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1.
World J Urol ; 41(12): 3829-3838, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37966505

ABSTRACT

PURPOSE: To analyze the 10-year biochemical relapse-free survival (BRFS), locoregional relapse-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) in patients diagnosed with localized prostate adenocarcinoma treated with radiotherapy (RT) ± androgen deprivation therapy (ADT), according to the risk groups based on multiparametric magnetic resonance imaging (mpMRI) instead of digital rectal exam (DRE). METHODS: We retrospectively evaluated 140 consecutive patients diagnosed with localized prostate adenocarcinoma, stratified into different risk groups-low (LR), intermediate (IR), and high (HR) by mpMRI results. RESULTS: After a median follow-up of 104 months, in LR group (n = 15), 10-year BRFS was 86.7%, 10-year LRFS was 86.7%, 10-year MFS was 93.3%, and 10-year OS was 100%. In IR group (n = 80), 10-year BRFS was 80.5%, 10-year LRFS was 86.1%, 10-year MFS was 92.6%, and 10-year OS was 76%. In HR group (n = 45), 10-year BRFS was 72.8%, 10-year LRFS was 78.7%, 10-year MFS was 82.1%, and 10-year OS was 77% (2 deaths from prostate cancer). According to mpMRI results, 36 (25.7%) patients change the risk group and 125 (89.28%) patients change the TNM stage. There was a trend for higher metastatic relapse in patients who switched from IR to HR (due to mpMRI) versus the patients who remained in the IR (20%, vs. 1.81% p = 0.059). Multivariate analysis showed that locoregional relapse was strongly associated with distant relapse (OR = 9.28; 95%CI: 2.60-33.31). There were no cases of acute grade 3 toxicity. Late grade 3 genitourinary, gastrointestinal, and sexual toxicity were 2.8%, 0.7%, and 1.2%, respectively. CONCLUSION: This is the first study with a 10-year median follow-up of patients diagnosed with localized prostate cancer treated with radiotherapy according to the risk groups established by mpMRI. Our findings show that mpMRI is a key tool to diagnose and establish risk groups in these patients, to optimize their treatment.


Subject(s)
Adenocarcinoma , Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/pathology , Androgen Antagonists/therapeutic use , Retrospective Studies , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/drug therapy , Recurrence , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/radiotherapy , Adenocarcinoma/drug therapy , Prostate-Specific Antigen
2.
Methods Mol Biol ; 2565: 297-309, 2023.
Article in English | MEDLINE | ID: mdl-36205902

ABSTRACT

Cultured bovine chromaffin cells have been characterized as a successful model to study changes in the cytoskeleton during the secretory process. In this sense, the distribution and dynamics of the F-actin cytoskeleton can be studied by confocal microscopy using appropriate molecular tools such as LifeAct, a peptide that stains the structures of F-actin. In this work, we describe some methodological protocols making possible to study, under controlled stimulus conditions, the local dynamic changes of F-actin in the cortical zone and also to detect the simultaneous displacements of chromaffin granules and organelles in active zones.


Subject(s)
Actins , Chromaffin Cells , Actin Cytoskeleton , Animals , Cattle , Chromaffin Granules , Microscopy, Confocal/methods
3.
Int J Mol Sci ; 23(16)2022 Aug 14.
Article in English | MEDLINE | ID: mdl-36012367

ABSTRACT

The heteromeric assembly of α3 and ß4 subunits of acetylcholine nicotinic receptors (nAChRs) seems to mediate the secretory response in bovine chromaffin cells. However, there is no information about the localization of these nAChRs in relationship with the secretory active zones in this cellular model. The present work presents the first evidence that, in fact, a population of these receptors is associated through the F-actin cytoskeleton with exocytotic machinery components, as detected by SNAP-25 labeling. Furthermore, we also prove that, upon stimulation, the probability to find α3ß4 nAChRs very close to exocytotic events increases with randomized distributions, thus substantiating the clear dynamic behavior of these receptors during the secretory process. Modeling on secretory dynamics and secretory component distributions supports the idea that α3ß4 nAChR cluster mobility could help with improving the efficiency of the secretory response of chromaffin cells. Our study is limited by the use of conventional confocal microscopy; in this sense, a strengthening to our conclusions could come from the use of super-resolution microscopy techniques in the near future.


Subject(s)
Chromaffin Cells , Receptors, Nicotinic , Acetylcholine , Animals , Biological Transport , Cattle , Chromaffin Cells/metabolism , Nicotinic Antagonists , Receptors, Nicotinic/metabolism
4.
Int J Mol Sci ; 23(3)2022 Jan 19.
Article in English | MEDLINE | ID: mdl-35163009

ABSTRACT

The fusion of membranes is a central part of the physiological processes involving the intracellular transport and maturation of vesicles and the final release of their contents, such as neurotransmitters and hormones, by exocytosis. Traditionally, in this process, proteins, such SNAREs have been considered the essential components of the fusion molecular machinery, while lipids have been seen as merely structural elements. Nevertheless, sphingosine, an intracellular signalling lipid, greatly increases the release of neurotransmitters in neuronal and neuroendocrine cells, affecting the exocytotic fusion mode through the direct interaction with SNAREs. Moreover, recent studies suggest that FTY-720 (Fingolimod), a sphingosine structural analogue used in the treatment of multiple sclerosis, simulates sphingosine in the promotion of exocytosis. Furthermore, this drug also induces the intracellular fusion of organelles such as dense vesicles and mitochondria causing cell death in neuroendocrine cells. Therefore, the effect of sphingosine and synthetic derivatives on the heterologous and homologous fusion of organelles can be considered as a new mechanism of action of sphingolipids influencing important physiological processes, which could underlie therapeutic uses of sphingosine derived lipids in the treatment of neurodegenerative disorders and cancers of neuronal origin such neuroblastoma.


Subject(s)
Exocytosis/drug effects , Neuroendocrine Cells/metabolism , Sphingosine/metabolism , Animals , Biological Transport , Humans , Membrane Fusion , SNARE Proteins/metabolism , Sphingosine/pharmacology
5.
Pflugers Arch ; 473(11): 1775-1793, 2021 11.
Article in English | MEDLINE | ID: mdl-34510285

ABSTRACT

The hypersecretory phenotype of adrenal chromaffin cells (CCs) from early spontaneously hypertensive rats (SHRs) mainly results from enhanced Ca2+-induced Ca2+-release (CICR). A key question is if these abnormalities can be traced to the prehypertensive stage. Spontaneous and stimulus-induced catecholamine exocytosis, intracellular Ca2+ signals, and dense-core granule size and density were examined in CCs from prehypertensive and hypertensive SHRs and compared with age-matched Wistar-Kyoto rats (WKY). During the prehypertensive stage, the depolarization-elicited catecholamine exocytosis was ~ 2.9-fold greater in SHR than in WKY CCs. Interestingly, in half of CCs the exocytosis was indistinguishable from WKY CCs, while it was between 3- and sixfold larger in the other half. Likewise, caffeine-induced exocytosis was ~ twofold larger in prehypertensive SHR. Accordingly, depolarization and caffeine application elicited [Ca2+]i rises ~ 1.5-fold larger in prehypertensive SHR than in WKY CCs. Ryanodine reduced the depolarization-induced secretion in prehypertensive SHR by 57%, compared to 14% in WKY CCs, suggesting a greater contribution of intracellular Ca2+ release to exocytosis. In SHR CCs, the mean spike amplitude and charge per spike were significantly larger than in WKY CCs, regardless of age and stimulus type. This difference in granule content could explain in part the enhanced exocytosis in SHR CCs. However, electron microscopy did not reveal significant differences in granule size between SHRs and WKY rats' adrenal medulla. Nonetheless, preSHR and hypSHR display 63% and 82% more granules than WKY, which could explain in part the enhanced catecholamine secretion. The mechanism responsible for the heterogeneous population of prehypertensive SHR CCs and the bias towards secreting more medium and large granules remains unexplained.


Subject(s)
Chromaffin Cells/physiology , Hypertension/physiopathology , Animals , Calcium/metabolism , Catecholamines/metabolism , Chromaffin Cells/metabolism , Exocytosis/physiology , Hypertension/metabolism , Male , Phenotype , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Ryanodine/metabolism
6.
Sci Rep ; 9(1): 18471, 2019 12 05.
Article in English | MEDLINE | ID: mdl-31804600

ABSTRACT

FTY-720 (Fingolimod) was one of the first compounds authorized for the treatment of multiple sclerosis. Among its other activities, this sphingosine analogue enhances exocytosis in neuroendocrine chromaffin cells, altering the quantal release of catecholamines. Surprisingly, the size of chromaffin granules is reduced within few minutes of treatment, a process that is paralleled by the homotypic fusion of granules and their heterotypic fusion with mitochondria, as witnessed by dynamic confocal and TIRF microscopy. Electron microscopy studies support these observations, revealing the fusion of several vesicles with individual mitochondria to form large, round mixed organelles. This cross-fusion is SNARE-dependent, being partially prevented by the expression of an inactive form of SNAP-25. Fused mitochondria exhibit an altered redox potential, which dramatically enhances cell death. Therefore, the cross-fusion of intracellular organelles appears to be a new mechanism to be borne in mind when considering the effect of FTY-720 on the survival of neuroendocrine cells.


Subject(s)
Chromaffin Granules/drug effects , Fingolimod Hydrochloride/toxicity , Multiple Sclerosis/drug therapy , Neuroendocrine Cells/drug effects , Animals , Cattle , Cells, Cultured , Chromaffin Granules/metabolism , Chromaffin Granules/pathology , Humans , Microscopy, Electron, Transmission , Mitochondria/drug effects , Mitochondria/pathology , Mitochondrial Dynamics/drug effects , Neuroendocrine Cells/cytology , Neuroendocrine Cells/metabolism , Primary Cell Culture , Synaptosomal-Associated Protein 25/metabolism , Toxicity Tests
7.
Enferm. nefrol ; 22(4): 406-414, oct.-dic. 2019. ilus, tab, graf
Article in Spanish | IBECS | ID: ibc-188356

ABSTRACT

Introducción: Las personas con enfermedad renal deben recibir una atención integral que incluya programas de ejercicio físico adaptado a sus necesidades. Objetivo: Evaluar la satisfacción de los pacientes con enfermedad renal crónica en estadios IV y V ante un programa de ejercicio físico domiciliario. Material y Método: Estudio descriptivo transversal en pacientes que realizaron un programa completo de entrenamiento físico domiciliario de 12 semanas de duración. Tras esta intervención, respondieron de forma anónima a un cuestionario ad-hoc validado por expertos, sobre su opinión acerca del programa. Resultados: Participaron 62 pacientes. 24 estaban en programa de hemodiálisis, 17 en diálisis peritoneal y 7 en situación de enfermedad renal crónica estadio IV. 34 eran hombres. La edad media fue de 67,4+/-14,9 años. 52 pacientes realizaron el programa solos en su domicilio. 33 de los pacientes les pareció muy correcto que el programa fuera domiciliario, 15 correcto y 2 poco correcto. 47 de los participantes consideraron muy correcto que la persona que dirigiera el programa fuera una enfermera conocida. 19 consideró que tras el programa habían mejorado mucho, 14 que habían mejorado, 9 que habían mejorado poco y 3 que no habían mejorado. 39 estuvieron muy satisfechos de haber podido participar en el programa, 6 satisfechos, 1 poco satisfecho y 1 de los pacientes no estuvo satisfecho. No hubo diferencias significativas en las respuestas en relación al sexo, edad, tipo de tratamiento, o realizar el programa solo o acompañado. Conclusiones: El programa de ejercicio físico domiciliario fue bien valorado por los pacientes que en su mayoría manifestaron haber mejorado y consideraron adecuado que fuera una enfermera la que dirigiera el programa


Objective: To evaluate patient satisfaction chronic kidney disease in stages IV and V after a home physical exercise program. Material and methods: Descriptive cross-sectional study in patients who carried out a complete 12-week home physical training program. After this intervention, they responded anonymously to an ad-hoc questionnaire validated by experts, about their opinion about the program. Results: 62 patients participated. 24 were on a hemodialysis program, 17 on peritoneal dialysis and 7 on stage IV chronic kidney disease. 34 were men. The mean age was 67.4 +/- 14.9 years. 52 patients carried out the program alone at home. 33 of the patients considered as very correct that the program was domiciliary, 15 correct and 2 not correct. 47 of the participants considered as very correct that the person leading the program was a well-known nurse. 19 responded that after the program the improvement was a lot, 14 a good improvement, 9 little improvement and 3 that had not improved. 39 were very satisfied to participate in the program, 6 satisfied, 1 not very satisfied and 1 of the patients was not satisfied. There were no significant differences in the answers in relation to sex, age, type of treatment, or if the program was done alone or accompanied. Conclusions: The home physical exercise program was well valued by the patients, who mostly said they had improved and considered as appropriate that a nurse leads the program


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Renal Insufficiency, Chronic/rehabilitation , Exercise Therapy/methods , Patient Satisfaction , Comprehensive Health Care , Severity of Illness Index
8.
Rep Pract Oncol Radiother ; 24(5): 472-480, 2019.
Article in English | MEDLINE | ID: mdl-31452628

ABSTRACT

AIM: To analyse the efficacy and toxicity of postprostatectomy SRT in patients with a BCR evaluated with mpMRI. BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has the ability to detect the site of pelvic recurrence in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). However, we do not know the oncological outcomes of mpMRI-guided savage radiotherapy (SRT). RESULTS: Local, lymph node, and pelvic bone recurrence was observed in 13, 4 and 2 patients, respectively. PSA levels were significantly lower in patients with negative mpMRI (0.4 ng/mL [0.4]) vs. positive mpMRI (2.2 ng/mL [4.1], p = 0.003). Median planning target volume doses in patients with visible vs. non-visible recurrences were 76 Gy vs. 70 Gy. Overall, mean follow-up was 41 months (6-81). Biochemical relapse-free survival (bRFS) at 3 years was 82.3% and 82.5%, respectively, for the negative and positive mpMRI groups (p = 0.800). Three-year rates of late grade ≥2 urinary and rectal toxicity were 14.8% and 1.9%, respectively; all but one patient recovered without sequelae. CONCLUSION: SRT to the macroscopic recurrence identified by mpMRI is a feasible and well-tolerated option. In this study, there were no differences in bRFS between MRI-positive and MRI-negative patients, indicating effective targeting of MRI-positive lesions.

9.
Chemosphere ; 217: 558-566, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30445401

ABSTRACT

In this study, we assessed total mercury levels in hair specimens of 661 children, aged 6 to 11, participating in the BIOVAL programme, a human biomonitoring study carried out by the Health Department of the Regional Government of Valencia (Spain). The reference value (95th percentile) determined for this population, within this programme, was 3.25 µg g-1. Hg concentrations ranged between 0.03 µg g-1 and 8.71 µg g-1, with a geometric mean of 0.79 (CI 95%: 0.73-0.85) µg g-1. This mean value was five times higher than the average levels found in children of 17 other European countries (0.145 µg g-1). About 13% of children had hair mercury levels above the FAO/WHO JECFA guideline of 2.3 µg g-1 and 18% of children had levels above the EFSA health-based guidance value of 1.9 µg. Multiple regression analysis revealed that fish consumption, mother's country of birth (Spain or abroad) and the employment situation of parents were the main predictors of mercury in hair.


Subject(s)
Environmental Monitoring/methods , Hair/chemistry , Mercury/chemistry , Animals , Child , Female , Fishes , Humans , Male , Mercury/analysis , Risk Assessment , Spain
10.
Methods Mol Biol ; 1860: 379-389, 2019.
Article in English | MEDLINE | ID: mdl-30317519

ABSTRACT

Cultured bovine chromaffin cells have been tested as a successful neuroendocrine model to study the secretory process. Changes in the dynamics of the secretory vesicles and the exocytotic machinery microdomains could be studied in control and stimulated conditions using appropriate molecular tools such as fluorescent SNARE protein expression or fluorochrome vesicular labeling in these neuroendocrine cells. Since most of these changes occur in or near the plasma membrane, the use of the total internal reflection fluorescent microscopy (TIRFM) and the implement of particle motion analysis could be essential tools to study the structural and dynamic changes of secretory machinery related with its function in this exocytotic cell model.


Subject(s)
Chromaffin Cells/metabolism , Secretory Vesicles/metabolism , Synaptosomal-Associated Protein 25/metabolism , Adrenal Medulla/cytology , Animals , Cattle , Exocytosis , Fluorescent Dyes/chemistry , Membrane Fusion , Microscopy, Fluorescence/instrumentation , Microscopy, Fluorescence/methods , Primary Cell Culture/instrumentation , Primary Cell Culture/methods , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Secretory Vesicles/chemistry , Synaptosomal-Associated Protein 25/chemistry , Synaptosomal-Associated Protein 25/isolation & purification
11.
Front Cell Neurosci ; 12: 344, 2018.
Article in English | MEDLINE | ID: mdl-30356839

ABSTRACT

Neuroendocrine chromaffin cells represent an excellent model to study the molecular mechanisms associated with the exo-endocytotic cycle of neurotransmitter release. In this study, EGFP-Lifeact and confocal microscopy has been used to analyze the re-organization of the cortical F-actin cytoskeleton associated to organelle transport during secretion with unprecedented detail. In these cells secretory events accumulate in temperature-sensitive and myosin II-dependent F-actin expansions and retractions affecting specific regions of the sub-membrane space. Interestingly, not only vesicles but also mitochondria are transported toward the plasmalemma during these expansions. Simultaneously, we found F-actin cytoskeletal retraction withdraws vesicles from the sub-plasmalemmal space, forming novel empty internal spaces into which organelles can be transported. In addition to these well-coordinated, F-actin-myosin II dependent processes that drive the transport of the majority of vesicles, fast transport of chromaffin vesicles was observed, albeit less frequently, which used F-actin comet tails nucleated from the granular membrane. Thus, upon cell stimulation F-actin structures use diverse mechanisms to transport organelles to and from the membrane during the exo-endocytotic cycle taking place in specific areas of cell periphery.

12.
FEBS Lett ; 592(21): 3493-3503, 2018 11.
Article in English | MEDLINE | ID: mdl-29962039

ABSTRACT

Membrane fusion is a key event in exocytosis of neurotransmitters and hormones stored in intracellular vesicles. In this process, soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins are essential components of the exocytotic molecular machinery, while lipids have been seen traditionally as structural elements. However, the so-called signalling lipids, such as sphingosine and arachidonic acid, interact with SNAREs and directly modulate the frequency and mode of fusion events. Interestingly, recent work has proved that the sphingosine analogue FTY-720, used in the treatment of multiple sclerosis, mimics the effects of signalling lipids. In the present Review, we discuss recent investigations suggesting that endogenous signalling lipids and synthetic analogues can modulate important physiological aspects of secretion, such as quantal release, vesicle recruitment into active sites, vesicle transport and even organelle fusion in the cytosol. Therefore, these compounds are far from being merely structural components of cellular membranes.


Subject(s)
Arachidonic Acid/metabolism , Exocytosis/physiology , Signal Transduction , Sphingosine/metabolism , Animals , Humans , Membrane Fusion , Protein Binding , SNARE Proteins/metabolism
13.
Front Cell Neurosci ; 11: 135, 2017.
Article in English | MEDLINE | ID: mdl-28522964

ABSTRACT

Cultured bovine chromaffin cells have been used extensively as a neuroendocrine model to study regulated secretion. In order to extend such experimental findings to the physiological situation, it is necessary to study mayor cellular structures affecting secretion in cultured cells with their counterparts present in the adrenomedullary tissue. F-actin concentrates in a peripheral ring in cultured cells, as witnessed by phalloidin-rodhamine labeling, while extends throughout the cytoplasm in native cells. This result is also confirmed when studying the localization of α-fodrin, a F-actin-associated protein. Furthermore, as a consequence of this redistribution of F-actin, we observed that chromaffin granules and mitochondria located into two different cortical and internal populations in cultured cells, whereas they are homogeneously distributed throughout the cytoplasm in the adrenomedullary tissue. Nevertheless, secretion from isolated cells and adrenal gland pieces is remarkably similar when measured by amperometry. Finally, we generate mathematical models to consider how the distribution of organelles affects the secretory kinetics of intact and cultured cells. Our results imply that we have to consider F-actin structural changes to interpret functional data obtained in cultured neuroendocrine cells.

14.
BMC Complement Altern Med ; 16(1): 445, 2016 Nov 08.
Article in English | MEDLINE | ID: mdl-27825331

ABSTRACT

BACKGROUND: Hippocratea celastroides Kunth, commonly known as "cancerina", is used in Mexican Traditional Medicine for the treatment of gastric and intestinal infections, systemic and skin inflammation, injuries and gastritis. The aim of this research was to assess the anti-Helicobacter pylori activities of hydro-ethanolic root-bark extracts from Hippocratea celastroides Kunth in naturally infected dogs, after testing their acute and subacute toxicities in mice. METHODS: To determine in vivo acute toxicity, a hydro-ethanolic extract was obtained and administered orally in female and male Balb-C mice, at doses ranging from 2000 to 5000 mg/kg. For the subacute study, a hydro-ethanolic extract was given to male and female Balb-C mice at doses ranging from 200 to 2000 mg/kg body weight. The animals were observed daily over a period of 42 days for signs of toxicity. In the pre-clinical anti-Helicobacter spp. assay, 60 dogs were included. Eighteen and 19 dogs for the experimental and control groups respectively, concluded the study. The experimental treatment consisted of H. celastroides hydro-ethanolic extract and the control treatment of amoxicillin-clarithromycin-omeprazole. RESULTS: Oral LD50 (lethal dose 50) values for hydro-ethanolic extract were indeterminable at the highest tested doses. Under the subacute administration, neither mortality nor any sign of toxicity were observed when the hydro-ethanolic extract was administered. There were no significant alterations in biochemical parameters. The prevalence of Helicobacter spp. infection in dogs was 97.1 % for the experimental group and 100 % for the control group. Effectiveness was of 33.3 and 55 % in the experimental and control group respectively. The oral administration of H. celastroides was well-tolerated and safe. CONCLUSION: The root-bark of H. celastroides produced no signs of toxicity, and manifested pharmacological activity that indicated the possibility of an alternative treatment for H. pylori infection. Effectiveness is still low so it is necessary to continue research.


Subject(s)
Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Hippocrateaceae/chemistry , Plant Extracts/administration & dosage , Animals , Dogs , Drug Evaluation, Preclinical , Female , Helicobacter Infections/microbiology , Helicobacter pylori/physiology , Hippocrateaceae/toxicity , Humans , Lethal Dose 50 , Male , Mice , Mice, Inbred BALB C , Plant Extracts/toxicity , Plant Roots/chemistry
15.
J Neurochem ; 137(6): 860-6, 2016 06.
Article in English | MEDLINE | ID: mdl-26843469

ABSTRACT

In addition to playing a fundamental structural role, the F-actin cytoskeleton in neuroendocrine chromaffin cells has a prominent influence on governing the molecular mechanism and regulating the secretory process. Performing such roles, the F-actin network might be essential to first transport, and later locate the cellular organelles participating in the secretory cycle. Chromaffin granules are transported from the internal cytosolic regions to the cell periphery along microtubular and F-actin structures. Once in the cortical region, they are embedded in the F-actin network where these vesicles experience restrictions in motility. Similarly, mitochondria transport is affected by both microtubule and F-actin inhibitors and suffers increasing motion restrictions when they are located in the cortical region. Therefore, the F-actin cortex is a key factor in defining the existence of two populations of cortical and perinuclear granules and mitochondria which could be distinguished by their different location and mobility. Interestingly, other important organelles for controlling intracellular calcium levels, such as the endoplasmic reticulum network, present clear differences in distribution and much lower mobility than chromaffin vesicles and mitochondria. Nevertheless, both mitochondria and the endoplasmic reticulum appear to distribute in the proximity of secretory sites to fulfill a pivotal role, forming triads with calcium channels ensuring the fine tuning of the secretory response. This review presents the contributions that provide the basis for our current view regarding the influence that F-actin has on the distribution of organelles participating in the release of catecholamines in chromaffin cells, and summarizes this knowledge in simple models. In chromaffin cells, organelles such as granules and mitochondria distribute forming cortical and perinuclear populations whereas others like the ER present homogenous distributions. In the present review we discuss the role of transport systems and the existence of an F-actin cortical structure as the main factors behind the formation of organelle subpopulations in this neuroendocrine cell model. This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015). Cover image for this issue: doi: 10.1111/jnc.13322.


Subject(s)
Actin Cytoskeleton/metabolism , Actins/physiology , Chromaffin Cells/ultrastructure , Organelles/physiology , Animals , Chromaffin Granules , Humans
16.
J Cell Sci ; 127(Pt 23): 5105-14, 2014 Dec 01.
Article in English | MEDLINE | ID: mdl-25300794

ABSTRACT

Knowledge of the distribution of mitochondria and endoplasmic reticulum (ER) in relation to the position of exocytotic sites is relevant to understanding the influence of these organelles in tuning Ca(2+) signals and secretion. Confocal images of probes tagged to mitochondria and the F-actin cytoskeleton revealed the existence of two populations of mitochondria, one that was cortical and one that was perinuclear. This mitochondrial distribution was also confirmed by using electron microscopy. In contrast, ER was sparse in the cortex and more abundant in deep cytoplasmic regions. The mitochondrial distribution might be due to organellar transport, which experiences increasing restrictions in the cell cortex. Further study of organelle distribution in relation to the position of SNARE microdomains and the granule fusion sites revealed that a third of the cortical mitochondria colocalized with exocytotic sites and another third located at a distance closer than two vesicle diameters. ER structures were also present in the vicinity of secretory sites but at a lower density. Therefore, mitochondria and ER have a spatial distribution that suggests a specialized role in modulation of exocytosis that fits with the role of cytosolic Ca(2+) microdomains described previously.


Subject(s)
Chromaffin Cells/metabolism , Chromaffin Cells/ultrastructure , Endoplasmic Reticulum/ultrastructure , Exocytosis , Mitochondria/ultrastructure , Animals , Calcium Signaling , Cattle , Cells, Cultured , Endoplasmic Reticulum/metabolism , Energy Metabolism , Microscopy, Confocal , Microscopy, Electron, Transmission , Microscopy, Fluorescence , Mitochondria/metabolism , Time Factors , Transfection
17.
Case Rep Gastroenterol ; 6(3): 668-76, 2012 Sep.
Article in English | MEDLINE | ID: mdl-23185148

ABSTRACT

A diverticulum is a bulging sack in any portion of the gastrointestinal tract. The most common site for the formation of diverticula is the large intestine. Small intestine diverticular disease is much less common than colonic diverticular disease. The most common symptom is non-specific epigastric pain and a bloating sensation. Major complications include diverticulitis, gastrointestinal bleeding, acute perforation, pancreatic or biliary (in the case of duodenal diverticula) disease, intestinal obstruction, intestinal perforation, localized abscess, malabsorption, anemia, volvulus and bacterial overgrowth. We describe the clinical case of a 65-year-old female patient with a diagnosis on hospital admittance of acute appendicitis and a intraoperative finding of diverticular disease of the small intestine, accompanied by complications such as intestinal perforation, bleeding and abdominal sepsis. This was surgically treated with intestinal resection and ileostomy and a subsequent re-intervention comprising perforation of the ileostomy and stomal remodeling. The patient remained hospitalized for approximately 1 month with antibiotics and local surgical wound healing, as well as changes in her diet with food supplements and metabolic control. She showed a favorable clinical evolution and was dismissed from the hospital to her home. We include here a discussion on trends in medical and surgical aspects as well as early handling or appropriate management to reduce the risk of fatal complications.

18.
Rev. cuba. anestesiol. reanim ; 10(1): 67-71, ene.-abr. 2011.
Article in Spanish | LILACS | ID: lil-739052

ABSTRACT

Introducción: El tratamiento de la Insuficiencia Renal Crónica Terminal mediante hemodiálisis tiene sus comienzos en 1944 y desde entonces la lucha por la supervivencia de estos pacientes ha conducido al desarrollo de múltiples variantes de acceso vascular. Objetivos: Dar a conocer una técnica alternativa para casos donde ya se han agotado las vías de acceso venoso convencionales. Presentación de caso: Se revisó la técnica de acceso descrita por diferentes autores con buenos resultados y al tener una paciente cuyo árbol vascular estaba agotado y con una emergencia dialítica, se decidió utilizar la vía paraesternal (toracotomía mínima) para abordar la aurícula y colocar el catéter de hemodiálisis en la vena cava inferior a través de la misma, con resultados satisfactorios. Conclusiones: La supervivencia del catéter fue de 15 meses, con buenos resultados. Se considera esta técnica una alternativa posible en aquellos pacientes sin otra posibilidad para el mantenimiento de su vida.


Introduction: The treatment of terminal chronic renal insufficiency by hemodialysis started in 1944 and since then the fight for the survival of these patients has led up to the development of multiple variants of vascular approach. Objectives: To make known an alternative technique for cases where the conventional routes of venous approach are exhausted. Case presentation: The approach technique was reviewed by different authors achieving good results due to the presence of a patient whose vascular tree was exhausted and also with a dialytic emergence, we decide to use the parasternal route (minimal thoracotomy) to approach the auricle and to place the hemodialysis catheter in the inferior vena cava thought it with satisfactory results. Conclusions: The catheter's survival was of 15 months with good results. It is considered that this technique is a potential alternative in those patients without another possibility of treatment for its life.

19.
Rev. cuba. anestesiol. reanim ; 10(1): 21-33, ene.-abr. 2011.
Article in Spanish | LILACS | ID: lil-739053

ABSTRACT

Introducción: Los fármacos modificadores de la hemostasia tienen múltiples indicaciones en las enfermedades cardiovasculares, por lo que con frecuencia el anestesiólogo se enfrenta a un paciente con éste tratamiento que requiere intervención quirúrgica. Objetivo: Actualizar la información sobre la conducta perioperatoria de los pacientes tratados con fármacos anticoagulantes y antiagregantes. Desarrollo: Para ello, se consultó la bibliografía relacionada con el tema a través de la red nacional de información médica y sus enlaces. El perioperatorio es un período de alto riesgo trombótico. Un paciente con riesgo y sin la adecuada cobertura antiagregante ó anticoagulante se enfrenta a un mayor riesgo de complicaciones cardíacas, cerebrales o vasculares periféricas. El concepto que el antiagregante se debe siempre suprimir, debe ser analizado, así como aquel que descarta la práctica de la anestesia regional en pacientes que requieren tromboprofilaxis, Toda estrategia debe ser individualizada y no sistematizada. Conclusiones: El anestesiólogo y el cirujano deben evaluar detalladamente el riesgo hemorrágico de la intervención quirúrgica, así como el riesgo trombótico de la supresión del fármaco anticoagulante ó antiagregante, siempre en el contexto particular de cada paciente en su circunstancia específica.


The modifying drugs of the hemostasis have many indications in cardiovascular diseases, thus the anesthesiologist confronts a patient with this treatment requiring a surgical intervention. Objective: To update the information on perioperative behavior of patients treated with anticoagulant and antiaggregant drugs. Development: For that reason, the bibliography related to this subject through the Nation Network of Medical Information and its links. The perioperative is a period of high thrombotic risk. A patient at risk and without the proper antiaggregant or anticoagulant coverage faced a great risk of cardiac, cerebral or peripheral vascular complications. The concept that the antiaggregant drug must to be suppressed always must to be analyzed as well as those rule out the practice of the regional anesthesia in patients requiring thromboprophylaxis. All strategy must to be individualized and not systematized. Conclusions: The anesthesiologist and the surgeon must to assess in detail the hemorrhagic risk of the surgical intervention, as well as the thrombotic risk of the anticoagulant and antiaggregant drug suppression always in the particular context of each patient in its specific circumstance.

20.
Rev cuba anestesiol reanim ; 10(1)ene.-abr. 2011.
Article in Spanish | CUMED | ID: cum-45564

ABSTRACT

El tratamiento de la Insuficiencia Renal Crónica Terminal mediante hemodiálisis tiene sus comienzos en 1944 y desde entonces la lucha por la supervivencia de estos pacientes ha conducido al desarrollo de múltiples variantes de acceso vascular. Objetivos: Dar a conocer una técnica alternativa para casos donde ya se han agotado las vías de acceso venoso convencionales. Presentación de caso: Se revisó la técnica de acceso descrita por diferentes autores con buenos resultados y al tener una paciente cuyo árbol vascular estaba agotado y con una emergencia dialítica, se decidió utilizar la vía paraesternal (toracotomía mínima) para abordar la aurícula y colocar el catéter de hemodiálisis en la vena cava inferior a través de la misma, con resultados satisfactorios. La supervivencia del catéter fue de 15 meses, con buenos resultados. Se considera esta técnica una alternativa posible en aquellos pacientes sin otra posibilidad para el mantenimiento de su vida(AU)


The treatment of terminal chronic renal insufficiency by hemodialysis started in 1944 and since then the fight for the survival of these patients has led up to the development of multiple variants of vascular approach. Objectives: To make known an alternative technique for cases where the conventional routes of venous approach are exhausted. Case presentation: The approach technique was reviewed by different authors achieving good results due to the presence of a patient whose vascular tree was exhausted and also with a dialytic emergence, we decide to use the parasternal route (minimal thoracotomy) to approach the auricle and to place the hemodialysis catheter in the inferior vena cava thought it with satisfactory results. The catheter's survival was of 15 months with good results. It is considered that this technique is a potential alternative in those patients without another possibility of treatment for its life(AU)


Subject(s)
Humans , Catheters, Indwelling , Renal Dialysis , Vena Cava, Superior
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