/therapeutic use , Humans , Lumbar Vertebrae/injuries , Pregnancy , Thoracic Vertebrae/injuries , Thrombophlebitis/drug therapy , Time Factors
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