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1.
Exp Gerontol ; 190: 112427, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38604251

RESUMEN

BACKGROUND: Large scale population norms for peak oxygen uptake (VO2peak) during cycle ergometry (CE) have been published for men and women across a wide range of ages. Although upper body functional capacity has an important role in activities of daily living far less is known regarding the effect of age and sex on upper body functional capacity (i.e. arm crank ergometry; ACE). The aim of this review was to determine the effect of age and sex on VO2peak obtained during ACE and CE in the same participants. METHOD: The review was pre-registered with PROSEPERO (Ref: CRD42022349566). A database search using Academic Search Complete including CINAHL complete, CINHAL Ultimate, Medline, PubMed, SPORTDiscus was undertaken. RESULTS: The initial search yielded 460 articles which was reduced to 243 articles following removal of duplicates. Twenty-five articles were subsequently excluded based on title resulting in 218 articles considered for retrieval. Following review of the abstracts, 78 further articles were excluded leaving 140 to be assessed for eligibility. Eighty-five articles were subsequently excluded, resulting in 55 articles being included. The decrease in VO2peak with age during CE was consistent with previous studies. Decreases in VO2peak during ACE with age, although paralleling those of CE, appeared to be of greater functional importance. When changes in VO2peak were considered below the age of 50 years little change was observed for absolute VO2peak during ACE and CE. In contrast, relative VO2peak demonstrated decreases in VO2peak for both ACE and CE likely reflecting increases in body mass and body fat percentage with age. After 50 years of age absolute and relative VO2peak demonstrated more similar and subtle responses. Heterogeneity across studies for both absolute and relative VO2peak between ACE and CE was large. Although strict inclusion criteria were applied, the inter-individual variation in sample populations was likely the main source of heterogeneity. There was a considerable lack data sets available for ages above 40 years of age. CONCLUSIONS: These responses suggest that upper body VO2peak decreases in line with that of the lower body but, due to the lower peak values achieved during ACE, decreases in VO2peak may have more profound functional impact compared to that for the lower body. Using absolute and relative measures of VO2peak results in different age-related profiles when considered below 50 years of age. To further our understanding of whole body ageing more data is required for participants in mid and later life. The association between VO2peak and underlying physiological factors with age needs to be studied further, particularly in conjunction with activities of daily living and independent living.


Asunto(s)
Ejercicio Físico , Consumo de Oxígeno , Humanos , Consumo de Oxígeno/fisiología , Factores de Edad , Ejercicio Físico/fisiología , Femenino , Masculino , Factores Sexuales , Envejecimiento/fisiología , Envejecimiento/metabolismo , Prueba de Esfuerzo , Anciano , Persona de Mediana Edad , Adulto
2.
Exp Gerontol ; 184: 112338, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38016571

RESUMEN

The purpose of this study was to explore the effects of arm movements on postural control when standing under different sensory conditions in healthy young and older adults. Fifteen young (mean ± SD age; 21.3 ± 4.2 years) and 15 older (mean ± SD age; 73.3 ± 5.0 years) adults completed the modified Romberg test, which uses four task manipulations (i.e. eyes open and eyes closed on a firm and foam surface) to compromise the fidelity of sensory feedback mechanisms. Each participant completed the tasks under two arm movement conditions: restricted and free arm movements. Centre of pressure (COP) range and frequency were calculated to characterise postural performance and strategy, respectively. Older adults showed greater COP range with restricted compared to free arm movements during all modified sensory conditions, with these effects most prominent in the medio-lateral (ML) plane (all p < .05, Cohen's d = 0.69-1.61). Compared to the free arm movement condition, there was an increase in ML displacement and frequency when arm movements were restricted during only the most challenging (i.e. vestibular dominant) task in young adults (all p < .05, d = 0.645-0.83). Finally, main age effects for the arm restriction cost (p < .05) indicates a greater reliance on an upper body strategy in older compared to young adults, independent of sensory availability/accuracy. These findings indicate that older adults compensate for the loss of accuracy in sensory input by increasing reliance on upper body movement strategies.


Asunto(s)
Movimiento , Equilibrio Postural , Humanos , Anciano , Posición de Pie , Retroalimentación Sensorial
3.
Gait Posture ; 103: 73-79, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37121215

RESUMEN

BACKGROUND: It is firmly established that postural threat seems to lead to an increased reliance on an ankle control ('stiffening') strategy. However, little is known about how postural threat affects performance in challenging tasks that require the use of upper body postural control strategies for stability. It is logical to assume that in such conditions, being able to utilise an upper body strategy may reduce the reliance on such ankle stiffening strategy. RESEARCH QUESTION: The objective of this study was to determine how arm movement influences balance control during a challenging balance task performed under conditions of postural threat. METHODS: Thirty young adults (mean ± SD age; 22.0 ± 4.0 years) balanced in tandem stance whilst standing at both ground-level (no threat) and 0.8 m above ground (threat). In both conditions, participants performed the task under two different arm positions: restricted arm movements and free arm movements. Postural sway amplitude and frequency were calculated to infer postural stiffening response. Self-reported emotional responses were quantified by assessing balance confidence, fear of falling, perceived stability, and conscious balance processing. RESULTS: Independent of arm movements, postural threat evoked an increase in fear of falling and conscious balance processing, and reductions in balance confidence and perceived stability. These threat-related changes in emotional state were further amplified when arm movements were restricted. Whilst significant increases in sway frequency during threat were observed in both arm conditions, reductions in sway amplitude were only observed during the restricted arm movement condition. SIGNIFICANCE: We propose that these responses likely reflect a fear-related cautious strategy intended to reduce the postural destabilisation associated with individuals being unable to use their arms to counter any destabilisation, as would normally be the case in daily life.


Asunto(s)
Brazo , Miedo , Humanos , Adulto Joven , Miedo/fisiología , Movimiento/fisiología , Equilibrio Postural/fisiología
4.
Hum Mov Sci ; 89: 103093, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37088011

RESUMEN

Emerging evidence highlights that arm movements exert a substantial and functionally relevant contribution on quiet standing balance control in young adults. Ageing is associated with "non-functional" compensatory postural control strategies (i.e., lower limb co-contraction), which in turn, may increase the reliance on an upper body strategy to control upright stance. Thus, the primary purpose of this study was to compare the effects of free versus restricted arm movements on balance performance in young and older adults, during tasks of different difficulty. Fifteen young (mean ± SD age; 21.3 ± 4.2 years) and fifteen older (mean ± SD age; 73.3 ± 5.0 years) adults performed bipedal, semi-tandem and tandem balance tasks under two arm position conditions: restricted arm movements and free arm movements. Centre of pressure (COP) amplitude and frequency were calculated as indices of postural performance and strategy, respectively. Especially in older adults, restriction of arm movement resulted in increased sway amplitude and frequency, which was primarily observed for the mediolateral direction. Further, increasing balance task difficulty raised the arm restriction cost (ARC; a new measure to quantify free vs. restricted arm movement differences in postural control) that was more prominent in older adults. These findings indicate the ARC provides a measure of reliance on the upper body for balance control and that arm movement is important for postural control in older adults, especially during tasks of greater difficulty.


Asunto(s)
Envejecimiento , Movimiento , Adulto Joven , Humanos , Anciano , Equilibrio Postural , Extremidad Inferior , Posición de Pie
5.
Appl Ergon ; 66: 64-69, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28958431

RESUMEN

The purpose of this study was to investigate the effects of holding external loads on postural sway during upright stance across age decades. Sixty-five healthy adults (females, n = 35), aged 18-80 years were assessed in four conditions; (1) standing without holding a load, holding a load corresponding to 5% body mass in the (2) left hand, (3) right hand and (4) both hands. The centre of pressure (COP) path length and anteroposterior and mediolateral COP displacement were used to indirectly assess postural sway. External loading elicited reductions in COP measures of postural sway in older age groups only (P < 0.05). No changes were observed in younger or intermediate aged adults (P > 0.05). Holding external loads during standing is relevant to many activities of daily living (i.e. holding groceries). The reduction in postural sway may suggest this type of loading has a stabilising effect during quiet standing among older adults.


Asunto(s)
Factores de Edad , Equilibrio Postural/fisiología , Postura/fisiología , Soporte de Peso/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Presión , Adulto Joven
6.
Aust Dent J ; 52(3): 181-6, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17969285

RESUMEN

BACKGROUND: There is scant evidence supporting the criteria for establishing the suitability of a deciduous molar for a pulpotomy. Although some criteria, such as patient age, are logical the importance of other factors on tooth survival has not been established. METHODS: All pulpotomies performed at 20 school dental clinics over a period of 15 months were reported together with date of birth, gender, tooth treated, presenting signs and symptoms, pulp status and date and method of treatment. Operators performed the treatment according to their usual procedures. Data were analysed statistically using Statview 5.0 (SAS Institute). RESULTS: The outcome of pulpotomy of 465 deciduous teeth in 403 patients was evaluated. The mean age of the patients was 7.4 +/- 0.1 years. Two hundred and seventy-two teeth were vital and 193 were non-vital. One hundred and ninety-six teeth were treated with the one-step formocresol method and 269 with the two-step formocresol method. The age and gender of the patients did not differ between the vital and non-vital groups. There was no influence of mode of treatment on the asymptomatic survival of the teeth in the mouth. The median survival times were significantly longer in vital (32.7 +/- 1.4 months) than non-vital teeth (20.4 +/- 3.0 months; p < 0.0001). The only factors significantly influencing the survival of pulpotomized teeth were the age of the patient (p < 0.0001), the non-vitality of the pulp (p < 0.0001) and the presence of a radiolucency (p = 0.031). CONCLUSION: Both vital and non-vital teeth were able to survive for extended periods following pulpotomy but the presence of an associated radiolucency or a non-vital pulp at the time of treatment is negatively associated with time of survival.


Asunto(s)
Pulpotomía , Diente Primario , Factores de Edad , Niño , Preescolar , Fracaso de la Restauración Dental , Femenino , Formocresoles/uso terapéutico , Humanos , Estimación de Kaplan-Meier , Masculino , Diente Molar , Modelos de Riesgos Proporcionales , Pulpotomía/métodos , Servicios de Odontología Escolar , Pérdida de Diente , Diente no Vital , Resultado del Tratamiento
7.
Biochim Biophys Acta ; 596(3): 393-403, 1980 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-6244846

RESUMEN

The fluorescent probe 9-aminoacridine was used to measure the rate of decay of experimentally established pH gradients across liposome membranes. From the rate of decay, separate permeability coefficients for protons (PH) and hydroxyls (POH) were calculated and summed to yield the net proton-hydroxyl permeability (Pnet). The net permeability of protons and hydroxyls was found to be approximately 10(-4) cm/s, six orders of magnitude greater than that measured for sodium and pyrophosphate ions under similar conditions. This suggests that protons and/or hydroxyls cross lipid bilayers by a different mechanism than do other monovalent cations and anions. In addition, the measurements provide a standard for net proton-hydroxyl permeability in pure phospholipid bilayers for comparison with biological membranes.


Asunto(s)
Aminoacridinas , Liposomas , Difosfatos , Concentración de Iones de Hidrógeno , Cinética , Permeabilidad , Fosfolípidos
8.
Biochim Biophys Acta ; 455(3): 644-54, 1976 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-136992

RESUMEN

1. The proportion of ethanolamine phosphoglycerides in microsomal fractions of goldfish intestine increases at low environmental temperatures. The fatty acyl composition also changes, the proportion of C22:6 and C20:4 fatty acids increasing in positions 1 and 2 and position 2 respectively. The proportion of C16:0 and C18:0 fatty acids falls in position 1 and there is an apparent switch of C18:1 and C20:1 fatty acids from position 2 to position 1. 2. The proportion of choline phosphoglycerides does not depend on the previous environmental temperature of the fish. Temperature-dependent changes in fatty acyl composition in positions 1 and 2 take place in a way similar to that described for ethanolamine phosphoglycerides, but in this case C22:6 substitution is confined to position 2. 3. Choline phosphoglycerides have been further separated into 7 different molecular species. The amounts of species 3 to 7 increase and the amount of species 2 decreases at low adaptation temperature. These changes only account for part of total change in fatty acyl composition. The remaining changes occur by chain substitution within species. 4. Present results show temperature adaptation to be highly complex, involving both quantitative and qualitative changes in different phospholipids. The possible physiological significance of these changes are discussed together with the effects these changes might have on cholesterol-phospholipid interactions.


Asunto(s)
Aclimatación , Cyprinidae/fisiología , Carpa Dorada/fisiología , Mucosa Intestinal/fisiología , Lípidos de la Membrana/fisiología , Fosfolípidos/fisiología , Adenosina Trifosfatasas/metabolismo , Animales , Cromatografía en Capa Delgada , Membranas/ultraestructura , Microsomas/fisiología , Microsomas/ultraestructura , Temperatura
9.
Gait Posture ; 41(1): 252-7, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25455437

RESUMEN

Older adults are increasingly being encouraged to exercise but this may lead to muscle fatigue, which can adversely affect postural stability. Few studies have investigated the effects of upper body exercise on postural sway in groups at risk of falling, such as the elderly. The purpose of this study was to compare the effects arm crank ergometry (ACE), cycle ergometry (CE) and treadmill walking (TM) on postural sway in healthy older females. In addition, this study sought to determine the time necessary to recover postural control after exercise. A total of nine healthy older females participated in this study. Participants stood on a force platform to assess postural sway which was measured by displacement of the centre of pressure before and after six separate exercise trials. Each participant completed three incremental exercise tests to 85% of individual's theoretical maximal heart rate (HRMAX) for ACE, CE and TM. Subsequent tests involved 20-min of ACE, CE and TM exercise at a relative workload corresponding to 50% of each individual's predetermined heart rate reserve (HRE). Post fatigue effects and postural control recovery were measured at different times after exercise (1, 3, 5, 10, 15 and 30-min). None of the participants exhibited impaired postural stability after ACE. In contrast, CE and TM elicited significant post exercise balance impairments, which lasted for ∼ 10 min post exercise. We provide evidence of an exercise mode which does not elicit post exercise balance impairments. Older adults should exercise caution immediately following exercise engaging the lower limbs to avoid fall risk.


Asunto(s)
Brazo/fisiología , Ergometría/métodos , Ejercicio Físico/fisiología , Fatiga Muscular/fisiología , Equilibrio Postural/fisiología , Caminata/fisiología , Adulto , Anciano , Femenino , Frecuencia Cardíaca , Humanos , Salud de la Mujer
10.
Cell Prolif ; 27(4): 225-31, 1994 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10465017

RESUMEN

Data concerning changes in the rate of cell proliferation of stratified epithelia with increasing age are conflicting. In the present study young (3-month-old) and old (22-month-old) C57Bl/6NNia male mice were injected intraperitoneally with 2, 3, 4 or 8 mg vinblastine sulfate/kg body weight and killed after 1.5, 3, 4.5 or 6 h. The number of arrested metaphase figures per 1000 basal cells was counted in histological sections. Data were analysed using a multivariate analysis of variance. There was a significant difference between the accumulation of mitotic figures in footpad epidermis and palate epithelium and both tissues contained an increased number of mitotic figures with increasing periods of accumulation at all dose levels. In the footpad epidermis neither the age of the animal nor the dose of vinblastine had a significant effect on the number of mitotic figures. In contrast, for palate epithelium the accumulation of mitotic figures was significantly less in the old mice compared with the young mice and at a dose of vinblastine of 2 mg/kg compared with the higher doses. There was a statistically significant interaction between the dose of vinblastine and its period of action. It was concluded that the different tissues manifest a differential sensitivity to vinblastine and that only palate epithelium showed a significant reduction in proliferative activity with age.


Asunto(s)
Envejecimiento/fisiología , Antineoplásicos Fitogénicos/farmacología , Epidermis/patología , Hueso Paladar/citología , Vinblastina/farmacología , Animales , División Celular/efectos de los fármacos , División Celular/fisiología , Relación Dosis-Respuesta a Droga , Células Epiteliales/patología , Miembro Posterior/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Mitosis/efectos de los fármacos , Mitosis/fisiología
11.
J Med Chem ; 39(9): 1898-906, 1996 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-8627613

RESUMEN

A series of 3,3-dialkyl- and 3-alkyl-3-benzyl-substituted 2-pyrrolidinones (lactams) have been prepared and evaluated for their anticonvulsant activities. In the pentylenetetrazole mouse seizure model, 3,3-diethyl lactam 7c and 3-benzyl-3-ethyl lactam 7j are the most effective anticonvulsants (ED50 = 46 and 42 mg/kg, respectively) and have protective index (PI = TD50/ED50) values of 5.65 and 3.00, respectively. These protective index values compare favorably to those of the clinically used antiepileptic drugs ethosuximide (ED50 = 161 mg/kg), phenobarbital (ED50 = 22 mg/kg), and valproic acid (ED50 = 133 mg/kg), which have PI values of 2.35, 4.00, and 2.12, respectively. The benzyl compounds [3-substituents are Bn, H (7h); Bn, Me (7i); and Bn, Et (7j)] are also very effective anticonvulsants against seizures induced by maximal electroshock (ED50 = 41, 55, and 74 mg/kg, respectively) and have PI values of 3.51, 3.04, and 1.70, respectively. The corresponding PI values for phenobarbital and valproic acid are 1.37 and 5.18, respectively. As a class of anticonvulsants, the 3,3-disubstituted 2-pyrrolidinones have a broad spectrum of action and may be useful for the treatment of human epilepsies.


Asunto(s)
Anticonvulsivantes/farmacología , Pirrolidinonas/farmacología , Animales , Anticonvulsivantes/química , Humanos , Espectroscopía de Resonancia Magnética , Ratones , Neuronas/efectos de los fármacos , Neuronas/fisiología , Pirrolidinonas/química
12.
J Med Chem ; 40(1): 44-9, 1997 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-9016327

RESUMEN

A series of 3-substituted 2-piperidinone (delta-valerolactam) and hexahydro-2H-azepin-2-one (epsilon-caprolactam) derivatives were prepared and evaluated as anticonvulsants in mice. In the 2-piperidinone series, 3,3-diethyl compound 7b is the most effective anticonvulsant against pentylenetetrazole-induced seizures (ED50, 37 mg/kg; PI (TD50/ED50), 4.46), and 3-benzyl compound 4c (ED50, 41 mg/kg; PI, 7.05) is the most effective anticonvulsant against seizures induced by maximal electroshock. By contrast, none of the epsilon-caprolactams tested had anticonvulsant effects below doses causing rotorod toxicity. log P values were correlated with neurotoxicity and [35S]TBPS displacement, but not with anticonvulsant activity. Electrophysiological evaluations of selected compounds from each series indicated that both the delta-valero-lactams and epsilon-caprolactams potentiated GABA-mediated chloride currents in rat hippocampal neurons.


Asunto(s)
Anticonvulsivantes/síntesis química , Caprolactama/síntesis química , Piperidonas/síntesis química , Animales , Anticonvulsivantes/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/metabolismo , Caprolactama/farmacología , Electrofisiología , Etosuximida/farmacología , Ratones , Fenobarbital/farmacología , Piperidonas/farmacología , Ratas , Ácido Valproico/farmacología
13.
J Histochem Cytochem ; 26(10): 862-4, 1978 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-722049

RESUMEN

The ultrastructural localization of alkaline phosphatase in eosinophil leucocytes, obtained from experimentally-induced peritoneal exudates in rats, has been studied using an osmiophilic technique with 2-naphthylthiolphosphoryl dichloride as substrate, fast Blue BBN as diazonium salt and postosmication with 1% aqueous osmium tetroxide. With this method identical incubation procedures could be used for both light and electron microscope examination. Eosinophils were the only cells which contained alkaline phosphatase. The enzyme was predominantly associated with the outer surface of the plasma membrane, being present in much lower concentrations in cytoplasmic cisternae. Eosinophil granules only rarely showed reaction product. The plasma membrane location of alkaline phosphatase in eosinophil leucocytes is identical to that recently demonstrated in the human neutrophil.


Asunto(s)
Fosfatasa Alcalina/análisis , Eosinófilos/enzimología , Animales , Membrana Celular/enzimología , Citoplasma/enzimología , Gránulos Citoplasmáticos/enzimología , Eosinófilos/ultraestructura , Masculino , Ratas
14.
Exp Gerontol ; 24(4): 331-40, 1989.
Artículo en Inglés | MEDLINE | ID: mdl-2583249

RESUMEN

Glucose metabolism in regionally distinct epidermis and oral epithelia of young adult and aged mice was studied using 5-3H glucose and differentially labelled 14C-glucose. The results obtained with 3H-glucose indicate there is active utilization of glucose by all the epithelia examined. However, an enhanced utilization of glucose was observed in old ear epidermis when compared to that in young mice. The measurements of respiratory 14CO2 in the young and old epidermis indicated that aerobic glycolysis was significantly greater in ear epidermis and buccal epithelium from old than from young mice. Pentose phosphate activity was significantly reduced in palate epithelium from old animals when compared with that of young animals. Incorporation of radioactively labelled leucine and histidine revealed some regional differences between the epithelia examined. However, no age-associated differences were observed in any of the tissues. It is concluded that the observed metabolic changes reflect regionally specific adaptations to local factors rather than representing a programmed biological event.


Asunto(s)
Envejecimiento/metabolismo , Epitelio/metabolismo , Glucosa/metabolismo , Biosíntesis de Proteínas , Animales , Epidermis/metabolismo , Humanos , Ratones , Ratones Endogámicos C57BL , Mucosa Bucal/metabolismo , Ratas
15.
Biochem Pharmacol ; 32(22): 3369-74, 1983 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-6140010

RESUMEN

The activity of tyrosine hydroxylase (TH) in the corpus striatum of haloperidol treated and control rats has been examined. The activation of TH by haloperidol caused a decrease in the Km for tetrahydrobiopterin but no change in the Vmax. This effect was totally abolished when homogenates were prepared at high values of pH. A similar activation could be produced in vitro by preincubating with S-adenosylmethionine; conversely, enzyme activity was reduced by preincubating with S-adenosylhomocysteine. ATP and cyclic AMP activated the enzyme when incubated together with TH in vitro but the activity was reduced when the enzyme was preincubated with these substances. A possible role for carboxymethylation in controlling tyrosine hydroxylase activity is discussed.


Asunto(s)
Cuerpo Estriado/enzimología , Homocisteína/análogos & derivados , S-Adenosilhomocisteína/farmacología , S-Adenosilmetionina/farmacología , Tirosina 3-Monooxigenasa/metabolismo , Adenosina Trifosfato/farmacología , Animales , AMP Cíclico/farmacología , Activación Enzimática/efectos de los fármacos , Haloperidol/farmacología , Concentración de Iones de Hidrógeno , Cinética , Ratas , Ratas Endogámicas
16.
Brain Res Bull ; 15(5): 453-8, 1985 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-4063839

RESUMEN

The auditory evoked potentials produced in response to a click stimulus were measured in the conscious sheep. The early components, the brain stem evoked potentials (BSEPs) were reproducible and similar to those observed in the other animals as well as man and appeared to have frequencies that are the three subharmonics of the main frequency component of the click stimulus. The longer latency components were more variable in latency and amplitude, but the frequencies were similar to that observed in humans.


Asunto(s)
Tronco Encefálico/fisiología , Potenciales Evocados Auditivos , Ovinos/fisiología , Animales , Vías Auditivas/fisiología , Percepción Auditiva/fisiología , Humanos , Tiempo de Reacción/fisiología
17.
Epilepsy Res ; 37(2): 121-31, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10510978

RESUMEN

Some 3,3-disubstituted 2-pyrrolidinones and 2-piperidinones (five- and six-membered ring lactams, respectively) possess potent in vivo anticonvulsant activity. In vitro these lactams potentiate GABA(A) receptor-mediated chloride currents, which is thought to be the mechanism by which they exert their therapeutic effects. However, the apparent affinity for these GABA(A) interactions is low: EC50s range from hundreds of micromolar to low millimolar values. In order to more completely characterize the activities of these compounds, it was necessary to know the concentrations required to curtail epileptiform activity in an intact neural network, and the mechanism by which this occurs. To address these questions, we used two methods of inducing ictal activity in hippocampal-entorhinal cortical slices: 4-aminopyridine (4-AP) and low Mg2+. We found that 3,3-diethyl-2-pyrrolidinone (diethyl-lactam) prevents seizure-like discharges with IC50s of 1.1 and 2.1 mM in the two models, respectively. These values are nearly identical to the EC50 value obtained in whole-cell studies of diethyl-lactam's GABA(A) receptor modulation. The addition of the GABA(A) antagonist picrotoxin to the low Mg2+ ACSF produced seizures which persisted during diethyl-lactam application. Neither 3-benzyl-3-ethyl-2-piperidinone (3-BEP) nor alpha-ethyl-alpha-methyl-gamma-thiobutyrolactone (alpha-EMTBL), two compounds which are similar to diethyl-lactam, but demonstrate picrotoxin-insensitive inhibition of voltage-dependent currents, diminished low Mg2+/picrotoxin seizure activity. Our results support the hypothesis that diethyllactam and related compounds exert their anticonvulsant activity primarily, if not exclusively, by modulating the GABA(A) receptor.


Asunto(s)
4-Butirolactona/análogos & derivados , Anticonvulsivantes/farmacología , Hipocampo/fisiopatología , Lactamas/farmacología , Piperidinas/farmacología , Convulsiones/inducido químicamente , 4-Butirolactona/farmacología , Animales , Bloqueadores de los Canales de Calcio/farmacología , Electrofisiología , Hipocampo/efectos de los fármacos , Técnicas In Vitro , Ratones , Fenitoína/farmacología , Bloqueadores de los Canales de Potasio , Receptores de GABA-A/efectos de los fármacos , Convulsiones/fisiopatología , Bloqueadores de los Canales de Sodio , Transmisión Sináptica/efectos de los fármacos , Ácido gamma-Aminobutírico/fisiología
18.
Chem Phys Lipids ; 40(2-4): 189-205, 1986.
Artículo en Inglés | MEDLINE | ID: mdl-3017592

RESUMEN

There are few explanations which account for the manner in which the catastrophic physiological consequences of anaesthesia, cold narcosis or, for the matter, a short, sharp upper-cut, come about. Most studies terminate with the presentation of ever-better correlations between an end-point in a model system (dough consistency, rubber elasticity, bacterial, protozoal or animal mobility, liposome permeability, luciferase activity, etc.) and oil/water partition coefficients or with some arbitrary biological end-point. From what is currently known about the permeating pathways of non-electrolytes, ions and protons across membranes e.g. liposomes, the effect of anaesthetics on such pathways and the effect of temperature and pressure on both liposomes and whole animals, it is possible to develop a testable hypothesis. It is called the 'proton pump-leak' hypothesis and involves a number of linked biophysical and biochemical processes. It assumes that a living animal or plant is in a steady-state regarding all concentration gradients; passive leaks across membranes are balanced by temperature, pressure, and energy dependent ion/ion and/or proton/ion pumps (enzyme), working within an aqueous phase. Consciousness is dependent upon inter-neuronal communication via release of transmitter substances. Transmitter substances, characteristically either weak bases or weak acids e.g. catecholamines, accumulate passively in vesicles rich in acid-buffer, held to a low pH by the activity of H+/K+ energy-driven pumps. Interference with this finely-balanced system either by changing the chemical potential of the hydrophobic (membrane) phase at NTP (with anaesthetics), or by changing the chemical potential of both hydrophobic and aqueous (pump) phases by hyperbaric, hypothermic, or anoxic conditions imposed (inevitably) on the whole animal, would result in the resetting of the steady-state parameters.


Asunto(s)
Anestesia General , Liposomas , Inconsciencia , Animales , Humanos , Modelos Neurológicos , Permeabilidad , Protones , Transmisión Sináptica , Termodinámica
19.
Arch Oral Biol ; 33(4): 221-9, 1988.
Artículo en Inglés | MEDLINE | ID: mdl-3165257

RESUMEN

To determine whether stratified squamous epithelia from aged animals differ from those of young animals, specimens of skin from the pinna of the ear, the back and footpad and mucosa from the palate, cheek and ventral surface of the tongue were excised from 10 young (3-4 month-old) and 10 old (23-24 month-old) C57B1/6NNia mice and prepared for light microscopy. Tracings were prepared of the nucleated cell compartment and epithelial thickness, the number of nucleated cells/mm2 surface, the basement membrane: surface ratio, cell density and the number of basal cells/mm basement membrane were determined. To evaluate the epithelial labelling index and tissue renewal, a further group of young and old mice were injected with 1 microCi/g [3H]-thymidine and killed after 1 h or 2, 4, 5, 6 or 8 days and sections were prepared for autoradiography. Whereas the epidermis from the ear and footpad showed a statistically-significant increase in thickness, the epithelium from the palate was thinner in the old animals. The other tissues examined showed no change. Cell density decreased with age in the palate; cell size increased with age in the ear and footpad. No statistically-significant differences in labelling index or minimum transit time were observed between young and old animals in any of the tissues. Thus, there is no single age-associated change in epithelial structure or renewal common to all epithelia.


Asunto(s)
Envejecimiento/fisiología , Mucosa Bucal/citología , Piel/citología , Animales , División Celular , Células Epiteliales , Ratones , Ratones Endogámicos C57BL , Mucosa Bucal/crecimiento & desarrollo
20.
Arch Oral Biol ; 26(12): 1063-7, 1981.
Artículo en Inglés | MEDLINE | ID: mdl-6951513

RESUMEN

The composition and proliferation of skin from the ear, tail and footpad oral mucosa form the palate, cheek and tongue of adult mice were examined. The thickness of the nucleated cell layer of skin showed an approximately two-fold variation; a similar range was found between that of oral mucosae but that was considerably thicker than skin. No direct correlation between epithelial thickness and the number of nucleated cells was observed. Proliferative activity, assessed following the administration of vinblastine sulphate, and turnover of the epithelium showed a broad range of activities but more rapid in the oral epithelia than in the epidermis, suggesting a relationship between functional stress and proliferative activity. The criteria used clearly distinguish between morphologically different epithelia and should prove useful examining experimentally produced changes in epithelial histodifferentiation.


Asunto(s)
Mucosa Bucal/citología , Piel/citología , Animales , Recuento de Células , División Celular , Núcleo Celular/ultraestructura , Células Epiteliales , Masculino , Ratones , Ratones Endogámicos C3H , Mitosis
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