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1.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 50(2): [100827], Abr-Jun 2023. ilus, graf
Article in English | IBECS | ID: ibc-219223

ABSTRACT

Introduction: Frasier syndrome is a genetic disorder produced by a mutation in intron 9 of the WT1 gene, responsible for renal and genital dysfunctions. Clinical findings: It is characterized by discrepancy between the individual karyotype and the individual phenotype and corticosteroid-resistant nephrotic syndrome due to focal segmental glomerulosclerosis. Patients usually have a female phenotype with a 46 XY karyotype, which increases the risk of gonadoblastoma in 50% of cases. Kidney disease requires kidney transplantation in adulthood. Cardiovascular and bone-derived comorbidities such as hyperlipidaemia and osteopenia/osteoporosis, respectively, are also common. Main diagnoses: Mutations of the WT1 gene can lead to different clinical entities, most notably Denysh-Drash syndrome, Frasier syndrome, or isolated focal segmental glomerulosclerosis. We present a clinical case of a woman who debuted in childhood with difficult-to-control nephrotic syndrome, the lack of pubertal development, primary amenorrhoea and the absence of ovaries on imaging tests in adolescence, alerted to an underlying genetic problem that, after cytogenetic studies, allowed a diagnosis of Frasier syndrome. Therapeutic interventions: It is recommended to remove the gonads due to increased risk of developing gonadoblastoma. Treatment of associated dyslipidaemia and osteopenia is also necessary. Conclusion: Frasier syndrome is an unusual cause of infertility due to gonadal dysgenesis and is associated with kidney problems.(AU)


Introducción: El síndrome de Frasier es un trastorno genético producido por una mutación en el intrón 9 del gen WT1, responsable de disfunciones a nivel renal y genital. Principales síntomas: Se caracteriza por disgenesia gonadal con discrepancia entre cariotipo-fenotipo y síndrome nefrótico resistente a corticoides debido a glomeruloesclerosis focal y segmentaria. Las pacientes presentan habitualmente fenotipo femenino con cariotipo 46 XY, lo que aumenta el riesgo de gonadoblastoma en un 50% de los casos. La enfermedad renal obliga a trasplante renal en la edad adulta. Son habituales también las comorbilidades derivadas a nivel cardiovascular y óseo como hiperlipidemia y osteopenia/osteoporosis, respectivamente. Diagnósticos principales: Las mutaciones del gen WT1 pueden conducir en distintas entidades clínicas entre las que destaca el síndrome de Denys-Drash, el síndrome de Frasier o la glomeruloesclerosis focal y segmentaria aislada. Se presenta un caso clínico de una mujer que debutó en la infancia con síndrome nefrótico de difícil control y que, durante la adolescencia, ante la falta de desarrollo puberal, la amenorrea primaria y la ausencia de ovarios en las pruebas de imagen alertaron de un problema genético subyacente que, tras estudios citogenéticos, permitió el diagnóstico de síndrome de Frasier. Intervenciones terapéuticas: Se recomienda la exéresis de las gónadas debido al riesgo incrementado de gonadoblastoma. El tratamiento de la dislipemia y la osteopenia asociadas también es necesario. Conclusión: El síndrome de Frasier es una causa inusual de infertilidad debido a una disgenesia gonadal y se asocia con problemas a nivel renal.(AU)


Subject(s)
Humans , Female , Child , Gonadoblastoma , Glomerulonephritis, Membranous , Frasier Syndrome , Gonadal Dysgenesis , Inpatients , Physical Examination
4.
J Neuroimmune Pharmacol ; 13(1): 24-38, 2018 03.
Article in English | MEDLINE | ID: mdl-28808887

ABSTRACT

Polyphenols have beneficial neurological effects delaying cognitive and motor decline in aging due to their antioxidant, antiinflammatory and neuroprotective properties. These effects could be related to SIRT1 activation (implicated in synaptic plasticity, memory and inflammation) and monoaminergic synthesis modulation. In this work, we studied in old male rats, the in vivo effects of long-term administration of different polyphenols (silymarin, quercetin and naringenin; 20 mg/kg/day i.p, 4 weeks) (Sprague-Dawley, 18 months) on cognition and motor coordination. We also analyzed in different brain regions: tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities, which mediate central monoaminergic neurotransmitters synthesis; and immunoreactivities of SIRT1 and NF-κB (total and acetylated forms). Results indicated that chronic polyphenolic treatments showed restorative effects on cognition and motor coordination consistently with the biochemical and molecular results. Polyphenols reversed the age-induced deficits in monoaminergic neurotransmitters (serotonin, noradrenaline, and dopamine), increasing TPH and TH activity. In addition, polyphenolic treatments increased SIRT1 levels and decreased NF-κB levels in hippocampus. These results confirm polyphenolic treatments as a valuable potential therapeutic strategy for attenuating inflamm-aging and brain function decline.


Subject(s)
Aging/drug effects , Cognition/drug effects , Hippocampus/drug effects , Neuroprotective Agents/pharmacology , Animals , Biogenic Monoamines/biosynthesis , Flavanones/pharmacology , Hippocampus/metabolism , Male , Psychomotor Performance/drug effects , Quercetin/pharmacology , Rats , Rats, Sprague-Dawley , Silymarin/pharmacology , Sirtuin 1/biosynthesis
5.
Curr Neuropharmacol ; 16(2): 126-136, 2018 Jan 30.
Article in English | MEDLINE | ID: mdl-28676015

ABSTRACT

BACKGROUND: Classically the oxidative stress and more recently inflammatory processes have been identified as the major causes of brain aging. Oxidative stress and inflammation affect each other, but there is more information about the effects of oxidative stress on aging than regarding the contribution of inflammation on it. METHODS: In the intense research for methods to delay or mitigate the effects of aging, are interesting polyphenols, natural molecules synthesized by plants (e.g. resveratrol). Their antioxidant and anti-inflammatory properties make them useful molecules in the prevention of aging. RESULTS: The antiaging effects of polyphenols could be due to several related mechanisms, among which are the prevention of oxidative stress, SIRT1 activation and inflammaging modulation, via regulation of some signaling pathways, such as NF-κB. CONCLUSION: In this review, we describe the positive effects of polyphenols on the prevention of the changes that occur during aging in the brain and their consequences on cognition, emphasizing the possible modulation of inflammaging by polyphenols through a SIRT1-mediated mechanism.


Subject(s)
Aging/drug effects , Antioxidants/pharmacology , Brain/drug effects , Brain/metabolism , Sirtuin 1/metabolism , Stilbenes/pharmacology , Animals , Humans , Oxidative Stress/drug effects , Polyphenols/chemistry , Polyphenols/metabolism , Polyphenols/pharmacology , Resveratrol
6.
Curr Med Chem ; 22(22): 2690-711, 2015.
Article in English | MEDLINE | ID: mdl-26087763

ABSTRACT

Oxidative damage is related to aging and a wide range of human disorders. Mitochondria are in large part responsible for free radical production and they are also main targets of the attack of these toxic molecules. The resulting deleterious effects of the damage to mitochondria can be prevented by antioxidants. Melatonin is an endogenously-produced indoleamine that modulates numerous functions, including mitochondria-related functions; this result from its capacity to penetrate all morphophysiological barriers and to enter all subcellular compartments due to its amphiphilic nature. Furthermore, this indoleamine and its metabolites are powerful antioxidants and scavengers of free radicals, protecting cellular membranes, the electron transport chain and mitochondrial DNA from oxidative damage. These properties may make melatonin a potent protector against a variety of free radical-related diseases. By comparison, other conventional antioxidants have less efficacy due to their limited access to the mitochondria. In recent years, research has focused on the advancement of mitochondria-targeted antioxidants, such as MitoQ (composed by the lipophilic triphenylphosphonium cation conjugated to the endogenous antioxidant coenzyme Q10) and MitoE (composed by the triphenylphosphonium cation attached to the antioxidant α-tocopherol). Mitochondria-targeted antioxidants accumulate in several hundred-fold greater concentrations within mitochondria and protect these critical organelles from oxidative damage. Melatonin also seems to be a mitochondria-targeted antioxidant and has similar protective actions as the synthetic antioxidants. Further work is required to determine the therapeutic properties of these antioxidants in ameliorating diseases related to mitochondrial dysfunction.


Subject(s)
Antioxidants/pharmacology , Melatonin/pharmacology , Mitochondria/drug effects , Oxidative Stress/drug effects , Humans
7.
Age (Dordr) ; 37(3): 9777, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25895558

ABSTRACT

Resveratrol is a polyphenol exhibiting antioxidant and neuroprotective effects in neurodegenerative diseases. However, neuroprotective properties during normal aging have not been clearly demonstrated. We analyzed the in vivo effects of chronic administration of resveratrol (20 mg/kg/day for 4 weeks) in old male rats (Wistar, 20 months), on tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities which mediate central monoaminergic neurotransmitters synthesis, and besides, on hippocampal-dependent working memory test (radial maze). Our results show an age-related decline in neurochemical parameters that were reversed by resveratrol administration. The resveratrol treatment enhances serotonin (5-HT) levels in pineal gland, in hippocampus, and in striatum, and those of noradrenaline (NA) in hippocampus and also dopamine (DA) in striatum. These changes were largely due to an increased activity of TPH-1 (463 % in pineal gland), TPH-2 (70-51 % in hippocampus and striatum), and TH (150-36 % in hippocampus and striatum). Additionally, the observed hippocampal effects correlate with a resveratrol-induced restorative effect on working memory (radial maze). In conclusion, this study suggests resveratrol treatment as a restoring therapy for the impaired cognitive functions occurring along normal aging process, by preventing 5-HT, DA, and NA neurotransmission decline.


Subject(s)
Aging/drug effects , Cognition/drug effects , Stilbenes/pharmacology , Animals , Body Temperature/drug effects , Body Weight/drug effects , Brain/metabolism , Chromatography, High Pressure Liquid , Male , Rats , Rats, Wistar , Resveratrol , Stilbenes/administration & dosage , Tryptophan Hydroxylase/metabolism , Tyrosine 3-Monooxygenase/metabolism
8.
Osteoarthritis Cartilage ; 21(9): 1346-54, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23973149

ABSTRACT

OBJECTIVE: The aim of this study was to determine in intact and inflamed knee joints of the rat, the effect of the bradykinin (BK) B2 receptor antagonist fasitibant (MEN16132) on nociceptor mechanosensitivity and hyperalgesia. METHODS: Joint afferent sensory fibers of the medial articular nerve of anesthetized animals were electrophysiologically recorded, measuring nerve impulse activity evoked by passive innocuous and noxious movements of the joint, in intact and kaolin and carrageenan-injected joints. Knee joints of rats were also acutely inflamed by intra-articular injection of carrageenan alone. Long term duration of fasitibant antinociceptive effects were behaviorally evaluated using the incapacitance test. RESULTS: BK (100 µM) injected into the saphenous artery, induced excitation and sensitization of multi- and single unit recordings. Fasitibant (300 µM) injected prior to BK, reduced its excitatory effects as well as the overall increase of movement-evoked activity resulting from repeated injections of BK. Fasitibant did not affect movement-evoked activity of sensory fibers of intact, non-inflamed knee joints. Intra-articular fasitibant (100 µg/knee) significantly reduced the carrageenan-induced inflammatory hyperalgesia measured with the incapacitance test up to four days after treatment. This antinociceptive effect was not obtained with systemic endovenous injection of the drug. CONCLUSIONS: Fasitibant prevents B2 receptor-mediated activation and sensitization of peripheral joint afferents and the ensuing inflammatory hyperalgesia, and may be a useful, novel drug for arthritis pain treatment.


Subject(s)
Arthralgia/drug therapy , Arthritis, Experimental/drug therapy , Bradykinin B2 Receptor Antagonists , Nociceptors/drug effects , Ornithine/analogs & derivatives , Osteoarthritis, Knee/drug therapy , Sulfonamides/pharmacology , Action Potentials/physiology , Animals , Arthralgia/physiopathology , Arthritis, Experimental/physiopathology , Behavior, Animal/drug effects , Disease Models, Animal , Injections, Intra-Articular , Knee Joint/drug effects , Knee Joint/innervation , Male , Neurons, Afferent/drug effects , Neurons, Afferent/physiology , Nociceptors/physiology , Ornithine/pharmacology , Osteoarthritis, Knee/physiopathology , Rats , Rats, Wistar , Treatment Outcome
9.
Med. intensiva (Madr., Ed. impr.) ; 37(2): 99-109, mar. 2013. tab
Article in Spanish | IBECS | ID: ibc-113783

ABSTRACT

La Hipertensión Intraabdominal (HIA) y el Síndrome Compartimental Abdominal (SCA) son entidades frecuentes en los pacientes graves y cursan con una alta mortalidad. En esta revisión se actualizan los aspectos más debatidos sobre la HIA y el SCA: factores desencadenantes, epidemiología, pronóstico, métodos de medición de la presión intraabdominal (PIA), consecuencias fisiopatológicas y medidas terapéuticas, tanto médicas como quirúrgicas. Se plantea que, simultáneamente a los mecanismos de lesión estrictamente físicos, como la compresión directa de vasos y órganos intraabdominales, la transmisión de la PIA a otros compartimentos y el descenso del gasto cardíaco, pueden intervenir también una serie de mediadores inmunoinflamatorios generados en el propio intestino. La hipoperfusión, la isquemia mantenida y el fenómeno isquemia-reperfusión actuarían sobre la microbiota, el epitelio y sistema inmune intestinal desencadenando el Síndrome de Distrés Intestinal Agudo, una respuesta inflamatoria sistémica y una eventual disfunción multiorgánica que pueden aparecer en fases tardías del SCA (AU)


Seriously ill patients frequently present intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) as complications, and the associated mortality is very high. This review offers an update on the most controversial aspects of these entities: factors favoring their appearance, the most common causes, prognosis, and methods of measuring intra-abdominal pressure (IAP), physiopathological consequences in relation to the different organs and systems, and the currently accepted treatment measures (medical and/or surgical). Simultaneously to the strictly physical mechanisms of injury, such as direct compression of intra-abdominal organs and vessels, the transmission of IAP to other compartments, and the drop in cardiac output, a series of immune-inflammatory mediators generated in the intestine itself may also intervene. Hypoperfusion, sustained ischemia and the ischemia-reperfusion phenomenon, would act upon the microbiota, intestinal epithelium and intestinal immune system, triggering a systemic inflammatory response and multiorgan dysfunction that appears in the final stages of ACS (AU)


Subject(s)
Humans , Compartment Syndromes/complications , Intestinal Diseases/complications , Intra-Abdominal Hypertension/complications , Risk Factors , Critical Illness , Systemic Inflammatory Response Syndrome/complications
10.
Med Intensiva ; 37(2): 99-109, 2013 Mar.
Article in Spanish | MEDLINE | ID: mdl-22244213

ABSTRACT

Seriously ill patients frequently present intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) as complications, and the associated mortality is very high. This review offers an update on the most controversial aspects of these entities: factors favoring their appearance, the most common causes, prognosis, and methods of measuring intra-abdominal pressure (IAP), physiopathological consequences in relation to the different organs and systems, and the currently accepted treatment measures (medical and/or surgical). Simultaneously to the strictly physical mechanisms of injury, such as direct compression of intra-abdominal organs and vessels, the transmission of IAP to other compartments, and the drop in cardiac output, a series of immune-inflammatory mediators generated in the intestine itself may also intervene. Hypoperfusion, sustained ischemia and the ischemia-reperfusion phenomenon, would act upon the microbiota, intestinal epithelium and intestinal immune system, triggering a systemic inflammatory response and multiorgan dysfunction that appears in the final stages of ACS.


Subject(s)
Intestinal Diseases/etiology , Intra-Abdominal Hypertension/complications , Acute Disease , Humans , Intra-Abdominal Hypertension/etiology , Intra-Abdominal Hypertension/physiopathology , Intra-Abdominal Hypertension/therapy , Risk Factors , Syndrome
11.
Transplant Proc ; 44(9): 2564-6, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23146455

ABSTRACT

INTRODUCTION: The use of proliferation signal inhibitors (PSIs) for calcineurin-inhibitor (CNI) minimization or conversion protocols has been promoted for heart transplantation (HT) in the contexts of renal insufficiency, cardiac allograft vasculopathy (CAV), or malignancy. We evaluated our experience with conversion of patients from a CNI-based to a PSI-based immunosuppressive regimen. We focused on improvement in renal function. METHODS: This prospective follow-up included 96 HT patients converted to a PSI-based regimen from 2001 to 2010. We evaluated changes in creatinine clearance (CrCl) prior to at 1 year and at the end of follow-up after conversion. RESULTS: Ninety-six patients including 86% men showed a mean age of 62 ± 8 years. They were converted to a PSI-based regimen at 6.3 ± 4 years post-HT due to the following causes: CNI toxicity (45%), CAV (16%), cancer (16%), CNI toxicity + CAV (17%), or CNI toxicity + cancer (6%). CNI withdrawal was achieved in 77 cases (80%) and minimization in 19 (20%). Everolimus was used in 54 (56%) and sirolimus in 42 (44%) cases. Median follow-up time was 3.8 years. PSI discontinuation due to side effects was common (38%). There were 43 deaths mainly due to cancer and CAV. CrCl improved albeit not significantly in the withdrawal group from a median of 51 mL/min preconversion to 59 mL/min at the last follow-up (P = .12). In the minimization group, median CrCl worsened from a median of 61 mL/min preconversion to 51 mL/min at the last follow-up (P = .001). In the 58 cases (61%) of CNI nephrotoxicity, median CrCl improved from a median of 41 mL/min preconversion to 49 mL/min at the last follow-up (P = .04). CONCLUSION: Despite high rates of discontinuation of PSIs during long-term follow-up, the conversion regimen seemed to be useful to diminish CNI-related renal insufficiency especially with CNI withdrawal.


Subject(s)
Drug Substitution , Heart Transplantation , Immunosuppressive Agents/therapeutic use , Kidney/drug effects , Renal Insufficiency/prevention & control , Signal Transduction/drug effects , Sirolimus/analogs & derivatives , Aged , Biomarkers/blood , Calcineurin Inhibitors , Cause of Death , Creatinine/blood , Cyclosporine/therapeutic use , Drug Therapy, Combination , Everolimus , Female , Follow-Up Studies , Glomerular Filtration Rate/drug effects , Heart Transplantation/adverse effects , Heart Transplantation/immunology , Heart Transplantation/mortality , Humans , Immunosuppressive Agents/adverse effects , Kidney/metabolism , Kidney/physiopathology , Male , Middle Aged , Prospective Studies , Recovery of Function , Renal Insufficiency/blood , Renal Insufficiency/chemically induced , Renal Insufficiency/physiopathology , Sirolimus/adverse effects , Sirolimus/therapeutic use , Tacrolimus/therapeutic use , Time Factors , Treatment Outcome
14.
Todo hosp ; (270): 80-84, mayo 2011. graf, tab, ilus
Article in Spanish | IBECS | ID: ibc-102349

ABSTRACT

El objetivo del trabajo es proponer un sistema de indicadores de gestión a partir de los datos normalizados del Sistema de Información conómico ( SIE) de la Agencia Valenciana de Salud que aplica a los laboratorios públicos de la Comunidad Valenciana. Como resultados se obtienen indicadores de costes, de complejidad, de rendimiento de personal y de rendimiento de material y se establece una comparación con los datos del SIE 2008 de los 9 laboratorios participantes. En conclusión, la obtención de los indicadores de gestión a partir del Sistema de Información Económico, no supone ningún trabajo adicional para el laboratorio; la información es homogénea y la comparación interlaboratorios proporciona una información de gran utilidad para la gestión de los laboratorios (AU)


No disponible


Subject(s)
Humans , Laboratories, Hospital/economics , Clinical Laboratory Techniques/economics , Clinical Laboratory Information Systems/organization & administration , Pilot Projects
15.
Neurologia ; 25(3): 156-62, 2010 Apr.
Article in Spanish | MEDLINE | ID: mdl-20492861

ABSTRACT

INTRODUCTION: clinical pathways are standard health care methods to coordinate clinical work, reduce inter-clinician variability, improve patient care and increase staff and patient satisfaction. The aim of this study is to develop a clinical pathway capable of organising and developing standard procedures for diagnosis, treatment and care in patients with multiple sclerosis and to coordinate all medical specialists involved in this disease. METHODS: a multidisciplinary unit for the care of MS patients was developed. All of them and quality specialists analysed some international evidence-based studies, clinical guides, international guidelines and other clinical neurological pathways in several meetings and designed several documents for the clinical pathways. RESULTS: a clinical pathway was created consisting of a scientific-technical framework, which arranges the care in relation to the diagnosis and reatment. The framework is accompanied by various patient-information documents on the disease, an information sheet on diagnostic procedures and a map of the process. Quality standards were established to achieve continuous improvement in patient care. CONCLUSIONS: a clinical pathway for the care of MS patients in a multidisciplinary unit homogenises and organises the care which the MSpatient should receive from the initial symptoms to the progressive stages. This clinical pathway improves the quality of patient care, reduces the variability in work protocols and rationalises the use of the available health care resources.


Subject(s)
Critical Pathways , Multiple Sclerosis/therapy , Data Interpretation, Statistical , Humans , Multiple Sclerosis/diagnosis , Patient Satisfaction , Quality Control
16.
Neurología (Barc., Ed. impr.) ; 25(3): 156-162, abr. 2010. ilus
Article in Spanish | IBECS | ID: ibc-94701

ABSTRACT

Introducción: Las vías clínicas (VC) son herramientas para coordinar el trabajo asistencial, reducir la variabilidad entre el personal sanitario y mejorar la atención y el cuidado del paciente. La esclerosis múltiple (EM) es una enfermedad neurológica crónica que afecta a pacientes jóvenes y es incapacitante. El objetivo es desarrollar una vía clínica para mejorar el diagnóstico, el tratamiento y la atención de los pacientes con EM y, asimismo, facilitar la coordinación de todos los especialistas implicados en este proceso. Método: Siguiendo el modelo FOCUS-PDCA se organiza un equipo de trabajo integrado por diferentes profesionales implicados en la atención del paciente con EM. Se realiza una revisión bibliográfica exhaustiva y se llega a consenso; así, se diseñan los documentos de la VC con base en la evidencia científica. Resultados: Se crea una vía clínica compuesta por los siguientes elementos: una matriz temporal con una serie de anexos para ordenar el proceso diagnóstico y el tratamiento, un impreso de información a los pacientes sobre las pruebas diagnósticas, una hoja de información sobre la enfermedad y un mapa de procesos, una encuesta de evaluación de la calidad percibida y un documento con indicadores de calidad para evaluar la VC. Conclusiones: El desarrollo de una VC de EM facilita la atención multidisciplinaria y mejora la calidad asistencial. Esta propuesta es novedosa al enfocar la atención integral de la EM desde su inicio, tanto en aspectos diagnósticos como terapéuticos, incluyendo el ámbito ambulatorio (AU)


Introduction: Clinical pathways are standard health care methods to coordinate clinical work, reduce inter-clinician variability, improve patient care and increase staff and patient satisfaction. The aim of this study is to develop a clinical pathway capable of organising and developing standard procedures for diagnosis, treatment and care in patients with multiple sclerosis and to coordinate all medical specialists involved in this disease. Methods: A multidisciplinary unit for the care of MS patients was developed. All of them and quality specialists analysed some international evidence-based studies, clinical guides, international guidelines and other clinical neurological pathways in several meetings and designed several documents for the clinical pathways. Results: A clinical pathway was created consisting of a scientific-technical framework, which arranges the care in relation to the diagnosis and reatment. The framework is accompanied by various patient-information documents on the disease, an information sheet on diagnostic procedures and a map of the process. Quality standards were established to achieve continuous improvement in patient care. Conclusions: A clinical pathway for the care of MS patients in a multidisciplinary unit homogenises and organises the care which the MSpatient should receive from the initial symptoms to the progressive stages. This clinical pathway improves the quality of patient care, reduces the variability in work protocols and rationalises the use of the available health care resources (AU)


Subject(s)
Humans , Multiple Sclerosis/therapy , Clinical Protocols/standards , Hospital Units/organization & administration , Practice Patterns, Physicians' , Outcome and Process Assessment, Health Care
17.
Clin. transl. oncol. (Print) ; 12(2): 81-91, feb. 2010. tab, ilus
Article in English | IBECS | ID: ibc-123891

ABSTRACT

Chemotherapy-induced peripheral neuropathy (CIN) is a common toxicity of anticancer treatment and its incidence is growing. It significantly affects quality of life and is a dose-limiting factor that interferes with treatment. Its diagnosis can be established in clinical terms but some complementary tests can help when the diagnosis is difficult. There is still no proven method to prevent it that has become a standard of care in spite of the huge amount of investigation carried out in recent years. There are promising strategies that could help reduce the burden of this complication. This review will suggest an approach to the diagnosis of these disorders and provide an update on new therapies (AU)


Subject(s)
Humans , Animals , Male , Female , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/diagnosis , Dietary Supplements , Neuroprotective Agents/therapeutic use , Peripheral Nerves , Peripheral Nerves/physiology , Platinum Compounds/adverse effects , Platinum Compounds/pharmacology , Vitamins/therapeutic use
18.
Mol Phylogenet Evol ; 54(3): 857-69, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19874906

ABSTRACT

Phylogenetic analyses using up to 1532 base pairs (bp) of mitochondrial DNA from 106 specimens of Neotropical Mabuya, including 18 of the 19 recognized South American and Mesoamerican species, indicate that most species of the genus are monophyletic, including M. nigropunctata that had previously been reported to be paraphyletic. The present results shows that this species includes three highly divergent and largely allopatric lineages restricted to occidental, meridional, and oriental Amazonia. Our dataset demonstrates that previous claims regarding the paraphyletic status of M. nigropunctata and the phylogenetic relationships within this species complex based on the analysis of three mitochondrial and four nuclear genes (approx. 5000bp) were erroneous and resulted from two contaminated cytochrome b sequences. The phylogenetic results indicate that diversification in the Neotropical genus Mabuya started approximately in the Middle Miocene (15.5-13.4Ma). The divergence dates estimated for the Mabuya nigropunctata species complex suggest that the major cladogenetic events that produced the three main groups (occidental (oriental+meridional)) occurred during the Late Miocene. These estimations show that diversification within the M. nigropunctata species complex was not triggered by the climatic changes that occurred during the Pleistocene, as has been suggested by several authors. Rather, our data support the hypothesis that the late tertiary (essentially Miocene epoch) was a period that played a very important role in the generation of biological diversity in the Amazonian forests. Speciation between Mabuyacarvalhoi, endemic to the coastal mountain range of Venezuela, and M. croizati, restricted to the Guiana Shield, occurred during the Middle Miocene and may have been as the result of a vicariant event produced by the formation of the present day Orinoco river drainage basin and the consequent appearance of the Llanos del Orinoco, which acted as a barrier to dispersal between these two species. The split between M. bistriata and M. altamazonica and between the occidental and (meridional+oriental) clades of M. nigropunctata fits very well with the biogeographic split between the eastern and western Amazon basins reported for several other taxa.


Subject(s)
Evolution, Molecular , Genetic Speciation , Lizards/classification , Phylogeny , Animals , Cell Nucleus/genetics , DNA, Mitochondrial/genetics , Geography , Lizards/anatomy & histology , Lizards/genetics , Sequence Analysis, DNA
19.
Neurologia ; 24(7): 435-8, 2009 Sep.
Article in Spanish | MEDLINE | ID: mdl-19921551

ABSTRACT

INTRODUCTION AND OBJECTIVE: There are 4 immunomodulator treatments approved as first line therapy for patients with re-lapsing-remitting multiple sclerosis (RRMS). The objective of this study is to assess if glatiramer acetate (GA) is useful or not in patients who have discontinued interferon beta due to a suboptimal response or adverse events. METHODS: This is an observational and retrospective study in RRMS patients who discontinued IFN-beta therapy (2.9+/-2.4 years of treatment) and switched to GA (1.9+/-1.4 years). They were classified in 2 groups depending on the reason for discontinuation: suboptimal response or side effects. In both treatments we analysed number of relapses, treatment duration and causes of discontinuation. RESULTS: We included 58 patients of which 20 discontinued IFN-beta for lack of effectiveness whereas 38 were due to adverse events. Patients who discontinued for suboptimal response changed from 1.38 +/- 0.95 relapses per year with IFN-beta to 0.52+/-0.86 with GA. Patients who discontinued for adverse events changed from 0.33 +/- 0.64 relapses per year with IFN-beta to 0.37+/-0.79 with GA. CONCLUSIONS: GA can be considered a good alternative treatment for MS patients with a suboptimal response or adverse events with IFN-beta which confirms the existence of different mechanisms of action in both drugs.


Subject(s)
Immunosuppressive Agents/therapeutic use , Interferon-beta/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Peptides/therapeutic use , Adult , Disease Progression , Female , Glatiramer Acetate , Humans , Interferon-beta/adverse effects , Male , Middle Aged , Retrospective Studies , Treatment Outcome
20.
Rev Clin Esp ; 209(9): 415-23, 2009 Oct.
Article in Spanish | MEDLINE | ID: mdl-19852909

ABSTRACT

INTRODUCTION: We performed this study to compare the achievement of lipid targets as well as the change on C reactive protein (CRP) values of two different strategies, the combination of ezetimibe plus statins compared to the doubling of the previous statin dose. METHODS: Retrospective longitudinal study of 111 dyslipidemic patients, treated with statins, whose cholesterol values were still elevated. In 59 patients the previous statin dose was doubled, in 52 patients ezetimibe was added to the statin. Differences on lipid parameters and CRP were measured. RESULTS: Patients treated with the association of ezetimibe plus statins obtained a higher reduction of LDL-cholesterol levels (38% vs. 18.1%, p<0.001), compared with those doubling the statin dose. A reduction on CRP values was observed only in patients on combined therapy (22.5%; p<0.005), CRP change was not related to lipids variation. More patients with high coronary risk treated with ezetimibe plus statin, reached lipid goals (LDL<100 mg/dl) compared to those whose statin dose was doubled (47% vs 19%; p<0.001) and the same happened on very high coronary risk patients (LDL<70 mg/dl) (43% vs 2%; p<0,001). More patients in the group ezetimibe plus statin achieved the combined target lipid control and CRP<3 mg/l (19% vs. 3%, p=0.002). DISCUSSION: Combination treatment of ezetimibe with statins on high coronary risk patients showed a better achievement of LDL-cholesterol goals with a reduction of CRP values.


Subject(s)
Azetidines/therapeutic use , C-Reactive Protein/analysis , Cholesterol, LDL/blood , Dyslipidemias/blood , Dyslipidemias/drug therapy , Aged , Coronary Disease/blood , Coronary Disease/etiology , Dyslipidemias/complications , Ezetimibe , Female , Humans , Longitudinal Studies , Male , Retrospective Studies , Risk Factors
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