Oscar Kurt Bitzer-Quintero

Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle.

Genotoxicity of paraquat: micronuclei induced in bone marrow and peripheral blood are inhibited by melatonin

The ability of melatonin to influence paraquat-induced genotoxicity was tested using micronucleated polychromatic erythrocytes as an index of damage in both bone marrow and peripheral blood cells of mice. Melatonin (10 mg/kg) or an equal volume of saline were administered intraperitoneally (ip) to mice 30 min prior to an ip injection of paraquat (20 mg/kgx2), and thereafter at 6-h intervals until the conclusion of the study (72 h). The number of the micronucleated polychromatic erythrocytes increased after paraquat administration both in peripheral blood and bone marrow cells. Melatonin administration to paraquat-treated mice significantly reduced micronuclei formation in both peripheral blood and bone marrow cells; these differences were apparent at 24, 48 and 72 h after paraquat administration. The induction of micronuclei was time-dependent with peak values occurring at 24 and 48 h. The reduction in paraquat-related genotoxicity by melatonin is likely due in part to the antioxidant activity of the indole. We did not observe effects of melatonin over paraquat in paraquat+melatonin groups incubated at 0, 60 and 120 min. Mitomycin C, which was used as a positive control, also caused the expected large rises in micronuclei in both bone marrow and peripheral blood cells at 24, 48 and 72 h after its administration.

Antioxidant activity of tryptophan in rats under experimental endotoxic shock.

Tryptophan (TRP), the precursor of the scavenger or immunomodulator molecules melatonin (MLT) and picolinic acid, can be found in the diet; and could be an alternative nutritional supplement used to regulate the immune response in the generation of free radicals. In an experimental model, the systemic administration of lipopolysaccharide (LPS), to promote the synthesis of pro-inflammatory cytokines, reactive oxygen species, and antioxidant enzymes, was performed on adult female, pregnant and lactating rats fed with a diet of TRP content (0.5mg/100g protein). Lung tissue was evaluated for levels of the products of lipoperoxidation (LPOs), malonaldehyde (MDA) and 4-hydroxy alkenals (4-HDA); nitrites (NO2), glutathione peroxidase (Gpx) enzyme activity, and the serum concentration of interferon-gamma (IFN-gamma), which were measured in the following groups: control (CTRL), LPS, MLT, TRP, LPS plus MLT (LPS+MLT), and LPS plus TRP (LPS+TRP). Results showed that the lung tissue levels of MDA and 4-HDA in the LPS+TRP group were significantly lower than in the TRP group. Statistically significant differences were not observed in nitric oxide levels among the groups LPS+MLT and LPS+TRP compared to the group under endotoxic shock (LPS). The Gpx enzyme activity was modified in the LPS+MLT vs the LPS group, but the difference was not statistically significant. The LPS+MLT group showed a smaller serum concentration (98%) of IFN-gamma than the LPS group. Statistically significant differences were not observed among the animals of the LPS+TRP and the LPS groups.

Protective effects of melatonin against caustic esophageal burn injury in rats

Abstract:  Caustic ingestion is one of the most life‐threatening events in the pediatric age group, which requires the immediate management and subsequent treatment of its most significant complication, i.e. alterations in esophageal structure. We investigated whether melatonin could reduce the esophageal burn damage induced by sodium hydroxide. It was assumed that melatonin could be effective because of its function as a direct free radical scavenger, its antioxidative actions and its ability to diminish tissue hydroxyproline (HP) levels. Esophageal burns were induced in male rats by the administration of 10% sodium hydroxide. Lipid peroxidation (LPO) products were then measured at the following times: 0, 1, 6, 24, 48 and 72 hr after treatment. Tissue HP concentrations in the injured area were assessed at 14 days after the administration of sodium hydroxide. The groups received either systemic melatonin or normal saline. There were two, non‐ischemic, sham control groups treated with or without melatonin. LPO products, malondialdehyde (MDA) and 4‐hydroxyalkenal (4‐HDA), increased immediately after the administration of sodium hydroxide; this indicates the participation of free radicals in the development of damage. Melatonin diminished the oxidative response and the amount of HP in the late phase of the lesion. Melatonin reduced oxidative damage in the early phase of the esophageal burns induced by sodium hydroxide.

Different Patterns in the Histology and Autofluorescence of the Harderian Glands of the Syrian Hamster, Rat, Mouse, Mongolian Gerbil and Guinea Pig

The purpose of this study was to compare the natural fluorescence in the Harderian glands of the Syrian hamster, rat, mouse, Mongolian gerbil and guinea pig (both sexes). For each species, 10 animals (five males and five females) were used. Histological autofluorescence studies were performed using a fluorescence microscope (450–490 nm filter). Two different types of fluorescent cells were observed in both hamster (type AFI high intensity and type AFII, low fluorescence) and rat (type AFI, low fluorescence and type AFII, high fluorescence) Harderian glands. The fluorescence was basally located in all mice cells, whereas it was observed near the epithelial cell nuclei in the Mongolian gerbil (occupying two‐thirds and one‐third of the cells in males and females, respectively). A high intensity of fluorescence was present throughout the acinar cells in the guinea pig. The patterns of fluorescence identified exhibited a sexual dimorphism in all species studied. These results demonstrate that the Harderian glands of the animal species examined exhibit a variety of histological autofluorescence patterns.

The Orbital Harderian Gland of the Male Atlantic Bottlenose Dolphin (Tursiops truncatus): A Morphological Study

The ultrastructure of the Atlantic Bottlenose dolphin Harderian gland (HG) has been described but some questions remain unanswered. The purpose of this work was to define the glands structure, ultrastructure and the differences between cells (types I and II) of the male dolphin using optic, fluorescence and electron transmission microscopy. Three different cells were observed under optic and fluorescence microscopic examination, while only two cell types (types I and II) were distinguished by electron transmission microscopy. Type I (oval nuclear envelope) exhibited three different cell populations and type II (indented nuclear envelope) exhibited two different cell populations. Although, we observed both types of vesicles in both types of cells they differed, principally, in quantity. The glands also possessed prominent duct systems, with three orders of complexity. The dolphin orbital HG appears to function as a mixed heterologous gland with two types of cells that exhibit both types of vesicles and other distinguishable differences.

Molecular epidemiology of HIV type 1 in Mexico: emergence of BG and BF intersubtype recombinants.

The molecular epidemiology of subtypes and intersubtype recombinants (IRs) of human immunodeficiency virus type 1 (HIV-1) in Mexico has not been characterized fully. Understanding its regional distribution, prevalence, adaptability, viral fitness, pathogenicity, and immunogenicity is decisive for any design of an effective HIV vaccine. The aim of this study was to describe the presence of IRs types BG and BF in a Mexican population. Protease and reverse transcriptase regions of the pol gene were sequenced using an automated sequencing system. A phylogenic tree was constructed and genetic distances were calculated using MEGA 3.1. Recombination analysis was done by bootscan using SimPlot software. Two hundred and twenty-three HIV-1-positive individuals were enrolled in the study. At baseline, the mean plasma viral load was 285,500 HIV-1 RNA copies/ml and the mean CD4 cell count was 213 cells/ml. Subtype B was found in 220 (98.6%) samples, whereas IRs were found in three patients (1.4%): two (0.9%) with BG and one (0.45%) with BF. IRs were observed in 2/124 (1.6%) samples from treated patients and in 1/99 (1.0%) from naive patients. The presence of these HIV forms at low frequency points to the need for research on the diversity, geographic distribution, and evolution of other subtypes including circulating recombinant forms and IRs to understand the molecular epidemiology and tendencies of the HIV infection in Mexico.

Neurotoxicity of dextrorphan

BACKGROUND The noncompetitive NMDA antagonists phencyclidine (PCP) and dizocilpine (MK-801) have been considered for use as neuroprotective therapeutic agents, although both produce injury in neurons of cingulate and retrosplenial cortices in rodents. The low-affinity, noncompetitive NMDA antagonist dextrorphan has been considered for use as a neuroprotective therapeutic drug. The aim of the present work was to evaluate the neurotoxicity of dextrorphan. METHODS Sprague-Dawley male rats were used and injected with either saline or dextrorphan (30 mg/kg i.p.). The animals were sacrificed 30 min later, and the brain was examined for histopathological changes. RESULTS After systemic administration of the drug, hyperchromatic and shrunken nuclei with chromatin condensation and disruption were observed. Also, granular and vacuolated cytoplasm was apparent in pyramidal neurons in the retrosplenial (posterior cingulate) cortex. Status spongiosus (spongy degeneration) of the neuropil was also detected. CONCLUSIONS Morphological changes are similar to those described previously, which are induced by high-affinity, noncompetitive NMDA antagonists, such as MK-801.

Purine nucleoside phosphorylase and the enzymatic antioxidant defense system in breast milk from women with different levels of arsenic exposure

Purine nucleoside phosphorylase (PNP) is an ubiquitous enzyme which plays an important role in arsenic (As) detoxification. As is a toxic metalloid present in air, soil and water; is abundant in the environment and is readily transferred along the trophic chain, being found even in human breast milk. Milk is the main nutrient source for the growth and development of neonates. Information on breast milk synthesis and its potential defense mechanism against As toxicity is scarce. In this study, PNP and antioxidant enzymes activities, as well as glutathione (GSH) and total arsenic (TAs) concentrations, were quantified in breast milk samples. PNP, superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) activities and GSH concentration were determined spectrophotometrically; TAs concentration ([TAs]) was measured by atomic absorption spectrometry. Data suggest an increase in PNP activity (median = 0.034 U mg protein-1) in the presence of TAs (median = 1.16 g L(-1)). To explain the possible association of PNP activity in breast milk with the activity of the antioxidant enzymes as well as with GSH and TAs concentrations, generalized linear models were built. In the adjusted model, GPx and GR activities showed a statistically significant (p<0.01) association with PNP activity. These results may suggest that PNP activity increases in the presence of TAs as part of the detoxification mechanism in breast milk.

[Lipid peroxidation and the response of the antioxidant defense system in the obese type 2 diabetic compared with the non-obese type 2 diabetic].

Objective: To investigate the prevalence of trematode Aspidogastrea in the freshwater mussels in the Yangtze River basin within Anhui province, China. Methods: We initially harvested the freshwater mussels living in the Yangtze River running through Anhui area, and labeled them with corresponding number. Then the samples were dissected for isolating the flukes, which were identified by conventional staining. Results: Infection rate of trematode Aspidogastrea in freshwater mussels in the Yangtze River basin within the territory of Anhui province was 30.38℅(103/339)in general, and a total of 912 flukes of Aspidogastrea were detected in the 103 mussels, with average infection rate of 8.85 for each mussel. Conclusion: Trematode Aspdogastrea is prevalent in the freshwater bivalves living in the Yangtze River basin running through Anhui area, and the treamatode was identified as Aspidogaster sp. belong to Aspidogaste under Aspidogastridae of Aspidogastrea.Objective: to assess the use of oral nutritional supplements analyzing the reason for prescription and its implication in caloric-protein intake. Setting: study performed at a university hospital of 350 beds with medical and surgical specialties. Subjects, patients: Patients inclusion was done by selecting all starting oral nutritional supplement prescription. Exclusion criteria were being younger than 18 years, being admitted to the Intensive Care Unit, having cognition or communication impairments, being on concomitant parenteral nutrition or requiring complete enteral diet, and/or using nasogastric tube for feeding. We also excluded special enteral diets, specifically designed for certain conditions. Interventions: One-year long prospective study on prescription of oral nutritional supplements. Through clinical chart review and personal interview, we recorded demographic data, nutritional parameters, characteristics of the diet and supplement, and caloricprotein intake prescribed and ingested. The data were introduced in an Access97 database and processed by means of SPSS software for Windows®. We performed a descriptive study of quantitative and qualitative variables, a χ2 analysis between qualitative variables, and a comparative analysis between means of all paired data by means of the student’s t test, and variance analysis between quantitative variables. The significance level was set at p < 0.05. Results: we were only able to analyze 77 out of 130 prescriptions for nutritional supplements since we could not adequately interview the remaining patients, mainly due to neurological impairments. Mean age was 74.8 years (SD = 12) and 50.6% were women. The departments prescribing the highest number of supplements were hematology (22.1%) and internal medicine (20.8%). GI neoplasm was the most frequent diagnosis at admission (27.3%). The most frequent indication was kwashiorkor (45.5%), with 15.6% of patients being well nourished. Mean therapy duration was 11 days (SD = 11.1), and the main reason for termination was hospital discharge (70.1%). The supplement was concomitantly prescribed with the meals in 70.6% of the cases, and more than halfMaterial y metodos: Estudio retrospectivo de 55 pacientes de 65,4 ± 14,7 anos, 35,7% mujeres y 64,3% varones con un IMC 27,87 ± 5,56 kg/m (0% con IMC 30 kg/m ) en tratamiento con NPT con una duracion de 28 ± 5 dias (mas de 20 dias en el 75% de los casos). El 16,1% presentaba Diabetes Mellitus previa al inicio de NPT. En el 64,3% de los pacientes, la fistula ocurria tras cirugia reciente: en un 38.8% tras reseccion de colon, 16,6% de intestino delgado y 13,9% de estomago. La NPT se planificaba para aportar diariamente 1,5 × Gasto Energetico Basal, 1,5 g/kg/dia de proteinas, 6 mg de vitamina B 12 y 414 μg de acido folico. Ninguna solucion contenia hierro.Objective. To assess the impact of weight loss in clinical progression of the comorbidities in a group of morbid obese patients submitted to surgical treatment with the duodenal switch technique. Study setting. Between 2001-2006, we have operated by the duodenal crossing technique a total of 118 morbid obese patients (97 women and 21 men), mean age 42.6 years. Average pre-surgical BMI was 49.7, with average overweight of 69.1 kg. After surgical intervention, we have prospectively assessed the progression of the main comorbidities (arterial hypertension, diabetes, OSAS, osteoarticular pathology, dyslipidemia), according to the subscale of the BAROS scoring system. Postsurgical controls are done at months 3, 6, 12, 18, and 24 and annually thereafter. We have followed-up 110 patients, of whom 90 presented comorbidities, being the ones studied. Results. At 3 months post-surgery, we observed a decrease in the mean value of %WL to 31%, and a mean BMI value of 41.3, the percentage of lost BMI being 40.3%. Most of the weight loss occurred within 2 years, with %WL of 74.8% and a percentage of lost BMI of 97.7%. In 68 patients (75.5%) there was resolution of their comorbidities, 14.4% having improvement, and 10% with no improvement in spite of the surgery. Of patients achieving complete resolution, almost all of them achieved it within two years after surgery. Cure rates correlate with weight loss, so that at 3 months, with a mean weight loss of 25 kg (BMI decrease of 8.4 points) the comorbidity resolution rate is 45.5%. At 12 months, with a mean decrease in BMI of 16.4 points, %WL of 61.6% and % of lost BMI of 70.4%, the comorbidity resolution rate is 89.7%. At two years, by the time most of the main comorbidities resolved (68 patients), the BMI decreased by 22.4 points, the %WL 74.8% and the % of lost BMI 97.9%. Conclusion. The aim of bariatric surgery is weight loss and overweight-associated comorbidities improvement. In our study, most of the comorbidities improvement started at the third month, with the highest improvement rate occurring within two years, verifying that there is a direct relationship between post-surgical weight loss comorbidities improvement and resolution in most of the cases.Objective: To investigate the breeding rate and breeding density of Carpoglyphus lactis in stored Fructus Jujubae in Anhui, China in order to provide a scientific basis for prevention of Carpoglyphus lactis(C. lactis) from spoiling the dried fruit of such category. Methods： By the breeding nature of C. lactis, we collected samples of Fructus Jujubae, which were kept over 6 months in general, from the dried fruit shop and (or) Chinese herbal medicine warehouse, and isolated C. lactis from those samples. The mite specimens were prepared, and microscopically and morphologically identified. Species classification was done in accordance with Hughes (1976). Result:C. lactis was identified in 19 of the 300 samples, with breeding density and breeding rate of 6.52 heads/g and 6.33%. Constitute ratio at distinct developmental phase was associated with adult (including nymph, 85.71%), larva(12.27%), hypopus (0.56%) and egg(1.45%), respectively. The richness index, diversity index and evenness index was1.644, 1.644 and 0.923, respectively. Conclusion： Carpoglyphus lactis appears infesting in large quantity in the Fructus Jujubae stored in the above places in Anhui province, and the density is higher. Therefore, it is urgent to take effective measures to prevent C. lactis from spreading over other dried products stored in the same room and potential human intestinal acariasis as a result of the biological contamination.Objective: To determine possible associations between the risk of breast cancer in Brazilian women and demographic, social and economical variables, and past dietary intake. Methods: A case-control study was conducted in Joinville, Santa Catarina, Brazil, between june and november 2003 involving a group of 33 women recently diagnosed with breast cancer and a control group of 33 healthy women volunteers. Personal details, health history and past dietary intake were obtained via questionnaires and interviews. Data between groups were compared using χ2, Fisher, and Student’s t test, whilst associations were evaluated using a non-conditional logistic regression method and odds ratio (OR). Results: Statistically significant differences between the two groups were revealed with respect to age distribution (P = 0.007), family income level (P = 0.02), educational level (P 45 years), low family income (<