Proviral HIV-DNA predicts viral rebound and viral setpoint after structured treatment interruptions

In HIV-1-infected patients with long-term undetectable viraemia on highly active antiretroviral treatment (HAART), we found that pre-HAART plasma viraemia and the baseline proviral DNA level were significantly associated with the viraemia setpoint during scheduled treatment interruptions. In long-term treated patients, pre-HAART viraemia may not be available, and in these circumstances proviral DNA, measured at the time of scheduled treatment interruption, can help to identify patients likely to reach a low viraemia setpoint after treatment interruption.     

Sympathetic Input to Multiple Cell Types in Mouse and Human Colon Produces Region-Specific Responses

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Überlegungen und Hochrechnungen zur Epidemiologie des „Acquired Immunodeficiency Syndrome“ in der Bundesrepublik Deutschland

Zusammenfassung Aufgeschlüsselt nach Bevölkerungskollektiven mit unterschiedlichen sexuellen Verhaltensweisen wird anhand der bisher bekannten bzw. größenordnungsmäßig abgeschätzten epidemiologischen Daten des Acquired Immunodeficiency Syndrome eine Hochrechnung der Morbiditäts- und Mortalitätsziffern für die Bundesrepublik Deutschland mittels Computer-Simulation vorgenommen; danach könnten in den nächsten 15 Jahren bis ca. 41 000 Personen erkranken. Die Bedeutung der weiblichen Prostituierten und der männlichen Bisexuellen als Vektoren der Infektion aus den bisherigen Risikogruppen in Bevölkerungsteile mit ausschließlich heterosexuellen Verhaltensweisen, der Einfluß infektiologischer Schutzmaßnahmen sowie der Effekt sexueller Verhaltensänderungen breiter Bevölkerungsschichten kann mit diesem Programm ebenfalls untersucht werden.

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Considerations and simulations regarding the epidemiology of the acquired immunodeficiency syndrome in the federal republic of Germany

Summary A computer simulation of the morbidity and mortality rates of the Acquired Immunodeficiency Syndrome in the Federal Republic of Germany was performed. Since sexual intercourse is the main mode of transmission, the population was divided into six groups with different sexual behaviour. In several variations of the program it is demonstrated that during the next 15 years up to 41,000 AIDS patients can be expected. The importance of female prostitutes and male bisexuals as vectors who may transmit the infection into exclusively heterosexual groups is shown. Using this program, the effect of prophylaxis against infection as well as of changes of sexual behaviour within the population at large can also be examined.

     

Temporäre mechanische Linksherzentlastung

Zusammenfassung Hintergrund  Die Implantation eines mechanischen Herzunterstützungssystem (MCSS) bei Patienten mit idiopathischer dilatativer Kardiomyopathie im Endstadium kann zu einer Verbesserung der Herzfunktion führen und die Explantation des Systems erlauben. Wir berichten über die Effekte der ventrikul?ren Entlastung auf die Herzfunktion, die humoralen Anti-β₁-Adrenozeptor-Autoantik?rper (A-β₁-AAK) sowie die myokardiale Fibrose. Methoden  13 Patienten mit nichtisch?mischer dilatativer Kardiomyopathie im Endstadium (NYHA IV-D) erhielten ein monoventrikul?res (zw?lf Patienten) oder ein biventrikul?res (ein Patient) Herzentlastungssystem. Alle hatten zur Zeit der Implantation einen Cardiac Index <1,61·min⁻¹·m² K?rperoberfl?che, eine linksventrikul?re Auswurffraktion (LVEF) von <16%, einen linksventrikul?ren enddiastolischen Diameter (LVEDd)>68 mm und einen positiven A-β₁-AAK-Nachweis. Echokardiographische Auswertungen, Serumtests auf A-β₁-AAK und histologische Untersuchungen hinsichtlich myokardialer Fibrose wurden vor und nach Implantation eines MCSS durchgeführt. Ergebnisse  Die durchschnittliche Unterstützungsdauer betrug 236±201 Tage (30 bis 794 Tage). Innerhalb dieses Zeitraums verbesserte sich die LVEF von ≤15 auf im Durchschnitt 46% und der LVEDd von 74 auf 56 mm. Die A-β₁-AAK waren nach im Mittel 11,7 Wochen im Serum nicht mehr nachweisbar. Ein Wiederanstieg konnte auch nach Explantation bei keinem Patienten beobachtet werden. Ein hochpathologischer Fibroseanteil im Myokard war etwa ein Jahr nach Explantation ebenfalls nicht mehr zu beobachten. Ein Patient dekompensierte sechs Monate nach Explantation und wurde daraufhin mit einem externen monoventrikul?ren System unterstützt. Die nachfolgende Transplantation verlief erfolgreich. Ein weiterer Patient starb unmittelbar nach Explantation an der Folge einer an?sthesiologischen Komplikation. Die mittlere Nachbeobachtungsdauer bei elf Patienten nach Explantation betr?gt (Stand 31. 5. 1997) 12,6±9,77 Monate (drei bis 26 Monate). Kumulativ konnten 139 Patientenmonate nachbeobachtet werden. Schlu?folgerung  Bei ausgew?hlten Patienten mit terminaler idiopathischer dilatativer Kardiomyopathie kann durch eine tempor?re mechanische Herzunterstützung eine weitgehende Normalisierung der Herzfunktion erreicht werden. Die pr?operative myokardiale Fibrose ist ein Jahr nach Explantation nicht mehr nachweisbar. Die A-β₁-AAK verschwinden in der Phase der mechanischen Entlastung des Herzens und treten nach Explantation des Systems nicht mehr auf. “Weaning” von der mechanischen Herzunterstützung kann eine Alternative zur Herztransplantation darstellen.      

Cellular immune reactions in the lung

The lung constantly interacts with the environment through thousands of liters of air that are inhaled daily. This continually transports toxic chemicals and particles or pathogenic microorganisms deep into the respiratory system, posing a challenge to physicochemical barriers and the local immune system. Thus, complex structures and mechanisms have evolved to recognize and fend off environmental dangers while at the same time allowing efficient gas exchange. Here we review our current knowledge regarding cellular mechanisms of the immune system in context with the highly specialized anatomical features of the airways and especially the alveolar compartment. The focus is on fungal and viral infections, merging anatomical aspects well known to pulmonologists with fundamental immunological concepts. We discuss the specialized morphological constraints of immune cells compressed under a continuous layer of the surfactant lining within alveoli as well as the importance of functional polarization of respiratory tract epithelia. Furthermore, we summarize the different types of innate and adaptive immune cells and their relative contribution to lung homeostasis with respect to localization. Finally, we provide a list of currently unresolved questions with high relevance for the field that might serve as food for thought regarding future research directions.     

Effects of intranasal oxytocin on pupil dilation indicate increased salience of socioaffective stimuli

To investigate the mechanisms by which oxytocin improves socioaffective processing, we measured behavioral and pupillometric data during a dynamic facial emotion recognition task. In a double‐blind between‐subjects design, 47 men received either 24 IU intranasal oxytocin (OXT) or a placebo (PLC). Participants in the OXT group recognized all facial expressions at lower intensity levels than did participants in the PLC group. Improved performance was accompanied by increased task‐related pupil dilation, indicating an increased recruitment of attentional resources. We also found increased pupil dilation during the processing of female compared with male faces. This gender‐specific stimulus effect diminished in the OXT group, in which pupil size specifically increased for male faces. Results suggest that improved emotion recognition after OXT treatment might be due to an intensified processing of stimuli that usually do not recruit much attention.     

Identification of altered dipeptidyl-peptidase activities as potential biomarkers for unipolar depression

Background

Changes in circulatory aminopeptidases [dipeptidyl-peptidase-IV (DPP-IV), Prolyl-oligopeptidase (POP) and Leucine aminopeptidase (LAP)] activities have been found to be associated with psychiatric illnesses and inflammatory diseases.

Methods

The discriminatory indices of aminopeptidases activities were assessed by enzymatic assays in plasma samples from 240 unipolar depression (UD) patients and 264 matched controls. In addition the relationship between soluble and cellular DPP-IV activity was determined in plasma and blood cells from healthy subjects.

Results

Greater than 95% of the plasma DPP-IV activity could be blocked by inhibitors, demonstrating the specificity of the assay. Also, DPP-IV protein and activity levels were strongly correlated. In contrast, only 50% of the membrane-bound activity in blood cells was inhibited, which suggested that other similar peptidases may be present in these cells. UD patients had decreased plasma levels of DPP-IV and POP activities compared to healthy controls with a concomitant increase in LAP activity. Finally, testing of the LAP/DPP-IV ratio resulted in good discrimination of UD patients from controls with an area under the curve—receiver operating characteristic of 0.70.

Limitations

Further biological validation studies using different cohorts are warranted.

Conclusions

The finding that plasma DPP-IV activity was decreased and LAP activity was increased in UD patients suggests the potential value for testing the levels of these enzymes for improved classification of patients. In addition, the changes in these enzymes, suggests that the proteolytic maturation of their proneuropeptide and prohormone subtrates may also be affected in UD, resulting in altered production of the associated bioactive peptides.     

Emerging role of epigenetics and miRNA in diabetic cardiomyopathy

The prevalence of heart failure independent of coronary artery disease and hypertension is increasing rapidly in diabetic patients. Thus, this pathophysiology has been recognized as a distinct clinical entity termed “diabetic cardiomyopathy.” Several studies support the notion that diabetes is a threatening insult for the myocardium resulting in functional, cellular, and structural changes manifesting as a cardiac myopathy. Recent data suggested that epigenetics including DNA and histone modifications as well as microRNAs play an important role in the development of cardiac diseases. The role of epigenetics in diabetes is largely recognized; however, its role in diabetes-associated cardiomyopathy remains elusive. Thus, molecular, cellular, and functional modulations in the diabetic cardiomyopathy will be investigated in this review. Moreover, particular attention will be drawn on the epigenetic mechanisms that may play an important role in the pathophysiology of diabetic cardiomyopathy.     

Anxiety as Predictor of the Cortisol Awakening Response in Patients with Coronary Heart Disease

Background

Anxiety is associated with worse outcomes in patients with coronary heart disease (CHD). A dysregulation of the HPA axis is a potential mechanism linking psychological factors and coronary disease. No study has yet investigated the relationship between anxiety and cortisol among patients with established CHD.

Purpose

The aim of this study was to assess the association between anxiety and the cortisol awakening response in patients with CHD.

Method

Four salivary cortisol samples were used to assess two measures of the cortisol awakening response (CAR) in 47 patients with established CHD. Anxiety was measured using the Hospital Anxiety and Depression Scale (HADS).

Results

Higher anxiety values were associated with a higher total output of cortisol in the first hour after awakening (AUCg, area under the curve with respect to ground) (p?=?0.04) and a nonsignificant trend towards a more pronounced increase (AUCi, area under the curve with respect to increase) (p?=?0.08). In patients who had a history of myocardial infarction (MI), the cortisol output was lower compared to patients who had no previous MI (p?=?0.02). In linear regression analyses, anxiety emerged as significant predictor of AUCg and AUCi after controlling for MI, ejection fraction (LVEF, left ventricular ejection fraction), and depression.

Conclusions

Our results provide further indications for an association between anxiety and a dysregulation of the HPA axis. History of MI emerged as second predictor of cortisol output in the morning.