Brucella central carbon metabolism: an update.

The brucellae are facultative intracellular pathogens causing brucellosis, an important zoonosis. Here, we review the nutritional, genetic, proteomic and transcriptomic studies on Brucella carbon uptake and central metabolism, information that is needed for a better understanding of Brucella virulence. There is no uniform picture across species but the studies suggest primary and/or secondary transporters for unknown carbohydrates, lactate, glycerol phosphate, erythritol, xylose, ribose, glucose and glucose/galactose, and routes for their incorporation to central metabolism, including an erythritol pathway feeding the pentose phosphate cycle. Significantly, all brucellae lack phosphoenolpyruvate synthase and phosphofructokinase genes, which confirms previous evidence on glycolysis absence, but carry all Entner-Doudoroff (ED) pathway and Krebs cycle (and glyoxylate pathway) genes. However, glucose catabolism proceeds through the pentose phosphate cycle in the classical species, and the ED pathway operates in some rodent-associated brucellae, suggesting an ancestral character for this pathway in this group. Gluconeogenesis is functional but does not rely exclusively on classical fructose bisphosphatases. Evidence obtained using infection models is fragmentary but suggests the combined or sequential use of hexoses/pentoses, amino acids and gluconeogenic substrates. We also discuss the role of the phosphotransferase system, stringent reponse, quorum sensing, BvrR/S and sRNAs in metabolism control, an essential aspect of the life style of facultative intracellular parasites.

Epigenetic changes in neurology: DNA methylation in multiple sclerosis. / Modificaciones epigenéticas en neurología: alteraciones en la metilación del ADN en la esclerosis múltiple.

INTRODUCTION: Epigenetics is defined as the study of the mechanisms that regulate gene expression without altering the underlying DNA sequence. The best known is DNA methylation. Multiple Sclerosis (MS) is a disease with no entirely known etiology, in which it is stated that the involvement of environmental factors on people with a genetic predisposition, may be key to the development of the disease. It is at this intersection between genetic predisposition and environmental factors where DNA methylation may play a pathogenic role. DEVELOPMENT: A literature review of the effects of environmental risk factors for the development of MS can have on the different epigenetic mechanisms as well as the implication that such changes have on the development of the disease. CONCLUSION: Knowledge of epigenetic modifications involved in the pathogenesis of MS, opens a new avenue of research for identification of potential biomarkers, as well as finding new therapeutic targets.

Comparative case-control study of homocysteine, vitamin B12, and folic acid levels in patients with epilepsy. / Estudio comparativo de los niveles plasmáticos de homocisteína, vitamina B12 y ácido fólico en pacientes epilépticos frente a controles.

INTRODUCTION: Increased blood homocysteine levels are a known cardiovascular risk factor. Epileptic patients on long-term treatment with antiepileptic drugs may present higher homocysteine levels and, consequently, a potential increase in cardiovascular risk. MATERIAL AND METHODS: We conducted an observational case-control study to compare plasma levels of homocysteine, folic acid, and vitamin B12. RESULTS: Our study included a total of 88 subjects: 52 patients with epilepsy and 36 controls. Epileptic patients showed higher homocysteine levels (P=.084) and lower levels of folic acid (P<.05). CONCLUSION: Homocysteine levels should be monitored in epileptic patients on long-term treatment with antiepileptic drugs. We suggest starting specific treatment in patients with high homocysteine levels.

[Predictive value of breast imaging report and database system (BIRADS) to detect cancer in a reference regional hospital]. / Valor predictivo del sistema BIRADS para detección de cáncer de mama con mamografía en biopsias por punción con aguja gruesa: Revisión de 5 años en un hospital de referencia.

BACKGROUND: To validate the BIRADS in mammography, the calculation of its predictive value in each center is required, as recommended by the American College of Radiology. AIM: To determine the predictive value of the BIRADS system in our center. MATERIAL AND METHODS: All ultrasound guided needle percutaneous biopsies, performed at our center between 2006 and 2010 were reviewed. Predictive value, sensitivity, specificity and diagnostic accuracy of BIRADS were calculated, with a confidence interval of 95%. RESULTS: Of 1,313 biopsies available, 1,058 met the inclusion criteria. Fifty eight percent of biopsies were performed to women with mammographies classified as BIRADS 4 or 5. The presence of cancer in mammographies classified as BIRADS 0 was 4%. The prevalence of cancer for mammographies BIRADS 1, 2, 3, 4 and 5 were 0, 3, 2.7, 17.7 and 72.4% respectively. The positive and negative predictive values of BIRADS classification were 55 and 92 % respectively. CONCLUSIONS: In our institution BIRADS classification 4 and 5 has a high positive predictive value for detecting cancer as in developed countries.

Epigenetics and epilepsy.

INTRODUCTION: Epigenetics is the study of heritable modifications in gene expression that do not change the DNA nucleotide sequence. Some of the most thoroughly studied epigenetic mechanisms at present are DNA methylation, post-transcriptional modifications of histones, and the effect of non-coding RNA molecules. Gene expression is regulated by means of these mechanisms and disruption of these molecular pathways may elicit development of diseases. DEVELOPMENT: We describe the main epigenetic regulatory mechanisms and review the most recent literature about epigenetic mechanisms and how those mechanisms are involved in different epileptic syndromes. CONCLUSION: Identifying the epigenetic mechanisms involved in epilepsy is a promising line of research that will deliver more in-depth knowledge of epilepsy pathophysiology and treatments.

Unlocking the Hidden Dimensions of Cancer Care: Cross-Cultural Adaptation and Feasibility Study of ESAS-FS, Assessing Spiritual Pain and Financial Distress in a Spanish-speaking Population with Advanced Cancer.

INTRODUCTION: Spiritual pain and financial distress are two important dimensions of cancer care that are often overlooked. Both dimensions can have a significant impact on the quality of life of patients with cancer and their families. METHODS: This study conducted a cross-cultural adaptation, feasibility study, and psychometric properties of the Edmonton Symptom Assessment System-Financial and Spiritual (ESAS-FS) in a Spanish-speaking population with advanced cancer. The ESAS-FS is a patient-reported outcome measure that assesses 12 symptoms, including spiritual pain and financial distress. RESULTS: In the cross-cultural adaptation process, the terms "spiritual pain" and "financial distress" were refined to "sufrimiento espiritual" and "preocupación por asuntos económicos" respectively, with strong professional consensus and high patients' acceptancy (relevant questions 80%, appropriate terms 91%). A cohort of 100 onco-hematologic patients revealed that 70% experienced spiritual pain (mean 2.9/10), while 49% reported financial distress (mean 2.2/10). Symptomatic analyses illustrated significant associations of spiritual pain with various symptoms like fatigue, drowsiness, and depression. Similarly, financial distress correlated notably with drowsiness, depression, and anxiety. Moreover, a distinct correlation was observed between spiritual pain and financial distress. CONCLUSION: The findings of this study suggest that the ESAS-FS is a valuable tool for assessing spiritual pain and financial distress in Spanish-speaking patients with advanced cancer. The tool can be used to identify patients who are experiencing these dimensions of distress and to provide them with appropriate care.

[Epidemiological profile of late mortality in severe polytraumatisms]. / Perfil epidemiológico de la mortalidad tardía de los politraumatismos graves.

OBJECTIVE: A study is made of the epidemiology, chronogramand causes of late mortality in traumatized patients. DESIGN: A prospective, observational cohort study of adult trauma patients was carried out. SETTINGS: Province of Guipúzcoa (Basque Country, Spain). Intensive care unit of a tertiary hospital. PATIENTS: Patients with severe trauma (Injury Severity Score > 15), admitted to the ICU from January 1995 to December 2009, with late death (> 7 days). VARIABLES: Epidemiological, laboratory test, hemodynamic and transfusional data were collected. Severity scores: Abbreviated Injury Scale (AIS) and ISS. RESULTS: Patients: 2003; ISS: 24.3±14.2. Total deaths: 405 (20%). Late mortality (>7 days): 102 (25.2%) patients, 9 years older and with a lower (18 points) ISS score than the patients who died early (48 hours). Most frequent injuries: AIS-Head-Cervical spine ≥ 4 (52%); AIS-Abdomen ≥ 4 (19.6%); AIS-Chest ≥ 4 (11.7%); AIS-Extremities ≥ 4 (4.9%). Causes of death: 1) brain death (14.7%); 2) multiorgan failure (67.6%), in two injury contexts: a) severe brain trauma in the vegetative state and high spinal cord injuries with tetraplegia (35.3%); and b) non-neurological injuries (32.3%) with a high prevalence of hypovolemic shock, multiple transfusion and coagulopathy; 3) miscellaneous (10.7%): post-resuscitation anoxic-ischemic encephalopathy, pulmonary embolism and massive stroke; 4) non-evaluable (7%). CONCLUSIONS: Age, severity and type of injuries have an influence upon the time distribution and causality of late mortality. Brain death remains predominant, with multiorgan failure as the most frequent cause. This knowledge should contribute to the identification of problems, and to better organization of the structural and educational resources, thereby reducing the likely factors leading to death from trauma.

Epigenetic changes in headache.

INTRODUCTION: Multiple factors, including both genetic and environmental mechanisms, appear to play a role in the aetiology of headache. An interesting area of study is the possible involvement of epigenetic mechanisms in headache development and the transformation to chronic headache, and the potential role of these factors as a therapeutic target. METHODS: We performed a literature review of the involvement of different epigenetic mechanisms in headache, mainly using the Medline/PubMed database. To this end, we used the following English search terms: headache, migraine, epigenetics, DNA methylation, histones, non-coding RNA, and miRNA. RESULTS: A total of 15 English-language publications related to the above terms were obtained. CONCLUSION: There is limited but consistent evidence of the relationship between epigenetics and headache; it is therefore essential to continue research of epigenetic changes in headache. This may help to understand the pathophysiology of headache and even to identify candidate biomarkers and new, more effective, therapeutic targets.

Blood biomarkers in Alzheimer's disease.

INTRODUCTION: Early diagnosis of Alzheimer disease (AD) through the use of biomarkers could assist in the implementation and monitoring of early therapeutic interventions, and has the potential to significantly modify the course of the disease. DEVELOPMENT: The classic cerebrospinal fluid and approved structural and functional neuroimaging biomarkers are of limited clinical application given their invasive nature and/or high cost. The identification of more accessible and less costly biomarkers, such as blood biomarkers, would increase their use in clinical practice. We review the available published evidence on the main blood biochemical biomarkers potentially useful for diagnosing AD. CONCLUSIONS: Blood biomarkers are more cost- and time-effective than CSF biomarkers. However, immediate applicability in clinical practice is relatively unlikely. The main limitations come from the difficulty of measuring and standardising thresholds between different laboratories and the failure to replicate results. Of all the molecules studied, apoptosis and neurodegeneration biomarkers and the biomarker panels obtained through "omics" approaches, such as isolated or combined metabolomics, offer the most promising results.

[Evaluation of a follow-up program for diabetes after hospital discharge]. / Evaluación de un protocolo de seguimiento para diabetes tras el alta hospitalaria.

BACKGROUND: Given the higher rate of hospital admissions among diabetic patients, discharge should be used to optimize outpatient treatment. We evaluate a follow-up program for diabetic patients after hospital discharge to determine the evolution of glycemic control. METHOD: Retrospective collection of data on 375 diabetic patients enrolled in the follow-up program for optimization treatment: telephonic follow-up where treatment was adjusted if needed; and three months after discharge an in-person consultation was scheduled. Factors potentially associated with a 1% improvement in HbA1c were studied by multivariate logistic regression. RESULTS: Seventy-three percent of enrolled patients completed the follow-up program; each patient received an average of 4.6 phone calls. Globally, basal mean HbA1c was significantly lower three months later regarding the initial value (8.6 vs. 7.2%); the most relevant lowering was found in the group of hyper-glycemia by poor metabolic control (from 9.9 to 7.7%), combined hyperglycemia (from 9.3 to 7.3%) and debut (from 8.3 to 6.4%). Twenty percent of patients reported capillary hypoglycemia, with two severe events. A shorter duration of diabetes, absence of corticotherapy and absence of hypoglycemia during the follow-up period were independent predictors for a 1% reduction in three-months HbA1c. CONCLUSION: In patients whose treatment is changed on hospital discharge, a program allowing frequent treatment adjustment would improve HbA1c levels. These results could help to organize health resources more rationally.

The virulence plasmid of Yersinia, an antihost genome.

The 70-kb virulence plasmid enables Yersinia spp. (Yersinia pestis, Y. pseudotuberculosis, and Y. enterocolitica) to survive and multiply in the lymphoid tissues of their host. It encodes the Yop virulon, an integrated system allowing extracellular bacteria to disarm the cells involved in the immune response, to disrupt their communications, or even to induce their apoptosis by the injection of bacterial effector proteins. This system consists of the Yop proteins and their dedicated type III secretion apparatus, called Ysc. The Ysc apparatus is composed of some 25 proteins including a secretin. Most of the Yops fall into two groups. Some of them are the intracellular effectors (YopE, YopH, YpkA/YopO, YopP/YopJ, YopM, and YopT), while the others (YopB, YopD, and LcrV) form the translocation apparatus that is deployed at the bacterial surface to deliver the effectors into the eukaryotic cells, across their plasma membrane. Yop secretion is triggered by contact with eukaryotic cells and controlled by proteins of the virulon including YopN, TyeA, and LcrG, which are thought to form a plug complex closing the bacterial secretion channel. The proper operation of the system also requires small individual chaperones, called the Syc proteins, in the bacterial cytosol. Transcription of the genes is controlled both by temperature and by the activity of the secretion apparatus. The virulence plasmid of Y. enterocolitica and Y. pseudotuberculosis also encodes the adhesin YadA. The virulence plasmid contains some evolutionary remnants including, in Y. enterocolitica, an operon encoding resistance to arsenic compounds.

Blood biomarkers in Alzheimer's disease. / Biomarcadores sanguíneos en la enfermedad de Alzheimer.

INTRODUCTION: The early diagnosis of Alzheimer's disease (AD) via the use of biomarkers could facilitate the implementation and monitoring of early therapeutic interventions with the potential capacity to significantly modify the course of the disease. DEVELOPMENT: Classic cerebrospinal fluid biomarkers and approved structural and functional neuroimaging have a limited clinical application given their invasive nature and/or high cost. The identification of more accessible and less costly biomarkers, such as blood biomarkers, would facilitate application in clinical practice. We present a literature review of the main blood biochemical biomarkers with potential use for diagnosing Alzheimer's disease. CONCLUSIONS: Blood biomarkers are cost and time effective with regard to cerebrospinal fluid biomarkers. However, the immediate applicability of blood biochemical biomarkers in clinical practice is not very likely. The main limitations come from the difficulties in measuring and standardising thresholds between different laboratories and in failures to replicate results. Among all the molecules studied, apoptosis and neurodegeneration biomarkers and the biomarker panels obtained through omics approaches, such as isolated or combined metabolomics, offer the most promising results.

Radioterapia intraoperatoria de la mama con intrabeam, experiencia de la Unidad de Mastología del Hospital Italiano de Buenos Aires / Intraoperative radiotherapy of the breast with intrabeam, experience of the Mastology Unit of the Italian Hospital of Buenos Aires

Objetivo: La radioterapia intraoperatoria (IORT) es la radioterapia que se administra directamente al lecho tumoral. Existen varias modalidades de IORT. La empleada en nuestro centro es la que utiliza el dispositivo Intrabeam, el cual a través de rayos X de baja energía y un aplicador esférico que se adapta al lecho tumoral, permite la administración de la radiación a los tejidos con mayor riesgo de recidiva. Presentamos nuestra experiencia inicial de IORT con el dispositivo Intrabeam. Material y método: Se seleccionaron 51 pacientes con cáncer de mama para IORT con Intrabeam ® según protocolo TARGIT-A, desde febrero 2021 hasta mayo 2022. Los indicaciones fueron: pacientes mayores a 45 años, con tumores unifocales, < 3 cm de diámetro, luminales A o B, con axila clínica e imagenológicamente negativa. También se incluyen pacientes con carcinoma intraductal, de bajo grado o de grado intermedio. Resultados: La edad media fue de 66 años. Según el examen histológico definitivo, el tamaño tumoral promedio fue de 11.9 mm, con 95% de las pacientes con tumores menores a 2 cm. El 82.3% de nuestras pacientes completaron su tratamiento radiante sólo con la radioterapia intraoperatoria, pero en 9 casos (17.6%) fue necesario agregar radioterapia externa del volumen mamario. 10 pacientes (25.6%) tuvieron complicaciones, 2 casos fueron seromas que precisaron varias aspiraciones para su resolución. El resultado estético es muy bueno. Conclusiones: La IORT con Intrabeam es una alternativa segura y bien tolerada frente a la radioterapia externa en pacientes seleccionadas, con un buen resultado estético a corto plazo(AU)

Objetive: Intraoperative radiation therapy (IORT) is a radiation therapy delivered directly to the tumor bed. There are several modalities of IORT. The one used in our center is the one that uses the Intrabeam device, which through low-energy X-rays and a spherical applicator that adapts to the tumor bed, allows the administration of radiation to the tissues with the highest risk of recurrence. We present our initial experience with the Intrabeam device at our center. Material and method: From February 2021 to May 2022, 51 patients with breast cáncer were selected for IORT with Intrabeam® according to the TARGIT-A protocol. The indications were: patients older than 45 years, with unifocal tumors, < 3 cm in diameter, luminal A or B, with negative clinical and imaging axilla. Patients with intraductal, low-grade or intermediate-grade carcinoma were also included. Results: The mean age was 66 years. According to the definitive histological examination, the average tumor size was 11.9 mm, 95% of the patients with tumors smaller than 2 cm. 82.3% of our patients completed their radiant treatment with intraoperative radiotherapy alone, but in 9 cases (17.6%) it was necessary to add external radiotherapy of the breast volume. 10 patients (25.6%) had complications, 2 cases were seromas that required several aspirations for their resolution. The aesthetic result is very good. Conclusions: IORT with Intrabeam is a safe and well tolerated alternative versus external radiotherapy in selected patients and provides a good shortterm aesthetic result(AU)

Pathogens and fecal indicators in waste stabilization pond systems with direct reuse for irrigation: Fate and transport in water, soil and crops.

Wastewater use for irrigation is expanding globally, and information about the fate and transport of pathogens in wastewater systems is needed to complete microbial risk assessments and develop policies to protect public health. The lack of maintenance for wastewater treatment facilities in low-income areas and developing countries results in sludge accumulation and compromised performance over time, creating uncertainty about the contamination of soil and crops. The fate and transport of pathogens and fecal indicators was evaluated in waste stabilization ponds with direct reuse for irrigation, using two systems in Bolivia as case studies. Results were compared with models from the literature that have been recommended for design. The removal of Escherichia coli in both systems was adequately predicted by a previously-published dispersed flow model, despite more than 10years of sludge accumulation. However, a design equation for helminth egg removal overestimated the observed removal, suggesting that this equation may not be appropriate for systems with accumulated sludge. To assess the contamination of soil and crops, ratios were calculated of the pathogen and fecal indicator concentrations in soil or on crops to their respective concentrations in irrigation water (termed soil-water and crop-water ratios). Ratios were similar within each group of microorganisms but differed between microorganism groups, and were generally below 0.1mLg(-1) for coliphage, between 1 and 100mLg(-1) for Giardia and Cryptosporidium, and between 100 and 1000mLg(-1) for helminth eggs. This information can be used for microbial risk assessments to develop safe water reuse policies in support of the United Nations' 2030 Sustainable Development Agenda.

Preliminary study of the lymphatic drainage system of the nose and paranasal sinuses and its role in detection of sentinel metastatic nodes.

CONCLUSIONS: The normal nasal lymphatic drainage runs via the facial vessels into the neck lymphatic nodes of levels I-II and this drainage pattern was found in our patients with sinonasal tumors. We found only one true-positive sentinel lymph node (SLN). Our pathological material was very limited and so further investigations are required before any valid conclusions can be drawn concerning the clinical value of SLNs in nasal tumors. Objectives. To detect the lymph collection route of the nasal fossae and paranasal sinuses and to identify the first echelon in the tumor metastatic cascade in order to prevent the risk of occult metastases in N0 necks in patients with primary head and neck squamous cell carcinoma (SCC). MATERIAL AND METHODS: Our control group comprised 30 patients (20 females; age range 19-50 years) suffering from chronic otitis media who had an anatomically normal nose and a cNO neck on palpation. The pathological group comprised 6 patients (2 females; age range 40-85 years) suffering from sinonasal tumors: 3 SCC, 1 recurrent melanoma, 1 ameloblastoma and 1 inverted papilloma. All had a clinically staged cNO neck on palpation and CT. In the control group, lymphoscintigraphy was carried out by means of unilateral injection of radioactive gold into the head of the inferior turbinate. The tracer was identified using a gamma camera 3 and 6 h after the injection. In the pathological group the chosen tracer was technetium, which was administered 1 day prior to surgery by means of injections into the heads of the inferior and middle turbinates, into the nasal septum and into the retromaxillary gingival mucosa. The tracer was identified transcutaneously using a navigator probe in the gamma camera at 15 min, 30 min and 1 h post-injection. A mark was drawn on the skin corresponding to the hot spot of the SLN. The study was repeated 30 min before surgery. The neck incision was selected according to the location of the SLN. A hand-held gamma probe was used in the operating theatre to detect in situ the radioactivity of the surgical excisional nasal area and the cervical SLN. Once the SLN was excised its radioactivity was confirmed ex situ, taking into account that the activity counts were at least three times greater than background. Postoperatively, all SLNs were histopathologically examined and cytokeratin staining was carried out immunohistochemically using the monoclonal antibody cocktail AE1/AE3. Results. In the control group, intense activity at the injection tracer site and lower activity in the submandibular area (level I) were detected in 26.6% of cases. Nasal radioactivity persisted for 6 h post-injection and submandibular radioactivity increased, also reaching the area corresponding to neck node level II (70%). In two cases (6.6%), radioactivity was observed in the retropharyngeal nodes. In the pathological group, the SLN was found in the submandibular area (level I) in three cases, and in the ameloblastoma patient three SLNs were found at levels I-II. Three cases were false positives, and no metastases were detected using any of the histopathological procedures. The only one true positive corresponded to a female with an SCC of the maxillary infrastructure with invasion of the gingival mucosa. The histopathological code was 1 and a metastasis was detected on hematoxylin-eosin examination. In the other two cases no SLNs were detected.

Comparison of treatment with continuous subcutaneous insulin infusion versus multiple daily insulin injections with bolus calculator in patients with type 1 diabetes.

OBJECTIVES: A study of the glycemic control, quality of life, and fear and perception of hypoglycemia by comparing continuous subcutaneous insulin infusion (CSII) group with multiple daily inyections (MDI) with bolus calculator group. MATERIAL AND METHODS: This is a retrospective cohort study with following up during the first 12 months that CSII group (n=30) begins the use of "bolus wizard" and the MDI-calculator (n=30) group begins the use of the bolus calculator (Accu-Chek(®) Aviva Expert). PRIMARY OUTCOME: HbA1c (3, 6 and 12 months). Questionnaires used: EsDQOL (quality of life), FH-15 (fear of hypoglycemia), and Clarke (perception of hypoglycemia). STATISTICAL ANALYSIS: T Student and nonparametric tests. RESULTS: The average reduction in HbA1c during the study was significantly higher in CSII group (-0.56±0.84%) compared with the MDI group (0.097±0.94%), P=.028. The average basal insulin dose was significantly higher in the MDI group (at baseline, 6 and 12 months). No significant differences were found between the 2 treatment groups after analyzing the EsDQOL, FH-15 and Clarke questionnaires. In the CSII group, perceived quality of life assessed by the EsDQOL questionnaire was found to be better at the end of the study than at the beginning of using the insulin pump. CONCLUSIONS: The average reduction in HbA1c was significantly higher in the CSII group. In the CSII group, perceived quality of life was better at the end of the study than at the beginning.

Yersinia enterocolitica can deliver Yop proteins into a wide range of cell types: development of a delivery system for heterologous proteins.

Y. enterocolitica translocates virulence proteins, called Yop effectors, into the cytosol of eukaryotic cells. Here we investigated whether Y. enterocolitica could translocate Yops into a range of eukaryotic cells including neurons and insect cells. Y. enterocolitica translocated the hybrid reporter protein YopE-Cya into each of the eukaryotic cell types tested. In addition, Y. enterocolitica was cytotoxic for each of the adherent cell types. Thus we detected no limit to the range of eukaryotic cells into which Y. enterocolitica can translocate Yops. The Yop effectors YopE, YopH and YopT were each cytotoxic for the adherent cell types tested, showing that not only is Y. enterocolitica not selective in its translocation of particular Yop effectors into each cell type, but also that the action of these Yop effectors is not cell type specific. Invasin and/or YadA, two powerful adhesins were required for translocation of Yop into non-phagocytic cells but not for translocation into macrophages. To use the Yersinia translocation system for broad applications, a Y. enterocolitica translocation strain and vector for the delivery of heterologous proteins into eukaryotic cells was constructed. This strain + vector combination lacks the translocated Yop effectors and allows delivery into eukaryotic cells of heterologous proteins fused to the minimal N-terminal secretion/translocation signal of YopE. Using this strategy translocation of a YopE-Diphtheria toxin subunit A hybrid protein into several cell types has been shown.

Microvascular angina in systemic hypertension: diagnosis and treatment with enalapril.

The causes of hypertensive microvascular ischemia are reviewed along with diagnostic factors. Stress/rest thallium-201 scintigraphy is shown to have a predictive value of 78% for a diagnosis of microvascular disease in hypertensive patients with exertional angina and left ventricular hypertrophy. Lack of isotope uptake at peak stress correlates well with the decrease in coronary flow reserve in ischemic segments, which is 2-3 times lower than in normal subjects. Treatment with enalapril produces regression of left ventricular hypertrophy, normalization of thallium-201 uptake, and an increase in exercise capacity in patients with microvascular angina.

Congestive heart failure due to hypertensive ventricular diastolic dysfunction.

Left ventricular (LV) diastolic dysfunction is the first discernible manifestation of heart disease in hypertensive patients. Arterial hypertension with LV hypertrophy leads to reduced preload followed by impaired cardiac output (systolic dysfunction stemming from primary diastolic dysfunction). Diastolic dysfunction leads more often than systolic dysfunction to hypertensive heart failure and is in many cases clearly distinguishable from heart failure with low ejection fraction (EF). Mortality due to heart failure from impaired inotropism is higher than mortality due to diastolic dysfunction, but morbidity is lower. Hypertensive cardiomyopathies can be divided into 4 ascending categories, according to the pathophysiologic and clinical impact of hypertension on the heart: Degree I: LV diastolic dysfunction with no associated LV hypertrophy Degree II: LV diastolic dysfunction with echocardiographic LV hypertrophy Degree IIA: Normal exercise capacity in terms of maximal oxygen consumption Degree IIB: Impaired exercise capacity in terms of maximal oxygen consumption Degree III: Congestive heart failure (severe dyspnea and radiographically determined pulmonary edema with normal (> or = 50%) EF Degree IIIA: LV mass/volume ratio > 1.8 with little or no myocardial ischemia Degree IIIB: LV mass/volume ratio < 1.8 with significant myocardial ischemia Degree IV: Profile of dilated cardiomyopathy; LV hypertrophy and impaired EF (< 50%).