Markers for HIV-disease progression in untreated patients and patients receiving AZT: Evaluation of viral activity, AZT resistance, serum cholesterol, β2-microglobulin, CD4+ cell counts, and HIV antigen

In order to find parameters which allow the assessment of the clinical state of HIV patients with or without antiviral therapy, viral cultures on lymphocytes and monocytes/macrophages, CD4-cell counts, HIV antigen, 2-microglobulin and serum cholesterol were evaluated for their predictive value. As had been shown previously for lymphocytes, the efficiency of viral isolation on macrophages also depends on the disease stage (CDC) of the patients and thus has a high predictive value. A multivariant discriminant analysis showed that the combination of 2-microglobulin, viral antigen, CD4+ cell count and HDL cholesterol predicted the outcome of viral cultures with 80% accuracy. While viral antigen, CD4+ cell counts and 2-microglobulin had been known, HDL cholesterol deserves further evaluation as prognostic parameter. The analysis of HIV derived from patients with AZT showed a 20–200-foldin vitro drug resistance after seven to 24 months of therapy. DNA sequence determination of such strains isolated from AZT patients over time showed only two of the amino acid exchanges described in the literature for resistant strains and an additional Val60-Ile transition after 32 months of therapy.Um Parameter zu finden, die es erlauben, den klinischen Status HIV-Infizierter exakt zu bestimmen, wurden die Virusanzucht auf Lymphozyten und Makrophagen, CD4+-Zellzahlen, Cholesterin-Werte, 2-Mikroglobulin-Spiegel und virales Antigen hinsichtlich ihres prädiktiven Wertes verglichen. Wie bereits für die Virusanzucht auf Lymphozyten beschrieben, war auch die HIV-Kultur auf Makrophagen vom Gesundheitszustand der Patienten (bestimmt nach CDC) abhängig und hat somit hohen prädiktiven Wert. Eine multivariante Diskriminanzanalyse zeigte, daß das Ergebnis der Viruskultur unabhängig vom Zellsystem durch eine Kombination von 2-Mikroglobulin, Virusantigen, CD4+-Zellzahlen und HDL-Cholesterin-Werten zu 80% voraussagbar ist. HDL-Cholesterin verdient daher, als neuer prognostischer Parameter weiter erforscht zu werden. Die Analyse von HIV-Isolaten aus AZT-behandelten Patienten zeigte eine 20–200- fachein vitro Resistenz gegenüber der Substanz nach sieben bis 24 Monaten der Therapie. Sequenzbestimmungen bei einem der 100fach resistenten Isolate ergaben nur zwei der in der Literatur beschriebenen Aminosäure-Austrausche und eine neue Mutation (Val₆₀ zu Ile) in einem Virus nach 32 Monaten der Therapie.     

Accuracy of forensic age estimation using cementum annulation and dentin translucency in adult: a systematic review and meta-analysis

International Journal of Legal Medicine - Identification of the living and the dead individual is essential in routine forensic dental examinations. Age determination can be of great value in...     

Pyrido[3,2-e][1,4] diazepine - Synthese und Prüfung auf Anti-HIV-1-Wirkung

Pyrido[3,2-e][1,4] diazepines - Synthesis and Anti-HIV-1-Activity Tests Starting from the commercially available 6-methyl-2-pyridylamine ( 1 ) the pyrido[3,2-e][1,4]diazepine 14a was synthesized in 12 steps with 7% total yield. 14a , the N-methyl derivative 14b , the thiolactam 15a , the amidine 16 . and the 1,2,4-triazole 17 were tested for anti-HIV-1-activity. None of the compounds tested possesses antiviral activity comparable to that of zidovudine (3′ -azido-3′-desoxythymidine = AZT).     

Solvent/Detergent Treatment of Human Plasma - A Very Robust Method for Virus Inactivation. Validated Virus Safety of OCTAPLAS®

OCTAPLAS® is a cell-free standardized blood group specific human coagulation active plasma for transfusion. The viral safety is mainly based on the treatment with solvent/detergent. SD is known to irreversibly inactivate the lipid enveloped viruses including HTV 1+2, HBV and HCV and has been recommended both by European guidelines and the FDA. The potential limitation of each inactivation method should be validated according to the current EU-guidelines CPMP/BWP/268/95 and CPMP/BWP/269/95. Our studies demonstrate that the SD method inactivates lipid enveloped viruses within a few minutes to below the limit of detection. The concentration of the SD reagents as well as several other process parameters chosen for the virus inactivation step of plasma pools of different protein and lipid composition result in a high safety margin towards the clinically relevant viruses.