Prenatal nicotine exposure leads to epigenetic alterations in peripheral nervous system signaling genes in the testis of the rat.

BACKGROUND: Prenatal nicotine exposure (PNE) has been documented to cause numerous deleterious effects on fetal development. However, the epigenetic changes promoted by nicotine exposure on germ cells are still not well understood. OBJECTIVES: In this study, we focused on elucidating the impact of prenatal nicotine exposure on regulatory epigenetic mechanisms important for germ cell development. METHODS: Sprague-Dawley rats were exposed to nicotine during pregnancy and male progeny was analyzed at 11 weeks of age. Testis morphology was analyzed using frozen testis sections and expression of germ cell markers was examined by RT-qPCR; histone modifications were assessed by Western Blot (WB). DNA methylation analysis was performed by methylation-specific PCR of bisulfite converted DNA. Genome-wide DNA methylation was analyzed using Methylated DNA immunoprecipitation (MeDIP)-seq. We also carried out transcriptomics analysis of pituitary glands by RNA-seq. RESULTS: We show that gestational exposure to nicotine reduces germ cell numbers, perturbs meiosis, affects the expression of germ line reprogramming responsive genes, and impacts the DNA methylation of nervous system genes in the testis. PNE also causes perturbation of gene expression in the pituitary gland of the brain. CONCLUSIONS: Our data demonstrate that PNE leads to perturbation of male spermatogenesis, and the observed effects are associated with changes of peripheral nervous system signaling pathways. Alterations in the expression of genes associated with diverse biological activities such as cell migration, cell adhesion and GABA signaling in the pituitary gland underscore the complexity of the effects of nicotine exposure during pregnancy.

Deposition of Gadolinium in the Central and Peripheral Nervous Systems and Its Effects on Sensory, Cognitive, and Athletic Implications after Multiple Injections of Gadolinium-Based Contrast Agents in Rats.

BACKGROUND AND PURPOSE: After repeat administration of gadolinium-based contrast agents (GBCAs), the association between gadolinium retention in the central and peripheral nervous systems and the main manifestations of myelopathy and progressive neurologic symptoms remains unclear. We investigated the effects of the repeat administration of GBCAs on gadolinium retention in the central and peripheral nervous systems and the sensory, cognitive, and athletic implications. MATERIALS AND METHODS: Forty-eight male Wistar rats (6 weeks of age) were randomly divided into 4 experimental groups (12 rats in each group): the gadodiamide group (linear and nonionic GBCAs), the gadopentetate dimeglumine group (linear and ionic GBCAs), the gadoterate meglumine group (macrocyclic and ionic GBCAs), and the control group (0.9% saline solution). The brains of the rats were scanned using 9.4T MRI. Sensory behavioral tests were performed to assess the effect of GBCAs on pain sensitivity function. Gadolinium deposition in the brain, spinal cord, and peripheral nerves was determined by inductively coupled plasma mass-spectrometry. Transmission electron microscopy was used to observe the microscopic distribution of gadolinium after deposition in the spinal cord. The histopathologic features in the spinal cord were analyzed by H&E staining, Nissl staining, glial fibrillary acidic protein staining, and neuron-specific enolase staining after administration of GBCAs. RESULTS: All GBCAs resulted in gadolinium deposition in the central and peripheral nerve tissues, with the highest deposition in the sciatic nerve tissue (mean, 62.86 [SD, 12.56] nmol/g). Decreased muscle power, impairment of spatial cognitive function power, and pain hypersensitivity to thermal and mechanical stimuli were observed after exposure to gadodiamide. At the spinal cord, transmission electron microscopy found that the region of gadolinium depositions had a spheric structure similar to "sea urchins" and was mainly located near the vascular basement membrane. CONCLUSIONS: Multiple injections of GBCAs caused gadolinium deposition in the brain, spinal cord, and peripheral nerves, especially in the spinal cords of the gadodiamide group. Gadodiamide led to pain hypersensitivity and decreased muscle power and cognitive ability. For the patients who are hypersensitive to pain and need multiple MRI examinations, we recommend using macrocyclic GBCAs and the lowest dose possible.

Aplicación y seguimiento del tratamiento del dolor neuropático periférico con capsaicina 179 mg realizado por enfermeras / Application and follow-up of the peripheral neuropathic pain treatment with capsaicin 179 mg conducted by nurses

Objetivo: evaluar la efectividad del tratamiento con parches de capsaicina 179 mg en personas con dolor neuropático periférico aplicado y en seguimiento realizado por enfermeras. Método: serie de casos longitudinal retrospectiva efectuada en la Unidad de Dolor del Hospital Universitario Son Llàtzer (Palma) entre 2018 y 2020. La población de estudio fue de 163 personas con ese tratamiento. Se llevó a cabo medición basal al mes, a los tres y a los seis meses. Se midieron sexo, edad, tiempo de evolución, aplicaciones realizadas, mejora en intensidad (NPRS: 0 a 10 puntos) y extensión del dolor, calidad de vida relacionada con la salud (EQ-5D-3L: 0 peor a 1 mejor), impresión de mejoría global del paciente (PGI-I: mejora; empeora o no mejora), uso de fármacos adyuvantes y efectos secundarios. Se llevó a cabo estadística descriptiva. Resultados: se incluyeron 133 pacientes con registros completos (= 57 años; = 30,2 meses de evolución; = 1,6 aplicaciones por persona). Se redujo la zona de dolor [Sí reduce (Mes 1: 67%; Mes 3: 41%; Mes 6: 20%)] y la intensidad del dolor pasó de = 7,35 a 6,32 al sexto mes. La calidad de vida fue superior a la media basal (0,37 sobre 1) en todas las mediciones. Mejoró la PGI [Mejora (Mes 1: 64,6%: Mes 3: 58,9%; Mes 6: 53,6 %)]. Disminuyó el uso de medicación adyuvante [Sí reduce (Mes 1: 28%; Mes 3: 30%; Mes 6: 67%)]. Los efectos adversos fueron dolor (78,9%), eritema (67,7%) y prurito (63,9%). Conclusión: el tratamiento aplicado por enfermeras fue eficaz y seguro. El seguimiento debe ser prolongado para detectar necesidades y cambios.(AU)

Objective: to evaluate the efficacy of the treatment with capsaicin 179mg patches applied and on follow-up by nurses in persons with peripheral neuropathic pain. Method: a longitudinal retrospective series of cases conducted at the Pain Unit of the Hospital Universitario Son Llàtzer between 2018 and 2020. The study population consisted of 196 persons with that treatment. Basal measurement was conducted at one month, at three and six months. The following were measured: gender, age, time of evolution, applications conducted, improvement in intensity (NPRS scale: 0 to 10 points) and extent of pain, health-related quality of life (EQ-5D-3L: 0=the worst to 1=the best), patient global impression of improvement (PGI-I: improvement, worsening or no improvement), use of adjuvant drugs and side effects. Descriptive statistics was applied. Results: 133 patients were included with complete records(= 57 years; = 30.2 months of evolution; = 1.6 applications per person). There was a reduction in the pain area [Reduced (Month 1: 67%; Month 3: 41%; Month 6: 20%)] and pain intensity moved from = 7.35 to 6.32 at month six. Quality of life was superior to the mean baseline (0.37 of 1) in all measurements. There was improvement in PGI [Improvement (Month 1: 64.6%: Month 3: 58.9%; Month 6: 53.6 %)]. There was a reduction in the use of adjuvant medication [Reduced (Month 1: 28%; Month 3: 30%; Month 6: 67%)]. The adverse effects were pain (78.9%), erythema (67.7%) and itching (63.9%). Conclusion: the treatment applied by nurses was effective and safe. There must be follow-up at long term in order to detect any needs and changes.(AU)