Predictors of adverse effects to antiseizure drugs in adult patients with epilepsy from Colombia: A case-control study.

INTRODUCTION: Adverse drug reactions (ADRs) to antiseizure therapy can worsen the quality of life, reduce adherence, and potentially lead to treatment discontinuation and uncontrolled seizures. OBJECTIVES: The aim of the study was to develop a prognostic model for ADRs to antiseizure therapy in adult patients with epilepsy from Colombia. METHODS: This case-control study included adult patients with epilepsy, who were separated into two groups: one group with ADRs to antiseizure therapy (cases), as determined by a complete evaluation conducted by an epileptologist, and another group without ADRs (controls). Variables were analyzed to identify statistical differences between the two groups and were then selected to construct a prognostic model using logistic regression. The Bonferroni method was applied for multiple comparisons. RESULTS: Three hundred fifty-four patients with epilepsy were studied. One hundred and fifty (42%) patients had ADRs and 204 (57%) patients did not have ADs. A total of 362 ADRs were reported, with a third of them being general symptoms and most frequently occurring with older-generation antiseizure drugs (58%). Female sex, drug-resistant epilepsy, LEV, and CZP were risk factors, whereras the presence of tumoral etiology, absence of seizure triggers, and VPA were identified as protective factors. A prognostic model was constructed using previously reported risk factors for ADRs to antiseizure therapy and other variables available in this population study. In the multivariable analysis, the number of previously used antiseizure drugs (1, 2, or ≥3), TPM, CZP, LEV, PHT, and female sex were predictors of ADRs. The corrected p-values were estimated by the Bonferroni method; however, not all the variables achieved statistical significance with this adjustment. CONCLUSIONS: In adult patients with epilepsy from Colombia, we found that the number of previously used antiseizure drugs, TPM, CZP, LEV, PHT, and female sex were predictive factors for ADRs to antiseizure therapy.

Paclitaxel Regulates TRPA1 Function and Expression Through PKA and PKC.

Paclitaxel (PTX) is a frequently used anticancer drug that causes peripheral neuropathy. Transient receptor potential ankyrin 1 (TRPA1), a plasma membrane calcium channel, has been associated with PTX toxicity and with other chemotherapy agents such as oxaliplatin and vincristine. However, the effect of PTX on the functional expression and calcium currents of TRPA1 has not been determined. The present study shows the effect of PTX on TRPA1 activity in a neuronal cell line (SH-SY5Y). The effect of PTX on the expression of TRPA1 was assessed through quantitative PCR and Western blot analyses to determine the relative mRNA and protein expression levels. To assess the effect on calcium flux and currents, cells were exposed to PTX; simultaneously, a specific agonist and antagonist of TRPA1 were added to evaluate the differential response in exposed versus control cells. To assess the effect of PKA, PKC and PI3K on PTX-induced TRPA1 increased activity, selective inhibitors were added to these previous experiments. PTX increased the mRNA and protein expression of TRPA1 as well as the TRPA1-mediated Ca2+ currents and intracellular Ca2+ concentrations. This effect was dependent on AITC (a selective specific agonist) and was abolished with HC-030031 (a selective specific antagonist). The inhibition of PKA and PKC reduced the effect of PTX on the functional expression of TRPA1, whereas the inhibition of PI3K had no effects. PTX-induced neuropathy involves TRPA1 activity through an increase in functional expression and is regulated by PKA and PKC signaling. These findings support the role of the TRPA1 channel in the mechanisms altered by PTX, which can be involved in the process that lead to chemotherapy-induced neuropathy.

Role of TRPV4 Channel in Human White Adipocytes Metabolic Activity.

BACKGROUND: Intracellular calcium (Ca2+) homeostasis plays an essential role in adipocyte metabolism and its alteration is associated with obesity and related disorders. Transient receptor potential vanilloid 4 (TRPV4) channels are an important Ca2+ pathway in adipocytes and their activity is regulated by metabolic mediators such as insulin. In this study, we evaluated the role of TRPV4 channels in metabolic activity and adipokine secretion in human white adipocytes. METHODS: Human white adipocytes were freshly cultured and the effects of the activation and inhibition of TRPV4 channels on lipolysis, glucose uptake, lactate production, and leptin and adiponectin secretion were evaluated. RESULTS: Under basal and isoproterenol-stimulated conditions, TRPV4 activation by GSK1016709A decreased lipolysis whereas HC067047, an antagonist, increased lipolysis. The activation of TRPV4 resulted in increased glucose uptake and lactate production under both basal conditions and insulin-stimulated conditions; in contrast HC067047 decreased both parameters. Leptin production was increased, and adiponectin production was diminished by TRPV4 activation and its inhibition had the opposite effect. CONCLUSION: Our results suggested that TRPV4 channels are metabolic mediators involved in proadipogenic processes and glucose metabolism in adipocyte biology. TRPV4 channels could be a potential pharmacological target to treat metabolic disorders.

Decellularization and In Vivo Recellularization of Abdominal Porcine Fascial Tissue.

BACKGROUND: Tissue decellularization has evolved as a promising approach for tissue engineering applications. METHODS: In this study, we harvested fascial tissue from porcine anterior abdominal wall and the samples were decellularized with a combination of agents such as Triton X-100, trypsin and DNAase. Afterwards, we evaluated cell removal by histological analysis and DNA quantification. Mechanical functionality was evaluated by applying a range of hydrostatic pressures. A sample of decellularized fascia was transplanted into a rabbit and after 15 days a biopsy of this tissue was examined; the animal was observed during 6 months after surgery. RESULTS: The extracellular matrix was retained with a complete decellularization as evidenced by histologic examination. The DNA content was significantly reduced. The scaffold preserved its tensile mechanical properties. The graft was incorporated into a full thickness defect made in the rabbit abdominal wall. This tissue was infiltrated by granulation and inflammatory cells and the histologic structure was preserved 15 days after surgery. The animal did not develop hernias, infections or other complications, after a 6-months of follow up. CONCLUSIONS: The protocol of decellularization of fascial tissue employed in this study proved to be efficient. The mechanical test demonstrated that the samples were not damaged and maintained its physical characteristics; clinical evolution of the rabbit, recipient of the decellularized fascia, demonstrated that the graft was effective as a replacement of native tissue.In conclusion, a biological scaffold derived from porcine fascial tissue may be a suitable candidate for tissue engineering applications.

Perfil clínico y sociodemográfico de la neurosífilis: estudio retrospectivo en un centro de referencia de Colombia / Clinical and socio-demographic profile of neurosyphilis: a retrospective study in a reference centre in Colombia

Introducción. La neurosífilis es causada por Treponema pallidum y puede afectar al sistema nervioso central en cualquier momento de la infección. Desde inicios de este siglo, su incidencia ha ido en aumento, aun en la era postantibiótica. En países en vías de desarrollo, el problema tiene mayor magnitud y los estudios son escasos. Objetivo. Describir las características de la población con neurosífilis en un hospital de tercer nivel de Pereira, Colombia. Pacientes y métodos. Estudio descriptivo de corte transversal de pacientes con neurosífilis que acudieron a un centro de tercer nivel de Pereira, Colombia, entre 2012 y 2017. Los criterios diagnósticos se basaron en las siguientes variables: prueba treponémica en sangre, VDRL y análisis citoquímico del líquido cefalorraquídeo. Se consideraron variables sociodemográficas, clínicas y de laboratorio. Resultados. Se incluyó a 16 pacientes, 11 con neurosífilis definitiva y cinco con neurosífilis probable, con una edad media de 59,5 ± 13,78 años. El 75% (n = 12) de los casos eran hombres. La coinfección por virus de la inmunodeficiencia humana fue del 25%. Todos los pacientes tenían FTA-ABS positivo en sangre y 11 presentaron VDRL reactiva en el líquido cefalorraquídeo. La forma más frecuente de neurosífilis fue la tardía (62,5%), y predominó la parálisis general. Las manifestaciones clínicas más frecuentes fueron las alteraciones neuropsiquiátricas (46,9%), con predominio de la desorientación, los cambios en el comportamiento y el deterioro cognitivo, seguidos de las alteraciones motoras (36,7%). Conclusiones. La neurosífilis tardía fue la presentación más prevalente, caracterizada por manifestaciones neuropsiquiátricas. Una cuarta parte de los pacientes presentaba infección por virus de la inmunodeficiencia humana

Introduction. Neurosyphilis is the Treponema pallidum infection of the central nervous system and can occur at any time after the initial infection. In the 21st century, the incidence of neurosyphilis has increased in the post-antibiotic era. The highest rates of neurosyphilis are from low-income countries and the published studies are limited. Aim. To determine the clinical and sociodemographic characteristics of neurosyphilis patients in a tertiary care center in Pereira, Colombia. Patients and methods. Retrospective study of diagnosed neurosyphilis patients in a tertiary care center in Pereira, Colombia, between 2012 to 2017. The diagnosis was established based on serologic treponemal tests, VDRL in CSF, and CSF analysis. Sociodemographic, clinical, and laboratory parameters variables were obtained. Results. Sixteen patients were included, 11 with definitive neurosyphilis and 5 with probable neurosyphilis. The median age was 59.50 ± 13.78 years. Men accounted for 75% (n = 12) of the patients. Four patients were (25%) HIV-infected. All the patients had positive peripheral FTA-ABS and 11 had reactive VDRL in CSF. The most frequent form was late neurosyphilis (62.5%), being general paralysis the most common. The most frequently clinical manifestations were neuropsychiatric alterations (46.9%), predominantly disorientation, behavioral changes, and cognitive impairment, followed by motor changes (36.7%). Conclusions. Late neurosyphilis was the most prevalent form, predominantly neuropsychiatric alterations. only a quarter of patients presented HIV coinfection

Multivariable prediction model of drug resistance in adult patients with generalized epilepsy from Colombia: A case-control study.

INTRODUCTION: Patients with drug-resistant epilepsy (DRE) account for most of the burden of epilepsy, and they have poor prognosis in seizure control, higher morbidity, and mortality. OBJECTIVES: The objective of the study was to develop a prognostic model of drug resistance in adult patients with generalized epilepsy from Colombia. METHODS: In this case-control study of patients with generalized epilepsy, patients were separated into two groups: one group with DRE (cases) according to the new International League Against Epilepsy (ILAE) definition after a complete evaluation performed by an epileptologist and the other group without DRE (control). Variables were analyzed to identify statistical differences between groups and were then selected to construct a prognostic model from a logistic regression. RESULTS: One hundred thirty-three patients with generalized epilepsy were studied. Thirty-eight (28.5%) patients had DRE, and 95 (71.5%) did not have DRE. History of status epilepticus, abnormal findings from neurological examination, aura, any degree of cognitive impairment, epileptic seizures at any moment of the day, and any comorbidity were risk factors. The presence of seizures only in the waking state and idiopathic etiology were protective factors. A prognostic model was constructed with previously reported risk factors for DRE and other variables available in the population of this study. In the multivariable analysis, the history of status epilepticus (odds ratio (OR): 5.6, confidence interval (CI): 1.1-20.0, p = 0.031), abnormal findings from neurological examination (OR: 5.7, CI: 2.3-13.9, p = 0.000), and aura (OR: 6.1, CI: 1.8-20.8, p = 0.003) were strongly associated with DRE. CONCLUSIONS: In adult patients with generalized epilepsy, aura, abnormal findings from neurological examination, and history of status epilepticus were predictive factors for DRE.

Estimulación cerebral profunda en enfermedad de Parkinson / Deep brain stimulation in Parkinson disease

RESUMEN Introducción: la enfermedad de Parkinson es considerada la segunda causa de enfermedad neurodegenerativa, en la que se destacan signos y síntomas motores como temblor, bradicinesia, rigidez e inestabilidad postural, acompañados de síntomas no motores como alteraciones del sueño, autonómicas, cognitivas, gastrointestinales, entre otras. El tratamiento farmacológico de la enfermedad al inicio suele ser útil, pero cuando los síntomas persisten, el tratamiento falla o no se toleran sus reacciones adversas, es necesario considerar alternativas como la estimulación cerebral profunda. Metodología: revisión narrativa con énfasis en los aspectos clínicos de la terapia con estimulación cerebral profunda en los pacientes con enfermedad de Parkinson. Discusión: la estimulación cerebral profunda es una técnica quirúrgica en la que se implantan electrodos en regiones cerebrales específicas, generalmente el núcleo subtalámico, globo pálido interno o núcleo ventral intermedio del tálamo, y se conectan a un marcapasos subcutáneo desde donde se modula eléctricamente la actividad de estas áreas. Esta terapia ha mostrado ser costo-efectiva, aporta beneficios considerables en la mejoría de los síntomas de la enfermedad de Parkinson y cuenta con evidencia clínica en los pacientes que han sido seleccionados correctamente.

SUMMARY Introduction: Parkinson's disease is considered the second cause of neurodegenerative disease, in which motor signs and symptoms such as tremor, bradykinesia, rigidity and postural instability are highlighted, accompanied by non-motor symptoms such as sleep, autonomic, cognitive, gastrointestinal among others disturbances. The pharmacological treatment of the disease at the beginning is usually useful, but when the symptoms persist, the treatment fails or its adverse reactions are not tolerated, it is necessary to consider alternatives such as deep brain stimulation. Methodology: This is a narrative review with emphasis on the clinical aspects of deep brain stimulation therapy in patients with Parkinson's disease. Discussion: Deep brain stimulation is a surgical technique in which electrodes are implanted in specific brain regions, usually the subthalamic nucleus, globus pallidus interna or ventral intermediate nucleus of the thalamus, and are connected to a subcutaneous pacemaker from which the activity of these areas is modulated electrically. This therapy has been shown to be cost-effective, provides considerable benefits in improving the symptoms of Parkinson's disease and has clinical evidence in patients who have been correctly selected.