RESUMEN
We studied the levels of lymphocyte surface-associated sialylglycans and the expression of neuraminidase NEU1 and sialyltransferase ST6GAL1 genes in lymphocytes in erythremia patients and healthy donors as well as the levels of sialic acids in plasma and sialylation of alpha-acid glycoprotein and fibronectin. Moreover, we also investigated the type of sialic acids binding with its glycans using sialospecific lectins MAA and SNA. fibronectin protein in lymphocytes and its cell surface in erythremia disease as compared to healthy donors. It was shown that the levels of free sialic acids and neuraminidase activity in plasma are increased in erythremia disease as compared to healthy donors; however, MAA-II-binding activity of tested glycoproteins is decreased, fibronectin-1 mRNA expression in lymphocytes is increased in patients with erythremia. The decreasing of plasma fibronectin concentration and its heparin-binding activity as well as increasing of lymphocyte content with surface-associated and intracellular fibronectin were revealed in erythremia disease in comparison with healthy donors. Positive correlation between plasma fibronectin level and its heparin-binding activity and negative correlation between plasma fibronectin level and quantity of lymphocytes which express fibronectin inside the cell and on cell surface was detected. Enhanced levels of α2,3- and α2,6-linked residues of glycocojugates were detected on lymphocyte cell surface in erythremia disease using sialospecific lectins and flow cytometer as well as fluorescent confocal microscope. The level of NEU1 and ST6GAL1 mRNA expressions is significantly increased in lymphocytes in erythremia disease. Results of this study are clarified the mechanisms of disturbed in erythremia disease glycobiological processes and may therefore present new approaches for therapeutic opportunities.
Asunto(s)
Antígenos CD/metabolismo , Membrana Celular/metabolismo , Linfocitos/metabolismo , Neuraminidasa/metabolismo , Policitemia Vera/metabolismo , Procesamiento Proteico-Postraduccional , Ácidos Siálicos/metabolismo , Sialiltransferasas/metabolismo , Anciano , Antígenos CD/genética , Estudios de Casos y Controles , Membrana Celular/química , Membrana Celular/patología , Femenino , Fibronectinas/genética , Fibronectinas/metabolismo , Expresión Génica , Heparina/metabolismo , Humanos , Lectinas/metabolismo , Linfocitos/química , Linfocitos/patología , Masculino , Persona de Mediana Edad , Neuraminidasa/genética , Orosomucoide/genética , Orosomucoide/metabolismo , Policitemia Vera/genética , Policitemia Vera/patología , Unión Proteica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Sialiltransferasas/genéticaRESUMEN
This review is devoted to the action of amyloid-beta peptide on the functional activity of intracellular and plasmalemmal calcium-regulated structures in cultured hyppocampal neurons: mitochondria and voltage-gated calcium channels. A comparative analysis of relative changes of plasmalemmal structures in such neurodegenerative diseases as Alzheimer's illness and diabetic neuropathy has been made.
Asunto(s)
Enfermedad de Alzheimer/etiología , Señalización del Calcio , Neuropatías Diabéticas/etiología , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/farmacología , Animales , Canales de Calcio/metabolismo , Señalización del Calcio/fisiología , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Neuropatías Diabéticas/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , RatasRESUMEN
In experiments on mice of lines C57BL/6J and CBA/CaLac, the possibility of strengthening of analgesic effect of corvitin by the action of red polarized light (PL) on the acupoint (AP) E-36 was studied. The pain behavioral response (licking of the painful area) was caused by injection of 5% formalin in hind limb (0.25 microl subcutaneously). The duration of pain response was studied before and after systemic introduction of corvitin (10 mg/kg, intraperitoneal) or joint use of corvitin and red PL (10 minute session). It is established, that after application of red PL on the antinociceptive AP E-36 in all animals an authentic strengthening of antinociceptive effect of corvitin takes place. In C57BL/6J mice, application of corvitin alone weakened the pain response by 29.7% and during combined use of red PL and corvitin, it grew up to 53.1%. Mice of line CBA/CaLac were less sensitive both to corvitin, and PL. In this line, corvitin used alone reduced the duration of pain response by 14%, and by 32.4% during combined use with red PL. Non-traumatic, without side effects, the method of influence by low-intensive PL can be recommended to patients accepting corvitin for strengthening its efficiency.
Asunto(s)
Puntos de Acupuntura , Analgésicos/uso terapéutico , Flavonoides/uso terapéutico , Luz , Manejo del Dolor , Analgésicos/administración & dosificación , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/efectos de la radiación , Terapia Combinada , Flavonoides/administración & dosificación , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Dolor/tratamiento farmacológico , Dimensión del Dolor , Umbral del Dolor , Especificidad de la EspecieRESUMEN
Anomalous accumulation of beta-amyloid peptide in cerebral neurons plays central role in pathogenesis of Alzheimer's disease (AD). One of the essential pathogenetic factors at AD is disturbance of calcium homeostasis in neurons of central nervous system. It was determined in this work that 24-hour incubation of hippocampal cell culture with beta-amyloid peptide caused more than twofold elevation of basal calcium concentration relatively to control value (153.4 +/- 11.5 and 71.7 +/- 5.4 nM respectively; P < 0.05, n=7). Using whole cell patch-clamp technique it was detected that calcium current density in beta-amyloid-treated cells was 70% higher (P < 0.05, n=12) than in control ones. Obtained data broaden our comprehension of disturbance of molecular mechanisms of calcium homeostasis in neurons in AD, particularly mechanisms of elevation of basal calcium concentration by means of enhancement of calcium influx through plasmalemmal voltage-gated calcium channels.
Asunto(s)
Péptidos beta-Amiloides/farmacología , Canales de Calcio/metabolismo , Calcio/metabolismo , Membrana Celular/efectos de los fármacos , Hipocampo/efectos de los fármacos , Neuronas/efectos de los fármacos , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/fisiología , Animales , Señalización del Calcio/efectos de los fármacos , Técnicas de Cultivo de Célula , Membrana Celular/metabolismo , Células Cultivadas , Hipocampo/citología , Hipocampo/metabolismo , Homeostasis , Masculino , Neuronas/citología , Neuronas/metabolismo , Técnicas de Placa-Clamp , Ratas , Ratas WistarRESUMEN
The review considers the structure and function of high-and low-voltage potential activated calcium channels in sensory neurons. A special attention is paid to compression of the function of these channels in normal conditions and during development of pathological conditions. The role of low-voltage activated T-type calcium channels during such forms of pathology as neuropathy, acidosis and alkalosis because the changes in synaptic transmission occurring during these forms of pathological changes are most intensively altered during changes in functional structures of these type of channels. During studying of high-voltage activated calcium channels main attention has been concentrated on changes in the function of N-type potential activated calcium channels.
Asunto(s)
Acidosis , Alcalosis , Canales de Calcio Tipo N/metabolismo , Canales de Calcio Tipo T/metabolismo , Neuralgia , Neuronas Aferentes , Acidosis/metabolismo , Acidosis/patología , Potenciales de Acción/fisiología , Alcalosis/metabolismo , Alcalosis/patología , Animales , Canales de Calcio Tipo N/fisiología , Canales de Calcio Tipo T/fisiología , Humanos , Neuralgia/metabolismo , Neuralgia/patología , Neuronas Aferentes/metabolismo , Neuronas Aferentes/patologíaRESUMEN
The review describes the mechanisms of function and regulation of store-operated (so called SOC) channels and their connections with different intracellular calcium regulating structures. The function of both ryanodine sensitive and inisitol-1,3-phosphate sensitive endoplasmic reticulum are presented. The mechanisms of their connections with mitochondria and potential-activated channels are shown. Main attention is concentrated on compensatory calcium entry (CCE) connected with depletion of endoplasmic reticulum, the role of different transient receptor potential (TRP) channels in this process and possible mechanisms of their activation.
Asunto(s)
Señalización del Calcio , Membrana Celular/metabolismo , Retículo Endoplásmico/metabolismo , Mitocondrias/metabolismo , Animales , HumanosRESUMEN
We studied the dynamic contribution of endoplasmic reticulum and mitochondria to depolarization-induced Ca2+ transients in small (18-24 microm) DRG neurons of rats. We have used the application of 10 microM of mitochondrial protonophore CCCP for switching off the calcium uptake by mitochondrial uniporter. For depletion of the store of endoplasmic reticulum we applied 1 microM of thapsigargin. Depolarization-induced transients in control conditions and in conditions when one of the mechanisms (mitochondria or endoplasmic reticulum) does not participate in the forming of the shape of Ca2+ transient have been studied. This allowed us to clarify the kinetics of mitochondrial and endoplasmic reticulum uptake and release of calcium in the process of the neuronal activity. We have determined the main characteristics of functioning of above-named calcium stores in the process of cell excitation, such as time of the beginning of uptake, time and duration of maximum activity etc. We concluded, that mitochondria and endoplasmic reticulum are acting in opposite directions at least in the phase of the beginning of the transient. Mitochondria are limiting the amplitude of the transient during depolarization, at the same time the endoplasmic reticulum is increasing the amplitude of the transient by CICR (calcium-induced calcium release) mechanism. Mitochondria store calcium released from endoplasmic reticulum by application of 30 mM caffeine. Inhibition of the mitochondrial uniporter results in reduction of amplitude of repetitive caffeine application compared with control conditions. We have compared the kinetics of mitochondrial participation in the formation of calcium signal when the initial sources of calcium ions were different. Our results allow us to suggest a close functional dynamic interactions between mitochondria and endoplasmic reticulum during calcium signaling in sensory neurons.
Asunto(s)
Señalización del Calcio/fisiología , Calcio/metabolismo , Membrana Celular/metabolismo , Ganglios Espinales/citología , Neuronas Aferentes/metabolismo , Animales , Cafeína/farmacología , Señalización del Calcio/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Membrana Celular/fisiología , Células Cultivadas , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/fisiología , Ganglios Espinales/metabolismo , Ganglios Espinales/fisiología , Cinética , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/fisiología , Neuronas Aferentes/efectos de los fármacos , Neuronas Aferentes/fisiología , RatasRESUMEN
Spontaneous neuronal activity was studied in rat hippocampal cell cultures using patch clamp technique in cell-attached or loose-patch configuration. It was found that in spite of relatively low average frequency (1-2 Hz) of neuronal activity in the cell cultures, neurons often fire doublets or triplets of action potentials with interspike interval of 60 ms and less. Interspike interval histograms were substantially better fitted by double exponential decay functions than by single exponential ones. On average, estimated decay time constant for the fits were tau1 approximately 36, ms and tau2 approximately 1000 ms respectively. Spontaneous neuronal firing to a large extent depended on glutamatergic excitation and GABA(A)ergic inhibition: a blocker of AMPA/kainate receptor CNQX (10 microM) either substantially decreased or completely blocked spontaneous action potentials; a blocker of GABA(A) receptors bicuculine (10 microM) increased neuronal firing. Effect of glucose deprivation on action potential frequency was also studied. It was found that glucose deprivation reduces AP frequency to 25% of control. Taken together, these results support an idea that hypoglycaemia alters synaptic transmission in hippocampus.
Asunto(s)
Antagonistas de Aminoácidos Excitadores/farmacología , Glucosa/metabolismo , Hipocampo/metabolismo , Neuronas/metabolismo , Transmisión Sináptica/efectos de los fármacos , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Potenciales de Acción/efectos de los fármacos , Animales , Animales Recién Nacidos , Bicuculina/farmacología , Células Cultivadas , Antagonistas de Receptores de GABA-A , Hipocampo/citología , Hipocampo/fisiología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Técnicas de Placa-Clamp , Ratas , Ratas Wistar , Receptores AMPA/antagonistas & inhibidores , Receptores de Ácido Kaínico/antagonistas & inhibidoresRESUMEN
A comparative study of behavioral reactions (licking of back paw, sleeping, eating, running, washing) in mice with a genetic knockout (lines C57BL/6L and CBA/CaLac) and in control animals was carried out. Experiments have been performed in control conditions (without any influences), after a subcutaneous injection of 5% formalin solution, and also in a case when animals before an injection of formalin received analgin. It was established that the behavior of mice with a genetic knockout without any influences statistically authentically differs from mice without genotype infringements. Sleep duration in mice with a genetic knockout was 3-4 times less, and duration of eating was 5-13 times less than in control animals, but grooming (washing) was more intensive (in 2.4 times). Duration of painful reaction (licking of back paw) in response to formalin injection in mice with a genetic knockout was in 1.3 - 2.4 times less, than in mice of control group. Analgin in a doze of 8.3 mg/kg in genetic knockout mice suppressed pain more poorly, than in mice of control group. Analgesia incontrol group amounted 74.10%, and in genetic knockout mice it was 27.6-28.9%. The results allow concluding that mice with a genetic knockout differ from control animals both by initial behavior, and by reaction to a tonic pain. Analgin causes a weaker analgesic action in mice with a genetic knockout in comparison with animals of control group.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Conducta Animal/fisiología , Dipirona/uso terapéutico , Dolor/genética , Animales , Genotipo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Noqueados , Dolor/tratamiento farmacológico , Dolor/fisiopatología , Dimensión del Dolor , Especificidad de la EspecieRESUMEN
Dark repair of DNA was studied in embryos excised from the advanced sugar beet seeds. Significant increase (from 19 to 321%) in the level of dark DNA repair has been established for all studied conditions of the advanced treatment. Acute -irradiation has been used to investigate the ability of advanced seeds to repair additional DNA damages caused by a standard irradiation dose. It has been concluded that irradiation factor allows to test capacity of DNA repair systems. The later, we suggest, can be used to define the optimal conditions for the seed advancement.
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Reparación del ADN/efectos de la radiación , Semillas/efectos de la radiación , Beta vulgaris/embriología , Beta vulgaris/efectos de la radiación , ADN/biosíntesis , ADN/efectos de la radiación , Daño del ADN/efectos de la radiación , Oscuridad , Radiación IonizanteRESUMEN
Here we summarises the results of experimental investigation of changes in intracellular calcium homeostasis in sensory neurones of rats with streptozotocin-induced diabetes mellitus. Decrease in the calcium-accumulating function of both inositol-trisphosphate- as well as caffeine-sensitive endoplasmic reticulum has been detected both in primary sensory neurones of dorsal root ganglia and in secondary neurones of the spinal cord dorsal horn. Predominant depression in the functioning of metabotropic receptors of ligand-gated channels compared with those of ionotropic ones has been demonstrated. Changes in the pharmacological sensitivity of potential-operated calcium channels (predominantly of L-type), linked, probably, with alterations of functional connections between membrane channels and endoplasmic reticulum, are described. A predominant role of changes in the functioning of intracellular Ca(2+)-accumulating structures, leading to prolongation of depolarisation-induced Ca2+ transients in primary and secondary sensory neurones and corresponding changes in the transmission of nociceptive signals during diabetic neuropathy are discussed.
Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Ganglios Espinales/fisiopatología , Neuronas Aferentes/fisiología , Células del Asta Posterior/fisiopatología , Animales , Cafeína/farmacología , Calcio/metabolismo , Canales de Calcio Tipo L/metabolismo , Señalización del Calcio , Diabetes Mellitus Experimental/patología , Retículo Endoplásmico/metabolismo , Fosfatos de Inositol/farmacología , Neuronas Aferentes/patología , Ratas , Ratas Wistar , EstreptozocinaRESUMEN
The changes in neuronal Ca2+ homeostasis were studied on dorsal horn neurons from spinal cord rat slices and freshly isolated dorsal root ganglion neurons of mice in control condition and under streptozotocin (STZ)-induced diabetes. The cytoplasmic free Ca2+ concentration ([Ca2+]i) was measured using fura-2 and indo-1 based microfluorimetry. The recovery of depolarization-induced [Ca2+]i increase was delayed in diabetic neurons compared with normal animals. The amplitude of calcium release from caffeine-sensitive endoplasmic reticulum calcium stores became significantly smaller in diabetic neurons. The participation of mitochondria in [Ca2+]i homeostasis was determined by investigation of changes which occurred after addition of mitochondrial protonophore (CCCP) to the extracellular solution. In control cells 10 (M CCCP applied before membrane depolarization induced an increase of the amplitude of depolarization-induced [Ca2+]i transients and disappearance of their delayed recovery, indicating the participation of mitochondria in fast uptake of Ca2+ ions from the cytosol during the peak of the transient and subsequent slow release them back during its decay. In neurons from diabetic animals the increase of the peak transient amplitude under the action of CCCP became diminished, and the delayed elevation of [Ca2+]i disappeared in small size neurons. We conclude that streptozotocin-induced diabetes is associated with prominent changes in the mechanisms responsible for [Ca2+]i regulation in neurones of the nociceptive system, which presumably include a slow down of Ca2+ elimination from the cytoplasm by endoplasmic reticulum and mitochondria.
Asunto(s)
Calcio/fisiología , Diabetes Mellitus Experimental/fisiopatología , Nociceptores/fisiopatología , Transducción de Señal/fisiología , Animales , Citosol/fisiología , Colorantes Fluorescentes , Fura-2 , Ganglios Espinales/fisiopatología , Indoles , Ratones , Neuronas/fisiología , Ratas , Médula Espinal/fisiopatologíaRESUMEN
As many as 120 neonates and their mothers presenting with persistency of cytomegaly virus were studied for impact of maternal specific antibodies to cytomegaly virus on rhe pattern of clinical adaptation in children. 90% of children born of infected mothers display neurologic disturbances, 71.4% have jaundice accompanied by hyperbilirubinemia, 4.7% present with hemorrhagic syndrome. 11 neonates were diagnosed as having cytomegaloviral infection, four such diagnoses were made in a pathoanatomical setting. Thus, the studies made suggest that cytomegaly virus might be neurotrophic and that maternal specific antibodies have negative impact on postnatal adaptation of neonates.
Asunto(s)
Adaptación Fisiológica/inmunología , Infecciones por Citomegalovirus/inmunología , Complicaciones Infecciosas del Embarazo/inmunología , Adulto , Anticuerpos Antivirales/sangre , Especificidad de Anticuerpos , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/congénito , Infecciones por Citomegalovirus/fisiopatología , Femenino , Humanos , Recién Nacido , EmbarazoRESUMEN
The review summarizes experimental and clinical data about the influence of Lactobacillus on the immune system. A conclusion is made that the effect of Lactobacillus is a multifactor process. After entering the intestinal tract live microorganisms or biologically active substances produced by them may activate specific and nonspecific systems of microorganism protection. Experimental and clinical data about the action of Lactobacillus as adjuvants to the humoral immune response are presented. The mechanisms of anticancerogenic action of Lactobacillus and their cell wall components are analyzed in detail. The prospects for the use of Lactobacillus as probiotics in medicine are considered. The conclusion about positive value of the multifactor action of these microorganisms on the human immune system is made, since no negative effects are evoked by the discussed mechanisms of specific effect of Lactobacillus. This opens wide possibilities for the development of application schemes of probiotics from lactobacillus for the stimulation of several functions of the immune system, creation a new forms of antitumor drugs and combination of them with oral vaccines for improving their immunogenicity.
Asunto(s)
Sistema Inmunológico/inmunología , Lactobacillus/inmunología , Animales , Sistema Digestivo/inmunología , Sistema Digestivo/microbiología , Humanos , Sistema Inmunológico/microbiología , Inmunización , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiologíaRESUMEN
The mechanisms of protective action of Lactobacillus have been studied during development of the generalized infection induced by Klebsiella pneumoniae in CBA mice after weaning. The mice were infected intragastrically during the first day after weaning (1 x 10(9) bacterias per mice). Suspensions of Lactobacillus were introduced before and after infection during 10 days (1 x 10(6) bacterias per mice). It has been shown that introduction of Lactobacillus substantially decreased the level of the gut contamination by Klebsiella, prevented generalization of infection and death of animals. Significant higher levels of IgA in the blood serum, IgA and IgM in the gut content, percentage of splenocytes, expressing surface IgM and IgG were observed on the 7th day as compared with those in animals without Lactobacillus. Significantly lower percentage of splenocytes, expressing CD4 antigen was also observed. On the 11th day after infection the mice receiving lactobacillus have shown a tendency to an increase of IgA in the gut content, significantly lower concentrations of IgM in the gut content and a higher level of IgA to the blood serum as compared with the control. Other characteristics were comparable to those of the control group. A conclusion is made that introduction of Lactobacillus prevents development of the Klebsiella infection and protects the immune system from excessive antigenic action.
Asunto(s)
Enfermedades Intestinales/prevención & control , Infecciones por Klebsiella/prevención & control , Klebsiella pneumoniae , Lactobacillus acidophilus , Animales , Animales Recién Nacidos , Antígenos CD4/metabolismo , Inmunoglobulina A/metabolismo , Inmunoglobulina G/metabolismo , Inmunoglobulina M/metabolismo , Enfermedades Intestinales/metabolismo , Enfermedades Intestinales/microbiología , Infecciones por Klebsiella/metabolismo , Ratones , Ratones Endogámicos CBA , SuspensionesRESUMEN
The influence of intestinal colonization by the Klebsiella pneumonia strain 50/59 on the characteristics of local and humoral immunity has been studied on CBA mice after weaning. Bacteria have been introduced intragastrally in doses of 1 x 10(6) bacteria per mice. Observations have been performed in dynamics during 11 days. They have shown that intestinal colonization induces significant elevation of the concentration of IgA in serum, intestinal content and percentage of splenocytes, expressing receptors of IgA, IgM, CD4 on the 7th day. On the 11th day a significant decrease in these parameters was observed. A conclusion is made that intestinal colonization is not indifferent for the whole organism and induces complex influences on its immune system.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Inmunoglobulina A/análisis , Inmunoglobulina M/análisis , Intestinos/inmunología , Intestinos/microbiología , Klebsiella pneumoniae , Animales , Animales Recién Nacidos , Ratones , Ratones Endogámicos CBA , DesteteRESUMEN
The review summarizes recent data about the use of calcium channel blockers for the treatment of cardiovascular complications in patients with diabetes mellitus. It is shown that disturbances of Ca ion homeostasis play an important role in the pathogenesis of such diabetic complications as cardiomyopathy, microangiopathy, hypertension and the use of modern calcium channel antagonists for their treatment seems to be quite justified. However, despite definite positive effects of such treatment, these drugs should be used with care, especially if combined with derivatives of sulphonylurea as activators of the beta-cell function. Calcium channel blockers may intervene in the mechanism of the activity of beta-cells in which activation of the calcium channels is an obligatory link for triggering insulin secretion. Nevertheless, according to most of the authors, in such cases Ca antagonists can be recommended in moderate doses under continuous control of the hormonal status of the patient.