Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGF-II immunoreactivity in postmenopausal women with osteoporosis.

Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12-24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo. INTRODUCTION: Recombinant teriparatide [human PTH(1-34)], a bone formation agent for the treatment of osteoporosis when given once daily subcutaneously, increases biochemical markers of bone turnover and activation frequency in histomorphometry studies. MATERIALS AND METHODS: We studied the mechanisms underlying this bone-forming action of teriparatide at the basic multicellular unit by the appearance of cement lines, a method used to directly classify surfaces as modeling or remodeling osteons, and by the immunolocalization of IGF-I and IGF-II. Transiliac bone biopsies were obtained from 55 postmenopausal women treated with teriparatide 20 or 40 microg or placebo for 12-24 months (median, 19.8 months) in the Fracture Prevention Trial. RESULTS: A dose-dependent relationship was observed in modeling and mixed remodeling/modeling trabecular hemiosteons. Trabecular and endosteal hemiosteon mean wall thicknesses were significantly higher in both teriparatide groups than in placebo. There was a dose-dependent relationship in IGF-II immunoreactive staining at all bone envelopes studied. The greater local IGF-II presence after treatment with teriparatide may play a key role in stimulating bone formation. CONCLUSIONS: Direct evidence is presented that 12-24 months of teriparatide treatment induced modeling bone formation at quiescent surfaces and resulted in greater bone formation at remodeling sites, relative to placebo.     

Esophagogastric decompression and enteral feeding following cholecystectomy: a controlled, randomized prospective trial

One hundred fourteen patients scheduled to undergo elective cholecystectomy were prospectively randomized into one of four treatment groups to study the potential benefits of esophagogastric decompression with and without immediate postoperative enteral nutrition. Group I was the control, and patients received only iv fluids and were allowed to eat as tolerated. Group II patients received iv fluids and esophagogastric decompression. Group III patients received esophagogastric decompression and enteral sterile water through the duodenal feeding lumen. Group IV patients received esophagogastric decompression and infusion of an elemental diet through the feeding lumen. The surgical techniques were standardized for all patients. The results of the study indicated no statistically or clinically significant differences among any of the treatment groups regarding; (1) need for parenteral analgesics or antiemetics, (2) tolerance of regular diet, (3) postoperative day of discharge, and (4) postoperative day that other discharge criteria were met. It is concluded that there is no objective benefit to the routine use of esophagogastric decompression with or without enteral nutrition in elective cholecystectomy patients.     

Canine myocardial reperfusion injury: protection by a free radical scavenger, N-2-mercaptopropionyl glycine

Oxygen-derived free radicals and their metabolites may contribute to the extension of irreversible cellular injury, which occurs on reperfusion of the previously ischemic myocardium. Therefore, therapy directed against the toxic effects of reactive oxygen species may provide protection to the ischemic myocardium, which undergoes subsequent reperfusion. We evaluated the effectiveness of N-2-mercaptopropionyl glycine (MPG), a free radical scavenger, to limit the extent of irreversible injury resulting from 90 min of ischemia followed by 6 h of reperfusion in a canine model of myocardial infarction. In three groups of dogs, MPG (20 mg/kg) was administered as a constant infusion into the left atrium. Group I received MPG for 2 h, starting 15 min before occlusion of the left circumflex coronary artery and ending 15 min after reperfusion. Group II received MPG for 1 h, starting 15 min before reperfusion. Group III received MPG for 1 h beginning 45 min after reperfusion. Each group was compared with its respective saline control group. Infarct size was reduced by 35% in Group I (32.2 +/- 5.1% vs. 47.7 +/- 3.4% of the area at risk, p less than 0.05) and Group II (31.4 +/- 3.6% vs. 47.5 +/- 5.1% of the area at risk, p less than 0.025) in comparison with the saline treated control animals. In contrast, in Group III infarct size did not differ significantly from the saline-treated control group (45.9 +/- 3.3% vs. 47.7 +/- 3.5% of the area at risk). The percent of left ventricle at risk did not differ among the groups. The beneficial effects of MPG could not be explained on the basis of hemodynamic differences. In addition, MPG did not influence regional myocardial blood flow. In vitro studies indicated that MPG effectively scavanges O2- generated by the hypoxanthine-xanthine oxidase reaction, as well as by PMA-activated polymorphonuclear leukocytes. Based on these observations, we propose that MPG exerts its beneficial effects by protecting against free radical-mediated damage during the early phase of reperfusion.     

Spinal fusion for back pain: a clinical and radiological review.

Eighty-one patients who had spinal fusions performed for back pain over a 7-year period were reviewed; 74% were satisfied with the outcome of their surgery, mainly because of the degree of pain relief obtained. Based on lateral radiographs of the fusion area in flexion and extension, there was a 34% pseudarthrosis rate in first-time fusions. However, there was no clear relationship between the integrity of fusion and clinical success, indicating that many factors other than bony fusion influence the eventual outcome of the operation.     

Disinhibition in the rat septum mediated by M1 muscarinic receptors

Acetylcholine (ACh) has been documented as an important central neurotransmitter. We have investigated the actions of ACh within the dorsolateral septal nucleus of the rat to examine its actions within this nucleus, specifically how it may interact to modulate the inhibitory action of gamma-aminobutyric acid (GABA), the known inhibitory transmitter in this area. Our results demonstrate that ACh, acting on M1 muscarinic receptors leads to disinhibition by decreasing GABA release.     

Nemaline myopathy of cats

An apparently inherited myopathy, characterized by the presence of large numbers of nemaline rods in skeletal muscle fibers, was investigated in five cats. Onset of signs varied from 6 months to 1.5 years of age and consisted of reluctance to move, jerky gait and muscle twitching, hyporeflexia, and muscle wasting, which was most prominent in the proximal muscles of the forelimbs. All of the cats, three males and two females, were from the same dam. In addition to the presence of rods, the myopathy was characterized by marked fiber size variation, with atrophy of type 1 and type 2a muscle fibers. In addition, there was infolding of the sarcolemma and fiber splitting. Ultrastructurally, the rods closely resembled those described in human nemaline myopathy.     

Dopamine-D1 and δ-opioid receptors co-exist in rat striatal neurons

Cocaine's enhancement of dopaminergic neurotransmission in the mesolimbic pathway plays a critical role in the initial reinforcing properties of this drug. However, other neurotransmitter systems are also integral to the addiction process. A large body of data indicates that opioids and dopamine together mediate emotional and reinforced behaviors. In support of this, cocaine-mediated increases in activation of dopamine D1 receptors (D1R) results in a desensitization of δ-opioid receptor (DOR) signaling through adenylyl cyclase (AC) in striatal neurons. To further define cellular mechanisms underlying this effect, the subcellular distribution of DOR and D1R was examined in the rat dorsolateral striatum. Dual immunoperoxidase/gold-silver detection combined with electron microscopy was used to identify DOR and D1R immunoreactivities in the same section of tissue. Semi-quantitative analysis revealed that a subset of dendritic cellular profiles exhibited both DOR and D1R immunoreactivities. Of 198 randomly sampled D1R immunoreactive profiles, 43% contained DOR. Similarly of 165 DOR-labeled cellular profiles, 52% contained D1R. The present data provide ultrastructural evidence for co-existence between DOR and D1R in striatal neurons, suggesting a possible mechanism whereby D1R modulation may alter DOR function.