A combination of electrochemistry and mass spectrometry to monitor the interaction of reactive species with supported lipid bilayers.

Reactive oxygen and nitrogen species (RONS), e.g. generated by cold physical plasma (CPP) or photodynamic therapy, interfere with redox signaling pathways of mammalian cells, inducing downstream consequences spanning from migratory impairment to apoptotic cell death. However, the more austere impact of RONS on cancer cells remains yet to be clarified. In the present study, a combination of electrochemistry and high-resolution mass spectrometry was developed to investigate the resilience of solid-supported lipid bilayers towards plasma-derived reactive species in dependence of their composition. A 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer was undisturbed by 200 µM H2O2 (control) but showed full permeability after CPP treatment and space-occupying oxidation products such as PoxnoPC, PAzePC, and POPC hydroperoxide were found. Electron paramagnetic resonance spectroscopy demonstrated the presence of hydroxyl radicals and superoxide anion/hydroperoxyl radicals during the treatment. In contrast, small amounts of the intramembrane antioxidant coenzyme Q10 protected the bilayer to 50% and LysoPC was the only POPC derivative found, confirming the membrane protective effect of Q10. Such, the lipid membrane composition including the presence of antioxidants determines the impact of pro-oxidant signals. Given the differences in membrane composition of cancer and healthy cells, this supports the application of cold physical plasma for cancer treatment. In addition, the developed model using the combination of electrochemistry and mass spectrometry could be a promising method to study the effect of reactive species or mixes thereof generated by chemical or physical sources.

[Gastroenterological function tests in the GP's office]. / Funktionstests für Magen und Darm sind auch beim Hausarzt einfach durchzuführen. Zu viel Säure, zu wenig Enzyme oder Fehlbesiedlung?

Breath tests are quick, noninvasive, simple to perform and reliable. In particular in patients with diarrhea, bloating, nausea and uncharacteristic abdominal symptoms, the H2 breath test is highly useful. Using this procedure, malabsorption of various different carbohydrates, the absorptive performance of the upper abdominal tract, the orocecal transit time, or bacterial overgrowth in the small bowel, can be determined. Using 24-hour pH-metry, the acidity in the stomach and esophagus can be measured, and reflux disease, for example, diagnosed. Today, elevated fat in the stool is detected on the basis of the beta carotene level in the serum. Further function tests for the detection of pancreatic insufficiency, such as the determination of fecal pancreatic elastase, are also available.

[Pain therapy in cancer patients]. / Umfassende Palliativversorgung: Sieben Grundregeln für die Schmerztherapie.

Rigorous and appropriate pain therapy is a major element in palliative medicine, and affords the patient the possibility of being better able to organize the remaining time left to him. Every person has a legal right to, receive appropriate treatment for his/her pain, which in advanced disease states, is a multidimensional condition. This means that in addition to nursing staff and physicians, spiritual counselors, social workers, physiotherapists and volunteer helpers must be included in the pain-management team. Despite all our efforts, the ideal of complete freedom from pain is unrealistic. Nevertheless, the simple expression of solidarity with the terminally-ill patient, as is reflected by the provision of sympathetic attention, has in itself a positive impact on pain. By offering comprehensive and nationwide palliative care that is oriented to the needs of the terminal patient, society helps to provide a culture of the dying, and thus also of the living, that reflects humanistic principles.

[Diagnostics of the HIV infection]. / Die akute HIV-Infektion wird häufig übersehen. Dran denken, und bei Verdacht nicht mit dem H1V-test zögern!

Diagnostics of the HIV Infection The clinical picture of an acute HIV infection resembles that of mononucleosis with lymphadenopathy, fatigue and fever. In this phase, the infection can be diagnosed with certainty only through direct virus detection. During the subsequent latent phase, recurring or serious progressive skin manifestations from different illnesses, prominent candidiasis of the oral cavity and community acquired pneumonia frequently occur. Ulcerations in atypical locations of the gastrointestinal tract could also indicate an HIV infection. For cases of clear lymphopenia, an HIV infection should be definitely considered. Above all, the presence of non-Hodgkin's lymphoma is characteristic of the complete clinical picture of AIDS. An appropriate diagnostic test (antibody test or detection of HIV) is urgently indicated in situations that carry a high risk for HIV transmission. This applies, above all, to patients whose partner is HIV positive, to patients who frequently change sex partners, to prostitutes and to intravenous drug users.

[Cardiac diseases in HIV-seropositive patients]. / Kardiale Erkrankungen bei HIV-seropositiven Patienten. HIV macht auch dem Herzen zu schaffen.

HIV-associated cardiopathies have a poor prognosis, in particular in patients with low CD4 counts or accompanying encephalopathy. The pathogenesis is multifactorial and the therapeutic options are limited. Pericardiac effusions are also associated with a poor prognosis. Other cardiac manifestations of HIV infection are opportunistic infections, infectious endocarditis (in particular i.v. drug use), neoplasia, and pulmonary hypertension. Premature development of vascular diseases is often observed in patients receiving combination antiretroviral treatment. A number of antiretroviral agents, but also antibiotics and chemotherapeutic agents have cardiotoxic side effects. Echocardiography is a good, noninvasive and inexpensive screening method that should be performed at least once a year in all asymptomatic HIV patients.

[Opportunistic diseases--current aspects in 2004]. / Opportunistische Erkrankungen nehmen wieder zu. Aktuelle Aspekte 2004.

Opportunistic diseases (OD) are still the most common cause of death in patients with HIV infection. The occurrence of OD is the most important single prognostic factor for survival. While in the pre-HAART era, many patients died of the wasting syndrome, today, ever more patients suffer from obesity and its consequences. Tuberculosis is widespread among those affected with HICV, and when treating it must be remembered that tuberculostatic agents and antiretroviral drugs interact with cytochrome P450. Until recently, the combination of rifampicin with protease inhibitors and non-nucleoside reverse-transcriptase inhibitors was contraindicated. Now, however, the Centers for Disease Control (CDC) has updated its recommendations for treatment.

[Antiretroviral therapy in 2004]. / Empfehlungen zur antiretroviralen Therapie im internationalen Vergleich. Welche ART ist "up to date"?

Since its inception, highly active antiretroviral therapy (HAART) has undergone constant further development. The German Aids Society (DIG), but also the British HIV Association (BHIVA) and the North American Department of Health and Human Services (DHHS) have all issued recommendations on HAART. A comparison of these recommendations reveals that despite the many points they have in common, gaps in our knowledge, and shortcomings in both the diagnosis and treatment of HIV infections still persist.

Determinants of long-term highly active antiretroviral treatment efficacy.

OBJECTIVES: Predictors of the efficacy of highly active antiretroviral therapy (HAART) have been investigated in several studies. To increase current knowledge, the study aimed to acquire comprehensive data over an extended observation time, to obtain information on possible performance differences among individual drugs, and to identify factors with influence on the initial response to a HAART regimen and the sustainability of the response. METHODS: The data were obtained from a prospective, single University Medical School HIV cohort. Clinical, laboratory, and treatment parameters for 475 patients were collected over 4.5 years. HAART efficacy was determined by analysis of variance and multivariate survival analysis. RESULTS: The overall initial complete response (CR) (<500 HIV-1 RNA copies/mL) was 76.3%. Use of indinavir [odds ratio (OR)=2.747, P=0.0009] and the number of new nucleoside reverse transcriptase inhibitors (NRTIs) (OR=1.862, P=0.0017) were positively associated with CR, while initial peripheral blood HIV RNA concentration (OR=0.383, P<0.0001), use of saquinavir hard gel capsules (OR=0.531, P=0.0302), the number of successive HAART regimens (OR=0.631, P<0.0001), and the number of previously used NRTIs (OR=0.728, P=0.0081) were negatively associated with CR. Sustainability of CR was positively correlated with use of indinavir [hazard ratio of relapse (HR)=0.255, P<0.0001] and haemoglobin levels (HR=0.873, P=0.0124), but negatively correlated with initial HIV RNA concentration (HR=1.273, P=0.0003) and the number of previously used NRTIs (HR=1.587, P<0.0001). A higher number of consecutive HAART regimens was associated with a markedly reduced CR, but with only a slightly higher risk of relapse. CONCLUSIONS: The initial response to HAART, as well as long-term efficacy, depends strongly on a few fundamental parameters that can easily be assessed in a clinical setting. There is a need for effective suppression of HIV replication over decades, and these factors should be considered early in treatment planning to identify patients with an unfavourable profile of risk factors for treatment failure.

IFN-alpha: therapeutic options in HIV and HIV/HCV, HIV/HBV dual infection.

The antiviral effects of interferon-alpha (IFN-alpha) are well documented for the treatment of hepatitis B or C infections, whereas antiretroviral effects for treatment of HIV-1 infection have been investigated up to now only in small-sized preclinical studies. New preclinical and clinical data on IFN-alpha for HIV, HCV, HBV and especially on co-infections of HIV with HCV or HBV were presented at a symposium of the ConVir conference 2002. This short paper summarizes the presented data on IFN-alpha treatment for HIV and/or HCV or HBV infections.

[Antiretroviral therapy 2003. The current status]. / Antiretrovirale Therapie 2003. Eine Standortbestimmung.

In the year 2003, the basis of antiretroviral treatment comprising nucleoside and nucleotide reverse transcriptase inhibitors (NRTI, NNRTI, NtRTI) and protease inhibitors (PI) will be extended to include entry inhibitors (EI). A representative of this class of drugs, enfurvitide (T20), is about to receive official approval. In the meantime, initial data on long-term treatment with tenofovir, which has been available in Germany since February 2002, have become available. Further medications are in the pipe-line of clinical development, for example, the NRTI emtricitabine (FTC) and the Pis amdoxovir and Atazanavir. Results from studies employing immunomodulatory approaches have so far proved disappointing. In contrast, a number of smaller studies on vaccination have provided promising data. Recommendations for antiretroviral treatment of HIV infection were updated in the summer of 2002.

[Opportunistic diseases. Risk can be estimated]. / Opportunistische Erkrankungen. Das Risiko lässt sich abschätzen.

The role of opportunistic diseases in daily clinical routine is once again expanding. The signs of a change in the trend towards increasing incidence observed in the year 2000 have unfortunately been confirmed. The risk of contracting an opportunistic infection can be estimated with the aid of the CD4 cell count and the viral burden. CM viremia can also be employed as a predictor if highly active antiretroviral therapy (HAART) fails to cure cytomegaly. In the age of HAART, the spectrum of diseases resulting in hospitalization of HIV patients has undergone a change. A notable increase has been observed in hospitalizations for toxic side effects of medication, respiratory infections and liver diseases, in particular hepatitis. Following the introduction of HAART, the mortality rate of HIV-infected patients dramatically decreased, but the results of an American study show that, since 1999. It is on the increase again.

[Opportunistic diseases again on the increase? Study shows tendency for change in the trend]. / Opportunistische Erkrankungen wieder auf dem Vormarsch? Studie zeigt Tendenz zur Trendwende auf.

Since the HAART, primary and secondary prophylaxis, a better understanding of HIV infection and, last, but not least, improved patient compliance with treatment due to a facilitated treatment regimen, have all contributed to achieving a reduction in the number of opportunistic diseases. However, they are no longer decreasing as rapidly as before, but appear to have leveled off. In the first months of HAART a so-called immune reconstitution syndrome, an acute variegated clinical picture may appear, which must be differentiated diagnostically from intolerance of HAART.

[Established and new drugs. Antiretroviral therapy 2002]. / Altbewährtes und Neues. Antiretrovirale Therapie 2002.

The nucleosidal reverse transcriptase inhibitors (NRTI), the protease inhibitors (PI) and the non-nucleosidal reverse transcriptase inhibitors remain the pillars of antiretroviral therapy (ART). In the spring of 2002, they were joined by a representative of a further class of substances, the nucleotidal reverse transcriptase inhibitors (NTRTI). The use of PI, but also of other substances, is associated with undesired effects, in particular on lipid and glucose metabolism. The aim of treatment is to achieve maximum reduction in the amount of virus in the blood. The question as to the timing of treatment--early or late--continues to arouse controversial discussion.