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Biomedical subjects

M A George

Publications and source records attributed to M A George.

At least 19 recordsLinked to original sources
PubMed2001

Evidence for the ability of hippocampal neurons to develop acute tolerance to ethanol in behaving rats.

BACKGROUND: The cellular mechanisms underlying acute tolerance to alcohol are unclear. This study aimed to determine whether hippocampal neurons have the ability to develop acute tolerance to alcohol in behaving rats. METHODS: Intrahippocampal microdialysis was performed in freely behaving rats, and the firing of single neurons in the dialysis area was recorded. The control microdialysis fluid, artificial cerebrospinal fluid (ACSF), was replaced with 1 M ethanol in ACSF for a 30 min period. One hour later, the ethanol perfusion was repeated. To test the functional integrity of the microdialysis probe in situ, each microdialysis session was completed with recording the effect of a 10-20 min perfusion of 500 microM N-methyl-D-aspartate (NMDA). The extracellular concentration profile of ethanol during intrahippocampal microdialysis with 1 M ethanol was estimated in a separate study in anesthetized rats. The ethanol content was measured in tissue slices surrounding the probe with gas chromatography (GC), and the generated data were analyzed with a mathematical model for microdialysis to estimate the concentration of ethanol at the recording site. RESULTS: The predominant effect of the first intrahippocampal microdialysis with ethanol was a decrease in firing rate in both pyramidal cells and interneurons. In contrast, such firing rate decrease did not develop during the second ethanol perfusion. Subsequent NMDA perfusion still induced robust changes in the electrical activity of the neurons. The estimated extracellular ethanol concentration at the recording site was 45-70 mM. CONCLUSION: This study revealed that hippocampal neurons have the ability to develop acute tolerance to a single exposure of clinically relevant concentrations of ethanol in behaving rats, without influences from the rest of the body.

Action Potentials↗
PubMed2001

Adrenergic blockade reduces skeletal muscle glycolysis and Na(+), K(+)-ATPase activity during hemorrhage.

BACKGROUND: Recent evidence suggests that hyperlactatemia in shock may reflect accelerated aerobic glycolysis linked to activity of the Na(+), K(+)-ATPase rather than hypoxia. Epinephrine stimulates glycolysis in resting muscle largely by stimulating Na(+), K(+)-ATPase activity. This study evaluates the effects of hemorrhagic shock, with and without combined alpha- and beta-adrenergic receptor blockade, on lactate production, glycogenolysis, Na(+)-K(+) pump activity, and high-energy phosphates in rat skeletal muscle. METHODS: Male Sprague-Dawley rats in four treatment groups were studied: unhemorrhaged control not receiving blockers (CN), controls receiving blockers (CB), shocked animals not receiving blockers (SN), and shocked rats receiving blockers (SB). Shocked rats (SN and SB) were bled to a MAP of 40 mm Hg, maintained for 60 min. Blocker groups (CB and SB) received propranolol and phenoxybenzamine. Arterial blood was drawn for plasma lactate, epinephrine, norepinephrine, and gas analysis. Lactate, glycogen, glucose 6-phosphate, ATP, phosphocreatine, and intracellular Na(+) and K(+) were determined in extensor digitorum longus and soleus muscles. For comparison, muscles were exposed to epinephrine and/or ouabain in vitro. RESULTS: With the exception of P(a)CO(2), HCO(3), and base excess in the SN group, no significant differences in arterial blood gas parameters were noted. Adrenergic blockade significantly reduced plasma lactate concentration. In shocked rats, adrenergic blockade significantly reduced muscle lactate and glucose 6-phosphate accumulation. Intracellular Na(+):K(+) ratio was decreased in SN rats, implying increased Na(+)-K(+) pump activity. Adrenergic blockade raised the intracellular Na(+):K(+) ratio in shocked animals, implying decreased pump activity. Epinephrine exposure in vitro stimulated muscle lactate production, raised glucose 6-phosphate content, and significantly reduced soleus phosphocreatine stores. CONCLUSIONS: Neither hypoxia nor defective oxidative metabolism appeared responsible for increased glycolysis during hemorrhagic shock. Adrenergic blockade concurrently reduced plasma lactate, muscle levels of lactate and glucose 6-phosphate, and muscle Na(+)-K(+) pump activity during shock. Rapid skeletal muscle aerobic glycolysis in response to increased plasma epinephrine levels may be an important contributor to increased glycolysis in muscle and increased plasma lactate during hemorrhagic shock.

Adenosine Triphosphate↗
PubMed2000

The effect of nitrogen diffusion hardening on the surface chemistry and scratch resistance of Ti-6A1-4V alloy.

Modular, head-stem, mixed-metal connections are susceptible to mechanically mediated electrochemical interactions. Any attempt to improve the performance of these connections should center around increasing their resistance to mechanical damage, particularly the titanium alloy (Ti64). This study investigated the effect of a nitrogen-diffusion-hardening process on Ti64, with specific reference to changes in composition, chemistry, electrochemistry and its ability to resist and/or repassivate scratch damage. The nitrogen-diffusion-hardened Ti64 alloy had TiN and TiNO complexes at the immediate surface and sub-surface layers. The diffusion-hardened samples also had a deeper penetration of oxygen compared to regular Ti64 alloy samples. The electrochemical impedance spectroscopy data corroborated the increased thickness of the barrier oxide on the diffusion-hardened samples. The nitrogen-diffusion-hardened samples were more resistant to scratch damage and repaired/repassivated faster after such damage. The results suggest that the nitrogen-diffusion-hardened titanium alloy should exhibit increased resistance to mechanical-electrochemical interactions in mixed-metal modular interfaces in total hip prostheses.

Alloys↗
PubMed1999

Surface topography, corrosion and microhardness of nitrogen-diffusion-hardened titanium alloy.

Mechanical-electrochemical interactions accelerate corrosion in mixed-metal modular hip prostheses. These interactions can be reduced by improving the modular component machining tolerances or by improving the resistance of the components to scratch or fretting damage. Wrought cobalt-alloy (CoCrMo) is known to have better tribological properties compared to the titanium alloy (Ti64). Thus, improving the tribological properties of this mixed-metal interface should center around improving the tribological properties of the Ti64 alloy. This study used scanning probe microscopy (contact, tapping and phase contrast mode), scanning electron microscopy, corrosion testing, and microhardness testing to determine the effect of a nitrogen-diffusion hardening process on the surface morphology, electrochemistry and surface hardness of the Ti64 alloy. The nitrogen-diffusion-hardened titanium alloy samples (N-Ti64) had a more pronounced grain structure, more nodular surface, and significantly (P<0.01) higher mean roughness values than the control-Ti64 samples. The N-Ti64 samples also exhibited at least equivalent corrosion behavior and a definite increase in surface hardness compared to the control Ti64 samples. The equivalent corrosion behavior and improved surface hardness indicate the potential for N-Ti64 samples to resist similar and mixed-metal scratch and fretting damage. The use of N-Ti64 as opposed to control-Ti64 may therefore reduce the occurrence of mechanical-electrochemical degradation in mixed-metal modular total hip prostheses.

Alloys↗
PubMed1999

Gender differences in blood levels, but not brain levels, of ethanol in rats.

Female rodents tend to drink more alcohol than males, a difference that emerges at puberty and appears to vary over the female estrous cycle. In addition, male and female rodents display different responses to alcohol; for example, female rats are reported to have faster elimination rates than males. We were interested in whether circulating ovarian hormones influence alcohol distribution to or elimination from the brain of rats, which might explain observed differences in drinking behavior. We administered 0.8 g/kg of ethanol via intraperitoneal injection to age-matched male and female Sprague-Dawley rats. Extracellular brain ethanol was sampled using microdialysis, and vascular ethanol concentrations were determined via tail blood collection, in two separate experiments. Ethanol pharmacokinetic parameters were calculated for both compartments. There were no differences in pharmacokinetic parameters due to gender or estrous cycle stage in brain ethanol concentration profiles. There were, however, differences in blood ethanol profiles: females showed faster elimination rates and a smaller area under the ethanol concentration versus time curve than males. In addition, the maximum concentration varied significantly across the estrous cycle. These results suggest that (1) circulating ovarian hormones do not influence alcohol distribution to the brain, but do influence distribution to more peripheral tissues such as the tail; and (2) apparent differences in tail blood alcohol levels may not reflect differences in brain levels.

Animals↗
PubMed1996

The distribution of alpha- and gamma-tubulin in fresh and aged human and mouse oocytes exposed to cryoprotectant.

The distribution of alpha- and gamma-tubulin in human and mouse oocytes has been investigated immunocytochemically. Comparisons have been made between freshly recovered and aged oocytes (both human and mouse), and also between human oocytes before and after exposure to cryoprotectant. Control fresh human oocytes had compact anastral spindles oriented orthogonal to the oolemma, with the pole adjacent to the oolemma being smaller than that directed towards the centre of the oocyte. Each pole was associated with a ring of particulate gamma-tubulin staining that extended a short distance into the body of the spindle. No alpha- and gamma-tubulin staining was found elsewhere in the ooplasm. Human oocytes which had failed to fertilize after an 18 h incubation with spermatozoa and had spent a further 6-8 h in culture showed an increased incidence of spindle abnormalities and of the proliferation of ooplasmic microtubules, which became more pronounced with age post-ovulation. The gamma-tubulin staining pattern of these aged human oocytes revealed greater staining over the whole of the spindle than in fresh oocytes. Examination of mouse oocytes aged in vitro or in vivo showed similar evidence of microtubule proliferation and disorganization, and the gamma-tubulin staining pattern was a sensitive indicator of ageing. The spindles of most fresh human oocytes exposed to 1.5 M dimethyl sulphoxide (DMSO) at 4 degrees C differed from controls in being slightly reduced in size or in having more pointed spindle poles with smaller diameters, both indications that some dismantling of the microtubules had occurred. The distribution of gamma-tubulin in these oocytes extended over more of the spindle. Restoration of DMSO-exposed oocytes to control medium at 37 degrees C for an extended period restored spindle structure to a state closely resembling that in controls. However, recovery of an exclusively polar gamma-tubulin staining did not occur. In both controls and DMSO-exposed human oocytes, chromosomes were arranged on the metaphase equatorial plate. In contrast, exposure of oocytes to 4 degrees C in the absence of DMSO caused dismantling of the spindle. It is concluded that (i) changes in microtubule organization with ageing of oocytes makes them unsuitable for use therapeutically after re-insemination or intracytoplasmic sperm injection, (ii) conditions of cryoprotectant addition previously found optimal for the stabilization of the spindle in the mouse oocyte also appear to be effective in stabilizing the spindle of the human oocyte, and (iii) the distribution of gamma-tubulin in relation to the spindle of the human oocyte appears to be sensitive to age and conditions.

Animals↗
PubMed1995

Histaminase activity in patients with vernal keratoconjunctivitis.

PURPOSE: To investigate the activity of histamine-degradating enzymes in tears and plasma of patients with vernal keratoconjunctivitis (VKC). METHOD: Tear and plasma samples were collected from patients with VKC and from age-matched control subjects. Histamine was measured by enzyme-linked immunosorbent assay in acid samples treated with perchloric to deactivate histaminase and in untreated samples. Tear cytology, skin test reactivity to histamine, and the sum clinical score of allergic signs and symptoms in patients with VKC also were evaluated. Nineteen patients with active VKC and six age-matched control subjects participated in this study. RESULTS: In untreated samples, tear histamine (mean +/- standard error of the mean) was 11.15 +/- 2.16 ng/ml in patients with VKC and 0.855 +/- 0.225 ng/ml in control tears (P < 0.001). In treated samples, mean tear histamine was 22.25 +/- 4.17 ng/ml in patients with VKC versus 10.64 +/- 2.85 ng/ml in control subjects (not statistically different). The ratio of histamine in treated to untreated samples (indicating histaminase activity) was significantly lower in patients with VKC (2.30 +/- 0.263) than in control subjects (17.57 +/- 5.97; P = 0.0001). Plasma histamine levels in untreated and treated samples were significantly higher in patients with VKC (untreated, 2.23 +/- 0.334 ng/ml; treated, 4.37 +/- 0.357 ng/ml) than in control subjects (untreated, 0.254 +/- 0.068, P = 0.0002; treated, 2.96 +/- 0.171 ng/ml, P = 0.0082). The enzymatic breakdown of histamine (treated/ untreated) in plasma was significantly decreased in patients with VKC (2.54 +/- 0.447) compared with control subjects (14.78 +/- 4.86; P = 0.0012). Skin reactivity to histamine was not increased in VKC. Tear histamine levels were significantly correlated to tear lymphocyte content in the general population and to tear basophils in the patients with tarsal-vernal VKC only. An increased number of tear eosinophils were correlated with elevated enzyme activity only in patients with tarsal-vernal VKC and to the clinical score only in limbal-vernal patients. CONCLUSION: The enzymatic degradation of histamine was significantly decreased in patients with VKC compared with control subjects in both tears and plasma, suggesting that this dysfunction may be a primary factor in the pathophysiology of VKC.

Adolescent↗
PubMed1995

Evaluation of 0.05% levocabastine versus 4% sodium cromolyn in the allergen challenge model.

PURPOSE: This study was conducted to evaluate the efficacy of 0.05% levocabastine compared with 4% cromolyn for treating allergic conjunctivitis induced by ocular allergen challenge. METHODS: Subjects who met all entry criteria and reacted positively to ocular allergen challenge at two previous visits (n = 50) received placebo in one eye and cromolyn in the fellow eye, four times daily for 2 weeks. On day 18, subjects received the final dose of cromolyn in the pretreated eye and one drop of levocabastine in the fellow eye. Subjects were challenged and evaluated after 3, 5, and 10 minutes. Four hours after drug administration, subjects were rechallenged and evaluated after 3, 5, and 10 minutes. RESULTS: Levocabastine was significantly more effective than cromolyn in inhibiting itching, hyperemia, eyelid swelling, chemosis, and tearing after the initial challenge and 4-hour rechallenge (P < 0.05). CONCLUSION: These results suggest that levocabastine is superior to cromolyn for treating allergen-induced conjunctivitis and has a duration of action of at least 4 hours.

Allergens↗
PubMed1994

Evaluation of the new ophthalmic antihistamine, 0.05% levocabastine, in the clinical allergen challenge model of allergic conjunctivitis.

The objective of this study was to evaluate the efficacy of 0.05% levocabastine, a new antihistamine formulated for ophthalmic use, compared with the placebo vehicle for the treatment of allergic conjunctivitis induced by ocular allergen challenge. Subjects who reacted. positively in both eyes on two separate occasions to ocular allergen challenge with grass, ragweed, or cat dander (N = 47) received one dose of 1 to 2 drops of 0.05% levocabastine in one eye and its vehicle in the other eye. After 10 minutes, the predetermined dose of allergen was instilled in both eyes. Signs and symptoms of allergic conjunctivitis were evaluated with biomicroscopy and subjective evaluation of itching after 3, 5, and 10 minutes. Four hours after drug administration, subjects were rechallenged and reevaluated to determine levocabastine's duration of action. Results showed that levocabastine was significantly more effective than placebo in inhibiting itching, hyperemia, eyelid swelling, chemosis, and tearing after the initial challenge and in inhibiting all parameters except eyelid swelling after the rechallenge 4 hours later (p < 0.05). These results demonstrate that levocabastine, currently the only ophthalmic antihistamine available that is not combined with a vasoconstrictor, is efficacious in the inhibition of itching, as well as all of the allergic signs of a vascular origin, with a duration of action of at least 4 hours. Because of its strong effects on itching and hyperemia, chemosis, lid swelling, and tearing, levocabastine would be a valuable therapeutic agent to add to the heterogeneous family of antiallergic compounds presently available for the treatment of seasonal allergic conjunctivitis.

Adolescent↗
PubMed1994

Assessment of the developmental potential of frozen-thawed mouse oocytes.

Mouse oocytes were cryopreserved by a protocol shown previously to minimize damage to the zona pellucida and cytoskeletal system. After thawing, the incidence of fertilization did not differ from that in control groups of oocytes, and after fertilization, the ability of the fertilized frozen-thawed oocytes to develop to the blastocyst stage in vitro was only slightly less (77%) than that of the controls (87 and 89%). Transfer of frozen-thawed and fertilized oocytes after their culture to the blastocyst stage in vitro resulted in a lower implantation rate (46%) than for the controls (68-73%), but of the implanting embryos the same proportions in experimental and control groups survived to yield viable fetuses. In contrast, transfer after culture in vitro to the 2- to 4-cell stage resulted in similar implantation rates for control and frozen-thawed fertilized oocytes (70-84%), but the spontaneous abortion rate was higher for the embryos derived from frozen-thawed oocytes. Overall the cumulative survival rate for frozen oocytes transferred at the 2-cell stage (36%) was better than after transfer at the blastocyst stage (30%), but both were less than for the transfer at any stage of the control oocytes (47-55%). The cumulative survival of cryopreserved oocytes to viable fetuses was 30-40% less than that of the control oocytes. These results are compared with those from previous studies and the main remaining obstacles to completely successful cryopreservation are identified.

Animals↗
PubMed1993

Use of fetal bovine serum substitutes for the protection of the mouse zona pellucida against hardening during cryoprotectant addition.

The addition of 20% fetal bovine serum (FBS) to media used for mouse oocyte cryopreservation prevents hardening of the zona pellucida that otherwise can occur due to premature release of cortical granule contents (George et al., Hum. Reprod., 7, 401-412, 1992). Protection of human oocytes would ideally be achieved by using a human macromolecular source or a more defined bovine source than total FBS. Here we investigate whether FBS can be replaced by human serum, human cord serum, human serum albumin or fetuin, the major protein component of FBS. Only fetuin was found to be effective.

Animals↗
PubMed1993

Cytoskeletal organization and zona sensitivity to digestion by chymotrypsin of frozen-thawed mouse oocytes.

Mouse oocyte-cumulus masses were added to 1.5 dimethyl sulphoxide (DMSO) + 20% fetal bovine serum (FBS) that had been precooled at +4 degrees C, were frozen by slow cooling to an intermediate temperature of -60 degrees C before being plunged into liquid nitrogen at -196 degrees C, subjected to a controlled thaw, expelled into 1.5 M DMSO + FBS at 4 degrees C, and then washed in medium + FBS at 37 degrees C. Of 7733 oocytes treated, 78.4% were viable (controls; no treatment: 94.2% of 2764 oocytes; cryoprotectant only: 92.2% of 2991 oocytes). The oocyte losses were not due to complete loss of all oocytes from some straws or mice, since analysis of individual straws containing oocytes from a single mouse revealed considerable inter-straw/mouse variation. Amongst surviving oocytes, no significant differences between frozen and control oocytes in spindle, chromosomal or microfilament organization were recorded. Two significant differences were observed: (i) fewer frozen-thawed oocytes had zonae resistant to chymotrypsin digestion, and (ii) spindle organization in control oocytes, but not frozen-thawed oocytes, was improved by 3 h incubation at 37 degrees C. More of the abnormal than the normal frozen-thawed and control oocytes were surrounded by zonae which were resistant to digestion by chymotrypsin.

Actin Cytoskeleton↗
PubMed1992

Preservative-free artificial tear preparations. Assessment of corneal epithelial toxic effects.

Scanning electron microscopy was used to evaluate the corneal epithelium of rabbit eyes after administration of two preservative-free ocular lubricants, preservative-free artificial tear-1 (Hypotears PF) and preservative-free artificial tear-2 (Refresh), and 0.02% benzalkonium chloride. Animals were randomly assigned to either mild or exaggerated use regimens. A quantitative rating system was used to assess epithelial damage. With mild use, scanning electron microscopy revealed normal epithelial morphologic characteristics for both preservative-free artificial tear solutions (mean relative damage score, solution 1, 0.75 +/- 0.16; solution 2, 1.02 +/- 0.23), which were not significantly different from eyes treated with phosphate-buffered saline (1.38 +/- 0.38) or a mild dosage regimen of 0.02% benzalkonium chloride (1.20 +/- 0.12). Exaggerated use with preservative-free artificial tear solutions (solution 1, 1.31 +/- 0.21; solution 2, 1.35 +/- 0.08) induced minimal damage that was not different from control eyes treated with phosphate-buffered saline (1.26 +/- 0.13). Compared with an exaggerated use of 0.02% benzalkonium chloride (4.0 +/- 0.16), both preservative-free artificial tear solutions induced significantly less epithelial damage (P = .0001). These results suggest that with frequent-dosage regimens, preservation-free artificial tear solutions-1 and -2 are free of the toxic effects associated with preserved solutions.

Animals↗
PubMed1992

Use of fetal bovine serum to protect against zona hardening during preparation of mouse oocytes for cryopreservation.

Addition of 20% fetal bovine serum (FBS) to media used for cryopreservation does not reduce the premature release of cortical granules but does prevent their action on the zona pellucida and thereby prevents zona hardening. In this paper, it is shown that the washing period required for removal of FBS is less than 12 min for cumulus-free oocytes and between 150 and 170 min for cumulus-intact oocytes. When these washing periods are observed after exposure of oocytes to the cryoprotectant dimethylsulphoxide (DMSO; 1.5 M) in the presence of 20% FBS, a subsequent exposure to calcium ionophore A23187 or a second exposure to 1.5 M DMSO both lead to zona hardening. This result suggests that sufficient cortical granules remain to elicit a block to polyspermy at fertilization. Oocytes, which had been exposed to DMSO and FBS and then washed free of both, were fertilized in vitro; the incidence of polyspermy was not found to be elevated over the level found in controls.

Animals↗