Nicorandil Affects Mitochondrial Respiratory Chain Function by Increasing Complex III Activity and ROS Production in Skeletal Muscle Mitochondria.

Adenosine triphosphate (ATP)-dependent potassium channels openers (KATP) protect skeletal muscle against function impairment through the activation of the mitochondrial KATP channels (mitoKATP). Previous reports suggest that modulators of the mitochondrial KATP channels have additional effects on isolated mitochondria. To determine whether the KATP channel opener nicorandil has non-specific effects that explain its protective effect through the mitochondrial function, chicken muscle mitochondria were isolated, and respiration rate was determined pollarographically. The activity of the electron transport chain (ETC) complexes (I-IV) was measured using a spectrophotometric method. Reactive oxygen species (ROS) levels and lipid peroxidation were assessed using flow cytometry and thiobarbituric acid assay, respectively. Both KATP channel opener nicorandil and KATP channel blocker 5-hydroxydecanoate (5-HD) decreased mitochondrial respiration; nicorandil increased complex III activity and decreased complex IV activity. The effects of nicorandil on complex III were antagonized by 5-HD. Nicorandil increased ROS levels, effect reverted by either 5-HD or the antioxidant N-2-mercaptopropionyl glycine (MPG). None of these drugs affected lipid peroxidation levels. These findings suggest that KATP channel opener nicorandil increases mitochondrial ROS production from complex III. This results by partially blocking electron flow in the complex IV, setting electron carriers in a more reduced state, which is favored by the increase in complex III activity by nicorandil. Overall, our study showed that nicorandil like other mitochondrial KATP channel openers might not act through mitoKATP channel activation.

Nicorandil improves post-fatigue tension in slow skeletal muscle fibers by modulating glutathione redox state.

Fatigue is a phenomenon in which force reduction has been linked to impairment of several biochemical processes. In skeletal muscle, the ATP-sensitive potassium channels (KATP) are actively involved in myoprotection against metabolic stress. They are present in sarcolemma and mitochondria (mitoKATP channels). K+ channel openers like nicorandil has been recognized for their ability to protect skeletal muscle from ischemia-reperfusion injury, however, the effects of nicorandil on fatigue in slow skeletal muscle fibers has not been explored, being the aim of this study. Nicorandil (10 µM), improved the muscle function reversing fatigue as increased post-fatigue tension in the peak and total tension significantly with respect to the fatigued condition. However, this beneficial effect was prevented by the mitoKATP channel blocker 5-hydroxydecanoate (5-HD, 500 µM) and by the free radical scavenger N-2-mercaptopropionyl glycine (MPG, 1 mM), but not by the nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 µM). Nicorandil also decreased lipid peroxidation and maintained both reduced glutathione (GSH) levels and an elevated GSH/GSSG ratio, whereas total glutathione (TGSH) remained unaltered during post-fatigue tension. In addition, NO production, measured through nitrite concentrations was significantly increased with nicorandil during post-fatigue tension; this increase remained unaltered in the presence of nicorandil plus L-NAME, nonetheless, this effect was reversed with nicorandil plus MPG. Hence, these results suggest that nicorandil improves the muscle function reversing fatigue in slow skeletal muscle fibers of chicken through its effects not only as a mitoKATP channel opener but also as NO donor and as an antioxidant.

Bowel obstruction: signs indicating the need for urgent surgery.

Bowel obstruction is common in emergency departments. Obstruction is more common in the small bowel than in the large bowel. The most common cause is postsurgical adhesions. Nowadays, bowel obstruction is diagnosed with multidetector computed tomography (MDCT). MDCT studies for suspected bowel obstruction should focus on four points that need to be mentioned in the report: confirming the obstruction, determining whether there is a single transition point or whether the obstruction is found in a closed loop, establishing the cause of the obstruction, and seeking signs of complications. Identifying signs of ischemia is important in the management of the patient because it enables patients at higher risk of poor outcomes after conservation treatment who could benefit from early surgical intervention to avoid greater morbidity and mortality associated with strangulation and ischemia of the obstructed bowel loop.

Identification of a novel HLA-DPB1 allele, DPB1*131:01, by sequence-based typing.

This report identifies a novel HLA-DPB1 allele, DPB1* 131:01.

Long-Term Phytoplankton Dynamics in a Complex Temporal Realm.

Faced with an environment of accelerated change, the long-term dynamics of biotic communities can be approached to build a consistent and causal picture of the communities' life. We have undertaken a 25-year monthly-sampling study on the phytoplankton of a meso-oligotrophic lake, paying attention to controlling factors of overall biomass (TB) and taxonomical group biomass (TGBs). Long-term series included decreased trends of TB and TGBs, and multi-scale periodicity. A decadal TB periodicity emerged related to nitrogen concentration and Cryptophytes. Annual periodicities were mainly related to air and water temperature controlling the abundance of Chlorophytes or Dinoflagellates. Intra-annual cycles could arise from autogenic processes. The analysis by periods revealed relevant dynamics (for example, Diatom periodicities), hidden in the analysis of the complete series. These results allow us to establish that: i) two organizational levels of phytoplankton change differently in time scales from months to decades; ii) controlling factors (climate, water physics and chemistry) act at different time scales and on different TGBs, and iii) different combinations of the "taxonomical group-control factor-trend and periodicity" set throughout the studied time explain total biomass dynamics. A holistic approach (multiple complementary analyses) is necessary to disentangle the different actors and relationships that explain non-stationary long-term phytoplankton dynamics.

Prevalence of eosinophilic esophagitis: A multicenter study on a pediatric population evaluated at thirty-six Latin American gastroenterology centers. / Prevalencia de esofagitis eosinofílica: estudio multicéntrico en población pediátrica evaluada en 36 centros de gastroenterología de América Latina.

INTRODUCTION AND OBJECTIVE: Eosinophilic esophagitis is a chronic, immune-mediated disease described in case series and publications worldwide. Over the past twenty years, the authors of different studies have attempted to evaluate its incidence and prevalence. The objetive of the present study was to estimate the prevalence of eosinophilic esophagitis in a group of children seen at 36 pediatric gastroenterology centers in ten Latin American countries. MATERIALS AND METHODS: A multicenter, observational, and cross-sectional study was conducted that estimated the period prevalence of eosinophilic esophagitis in children seen at outpatient consultation and that underwent diagnostic upper gastrointestinal endoscopy for any indication at 36 centers in 10 Latin American countries, within a 3-month time frame. RESULTS: Between April and June 2016, 108 cases of eosinophilic esophagitis were evaluated. Likewise, an average of 29,253 outpatient consultations and 4,152 diagnostic upper gastrointestinal endoscopies were carried out at the 36 participating centers. The period prevalence of eosinophilic esophagitis in the population studied (n=29,253) was 3.69 cases×1,000 (95% CI: 3.04 to 4.44), and among the children that underwent routine upper gastrointestinal endoscopy (n=4,152), it was 26x1,000 (95% CI: 22.6 to 29.4). CONCLUSIONS: The general period prevalence of eosinophilic esophagitis in a group of children evaluated at 36 Latin American pediatric gastroenterology centers was 3.69×1,000, and in the children that underwent endoscopy, it was 26×1,000. There was important prevalence variability between the participating countries and centers. The present analysis is the first study conducted on the prevalence of pediatric eosinophilic esophagitis in Latin America.

Changes in mitochondrial functionality and calcium uptake in hypertensive rats as a function of age.

We studied whether mitochondrial functions and Ca2+ metabolism were altered in Wistar Kyoto normotensive (WKY) and spontaneous hypertensive rats (SHR). Ca2+ uptake was decreased in SHR compared to WKY rats. Accumulation of Ca2+ was more efficient in WKY than in SHR rats. mDeltaPsi was lower in SHR compared to WKY rats. Basal complex IV activity was higher in SHR than WKY rats, whereas basal L-citrulline production, an indicator of nitric oxide synthesis, was decreased in SHR and dependent on Ca2+ concentration (p<0.05). Impact of Ca2+ was counteracted by EGTA. These data show an age-dependent decreased mitochondrial functions in brain mitochondria during hypertension.

Concordance between Lactose Quick Test, hydrogen-methane breath test and genotyping for the diagnosis of lactose malabsorption in children.

BACKGROUND: Lactose intolerance is a frequent condition in certain populations. Different methods for diagnosis exist. There is scarce literature regarding Lactose Quick Test (LQT) and concordance with other methods for lactose intolerance diagnosis in children. METHODS: Prospectively, we included children who underwent gastroduodenoscopy for evaluation of abdominal pain. We obtained a duodenal sample for LQT and blood sample for genetic test to evaluate LCT C>T-13910 variant. Later, patients underwent breath test with lactose, to evaluate malabsorption. We evaluated the concordance between the three different tests. KEY RESULTS: We included 46 patients, 56.5% women. Mean age was 13.2 years (range 9-18 years). 66.6% of patients had lactose malabsorption according to breath test; 64.4% were homozygous CC; and 91.3% had hypolactasia (mild or severe) according to LQT. None of the patients with normolactasia had altered breath test. Genetic test had a substantial agreement (k = 0.675) with breath test and fair agreement (k = 0.301) with LQT. LQT had fair agreement (k = 0.348) with breath test. CONCLUSIONS & INFERENCES: Genetic test had better concordance with breath test than LQT to diagnose lactose malabsorption, however, none of the patients with normal LQT had lactose malabsorption. In patients who undergo gastroduodenoscopy to study abdominal pain, it seems reasonable to perform LQT, and, in those with hypolactasia, to perform breath test.

Aids knowledge and risk behaviors among Midwest migrant farm workers.

The objectives of this study were to investigate the AIDS/HIV knowledge of Latino adolescent and adult migrant farm workers in Michigan, to determine risk behaviors related to HIV, and to determine differences in generational norms regarding sexual activity. For the most part, the Latino migrant population seemed knowledgeable about sexual modes of HIV transmission, although casual contact, through kissing and going to school or work with an infected individual, was also seen as a possible route of transmission for some. Several condom beliefs were identified that may be barriers to use, including the beliefs that condoms are only for use with prostitutes (35 % agreed) and that condoms are only for gay men (54% agreed). Only a small proportion (10%) agreed that condoms were good protection from AIDS. Most respondents knew what condoms were, although only 51% of the sample knew friends who used them. Adolescent females in the camps generally disapproved of premarital sex, while males and older females were more accepting. All these factors make it pertinent to implement HIV/AIDS education programs that are culturally sensitive, gender-specific, and effective in both generations.

[Selective intra-arterial embolization in spontaneous rupture of hepatocarcinoma]. / Embolización selectiva intraarterial en ruptura espontánea de hepatocarcinoma.

We present the case of a patient with no previous history of liver disease, who required urgent medical care due to dizziness and hypotension. A diagnosis of hemoperitoneum was made by means of ultrasound and fine needle aspiration. The hemoperitoneum source was the spontaneous rupture of a liver tumor whose CT axial scan appearance was suggestive of hepatocarcinoma. The hemorrhage was controlled using intraarterial selective embolization. The rupture of a hepatocarcinoma is a surgical emergency with high mortality. Its early detection using an adequate diagnostic sequence, allows the surgeon to establish a therapeutic procedure as soon possible. Selective intraarterial embolization with alcohol has proved to be an effective procedure in the management of this kind of hemorrhage with a minimum surgical preparation, and allows further surgical interventions. Nevertheless mortality is still high due to the severity of the clinical entity.

[Evaluation of a school vaccination program in Cádiz]. / Evaluación de un programa de vacunación escolar en Cádiz.

This study reports the evaluation of a school vaccination program in the city of Cádiz developed by the School Health Area of city council. We have tried to determine how successfully the objectives previously established have been reached, and to purpose new guide lines for the future. The whole school population of Cádiz was the object of the study. We have analysed the coverage reached at the end of the scholar course 1987-1988 for tetanus and polio vaccination in children attending 1st, 2nd, 3rd, 4th, and 8th primary school levels (EGB). And also, for the rubella vaccination in girls attending 5th level. In the former, it has been found a global coverage of 62.1% for boys well vaccinated (WV) in 1st, 2nd, 3rd and 4th primary school levels, and 27.5% in 8th primary school level boys (WV). And in the latter the coverage obtained was 64% in 5th primary school level girls. Even though none of the proposed objectives have been reached (75%, 40% and 85% respectively) the results have been satisfactory and have enabled us to draw up a group of recommendations which may increase the grade of immunization of our school children in the future: to look for a more collaboration with the schools and to meet periodically with children's parents. Also, a continuous evaluation of the health programs is needed.

[Blood pressure, physical activity and anthropometry in adolescents]. / Presión sanguínea, activadad física y antropometría en adolescentes.

The relationship of blood pressure with physical activity and anthropometry was studied in 295 adolescents (mean age, 15.3 years) who entered 1. "formación profesional" (a technological training) in 1990 in Puerto Real, a village of Cádiz, Spain. Systolic and diastolic (fifth-phase Korotkoff) blood pressure, and anthropometrics measurements (weight, height and triceps and subscapular skinfolds thickness) were measured with standardized techniques. Habitual and sports physical activity were assessed by a self-reported questionnaire. The results reported in this study suggest that systolic blood pressure is associated with habitual physical activity in girls, and that the systolic blood pressure is associated weakly with sports activity in girls and in boys. The stronger predictor of blood pressure was Quetelet Index (kg/m2).

Importance of oxidative damage on the electron transport chain for the rational use of mitochondria-targeted antioxidants.

The electron transport chain (ETC) has become a promising pharmacological target as ETC impairment by reactive oxygen species (ROS) has been detected in several diseases. Therefore, for a better understanding of the actions of mitochondria-targeted antioxidants, it must be considered the interplay between the sources of ROS during disease, the chemical interconversions of ROS and their differential reactivity with ETC components. This review contrasts these aspects with available data about mitochondrial damage in specific diseases to give an insight into the importance of ROS chemistry in the rational use of mitochondria-targeted antioxidants, putting emphasis on the case of MitoQ.

Effects of D-amino acids on lipoperoxidation in rat liver and kidney mitochondria.

The effects of the amino acids D-ser, D-asp, and D-ala on lipoperoxidation under conditions of hypertension, alcoholism, and ammonemia in rat liver and kidney mitochondria were studied. Under normal conditions, D-alanine increased in 54% free radicals production in liver mitochondria (p < 0.05). The D-amino acids had no effect on kidney mitochondria. D-ser and D-ala increased lipoperoxidation in spontaneously hypertensive rats (SHR) as compared with their normotensive genetic control Wistar-Kyoto (WKY) rats (p < 0.05). During hypertension and in oxidative stress in the presence of calcium, only D-ala produced 46% and 29% free radicals in liver and kidney mitochondria (p < 0.05), respectively. During chronic alcoholism, D-ser increased lipoperoxidation in 80% in kidney mitochondria (p < 0.05), as compared to control. During ammonemia, D-ser produced 41% free radicals.

Functional characterization of brain mitochondrial nitric oxide synthase during hypertension and aging.

Nitric oxide (NO*) plays an important role in various physiological processes. The aim of the present study was to investigate if brain mitochondrial nitric oxide synthase (mtNOS) is active and functional during hypertension. L-citrulline production, an indicator of nitric oxide synthesis, was concentration-dependent on L-arginine in all strains and all ages tested, and was inhibited by 7-Nitroindazole (7-NI). Brain mitochondria of 1 month-old (prehypertensive) spontaneously hypertensive rats (SHR) exhibited a significantly (p < 0.05) low basal L-citrulline content as compared to age-matched Wistar (W) and Wistar-Kyoto (WKY) rats. L-citrulline synthesis in SHR rats showed a significant (p < 0.01) low response to L-arginine in 3 and 7 months-old rats. Respiratory rates in states 3 and 4 increased with low L-arginine concentration in all strains and all ages. The results suggest that in rat brain mitochondria, L-citrulline synthesis is constant once age-related hypertension is installed and NO* does not regulate oxidative phosphorylation.

Panic anxiety, under the weather?

The relationship between weather conditions and psychiatric disorders has been a continuous subject of speculation due to contradictory findings. This study attempts to further clarify this relationship by focussing on specific conditions such as panic attacks and non-panic anxiety in relation to specific meteorological variables. All psychiatric emergencies attended at a general hospital in Barcelona (Spain) during 2002 with anxiety as main complaint were classified as panic or non-panic anxiety according to strict independent and retrospective criteria. Both groups were assessed and compared with meteorological data (wind speed and direction, daily rainfall, temperature, humidity and solar radiation). Seasons and weekend days were also included as independent variables. Non-parametric statistics were used throughout since most variables do not follow a normal distribution. Logistic regression models were applied to predict days with and without the clinical condition. Episodes of panic were three times more common with the poniente wind (hot wind), twice less often with rainfall, and one and a half times more common in autumn than in other seasons. These three trends (hot wind, rainfall and autumn) were accumulative for panic episodes in a logistic regression formula. Significant reduction of episodes on weekends was found only for non-panic episodes. Panic attacks, unlike other anxiety episodes, in a psychiatric emergency department in Barcelona seem to show significant meteorotropism. Assessing specific disorders instead of overall emergencies or other variables of a more general quality could shed new light on the relationship between weather conditions and behaviour.

Hatching gland cells of trout embryos as the target of positional information.

HGCs were found in the head epidermis, yolk sac and pharynx epithelium of trout embryos. These cells usually appear in clusters, closely related positionally to neighbouring cells. The differentiation and specialization of HGCs seem to be mainly dependent on cell-cell interactions, which provides, in part, the positional information necessary for the cells to differentiate and localize in the appropriate place. The final secretory process is the result of a sequence of events by which the maturation of enzymatic granules occurs. The electron-density of the granules varies according to the proximity of the secretory stage. Exocytosis of the secretory granules were observed. After secretion, each HGC undergoes cellular death by apoptosis (programmed cell death).

CMV-driven expression of green fluorescent protein (GFP) in male germ cells of transgenic mice and its effect on fertility.

To determine if the expression of green fluorescent protein (GFP) during spermatogenesis can compromise the fertility of transgenic animals, we have produced mouse transgenic lines expressing GFP in the testis under the control of the potent immediate early promoter and enhancer region of the human cytomegalovirus (CMV). GFP expression was detected in the germ cells with no apparent effect on the fertility of any of the five transgenic lines studied. We demonstrate that the CMV promoter is transcriptionally active in the testes of mice aged 7 days. However, protein could be visually detected only after day 10. GFP was not found either in mature spermatozoa or in Sertoli cells, but it was evident in round spermatids from seminiferous tubules and in cytoplasmic drops of spermatozoa from the epididymis. We also detected GFP in spermatogonia expressing c-kit, which indicates that GFP expression driven by the CMV promoter takes place during the proliferative phase of spermatogenesis. The expression of GFP during spermatogenesis did not affect the fertility of transgenic mice.

[Experimental induction of abnormalities by the instillation of ethanol in embryonated eggs of chickens (Gallus gallus)]. / Inducción experimental á malformaciones por instilacion de etanol en huevos embrionados de pollo (Gallus gallus).

The teratogenic effect of alcohol on chick embryos has been confirmed by many investigators. However, how this occurs is unknown. The aim of this study was to establish a teratogenic pattern of alcohol effects, on the first stages of development in avians. Fertilized eggs were infused through the air space of the shell on day 0, with ethanol in concentrations of 20%, 40% and 60%. The control group was infused with 0.1 ml of NaCl at 0.9%. At a second stage, the eggs were treated on the 4th day of incubation, using the same method. In both groups the eggs were removed on the 11th day of incubation. The teratological manifestations that appeared more frequently were evisceration, haemorrhagic embryos, oedema, cranial deformities, lack of eyes, and umbilical hernia, showing every embryo a clear reduction in size and body weight.