RESUMEN
It is widely accepted that obesity is a systemic comorbidity factor in psoriasis. At the same time, there is rapidly growing evidence that the adipose tissue is not only systemically but also locally involved in the pathophysiology of psoriasis and in response to successful anti-psoriatic treatment.
Asunto(s)
Obesidad , Psoriasis , Grasa Subcutánea , Humanos , Obesidad/metabolismo , Obesidad/patología , Obesidad/fisiopatología , Psoriasis/metabolismo , Psoriasis/patología , Psoriasis/fisiopatología , Grasa Subcutánea/metabolismo , Grasa Subcutánea/patología , Grasa Subcutánea/fisiopatologíaRESUMEN
Cross-talk between the hair follicles (HFs) in different stages of their cycling and adjacent adipose tissue is a new important topic which is of both theoretical and practical interest. Objective - to analyze available data on possible interrelationship of dermal adipose tissue and hair follicle cycling. Experimental results obtained in rodents clearly demonstrate that HFs cycling is connected to adjacent dermal adipose tissue. Recently uncovered adipocyte-myofibroblast transition can be significantly involved in miniaturization of HFs and be an important pathophysiological step in androgenetic alopecia. Improvement of adipogenic environment of HFs can be important both in treatment of alopecia and in surgical hair restoration procedures.
Asunto(s)
Adipocitos/fisiología , Tejido Adiposo/citología , Alopecia/patología , Folículo Piloso/fisiología , Miofibroblastos/fisiología , Animales , HumanosRESUMEN
Very high frequency ultrasound (VHF-US) is new therapy method with a broad application spectrum in dermatology and aesthetic medicine. In this method, ultrasound waves with frequencies over 10 MHz, which were for a long time only used in ultrasound diagnostics, are applied for therapeutic purposes. Such US waves demonstrate specific biophysical efficiencies which warrant their application for the treatment of the skin efflorescences, chronic wounds and hypertrophic scars as well as in anti-aging and skin improvement procedures in aesthetic medicine. VHF-US can be applied not only for stand-alone treatments, but also as a supportive pre- and posttreatment method in combination with laser, radiofrequency currents, injection lipolysis, etc. as well as in aesthetic plastic surgery.
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Técnicas Cosméticas/tendencias , Dermatología/tendencias , Enfermedades de la Piel/terapia , Terapia por Ultrasonido/tendencias , Cicatrización de Heridas/efectos de la radiación , Medicina Basada en la Evidencia , Humanos , Resultado del Tratamiento , Ondas UltrasónicasRESUMEN
Although considerable evidence suggests that the chemical synapse is a lynchpin underlying affective disorders, how molecular insults differentially affect specific synaptic connections remains poorly understood. For instance, Neurexin 1a and 2 (NRXN1 and NRXN2) and CNTNAP2 (also known as CASPR2), all members of the neurexin superfamily of transmembrane molecules, have been implicated in neuropsychiatric disorders. However, their loss leads to deficits that have been best characterized with regard to their effect on excitatory cells. Notably, other disease-associated genes such as BDNF and ERBB4 implicate specific interneuron synapses in psychiatric disorders. Consistent with this, cortical interneuron dysfunction has been linked to epilepsy, schizophrenia and autism. Using a microarray screen that focused upon synapse-associated molecules, we identified Cntnap4 (contactin associated protein-like 4, also known as Caspr4) as highly enriched in developing murine interneurons. In this study we show that Cntnap4 is localized presynaptically and its loss leads to a reduction in the output of cortical parvalbumin (PV)-positive GABAergic (γ-aminobutyric acid producing) basket cells. Paradoxically, the loss of Cntnap4 augments midbrain dopaminergic release in the nucleus accumbens. In Cntnap4 mutant mice, synaptic defects in these disease-relevant neuronal populations are mirrored by sensory-motor gating and grooming endophenotypes; these symptoms could be pharmacologically reversed, providing promise for therapeutic intervention in psychiatric disorders.
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Dopamina/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Transducción de Señal , Transmisión Sináptica/genética , Ácido gamma-Aminobutírico/metabolismo , Animales , Antipsicóticos/farmacología , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Sinapsis Eléctricas/genética , Sinapsis Eléctricas/ultraestructura , Femenino , Genotipo , Humanos , Masculino , Ratones , Polimorfismo de Nucleótido SimpleRESUMEN
Cell survival is a stochastic process with the stochastic component being strongly dependent on the irradiation conditions. This process is described by a stochastic model which allows differentiation between the deterministic and stochastic components of survival. The proposed model is tested for four irradiation experiments (2 with ionizing radiation and 2 with ultrasound) and very good agreement with experimental results is demonstrated. It identifies the higher stochasticity of the cell survival for the temporally varying radiation fields and provides the possibility to compare the stochasticity of survival in different radiation fields.
Asunto(s)
Modelos Biológicos , Ultrasonido/efectos adversos , Animales , Muerte Celular/efectos de la radiación , Línea Celular , Supervivencia Celular/efectos de la radiación , Humanos , Ratones , Ratas , Procesos Estocásticos , Factores de TiempoRESUMEN
1. The pathogenesis of diabetic neuropathy is a complex phenomenon, the mechanisms of which are not fully understood. Our previous studies have shown that the intracellular calcium signaling is impaired in primary and secondary nociceptive neurons in rats with streptozotocin (STZ)-induced diabetes. Here, we investigated the effect of prolonged treatment with the L-type calcium channel blocker nimodipine on diabetes-induced changes in neuronal calcium signaling and pain sensitivity. 2. Diabetes was induced in young rats (21 p.d.) by a streptozotocin injection. After 3 weeks of diabetes development, the rats were treated with nimodipine for another 3 weeks. The effect of nimodipine treatment on calcium homeostasis in nociceptive dorsal root ganglion neurons (DRG) and substantia gelatinosa (SG) neurons of the spinal cord slices was examined with fluorescent imaging technique. 3. Nimodipine treatment was not able to normalize elevated resting intracellular calcium ([Ca(2+)]( i )) levels in small DRG neurons. However, it was able to restore impaired Ca(2+) release from the ER, induced by either activation of ryanodine receptors or by receptor-independent mechanism in both DRG and SG neurons. 4. The beneficiary effects of nimodipine treatment on [Ca(2+)]( i ) signaling were paralleled with the reversal of diabetes-induced thermal hypoalgesia and normalization of the acute phase of the response to formalin injection. Nimodipine treatment was also able to shorten the duration of the tonic phase of formalin response to the control values. 5. To separate vasodilating effect of nimodipine Biessels et al., (Brain Res. 1035:86-93) from its effect on neuronal Ca(2+) channels, a group of STZ-diabetic rats was treated with vasodilator - enalapril. Enalapril treatment also have some beneficial effect on normalizing Ca(2+) release from the ER, however, it was far less explicit than the normalizing effect of nimodipine. Effect of enalapril treatment on nociceptive behavioral responses was also much less pronounced. It partially reversed diabetes-induced thermal hypoalgesia, but did not change the characteristics of the response to formalin injection. 6. The results of this study suggest that chronic nimodipine treatment may be effective in restoring diabetes-impaired neuronal calcium homeostasis as well as reduction of diabetes-induced thermal hypoalgesia and noxious stimuli responses. The nimodipine effect is mediated through a direct neuronal action combined with some vascular mechanism.
Asunto(s)
Calcio/metabolismo , Diabetes Mellitus Experimental/metabolismo , Nimodipina/farmacología , Umbral del Dolor/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Bloqueadores de los Canales de Calcio/farmacología , Bloqueadores de los Canales de Calcio/uso terapéutico , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/metabolismo , Evaluación Preclínica de Medicamentos , Homeostasis/efectos de los fármacos , Masculino , Neuronas Aferentes/efectos de los fármacos , Neuronas Aferentes/metabolismo , Nimodipina/uso terapéutico , Ratas , Ratas WistarRESUMEN
Xerostomia and pathological thirst are troublesome complications of diabetes mellitus associated with impaired functioning of salivary glands; however, their cellular mechanisms are not yet determined. Isolated acinar cells were loaded with Ca2+ indicators fura-2/AM for measuring cytosolic Ca2+ concentration ([Ca2+]i) or mag-fura-2/AM-inside the endoplasmic reticulum (ER). We found a dramatic decrease in pilocarpine-stimulated saliva flow, protein content and amylase activity in rats after 6 weeks of diabetes vs. healthy animals. This was accompanied with rise in resting [Ca2+]i and increased potency of acetylcholine (ACh) and carbachol (CCh) but not norepinephrine (NE) to induce [Ca2+]i transients in acinar cells from diabetic animals. However, [Ca2+]i transients mediated by Ca2+ release from ER stores (induced by application of either ACh, CCh, NE, or ionomycin in Ca2+-free extracellular medium) were decreased under diabetes. Application of inositol-1,4,5-trisphosphate led to smaller Ca2+ release from ER under the diabetes. Both plasmalemma and ER Ca2+-ATPases activity was reduced and the latter showed the increased affinity to ATP under the diabetes. We conclude that the diabetes caused impairment of salivary cells functions that, on the cellular level, associates with Ca2+ overload, increased Ca2+-mobilizing ability of muscarinic but not adrenergic receptors, decreased Ca2+-ATPases activity and ER Ca2+ content.
Asunto(s)
Señalización del Calcio/fisiología , ATPasas Transportadoras de Calcio/metabolismo , Calcio/metabolismo , Diabetes Mellitus Experimental/metabolismo , Glándula Submandibular/metabolismo , Acetilcolina/análogos & derivados , Acetilcolina/metabolismo , Animales , Células Cultivadas , Diabetes Mellitus Experimental/complicaciones , Retículo Endoplásmico/metabolismo , Colorantes Fluorescentes/metabolismo , Fura-2/análogos & derivados , Fura-2/química , Fura-2/metabolismo , Homeostasis , Inositol 1,4,5-Trifosfato/metabolismo , Ionomicina/metabolismo , Ionóforos/metabolismo , Masculino , Norepinefrina/metabolismo , Páncreas/citología , Páncreas/metabolismo , Ratas , Ratas Wistar , Saliva/química , Saliva/metabolismo , Sed , Xerostomía/etiología , Xerostomía/metabolismoRESUMEN
Development of diabetic sensory polyneuropathy is associated with alterations in intracellular calcium homeostasis in primary and secondary nociceptive neurons. We have shown previously that in a model of streptozotocin (STZ)-induced diabetes, the calcium signal is prolonged and calcium release from ryanodine-sensitive calcium stores down-regulated in neurons of the nociceptive system. The aim of the present study was a more detailed characterization of calcium homeostasis in primary (dorsal root ganglia, DRG) and secondary (dorsal horn, DH) nociceptive neurons in STZ-induced diabetes. Fluorescence video-imaging was used to measure free cytosolic [Ca2+] ([Ca2+]i) in lumbar nociceptive neurons of control and streptozotocin-diabetic rats. Resting [Ca2+]i rose progressively in these neurons with the duration of diabetes and calcium mobilization from the endoplasmic reticulum (ER) decreased during diabetes. The amplitude of calcium release from both ryanodine- and IP3-sensitive calcium stores induced by caffeine, ionomycin, ATP or glutamate was significantly (P<0.01) lower in DRG and DH neurons from 6-week STZ-diabetic rats. Diabetes-induced changes in the calcium homeostasis were similar in DRG and DH neurons indicating that they might be general for many types of neurons from the central and peripheral nervous systems.
Asunto(s)
Calcio/metabolismo , Neuropatías Diabéticas/metabolismo , Retículo Endoplásmico/metabolismo , Neuronas Aferentes/metabolismo , Nociceptores/metabolismo , Animales , Cafeína/farmacología , Diabetes Mellitus Experimental/metabolismo , Ganglios Espinales/citología , Ganglios Espinales/metabolismo , Homeostasis/fisiología , Inositol 1,4,5-Trifosfato/metabolismo , Ionomicina/farmacología , Ionóforos/farmacología , Masculino , Neuronas Aferentes/efectos de los fármacos , Nociceptores/efectos de los fármacos , Inhibidores de Fosfodiesterasa/farmacología , Ratas , Ratas Wistar , Canal Liberador de Calcio Receptor de Rianodina/metabolismoRESUMEN
Elevations of cytosolic free Ca2+ concentration ([Ca2+]i) induced by addition of ATP have been compared in rat dorsal horn neurones in slices and after their isolation. ATP application induced in neurones in situ a rise of [Ca2+]i by 201 +/- 12 nM. In Ca2+-free external solution the rise was 156 +/- 14 nM (n = 45 of 76), indicating the presence of active purinergic metabotropic receptors in about 59% of neurones. [Ca2+]i transients induced by 2MeSATP in Ca2+-free external solution were completely abolished by 10 microM PPADS, indicating that some of the corresponding receptors are of the P2Y1 type. In acutely isolated neurones which lost their dendrites, there were no metabotropic response. The results confirm the presence of metabotropic postsynaptic purinoreceptors located in the dendritic tree of dorsal horn neurones.
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Dendritas/metabolismo , Células del Asta Posterior/metabolismo , Receptores Purinérgicos P2/metabolismo , Adenosina Trifosfato/farmacología , Animales , Calcio/metabolismo , Dendritas/efectos de los fármacos , Masculino , Células del Asta Posterior/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
AIMS/HYPOTHESIS: Distal neuropathy is the most common complication of diabetes mellitus, making it important to reveal the cellular mechanisms leading to its development, one of which might be the alteration in intracellular calcium homeostasis in primary and secondary nociceptive neurons. We aimed to investigate these possible changes. METHODS: Control and streptozotocin-treated diabetic rats and mice were used. Changes in intracellular free calcium concentrations ([Ca(2+)]i) were measured fluorometrically in primary nociceptive neurons from dorsal root ganglia and in secondary nociceptive neurons from substantia gelatinosa of spinal dorsal horn slices. RESULTS: Measurements of [Ca(2+)]i increases induced in dorsal root ganglion and dorsal horn neurons by membrane depolarization did not show any substantial difference in their peak amplitudes in control and diabetic animals. However, a definite prolongation of the decay phase of the transients was observed under diabetic conditions. Caffeine application to dorsal root ganglion and dorsal horn neurons induced a transient elevation of [Ca(2+)]i which was less prominent in cells from diabetic animals. Short-term application of a calcium channel blocker nifedipine showed a substantial amplification of its action in diabetic neurons. However, chronic administration of nimodipine induced a clear increase in the peak values of transients in dorsal root ganglion neurons of diabetic animals compared with those of untreated animals. CONCLUSION/INTERPRETATION: The described changes of calcium signalling in nociceptive neurons could be the reason for the development of distal polyneuropathy and its symptoms in the early stages of diabetes mellitus.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Calcio/metabolismo , Diabetes Mellitus Experimental/metabolismo , Homeostasis , Neuronas/metabolismo , Nociceptores/metabolismo , Animales , Cafeína/farmacología , Ganglios Espinales/metabolismo , Masculino , Potenciales de la Membrana , Ratones , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Nifedipino/farmacología , Nociceptores/efectos de los fármacos , Ratas , Ratas Wistar , Transducción de Señal , Sustancia Gelatinosa/metabolismoRESUMEN
We have previously found that spinal dorsal horn neurons from streptozotocin-diabetic rats, an animal model for diabetes mellitus, show the prominent changes in the mechanisms responsible for [Ca2+]i regulation. The present study aimed to further characterize the effects of streptozotocin-induced diabetes on neuronal calcium homeostasis. The cytoplasmic Ca2+ concentration ([Ca2+]i) was measured in Fura-2AM-loaded dorsal horn neurons from acutely isolated spinal cord slices using fluorescence technique. We studied Ca2+ entry through plasmalemmal Ca2+ channels during potassium (50 mM KCl)-induced depolarization. The K+-induced [Ca2+]i elevation was inhibited to a different extent by nickel ions, nifedipine and omega-conotoxin suggesting the co-expression of different subtypes of plasmalemmal voltage-gated Ca2+ channels. The suppression of [Ca2+]i transients by Ni2+ (50 microM) was the same in control and diabetic neurons. On the other hand, inhibition of [Ca2+]i transients by nifedipine (50 microM) and omega-conotoxin (1 microM) was much greater in diabetic neurons compared with normal animals. These data suggest that under diabetic conditions the activity of N- and L- but not T-type voltage-gated Ca2+ channels substantially increased in dorsal horn neurons.
Asunto(s)
Canales de Calcio Tipo L/fisiología , Diabetes Mellitus Experimental/fisiopatología , Neuropatías Diabéticas/fisiopatología , Células del Asta Posterior/química , Células del Asta Posterior/fisiología , Animales , Calcio/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Colorantes Fluorescentes , Fura-2/análogos & derivados , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Níquel/farmacología , Nifedipino/farmacología , Cloruro de Potasio/farmacología , Ratas , Ratas Wistar , Estimulación Química , omega-Conotoxinas/farmacologíaRESUMEN
Intracellular calcium signalling was studied in the dorsal horn from neurons of rats with streptozotocin-induced diabetes versus control animals. The cytoplasmic Ca2+ concentration ([Ca2+]i) was measured in Fura-2 acetoxymethyl ester-loaded dorsal horn neurons from acutely isolated spinal cord slices using a fluorescence technique. The recovery of depolarization-induced [Ca2+]i increase was delayed in diabetic neurons compared with normal animals. In normal neurons, [Ca2+]i after the end of KCl depolarization recovered to the basal level monoexponentially with a time constant of 8.0+/-0.5 s (n = 23), while diabetic neurons showed two exponentials in the [Ca2+]i recovery. The time constants of these exponentials were 7.2+/-0.5 and 23.0+/-0.6 s (n = 19), respectively. The amplitude of calcium release from caffeine-sensitive endoplasmic reticulum calcium stores became significantly smaller in diabetic neurons. The amplitudes of [Ca2+]i transients evoked by 30 mM caffeine were 268+/-29 nM (n = 13) and 31+/-9 nM (n = 17) in control and diabetic neurons, respectively. We conclude that streptozotocin-induced diabetes is associated with prominent changes in the mechanisms responsible for [Ca2+]i regulation, which presumably include a slowdown of Ca2+ elimination from the cytoplasm by the endoplasmic reticulum.
Asunto(s)
Calcio/fisiología , Diabetes Mellitus Experimental/fisiopatología , Células del Asta Posterior/fisiología , Transducción de Señal/fisiología , Animales , Cafeína/farmacología , Citoplasma/metabolismo , Colorantes Fluorescentes , Fura-2/análogos & derivados , Técnicas In Vitro , Masculino , Potenciales de la Membrana/efectos de los fármacos , Células del Asta Posterior/efectos de los fármacos , Cloruro de Potasio/farmacología , Ratas , Ratas Wistar , Valores de Referencia , Médula Espinal/fisiología , Médula Espinal/fisiopatologíaRESUMEN
The stochastic aspects of alpha-particle traversals through nuclei of bone-lining cells from nonuniform radioactive labels are worked out. Both the residence time of the target and the hit rate are considered random variables. It is shown that with any type of bone remodeling the fraction of cells not hit increases with increasing nonuniformity of the label concentration. Thus, a completely uniform concentration represents the most dangerous situation. A possible negative correlation between residence times and hit rates, observed in some experiments, tends to decrease the probability of alpha-particle hits. As a practical application, the theory is applied to the International Commission on Radiological Protection model of the distribution of 239Pu in the human body. In the case of 50 years of chronic ingestion of 1 annual limit of intake (ALI) per year for class W and chronic inhalation of 1 ALI/year for class Y compounds, more than 19.4 and 8.5% of the nuclei of bone-lining cells are traversed by at least one alpha-particle, respectively.
Asunto(s)
Partículas alfa , Huesos/efectos de la radiación , Humanos , ProbabilidadRESUMEN
The most important but still unresolved problem in bioelectromagnetics is the interaction of weak electromagnetic fields (EMFs) with living cells. Thermal and other types of noise pose restrictions in cell detection of weak signals. As a consequence, some extant experimental results that indicate low-intensity field effects cannot be accounted for, and this renders the results themselves questionable. One way out of this dead end is to search for possible mechanisms of signal amplification. In this paper, we discuss a general mechanism in which a weak signal is amplified by system noise itself. This mechanism was discovered several years ago in physics and is known, in its simplest form, as a stochastic resonance. It was shown that signal amplification may exceed a factor of 1000, which renders existing estimations of EMF thresholds highly speculative. The applicability of the stochastic resonance concept to cells is discussed particularly with respect to the possible role of the cell membrane in the amplification process.
Asunto(s)
Fenómenos Fisiológicos Celulares , Campos Electromagnéticos , Algoritmos , Fenómenos Biofísicos , Biofisica , Membrana Celular/química , Membrana Celular/fisiología , Electroquímica , Electrofisiología , Humanos , Modelos Teóricos , Procesos EstocásticosRESUMEN
The statistics of hits to the nuclei of bone cells irradiated from alpha sources labeling bone tissue is described. It is shown that the law of remodeling of a bone structural unit (BSU), which describes the distribution of quiescence periods of this unit, affects the statistics of hits. It the irradiation of bone cells occurs during the whole cell cycle, the mean number of hits is independent of the law of remodeling. In this case the variance of hits has the minimum value for constant quiescence periods of BSUs (deterministic remodeling) and the maximum value for exponentially distributed quiescence periods (random remodeling). For the first generation of bone cells, i.e. for the cells which existed at the moment of the uptake of the nuclide, the mean number of hits depends on the law of remodeling. For random remodeling the mean number is equal to the mean value for the complete remodeling cycle. For deterministic remodeling the mean is only half this value. For the first generation of bone cells, changing the law of remodeling from random to deterministic increases the probability of no hits to the nuclei of bone cells. For the same mean value of hits, the difference does not exceed 13.3% of the total number of cells. For the subsequent generations of bone cells, such a change of the law of remodeling decreases the probability of no hits by 20.4%.
Asunto(s)
Partículas alfa , Huesos/citología , Núcleo Celular/efectos de la radiación , Remodelación Ósea , Estadística como AsuntoRESUMEN
Factors relating the local concentration of a bone-seeking alpha-particle emitter to the mean hit rate have been determined for nuclei of bone lining cells using a Monte Carlo procedure. Cell nuclei were approximated by oblate spheroids with dimensions and location taken from a previous histomorphometric study. The Monte Carlo simulation is applicable for planar and diffuse labels at plane or cylindrical bone surfaces. Additionally, the mean nuclear dose per hit, the dose mean per hit, the mean track segment length and its second moment, the percentage of stoppers, and the frequency distribution of the dose have been determined. Some basic features of the hit statistics for bone lining cells have been outlined, and the consequences of existing standards of radiation protection with regard to the hit frequency to cell nuclei are discussed.
Asunto(s)
Partículas alfa , Huesos/citología , Núcleo Celular/efectos de la radiación , Plutonio , Animales , Perros , Humanos , Método de Montecarlo , Dosis de RadiaciónRESUMEN
A description of the stochastic dynamics of radiation cell death based on the first-passage model is given. Both quasistochastic and stochastic methods of description are considered. Distributions of the time to cell death for stable and unstable populations are obtained. These results are used to analyze the dynamics of interphase death of thymocytes and bone marrow cells.
Asunto(s)
Muerte Celular/fisiología , Muerte Celular/efectos de la radiación , Animales , Células de la Médula Ósea , Interfase/efectos de la radiación , Modelos Biológicos , Ratas , Procesos Estocásticos , Linfocitos T/efectos de la radiaciónRESUMEN
An attempt to describe the dose dependence of cell inactivation by a stochastic differential equation is made. For this, a stochastic variable in dose radiosensitivity is introduced. Some solutions of the stochastic equation are obtained and and analyzed. How to obtain the value of the noise intensity of radiosensitivity from the experimental data is shown. Comparison of the theory with experimental data gives good results.