Don't Look Back and Spray! Risk of Endoscope Adhesion with Hemospray Application in Retroflexion in a Pediatric Patient.

Although the vast majority of recognized pediatric upper gastrointestinal bleeding (GIB) resolves spontaneously, gastrointestinal hemorrhage is the most common indication for urgent or emergent therapeutic endoscopy in pediatric practice. The application of hemostatic powders, including TC-325 (Hemospray, Cook Medical, Winston-Salem, NC, USA), has shown considerable impact on the control of acute bleeding, with the advantage of potentially covering an extensive area and requiring less technical expertise. We report a case of transient adherence of an esophagogastroduodenoscopy following Hemospray application in a 22-month-old with upper GIB. Our experience does not detract from the significant gains in the management of pediatric GIB from Hemospray; however, it does raise a cautionary note toward the application technique utilized.

Fluid therapy and traumatic brain injury: A narrative review / Fluidoterapia y daño cerebral traumático: una revisión narrativa

Traumatic brain injury (TBI) is an important health and social problem. The mechanism of damage of this entity could be divided into two phases: (1) a primary acute injury because of the traumatic event; and (2) a secondary injury due to the hypotension and hypoxia generated by the previous lesion, which leads to ischemia and necrosis of neural cells. Cerebral edema is one of the most important prognosis markers observed in TBI. In the early stages of TBI, the cerebrospinal fluid compensates the cerebral edema. However, if edema increases, this mechanism fails, increasing intracranial pressure. To avoid this chain effect, several treatments are applied in the clinical practice, including elevation of the head of the bed, maintenance of normothermia, pain and sedation drugs, mechanical ventilation, neuromuscular blockade, controlled hyperventilation, and fluid therapy (FT). The goal of FT is to improve the circulatory system to avoid the lack of oxygen to organs. Therefore, rapid and early infusion of large volumes of crystalloids is performed in clinical practice to restore blood volume and blood pressure. Despite the relevance of FT in the early management of TBI, there are few clinical trials regarding which solution is better to apply. The aim of this study is to provide a narrative review about the role of the different types of FT used in the daily clinical practice on the management of TBI. To achieve this objective, a physiopathological approach to this entity will be also performed, summarizing why the different types of FT are used (AU)

El traumatismo craneoencefálico (TCE) es un importante problema sanitario y social. El mecanismo de daño de esta entidad se podría dividir en dos fases: 1) una lesión aguda primaria a causa del evento traumático, y 2) una lesión secundaria por la hipotensión e hipoxia generada por la lesión anterior, que conduce a la isquemia y necrosis de las células neurales. El edema cerebral es uno de los marcadores pronósticos más importantes observados en el TCE. En las primeras etapas de TCE, el líquido cefalorraquídeo compensa el edema cerebral. Sin embargo, si aumenta el edema, este mecanismo falla, aumentando la presión intracraneal. Para evitar este efecto en cadena, en la práctica clínica se aplican varios tratamientos, entre ellos la elevación de la cabecera de la cama, el mantenimiento de la normotermia, los fármacos para el dolor y la sedación, la ventilación mecánica, el bloqueo neuromuscular, la hiperventilación controlada y la fluidoterapia (FT). El objetivo de la FT es mejorar el sistema circulatorio para evitar la falta de oxígeno a los órganos. Por lo tanto, en la práctica clínica se realiza una infusión rápida y temprana de grandes volúmenes de cristaloides para restablecer el volumen sanguíneo y la presión arterial. A pesar de la relevancia de la FT en el manejo temprano del TCE, existen pocos ensayos clínicos sobre qué solución es mejor aplicar. El objetivo de este estudio es proporcionar una revisión narrativa sobre el papel de los diferentes tipos de FT utilizados en la práctica clínica diaria en el manejo del TCE. Para lograr este objetivo, también se realizará un abordaje fisiopatológico de esta entidad, resumiendo por qué se utilizan los diferentes tipos de FT (AU)

Fluid therapy and traumatic brain injury: A narrative review.

Traumatic brain injury (TBI) is an important health and social problem. The mechanism of damage of this entity could be divided into two phases: (1) a primary acute injury because of the traumatic event; and (2) a secondary injury due to the hypotension and hypoxia generated by the previous lesion, which leads to ischemia and necrosis of neural cells. Cerebral edema is one of the most important prognosis markers observed in TBI. In the early stages of TBI, the cerebrospinal fluid compensates the cerebral edema. However, if edema increases, this mechanism fails, increasing intracranial pressure. To avoid this chain effect, several treatments are applied in the clinical practice, including elevation of the head of the bed, maintenance of normothermia, pain and sedation drugs, mechanical ventilation, neuromuscular blockade, controlled hyperventilation, and fluid therapy (FT). The goal of FT is to improve the circulatory system to avoid the lack of oxygen to organs. Therefore, rapid and early infusion of large volumes of crystalloids is performed in clinical practice to restore blood volume and blood pressure. Despite the relevance of FT in the early management of TBI, there are few clinical trials regarding which solution is better to apply. The aim of this study is to provide a narrative review about the role of the different types of FT used in the daily clinical practice on the management of TBI. To achieve this objective, a physiopathological approach to this entity will be also performed, summarizing why the different types of FT are used.

High Flow Nasal Cannula Therapy in the Emergency Department: Main Benefits in Adults, Pediatric Population and against COVID-19: A Narrative Review.

This review aims to summarize the literature's main results about high flow nasal cannula therapy (HFNC) HFNC benefits in the Emergency Department (ED) in adults and pediatrics, including new Coronavirus Disease (COVID-19). HFNC has recently been established as the usual treatment in the ED to provide oxygen support. Its use has been generalized due to its advantages over traditional oxygen therapy devices, including decreased nasopharyngeal resistance, washing out of the nasopharyngeal dead space, generation of positive pressure, increasing alveolar recruitment, easy adaptation due to the humidification of the airways, increased fraction of inspired oxygen and improved mucociliary clearance. A wide range of pathologies has been studied to evaluate the potential benefits of HFNC; some examples are heart failure, pneumonia, chronic pulmonary obstructive disease, asthma, and bronchiolitis. The regular use of this oxygen treatment is not established yet due to the literature's controversial results. However, several authors suggest that it could be useful in several pathologies that generate acute respiratory failure. Consequently, the COVID-19 irruption has generated the question of HFNC as a safety and effective treatment. Our results suggested that HFNC seems to be a useful tool in the ED, especially in patients affected by acute hypoxemic respiratory failure, acute heart failure, pneumonia, bronchiolitis, asthma and acute respiratory distress syndrome in patients affected by COVID-19. Its benefits in hypercapnic respiratory failure are more discussed, being only observed benefits in patients with mild-moderate disease. These results are based in clinical as well as cost-effectiveness outcomes. Future studies with largest populations are required to confirm these results as well as establish a practical guideline to use this device.

Metastatic colorectal micropapillary carcinoma presenting as lymphangitic lung carcinomatosis.

Pulmonary lymphangitic carcinomatosis denotes the infiltration of tumor cells into the lung parenchymal lymphatic channels. Breast, lung, stomach, and colon adenocarcinoma are the most common origin of this invasion pattern. The micropapillary variant of colorectal adenocarcinoma has a high rate of lymph node metastases and poor overall survival. A 49 year-old man with a 6 months history of persistent cough and a relevant occupational chemical exposure had a computed tomography that showed bilateral interstitial lung infiltrates. The lung biopsy demonstrated a micropapillary adenocarcinoma with diffusely obstruction of the lung parenchymal lymphatics. The immunohistochemistry confirmed a colorectal origin. The colonoscopy evidenced a mass with identical morphology. Colorectal micropapillary carcinoma with metastatic lung lymphangitic carcinomatosis can occur, as a persistent cough, as presenting symptom in extraordinarily rare cases. To the best of our knowledge, this is the first case of an alive patient with colorectal metastatic micropapillary carcinoma presenting with lymphangitic lung carcinomatosis.

Immunotyping of tumor-infiltrating lymphocytes in triple-negative breast cancer and genetic characterization.

Tumor-infiltrating lymphocytes (TILs) reflect the host immune response against cancer cells. Immunomodulators have been recently suggested as a novel therapeutic strategy against triple-negative breast cancer (TNBC). However, the TIL profile in TNBC has not been thoroughly investigated. In the present study, the percentage, immunophenotype and genetic profiles of TILs in pre-surgical tumor samples of patients with TNBC were evaluated prior to neoadjuvant chemotherapy (NAC). Patients diagnosed with breast cancer at Hospital San José TecSalud were consecutively and prospectively enrolled in the present study between August 2011 and August 2015. The pathological response to NAC was evaluated using the de Miller-Payne and MD Anderson Cancer Center system. TIL percentage (low, intermediate, and high) was evaluated using special hematoxylin-eosin staining on the core needle biopsies. The immunophenotype of TILs was assessed by immunohistochemistry (IHC) for CD3+, CD4+ and CD8+. In addition, the gene expression profile of CD3, CD4, CD8, CD20, CD45, forkhead box P3, interleukin 6, programmed cell death 1 and CD274 molecule was assessed in all patients. A total of 26 samples from patients with TNBC prior to NAC were included in the present study. TILs were low in 30.7%, intermediate in 38.4% and elevated in 30.7% of tumors. CD3+ and CD4+ counts were associated with the pathological response to NAC (P=0.04). Finally, an overexpression pattern of CD3, CD4, CD8, CD45 and CD20 genes was observed in patients with a partial or complete pathological response. The present results demonstrated that TILs may predict the pathological response to NAC in patients with TNBC. Furthermore, a more accurate association was identified between the high expression levels of CD3, CD4, CD8, CD45 and CD20 genes and partial and complete pathological response, compared with the association between high expression and IHC alone.

Rescue Snorkel Technique in a Giant Ruptured Aortic Aneurysm With Thoracic Endovascular Aortic Repair Failure.

A 67-year-old man was sent to our center because of progressively worsening chest pain. A giant ruptured thoracic aortic aneurysm was documented. We performed a successfully rescue snorkel technique for thoracic endovascular aortic repair failure because of type IA endoleak after the first endoprosthesis implantation. The patient was discharged after 6 weeks. (Level of Difficulty: Advanced.).

NOS3 Polymorphisms and Chronic Kidney Disease / Polimorfismos NOS3 e Insuficiência Renal Crônica

ABSTRACT Chronic kidney disease (CKD) is a multifactorial pathophysiologic irreversible process that often leads to a terminal state in which the patient requires renal replacement therapy. Most cases of CKD are due to chronic-degenerative diseases and endothelial dysfunction is one of the factors that contribute to its pathophysiology. One of the most important mechanisms for proper functioning of the endothelium is the regulation of the synthesis of nitric oxide. This compound is synthesized by the enzyme nitric oxide synthase, which has 3 isoforms. Polymorphisms in the NOS3 gene have been implicated as factors that alter the homeostasis of this mechanism. The Glu298Asp polymorphisms 4 b/a and -786T>C of the NOS3 gene have been associated with a more rapid deterioration of kidney function in patients with CKD. These polymorphisms have been evaluated in patients with CKD of determined and undetermined etiology and related to a more rapid deterioration of kidney function.

RESUMO A insuficiência renal crônica (IRA) é um processo fisiopatológico multifatorial e irreversível que frequentemente conduz a um estado terminal no qual o paciente passa a necessitar de tratamento por transplante renal. A maioria dos casos de IRA são devidos a doenças crônicas degenerativas; a disfunção endotelial é um dos fatores contribuintes na fisiopatologia. Um dos mecanismos mais importantes para o funcionamento adequado do endotélio é a regulação da síntese de óxido nítrico. Este composto é sintetizado por meio da enzima sintase do óxido nítrico, que tem três isoformas. Os polimorfismos no gene NOS3 tem sido implicados como fatores que alteram a homeostase desse mecanismo. Os polimorfismos Glu298Asp 4 b/a e -786T>C do gene NOS3 têm sido associados a uma deterioração mais rápida da função renal nos pacientes com IRA. Estes polimorfismos têm sido avaliados em pacientes com IRA de causas determinadas ou não-determinadas e relacionados a uma perda mais rápida da função renal.

NOS3 Polymorphisms and Chronic Kidney Disease.

Chronic kidney disease (CKD) is a multifactorial pathophysiologic irreversible process that often leads to a terminal state in which the patient requires renal replacement therapy. Most cases of CKD are due to chronic-degenerative diseases and endothelial dysfunction is one of the factors that contribute to its pathophysiology. One of the most important mechanisms for proper functioning of the endothelium is the regulation of the synthesis of nitric oxide. This compound is synthesized by the enzyme nitric oxide synthase, which has 3 isoforms. Polymorphisms in the NOS3 gene have been implicated as factors that alter the homeostasis of this mechanism. The Glu298Asp polymorphisms 4 b/a and -786T>C of the NOS3 gene have been associated with a more rapid deterioration of kidney function in patients with CKD. These polymorphisms have been evaluated in patients with CKD of determined and undetermined etiology and related to a more rapid deterioration of kidney function.

Determination of plasma lactate in the emergency department for the early detection of tissue hypoperfusion in septic patients.

OBJECTIVE: To determine the validity of plasma lactate in the emergency department for the early detection of tissue hypoperfusion in septic patients. MATERIALS AND METHODS: Longitudinal descriptive study. Non probabilistic sampling for convenience. Plasma lactate levels were determined in patients admitted to the emergency department with systemic inflammatory response data and clinical suspicion or documented infection. Follow-up was seven days. Complications were considered if the patients presented septic shock, severe sepsis, entry to intensive care or death. RESULTS: Ninety patients were included. The mean age was 57.4±20.31. Fifty five percent (n=49) were women. 25% (n=22) of the patients showed complications. Plasma lactate levels were 1.55mmol/L in uncomplicated patients and 3.72mmol/L for complicated patients (p<0.001). The area under the ROC curve was 0.72 (95% CI, 0.575-0.829). The cutoff point that best described the relationship with the probability of complications was that set at 4.2mmol/L. The variables studied that showed a significant association with the probability of complications were edema (p=0.004), and infections of the respiratory tract (p=0.037). A model that included lactate levels, using as adjustment variables edema and the presence of low respiratory tract infection explained between 0.234 and 0.349 of the dependent variant, correctly classifying 80% of the cases. CONCLUSION: Plasma lactate is useful in emergency departments as a predictive test for the early detection of patients with tissue hypoperfusion that evolve to severe sepsis, septic shock or death.

Pre-treatment with melatonin decreases abamectin induced toxicity in a nocturnal insect Spodoptera litura (Lepidoptera: Noctuidae).

AIM: Oxidative stress is an important component of the mechanism of pesticide toxicity. The aim of the present study was to investigate the time-dependent melatonin effects against abamectin-induced oxidative stress in a S.litura model. Larvae were divided into 5 different groups; (1) control group,(2) Melatonin group (4.3×10-5M/100ml diet), (3) Abamectin group 1.5ml/L, (4) Pre-melatonin treated group (PM) (4.3×10-5M/100ml diet) before abamectin exposure 1.5ml/L, (5) Post-melatonin treated group (TM) after abamectin exposure. Melatonin was supplemented via artificial diet in PM and TM animals during 24h. MAIN METHODS: Midgut, fatbody, and hemolymph, were collected for the analysis of oxidative stress markers (Total ROS, GSH, nitrite, TBARS, LPO), antioxidant enzyme levels (SOD, GST, CAT, POX, APOX) in fifth instar larvae. Midgut damage was examined by using morphological analysis. KEY FINDINGS: Our results observed that ABA group showed significant changes (p<0.001) in the ROS and carbonyl content in midgut. The increase of antioxidant enzyme levels (SOD, CAT, POX, and APOX) in midgut was led by the continuous free radical scavenger cascade of melatonin. Significant (p<0.01) increases in CAT and APOX levels were seen in the fatbody of PM and TM treated insects. SIGNIFICANCE: In conclusion, the results of the study revealed that abamectin toxicity generates oxidative stress in the insect, while pre-melatonin treatment reduces this damage due to its antioxidant properties, especially POX levels in midgut, fatbody, and hemolymph. Therefore, indoleamine can play a vital role curtailing the abamectin toxicity in time dependent manner in S.litura.

Melatonin's role as a co-adjuvant treatment in colonic diseases: A review.

Melatonin is produced in the pineal gland as well as many other organs, including the enterochromaffin cells of the digestive mucosa. Melatonin is a powerful antioxidant that resists oxidative stress due to its capacity to directly scavenge reactive species, to modulate the antioxidant defense system by increasing the activities of antioxidant enzymes, and to stimulate the innate immune response through its direct and indirect actions. In addition, the dysregulation of the circadian system is observed to be related with alterations in colonic motility and cell disruptions due to the modifications of clock genes expression. In the gastrointestinal tract, the activities of melatonin are mediated by melatonin receptors (MT2), serotonin (5-HT), and cholecystokinin B (CCK2) receptors and via receptor-independent processes. The levels of melatonin in the gastrointestinal tract exceed by 10-100 times the blood concentrations. Also, there is an estimated 400 times more melatonin in the gut than in the pineal gland. Gut melatonin secretion is suggested to be influenced by the food intake. Low dose melatonin treatment accelerates intestinal transit time whereas high doses may decrease gut motility. Melatonin has been studied as a co-adjuvant treatment in several gastrointestinal diseases including irritable bowel syndrome (IBS), constipation-predominant IBS (IBS-C), diarrhea-predominant IBS (IBS-D), Crohn's disease, ulcerative colitis, and necrotizing enterocolitis. The purpose of this review is to provide information regarding the potential benefits of melatonin as a co-adjuvant treatment in gastrointestinal diseases, especially IBS, Crohn's disease, ulcerative colitis, and necrotizing enterocolitis.

Melatonin as an antioxidant: under promises but over delivers.

Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes. In addition to these well-described actions, melatonin also reportedly chelates transition metals, which are involved in the Fenton/Haber-Weiss reactions; in doing so, melatonin reduces the formation of the devastatingly toxic hydroxyl radical resulting in the reduction of oxidative stress. Melatonin's ubiquitous but unequal intracellular distribution, including its high concentrations in mitochondria, likely aid in its capacity to resist oxidative stress and cellular apoptosis. There is credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant. Melatonin's capacity to prevent oxidative damage and the associated physiological debilitation is well documented in numerous experimental ischemia/reperfusion (hypoxia/reoxygenation) studies especially in the brain (stroke) and in the heart (heart attack). Melatonin, via its antiradical mechanisms, also reduces the toxicity of noxious prescription drugs and of methamphetamine, a drug of abuse. Experimental findings also indicate that melatonin renders treatment-resistant cancers sensitive to various therapeutic agents and may be useful, due to its multiple antioxidant actions, in especially delaying and perhaps treating a variety of age-related diseases and dehumanizing conditions. Melatonin has been effectively used to combat oxidative stress, inflammation and cellular apoptosis and to restore tissue function in a number of human trials; its efficacy supports its more extensive use in a wider variety of human studies. The uncommonly high-safety profile of melatonin also bolsters this conclusion. It is the current feeling of the authors that, in view of the widely diverse beneficial functions that have been reported for melatonin, these may be merely epiphenomena of the more fundamental, yet-to-be identified basic action(s) of this ancient molecule.

Potential benefits of melatonin in organ transplantation: a review.

Organ transplantation is a useful therapeutic tool for patients with end-stage organ failure; however, graft rejection is a major obstacle in terms of a successful treatment. Rejection is usually a consequence of a complex immunological and nonimmunological antigen-independent cascade of events, including free radical-mediated ischemia-reperfusion injury (IRI). To reduce the frequency of this outcome, continuing improvements in the efficacy of antirejection drugs are a top priority to enhance the long-term survival of transplant recipients. Melatonin (N-acetyl-5-methoxytryptamine) is a powerful antioxidant and ant-inflammatory agent synthesized from the essential amino acid l-tryptophan; it is produced by the pineal gland as well as by many other organs including ovary, testes, bone marrow, gut, placenta, and liver. Melatonin has proven to be a potentially useful therapeutic tool in the reduction of graft rejection. Its benefits are based on its direct actions as a free radical scavenger as well as its indirect antioxidative actions in the stimulation of the cellular antioxidant defense system. Moreover, it has significant anti-inflammatory activity. Melatonin has been found to improve the beneficial effects of preservation fluids when they are enriched with the indoleamine. This article reviews the experimental evidence that melatonin is useful in reducing graft failure, especially in cardiac, bone, otolaryngology, ovarian, testicular, lung, pancreas, kidney, and liver transplantation.

On the significance of an alternate pathway of melatonin synthesis via 5-methoxytryptamine: comparisons across species.

Melatonin is a phylogenetically ancient molecule. It is ubiquitously present in almost all organisms from primitive photosynthetic bacteria to humans. Its original primary function is presumable to be that of an antioxidant with other functions of this molecule having been acquired during evolution. The synthetic pathway of melatonin in vertebrates has been extensively studied. It is common knowledge that serotonin is acetylated to form N-acetylserotonin by arylalkylamine N-acetyltransferase (AANAT) or arylamine N-acetyltransferase (SNAT or NAT) and N-acetylserotonin is, subsequently, methylated to melatonin by N-acetylserotonin O-methyltransferase (ASMT; also known as hydroxyindole-O-methyltransferase, HIOMT). This is referred to as a classic melatonin synthetic pathway. Based on new evidence, we feel that this classic melatonin pathway is not generally the prevailing route of melatonin production. An alternate pathway is known to exist, in which serotonin is first O-methylated to 5-methoxytryptamine (5-MT) and, thereafter, 5-MT is N-acetylated to melatonin. Here, we hypothesize that the alternate melatonin synthetic pathway may be more important in certain organisms and under certain conditions. Evidence strongly supports that this alternate pathway prevails in some plants, bacteria, and, perhaps, yeast and may also occur in animals.

Melatonin role preventing steatohepatitis and improving liver transplantation results.

Liver steatosis is a prevalent process that is induced due to alcoholic or non-alcoholic intake. During the course of these diseases, the generation of reactive oxygen species, followed by molecular damage to lipids, protein and DMA occurs generating organ cell death. Transplantation is the last-resort treatment for the end stage of both acute and chronic hepatic diseases, but its success depends on ability to control ischemia-reperfusion injury, preservation fluids used, and graft quality. Melatonin is a powerful endogenous antioxidant produced by the pineal gland and a variety of other because of its efficacy in organs; melatonin has been investigated to improve the outcome of organ transplantation by reducing ischemia-reperfusion injury and due to its synergic effect with organ preservation fluids. Moreover, this indolamine also prevent liver steatosis. That is important because this disease may evolve leading to an organ transplantation. This review summarizes the observations related to melatonin beneficial actions in organ transplantation and ischemic-reperfusion models.

Melatonin's role in preventing toxin-related and sepsis-mediated hepatic damage: A review.

The liver is a central organ in detoxifying molecules and would otherwise cause molecular damage throughout the organism. Numerous toxic agents including aflatoxin, heavy metals, nicotine, carbon tetrachloride, thioacetamide, and toxins derived during septic processes, generate reactive oxygen species followed by molecular damage to lipids, proteins and DNA, which culminates in hepatic cell death. As a result, the identification of protective agents capable of ameliorating the damage at the cellular level is an urgent need. Melatonin is a powerful endogenous antioxidant produced by the pineal gland and a variety of other organs and many studies confirm its benefits against oxidative stress including lipid peroxidation, protein mutilation and molecular degeneration in various organs, including the liver. Recent studies confirm the benefits of melatonin in reducing the cellular damage generated as a result of the metabolism of toxic agents. These protective effects are apparent when melatonin is given as a sole therapy or in conjunction with other potentially protective agents. This review summarizes the published reports that document melatonin's ability to protect hepatocytes from molecular damage due to a wide variety of substances (aflatoxin, heavy metals, nicotine, carbon tetrachloride, chemotherapeutics, and endotoxins involved in the septic process), and explains the potential mechanisms by which melatonin provides these benefits. Melatonin is an endogenously-produced molecule which has a very high safety profile that should find utility as a protective molecule against a host of agents that are known to cause molecular mutilation at the level of the liver.

Role of the blood-brain barrier in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system associated with demyelination and axonal loss eventually leading to neurodegeneration. MS exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB). The BBB is a complex organization of cerebral endothelial cells, pericytes and their basal lamina, which are surrounded and supported by astrocytes and perivascular macrophages. In pathological conditions, lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Cytotoxic factors including pro-inflammatory cytokines, proteases, and reactive oxygen and nitrogen species accumulate and may contribute to myelin destruction. Dysregulation of the BBB and transendothelial migration of activated leukocytes are among the earliest cerebrovascular abnormalities seen in MS brains and parallel the release of inflammatory cytokines. In this review we establish the importance of the role of the BBB in MS. Improvements in our understanding of molecular mechanism of BBB functioning in physiological and pathological conditions could lead to improvement in the quality of life of MS patients.

Novel Point Mutations and A8027G Polymorphism in Mitochondrial-DNA-Encoded Cytochrome c Oxidase II Gene in Mexican Patients with Probable Alzheimer Disease.

Mitochondrial dysfunction has been thought to contribute to Alzheimer disease (AD) pathogenesis through the accumulation of mitochondrial DNA mutations and net production of reactive oxygen species (ROS). Mitochondrial cytochrome c-oxidase plays a key role in the regulation of aerobic production of energy and is composed of 13 subunits. The 3 largest subunits (I, II, and III) forming the catalytic core are encoded by mitochondrial DNA. The aim of this work was to look for mutations in mitochondrial cytochrome c-oxidase gene II (MTCO II) in blood samples from probable AD Mexican patients. MTCO II gene was sequenced in 33 patients with diagnosis of probable AD. Four patients (12%) harbored the A8027G polymorphism and three of them were early onset (EO) AD cases with familial history of the disease. In addition, other four patients with EOAD had only one of the following point mutations: A8003C, T8082C, C8201T, or G7603A. Neither of the point mutations found in this work has been described previously for AD patients, and the A8027G polymorphism has been described previously; however, it hasn't been related to AD. We will need further investigation to demonstrate the role of the point mutations of mitochondrial DNA in the pathogenesis of AD.