Role of respiratory NADH oxidation in the regulation of Staphylococcus aureus virulence.

The success of Staphylococcus aureus as a pathogen is due to its capability of fine-tuning its cellular physiology to meet the challenges presented by diverse environments, which allows it to colonize multiple niches within a single vertebrate host. Elucidating the roles of energy-yielding metabolic pathways could uncover attractive therapeutic strategies and targets. In this work, we seek to determine the effects of disabling NADH-dependent aerobic respiration on the physiology of S. aureus. Differing from many pathogens, S. aureus has two type-2 respiratory NADH dehydrogenases (NDH-2s) but lacks the respiratory ion-pumping NDHs. Here, we show that the NDH-2s, individually or together, are not essential either for respiration or growth. Nevertheless, their absence eliminates biofilm formation, production of α-toxin, and reduces the ability to colonize specific organs in a mouse model of systemic infection. Moreover, we demonstrate that the reason behind these phenotypes is the alteration of the fatty acid metabolism. Importantly, the SaeRS two-component system, which responds to fatty acids regulation, is responsible for the link between NADH-dependent respiration and virulence in S. aureus.

The Sensor Histidine Kinase ArlS Is Necessary for Staphylococcus aureus To Activate ArlR in Response to Nutrient Availability.

Staphylococcus aureus is a versatile opportunistic pathogen whose success is driven by its ability to adapt to diverse environments and host-imposed stresses. Two-component signal transduction systems, such as ArlRS, often mediate these adaptations. Loss of ArlRS or the response regulator ArlR alone impairs the ability of S. aureus to respond to host-imposed manganese starvation and glucose limitation. As sensor histidine kinases and response regulators frequently work as pairs, it has been assumed that ArlS senses and activates ArlR in response to these stimuli. However, recent work suggests that the sensor histidine kinase GraS can also activate ArlR, calling the contribution of ArlS in responding to manganese and glucose availability into question. The results of current studies reveal that ArlS is necessary to activate ArlR in response to manganese sequestration by the host immune effector calprotectin and glucose limitation. Although the loss of ArlS does not completely eliminate ArlR activity, this response regulator is no longer responsive to manganese or glucose availability in the absence of its cognate histidine kinase. Despite the residual activity of ArlR in the absence of ArlS, ArlR phosphorylation by ArlS is required for S. aureus to resist calprotectin-imposed metal starvation. Cumulatively, these findings contribute to the understanding of S. aureus signal transduction in response to nutritional immunity and support the previous observation indicating that ArlRS is activated by a common signal derived from host-imposed manganese and glucose limitation. IMPORTANCE The ability of pathogens, including Staphylococcus aureus, to sense and adapt to diverse environments partially relies on two-component systems, such as ArlRS. Recent work revealed that the response regulator ArlR can be cross-activated by the sensor histidine kinase GraS, rendering the role of its cognate partner, ArlS, in response to manganese and glucose limitation uncertain. The results of this study reveal that ArlS is necessary for the activation of ArlR in response to calprotectin and glucose limitation. Although a low level of ArlR activity remains in the absence of ArlS, ArlS phosphotransfer to ArlR is required for S. aureus to overcome calprotectin-induced nutritional stress. Collectively, this study provides fundamental information to understand how ArlRS mediates staphylococcal adaptation during infection.

Metal-independent variants of phosphoglycerate mutase promote resistance to nutritional immunity and retention of glycolysis during infection.

The ability of Staphylococcus aureus and other pathogens to consume glucose is critical during infection. However, glucose consumption increases the cellular demand for manganese sensitizing S. aureus to host-imposed manganese starvation. The current investigations were undertaken to elucidate how S. aureus copes with the need to consume glucose when metal-limited by the host. A critical component of host defense is production of the manganese binding protein calprotectin. S. aureus has two variants of phosphoglycerate mutase, one of which is manganese-dependent, GpmI, and another that is manganese-independent, GpmA. Leveraging the ability to impose metal starvation in culture utilizing calprotectin revealed that the loss of GpmA, but not GpmI, sensitized S. aureus to manganese starvation. Metabolite feeding experiments revealed that the growth defect of GpmA when manganese-starved was due to a defect in glycolysis and not gluconeogenesis. Loss of GpmA reduces the ability of S. aureus to cause invasive disease in wild type mice. However, GpmA was dispensable in calprotectin-deficient mice, which have defects in manganese sequestration, indicating that this isozyme contributes to the ability of S. aureus to overcome manganese limitation during infection. Cumulatively, these observations suggest that expressing a metal-independent variant enables S. aureus to consume glucose while mitigating the negative impact that glycolysis has on the cellular demand for manganese. S. aureus is not the only bacterium that expresses manganese-dependent and -independent variants of phosphoglycerate mutase. Similar results were also observed in culture with Salmonella enterica serovar Typhimurium mutants lacking the metal-independent isozyme. These similar observations in both Gram-positive and Gram-negative pathogens suggest that expression of metal-independent glycolytic isozymes is a common strategy employed by bacteria to survive in metal-limited environments, such as the host.

Intracellular Accumulation of Staphylopine Can Sensitize Staphylococcus aureus to Host-Imposed Zinc Starvation by Chelation-Independent Toxicity.

The host restricts the availability of zinc to prevent infection. To overcome this defense, Staphylococcus aureus and Pseudomonas aeruginosa rely on zincophore-dependent zinc importers. Synthesis of the zincophore staphylopine by S. aureus and its import are both necessary for the bacterium to cause infection. In this study, we sought to elucidate how loss of zincophore efflux impacts bacterial resistance to host-imposed zinc starvation. In culture and during infection, mutants lacking CntE, the staphylopine efflux pump, were more sensitive to zinc starvation imposed by the metal-binding immune effector calprotectin than those lacking the ability to import staphylopine. However, disruption of staphylopine synthesis reversed the enhanced sensitivity phenotype of the ΔcntE mutant to calprotectin, indicating that intracellular toxicity of staphylopine is more detrimental than the impaired ability to acquire zinc. Unexpectedly, intracellular accumulation of staphylopine does not increase the expression of metal importers or alter cellular metal concentrations, suggesting that, contrary to prevailing models, the toxicity associated with staphylopine is not strictly due to intracellular chelation of metals. As P. aeruginosa and other pathogens produce zincophores with similar chemistry, our observations on the crucial importance of zincophore efflux are likely to be broadly relevant.IMPORTANCEStaphylococcus aureus and many other bacterial pathogens rely on metal-binding small molecules to obtain the essential metal zinc during infection. In this study, we reveal that export of these small molecules is critical for overcoming host-imposed metal starvation during infection and prevents toxicity due to accumulation of the metal-binding molecule within the cell. Surprisingly, we found that intracellular toxicity of the molecule is not due to chelation of cellular metals.

Disruption of Phosphate Homeostasis Sensitizes Staphylococcus aureus to Nutritional Immunity.

To control infection, mammals actively withhold essential nutrients, including the transition metal manganese, by a process termed nutritional immunity. A critical component of this host response is the manganese-chelating protein calprotectin. While many bacterial mechanisms for overcoming nutritional immunity have been identified, the intersection between metal starvation and other essential inorganic nutrients has not been investigated. Here, we report that overexpression of an operon encoding a highly conserved inorganic phosphate importer, PstSCAB, increases the sensitivity of Staphylococcus aureus to calprotectin-mediated manganese sequestration. Further analysis revealed that overexpression of pstSCAB does not disrupt manganese acquisition or result in overaccumulation of phosphate by S. aureus However, it does reduce the ability of S. aureus to grow in phosphate-replete defined medium. Overexpression of pstSCAB does not aberrantly activate the phosphate-responsive two-component system PhoPR, nor was this two-component system required for sensitivity to manganese starvation. In a mouse model of systemic staphylococcal disease, a pstSCAB-overexpressing strain is significantly attenuated compared to wild-type S. aureus This defect is partially reversed in a calprotectin-deficient mouse, in which manganese is more readily available. Given that expression of pstSCAB is regulated by PhoPR, these findings suggest that overactivation of PhoPR would diminish the ability of S. aureus to resist nutritional immunity and cause infection. As PhoPR is also necessary for bacterial virulence, these findings imply that phosphate homeostasis represents a critical regulatory node whose activity must be precisely controlled in order for S. aureus and other pathogens to cause infection.

Acquisition of the Phosphate Transporter NptA Enhances Staphylococcus aureus Pathogenesis by Improving Phosphate Uptake in Divergent Environments.

During infection, pathogens must obtain all inorganic nutrients, such as phosphate, from the host. Despite the essentiality of phosphate for all forms of life, how Staphylococcus aureus obtains this nutrient during infection is unknown. Differing from Escherichia coli, the paradigm for bacterial phosphate acquisition, which has two inorganic phosphate (Pi) importers, genomic analysis suggested that S. aureus possesses three distinct Pi transporters: PstSCAB, PitA, and NptA. While pitA and nptA are expressed in phosphate-replete media, expression of all three transporters is induced by phosphate limitation. The loss of a single transporter did not affect S. aureus However, disruption of any two systems significantly reduced Pi accumulation and growth in divergent environments. These findings indicate that PstSCAB, PitA, and NptA have overlapping but nonredundant functions, thus expanding the environments in which S. aureus can successfully obtain Pi Consistent with this idea, in a systemic mouse model of disease, loss of any one transporter did not decrease staphylococcal virulence. However, loss of NptA in conjunction with either PstSCAB or PitA significantly reduced the ability of S. aureus to cause infection. These observations suggest that Pi acquisition via NptA is particularly important for the pathogenesis of S. aureus While our analysis suggests that NptA homologs are widely distributed among bacteria, closely related less pathogenic staphylococcal species do not possess this importer. Altogether, these observations indicate that Pi uptake by S. aureus differs from established models and that acquisition of a third transporter enhances the ability of the bacterium to cause infection.

The Two-Component System ArlRS and Alterations in Metabolism Enable Staphylococcus aureus to Resist Calprotectin-Induced Manganese Starvation.

During infection the host imposes manganese and zinc starvation on invading pathogens. Despite this, Staphylococcus aureus and other successful pathogens remain capable of causing devastating disease. However, how these invaders adapt to host-imposed metal starvation and overcome nutritional immunity remains unknown. We report that ArlRS, a global staphylococcal virulence regulator, enhances the ability of S. aureus to grow in the presence of the manganese-and zinc-binding innate immune effector calprotectin. Utilization of calprotectin variants with altered metal binding properties revealed that strains lacking ArlRS are specifically more sensitive to manganese starvation. Loss of ArlRS did not alter the expression of manganese importers or prevent S. aureus from acquiring metals. It did, however, alter staphylococcal metabolism and impair the ability of S. aureus to grow on amino acids. Further studies suggested that relative to consuming glucose, the preferred carbon source of S. aureus, utilizing amino acids reduced the cellular demand for manganese. When forced to use glucose as the sole carbon source S. aureus became more sensitive to calprotectin compared to when amino acids are provided. Infection experiments utilizing wild type and calprotectin-deficient mice, which have defects in manganese sequestration, revealed that ArlRS is important for disease when manganese availability is restricted but not when this essential nutrient is freely available. In total, these results indicate that altering cellular metabolism contributes to the ability of pathogens to resist manganese starvation and that ArlRS enables S. aureus to overcome nutritional immunity by facilitating this adaptation.

A Manganese-independent Aldolase Enables Staphylococcus aureus To Resist Host-imposed Metal Starvation.

The preferred carbon source of Staphylococcus aureus and many other pathogens is glucose, and its consumption is critical during infection. However, glucose utilization increases the cellular demand for manganese, a nutrient sequestered by the host as a defense against invading pathogens. Therefore, bacteria must balance glucose metabolism with the increasing demand that metal-dependent processes, such as glycolysis, impose upon the cell. A critical regulator that enables S. aureus to resist nutritional immunity is the ArlRS two-component system. This work revealed that ArlRS regulates the expression of FdaB, a metal-independent fructose 1,6-bisphosphate aldolase. Further investigation revealed that when S. aureus is metal-starved by the host, FdaB functionally replaces the metal-dependent isozyme FbaA, thereby allowing S. aureus to resist host-imposed metal starvation in culture. Although metal-dependent aldolases are canonically zinc-dependent, this work uncovered that FbaA requires manganese for activity and that FdaB protects S. aureus from manganese starvation. Both FbaA and FdaB contribute to the ability of S. aureus to cause invasive disease in wild-type mice. However, the virulence defect of a strain lacking FdaB was reversed in calprotectin-deficient mice, which have defects in manganese sequestration, indicating that this isozyme contributes to the ability of this pathogen to overcome manganese limitation during infection. Cumulatively, these observations suggest that the expression of the metal-independent aldolase FdaB allows S. aureus to alleviate the increased demand for manganese that glucose consumption imposes, and highlights the cofactor flexibility of even established metalloenzyme families. IMPORTANCE Staphylococcus aureus and other pathogens consume glucose during infection. Glucose utilization increases the demand for transition metals, such as manganese, a nutrient that the host limits as a defense mechanism against invading pathogens. Therefore, pathogenic bacteria must balance glucose and manganese requirements during infection. The two-component system ArlRS is an important regulator that allows S. aureus to adapt to both glucose and manganese starvation. Among the genes regulated by ArlRS is the metal-independent fructose 1,6-bisphosphate aldolase fdaB, which functionally substitutes for the metal-dependent isoenzyme FbaA and enables S. aureus to survive host-imposed manganese starvation. Unexpectedly, and differing from most characterized metal-dependent aldolases, FbaA requires manganese for activity. Cumulatively, these findings reveal a new mechanism for overcoming nutritional immunity as well as the cofactor plasticity of even well-characterized metalloenzyme families.

[Probiotic supplement (Lactobacillus acidophilus and bulgaricus) utility in the treatment of irritable bowel syndrome]. / Utilidad del suplemento de probioticos (Lactobacillus acidophilus y bulgaricus) en el tratamiento del sindrome de intestino irritable.

BACKGROUND: Irritable bowel syndrome (IBS) is a very common functional condition and a frequent cause of consultation in gastroenterology. With a multifactorial pathophysiology IBS is characterized by abdominal pain, distension and altered bowel habits. Loperamide, antispasmodics and antidepressants are symptomatic relievers of this disorder. Recently probiotics were incorporated to therapy, and could improve the symptomatology. METHODS: multicenter randomized placebo-controlled trial that included IBS patients, diagnosed with Rome III criteria. The patients were given pinaverium bromure and placebo or pinaverium bromure and probiotics for 3 weeks. The intensity of symptoms and the effect of therapy were evaluated with the Francis Score, before and after the treatment. Statistics were done with SPSS 12.0 (C.I 95%). RESULTS: 51 patients were evaluated, with an average age of 43 years old, mostly mestizo, 75% (38) married and 55% (28) female. There were statistical differences in four variables: abdominal pain, intensity of pain, days of pain and total score at the end of therapy. CONCLUSIONS: Probiotics used as supplement are effective in improving symptomatology of IBS.

Disruption of Glycolysis by Nutritional Immunity Activates a Two-Component System That Coordinates a Metabolic and Antihost Response by Staphylococcus aureus.

During infection, bacteria use two-component signal transduction systems to sense and adapt to the dynamic host environment. Despite critically contributing to infection, the activating signals of most of these regulators remain unknown. This also applies to the Staphylococcus aureus ArlRS two-component system, which contributes to virulence by coordinating the production of toxins, adhesins, and a metabolic response that enables the bacterium to overcome host-imposed manganese starvation. Restricting the availability of essential transition metals, a strategy known as nutritional immunity, constitutes a critical defense against infection. In this work, expression analysis revealed that manganese starvation imposed by the immune effector calprotectin or by the absence of glycolytic substrates activates ArlRS. Manganese starvation imposed by calprotectin also activated the ArlRS system even when glycolytic substrates were present. A combination of metabolomics, mutational analysis, and metabolic feeding experiments revealed that ArlRS is activated by alterations in metabolic flux occurring in the latter half of the glycolytic pathway. Moreover, calprotectin was found to induce expression of staphylococcal leukocidins in an ArlRS-dependent manner. These studies indicated that ArlRS is a metabolic sensor that allows S. aureus to integrate multiple environmental stresses that alter glycolytic flux to coordinate an antihost response and to adapt to manganese starvation. They also established that the latter half of glycolysis represents a checkpoint to monitor metabolic state in S. aureus Altogether, these findings contribute to understanding how invading pathogens, such as S. aureus, adapt to the host during infection and suggest the existence of similar mechanisms in other bacterial species.IMPORTANCE Two-component regulatory systems enable bacteria to adapt to changes in their environment during infection by altering gene expression and coordinating antihost responses. Despite the critical role of two-component systems in bacterial survival and pathogenesis, the activating signals for most of these regulators remain unidentified. This is exemplified by ArlRS, a Staphylococcus aureus global regulator that contributes to virulence and to resisting host-mediated restriction of essential nutrients, such as manganese. In this report, we demonstrate that manganese starvation and the absence of glycolytic substrates activate ArlRS. Further investigations revealed that ArlRS is activated when the latter half of glycolysis is disrupted, suggesting that S. aureus monitors flux through the second half of this pathway. Host-imposed manganese starvation also induced the expression of pore-forming toxins in an ArlRS-dependent manner. Cumulatively, this work reveals that ArlRS acts as a sensor that links nutritional status, cellular metabolism, and virulence regulation.

Tuberculosis y otras causas de morbilidad y mortalidad hospitalaria en pacientes con VIH/sida / Tuberculosis and other causes of morbidity and mortality in hospitalized patients with HIV/AIDS

Introducción: A diferencia de lo descrito en países desarrollados, en los que se informan las enfermedades crónicas no transmisibles como causa de hospitalización en pacientes con VIH, en este estudio las principales causas de admisión hospitalaria y muerte fueron las infecciones oportunistas, particularmente la tuberculosis, algo similar a lo reportado en otros países de ingresos bajos en América y África Occidental, aun con la disponibilidad de la terapia antirretroviral. Objetivos: Se determinaron las causas más frecuentes de morbilidad y mortalidad hospitalaria en pacientes con VIH. Material y métodos: Se analizaron los datos demográficos, clínicos y de laboratorio de pacientes ingresados con diagnóstico de VIH durante un año, en un hospital de Guayaquil, Ecuador. Resultados: De 151 pacientes, el 76% era del sexo masculino, con 37 años en promedio. El 56.3% conocía el diagnóstico de infección por VIH. Las principales causas de hospitalización y muerte fueron las enfermedades definitorias de sida, entre las que las formas meníngeas, como criptococosis, toxoplasmosis, sífilis y leucoencefalopatía en conjunto, siguen a la tuberculosis; el 93.5% de los fallecidos tenía recuento de CD4 menor de 200 células/mm3 (p = 0.007). Conclusión: De manera similar a lo informado en pacientes adultos jóvenes con VIH en países de bajos ingresos económicos, las infecciones oportunistas fueron la principal causa de hospitalización y muerte, relacionada con inmunosupresión intensa, estadios avanzados de la enfermedad y falta de terapia antirretroviral. Los resultados refuerzan la importancia del diagnóstico precoz y el tratamiento de la infección por VIH, así como la profilaxis de las infecciones oportunistas prevenibles.

Introduction: Unlike what has been described in developed countries where chronic non-communicable diseases are reported as the cause of hospitalization in patients with HIV, in this study the main cause of hospital admission and death were opportunistic infections, particularly tuberculosis similar to what was reported in other low-income countries in the Americas and West Africa even with the availability of antiretroviral therapy. Aim: The most frequent causes of hospital morbidity and mortality in patients with HIV were determined. Material and methods: The demographic, clinical, and laboratory data of patients admitted with a diagnosis of HIV for one year in a Guayaquil General Hospital were analyzed. Results: Of 151 patients, 76% were male with an average age of 37 years old. 56.3% knew the diagnosis of HIV infection. The main cause of hospitalization and death were AIDS-defining diseases where the meningeal forms: cryptococcosis, toxoplasmosis, syphilis and leukoencephalopathy together follow tuberculosis, and 93.5% of the deceased had a CD4 count of fewer than 200 cells/ mm3 (p = 0.007). Conclusion: Similar to what was reported in young adult patients with HIV in low-income countries, opportunistic infections were the main cause of hospitalization and death, related to severe immunosuppression, advanced stages of the disease, and without antiretroviral therapy. The results reinforce the importance of early diagnosis and treatment of HIV infection and the prophylaxis of preventable opportunistic infections.

Viruela símica grave en un paciente con infección por VIH, Ecuador / Severe mpox in a HIV patient, Ecuador. A case report

En mayo de 2022 se reportó un aumento de casos de viruela símica (mpox en inglés) en el mundo, cuyo comportamiento epidemiológico y clínico, particularmente en pacientes con infección por VIH, condujo a la declaración del brote de mpox 2022 como emergencia de salud pública internacional. Se presenta el caso de un paciente con infección por VIH que cursó con mpox grave y fulminante, con placas necróticas en párpado y membrana inflamatoria sobre la superficie ocular; mucosa oral con lesiones blanquecinas y úlceras en lengua; induración de tejidos blandos y lesiones necróticas en los pies. Tras múltiples complicaciones, se convirtió en la primera víctima fatal reportada en Ecuador en 2022. En pacientes con infección por VIH, mpox puede presentarse como un agente oportunista, causando lesiones cutáneas graves, con o sin manifestaciones sistémicas.

In May 2022 several cases of mpox were reported worldwide, whose epidemiological and clinical outcome, particularly in patients seropositive for HIV, led to declaring the 2022 mpox outbreak as a public health emergency. We describe a case of a patient with HIV infection and severe and fulminant mpox, with necrotic plaques on the eyelid and an inflammatory membrane on the ocular surface; oral mucosa with whitish lesions and ulcers on the tongue; soft tissues induration, and necrotic lesions on the feet. After multiple complications, he became the first fatality reported in Ecuador in 2022. In HIV-infected patients mpox can be considered an opportunistic agent, with severe skin lesions with or without systemic manifestations.

The Metallophore Staphylopine Enables Staphylococcus aureus To Compete with the Host for Zinc and Overcome Nutritional Immunity.

During infection, the host sequesters essential nutrients, such as zinc, to combat invading microbes. Despite the ability of the immune effector protein calprotectin to bind zinc with subpicomolar affinity, Staphylococcus aureus is able to successfully compete with the host for zinc. However, the zinc importers expressed by S. aureus remain unknown. Our investigations have revealed that S. aureus possesses two importers, AdcABC and CntABCDF, which are induced in response to zinc limitation. While AdcABC is similar to known zinc importers in other bacteria, CntABCDF has not previously been associated with zinc acquisition. Concurrent loss of the two systems severely impairs the ability of S. aureus to obtain zinc and grow in zinc-limited environments. Further investigations revealed that the Cnt system is responsible for the ability of S. aureus to compete with calprotectin for zinc in culture and contributes to acquisition of zinc during infection. The cnt locus also enables S. aureus to produce the broad-spectrum metallophore staphylopine. Similarly to the Cnt transporter, loss of staphylopine severely impairs the ability of S. aureus to resist host-imposed zinc starvation, both in culture and during infection. Further investigations revealed that together staphylopine and the Cnt importer function analogously to siderophore-based iron acquisition systems in order to facilitate zinc acquisition by S. aureus Analogous systems are found in a broad range of Gram-positive and Gram-negative bacterial pathogens, suggesting that this new type of zinc importer broadly contributes to the ability of bacteria to cause infection.IMPORTANCE A critical host defense against infection is the restriction of zinc availability. Despite the subpicomolar affinity of the immune effector calprotectin for zinc, Staphylococcus aureus can successfully compete for this essential metal. Here, we describe two zinc importers, AdcABC and CntABCDF, possessed by S. aureus, the latter of which has not previously been associated with zinc acquisition. The ability of S. aureus to compete with the host for zinc is dependent on CntABCDF and the metallophore staphylopine, both in culture and during infection. These results expand the mechanisms utilized by bacteria to obtain zinc, beyond Adc-like systems, and demonstrate that pathogens utilize strategies similar to siderophore-based iron acquisition to obtain other essential metals during infection. The staphylopine synthesis machinery is present in a diverse collection of bacteria, suggesting that this new family of zinc importers broadly contributes to the ability of numerous pathogens to cause infection.

Hematoma espontáneo del músculo psoas ilíaco secundario a anticoagulación como causa de muerte: reporte de caso / Spontaneous hematoma of the iliac psoas muscle secondary to anticoagulation as cause of death: case report

Resumen El uso de tromboprofilaxis posterior a las cirugías cervicales es una práctica recomendada a nivel mundial debido a que este tipo de pacientes presentan un mayor riesgo de desarrollar tromboembolismos venoso. Dentro de los efectos adversos de esta terapia se ha descrito la epistaxis, hematuria, formación de hematomas y sangrados. El hematoma espontáneo del músculo psoas iliaco, se considera una entidad poco frecuente, que suele asociarse a alteraciones de la coagulación, hemofilia o discrasias sanguíneas y como terapia anticoagulante, siendo este último la principal causa. En la autopsia médico legal, el hematoma del músculo psoas iliaco, suele ser un hallazgo incidental y en la mayoría de casos no contribuye en la causa de muerte. En el presente artículo se expone el caso de un masculino conocido con una enfermedad renal crónica, el cual desarrolló un hematoma espontáneo del músculo psoas iliaco, secundario al uso de enoxaparina como tromboprofilaxis posterior a una intervención quirúrgica en el cuello, que lo condujo a un shock mixto ocasionándole la muerte.

Abstract The use of thromboprophylaxis after cervical surgeries is a recommended practice worldwide due to the fact that these types of patients have a higher risk of developing venous thromboembolisms. Among the adverse effects of this therapy it has been described epistaxis, hematuria, formation of hematomas and bleeding. Spontaneous hematoma of the iliac psoas muscle is considered a rare entity, which is usually associated with coagulation disorders, hemophilia or blood dyscrasias and anticoagulant therapy, the latter being the main cause. In the medico-legal autopsy, the hematoma of the iliopsoas muscle is usually an incidental finding and in most cases does not contribute to the cause of death. This article describes the case of a male known with chronic kidney disease, who developed a spontaneous hematoma of the iliac psoas muscle, secondary to the use of enoxaparin as thromboprophylaxis after a surgical intervention in the neck, which led to a mixed shock causing death.

Daño axonal difuso en accidentes de tránsito: Reporte de caso y revisión bibliográfica / Diffuse axonal injury in traffic accidents: Case report and literature review

Resumen Los accidentes de tránsito son una de las principales causas de lesiones y muertes en la población general, se ha descrito que aproximadamente el 60% de las muertes por accidentes de tránsito son ocasionadas por el trauma craneoencefálico, siendo que el daño axonal difuso es una causa frecuente de coma y discapacidad grave. Dentro de los hallazgos más importantes en la autopsia médico legal a nivel macróscopico se encuentran las petequias en cuerpo calloso, hemorragias en sustancia blanca, entre otros y a nivel microscópico se observan edema axonal reactivo diseminado. En el presente artículo se comentará un caso de daño axonal difuso secundario a un accidente de tránsito, además se realizará una revisión del tema abarcando los puntos más importantes a tomar en cuenta desde el punto de vista médico legal.

Abstract Traffic accidents are one of the main causes of injuries and deaths in the general population, it has been described that approximately 60% of deaths from traffic accidents are caused by head trauma, diffuse axonal damage is a cause frequent coma and severe disability after head trauma, among the most important findings in the legal medical autopsy at the macroscopic level are the petechiae in the corpus callosum, hemorrhages in white matter, among others and at the microscopic level disseminated reactive axonal swelling. In this article, a case of diffuse axonal damage secondary to a traffic accident will be discussed, and a review of the subject will be carried out covering the most important points to be taken into account from the legal medical point of view.

Utilidad del suplemento de probioticos (Lactobacillus acidophilus y bulgaricus) en el tratamiento del Síndrome de Intestino Irritable / Probiotic supplement (Lactobacillus acidophilus and bulgaricus) utility in the treatment of irritable bowel syndrome

El Sindrome de Intestino Irritable (SII), es un transtorno funcional muy común y causa frecuente de consulta en gastroenterología, su fisiopatología es multifactorial y se caracteriza por dolor abdominal, distensión y alteración de los hábitos defecatorios, su terapia es básicamente sintomática (loperamida, antiespasmódicos, antidepresivos,etc).Recientemente se ha incorporado al tratamiento, el uso de probióticos que podrían mejorar su sintomatología. POBLACIÓN Y MÉTODO: Ensayo Clínico doble ciego aleatorizado simple, multicentrico que incluyó pacientes con diagnóstico de SII basado en criterios de Roma III. A estos se les administró Bromuro de Pinaverio mas placebo o Bromuro de Pinaverio mas Probiótico. La intensidad de los síntomas y el efecto del tratamiento fue valorado de acuerdo a Score de Francis antes y al final del tratamiento. Los cálculos fueron hechos con el programa SPSS 12.0.IC 95% RESULTADO. Se evaluaron 51 pacientes con promedio de edad de 43 años, mayoritariamente mestizos, 75%(38) casados y 55%(28) del sexo femenino, se encontró diferencias significativas en 4 variables de comparación: Dolor abdominal, Severidad del dolor, Días de dolor, y el Score total al final del tratamiento. CONCLUSIONES Los Probióticos utilizados como suplemento son efectivos en mejorar la sintomatología del SII.

Background: Irritable bowel syndrome (IBS) is a very common functional condition and a frequent cause of consultation in gastroenterology. With a multifactorial pathophysiology IBS is characterized by abdominal pain, distension and altered bowel habits. Loperamide, antispasmodics and antidepressants are symptomatic relievers of this disorder. Recently probiotics were incorporated to therapy, and could improve the symptomatology. Methods: multicenter randomized placebo-controlled trial that included IBS patients, diagnosed with Rome III criteria. The patients were given pinaverium bromure and placebo or pinaverium bromure and probiotics for 3 weeks. The intensity of symptoms and the effect of therapy were evaluated with the Francis Score, before and after the treatment. Statistics were done with SPSS 12.0 (C.I 95%). Results: 51 patients were evaluated, with an average age of 43 years old, mostly mestizo, 75% (38) married and 55% (28) female. There were statistical differences in four variables: abdominal pain, intensity of pain, days of pain and total score at the end of therapy. Conclusions: Probiotics used as supplement are effective in improving symptomatology of IBS.