RESUMO
AIMS: The recurrence of foot ulcers is a significant problem in people with diabetic neuropathy. The purpose of this study was to measure in-shoe plantar pressures and other characteristics in a group of neuropathic patients with diabetes who had prior foot ulcers which had remained healed. METHODS: This was an epidemiological cohort study of patients from diabetes clinics of two Swedish hospitals. From a database of 2625 eligible patients, 190 surviving patients with prior plantar ulcers of the forefoot (hallux or metatarsal heads) caused by repetitive stress were identified and 49 patients agreed to participate. Barefoot and in-shoe plantar pressures were measured during walking. Data on foot deformity, activity profiles and self-reported behaviour were also collected. RESULTS: Mean barefoot plantar peak pressure at the prior ulcer site (556 kPa) was lower than in other published series, although the range was large (107-1192 kPa). Mean in-shoe peak pressure at this location averaged 207 kPa when measured with an insole sensor. Barefoot peak pressure only predicted approximately 35% of the variance of in-shoe peak pressure, indicating variation in the efficacy of the individual footwear prescriptions (primarily extra-depth shoes with custom insoles). CONCLUSIONS: We propose that the mean value for in-shoe pressures reported in these patients be used as a target in footwear prescription for patients with prior ulcers. Although plantar pressure is only one factor in a multifaceted strategy to prevent ulcer recurrence, the quantitative focus on pressure reduction in footwear is likely to have beneficial effects.
Assuntos
Pé Diabético/reabilitação , Neuropatias Diabéticas/reabilitação , Caminhada/fisiologia , Cicatrização/fisiologia , Idoso , Pé Diabético/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Aparelhos Ortopédicos , Pressão/efeitos adversos , Recidiva , SapatosRESUMO
The prognostic value of distal blood pressure measurements has been studied in 314 consecutive diabetic patients with foot ulcers. Systolic toe blood pressure was measured with a strain-gauge technique, and ankle pressure was measured with strain-gauge or Doppler techniques. Wound healing was defined as intact skin for at least 6 mo. One hundred ninety-seven patients healed primarily, 77 had amputations, and 40 died before healing had occurred. In 294 of 300 patients, it was possible to measure either ankle or toe pressure. Fourteen patients were not available for pressure measurements. Of these, 10 patients healed primarily, and 4 died before healing occurred. Both ankle and toe pressures were higher (P less than .001) among patients who healed without amputation compared with those who underwent amputation or died before healing. No differences were seen in ankle or toe pressure levels among those who had amputations or died. No patient healed primarily with an ankle pressure less than 40 mmHg. An upper limit above which amputation was not required could not be defined. Primary healing was achieved in 139 of 164 patients (85%) with a toe pressure level greater than 45 mmHg, whereas 43 of 117 patients (36%; P less than .001) healed without amputation when toe pressure was less than or equal to 45 mmHg. In conclusion, a combination of ankle and toe pressure measurements is a useful tool to predict primary healing in diabetic foot ulcers.
Assuntos
Complicações do Diabetes , Doenças do Pé/fisiopatologia , Contração Miocárdica , Úlcera Cutânea/fisiopatologia , Sístole , Cicatrização , Idoso , Amputação Cirúrgica , Tornozelo , Diabetes Mellitus/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Dedos do Pé , UltrassomRESUMO
Human pregnancy-specific beta 1-glycoprotein (hPS beta G) consists of a set of glycoproteins present in placenta and maternal serum. This study characterized proteins in rat placenta that show immunological cross-reactivity with antisera to hPS beta G. Immunocytochemical studies using two independent preparations of anti-hPS beta G showed intense specific staining within basophilic cytotrophoblast cells of the basal zone of the gestation day 15 rat placenta. In contrast, basophilic cytotrophoblasts located in the labyrinth did not stain. Subsequent experiments used gel electrophoresis and immunoblot analysis to compare PS beta G in human placenta and serum with immunoreactive proteins in rat placenta and serum. A set of two or three proteins was detected in human villous tissue and pregnancy serum with apparent mol wt (Mr) ranging from 54,000-76,000. In contrast rat placenta showed a major immunoreactive protein with 120,000 Mr, while rat serum contained bands of 48,000 64,000 and 69,000 Mr. Explant cultures of rat basal zone tissue secreted two [35S]methionine-labeled proteins that were immunoreactive, a major 120,000 Mr species and a minor 76,000 Mr form, with pI values of 4.6-5.5; tunicamycin inhibited the secretion of both species. Thus, a 120,000 Mr glycoprotein appears to be the major tissue and secreted form of rat PS beta G analog in day 15 placenta. Finally, the cytochemical localization of PS beta G-like proteins in rat placenta showed a progressive gestational shift from giant trophoblast cells in the parietal yolk sac placenta on day 12 to the basal zone cytotrophoblast cells by day 15. Data indicate that the pregnant rat may provide an animal model for investigation of the biological function of PS beta G during late gestation.
Assuntos
Placenta/análise , Proteínas da Gravidez/isolamento & purificação , Glicoproteínas beta 1 Específicas da Gravidez/isolamento & purificação , Animais , Técnicas de Cultura , Eletroforese em Gel de Poliacrilamida , Feminino , Idade Gestacional , Immunoblotting , Imuno-Histoquímica , Proteínas da Gravidez/biossíntese , Glicoproteínas beta 1 Específicas da Gravidez/biossíntese , Ratos , Ratos Endogâmicos , Distribuição TecidualRESUMO
It was found that in the rat striatum DA was oxidized extrasynaptosomally to 11% by MAO-A and to 3% by MAO-B. The corresponding intrasynaptosomal oxidations were 84% and 2%, respectively. Those figures were virtually unchanged even if the rat brain MAO-B was selectively inhibited to 87% by deprenyl. In the human brain extrasynaptosomal oxidation was 16% and 66%, respectively, by MAO-A and -B. Intrasynaptosomally the corresponding figures were 12% and 6%, respectively. Selective inhibition of human caudate MAO-B was calculated to give a total reduction of DA oxidation of 63%. The differences between man and rat are due to the proportionately greater oxidation of DA by MAO-B in man, which is a consequence of a higher ratio of concentration of MAO-A/-B in the rat.
Assuntos
Encéfalo/metabolismo , Dopamina/metabolismo , Fenetilaminas/farmacologia , Selegilina/farmacologia , Animais , Humanos , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Neurônios/metabolismo , Oxirredução , Ratos , Sinaptossomos/metabolismo , Distribuição TecidualRESUMO
MAO-A and MAO-B activities within and outside dopaminergic synaptosomes in homogenates of striatal tissue from pig, cat, rat and human brains have been studied by using a specific "low substrate concentration technique" with dopamine. It was found that within the synaptosomes, MAO-A activity predominated in all species. Outside the synaptosomes there were more pronounced differences and only in the rat did MAO-A predominate, while in the other species MAO-B predominated. When estimating MAO-A and -B activities with a conventional method the activity of MAO-B predominated in man, cat and pig. Thus, also in species where the MAO-B activity (as estimated in a conventional way) was dominating, the intrasynaptosomal deamination of dopamine was brought about mainly by MAO-A. The "low substrate concentration technique", more adequately reflects physiological conditions by taking into account the higher concentration of monoamine transmitter substrates within the monoamine neurons. With this technique it was found that in all species (with the possible exception of man) the oxidation rate was higher within than that outside the DA-synaptosomes. In man the unavoidable longer time between death and estimation of the enzyme activity may be the cause of the deviating result.
Assuntos
Corpo Estriado/enzimologia , Dopamina/metabolismo , Monoaminoxidase/metabolismo , Sinaptossomos/enzimologia , Animais , Gatos , Humanos , Cinética , Masculino , Ratos , Especificidade da Espécie , Distribuição TecidualRESUMO
We have shown previously in the rat that lethal, acute cyanide intoxication dramatically decreased the levels of dopamine (DA) in the striatum, while the synthesis of DA was increased. The main brain metabolite of DA, homovanillic acid, was also diminished. However, the levels of the oxidatively deaminated metabolite of DA, 3,4-dihydroxyphenylacetic acid, were not significantly changed. In order to elucidate further these findings we examined the effects in vitro of sodium cyanide on rat and pig brain monoamine oxidase (MAO; EC 1.4.3.4). The MAO activity was measured radiochemically using [14C]5-hydroxytryptamine (5-HT; 100 microM), [14C]phenethylamine (PEA; 20 microM) and [14C]DA (100 microM) as substrates. The amounts of cyanide added were comparable to those tissue concentrations of cyanide usually considered to be fatal in rats. The effect of cyanide on MAO was immediate. In rat, as well as pig, striatal tissue we found that cyanide produced a dose-dependent increase in the activity of MAO-A (as measured with 5-HT), but not MAO-B (as measured with PEA). The change in MAO activity was also seen with DA as substrate (MAO-A and -B). Kinetic constants, Km and Vmax, were determined. In both rat and pig striatum the Vmax values for 5-HT were significantly increased, but the values for PEA were not affected. A significant decrease in the Km value for PEA was, however, found in the presence of high concentrations of cyanide.
Assuntos
Corpo Estriado/enzimologia , Monoaminoxidase/metabolismo , Cianeto de Sódio/farmacologia , Animais , Radioisótopos de Carbono , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Cinética , Masculino , Fenetilaminas/metabolismo , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo , SuínosRESUMO
In the present study, the pharmacological properties of fatty acid amide hydrolase (FAAH) in subcellular fractions of rat brain were investigated using palmitoylethanolamide (PEA) and arachidonyl ethanolamide (anandamide, AEA) as substrates. FAAH hydrolysed [(3)H]PEA in crude homogenates with median K(m) and V(max) values of 2.9 microM and 2.14 nmol.(mg protein)(-1).min(-1), respectively. [(3)H]PEA hydrolysis was inhibited both by non-radioactive AEA (with a K(i) value very similar to the K(m) value for [(3)H]AEA as substrate using the same assay) and by R(-)ibuprofen (mixed-type inhibition K(i) and K'(i) values 88 and 720 microM, respectively). FAAH activity towards both [(3)H]PEA and [(3) myelin = cytosol, but there were no differences between the relative activities towards the two substrates in any of the fractions. [(3)H]PEA hydrolysis in mitochondrial, myelin, microsomal, and synaptosomal fractions was inhibited by oleyl trifluoromethylketone, phenylmethylsulphonyl fluoride, and the R(-)- and S(+)-enantiomers of the nonsteroidal anti-inflammatory drug ibuprofen, with mean IC(50) values in the ranges 0.028-0.041, 0.37-0.52, 67-110, and 130-260 microM, respectively. It is concluded that the pharmacological properties of FAAH in the different subcellular fractions are very similar.
Assuntos
Amidoidrolases/metabolismo , Encéfalo/enzimologia , Ácidos Palmíticos/metabolismo , Amidas , Amidoidrolases/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Ácidos Araquidônicos/metabolismo , Ácidos Araquidônicos/farmacologia , Encéfalo/efeitos dos fármacos , Endocanabinoides , Etanolaminas , Hidrólise , Técnicas In Vitro , Cinética , Ácidos Palmíticos/farmacologia , Alcamidas Poli-Insaturadas , Ratos , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/enzimologia , Especificidade por Substrato , TrítioRESUMO
The regional distribution of the dopamine and serotonin uptake sites in human brain have been assessed and compared with the distribution of the transmitters and their metabolites measured in the same brains and also with a limited regional distribution of the uptake sites in rat and sheep brain. The affinity of the uptake sites for both transmitters was determined and found to be c. 0.2 ? M in all 3 species. Most dopamine uptake in all species was in caudate and putamen samples. Many regions of the human brain showed no dopamine uptake and little dopamine uptake was seen in sheep cortex or nigral preparations. Dopamine and metabolite concentrations were highest in the caudate, putamen and substantia nigra. Most serotonin uptake was seen in the hypothalamus in all 3 species; less was observed in the striatal regions; the cortical and nigral preparations of sheep brain showed little serotonin uptake though cortical preparations of rat brain had high levels of uptake. In the human brain, other regions did not show serotonin uptake. Highest concentrations of serotonin were found in the substantia nigra and medulla, intermediate concentrations in the putamen, globus pallidus, hypothalamus, olfactory tubercle and thalamus; very low concentrations of serotonin were found in other regions. The use of the human uptake site for pharmacological studies and as a marker for monoaminergic afferents in human health and disease is discussed.
RESUMO
Islet beta-cell monoamines are known to influence the insulin-releasing mechanisms. These amines are localized in the insulin-secretory granules and are inactivated by the enzyme monoamine oxidase (MAO), a hydrogen peroxide (H2O2)-generating enzyme. The activity of islet MAO may consequently be of importance for insulin secretion. In the present investigation, we studied the relation between islet MAO activity and plasma levels of insulin and glucose in obese (ob/ob) hyperglycemic mice and their lean littermates. In addition, the effect of glucose on the MAO activity of in vitro-cultured islets was studied. MAO activity was assayed with serotonin, dopamine (DA), and beta-phenylethylamine (PEA) as substrates. After an overnight fast in adult (age, 6 months) lean mice, islet MAO activity was increased by 35% to 70%. Plasma levels of glucose and insulin were markedly decreased as expected. However, fasting in adult obese mice either did not affect islet MAO activity (PEA and DA) or induced a slight decrease (serotonin) of approximately 25% (P < .05). Plasma glucose levels in adult obese mice were not significantly affected by the overnight fast. However, a correlation analysis based on individual adult obese mice (fed and fasted) showed a negative correlation between plasma glucose concentration and islet MAO activity with PEA (r = -.65, P < .02) and DA (r = -.66, P < .02), respectively. Further, a positive correlation (r = +.58, P < .05) was found between glucose level and islet MAO activity when using serotonin as substrate. There was no difference in islet MAO activity with PEA and DA as substrates in fed obese versus fed lean mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Glucose/metabolismo , Hiperglicemia/enzimologia , Ilhotas Pancreáticas/enzimologia , Monoaminoxidase/metabolismo , Obesidade/enzimologia , Animais , Glicemia/análise , Técnicas de Cultura , Modelos Animais de Doenças , Dopamina/metabolismo , Jejum/metabolismo , Feminino , Hiperglicemia/sangue , Insulina/sangue , Masculino , Camundongos , Camundongos Obesos , Obesidade/sangue , Fenetilaminas/metabolismo , Serotonina/metabolismoRESUMO
Changes in the content of monoamines such as dopamine (DA) and serotonin (5-HT) in the insulin granules are known to influence insulin release. The monoamines are inactivated by monoamine oxidase (MAO), a hydrogen peroxide-generating enzyme, which may be of importance for the redox state of the beta-cell. We studied the action of two different insulin secretagogues, the beta 2-adrenoceptor agonist terbutaline and glucose, on islet MAO activity and the plasma levels of insulin and glucose. MAO was assayed with 5-HT, DA, and beta-phenylethylamine as substrates. At 6 min (but not at 2 or 30 min) after terbutaline injection, marked increases of islet MAO activity and the plasma insulin levels were recorded. The plasma glucose levels were of the same magnitude at all time points. Injection of glucose moderately suppressed enzyme activity at 2 min. This occurred concomitantly with the peak increase in plasma levels of insulin and glucose. At 60 min, when the plasma levels of glucose and insulin were restored to basal, a slight increase in MAO activity was observed. At 2 min after injection of different doses of glucose mixed with a maximal dose of terbutaline, the insulin secretory response was either increased (submaximal glucose dose) or unaffected (maximal dose of glucose) by the beta 2-adrenoceptor stimulator. However, when a maximal dose of glucose was given at 6 min after terbutaline, i.e., when islet MAO activity was increased, the insulin response to glucose was suppressed. Starvation for 24 h induced an increase in islet MAO activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Glucose/farmacologia , Insulina/metabolismo , Ilhotas Pancreáticas/enzimologia , Monoaminoxidase/metabolismo , Receptores Adrenérgicos beta/efeitos dos fármacos , Animais , Jejum , Feminino , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Camundongos , Terbutalina/farmacologiaRESUMO
It has been shown that the pancreatic beta-cell monoamines are located in the secretory granules, and that they have an inhibitory influence on insulin secretion. Monoamines are inactivated by the enzyme, monoamine oxidase. We now studied in vivo the relation between adrenergic and cholinergic stimulation, insulin secretion and islet monoamine oxidase activity in the mouse. Monoamine oxidase was assayed with three different substrates, serotonin, dopamine and beta-phenylethylamine. The alpha 2-adrenoceptor agonist, clonidine, induced a moderate inhibition (12-18%) of islet monoamine oxidase activity, accompanied by reduced plasma insulin and elevated plasma glucose levels. The alpha 1-adrenoceptor agonist, phenylephrine, did not induce any changes in these parameters. A marked insulin release following the injection of a maximal dose of the beta 2-adrenoceptor agonist, terbutaline, was accompanied by an increase (30-50%) in islet monoamine oxidase activity. The largest increase in monoamine oxidase activity was observed with serotonin as substrate (50%). These effects on insulin secretion and monoamine oxidase activity could not be blocked by clonidine. Similarly, injection of the non-selective alpha-adrenoceptor agonist, adrenaline, which unlike clonidine does not penetrate the blood-brain barrier, had no effect on insulin release induced by a maximal dose of the nonselective beta-adrenoceptor agonist, isoprenaline. Adrenaline, however, markedly suppressed the insulin release induced by a maximal dose of glucose. Cholinergic muscarinic stimulation by a maximal insulin releasing dose of carbachol did not affect islet monoamine oxidase activity. The results suggest that beta 2-adrenoceptor stimulation of islet monoamine oxidase activity reduced the monoamine content and thereby facilitated the release of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Clonidina/farmacologia , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/enzimologia , Monoaminoxidase/metabolismo , Terbutalina/farmacologia , Animais , Glicemia/efeitos dos fármacos , Feminino , Injeções Intravenosas , Insulina/sangue , Secreção de Insulina , Camundongos , Especificidade por SubstratoRESUMO
Previous studies have shown that the amine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is rapidly converted to its corresponding amine, dopamine, in islet beta-cells. In the present investigation, we studied the effect of acute L-DOPA administration on islet monoamine oxidase (MAO) activity and on glucose-induced insulin secretory response in mice. It was observed that at 2 min after intravenous L-DOPA administration, there was a marked increase (+35%) in islet MAO activity, with serotonin as substrate. At 7 min, MAO activity towards dopamine was enhanced by 32% and that towards serotonin and phenylethylamine (PEA) was decreased by 23 and 25%, respectively. The inhibitor of L-aromatic amino acid decarboxylase, benserazide, abolished L-DOPA-induced changes of MAO activity, suggesting that the formed dopamine, and not L-DOPA itself, was responsible for the observed effects. At 60 min, no effect by L-DOPA administration on islet MAO activity was noticed. L-DOPA (125 or 250 mumol/kg), given together with glucose, induced a decrease in glucose-induced insulin response. L-DOPA (125 mumol/kg), given 7 min before glucose, totally suppressed glucose-induced insulin response. This inhibition was eliminated through pretreatment with benserazide. Enhancement of glucose-stimulated insulin response, after deposition of horseradish peroxidase (HRP) in beta-cell vacuolar system, was suppressed by L-DOPA. We conclude that acute L-DOPA-induced dopamine accumulation in pancreatic islets is accompanied by rapid changes in MAO activity, concomitant with an inhibitory effect on glucose-stimulated insulin response. Increased hydrogen peroxide production, following increased MAO activity, may possibly augment the inhibitory effect of dopamine accumulation on insulin release.
Assuntos
Glucose/farmacologia , Insulina/metabolismo , Ilhotas Pancreáticas/enzimologia , Levodopa/farmacologia , Monoaminoxidase/metabolismo , Animais , Benserazida/farmacologia , Feminino , Injeções Intravenosas , Ilhotas Pancreáticas/metabolismo , Levodopa/administração & dosagem , Camundongos , Pâncreas/efeitos dos fármacos , Pâncreas/enzimologia , Pâncreas/metabolismoRESUMO
Male rats were injected with ethanol (groups 3 and 5; 2.0 g/kg i.p.) or saline (groups 2 and 4) once a week for 52 weeks. The rats had access to ethanol as a voluntary choice for 24 h either once 6 days after the injection (groups 2 and 3) or twice 3 and 6 days after the injection (groups 4 and 5). At the beginning of the treatment ethanol injections inhibited voluntary ethanol intake if tested 6 days later (groups 3 and 5), but a tolerance developed to this inhibition. During tolerance development the rats in group 5 also drank less ethanol on day 3 than on day 6. No corresponding behaviour was seen in group 4. Thus part of the tolerance was a gradual reduction of the duration of inhibition. During the evaluation period (25 weeks) after the treatment, ethanol exposure (20 weeks) consisted of a continuous choice between ethanol and water. Of different ethanol concentrations both ethanol-injected groups (3 and 5) took the same voluntary dose of ethanol independent of the offered concentration. After 5 weeks without ethanol all rats were killed and a number of neurochemical variables were determined. Compared with almost unexposed rats (group 1) changes were seen in inositol phospholipid breakdown, muscarinic binding sites in hippocampus, noradrenaline concentrations in frontal cortex, hippocampus and hypothalamus, dopamine concentration in frontal cortex and 5-hydroxytryptamine concentration in hypothalamus. In most cases the largest changes were seen in group 5. None of the variables had a constant relation to ethanol intake in the total population. However, significant correlations were found in some of the groups.
Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Alcoolismo/fisiopatologia , Encéfalo/fisiopatologia , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Mapeamento Encefálico , Dopamina/fisiologia , Etanol/administração & dosagem , Ácido Homovanílico/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Injeções Intraperitoneais , Masculino , Monoaminoxidase/metabolismo , Norepinefrina/fisiologia , Ratos , Ratos Endogâmicos , Serotonina/fisiologiaRESUMO
Male rats were treated with one ethanol (2.0 g/kg i.p.) or saline injections once a week for 50 weeks. During this treatment period the rats had in addition access to ethanol (10% in drinking fluid) as a choice against water for 24 h prior to the injection. During the following evaluation period, animals had a continuous choice between ethanol and water and the concentration of the ethanol solution increased every 3rd week from 5 to 10, 15 and 25%, with 10% as a reference tested between the other concentrations. The animals were killed after an abstinence of 4 weeks, whereupon the concentrations of noradrenaline (NA), dopamine (DA), serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) were determined in the frontal cortex. In the remaining cerebral cortex, activity of monoamine oxidase, reuptake of NA and stimulated inositol phospholipid (PI) breakdown was also determined. Muscarinic binding sites were determined in the striatum. During treatment, saline injected rats had a constant voluntary 24 h ethanol intake. There was a decrease in the corresponding intake in the animals given the ethanol injections. The diminishing of the intake was more marked in rats starting treatment at an age of 19.4 weeks when compared to rats starting at an age of 5.4 weeks. In the evaluation period the ethanol intake was fairly constant for all groups. However, the regressions between intake of the reference concentration when plotted against the different tested concentrations were most marked in the group where ethanol injections started at an early age. In the total material there were significant F-values when concentrations of NA, 5-HIAA, 5-HT/5-HIAA in the cortex and muscarinic binding sites in the striatum were tested. Age could not be excluded as a contributing factor, but for muscarinic binding sites in the striatum, concentrations of DA and 5-HIAA in the cortex, and potassium stimulated PI breakdown in the cortex significant regressions with voluntary ethanol intake as dependent variable could be established. Since these intakes are stable, a causal relation with dependence may be involved.
Assuntos
Consumo de Bebidas Alcoólicas/fisiologia , Encéfalo/efeitos dos fármacos , Etanol/administração & dosagem , Neurotransmissores/metabolismo , Receptores de Neurotransmissores/efeitos dos fármacos , Fatores Etários , Alcoolismo/patologia , Animais , Encéfalo/patologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Masculino , Ratos , Ratos EndogâmicosRESUMO
Rats were tested for place learning in the Morris swim maze on days 110-114 of abstinence following 48 weeks of treatment with sodium barbital. A retarded acquisition of the swim-maze task, that could not be ascribed to motor impairments, was found in the barbital-treated rats. There was a significant difference in brain weight, but there were no significant differences between the control and barbital-treated rats in the frontal cortical concentrations of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), nor in the intra- and extrasynaptosomal activities of cerebral cortical monoamine oxidase towards NA and 5-HT. Postsynaptically, neither the cerebral cortical inositol phospholipid breakdown responses to carbachol and NA (mediated by muscarinic and alpha 1-adrenergic receptors, respectively), nor the striatal and cortical densities of muscarinic receptors labelled by [3H]quinuclidinyl benzilate [( 3H]QNB) were found significantly to be altered in the barbital-treated rats. A strong correlation between the density of striatal and cortical [3H]QNB binding sites was seen for the barbital-treated (r = 0.91) but not for the control (r = -0.05) rats. It is suggested that the deficit in performance of the barbital-treated rats in the Morris maze may be related to a cholinergic dysfunction.
Assuntos
Barbital/administração & dosagem , Barbitúricos/administração & dosagem , Desempenho Psicomotor/efeitos dos fármacos , Síndrome de Abstinência a Substâncias/fisiopatologia , Animais , Aminas Biogênicas/metabolismo , Química Encefálica/efeitos dos fármacos , Carbacol/farmacologia , Fosfatos de Inositol/farmacologia , Masculino , Monoaminoxidase/metabolismo , Norepinefrina/farmacologia , Ratos , Ratos Endogâmicos , Natação , Fatores de TempoRESUMO
The effect of ovariectomy on longitudinal bone growth was studied in growing rats. The operation was performed at ages 20, 40, and 60 days. Sham operations were made at age 40 days. At different postoperative intervals, the growth rate was determined with the tetracycline technique, and the width of the growth plate was registered. After a slight initial retardation, the growth rate after ovariectomy was significantly greater than in normal rats during a 40-60 day period. During the same period, the growth plate was wider. The increase in growth rate was greater and more rapid if ovariectomy was performed in older animals. The results indicate that ovariectomy increases longitudinal bone growth and that longitudinal bone growth and skeletal maturation depend less on ovarial function in young animals than that in more mature animals.
Assuntos
Desenvolvimento Ósseo , Castração , Fatores Etários , Animais , Feminino , Ratos , Ratos Endogâmicos , Tetraciclina , Tíbia/crescimento & desenvolvimentoRESUMO
The aim of this study was to evaluate if ketanserin, a selective serotoninantagonist, could improve wound healing in diabetic patients with foot ulcers and severe peripheral vascular disease. In a double blind study 40 diabetic patients with foot ulcer and a systolic toe pressure below 45 mmHg were randomly allocated to either ketanserin (20-40 mg three times a day) or placebo for a period of 3 months. The treatment was carried out on an out-patient basis by a combined medical/orthopedic foot care team at the Department of Internal Medicine, University Hospital, Lund, Sweden. Both groups were comparable regarding age, sex, duration and treatment of diabetes, cardiovascular disease and type of lesion. Wound healing (defined as intact skin for at least 3 months) or wound size reduction of 50% or more were sen in 11 out of 19 (58%) in the ketanserin group and in 7 out of 19 (37%) in the placebo group. Gangrene developed in 6 patients with placebo and 2 with ketanserin. Two patients died during the study and their ulcers were not evaluated. The systolic toe pressure was measured at admission, at end of run in, after 1 month and 3 months with strain gauge technique. Only one out of nine patients (11%) with a toe pressure below 30 mmHg in the placebo group healed or improved their ulcers compared to nine out of 16 (56%) in the ketanserin group. The healing rate in the ketanserin group was higher than expected considering the lower systolic toe pressure in this group compared to placebo at randomization (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Angiopatias Diabéticas/tratamento farmacológico , Doenças do Pé/tratamento farmacológico , Ketanserina/uso terapêutico , Úlcera Cutânea/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Idoso , Angiopatias Diabéticas/complicações , Método Duplo-Cego , Feminino , Doenças do Pé/etiologia , Humanos , Masculino , Úlcera Cutânea/etiologiaRESUMO
Clinical characteristics and outcome in 223 consecutive diabetic patients with deep foot infections are reported. Patients were treated by a multidisciplinary diabetic foot-care team at the University Hospital, Lund, Sweden, and were prospectively followed until healing or death. About 50% of patients lacked clinical signs of infection, such as a body temperature > 37.8 degrees C, a sedimentation rate > 70 mm/hour, and white blood cell count (WBC) > 10 x 10(9)/liter. Eighty-six percent had surgery before healing or death. Thirty-nine percent healed without amputation; 34% healed after a minor and 8% after a major amputation. Sixteen percent were unhealed at death, and 3% were unhealed at the end of the observation period. Of those unhealed at death or follow-up, 4 patients had had a major and 11 a minor amputation. After correction for age and sex, duration of diabetes < 14 years, palpable popliteal pulse, a toe pressure > 45 mmHg, and an ankle pressure > 80 mm Hg, absence of exposed bone and a white blood cell count < 12 x 10(9)/liter were all related to healing without amputation in a logistic regression analysis. We conclude that although only 1 in 10 had a major amputation, nearly all diabetic patients with a deep foot infection needed surgery and more than one third had a minor amputation before healing or death in spite of a well-functioning diabetic foot-care team responsible for all included patients.
Assuntos
Pé Diabético/cirurgia , Infecções/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Pé Diabético/terapia , Feminino , Humanos , Infecções/classificação , Infecções/terapia , Masculino , Pessoa de Meia-Idade , Osteomielite/cirurgia , Estudos Prospectivos , Resultado do TratamentoRESUMO
All patients operated upon for Morton's neuroma during 1991 who were examined with both magnetic resonance imaging and ultrasonography were included in this prospective study. The object of the study was to evaluate the diagnostic value of these two modalities. The preoperative diagnosis was purely clinical. Histology confirmed surgical findings. A 0.3 T scanner was used for the magnetic resonance imaging, and a 7.5 MHz linear transducer was used for the ultrasonography. The study includes nine patients. Eight neuromas were found at surgery. Of these, only five were diagnosed with magnetic resonance imaging and three with ultrasonography. This indicates that false negative diagnoses are common. At present we find these modalities of little or no value, but, with improved equipment and experience, they may become valuable.
Assuntos
Imageamento por Ressonância Magnética , Ossos do Metatarso/patologia , Neuroma/diagnóstico , Neoplasias do Sistema Nervoso Periférico/diagnóstico , Adulto , Feminino , Seguimentos , Humanos , Masculino , Ossos do Metatarso/cirurgia , Pessoa de Meia-Idade , Neuroma/cirurgia , Neoplasias do Sistema Nervoso Periférico/cirurgia , Cuidados Pré-Operatórios , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
Eight hallux valgus patients were marked with tantalum markers in conjunction with hallux valgus surgery (seven proximal osteotomies and one chevron osteotomy). Changes on weightbearing before surgery as well as corrective changes after surgery were analyzed with roentgen stereophotogrammetry (RSA) and with standard x-rays. RSA is accurate to 0.6 degrees in rotational changes and 0.3 mm in translation. Weightbearing changes were inconsistent, and minimal with both standard x-rays and RSA. It was possible to analyze the correction at the osteotomy site with RSA. In half the cases, the correction measured by RSA corresponded with that measured with standard x-rays, within measurement error; in the other cases, RSA showed that the correction was of a different size or direction than that measured on standard x-rays. Corrective changes in hallux valgus surgery are complex, including angular and translational changes at several levels and in several joints in order to produce a clinical resultant. Rotational changes can be evaluated with RSA. Although RSA in an optimal situation is very accurate, it is still limited to a laboratory setting.