Diclofenac sensitizes multi-drug resistant Acinetobacter baumannii to colistin.

Acinetobacter baumannii causes life-threatening infections that are becoming difficult to treat due to increasing rates of multi-drug resistance (MDR) among clinical isolates. This has led the World Health Organization and the CDC to categorize MDR A. baumannii as a top priority for the research and development of new antibiotics. Colistin is the last-resort antibiotic to treat carbapenem-resistant A. baumannii . Not surprisingly, reintroduction of colistin has resulted in the emergence of colistin-resistant strains. Diclofenac is a nonsteroidal anti-inflammatory drug used to treat pain and inflammation associated with arthritis. In this work, we show that diclofenac sensitizes colistin-resistant A. baumannii clinical strains to colistin, in vitro and in a murine model of pneumonia. Diclofenac also reduced the colistin MIC of Klebsiella pneumoniae and Pseudomonas aeruginosa isolates. Transcriptomic and proteomic analyses revealed an upregulation of oxidative stress-related genes and downregulation of type IV pili induced by the combination treatment. Notably, the concentrations of colistin and diclofenac effective in the murine model were substantially lower than those determined in vitro , implying a stronger synergistic effect in vivo compared to in vitro . A pilA mutant strain, lacking the primary component of the type IV pili, became sensitive to colistin in the absence of diclofenac. This suggest that the downregulation of type IV pili is key for the synergistic activity of these drugs in vivo and indicates that colistin and diclofenac exert an anti-virulence effect. Together, these results suggest that the diclofenac can be repurposed with colistin to treat MDR A. baumannii .

Identification of Determinants that Allow Maintenance of High-Level Fluoroquinolone Resistance in Acinetobacter baumannii.

Acinetobacter baumannii is associated with multidrug resistant (MDR) infections in healthcare settings, with fluoroquinolones such as ciprofloxacin being currently ineffective. Clinical isolates largely harbor mutations in the GyrA and TopoIV fluoroquinolone targets, as well as mutations that increase expression of drug resistance-nodulation-division (RND) efflux pumps. Factors critical for maintaining fitness levels of pump overproducers are uncharacterized despite their prevalence in clinical isolates. We here identify proteins that contribute to the fitness of FQR strains overexpressing three known RND systems using high-density insertion mutagenesis. Overproduction of the AdeFGH efflux pump caused hypersensitization to defects in outer membrane homeostatic regulation, including lesions that reduced LOS biosynthesis and blocked production of the major A. baumannii porin. In contrast, AdeAB pump overproduction, which does not affect the outer membrane pump component, was relatively tolerant to loss of these functions, consistent with outer membrane protein overproduction being the primary disruptive component. Surprisingly, overproduction of proton-transporting efflux pumps had little impact on cytosolic pH, consistent with a compensatory response to pump activity. The most striking transcriptional changes were associated with AdeFGH pump overproduction, resulting in activation of the phenylacetate (PAA) degradation regulon. Disruption of the PAA pathway resulted in cytosolic acidification and defective expression of genes involved in protection from peroxide stress. These results indicate that the RND outer membrane protein overproduction is compensated by cytoplasmic buffering and maintenance of outer membrane integrity in A. baumannii to facilitate fitness of FQR isolates.

Dual membrane-spanning anti-sigma factors regulate vesiculation in Bacteroides thetaiotaomicron.

Bacteroidota are abundant members of the human gut microbiota that shape the enteric landscape by modulating host immunity and degrading dietary- and host-derived glycans. These processes are mediated in part by Outer Membrane Vesicles (OMVs). Here, we developed a high-throughput screen to identify genes required for OMV biogenesis and its regulation in Bacteroides thetaiotaomicron (Bt). We identified a family of Dual membrane-spanning anti-sigma factors (Dma) that control OMV biogenesis. We conducted molecular and multiomic analyses to demonstrate that deletion of Dma1, the founding member of the Dma family, modulates OMV production by controlling the activity of the ECF21 family sigma factor, Das1, and its downstream regulon. Dma1 has a previously uncharacterized domain organization that enables Dma1 to span both the inner and outer membrane of Bt. Phylogenetic analyses reveal that this common feature of the Dma family is restricted to the phylum Bacteroidota. This study provides mechanistic insights into the regulation of OMV biogenesis in human gut bacteria.

LptD depletion disrupts morphological homeostasis and upregulates carbohydrate metabolism in Escherichia coli.

In a previous in silico study, we identified an essential outer membrane protein (LptD) as an attractive target for development of novel antibiotics. Here, we characterized the effects of LptD depletion on Escherichia coli physiology and morphology. An E. coli CRISPR interference (CRISPRi) strain was constructed to allow control of lptD expression. Induction of the CRISPRi system led to ∼440-fold reduction of gene expression. Dose-dependent growth inhibition was observed, where strong knockdown effectively inhibited initial growth but partial knockdown exhibited maximum overall killing after 24 h. LptD depletion led to morphological changes where cells exhibited long, filamentous cell shapes and cytoplasmic accumulation of lipopolysaccharide (LPS). Transcriptional profiling by RNA-Seq showed that LptD knockdown led to upregulation of carbohydrate metabolism, especially in the colanic acid biosynthesis pathway. This pathway was further overexpressed in the presence of sublethal concentrations of colistin, an antibiotic targeting LPS, indicating a specific transcriptional response to this synergistic envelope damage. Additionally, exposure to colistin during LptD depletion resulted in downregulation of pathways related to motility and chemotaxis, two important virulence traits. Altogether, these results show that LptD depletion (i) affects E. coli survival, (ii) upregulates carbohydrate metabolism, and (iii) synergizes with the antimicrobial activity of colistin.

Laryngeal Amyloidosis: What is the Role of Imaging?

OBJECTIVE/HYPOTHESIS: To review the imaging findings of laryngeal amyloidosis and to identify radiological findings suggestive of this disease. STUDY DESIGN: Retrospective case series. METHODS: A retrospective chart review of patients with pathologically confirmed laryngeal amyloidosis was performed from 2009 to 2022. Clinical and demographic factors were collected. A fellowship-trained head and neck radiologist reviewed all computed tomography (CT) scans and magnetic resonance imaging (MRI) findings within this cohort. RESULTS: 12 patients were identified and a total of 36 imaging studies analyzed. Localized amyloidosis was found in the supraglottic region (n = 6), glottic region (n = 7), and subglottic region (n = 5); six patients had disease spanning two subsites. The most common finding on the CT scan was a homogeneous and well-defined submucosal soft tissue mass. Punctate calcifications were present in three cases. The presence of contrast enhancement was identified in the majority of patients who underwent MRI (4/5). MRI showed consistent signal intensity, hypointense, or isointense on both T1-weighted and T2-weighted images. Diffusion-weighted sequences were obtained in every patient and did not demonstrate diffusion restriction. CONCLUSION: This is the largest series searching for unifying imaging characteristics of laryngeal amyloidosis. This research suggests that characteristics from CT and MR provide both similar and unique features of laryngeal amyloidosis on imaging. Both modalities identify a submucosal mass. CT is the preferred modality to demonstrate punctate calcifications, while MRI identifies enhancement and altered signal characteristics. The main benefit of serial imaging is the correlation with patient symptoms, identification of the extent of disease, and assisting in delineating appropriate timing for surgery.

Dual Membrane-spanning Anti-Sigma Factors Regulate Vesiculation in Gut Bacteroidota.

Bacteroidota are abundant members of the human gut microbiota that shape the enteric landscape by modulating host immunity and degrading dietary- and host-derived glycans. These processes are at least partially mediated by O uter M embrane V esicles (OMVs). In this work, we developed a high-throughput screen to identify genes required for OMV biogenesis and its regulation in Bacteroides thetaiotaomicron ( Bt ). Our screening led us to the identification of a novel family of D ual M embrane-spanning A nti-sigma factors (Dma), which regulate OMV biogenesis in Bt . We employed molecular and multiomic analyses to demonstrate that deletion of Dma1, the founding member of the Dma family, results in hypervesiculation by modulating the expression of NigD1, which belongs to a family of uncharacterized proteins found throughout Bacteroidota. Dma1 has an unprecedented domain organization: it contains a C-terminal ß-barrel embedded in the OM; its N-terminal domain interacts with its cognate sigma factor in the cytoplasm, and both domains are tethered via an intrinsically disordered region that traverses the periplasm. Phylogenetic analyses reveal that the Dma family is a unique feature of Bacteroidota. This study provides the first mechanistic insights into the regulation of OMV biogenesis in human gut bacteria.

Acquired butterfly vertebra as a sequela of eosinophilic granuloma.

Butterfly vertebras are an abnormal embryological formation of the spinal bodies that occur because of a lack of fusion of the chondrification centers of the vertebral bodies. Langerhans cell histiocytosis is an entity that frequently involves vertebral bodies resulting in flat vertebras, and recovery of the vertebral body height is a very unusual finding. We present a case report of a pediatric patient with a thoracic acquired butterfly vertebra which occurred secondary to a Langerhans cell histiocytosis involvement. It is extremely rare to find vertebra plana that regains its complete height but is even more infrequent to evidence of a butterfly vertebra deformity that is not congenital.

Interspecies recombination, not de novo mutation, maintains virulence after ß-lactam resistance acquisition in Streptococcus pneumoniae.

As opposed to de novo mutation, ß-lactam resistance in S. pneumoniae is often conferred via homologous recombination during horizontal gene transfer. We hypothesize that ß-lactam resistance in pathogenic streptococci is restricted to naturally competent species via intra-/interspecies recombination due to in vivo fitness trade-offs of de novo penicillin-binding protein (PBP) mutations. We show that de novo mutant populations have abrogated invasive disease capacity and are difficult to evolve in vivo. Conversely, serially transformed recombinant strains efficiently integrate resistant oral streptococcal DNA, gain penicillin resistance and tolerance, and retain virulence in mice. Large-scale changes in pbp2X, pbp2B, and non-PBP-related genes occur in recombinant isolates. Our results indicate that horizontal transfer of ß-lactam resistance engenders initially favorable or minimal cost changes in vivo compared with de novo mutation(s), underscoring the importance of recombination in the emergence of ß-lactam resistance and suggesting why some pathogenic streptococci lacking innate competence remain universally susceptible.

The Phenylacetic Acid Catabolic Pathway Regulates Antibiotic and Oxidative Stress Responses in Acinetobacter.

The opportunistic pathogen Acinetobacter baumannii is responsible for a wide range of infections that are becoming increasingly difficult to treat due to extremely high rates of multidrug resistance. Acinetobacter's pathogenic potential is thought to rely on a "persist and resist" strategy that facilitates its remarkable ability to survive under a variety of harsh conditions. The paa operon is involved in the catabolism of phenylacetic acid (PAA), an intermediate in phenylalanine degradation, and is the most differentially regulated pathway under many environmental conditions. We found that, under subinhibitory concentrations of antibiotics, A. baumannii upregulates expression of the paa operon while simultaneously repressing chaperone-usher Csu pilus expression and biofilm formation. These phenotypes are reverted either by exogenous addition of PAA and its nonmetabolizable derivative 4-fluoro-PAA or by a mutation that blocks PAA degradation. Interference with PAA degradation increases susceptibility to antibiotics and hydrogen peroxide treatment. Transcriptomic and proteomic analyses identified a subset of genes and proteins whose expression is affected by addition of PAA or disruption of the paa pathway. Finally, we demonstrated that blocking PAA catabolism results in attenuated virulence in a murine catheter-associated urinary tract infection (CAUTI) model. We conclude that the paa operon is part of a regulatory network that responds to antibiotic and oxidative stress and is important for virulence. PAA has known regulatory functions in plants, and our experiments suggest that PAA is a cross-kingdom signaling molecule. Interference with this pathway may lead, in the future, to novel therapeutic strategies against A. baumannii infections. IMPORTANCE Acinetobacter baumannii causes a wide range of infections that are difficult to treat due to increasing rates of multidrug resistance; however, the mechanisms that this pathogen uses to respond to stress are poorly understood. Here, we describe a new mechanism of stress signaling in Acinetobacter that is mediated by the metabolite phenylacetic acid (PAA). We found that disrupting PAA catabolism interfered with A. baumannii's ability to adapt to stress, leading to decreased antibiotic tolerance and hydrogen peroxide resistance. We propose that investigating this stress response could lead to the development of novel therapeutics. In fact, PAA derivatives constitute a group of FDA-approved nonsteroidal anti-inflammatory drugs that could potentially be repurposed as antivirulence therapies to target multidrug-resistant Acinetobacter infections.

Rapid, Multianalyte Detection of Opioid Metabolites in Wastewater.

By monitoring opioid metabolites, wastewater-based epidemiology (WBE) could be an excellent tool for real-time information on the consumption of illicit drugs. A key limitation of WBE is the reliance on costly laboratory-based techniques that require substantial infrastructure and trained personnel, resulting in long turnaround times. Here, we present an aptamer-based graphene field effect transistor (AptG-FET) platform for simultaneous detection of three different opioid metabolites. This platform provides a reliable, rapid, and inexpensive method for quantitative analysis of opioid metabolites in wastewater. The platform delivers a limit of detection 2-3 orders of magnitude lower than previous reports, but in line with the concentration range (pg/mL to ng/mL) of these opioid metabolites present in real samples. To enable multianalyte detection, we developed a facile, reproducible, and high-yield fabrication process producing 20 G-FETs with integrated side gate platinum (Pt) electrodes on a single chip. Our devices achieved the selective multianalyte detection of three different metabolites: noroxycodone (NX), 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), and norfentanyl (NF) in wastewater diluted 20× in buffer.

Entropy of a bacterial stress response is a generalizable predictor for fitness and antibiotic sensitivity.

Current approaches explore bacterial genes that change transcriptionally upon stress exposure as diagnostics to predict antibiotic sensitivity. However, transcriptional changes are often specific to a species or antibiotic, limiting implementation to known settings only. While a generalizable approach, predicting bacterial fitness independent of strain, species or type of stress, would eliminate such limitations, it is unclear whether a stress-response can be universally captured. By generating a multi-stress and species RNA-Seq and experimental evolution dataset, we highlight the strengths and limitations of existing gene-panel based methods. Subsequently, we build a generalizable method around the observation that global transcriptional disorder seems to be a common, low-fitness, stress response. We quantify this disorder using entropy, which is a specific measure of randomness, and find that in low fitness cases increasing entropy and transcriptional disorder results from a loss of regulatory gene-dependencies. Using entropy as a single feature, we show that fitness and quantitative antibiotic sensitivity predictions can be made that generalize well beyond training data. Furthermore, we validate entropy-based predictions in 7 species under antibiotic and non-antibiotic conditions. By demonstrating the feasibility of universal predictions of bacterial fitness, this work establishes the fundamentals for potentially new approaches in infectious disease diagnostics.

Dielectrophoresis assisted rapid, selective and single cell detection of antibiotic resistant bacteria with G-FETs.

The rapid increase in antibiotic resistant pathogenic bacteria has become a global threat, which besides the development of new drugs, requires rapid, cheap, scalable, and accurate diagnostics. Label free biosensors relying on electrochemical, mechanical, and mass based detection of whole bacterial cells have attempted to meet these requirements. However, the trade-off between selectivity and sensitivity of such sensors remains a key challenge. In particular, point-of-care diagnostics that are able to reduce and/or prevent unneeded antibiotic prescriptions require highly specific probes with sensitive and accurate transducers that can be miniaturized and multiplexed, and that are easy to operate and cheap. Towards achieving this goal, we present a number of advances in the use of graphene field effect transistors (G-FET) including the first use of peptide probes to electrically detect antibiotic resistant bacteria in a highly specific manner. In addition, we dramatically reduce the needed concentration for detection by employing dielectrophoresis for the first time in a G-FET, allowing us to monitor changes in the Dirac point due to individual bacterial cells. Specifically, we realized rapid binding of bacterial cells to a G-FET by electrical field guiding to the device to realize an overall 3 orders of magnitude decrease in cell-concentration enabling a single-cell detection limit, and 9-fold reduction in needed time to 5 min. Utilizing our new biosensor and procedures, we demonstrate the first selective, electrical detection of the pathogenic bacterial species Staphylococcus aureus and antibiotic resistant Acinetobacter baumannii on a single platform.

Cystic trigeminal schwannomas.

Trigeminal Schwannomas are less than 1% of intracranial tumors, of which only 7% have a cystic component. We documented 2 cases of males with cystic trigeminal Schwannomas, their symptoms, the diagnosis process and the imaging characteristics. In addition, a review of the literature is performed, with emphasis on the radiological classification of this rare entity, that constitutes a diagnostic challenge for the radiologist, who has an essential role in the approach to the disease and therefore in its management.

Modulation of stress response and productive performance of Litopenaeus vannamei through diet.

The high tolerance of Litopenaeus vannamei to a wide range of salinity (1-50 psu) makes this species an excellent candidate for culture under low salinity, decreasing shrimp epidemics and water pollution in some coastal areas. However, salinity levels outside the optimal range could impose several physiological constraints that would in turn affect growth and survival, particularly in the presence of additional stressors (e.g. high densities, handling practices, and hypoxia). Despite shrimp susceptibility to individual stressors has been widely addressed, information regarding response to chronic and acute stressors combined and its relation to diet is scarce. Thus, the aim of our study was to determine the effect of diet on the susceptibility to chronic (low salinity) and acute (hypoxia and escape response) stressors in terms of culture performance and physiological indicators. We evaluated overall performance during culture of L. vannamei at low salinity (6 psu), fed with an experimental diet with low protein and high carbohydrate content (26% protein and 6% fish meal plus probiotic mixture) and compared to a commercial formula with high protein and low carbohydrate content (40% crude protein and 20% fish meal without probiotic mixture). At the end of the rearing experiment, shrimp were exposed to two types of acute stress, hypoxia and escape. Biochemical (hemocyanin, total proteins, glucose, and lactate) and bioenergetic (adenylic energy charge and arginine phosphate levels) variables were measured to assess chronic stress response (salinity) and acute stress response (hypoxia or escape). The experimental diet resulted in higher muscle energy status that was not affected by low salinity, although lipid levels were lower under this condition. This diet partially counteracted the low performance at low salinity and promoted greater protein efficiency. Hypoxia induced strong hyperglycemic and lactate increase as response, whereas escape response was characterized by a depletion of arginine phosphate levels, with a stronger decrease in shrimp fed experimental diet, due to the high initial level of this reserve. Some data (glucose levels in hemolymph and lipids in hepatopancreas) suggest that shrimp under chronic stress conditions (low salinity and high densities) present a low ability to respond to subsequent acute stressors such as hypoxia or escape. This work indicates that diet can increase the energy status of shrimp, enabling them to overcome potential multifactorial stressors, which are common in farming systems.

Coordinated alpha and gamma control of muscles and spindles in movement and posture.

Mounting evidence suggests that both α and γ motoneurons are active during movement and posture, but how does the central motor system coordinate the α-γ controls in these tasks remains sketchy due to lack of in vivo data. Here a computational model of α-γ control of muscles and spindles was used to investigate α-γ integration and coordination for movement and posture. The model comprised physiologically realistic spinal circuitry, muscles, proprioceptors, and skeletal biomechanics. In the model, we divided the cortical descending commands into static and dynamic sets, where static commands (α s and γ s ) were for posture maintenance and dynamic commands (α d and γ d ) were responsible for movement. We matched our model to human reaching movement data by straightforward adjustments of descending commands derived from either minimal-jerk trajectories or human EMGs. The matched movement showed smooth reach-to-hold trajectories qualitatively close to human behaviors, and the reproduced EMGs showed the classic tri-phasic patterns. In particular, the function of γ d was to gate the α d command at the propriospinal neurons (PN) such that antagonistic muscles can accelerate or decelerate the limb with proper timing. Independent control of joint position and stiffness could be achieved by adjusting static commands. Deefferentation in the model indicated that accurate static commands of α s and γ s are essential to achieve stable terminal posture precisely, and that the γ d command is as important as the α d command in controlling antagonistic muscles for desired movements. Deafferentation in the model showed that losing proprioceptive afferents mainly affected the terminal position of movement, similar to the abnormal behaviors observed in human and animals. Our results illustrated that tuning the simple forms of α-γ commands can reproduce a range of human reach-to-hold movements, and it is necessary to coordinate the set of α-γ descending commands for accurate and stable control of movement and posture.

Conocimientos, actitudes y aceptación de la sal fluorada en una población peruana / Knowledge, attitudes and acceptance of fluoridated salt in a peruvian population

Determinar los conocimientos, actitudes y aceptación de la sal fluorada de los padres de familia atendidos en la Casa del Adulto Mayor y la Casa de la Mujer de la Municipalidad de Chorrillos. Lima û Perú. Materiales y métodos. La muestra estuvo conformada por 130 padres de familia. Se realizó una entrevista estructurada y se presentaron los datos mediante tablas de distribución de frecuencias. Resultados. Respecto al conocimiento sobre la sal fluorada, solo el 16,2% conocía de su existencia, y de este grupo, el 33,3% no estaba informado de sus beneficios. Respecto a las actitudes sobre la sal fluorada, el 76,9% refirió que no compraba ninguna marca en especial. La mayor parte no revisaba la etiqueta o leía solo la marca para identificar la sal de su elección (45,4% en ambos casos). El 86,9% manifestó no saber si vende sal fluorada cerca de su casa. Respecto a la aceptación, el 91,6% estaba de acuerdo con que la eficacia en la prevención de la caries es una buena razón para su consumo. El 97,7% consideró que los beneficios de la sal fluorada deberían darse a conocer en la etiqueta de la bolsa. El 93,1% estaría dispuesto a utilizar diariamente la sal fluorada en la preparación de las comidas de los niños, y el 96,2% recomendaría su uso a otros padres de familia. Conclusiones. La mayor parte de la población no presenta un conocimiento adecuado sobre la sal fluorada. Sin embargo, estarían dispuestos a consumirla y recomendarla si estuviesen mejor informados sobre los beneficios que aporta...

Objective. To determine the knowledge, attitudes and acceptance of the fluoridated salt of parents attended in the House of the Older Adult and the House of the Women, Municipality of Chorrillos. Lima - Peru. Material and methods. The sample consisted of 130 parents. An structured survey was made and data was presented by frequency distribution tables. Results. Regarding knowledge about fluoride salt, 16.2% knew of its existence. Of this group, 33.33% was not inofremed about their benefits. Regarding attitudes about fluoridated salt, 76.9% reported that they did not buy any brand in particular. The majority did not check the label or read only the mark to identify the salt of your choice (45.4% in both cases). 86.9% said that it did not know if they sell this productnear his home. With respect to the acceptance, 91.6% was in agreement with the effectiveness of caries prevention is a good reason for consumption. 97.7% considered the benefits of fluoridated salt should be disclosed in the label on the bag. 9.1% were willing to use fluoridated salt dialy to prepare meals for the children, and 96.2% would recommend its use to other parents Conclusions. The majority of the population does not have an adequate knowledge about the fluoridated salt. However, they would be willing to consume it and recommend it if they were better informed about the benefits...

Local and regional processes in community assembly.

Controversy on whether local (deterministic) or regional (stochastic) factors control the structure of communities persists after decades of research. The main reason for why it has not been resolved may lie in the nature of evidence which largely comes from realized natural communities. In such communities assembly history leaves a mark that may support either set of factors. To avoid the confounding effects of assembly history we controlled for these effects experimentally. We created a null community by mixing 17 rock pool communities. We then divided the null community into replicates and distributed among treatments representing a gradient of factors from local to regional. We hypothesized that if deterministic factors dominate the assembly of communities, community structures should show a corresponding gradient from being very similar and convergent to dissimilar and divergent. In contrast, if local processes are predominantly stochastic in nature, such a gradient of community configurations should emerge even in the homogeneous setting. Our results appear to partially support both hypotheses and thus suggest that both deterministic and stochastic processes contribute to the assembly of communities. Furthermore, we found that to satisfactorily explain patterns observed in natural communities environmental heterogeneity and regional processes must also be considered. In conclusion, although deterministic mechanisms seem to be important in the assembly of communities, in natural systems their signal may be diluted and masked whenever other factors exert meaningful influence. Such factors increase the number of possible paths to the point that the number of paths equals the number of communities in a metacommunity.

Influencia de la altitud sobre la regulación de la presión arterial en el ejercicio físico. Efectos sobre el sistema renina-angiotensina-aldosterona / The influence of altitude and exercise on the blood pressure regulating mechanisms renine-angiotensine-aldosterone

Objetivo: Investigar la influencia de la altitud moderada sobre la presión arterial y el sistema renina-angiotensina- aldosterona de mujeres jugadoras de voleibol de alto nivel (División de Honor de España).Hipótesis: El ejercicio físico intenso, unido a una menor presión parcial de oxígeno ambiental, deben modificar la presión arterial y, por tanto, sus mecanismos reguladores. Método: Se estudiaron 11 mujeres, jugadoras de voleibol de alto nivel, durante dos semanas en estado de normoxia (N1) (640 m. de altitud sobre el nivel del mar), durante las dos siguientes semanas en estado de hipoxia relativa (Primera semana: A1; segunda semana: A2) (2450 m. de altitud, en el Centro de Alto Rendimiento de Sierra Nevada, Granada, España) y nuevamente durante las dos semanas siguientes en normoxia (N2). Entrenaron dos veces al día, (3 horas al día), con niveles de entrenamiento similares. Cada día se determinaron la presión arterial al despertarse, antes y después de entrenar (tanto por la mañana, como por la tarde), los niveles de renina, angiotensia y aldosterona en sangre, el nivel de excreción de agua y el volumen urinario. Resultados: La aldosterona disminuye de forma significativa en la primera semana de hipoxia (A1) (valores de 157,0 pg/ml con una P<0,05 respecto a N1 y N2), al igual que la renina (valores de 12,82 pg/ml con una P£0,05 respecto a N1 y N2). La aldosterona aumenta en la segunda semana de hipoxia (A2) (169,3 pg/ml). También se produjo un incremento del volumen urinario (valores de 2918,1 ml con una P<0,05 respecto a N1 Y N2) y un incremento de la excreción de agua renal (valores de 2570,3 ml/día con una P<0,05). La presión arterial diastólica postentrenamiento mostró cambios significativos entre el estado de hipoxia y el de normoxia alcanzado valores de 69,72 y 73,45 mmHg en altitud con una P<0,05. Conclusiones: La renina disminuye en hipoxia, mientras que la aldosterona puede comportarse de forma variable. En altitud se incrementa el volumen urinario, la excreción de agua renal y la fracción de excreción de sodio a la vez que disminuyen el sodio y potasio urinarios. La presión arterial diastólica postentrenamiento sufre cambios muy significativos en altitud (AU)

Objective and hypothesis: To investigate the influence of moderate altitude on the Renine- angiotensine-aldosterone system in elyte volleybal women players. Intense physical exercise, combined with lower partial pressure of enviromental oxygen, should modify the blood pressure and therefore its regulating mechanisms. Method: Eleven elite women volleyball players were studied for a two week period in a state of normoxia (N1) at an altitude of 640 m above sea level, then during the following two weeks in a relative state of hypoxia (first week: A1; second week:A2), at a height of 2450 m in the Sierra Nevada High Performance Centre (Granada, Spain) and then again during the following two weeks in state of normoxia (N2). In each of those weeks, the players trained twice daily, each training session lasting abouth 3 hours, and at asimilar intensity. Blood pressure was taken each morning on waking, then before and after the training (morning and anfternoon) as well as the levels of Renine, angiotensine and aldosterone in blood and anothe levels of water excretion and quantity of urine. Results: Aldosterone values dropped significanty in th first week at hypoxia (A1) (values of 157,0 pg/ml with a p<0,05 in respect to N1 y N2), as well as renine (values of 12,82 pg/ ml with a p<0.05 in regards to N1 y N2). Nevertheless aldosterone increased during the second week hypoxia (A2) (169,3 pg/ml). There was also an increase in urinary volume (values of 2918,1 ml with a p<0.05 in respect to N1 and N2), and an increase of renal water excretion (values of 2570,3 ml/day with a p<0.05). Only the diastolic blood pressure wich was taken after the training showed any significant changes between the hypoxia and normoxia states, wich reached values of 69,72 and 73,45 mmHg in altitude, with a p<0.05 Conclusions: Renine decreases in hypoxia while aldosterone is variable. At altitude the volume of urine as well as renal water excretion and the sodium excretion increases while sodium and potassium decrease. The post-training diastolic blood pressure suffers significant changes at altitude (AU)