Molecular and Genetic Mechanisms of Neurotoxicity During Anti-seizure Medications Use.

Abstract: Epilepsy is a multifactorial pathology that has allowed the development of various drugs aiming to combat it. This effort was formally initiated in the 1940s when phenytoin began to be used. It eventually turned out to be a drug with great anticonvulsant efficacy. At present, several potentially good new generation anti-seizure medications (ASMs) have been developed. Most of them present more tolerability and less toxic effects. However, they continue to have adverse effects at different levels. In addition, some seizures are difficult to treat with ASMs, representing 30% of the total cases of people who suffer from epilepsy. This review aims to explore the genetic and molecular mechanisms of ASMs neurotoxicity, proposing the study of damage caused by epileptic seizures, in addition to the deterioration generated by anti-seizure drug administration within the central nervous system. It is beyond question that there is a need to develop drugs that lower the lower the risk of secondary and toxic effects of ASMs. Simultaneously, we must find strategies that produce fewer harmful interactions and more health benefits when taking anti-seizure drugs.

A Molecular Approach of Caloric Restriction and Vitamins for Cancer Prevention.

Each year, cancer claims the lives of around 10.0 million people worldwide. Food components have been shown to alter numerous intracellular signaling events that frequently go awry during carcinogenesis. Many studies suggest that dietary behaviors involving the consumption of antioxidant-rich foods, as well as caloric restriction, may play an important role in cancer prevention. Gene expression patterns, such as genetic polymorphisms, can influence the response to food components by altering their specific action on targets, as well as absorption, metabolism, and distribution, among other things. This review discusses two significant cancer prevention techniques: a vitamin-rich diet and caloric restriction. It also discusses the possible molecular interactions between the two dietary strategies and the first clues of a probable synergy that would come from combining caloric restriction with antioxidant use. Caloric restriction diets have positive effects on life expectancy and enable avoidance of age-related illnesses. As a result, this manuscript is based on the degenerative nature of cancer and intends to shed light on the biochemical features of not just calorie restriction but also vitamins. Both are thought to have an effect on oxidative stress, autophagy, and signaling pathways involved in energy metabolism and mitochondrial functions.

The Role of the Vagus Nerve in the Microbiome and Digestive System in Relation to Epilepsy.

The Enteric Nervous System (ENS) is described as a division of the Peripheral Nervous System (PNS), located within the gut wall and it is formed by two main plexuses: the myenteric plexus (Auerbach's) and the submucosal plexus (Meissner's). The contribution of the ENS to the pathophysiology of various neurological diseases such as Parkinson's or Alzheimer's disease has been described in the literature, while some other studies have found a connection between epilepsy and the gastrointestinal tract. The above could be explained by cholinergic neurons and neurotransmission systems in the myenteric and submucosal plexuses, regulating the vagal excitability effect. It is also understandable, as the discharges arising in the amygdala are transmitted to the intestine through projections the dorsal motor nucleus of the vagus, giving rise to efferent fibers that stimulate the gastrointestinal tract and consequently the symptoms at this level. Therefore, this review's main objective is to argue in favor of the existing relationship of the ENS with the Central Nervous System (CNS) as a facilitator of epileptogenic or ictogenic mechanisms. The gut microbiota also participates in this interaction; however, it depends on many individual factors of each human being. The link between the ENS and the CNS is a poorly studied epileptogenic site with a big impact on one of the most prevalent neurological conditions such as epilepsy.

Rats in Epilepsy Research: A Bibliometric Analysis of Citations Between 1969 and 2020 on Experimental Models in Epilepsy.

Epilepsy stands as a prominent neurological disorder, affecting a substantial number of individuals who, unfortunately, do not respond to conventional antiepileptic medications. To unravel the intricate mechanisms underlying epileptic seizures and explore potential therapeutic avenues, researchers have turned to animal models. Among these models, rats have emerged as one of the cornerstones of epilepsy research. This bibliometric analysis embarks on the crucial task of delving into the role of rat models in deciphering the mysteries of epileptic seizures and, notably, pinpointing the most prevalent models in use. Our study harnessed Scopus' citation tracking feature to review a range of research papers dating from 1969 to 2020, all dedicated to the exploration of epileptic seizures in rats. The citations that emerged from this rigorous process were subjected to thematic coding, primarily centered around the specific epileptic animal models employed, and subsequently, comprehensive descriptive statistics were computed. In this effort, we found a total of 1,318 publications that explore the world of rat studies, accumulating a substantial citation count of 44,824 references. This analysis illuminated the invaluable role that research employing rat models has played in shaping our current clinical understanding of epileptic seizures. Notably, several models have emerged as predominant forces in this field, including those induced by pilocarpine, pentylenetetrazole (PTZ), kainic acid (KA), electric kindling, and electroshock. This bibliometric exploration serves as a resounding reminder of the pivotal position that rat models occupy in advancing our comprehension of epilepsy. These findings resonate strongly, underscoring the continued importance of directing research and development funding toward this debilitating disorder, with the ultimate aim of maximizing the benefits for the patients grappling with this condition. The potential to revolutionize our approach to epilepsy and enhance the quality of life for those affected remains a beacon of hope, illuminated by the contributions of these tireless researchers and their trusty rat companions.

Molecular and Genetic Mechanisms of Neurotoxicity During Anti-seizure Medications Use

ABSTRACT Epilepsy is a multifactorial pathology that has allowed the development of various drugs aiming to combat it. This effort was formally initiated in the 1940s when phenytoin began to be used. It eventually turned out to be a drug with great anticonvulsant efficacy. At present, several potentially good new generation anti-seizure medications (ASMs) have been developed. Most of them present more tolerability and less toxic effects. However, they continue to have adverse effects at different levels. In addition, some seizures are difficult to treat with ASMs, representing 30% of the total cases of people who suffer from epilepsy. This review aims to explore the genetic and molecular mechanisms of ASMs neurotoxicity, proposing the study of damage caused by epileptic seizures, in addition to the deterioration generated by anti-seizure drug administration within the central nervous system. It is beyond question that there is a need to develop drugs that lower the lower the risk of secondary and toxic effects of ASMs. Simultaneously, we must find strategies that produce fewer harmful interactions and more health benefits when taking anti-seizure drugs.

Nutrición enteral precoz en pacientes con gastrectomía total por cáncer / Early enteral nutrition in patients subjected to a total gastrectomy

Background: Total parenteral nutrition has a high cost and frequency of complications. Enteral feeding is a feasible alternative that can be started early in the postoperative period. Aim: To assess digestive tolerance to early enteral feeding in cancer patients undergoing total gastrectomy and to compare early enteral feeding (EEF) with total parenteral nutrition plus enteral feeding (TPN+EF), initiated after overcoming postoperative ileus. Patients and methods: Subjects with a resectable gastric cancer were considered eligible for the study. During surgery a nasoenteral tube was placed and patients were prospectively randomized to EEF or TPN+EF. Digestive tolerance, effectiveness, complications and costs between both modalities of nutritional support were compared. Results: Twenty eight patients (15 male, aged 63ñ14 years old) were studied. Fourteen patients were randomized to EEF and 14 to TPN+EF. Diarrhea occurred in 14 and 29 percent of EEF and TPN+EF patients respectively, (p: NS). Patients with TPN+EF received an average of 28 Cal/kg/day and 1.1 g/kg/day proteins. Patients with EEF received an average of 29 Cal/kg/day and 0.8 g/kg/day proteins. At the eighth postoperative day, serum albumin was 3.9ñ0.7 and 3.2ñ0.5 g/dl in EEF and TPN+EF patients respectively (p <0.05), serum prealbumin was 16.9ñ5 and 12.3ñ4.3 mg/dl in EEF and TPN+EF patients respectively (p <0.05) and nitrogen balance was +2.4ñ1.5 and -1.6ñ0.6 g/24 h in EEF and TPN+EF patients respectively (p <0.05). Postoperative hyperglycemia was observed with a lower frequency and nutritional support costs and length of hospital stay were significantly lower in the EEF group. Conclusions: After total gastrectomy EEF is well tolerated, safe and effective, even during the early postoperative ileus. This therapeutic modality could be the first choice for nutritional support in these patients

Obesidad: factor de riesgo para esteatohepatitis y fibrosis hepática / Obesity as a risk factor for steatohepatitis and hepatic fibrosis

Background: Nonalcoholic fatty liver (NAFL) has been recognized as a cause of chronic liver disease. Its main risk factor is obesity. Aim: To describe the clinical and liver pathological findings in a group of patients who underwent surgery as obesity treatment. Patients and Methods: Sixty eight patients with severe or morbid obesity were subjected to surgery as obesity treatment. Each patient was evaluated with a complete clinical and laboratory medical assessment. A wedge of liver was excised during surgery. Liver biopsies were analyzed without knowledge of clinical and laboratory findings. The presence of steatosis, inflammation (portal or lobular), fibrosis and cirrhosis were recorded in the pathological analysis. Age and body mass index (BMI) were correlated with pathological data. Significance was set at a p value of less than 0.05. Results: Ninety one percent of patients had steatosis, 45 percent inflammation and 47 percent fibrosis. One patient had cirrhosis (1,4 percent). There was a statistically significant association between BMI and moderate or severe steatosis (p <0.03). There was also an association between BMI and portal (p=0.017) and lobular inflammation (p=0.034). A BMI over 40 kg/m2 (morbid obesity) was significantly associated with the presence of fibrosis (p=0.032). Moreover, the presence of moderate or severe steatosis was a risk factor for the development of hepatic fibrosis (p=0.026). Conclusions: Obesity is a major and independent risk factor for steatohepatitis and fibrosis. The degree of steatosis in the liver biopsy, is a risk factor for the development of fibrosis

Características clínicas y de laboratorio de pacientes con reflujo gastroesofágico crónico patológico / Clinical and laboratory features of patients with chronic gastroesophageal reflux

Background: Sixty percent of adults has typical symptoms of gastroesophageal reflux in Chile. Aim: To report the clinical and laboratory features of patients with gastroesophageal reflux. Patients and methods: Five hundred thirty four patients (255 male) with gastroesophageal reflux were included in a prospective protocol that included clinical analysis, manometry and endoscopy in all patients, barium swallow in 427, scintigraphy in 195, acid reflux test in 359, 24 h pH in 175, and differential potential of gastroesophageal mucosa in 73 patients. Results: There was no correlation between the severity of symptoms and the endoscopical severity. Patients with Barret esophagus were 12 years older, were male in a greater proportion and had a higher proportion of manometrically incompetent sphincters than patients with esophageal reflux but without esophagitis or with erosive esophagitis. Severity of acid reflux, measured with 24 h pH monitoring was proportional to the endoscopical damage of the mucosa. There was a close relationship between the mucosal change limit determined with differential potentials and with endoscopy. No short esophagi were found. Conclusions: Patients with symptoms of gastroesophageal reflux must be assessed using several objective measures to determine the severity of their pathological alterations

Cáncer de la vesícula biliar: resultados de la cirugía resectiva / Gallbladder cancer: results of resective surgery

El cáncer de vesícula biliar se mantiene como la primera causa de muerte por cáncer en mujeres en Chile y con tasas de mortalidad en sostenido aumento. La cirugía ha sido formulada como la terapia fundamental para este cáncer. Se presenta la experiencia prospectiva en el manejo quirúrgico de la enfermedad en pacientes con tumores T1b a T4 de la clasificación TNM, en el período enero de 1995 a diciembre de 2000. En este lapso egresaron 176 pacientes portadores de cáncer de vesícula, 134 (76,1 por ciento) de sexo femenino y edad promedio de 60,4 años (rango 28 a 92). Estos 176 pacientes corresponden al 2,3 por ciento del total de intervenciones quirúrgicas sobre la vesícula biliar en este mismo período. En 39 pacientes (22,8 por ciento) se demostró diseminación hepática o peritoneal en el intraoperatorio, 7 (3,9 por ciento) no fueron operados y hubo 9 pacientes (5,1 por ciento) con cáncer limitado a la mucosa. Se consideró 104 pacientes candidatos a cirugía ampliada, de los cuales 42 fueron explorados con intención resectiva. Los 61 pacientes restantes rechazaron segunda intervención por diferentes motivos. Hay seguimiento global de 92,6 por ciento de los 176 pacientes. Se practicó algún tipo de hepatectomía y linfadenectomía en 6 pacientes con tumor T1b, 7 pacientes T2, 13 pacientes T3 y 14 pacientes T4. Se resecó la vía biliar como procedimiento agregado en 10 pacientes. Hubo 9,3 por ciento de morbilidad y ausencia de mortalidad. La sobrevida para los pacientes con tumores T1b es 100 por ciento, con tumores T2 es 33 por ciento, 13 por ciento en los pacientes con tumores T3 y no hay sobrevida a 5 años para pacientes con tumores T4, sin embargo, se obtuvo sobrevida de 45 por ciento a 30 meses para los pacientes con tumores T4 resecados. No hubo diferencia estadísticamente significativa para ningún grupo de pacientes sometidos a cirugía radical en comparación con los sometidos sólo a colecistectomía

Evaluación subjetiva y objetiva de los resultados de la cirugía antirreflujo por video laparoscopía en pacientes con reflujo gastroesofágico / Subjective and objective assessment of the results of video laparoscopic anti-reflux surgery in patients with gastroesophageal reflux

Laparoscopic antireflux surgery is a minimally invasive procedure that should have similar results than classical surgical treatment. To report the results of a prospective study of laparoscopic antirelux surgery, 32 patients with gastroesophageal reflux and without Barret's esophagus, were subjected to endoscopy, amnometry and measurement of intraesophageal pH before and after laparoscopic surgery. Tehre were no postoperative deaths or complications. Gastroesophageal sphincter pressure and abdominal sphincter lenght increased from 9.1ñ3.9 to 13.0ñ3.5 mm Hg and from 8.1ñ6.2 to 13.5ñ5.4 cm after surgery (p<0.01). There was a decrease in acid reflux in 82 percent of patients. In conclusion, laparoscopic antireflux surgery reproduces exactly the results of open surgical procedures

Comparación de la anastomosis esofagoyeyunal mecánica vs manual para gastrectomía total en pacientes con cáncer gástrico / Comparison between mechanical and manual esophagojejunal anastomosis for total gastrectomy in gastric cancer patients

Se realizó un estudio prospectivo en 53 pacientes con cáncer gástrico sometidos a gastrectomía total comparando la técnica manual frente a la mecánica, en la anastomosis esofagoyeyunal. En 35 pacientes se realizó la técnica manual y en 18 la técnica con stapler. No hubo mortalidad operatoria en la serie. El tiempo operatorio, la incidencia de fístula y otras complicaciones postoperatorias fueron similares en ambos grupos. La frecuencia de infección de la herida operatoria, la presencia de absceso subfrénico y la estadía postoperatoria fueron significativamente menores en pacientes sometidos a la técnica mecánica. Este procedimiento es fácil de realizar, es reproducible de un cirujano a otro, no requiere de gran experiencia previa como la técnica manual y es una buena alternativa cuando es necesario hacer una anastomosis esofagoyeyunal alta

Vólvulo primario de intestino delgado en el adulto / Primary volvulus of the small intestine in adult

El vólvulo de intestino delgado primario es una condición en la cual existe una torsión de la totalidad o de un segmento del intestino delgado y su mesenterio, sin encontrarse malrotación intestinal, bridas adquiridas o congénitas o cualquier otra condición que facilite que se produzca el vólvulo. En el adulto generalmente ocurre en un segmento del intestino medio. Se presentan 4 casos de vólvulo primario del intestino delgado en el adulto, operado en el Servicio de Urgencia de la Clínica Alemana. Por su escasa frecuencia en nuestro medio, este cuadro presenta una importante dificultad diagnóstica. En todos los casos destaca en su presentación clínica, el comienzo agudo de dolor abdominal de gran intensidad, que no guarda relación con los hallazgos del examen clínico y con escasa repercusión en los estudios complementarios. Los cuatros pacientes fueron sometidos a intervención quirúrgica

Laparoscopía diagnóstica en algunos cánceres digestivos / Laparoscopic diagnosis of some digestive cancers

En un trabajo prospectivo 51 pacientes portadores de cáncer abdominal, con estudio completo de diseminación que incluía TAC, fueron sometidos, al momento de la cirugía, a una laparoscopia diagnóstica como última etapa de estudio prerresectivo. Veintiséis pacientes eran portadores de cáncer gástrico, la mitad fue resecable; 9 casos tenían cáncer de cabeza de páncreas, tres fueron resecables; 16 pacientes eran portadores de cáncer vesicular, hepático o de origen indeterminado, 5 de ellos fueron resecables. Se concluye que la laparsocopia contemporánea puede ser un valioso método para completar la etapificación en algunos cánceres digestivos en los que el estudio sugiere la eventual no resecabilidad