N-Acetylcysteine Attenuates Cisplatin Toxicity in the Cerebrum and Lung of Young Rats with Artificially Induced Protein Deficiency.

Neurotoxicity is a major obstacle in the effectiveness of Cisplatin in cancer chemotherapy. In this process, oxidative stress and inflammation are considered to be the main mechanisms involved in brain and lung toxicity. The aim of the present work was to study the influence of the amount of protein on some oxidative parameters in the brain and lungs of rats treated with Cisplatin (CP) and N-Acetylcysteine (NAC) as neuroprotectors. Four groups of Wistar rats, each containing six animals, were fed with a protein diet at 7% for 15 days. Thereafter, the groups were given either a unique dose of CP® 5 mg/kg or NAC® 5 mg/kg as follows: group 1 (control), NaCl 0.9% vehicle; group 2, CP; group 3, NAC; and group 4, NAC + CP. The animals were sacrificed immediately after the treatments. Blood samples were collected upon sacrifice and used to measure blood triglycerides and glucose. The brain and lungs of each animal were obtained and used to assay lipid peroxidation (TBARS), glutathione (GSH), serotonin metabolite (5-HIAA), catalase, and the activity of Ca+2, and Mg+2 ATPase using validated methods. TBARS, H2O2, and GSH were found to be significantly decreased in the cortex and cerebellum/medulla oblongata of the groups treated with CP and NAC. The total ATPase showed a significant increase in the lung and cerebellum/medulla oblongata, while 5-HIAA showed the same tendency in the cortex of the same group of animals. The increase in 5-HIAA and ATPase during NAC and CP administration resulted in brain protection. This effect could be even more powerful when membrane fluidity is increased, thus proving the efficacy of combined NAC and CP drug therapy, which appears to be a promising strategy for future chemotherapy in malnourished patients.

Inflammatory Process and Immune System in Major Depressive Disorder.

Major depressive disorder (MDD) is one of the most common psychiatric illnesses in the general population. In mental disorders, the activation of inflammatory pathways in the brain is a major producer of excitotoxicity and an inducer of oxidative stress. The occurrence of these 2 events is partly responsible for the neuronal damage inherent in patients with mental disorders. In the case of MDD, the release of hormone and increase in pro-inflammatory cytokines in plasma and indicators of oxidative stress have been identified as consequences of this event. The most important affectations in patients with MDD are changes in their cognitive and executive functions due to brain inflammation. Hence, these biomarkers can serve as diagnostic and severity classification tools and treatment. In this work, we described the communication pathway between the immune and neuroendocrine systems in MDD and suggested possible therapeutic options for the disease.

Intake of oligoelements with cytarabine or etoposide alters dopamine levels and oxidative damage in rat brain.

Research on the relationships between oligoelements (OE) and the development of cancer or its prevention is a field that is gaining increasing relevance. The aim was to evaluate OE and their interactions with oncology treatments (cytarabine or etoposide) to determine the effects of this combination on biogenic amines and oxidative stress biomarkers in the brain regions of young Wistar rats. Dopamine (DA), 5-Hydroxyindoleacetic acid (5-Hiaa), Glutathione (Gsh), Tiobarbituric acid reactive substances (TBARS) and Ca+2, Mg+2 ATPase enzyme activity were measured in brain regions tissues using spectrophometric and fluorometric methods previously validated. The combination of oligoelements and cytarabine increased dopamine in the striatum but decreased it in cerebellum/medulla-oblongata, whereas the combination of oligoelements and etoposide reduced lipid peroxidation. These results suggest that supplementation with oligoelements modifies the effects of cytarabine and etoposide by redox pathways, and may become promising therapeutic targets in patients with cancer.

Oleic acid reduces oxidative stress in rat brain induced by some anticancer drugs.

Oleic acid (OA) is a monounsaturated compound with many health-benefitting properties such as obesity prevention, increased insulin sensitivity, antihypertensive and immune-boosting properties, etc. The aim of this study was to analyze the effect of oleic acid (OA) and some anticancer drugs against oxidative damage induced by nitropropionic acid (NPA) in rat brain. Six groups of Wistar rats were treated as follows: Group 1, (control); group 2, OA; group 3, NPA + OA; group 4, cyclophosphamide (CPP) + OA; group 5, daunorubicin (DRB) + OA; and group 6, dexrazoxane (DXZ) + OA. All compounds were administered intraperitoneally route, every 24 h for 5 days. Their brains were extracted to measure lipoperoxidation (TBARS), H2O2, Ca+2, Mg+2 ATPase activity, glutathione (GSH) and dopamine. Glucose, hemoglobin and triglycerides were measured in blood. In cortex GSH increased in all groups, except in group 2, the group 4 showed the highest increase of this biomarker. TBARS decrease, and dopamine increase in all regions of groups 4, 5 and 6. H2O2 increased only in cerebellum/medulla oblongata of group 5 and 6. ATPase expression decreased in striatum of group 4. Glucose increased in group 6, and hemoglobin increased in groups 4 and 5. These results suggest that the increase of dopamine and the antioxidant effect of oleic acid administration during treatment with oncologic agents could result in less brain injury.

A microfluidic card-based electrochemical assay for the detection of sulfonamide resistance genes.

Most electroanalytical detection schemes for DNA markers require considerable time and effort from expert personnel to thoroughly follow the analysis and obtain reliable outcomes. This work aims to present an electrochemical assay performed inside a small card-based platform powered by microfluidic manipulation, requiring minimal human intervention and consumables. The assay couples a sample/signal dual amplification and DNA-modified magnetic particles for the detection of DNA amplification products. Particularly, the sul1 and sul4 genes involved in the resistance against sulfonamide antibiotics were analyzed. As recognized by the World Health Organization, antimicrobial resistance threatens global public health by hampering medication efficacy against infections. Consequently, analytical methods for the determination of such genes in environmental and clinical matrices are imperative. Herein, the resistance genes were extracted from E. coli cells and amplified using an enzyme-assisted isothermal amplification at 37 °C. The amplification products were analyzed in an easily-produced, low-cost, card-based set-up implementing a microfluidic system, demanding limited manual work and small sample volumes. The target amplicon was thus captured and isolated using versatile DNA-modified magnetic beads injected into the microchannel and exposed to the various reagents in a continuously controlled microfluidic flow. After the optimization of the efficiency of each phase of the assay, the platform achieved limits of detections of 44.2 pmol L-1 for sul1 and 48.5 pmol L-1 for sul4, and was able to detect down to ≥500-fold diluted amplification products of sul1 extracted from E. coli living cells in around 1 h, thus enabling numerous end-point analyses with a single amplification reaction.

Neurohabilitation of Cognitive Functions in Pediatric Epilepsy Patients through LEGO®-Based Therapy.

In the pediatric population, epilepsy is one of the most common neurological disorders that often results in cognitive dysfunction. It affects patients' life quality by limiting academic performance and self-esteem and increasing social rejection. There are several interventions for the neurohabilitation of cognitive impairment, including LEGO®-based therapy (LEGO® B-T), which promotes neuronal connectivity and cortical plasticity through the use of assembly sets and robotic programming. Therefore, the aim of this study was to analyze the effect of LEGO® B-T on cognitive processes in pediatric patients with epilepsy. Eligible patients were identified; in the treatment group, an initial evaluation was performed with the NEUROPSI and BANFE-2 neuropsychological tests. Then, the interventions were performed once a week, and a final test was performed. In the control group, after the initial evaluation, the final evaluation was performed. An overall improvement was observed in the LEGO® B-T patients, with a significant increase in BANFE-2 scores in the orbitomedial, anterior prefrontal, and dorsolateral areas. In addition, in the gain score analysis, the orbitomedial and memory scores were significantly different from the control group. LEGO® B-T neurohabilitation is a remarkable option for epilepsy patients, who are motivated when they observe improvements.

Effect of mosquito mats (pyrethroid-based) vapor inhalation on rat brain cytochrome P450s.

The effect of transfluthrin (TF) or D-allethrin (DA) pyrethroid (PYR) vapors, often contained as main ingredients in two commercially available mosquito repellent mats, on cytochrome P450 (CYP) enzymes of rat brain and liver was assessed. Immunodetection of CYP2E1 and CYP3A2 proteins revealed their induction in cerebrum and cerebellum, but not in liver microsomes of rats exposed by inhalation to TF or DA. This overexpression of proteins correlated with an increase of their catalytic activities. The specifically increased expression of CYP isoenzymes, due to PYR exposure in the rat brain, could perturb the normal metabolism of endogenous and xenobiotic compounds and leads to increased risks of neurotoxicity by bioactivation, lipid peroxidation and DNA damage.

Habilitation of Executive Functions in Pediatric Congenital Heart Disease Patients through LEGO®-Based Therapy: A Quasi-Experimental Study.

Congenital heart disease is defined as an abnormality in the cardiocirculatory structure or function. Various studies have shown that patients with this condition may present cognitive deficits. To compensate for this, several therapeutic strategies have been developed, among them, the LEGO® Education sets, which use the pedagogic enginery to modify cognitive function by didactic material based on mechanics and robotics principles. Accordingly, the goal of this study was to evaluate the effect of cognitive habilitation by using LEGO®-based therapy in pediatric congenital heart disease patients. This was a quasi-experimental study; eligible patients were identified, and their general data were obtained. In the treatment group, an initial evaluation with the neuropsychological BANFE-2 test was applied; then, once a week, the interventions were performed, with a final test at the end of the interventions. In the control group, after the initial evaluation, a second appointment was scheduled for the final evaluation. Our results show that >50% of children presented cognitive impairment; nevertheless, there was an overall improvement in treatment patients, showing a significant increase in BANFE scores in areas related to executive functions. LEGO®-based therapy may be useful to improve cognitive abilities; however, future research should be performed to strengthen the data.

A putative siderophore receptor of Gallibacterium anatis 12656-12 under Fur control also binds hemoglobin.

Pasteurellaceae family members obtain iron directly from host proteins or through siderophore-dependent mechanisms. Although Gallibacterum anatis expresses different virulence factors, its response to growth under iron restriction is unknown. G. anatis cultured in the presence of 2,2'-dipyridyl, up-expressed an approximately 65 kDa protein and repressed the expression of a 70 kDa protein. MALDI-TOF analysis of those proteins indicated homology with CirA (65 kDa), a protein involved in iron-siderophore acquisition in Mannheimia succinoproducens and a TonB-dependent receptor (70 kDa protein), a protein that binds chicken hemoglobin; however, G. anatis siderophore production was not detected by chromo azurol S (CAS)-BHI agar determination. This putative G. anatis siderophore receptor is under Fur control, but not the hemoglobin binding protein, as observed in G. anatis 12656-12 fur mutant (Ω fur 126.13) grown in the presence or not of 2,2'-dipyridyl. The addition of FeCl3 to the culture medium diminished the growth and biofilm production in approximately 30% and 35%, respectively, in the wild-type strain, but the growth of Ω fur 126.13 strain was not affected and biofilm production increased in 35%. G. anatis Ω fur 126.13 presented lower virulence when it was inoculated to 35-day-old chickens in comparison to the wild-type strain. The induction of more than one iron uptake mechanism could benefit pathogenic microorganisms such as Gallibacterium.

Importance of Cry Proteins in Biotechnology: Initially a Bioinsecticide, Now a Vaccine Adjuvant.

A hallmark of Bacillus thuringiensis bacteria is the formation of one or more parasporal crystal (Cry) proteins during sporulation. The toxicity of these proteins is highly specific to insect larvae, exerting lethal effects in different insect species but not in humans or other mammals. The aim of this review is to summarize previous findings on Bacillus thuringiensis, including the characteristics of the bacterium, its subsequent contribution to biotechnology as a bioinsecticide due to the presence of Cry proteins, and its potential application as an adjuvant. In several studies, Cry proteins have been administered together with specific antigens to immunize experimental animal models. The results have shown that these proteins can enhance immunogenicity by generating an adequate immune response capable of protecting the model against an experimental infectious challenge, whereas protection is decreased when the specific antigen is administered without the Cry protein. Therefore, based on previous results and the structural homology between Cry proteins, these molecules have arisen as potential adjuvants in the development of vaccines for both animals and humans. Finally, a model of the interaction of Cry proteins with different components of the immune response is proposed.

The Microbial Composition in Circumneutral Thermal Springs from Chignahuapan, Puebla, Mexico Reveals the Presence of Particular Sulfur-Oxidizing Bacterial and Viral Communities.

Terrestrial thermal springs are widely distributed globally, and these springs harbor a broad diversity of organisms of biotechnological interest. In Mexico, few studies exploring this kind of environment have been described. In this work, we explore the microbial community in Chignahuapan hot springs, which provides clues to understand these ecosystems' diversity. We assessed the diversity of the microorganism communities in a hot spring environment with a metagenomic shotgun approach. Besides identifying similarities and differences with other ecosystems, we achieved a systematic comparison against 11 metagenomic samples from diverse localities. The Chignahuapan hot springs show a particular prevalence of sulfur-oxidizing bacteria from the genera Rhodococcus, Thermomonas, Thiomonas, Acinetobacter, Sulfurovum, and Bacillus, highlighting those that are different from other recovered bacterial populations in circumneutral hot springs environments around the world. The co-occurrence analysis of the bacteria and viruses in these environments revealed that within the Rhodococcus, Thiomonas, Thermonas, and Bacillus genera, the Chignahuapan samples have specific species of bacteria with a particular abundance, such as Rhodococcus erytropholis. The viruses in the circumneutral hot springs present bacteriophages within the order Caudovirales (Siphoviridae, Myoviridae, and Podoviridae), but the family of Herelleviridae was the most abundant in Chignahuapan samples. Furthermore, viral auxiliary metabolic genes were identified, many of which contribute mainly to the metabolism of cofactors and vitamins as well as carbohydrate metabolism. Nevertheless, the viruses and bacteria present in the circumneutral environments contribute to the sulfur cycle. This work represents an exhaustive characterization of a community structure in samples collected from hot springs in Mexico and opens opportunities to identify organisms of biotechnological interest.

Conventional nutritional counselling maintains nutritional status of patients on continuous ambulatory peritoneal dialysis in spite of systemic inflammation and decrease of residual renal function.

AIM: To evaluate the effect of nutritional counselling on nutritional status in peritoneal dialysis patients. METHODS: Twenty-nine peritoneal dialysis patients were randomly selected to receive conventional nutritional counselling during 6 months of follow up. All patients had monthly clinical and biochemical evaluations, and assessments of dialysis adequacy, inflammation and nutritional status at 0, 3 and 6 months. RESULTS: Moderate-severe malnutrition decreased 28% whereas normal nutrition increased 23% at final evaluation (non-significant). Calorie and protein intake remained stable throughout the study (baseline vs final, calorie: 24 +/- 8 vs 23 +/- 5 Kcal/kg; protein: 1.1 +/- 0.5 vs 1.0 +/- 0.3 g/Kg, respectively). On the other hand, triceps (16 +/- 6 vs 18 +/- 8 mm) and subscapular (17 +/- 8 vs 20 +/- 5 mm) skinfold thicknesses, and mid-arm circumference (27 +/- 3 vs 28 +/- 3 mm) significantly increased; mid-arm muscle area displayed a non-significant trend to increase (30 +/- 9 vs 31 +/- 9 cm(2)) whereas serum albumin significantly increased at the end of study (2.67 +/- 0.46 vs 2.94 +/- 0.48 g/dL). At final evaluation, median renal creatinine clearance decreased (6.3 (0.8-15.3) vs 2.0 (0.1-6.3) L/week per 1.73 m(2)) whereas interleukin-6 increased (2.33 (1.9-7.0) vs 4.02 (2.1-8.4) pg/mL). CONCLUSION: Even though conventional nutritional counselling, as an isolated measure, did not significantly improve all nutritional parameters, it prevented a greater deterioration during 6 months. Nutritional counselling maintained the nutritional status in spite of a decrease in residual renal function and higher systemic inflammation.

Frequency of auditory involvement and of associated factors in patients with juvenile idiopathic arthritis. / Frecuencia de la afección auditiva y los factores asociados en pacientes con artritis idiopática juvenil.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disease characterized by the presence of arthritis in children under 16 years of age for more than 6 weeks in the absence of any other known cause. The extra-articular manifestations, especially in the audiovestibular system, are related to the involvement of the joints of the ossicular chain as a result of the inflammatory process in the synovium. Previous clinical studies in pediatric patients have shown conductive or sensorineural hearing loss. OBJECTIVE: The aim of this study was to assess the frequency of hearing impairment and of associated factors in patients with JIA. METHODOLOGY: A prospective, analytical study was conducted from January 2013 to August 2014 in 62 patients with JIA aged between 5 and 15 years. The study was approved by the local ethics committee and parents signed their informed consent. All subjects underwent audiological examination involving otomicroscopy, audiometry, tympanometry, stapedius reflex and test for transient otoacoustic emissions (TOAE); rheumatologic evaluation included joint examination and the application of a measure of functional ability (disability) using the Childhood Health Assessment Questionnaire (CHAQ). Measures of central tendency and of dispersion were used (chi-square for associations and P<.05 for statistical significance). RESULTS: Sixty-two patients were included: 56 girls and 6 boys, mean age 11.9 years and mean disease duration of 3.4 years; 46% had rheumatoid factor (RF)- positive polyarticular JIA, 40% had RF-negative polyarticular JIA, 15% had disease of systemic onset and 3% had oligoarthritis. Active disease was found in 29 patients and 33 were in remission with medication. Of the total of 124 ears evaluated according to the Jerger classification for tympanometry, abnormal findings were observed in 78 that were type As and in 1 that was type Ad, whereas there were 45 type A ears. Hearing loss was disclosed by speech audiometry, rather than by pure tone audiometry. The TOAE were absent in 4% of those assessed and the stapedius reflex was absent in less than 10%. Factors that had a positive correlation with hearing impairment were RF-positive polyarticular JIA, disease duration, degree of disability and the erythrocyte sedimentation rate level (P<.000). CONCLUSION: The presence of an abnormal tympanogram suggested early involvement in the structure of the tympanic-ossicular complex; however, 3.4 years later, no hearing loss had been reported.

Neuroprogression: the hidden mechanism of depression.

For many years, depressive disorder (DD) was considered a transient and natural disease of people's mood. Its etiology had been attributed mainly to biochemical alterations of the monoamines and their receptors. Nevertheless, its prevalence and considerable impact on the family and social environment of those afflicted by it have placed the disease as a global public health problem. Neuroprogression is the term used to describe the changes in several psychiatric conditions evidenced and observed in the clinical manifestations, biochemical markers, and cerebral structures of the patients with major depressive disorder (MDD), which frequently overlap with neurodegenerative disorders. DD is considered a potentially aggressive state of neuronal deterioration involving apoptosis, reduced neurogenesis, decreased neuronal plasticity, and increased immune response. Clinically, it encompasses a poor response to treatment and an increase in depressive episodes, both of which bring about vulnerability and decline of functions associated with structural changes in the brain. The interest of this work is to review the metabolic processes involved in the morphologic alterations in the limbic system reported in patients with MDD, as well as the neurologic bases of this complex pathology that include environmental stress, genetic vulnerability, alterations in the neurotransmission, and changes in the neuroplasticity, all of which today bring into limelight a mechanism of progressive neuronal damage.

Oseltamivir and indomethacin reduce the oxidative stress in brain and stomach of infected rats.

The aim of this study was to determine the effect of oseltamivir and indomethacin on lipid peroxidation (LP), GABA levels, and ATPase activity in brain and stomach of normal and infected rats (IR), as novel inflammation model. Female Sprague Dawley rats grouped five each, either in the absence or presence of a live culture of Salmonella typhimurium (S. typh), were treated as follows: group 1 (control), PBS buffer; group 2, oseltamivir (100 mg/kg); group 3, indomethacin (67 µg/rat); group 4, oseltamivir (100 mg/kg) + indomethacin (67 µg/rat). All drugs were given intraperitoneally for 5 days. IR received the same treatments and the brain and stomach of the rats were removed in order to measure levels of GABA, LP, and total ATPase, using validated methods. Levels of GABA increased in stomach and cortex of IR with oseltamivir, but decreased in striatum and cerebellum/medulla oblongata of IR with indomethacin. LP decreased in the three brain regions of IR with oseltamivir. ATPase increased in stomach of IR and non-IR with oseltamivir and in striatum and cerebellum/medulla oblongata of IR with indomethacin. Results suggest that the effect of free radicals produced in an infection and inflammatory condition caused by S. typh could be less toxic by a combination of oseltamivir and indomethacin.

Tissue-specific induction of the carcinogen-inducible cytochrome P450 isoforms in the gastrointestinal tract.

Gastrointestinal tissues are directly exposed to dietary xenobiotics. In spite of this, modulation of cytochrome P450 (CYP) enzymes in the gastrointestinal tract is not well established. CYP induction could facilitate transformation of chemical agents to potentially toxic or carcinogenic metabolites. This might also determine drug efficacy, burden of foreign chemicals on tissues or bioavailability of certain therapeutic agents. In order to assess the induction of the CYP subfamilies 1A1/2, 2B1/2, 2E1 and 3A2 in the gastrointestinal tract, male Wistar rats were treated with phenobarbital/ß-naphthoflavone (PB/NF), cyclohexanol/albendazole (CH/ABZ) or toluene (TL). Microsomal fractions were prepared from tissue samples of the esophagus, the stomach, the duodenum, the colon and the liver. Western blot and enzymatic activity analyses revealed an increase in the expression and activity of CYP1A1/2 and CYP3A2 isoenzymes in the esophageal, duodenal and colonic microsomes from animals treated with PB/NF. CYP1A1/2 and CYP3A2 were induced in hepatic and duodenum microsomes by treatment with CH/ABZ. Our results demonstrate differential induction of CYP along the gastrointestinal tract by known CYP hepatic inducers, being the treatment with PB/NF the best induction system of the CYPs.

Assessment of Mexican Arnica (Heterotheca inuloides Cass) and Rosemary (Rosmarinus officinalis) Extracts on Dopamine and Selected Biomarkers of Oxidative Stress in Stomach and Brain of Salmonella typhimurium Infected rats.

BACKGROUND: The effects of some natural products on dopamine (DA) and 5-hydroxyindole acetic acid (5-HIAA) in brain of infected models are still unclear. OBJECTIVE: The purpose of this study was to measure the effect of Mexican arnica/rosemary (MAR) water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. METHODS: Female Wistar rats (weight 80 g) in the presence of MAR or absence (no-MAR) were treated as follows: group 1, buffer solution (controls); oseltamivir (100 mg/kg), group 2; culture of Salmonella typhimurium (S.Typh) (1 × 106 colony-forming units/rat) group 3; oseltamivir (100 mg/kg) + S.Typh (same dose) group 4. Drug and extracts were administered intraperitoneally every 24 h for 5 days, and S.Typh was given orally on days 1 and 3. On the fifth day, blood was collected to measure glucose and hemoglobin. The brains and stomachs were obtained to measure levels of DA, 5-HIAA, glutathione (GSH), TBARS, H2O2, and total ATPase activity using validated methods. RESULTS: DA levels increased in MAR group treated with oseltamivir alone but decreased in no-MAR group treated with oseltamivir plus S.Typh. 5-HIAA, GSH, and H2O2 decreased in this last group, and ATPase activity increased in MAR group treated with oseltamivir plus S.Typh. TBARS (lipid peroxidation) increased in MAR group that received oseltamivir alone. Most of the biomarkers were not altered significantly in the stomach. CONCLUSION: MAR extract alters DA and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. SUMMARY: The purpose of this study was to measure the effect of Mexican arnica/rosemary water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. Results: Mexican arnica and rosemary extract alter dopamine and metabolism of 5-HIAA in the brain of young animals infected. Antioxidant capacity may be involved in these effects. Abbreviations used: AS: Automated system, ATP: Adenosine triphosphate, CNS: Central nervous system, CFU: Colony-forming unit, DA: Dopamine EDTA: Ethylenediaminetetraacetic acid, 5-HIAA: Äcido 5-hidroxindolacético (serotonina), GABA: γ-aminobutyric acid, GSH: Glutathione, H2O2: Hidrogen peroxide, HCLO4: Perchloric acid, iNOS: Inducible nitric oxide synthase, LPS: Lipopolysaccharides, MAR: Arnica/Rosemary, NaCl: Sodium Chloride, NOGSH: nitrosoglutathione, NOS: Nitric oxide, OPT: Ortho-phtaldialdehyde, Pbs: Phosphate buffered saline, pH: potential of Hydrogen, Pi: Inorganic phosphate, ROS: Reactive oxygen species, RNSs: Reactive nitrogen species Tba: Thiobarbaturic acid, TBARS: Thiobarbituric aid reactive, Tca: Trichloroacetic, Tris-HCL: Tris hydrochloride, TSA: Trypticasein Soya Agar.

Can the inflammation markers of patients with high peritoneal permeability on continuous ambulatory peritoneal dialysis be reduced on nocturnal intermittent peritoneal dialysis?

BACKGROUND: Patients with high peritoneal permeability have the greatest degree of inflammation on continuous ambulatory peritoneal dialysis (CAPD), which may be associated with their higher mortality. Nocturnal intermittent peritoneal dialysis (NIPD; "dry day") may decrease inflammation by reducing the contact between dialysate and peritoneum and/or providing better fluid overload control. Therefore, the aims of this study were to determine and compare serum and dialysate concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) of patients with high or high-average peritoneal transport on CAPD, changed to NIPD, and ultimately to continuous cyclic peritoneal dialysis (CCPD). METHODS: Crossover clinical trial in 11 randomly selected patients. All subjects had been on CAPD and were changed to NIPD, and ultimately to CCPD (6.4 +/- 3.1 months after initiation of study). All patients used glucose-based dialysate. Evaluations of clinical and biochemical parameters, dialysis adequacy, and serum and dialysis inflammation markers were performed at baseline on CAPD, 7 - 14 days after changing to NIPD, 7 - 14 days after switching to CCPD, and after 1 year of follow-up. All patients used only 1.5% glucose dialysate during evaluation days. CRP was determined by nephelometry, and IL-6 and TNF-alpha by ELISA. RESULTS: Seven patients were high transporters and 4 high average. Ultrafiltration increased (p < 0.05) when patients changed from CAPD [0.38 L (-0.3 - 1.1 L)] to NIPD [2.64 L (0.7 - 4.7 L)]; it then decreased on CCPD [0.88 L (0.4 - 1.3 L) and at the end of study [0.65 L (0.3 - 1.0 L)]. This better fluid overload control was accompanied by decreased weight and systolic and diastolic blood pressure when patients changed from CAPD (89 +/- 13 kg, 160 +/- 23 and 97 +/-9 mmHg, respectively) to NIPD (86 +/- 17 kg, 145 +/- 14 and 86 +/- 9 mmHg, respectively), and increased weight and systolic and diastolic blood pressure on CCPD (85 +/- 15 kg, 143 +/-23 and 88 +/- 14 mmHg, respectively) and at the end of follow-up (87 +/- 16 kg, 155 +/- 24 and 89 +/- 12 mmHg, respectively). Median serum CRP decreased (p = 0.03), from 3.8 (1.6 - 8.5) mg/L on CAPD to 1.0 (0.4 - 4.4) mg/L on NIPD, but increased on CCPD [1.8 (1.3 - 21) mg/L] and at the end of the study [3.2 (0.3 - 8.2) mg/L]. Dialysate CRP decreased nonsignificantly, from 0.10 (0 - 0.5) mg/L on CAPD to 0 (0 - 0.03) mg/L on NIPD, to 0.01 (0 - 0.08) mg/L on CCPD, and to 0 (0 - 0) mg/L at final evaluation. Serum TNF-alpha concentration decreased, from 0.14 (0.04 - 0.6) pg/mL on CAPD to 0.01 (0 - 0.08) pg/mL on NIPD, and then increased to 0.06 (0 - 0.4) pg/mL on CCPD and to 0.11 (0 - 0.2) pg/mL at the end of the study; whereas dialysate TNF-alpha decreased, from 0.08 (0.03 - 0.2) pg/mL on CAPD to 0.04 (0 - 0.2) pg/mL on NIPD, and to 0 (0 - 0) pg/mL and 0 (0 - 0.05) pg/mL on CCPD and final evaluation respectively. Serum IL-6 decreased (p = 0.07), from 2.5 (2.0 - 4.2) pg/mL on CAPD to 1.0 (0.7 - 2.0) pg/mL on NIPD, and to 1.0 (0.8 - 2.9) pg/mL on CCPD and 1.0 (0.5 - 9.8) pg/mL at the end of the study; whereas dialysate levels remained similar on CAPD [8.0 (3.7 - 13) pg/mL] and NIPD [7.8 (5.1 - 23) pg/mL], and increased on CCPD [11.2 (9.5 - 19) pg/mL] and at final evaluation [11.2 (8.3 - 15) pg/mL]. CONCLUSIONS: NIPD significantly decreased serum CRP and displayed a trend to decrease TNF-alpha and IL-6 serum concentrations compared with CAPD; whereas CCPD tended to reverse these effects. These results did not appear to be due to decreased local peritoneal inflammation, but they could be associated with better control of fluid overload on NIPD. Thus, NIPD, as Long as the residual renal function allows it, may be useful in reducing the systemic inflammation of patients with high peritoneal membrane permeability.

Effect of cerebrolysin on dopaminergic neurodegeneration of rat with oxidative stress induced by 3-nitropropionic acid.

The study tested the hypothesis that cerebrolysin protects the brain from free radicals in rats treated with 3-nitropropionic acid (3-NPA). To address this hypothesis, the levels of dopamine (DA) and some oxidative stress biomarkers were measured after administration of 3-NPA. Young male Fischer rats were treated for three days with cerebrolysin, 3-NPA or both substances. Their brains were extracted, and DA, lipid peroxidation (LP), glutathione (GSH), calcium, and H2O2 were measured using validated methods. In the cortex, hemispheres and cerebellum/medulla oblongata of the group treated with cerebrolysin and 3-NPA, the levels of DA and LP decreased. In addition, calcium and H2O2 levels decreased in the hemispheres of the same group, while GSH increased in cortex. The increased dopamine metabolism due to the administration of cerebrolysin led to increased formation of radical species and oxidative stress, especially when free radicals were generated by 3-NPA.

Comparative effects of catechin, epicatechin and N-Ω-nitroarginine on quinolinic acid-induced oxidative stress in rat striatum slices.

UNLABELLED: The aim of this work was to compare the effects of catechin (CAT), epicatechin (EPI) and N-ω-l-nitroarginine (L-NARG) on different endpoints of oxidative stress induced by quinolinic acid (QUIN) in a simple tissue preparation, rat striatal slices - with particular emphasis in the glutathione system - in order to provide revealing information on the antioxidant efficacy of these agents in an excitotoxic model. METHODS: Rat striatal slices were incubated for 1h in the presence of 100 µM QUIN and/or 85 µM CAT or EPI, or 100 µM L-NARG. Lipid peroxidation (LP) and the levels of reduced and oxidized glutathione (GSH and GSSG) were determined. RESULTS: The three agents tested completely blocked the QUIN-induced lipid peroxidation and recovered the QUIN-induced altered GSH/GSSG balance. No statistical differences were detected among the protective effects exerted by these antioxidants, suggesting similar efficacy and common antioxidant mechanisms. The antioxidant properties exhibited by these molecules on the excitotoxic model tested herein support an active role of glutathione and prompt their use as therapeutic tools in models of neurodegenerative disorders.