Sodium chloride-induced changes in oxidative stress, inflammation, and dysbiosis in experimental multiple sclerosis.

Objectives: The high-salt diet (HSD) has been associated with cognitive dysfunction by attacking the cerebral microvasculature, through an adaptive response, initiated in the intestine and mediated by Th17 cells. In the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE), it has been described that NaCl causes an increase in T cell infiltration in the central nervous system. NaCl also promotes macrophage response and Th17 cell differentiation, worsening the course of the disease. HSD may trigger an activation of the immune system and enhance inflammation. However, certain studies not only do not support this possibility, but support the opposite, as the effect of salt on immune cells may not necessarily be pathogenic. Therefore, this study aimed to evaluate the effect of an over intake of salt in rats with EAE, based on the clinical course, oxidative stress, markers of inflammation and the gut dysbiosis.Methods: 15 Dark Agouti rats were used, which were divided into control group, EAE group and EAE + NaCl group. Daily 0.027 g of NaCl dissolved in 300 µl of H2O was administered through a nasogastric tube for 51 days.Results: NaCl administration produced an improvement in clinical status and a decrease in biomarkers of oxidative stress, inflammation, and dysbiosis.Conclusion: The underlying mechanism by which NaCl causes these effects could involve the renin-angiotensin-aldosterone system (RAAS), which is blocked by high doses of salt.

Measuring single-virus fusion kinetics using an assay for nucleic acid exposure.

The kinetics by which individual enveloped viruses fuse with membranes provide an important window into viral-entry mechanisms. We have developed a real-time assay using fluorescent probes for single-virus genome exposure than can report on stages of viral entry including or subsequent to fusion pore formation and prior to viral genome trafficking. We accomplish this using oxazole yellow nucleic-acid-binding dyes, which can be encapsulated in the lumen of target membranes to permit specific detection of fusion events. Since increased fluorescence of the dye occurs only when it encounters viral genome via a fusion pore and binds, this assay excludes content leakage without fusion. Using this assay, we show that influenza virus fuses with liposomes of different sizes with indistinguishable kinetics by both testing liposomes extruded through pores of different radii and showing that the fusion kinetics of individual liposomes are uncorrelated with the size of the liposome. These results suggest that the starting curvature of such liposomes does not control the rate-limiting steps in influenza entry.

Sexual Behaviors and Factors Associated with Condomless Sexual Practice in Colombian Men Who Have Sex with Men at High Risk of HIV Transmission.

Men who have sex with men (MSM) have a disproportionate burden of HIV infection worldwide. In Colombia, the prevalence of HIV in MSM is ~ 43 times higher than in the general population (17% vs. 0.4%). This study determined the sexual behaviors, HIV serostatus, and associated factors with condomless sexual practice with both regular and casual partners in 92 MSM from Medellín, Colombia. The subjects were recruited through a community-based approach, and the data were collected by a structured survey and in-depth interviews. Participants were classified into three groups according to the number of sexual partners in the last three months, to compare the sociodemographic conditions and sexual behaviors. Univariate analysis was described by absolute and relative frequencies; bivariate analysis and multivariate logistic regression were used to compare the groups and to explore the associated factors with condomless sexual practice. The overall HIV estimated prevalence was 4.3%, while the estimated prevalence for MSM with > 10 sexual partners in the last three months was 14.8%. This last group showed higher average age, higher percentage of subjects who have had sex with people living with HIV, and increased frequency of previous sexually transmitted infections. Having condomless sex with casual partners was associated with the number of sexual partners in the last three months. This study demonstrates that Colombian MSM continue to have a high risk of HIV infection/transmission and reinforce the need to implement adequate prevention programs, PrEP and guarantee access to treatment for people living with HIV.

The nanotech potential of turmeric (Curcuma longa L.) in food technology: A review.

New trends in food are emerging in response to consumer awareness of the relationship between food and health, which has triggered the need to generate new alternatives that meet the expectations of the market. Revolutionary fields such as nanotechnology have been used for the encapsulation of nutritional ingredients and have great potential for the management of food additives derived from fruits and plant species. Turmeric, a spice that has been used as a dyeing agent, is recognized for its properties in Ayurveda medicine. This article aims to provide an overview of the characteristics of turmeric as an ingredient for the food industry, including its properties as a coloring agent, antioxidant, and functional ingredient. This article also highlights the potential of nanotechnology to enhance these properties of turmeric and increase the possibilities for the application of its components, such as cellulose and starch, in the development of nanostructures for food development.

Interactions of the Lysosomotropic Detergent O-Methyl-Serine Dodecylamide Hydrochloride (MSDH) with Lipid Bilayer Membranes-Implications for Cell Toxicity.

O-methyl-serine dodecylamine hydrochloride (MSDH) is a detergent that accumulates selectively in lysosomes, a so-called lysosomotropic detergent, with unexpected chemical properties. At physiological pH, it spontaneously forms vesicles, which disassemble into small aggregates (probably micelles) below pH 6.4. In this study, we characterize the interaction between MSDH and liposomes at different pH and correlate the findings to toxicity in human fibroblasts. We find that the effect of MSDH on lipid membranes is highly pH-dependent. At neutral pH, the partitioning of MSDH into the liposome membrane is immediate and causes the leakage of small fluorophores, unless the ratio between MSDH and lipids is kept low. At pH 5, the partitioning of MSDH into the membrane is kinetically impeded since MSDH is charged and a high ratio between MSDH and the lipids is required to permeabilize the membrane. When transferred to cell culture conditions, the ratio between MSDH and plasma membrane lipids must therefore be low, at physiological pH, to maintain plasma membrane integrity. Transmission electron microscopy suggests that MSDH vesicles are taken up by endocytosis. As the pH of the endosomal compartment progressively drops, MSDH vesicles disassemble, leading to a high concentration of increasingly charged MSDH in small aggregates inside the lysosomes. At sufficiently high MSDH concentrations, the lysosome is permeabilized, the proteolytic content released to the cytosol and apoptotic cell death is induced.

Detecting and Controlling Dye Effects in Single-Virus Fusion Experiments.

Fluorescent dye-dequenching assays provide a powerful and versatile means to monitor membrane fusion events. They have been used in bulk assays, for measuring single events in live cells, and for detailed analysis of fusion kinetics for liposomal, viral, and cellular fusion processes; however, the dyes used also have the potential to perturb membrane fusion. Here, using single-virus measurements of influenza membrane fusion, we show that fluorescent membrane probes can alter both the efficiency and the kinetics of lipid mixing in a dye- and illumination-dependent manner. R18, a dye that is commonly used to monitor lipid mixing between membranes, is particularly prone to these effects, whereas Texas Red is somewhat less sensitive. R18 further undergoes photoconjugation to viral proteins in an illumination-dependent manner that correlates with its inactivation of viral fusion. These results demonstrate how fluorescent probes can perturb measurements of biological activity and provide both data and a method for determining minimally perturbative measurement conditions.

Lipid vesicles affect the aggregation of 4-hydroxy-2-nonenal-modified α-synuclein oligomers.

Parkinson's disease (PD) and other synucleinopathies are characterized by accumulation of misfolded aggregates of α-synuclein (α-syn). The normal function of α-syn is still under investigation, but it has been generally linked to synaptic plasticity, neurotransmitter release and the maintenance of the synaptic pool. α-Syn localizes at synaptic terminals where it can bind to synaptic vesicles as well as to other cellular membranes. It has become clear that these interactions have an impact on both α-syn functional role and its propensity to aggregate. In this study, we investigated the aggregation process of α-syn covalently modified with 4-hydroxy-2-nonenal (HNE). HNE is a product of lipid peroxidation and has been implicated in the pathogenesis of different neurodegenerative diseases by modifying the kinetics of soluble toxic oligomers. Although HNE-modified α-syn has been reported to assemble into stable oligomers, we found that slightly acidic conditions promoted further protein aggregation. Lipid vesicles delayed the aggregation process in a concentration-dependent manner, an effect that was observed only when they were added at the beginning of the aggregation process. Co-aggregation of lipid vesicles with HNE-modified α-syn also induced cytotoxic effects on differentiated SHSY-5Y cells. Under conditions in which the aggregation process was delayed cell viability was reduced. By exploring the behavior and potential cytotoxic effects of HNE-α-syn under acidic conditions in relation to protein-lipid interactions our study gives a framework to examine a possible pathway leading from a physiological setting to the pathological outcome of PD.

Spontaneous Vesiculation and pH-Induced Disassembly of a Lysosomotropic Detergent: Impacts on Lysosomotropism and Lysosomal Delivery.

Lysosomotropic detergents (LDs) selectively rupture lysosomal membranes through mechanisms that have yet to be characterized. A consensus view, currently, holds that LDs, which are weakly basic, diffuse across cellular membranes as monomers in an uncharged state, and via protonation in the acidic lysosomal compartment, they become trapped, accumulate, and subsequently solubilize the membrane and induce lysosomal membrane permeabilization. Here we demonstrate that the lysosomotropic detergent O-methyl-serine dodecylamide hydrochloride (MSDH) spontaneously assembles into vesicles at, and above, cytosolic pH, and that the vesicles disassemble as the pH reaches 6.4 or lower. The aggregation commences at concentrations below the range of those used in cell studies. Assembly and disassembly of the vesicles was studied via dynamic light scattering, zeta potential measurements, cryo-TEM, and fluorescence correlation spectroscopy and was found to be reversible via control of the pH. Aggregation of MSDH into closed vesicles under cytosolic conditions is at variance with the commonly held view of LD behavior, and we propose that endocytotic pathways should be considered as possible routes of LD entry into lysosomes. We further demonstrate that MSDH vesicles can be loaded with fluorophores via a solution transition from low to high pH, for subsequent release when the pH is lowered again. The ability to encapsulate molecular cargo into MSDH vesicles together with its ability to disaggregate at low pH and to permeabilize the lysosomal membrane presents an intriguing possibility to use MSDH as a delivery system.

Lysosomotropic agents: impact on lysosomal membrane permeabilization and cell death.

Lysosomes are acidic organelles essential for degradation, signalling and cell homoeostasis. In addition, they play a key role in cell death. Permeabilization of the lysosomal membrane and release of hydrolytic enzymes to the cytosol accompanies apoptosis signalling in several systems. The regulatory mechanism of lysosomal stability is, however, poorly understood. Lipophilic or amphiphilic compounds with a basic moiety will become protonated and trapped within lysosomes, and such lysosomotropic behaviour is also found in many pharmacological drugs. The natural sphingolipid sphingosine exhibits lysosomotropic detergent ability and is an endogenous candidate for controlling lysosomal membrane permeabilization. The lysosomotropic properties of certain detergents might be of use in lysosome-targeting anticancer drugs and drug delivery system in the future. The present review summarizes the current knowledge on the targeting and permeabilizing properties of lysosomotropic detergents from a cellular and physicochemical perspective.

[Risk factors for multidrug-resistant Pseudomonas aeruginosa infection, in a tertiary hospital in Colombia]. / Factores de riesgo para infección por Pseudomonas aeruginosa multi-resistente en un hospital de alta complejidad.

INTRODUCTION: multi-resistant Pseudomonas aeruginosa (MR) is frequently associated with healthcare infections. Its epidemiology is complex and few studies help to understand it. A study about risk factors associated with this type of bacteria is needed. OBJECTIVE: To determine risk factors associated with MR P. aeruginosa infection in hospitalized patients from the Hospital Universitario San Vicente Foundation-Medellin. MATERIALS AND METHODS: case-control study to identify risk factors associated with infection by MR P. aeruginosa. RESULTS: 140 patients were included, 70 in each group. Bivariate analysis found association with previous use of carbapenems (OR 3.12 - IC 1.21 to 8.03, p = 0.02), aminoglycosides (OR 5.09 - CI: 1.38 to 18, 77, p = 0.01) and days of stay prior to isolation of the organism (OR 1.03 - CI: 1.01-1.05, p = 0.01). In multivariate analysis MR P. aeruginosa infection was associated with hospital stay (OR 1.03 - IC 1.01 to 1.05), use of aminoglycosides (OR 1.30 to 19.28) and treatment with two or more antimicrobials in the last 30 days (OR 3.09 - CI: 1.26 to 7.58). The risk of developing infection was 3% per day of hospital stay prior to isolation of the agent. CONCLUSION: Developing MR P. aeruginosa infection was associated with prior use of antimicrobials and prior hospital stay.

Neuroprotective and antioxidant effects of docosahexaenoic acid (DHA) in an experimental model of multiple sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating disease, whose etiology is not yet fully understood, although there are several factors that can increase the chances of suffering from it. These factors include nutrition, which may be involved in the pathogenesis of the disease. In relation to nutrition, docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (n-3 PUFA), has emerged as an important player in the regulation of neuroinflammation, being considered a pleiotropic molecule. This study aimed to evaluate the effect of DHA supplementation on clinical state and oxidative stress produced by experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Twenty-five Dark Agouti rats which were used divided into Control Group, Control+Vehicle Group, Control+DHA Group, EAE Group, and EAE+DHA Group. DHA was administered for 51 days by intraperitoneal (i.p.) injection at a dose of 40 mg/kg, once a day, 5 days a week. DHA supplementation produced a decrease in oxidative stress, as well as an improvement in the clinical score of the disease. DHA could exert a beneficial effect on the clinic of MS, through the activation of the antioxidant factor Nrf2.

Effect of the Combination of Different Therapies on Oxidative Stress in the Experimental Model of Multiple Sclerosis.

Oxidative stress is heavily involved in several pathological features of Multiple Sclerosis (MS), such as myelin destruction, axonal degeneration, and inflammation. Different therapies have been shown to reduce the oxidative stress that occurs in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Some of these therapies are transcranial magnetic stimulation (TMS), extra virgin olive oil (EVOO) and S-allyl cysteine (SAC). This study aims to test the antioxidant effect of these three therapies, to compare the efficacy of SAC versus TMS and EVOO, and to analyze the effect of combining SAC + TMS and SAC and EVOO. Seventy Dark Agouti rats were used, which were divided into Control group; Vehicle group; Mock group; SAC; EVOO; TMS; SAC + EVOO; SAC + TMS; EAE; EAE + SAC; EAE + EVOO; EAE + TMS; EAE + SAC + EVOO; EAE + SAC + TMS. The TMS consisted of an oscillatory magnetic field in the form of a sine wave with a frequency of 60 Hz and an amplitude of 0.7mT (EL-EMF) applied for two hours in the morning, once a day, five days a week. SAC was administered at a dose of 50 mg/kg body weight, orally daily, five days a week. EVOO represented 10% of their calorie intake in the total standard daily diet of rats AIN-93G. All treatments were maintained for 51 days. TMS, EVOO and SAC, alone or in combination, reduce oxidative stress, increasing antioxidant defenses and also lowering the clinical score. Combination therapies do not appear to be more potent than individual therapies against the oxidative stress of EAE or its clinical symptoms.

Mucinous appendix intussusception: Case report.

INTRODUCTION AND IMPORTANCE: Intussusception is an intestinal invagination of one bowel segment into another. It occurs mostly in children, but it can show in adults due to different etiologies. Appendiceal neoplasms are rare and can mimic an acute onset of appendicitis. Appendiceal mucinous neoplasm is one of the subtypes of appendiceal malignancies found in less than 1 % of appendectomies samples. CASE PRESENTATION: We present the case of a 32-year-old woman with abdominal pain in the right upper quadrant, whose computed tomography revealed an ileocolic intussusception and a low-density tubular image in the distal loop. She underwent diagnostic laparoscopy and laparoscopic right colectomy. Biopsy results confirmed a LAMN with acute appendicitis and intussusception. CLINICAL DISCUSSION: Appendiceal intussusception (AI) is associated with the alteration of peristalsis, in addition to multiple inflammatory conditions and diseases such as parasites, foreign bodies, Crohn's disease, and lymphoid hyperplasia. The pathophysiology of AI is not fully established, but the main appendicular alteration that has been associated with it is the presence of a tumor. AI lead points are typically pathological in 90 % of cases, 65 % of which are neoplastic in nature. Right hemicolectomy should be performed for tumors involving the periappendicular area or in those larger than 2 cm in size. Follow-up and surveillance colonoscopy is suggested. CONCLUSION: Intussusception is a rare diagnosis in adults. However, malignancy should be suspected if identified.

Cutaneous tuberculosis as a manifestation of Pott's Disease: A diagnostic challenge in patients with Non-HIV immunosuppression.

Tuberculosis (TB) is one of the most important public health issues in developing countries. The World Health Organization estimates that approximately 20%-40% of the world's population is infected. Pulmonary forms account for the majority of cases; however, it can manifest as extrapulmonary disease in 8.4%-13.7% of cases. Of these extrapulmonary forms of TB, only 1%-2% may have skin manifestations. Cutaneous tuberculosis (CTB) is relatively uncommon and is not a well-defined disease, which complicates diagnosis. We present two patients with Pott's disease that manifested as CTB, one with tuberculous gumma and the other with scrofuloderma. Both patients with non-HIV immunosuppression. The diagnosis of CTB was made by detecting Mycobacterium tuberculosis in skin samples by real-time polymerase chain reaction (Xpert MTB/RIF test) and Ziehl-Neelsen staining. The histologic findings described in these two forms of TB may vary or be absent in immunosuppressed patients, making diagnosis difficult.

Chlamydia psittaci seropositivity in workers exposed to birds and review of the literature: Evidence of circulation in Antioquia / Seropositividad de Chlamydia psittaci en trabajadores expuestos a aves y revisión de la literatura: evidencia de circulación en Antioquia.

Introduction: Psittacosis is a zoonotic disease caused by Chlamydia psittaci, a bacterium classified as an agent with bioterrorist potential. It has caused multiple outbreaks in exposed poultry workers around the world. Colombia has no epidemiological follow-up of the infection and a big knowledge gap. Objectives: To determine the antibodies' frequency against C. psittaci in workers with occupational exposure to birds and to review the literature on studies conducted in Colombia. Materials and methods: We conducted a cross-sectional descriptive study with analytical intent on workers in contact with birds and reviewed the related literature in Colombia. IgM and IgG serum antibodies against C. psittaci were detected by microimmunofluorescence. The sociodemographic and exposure characteristics were expressed as frequencies and summary measures. Associated factors were explored by bivariate and multivariate analysis. The scientific and gray literature review was done with a structured search. Results: We analyzed 54 workers in contact with birds. Antibody prevalence was 31.5%. Slaughtering and evisceration by non-veterinarians was a risk factor for antibody presence. There are only four previous studies on C. psittaci in Colombia. Conclusions: Here, we present the first evidence of C. psittaci circulation among workers exposed to birds in Antioquia and the second report in the country. These findings contribute to the "One Health" public health strategy.

Introducción: La psitacosis es una enfermedad zoonótica causada por Chlamydia psittaci. Esta bacteria es catalogada como un agente con potencial bioterrorista y ha causado múltiples brotes en trabajadores con exposición laboral a aves en diferentes lugares del mundo. En Colombia, no se hace seguimiento epidemiológico de la infección y existe una gran brecha en el conocimiento. Objetivos: Determinar la frecuencia de anticuerpos contra C. psittaci en trabajadores con exposición laboral a aves y sus factores asociados. Además, revisar la literatura en relación con los estudios sobre el tema realizados en Colombia. Materiales y métodos: Se llevó a cabo un estudio descriptivo, transversal, con intención analítica, en trabajadores en contacto con aves y se revisó la literatura científica relacionada en Colombia. Se detectaron anticuerpos IgM e IgG contra C. psittaci en suero por microinmunofluorescencia. La descripción de las características sociodemográficas y de exposición se hizo con frecuencias y medidas de resumen. Se exploraron factores asociados por análisis bivariados y multivariados. La revisión de la literatura científica y gris se hizo con búsqueda estructurada. Resultados: Se analizaron 54 trabajadores en contacto con aves y se encontró una prevalencia de anticuerpos del 31,5 %. El ejercer funciones de sacrificio y faenado de las aves sin ser médico veterinario fue un factor de riesgo para la presencia de anticuerpos. Solo se encontraron cuatro estudios previos sobre C. psittaci hechos en Colombia. Conclusiones: Este estudio constituye la primera evidencia de la circulación de C. psittaci en trabajadores en contacto con aves en Antioquia y el segundo reporte en el país. Estos hallazgos aportan desde la salud pública a la estrategia One Health.

Type IV secretion system core component VirB8 from Brucella binds to the globular domain of VirB5 and to a periplasmic domain of VirB6.

Type IV secretion systems are macromolecular assemblies in the cell envelopes of bacteria that function in macromolecular translocation. Structural biology approaches have provided insights into the interaction of core complex components, but information about proteins that undergo transient interactions with membrane components has not been forthcoming. We have pursued an unbiased approach using peptide arrays and phage display to identify interaction partners and interaction domains of type IV secretion system assembly factor VirB8. These approaches identified the globular domain from the VirB5 protein to interact with VirB8. This interaction was confirmed in cross-linking, pull-down, and fluorescence resonance energy transfer (FRET)-based interaction assays. In addition, using phage display analysis, we identified different regions of VirB6 as potential interaction partners of VirB8. Using a FRET-based interaction assay, we provide the first direct experimental evidence of the interaction of a VirB6 periplasmic domain with VirB8. These results will allow us to conduct directed structural biological work and structure-function analyses aimed at defining the molecular details and biological significance of these interactions with VirB8 in the future.

Plasma membrane calcium pump (PMCA) differential exposure of hydrophobic domains after calmodulin and phosphatidic acid activation.

The exposure of the plasma membrane calcium pump (PMCA) to the surrounding phospholipids was assessed by measuring the incorporation of the photoactivatable phosphatidylcholine analog [(125)I]TID-PC/16 to the protein. In the presence of Ca(2+) both calmodulin (CaM) and phosphatidic acid (PA) greatly decreased the incorporation of [(125)I]TID-PC/16 to PMCA. Proteolysis of PMCA with V8 protease results in three main fragments: N, which includes transmembrane segments M1 and M2; M, which includes M3 and M4; and C, which includes M5 to M10. CaM decreased the level of incorporation of [(125)I]TID-PC/16 to fragments M and C, whereas phosphatidic acid decreased the incorporation of [(125)I]TID-PC/16 to fragments N and M. This suggests that the conformational changes induced by binding of CaM or PA extend to the adjacent transmembrane domains. Interestingly, this result also denotes differences between the active conformations produced by CaM and PA. To verify this point, we measured resonance energy transfer between PMCA labeled with eosin isothiocyanate at the ATP-binding site and the phospholipid RhoPE included in PMCA micelles. CaM decreased the efficiency of the energy transfer between these two probes, whereas PA did not. This result indicates that activation by CaM increases the distance between the ATP-binding site and the membrane, but PA does not affect this distance. Our results disclose main differences between PMCA conformations induced by CaM or PA and show that those differences involve transmembrane regions.

Influenza Virus Membrane Fusion Is Promoted by the Endosome-Resident Phospholipid Bis(monoacylglycero)phosphate.

The phospholipid bis(monoacylglycero)phosphate (BMP) is enriched in late endosomal and endolysosomal membranes and is believed to be involved in membrane deformation and generation of intralumenal vesicles within late endosomes. Previous studies have demonstrated that BMP promotes membrane fusion of several enveloped viruses, but a limited effect has been found on influenza virus. Here, we report the use of single-virus fusion assays to dissect BMP's effect on influenza virus fusion in greater depth. In agreement with prior reports, we found that hemifusion kinetics and efficiency were unaffected by the addition of 10-20 mol % BMP to the target membrane. However, using an assay for fusion pore formation and genome exposure, we found full fusion efficiency to be substantially enhanced by the addition of 10-20 mol % BMP to the target membrane, while the kinetics remained unaffected. By comparing BMP to other negatively charged phospholipids, we found the effect on fusion efficiency mainly attributable to headgroup charge, although we also hypothesize a role for BMP's unusual chemical structure. Our results suggest that BMP function as a permissive factor for a wider range of viruses than previously reported. We hypothesize that BMP may be a general cofactor for endosomal entry of enveloped viruses.

An Atypical Cutaneous Metastasis in a Case of Clear Cell Renal Carcinoma.

Clear cell renal cell carcinoma (ccRCC) comprises most renal cell carcinoma (RCC) cases, with its incidence increasing in recent years. Metastases are most commonly found in the lungs, bones, liver, and brain. However, few patients present with cutaneous metastases, which are usually associated with poor outcomes. We present the case of a 52-year-old man with ccRCC and skin metastasis. Our aim was to highlight the variability in the presentation of cutaneous metastasis of ccRCC. Clinicians should be aware of the various manifestations and possible locations of RCC skin metastases to better identify these lesions and further guide treatment.

Lactose and Casein Cause Changes on Biomarkers of Oxidative Damage and Dysbiosis in an Experimental Model of Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Experimental Autoimmune Encephalomyelitis (EAE) in rats closely reproduces Multiple Sclerosis (MS), a disease characterized by neuroinflammation and oxidative stress that also appears to extend to other organs and their compartments. The origin of MS is a matter for discussion, but it would seem that altering certain bacterial populations present in the gut may lead to a proinflammatory condition due to the bacterial Lipopolysaccharides (LPS) in the so-called brain-gut axis. The casein and lactose in milk confer anti-inflammatory properties and immunomodulatory effects. The objectives of this study were to evaluate the effects of administration of casein and lactose on the oxidative damage and the clinical status caused by EAE and to verify whether both casein and lactose had any effect on the LPS and its transport protein -LBP-. METHODS: Twenty male Dark Agouti rats were divided into control rats (control), EAE rats, and EAE rats, to which casein and lactose, EAE+casein, and EAE+lactose, respectively, were administered. Fifty-one days after casein and lactose administration, the rats were sacrificed, and different organs were studied (brain, spinal cord, blood, heart, liver, kidney, small, and large intestine). In the latter, products derived from oxidative stress were studied (lipid peroxides and carbonylated proteins) as well as the glutathione redox system, various inflammation factors (total nitrite, Nuclear Factor-kappa B p65, the Rat Tumour Necrosis Factor-α), and the LPS and LBP values. RESULTS AND CONCLUSION: Casein and lactose administration improved the clinical aspect of the disease at the same time as reducing inflammation and oxidative stress, exerting its action on the glutathione redox system, or increasing GPx levels.