Inhalation of the Phosphodiesterase-3 Inhibitor Milrinone Attenuates Pulmonary Hypertension in a Rat Model of Congestive Heart Failure

Background: Most patients with congestive heart failure (CHF) develop pulmonary venous hypertension, but right ventricular afterload is frequently further elevated by increased pulmonary vascular resistance. To investigate whether inhalation of a vasodilatory phosphodiesterase-3 inhibitor may reverse this potentially detrimental process, the authors studied the effects of inhaled or intravenous milrinone on pulmonary and systemic hemodynamics in a rat model of CHF.

Methods: In male Sprague-Dawley rats, CHF was induced by supracoronary aortic banding, whereas sham-operated rats served as controls. Milrinone was administered as an intravenous infusion (0.2-1 [mu]g [middle dot] kg body weight-1 [middle dot] min-1) or by inhalation (0.2-5 mg/ml), and effects on pulmonary and systemic hemodynamics and lung water content were measured.

Results: In CHF rats, intravenous infusion of milrinone reduced both pulmonary and systemic arterial blood pressure. In contrast, inhalation of milrinone predominantly dilated pulmonary blood vessels, resulting in a reduced pulmonary-to-systemic vascular resistance ratio. Repeated milrinone inhalations in 20-min intervals caused a stable reduction of pulmonary artery pressure. No hemodynamic effects were detected when 0.9% NaCl was administered instead of milrinone or when milrinone was inhaled in sham-operated rats. No indications of potentially adverse effects of milrinone inhalation in CHF, such as left ventricular volume overload, were detected. Moreover, lung edema was significantly reduced by repeated milrinone inhalation.     

Antitumorale Wirkung von Interferonen und Interleukinen in Kombination mit Strahlentherapie

BACKGROUND: During the last 2 decades, cytokines such as interferons (IFN) have been used to modulate tumor response in radiotherapy. Initially, the focus was on antiviral and radiosensitizing effects of interferons but increasingly, the function of interferons and interleukins (IL) within the immune response to tumor cells is becoming important. METHOD: The cellular immune response toward tumor cells is reviewed. The role of cytokines in antigen presentation and activation of effector cells and their interactions with radiation are described. Preclinical strategies of the antitumor action of cytokines are presented and discussed based on the induction of IFN-gamma by IL-12. RESULTS: Recent advances in immunology have demonstrated the importance of local interactions between antigen-presenting cells (APC) and effector cells such as natural killer (NK) cells and T-lymphocytes for an effective immune reaction against tumors. Interferons stimulate such interactions, while IL-2 plays a central role in the activation of NK cells and T-lymphocytes. The interactions between APC and effector cells are suppressed by many tumors but can be stimulated by irradiation. Since systemic application of interferons is quite toxic, present strategies aim at local expression, e. g., the induction of IFN-gamma expression in Th1 cells by IL-12. CONCLUSION: The improved understanding of immunologic mechanisms has emphasized the role of the cytokine network in the interaction between tumor cells and effector cells such as NK cells and T-lymphocytes. This opens new possibilities for the application of cytokines as biological response modifiers, which may eventually help widening the therapeutic window in radiotherapy.     

Exposure to allergens of different cattle breeds and their relevance in occupational allergy

Introduction  

Cattle are an important source of allergens in the working area of farmers. Asthma caused by cow allergens is a significant occupational problem. Yet in allergological testing, the results of in vivo and in vitro diagnostic tests are often inconsistent even in cases with clearly cattle-related symptoms.     

Release of vasopressin from supraoptic neurons within the median eminence in vivo. A combined microdialysis and push-pull perfusion study in the rat

The present study was designed to investigate whether or not arginine vasopressin (AVP) is released from magnocellular neurons within the median eminence (ME) in vivo. Urethane-anesthetized adult male Wistar rats were equipped with a microdialysis probe aimed at the supraoptic (SON) or paraventricular nucleus (PVN), a push-pull perfusion probe resting in the ME, and a blood microdialysis probe within the jugular vein. Dialysis of the SON (but not the PVN) with Ringer's solution containing 56 mmol l⁻¹ K⁺ resulted in an increase in AVP release within the ME (to 492 ± 192% of release during basal conditions,P < 0.05) and into blood (to 138 ± 9%,P < 0.01) whereby the release probably occurred from axonal swellings and nerve terminals of supraoptic neurons which project through the internal zone of the ME to the posterior pituitary. The calculated amount of AVP released into the extracellular fluid of the ME was high enough (approximately 1 pg/μ1) to hypothesize that the neuropeptide could enter the portal blood capillaries in physiologically relevant concentrations. Taken together, the present study indicates that activation of magnocellular neurons is accompanied by release of AVP within the median eminence. We assume that AVP released in this way might mediate a communication between the hypothalamic-neurohypophysial system and the hypothalamic-pituitary-adrenal axis in response to selected stressful stimuli.     

Personality and quality of life: The importance of optimism and goal adjustment

This article concerns the relations between personality and quality of life. In the first part, we discuss different conceptualizations of personality and quality of life. We argue that personality affects quality of life by influencing how people approach and react to critical life situations. In the second part, we address the beneficial role played by two individual difference variables in promoting quality of life: dispositional optimism and goal adjustment. Literature is reviewed demonstrating that dispositional optimism facilitates subjective well-being and good health, mediated by a person's coping behaviors. In addition, we discuss studies that examine people who confront unattainable goals. The reported evidence supports the conclusion that individual differences in people's abilities to adjust to unattainable goals are associated with a good quality of life.     

Is progression in postencephalitic parkinson's disease late and age-related?

Summary Follow-up data are presented of ten patients with autopsy-proven postencephalitic Parkinson's syndrome (PEP) (mean age at death: 56.0 years) with regard to motor and psychic deterioration over a period of institutional observation between 3 and 30 years. Four patients showed deterioration of their Hoehn-Yahr score of at least one grade. These patients did not differ statistically with respect to age of occurrence of lethargic encephalitis, interval to PEP, age at start of PEP, duration of survival with PEP, and age at death. Motor deterioration in these patients seems to be attributed more to inherent disease progression, rather than to an age-related process. Clinical and pathological evidence for this conclusion is presented.