Biomedical subjects

M Fallon

Publications and source records attributed to M Fallon.

At least 73 records · Page 4Linked to original sources

PubMed1990

The effect of high-dose salmon calcitonin on bone mineral metabolism in the normal rat.

The paucity of information on the effect of long-term high-dose salmon calcitonin administration on normal bone mineral metabolism and histology prompted an investigation of the influence of high-dose synthetic calcitonin in the rat. Serum ionized calcium, osteocalcin or BGP (bone gla protein), and immunoreactive PTH were measured serially during calcitonin administration and bone histomorphometry analyzed at 6 weeks (after sacrifice). Daily injections of salmon calcitonin, 0.4 IU/100 g (group B) and 2 IU/100 g (group C), resulted in significant hypocalcemia at 4 hours for both experimental groups (P less than 0.004). Serum iPTH was significantly higher over the study period for both groups administered calcitonin. Serum BGP levels were significantly lower than controls during the study in group C (P less than 0.002) and to a lesser extent in group B (P less than 0.05). In group C, bone histomorphometry revealed increased resorption (osteoclast count), decreased trabecular bone volume, and decreased double-labeled tetracycline surface (bone formation). In group B an increase in osteoclast count but no alteration in bone formation was observed. To assess the role of PTH in the above findings, high-dose calcitonin was administered to parathyroidectomized rats. All of the above changes in bone histomorphometry were not observed in this group of animals. In conclusion, high doses of calcitonin promote hypocalcemia, secondary hyperparathyroidism, and osteoclastosis in the normal rat in a dose-dependent manner with very high-dose calcitonin impairing bone formation.

Animals↗

PubMed1990

1,25 Dihydroxyvitamin D3 modifies cyclosporine-induced bone loss.

We have previously shown that cyclosporin A (CsA) produces high bone remodeling with resorption exceeding formation and loss of bone volume in the rat. This may have important clinical implications where CsA is widely used in organ transplantation. 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) is a bone mineralizing hormone which also has immune modifying properties. Consequently, we studied the effect of combined CsA and 1,25(OH)2D3 administration over 28 days in four groups of rats. Group A received vehicle (n = 10), group B CsA (15 mg/kg) (n = 10) alone, group C 1,25(OH)2D3 plus CsA (n = 15), and group D 1,25(OH)2D3 alone (20 ng/100 g) (n = 15). Rats were bled periodically at day 0, 7, 14, and 28 and Ca, parathyroid hormone (PTH), 1,25(OH)2D, osteocalcin (bone Gla-protein, BGP), BUN, and creatinine were measured. Rats were sacrificed on day 28 and bones were examined histomorphometrically. Compared to controls, CsA resulted in significant elevation of BGP and a transient increase in 1,25(OH)2D with excess bone remodeling and loss of bone volume. 1,25(OH)2D3 administration produced hypercalcemia, a significant rise in BGP, with suppression of PTH and increased osteoid volume. Combined therapy prevented the loss of bone volume probably due to increased osteoid tissue and enhanced osteoblast activity. Renal dysfunction, a side-affect of CsA, was not a factor. In conclusion, 1,25(OH)2D3 combined with CsA restores bone volume which is accompanied by increases in serum calcium and BGP.

Animals↗

PubMed1990

Alterations of T helper/inducer and T suppressor/inducer cells in patients with recurrent aphthous ulcers.

The peripheral blood lymphocytes of patients with recurrent aphthous ulcers (RAU) were studied during various stages of their disease by two-color immunofluorescence with the use of monoclonal antibodies directed against human T cells (CD3), T helper cells (CD4), T suppressor cells (CD8), T helper/inducer cells (CDw29), and T suppressor/inducer cells (CD45R). All patients with severe RAU showed increased numbers of T helper/inducer cells (CDw29) and decreased numbers of T suppressor/inducer cells (CD45R). One of six patients with RAU showed a decreased T helper/T suppressor ratio (CD4/CD8). These findings suggest that patients with RAU may possess primary immunologic abnormalities.

Adult↗

PubMed1990

Nimodipine, an L-channel Ca2+ antagonist, reverses the negative summating potential recorded from the guinea pig cochlea.

Nimodipine, an L-type Ca2+ channel antagonist, was tested using sound-evoked cochlear potentials in guinea pigs to investigate whether these channels are involved in cochlear function. Perilymph spaces of guinea pig cochleae were perfused with artificial perilymph solutions containing 0.1-10 microM nimodipine at a rate of 2.5 microliters/min for 10 min. The cochlear potentials evoked by 10 kHz tone bursts of varying intensities were recorded from the basal turn of the scala vestibuli. Cochlear perfusion of nimodipine resulted in reversible, dose-related suppression of the compound action potential of the auditory nerve (CAP; N1-P1), a prolongation of N1 latency at suprathreshold levels, an elevated CAP threshold, a decrease in N1 latency at a constant amplitude measured at CAP threshold, a reduction in cochlear microphonics (CM), and a reduction of the negative summating potential (SP) to a point where it became positive (i.e., a reversal of SP). The endocochlear potential (EP) was not affected. These results support the hypothesis that L-type Ca2+ channels are directly involved in the operation of the organ of Corti. We speculate that L-type Ca2+ channels are integrally involved in generation of a negative summating potential and the dc motion of the cochlear partition described by others.

Animals↗

PubMed1990

Potassium induced release of GABA and other substances from the guinea pig cochlea.

Gamma-aminobutyric acid (GABA) has been proposed as a neurotransmitter of a subset of efferent nerve fibers in the mammalian cochlea. We tested this hypothesis by examining if GABA was released by high concentrations of K+ from the guinea pig cochlea. Artificial perilymph solutions containing either normal K+ (5 mM) or high K+ (50 mM) were perfused through the perilymphatic compartment of the guinea pig cochlea while collecting the effluent. Nineteen primary amines including GABA were quantified in the effluent by HPLC. This was carried out in normal animals and in animals pretreated with ethacrynic acid and kanamycin to destroy the organ of Corti. Significantly greater levels of GABA, taurine, glutamate, aspartate, glycine and three unidentified substances appeared in effluent collected during exposure of the cochlea to solutions containing higher K+ than normal K+. Compared to normal animals, destruction of the organ of Corti significantly decreased the K(+)-induced release of GABA, taurine, glutamate, aspartate, glycine and one of the unidentified substances; although significant release of glutamate and taurine still occurred in the destroyed ears. The release of GABA is consistent with it being a neurotransmitter in the cochlea. In addition the results: confirm the release of glutamate and taurine from the organ of Corti; suggest that additional substances may be released; and demonstrate the release of glutamate and taurine from tissue other than the organ of Corti.

Animals↗

PubMed1990

The effect of rigid fixation on the survival of onlay bone grafts: an experimental study.

Much attention has recently been focused on rigid fixation as a method of improving fracture healing. Whether such fixation, when applied to onlay grafting, improves graft take and volume is unknown. To examine this question, we compared survival of both endochondral and membranous grafts fixed rigidly and nonrigidly in areas of low motion (snout) and high motion (femur) in a rabbit model. Gross morphology, histologic analysis, and graft volume kinetics were evaluated. Findings demonstrate that in areas of high motion, the application of rigid fixation improves graft survival, whereas in a low-motion region, no differences in graft volume retention as a function of fixation were observed. Histologically, no differences with the method of fixation employed were seen, and similar revascularization patterns were noted. By kinetic analysis, rigid fixation appears to exert its most profound effect early in the postgraft period. Membranous bone grafts remain superior to endochondral grafts under all circumstances. From these studies, we conclude that rigid fixation is the method of choice in all circumstances where onlay bone grafts may be exposed to motion, shear, and torsional forces.

Analysis of Variance↗

PubMed1990

Salicylate, mefenamate, meclofenamate, and quinine on cochlear potentials.

The perilymphatic spaces of guinea pig cochleae were perfused with artificial perilymph, with and without drug, at a rate of 2.5 microliters/minute for 10 minutes. The compound action potential of the auditory nerve, cochlear microphonics, and the summating potential evoked by 10 kHz tone bursts of varying intensities were recorded from a wire inserted in the basal turn scala vestibuli. The endocochlear potential was recorded from the scala media. Sodium salicylate (1.25 to 10 mmol/L) reduced the magnitude of the compound action potential evoked by low-sound intensities without affecting the compound action potential evoked by high-sound intensities. Sodium salicylate also reduced cochlear microphonics and had no effect on summating potential. Cochlear perfusions of prostaglandin synthesis inhibitors, mefenamate (200 mumol/L), and meclofenamate (200 mumol/L), had no effect on the cochlear potentials. Quinine (10 to 100 mumol/L) reduced the compound action potential input-output function in a parallel fashion rather than selectively affecting the low-intensity compound action potential. Quinine (100 mumol/L) reduced cochlear microphonics and summating potential. Neither quinine (100 mumol/L) nor salicylate (5 mmol/L) affected endocochlear potential. These results suggest that salicylate-induced hearing loss is not caused by either antagonism of the hair cell transmitter or cyclooxygenase inhibition, nor is it caused by the same mechanism that causes quinine-induced hearing loss.

Acetates↗

PubMed1990

Identification and isolation of a phospholipase A2 activating protein in human rheumatoid arthritis synovial fluid: induction of eicosanoid synthesis and an inflammatory response in joints injected in vivo.

Eicosanoids are important mediators of the destructive arthropathy observed in rheumatoid arthritis. The rate-limiting step in the eicosanoid synthesis pathway is the availability of free arachidonic acid. The phospholipase enzymes release arachidonic acid from membrane phospholipids and thus play an important role in the regulation of eicosanoid production. We have previously demonstrated enhanced phospholipase A2 and C enzyme activities in cells from patients with rheumatoid arthritis and have also described a phospholipase A2 activating protein (PLAP) in mammalian cell lines. In an attempt to determine the biochemical basis of enhanced phospholipase A2 activity found in patients with inflammatory joint disease, we examined synovial fluid from patients with rheumatoid arthritis for PLAP. To determine whether PLAP was specific for rheumatoid disease, we assayed specimens from patients with other arthropathies. Histologic examination of rheumatoid joint tissue, with the use of immunohistochemical techniques, demonstrated high concentration of PLAP in monocytes, macrophages, chondrocytes, vascular smooth muscle, and endothelial cells. Human PLAP could be biochemically isolated from synovial fluid from patients with rheumatoid arthritis and was found to be similar to PLAP previously isolated from murine and bovine sources. To determine whether PLAP could directly mediate any aspect of inflammatory disease, purified PLAP was injected into rabbit knee joints. This resulted in an acute inflammatory arthritis with synovial cell proliferation and synovial fluid leukocytosis. Purified PLAP also induced eicosanoid formation both in vivo and in vitro. With enzyme-linked immunosorbent assays, we found more PLAP in synovial fluid specimens from patients with rheumatoid arthritis compared with samples from patients with other inflammatory arthropathies as well as osteoarthritis, a noninflammatory arthropathy. These data suggest that PLAP may be responsible, at least in part, for some aspects of the destructive inflammatory arthropathy that is observed in patients with rheumatoid arthritis.

Adult↗

PubMed1990

The bisphosphonate 2-PEBP inhibits cyclosporin A induced high-turnover osteopenia in the rat.

A bisphosphonate, 2-PEBP (2-(2-pyridinyl) ethylidene bisphosphonate), was administered to animals receiving cyclosporin A (CsA) in an attempt to modify the high-turnover osteopenia associated with CsA therapy. Four groups of female Sprague-Dawley rats were administered either vehicle or CsA (15 mg/kg per day) by gavage for 28 days, together with either normal saline solution or 2-PEBP (1.72 mg/kg per day) given by intraperitoneal injection on days 0,1, and 2. The groups thus comprised Group A, vehicle/normal saline; group B, vehicle/2-PEBP; group C, CsA/normal saline solution; group D, CsA/2-PEBP. All rats received tetracycline hydrochloride by intraperitoneal injection for histomorphometric labeling. Blood was sampled on days 0, 7, 14, 21, and 28 for ionized calcium, serum phosphate, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D), blood urea nitrogen (BUN), creatinine, magnesium, and bone gla protein (BGP). Rats were killed on day 28 for tibial bone histomorphometry. All results were compared with group A. There were no significant differences in weight, ionized calcium, PTH, and serum phosphate between groups. Weight increased significantly by day 28 in all groups. Groups C and D revealed significantly higher levels of 1,25(OH)2D, BUN, and creatinine on days 14 and 28. Magnesium was significantly lower in groups C and D on days 14 and 28. BGP increased significantly in group C and decreased significantly in group B during the study. Tibial bone histomorphometry revealed high-turnover osteopenia in group C, significant improvement in both bone formation and resorption parameters in group D and hyperostosis in group B. Serum BGP reflected the histomorphometric indices of bone formation in each group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

The quinoxalinediones DNOX, CNOX and two related congeners suppress hair cell-to-auditory nerve transmission.

We tested 6,7-dinitroquinoxaline-2,3-dione (DNQX); 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); 6,7-dichloro-3-hydroxy-2-quinoxalinecarboxylic acid (DHQC); and 3-hydroxy-2-quinoxalinecarboxylic acid (3HQC), new kainate and quisqualate receptor antagonists, upon cochlear potentials in guinea pig. Perilymph spaces of guinea pig cochleae were perfused with artificial perilymph solutions containing up to 1000 microM concentrations of DHQC and 3HQC, and 500 microM concentrations of DNQX and CNQX, at a rate of 2.5 microliters/min for 10 min. Cochlear potentials evoked by 10 kHz tone bursts of varying intensity were recorded from the basal turn scala vestibuli. Cochlear perfusion of the four drugs resulted in a dose-related suppression of the compound action potential of the auditory nerve (CAP; N1-P1), a prolongation of N1 latency at suprathreshold levels, an elevated CAP threshold, and a decreased N1 latency at CAP threshold. None of the drugs had significant effects on cochlear microphonics (CM) or the summating potential (SP). EC50 values (concentrations causing a 50% reduction in CAP amplitude at 68 dB SPL) were 8 microM for DNQX, 30 microM for DHQC, 35 microM for CNQX, and 1 mM for 3HQC. Results support the hypothesis that kainate and quisqualate receptors are involved in neurotransmission between the hair cell and afferent nerve.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1989

Suppression of auditory nerve activity in the guinea pig cochlea by 1-(p-bromobenzoyl)-piperazine-2,3-dicarboxylic acid.

1-(p-Bromobenzoyl)-piperazine-2,3-dicarboxylic acid (pBB-PzDA; 0.03-5 mM), an excitatory amino acid antagonist, was perfused through the guinea pig cochlea while monitoring various cochlear potentials. pBB-PzDA (1-5 mM) reversibly suppressed the amplitude of the compound action potential of the auditory nerve (CAP) and increased the latency of N1 (the first negative wave of the CAP) at all sound intensities. pBB-PzDA had no detectable effect on N1 latency at CAP threshold or presynaptic potentials such as the cochlear microphonics and the summating potential. At the single-cell level pBB-PzDA (5 mM) reversibly suppressed the firing of single auditory nerve ganglion cells. pBB-PzDA appeared to have the same potency in the cochlea as kynurenic acid. We conclude that the mechanism of action of pBB-PzDA is consistent with an antagonism of the hair-cell transmitter at the afferent auditory nerve.

Acoustic Stimulation↗

PubMed1989

Cyclosporin A in the oophorectomized rat: unexpected severe bone resorption.

Local factors, such as interleukin-1, may mediate the accelerated bone remodeling in the acute estrogen-deficient rat. Cyclosporin A (CsA), which in vitro inhibits some of these local factors, was administered to oophorectomized (OX) rats in an attempt to modify this high turnover state. Three groups of 15 rats were studied. Group A was sham operated, group B was OX, and group C was OX and received CsA (15 mg/kg per day) by gavage commencing 4 days postoophorectomy for 28 days. Estradiol levels were determined to confirm oophorectomy. Blood was sampled on days -7, 0, 7, 14, 21, and 28 for ionized calcium (Ca2+), 1,25-(OH)2-vitamin D, PTH, and bone gla protein (BGP). Rats received tetracycline hydrochloride for bone histomorphometric labeling. All results were compared to group A. Body weight was increased in group B (p less than 0.003) but not in group C. There was no difference in Ca2+ or PTH between the groups. BGP levels were higher in group B by day 28 (p less than 0.005); BGP levels were increased in group C from days 7-28 (p less than 0.002). 1,25-(OH)2-vitamin D was significantly increased in group C (p less than 0.0001) but not in group B. Tibial bone histomorphometry revealed increased measurements of bone formation and osteoclast number without a loss of bone volume (BV/TV) in group B. Group C showed a dramatic increase in bone turnover with significant loss of BV/TV (p less than 0.001). In conclusion, CsA in the OX rat resulted in unexpected enhanced bone remodeling with high BGP levels and severe bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Comparative actions of salicylate on the amphibian lateral line and guinea pig cochlea.

1. Salicylate actions on afferent nerve activity in the Xenopus lateral line and on cochlear potentials in guinea pig were investigated. 2. In the lateral line, salicylate (0.3-2.5 mM) suppressed spontaneous activity, water motion evoked excitation and responses to L-glutamate (1-2 mM) and kainate (10-20 microM). 3. In the guinea pig, salicylate (0.6-10 mM) suppressed the compound action potential (CAP) and increased N1 latency at low but not high sound intensities. 4. In the lateral line salicylate action may involve an antagonism of the hair-cell transmitter on the afferent nerve. 5. In the cochlea salicylate may suppress the active process or cochlear amplifier.

Action Potentials↗

PubMed1989

Osteonecrosis of the femoral head. Results of core decompression and grafting with and without electrical stimulation.

The effectiveness of core decompression and bone grafting with and without electrical stimulation was investigated in patients with avascular necrosis (AVN) of the femoral head. One hundred sixteen hips with AVN had decompression and grafting; 74 were also treated with direct current (DC). The DC stimulation was via a coil inserted directly into the femoral head. These were compared to 55 hips with AVN treated nonoperatively. Hips treated with electrical stimulation showed less roentgenographic progression and achieved a better clinical score than hips treated with decompression and grafting alone. Both groups had a significantly lower incidence of arthroplasty than the nonoperated controls. One patient developed a pulmonary embolus, but there were no fractures or other complications. Decompression and grafting are safe and reasonably effective in retarding the progression of AVN. Supplemental electrical stimulation seems to improve the results even further.

Arthroplasty↗

PubMed1989

Magnetic resonance imaging of the ischemic hip. Alterations within the osteonecrotic, viable, and reactive zones.

To explore the ability of magnetic resonance imaging (MRI) to depict the morphologic features of avascular necrosis (AVN) of the femoral head and to determine whether a classification based on stage of necrosis is possible, images of hips with 56 proved lesions were examined and correlated with roentgenographic stage, severity of pain and functional impairment, and available computed tomography (CT) scans. Six femoral heads with AVN were also studied ex vivo with MRI, CT, roentgenographic, and histologic examinations. These examinations were compared with 100 normal hips in 50 individuals and one normal proximal femoral specimen. The reactive interface between live and dead bone at the periphery of AVN lesions had a characteristic MRI appearance that facilitated diagnosis. Based on central signal intensity on two different pulse sequences, lesions could be separated into four classes that correlated with roentgenographic and clinical staging. Lesions that were isointense with fat on both sequences had an earlier roentgenographic stage and less severe symptoms than did lesions that were less intense than fat. Among hips with AVN in patients younger than 50 years of age, 67% had premature conversion to fatty intertrochanteric marrow outside the borders of the lesion. Detecting premature conversion to fatty marrow has important implications regarding the pathogenesis of AVN and may aid early diagnosis. MRI provides pathophysiologic information that is different from information obtained from conventional methods or various combinations of methods and may provide a basis for an improved system for grading AVN lesions.

Adult↗

PubMed1988

The effect of chronic caffeine administration on serum markers of bone mineral metabolism and bone histomorphometry in the rat.

Caffeine has been cited as a risk factor for osteoporosis in humans. In rats, caffeine increases calcium absorption and excretion and raises parathyroid hormone (iPTH) levels. This study investigated the effect of chronic caffeine administration on bone histomorphometry and serum markers of bone mineral metabolism. Twenty-seven male Sprague Dawley rats weighing approximately 300 g were divided into three groups: Group A (n = 8) served as controls, Group B (n = 9) received 2.5 mg/100 g caffeine in their drinking water, and Group C (n = 10) received 10 mg/100 g body weight caffeine in their drinking water. Animals were bled serially for the 8 week study period: Ionized calcium was measured from tail vein blood and serum iPTH and osteocalcin (BGP) from orbital sinus blood. All three groups received two doses of tetracycline for bone histomorphometry which was performed on a right tibial section from each animal. Ionized calcium was not different among the three groups at any time point. No alteration in serum iPTH levels was demonstrated except for day 56 when the high-dose group (C) showed a raised level (mean = 59.1, SE = +/- 8.9 pg/ml (P less than 0.05). By week 8 Group C showed a failure to gain weight compared with Group A. Group C mean weight = 384.0 +/- 6.6 g, Group A 427.4 +/- 10.8 g (P less than 0.005). Serum BGP was significantly increased in Group C compared with control (P less than 0.001). No differences in bone histomorphometry were observed among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1988

The active process is affected first by intense sound exposure.

Evidence exists to suggest that intense sound releases excess neurotransmitter from the inner hair cells. However, it has been previously reported that intense sound affects the cochlear micromechanics by altering the stereocilia. Therefore, we tested the hypothesis that intense sound affects structures involved in transduction before it affects the nerve endings. In order to test this hypothesis, we examined the interaction of intense sound with kynurenate which blocks the action of the neurotransmitter on the afferent nerve endings. Intracochlear perfusion of artificial perilymph containing 5 mM kynurenate did not reduce the effect of intense sound when we compare the results with a control group perfused with artificial perilymph alone. These results show that blockade of afferent transmitter receptors did not reduce the effect of acoustic trauma, and the acoustic trauma used herein affected structures involved in transduction before it affected the postsynaptic structures. We speculate that the active process is affected first during acoustic trauma. This interpretation is consistent with the notion that stereocilia are structures that make up part of the active process.

Action Potentials↗

PubMed1988

An ipsilateral cochlear efferent loop protects the cochlea during intense sound exposure.

One suggested physiological function of the efferent nerve fibers innervating the cochlea is that they protect the cochlea against the effects of intense sound exposure. In order to test this hypothesis, we studied the effects of intense sound in the presence and in the absence of strychnine which blocks the efferent nerve fibers. The results show that in presence of strychnine an ipsilateral intense sound has a greater effect on the cochlea than in the absence of strychnine. We conclude that the ipsilateral cochlear efferents may act as protectors against intense sound exposure.

Action Potentials↗