Automated preparation of 2‐[18F]fluoropropionate labeled peptides using a flexible,multi‐stage synthesis platform (iPHASE Flexlab)

Radiolabelled peptides are vital tools used in positron emission tomography imaging for the diagnosis of disease, drug discovery, and biomedical research. Peptides are typically labeled through conjugation to a radiolabelled prosthetic group, which usually necessitates complex, multi‐step procedures, especially for fluorine‐18 labeled peptides. Herein, we describe the automated synthesis and formulation of 2‐[¹⁸F]fluoropropionate labeled RGD‐peptides through use of the iPHASE Flexlab as an effective dual‐stage radiochemical synthesis module. The fully automated preparation of the monomeric RGD‐peptides, [¹⁸F]FP‐GalactoRGD and [¹⁸F]FP‐c(RGDy(SO₃)K), was accomplished in under 90 minutes with n.d.c. radiochemical yields ca. 7% from fluoride. Similarly, the automated preparation of the dimeric RGD‐peptides, [¹⁸F]F‐PRGD₂ and [¹⁸F]FP‐E(RGDy(SO₃)K)₂, was accomplished in under 105 minutes with n.d.c. yields ca. 4% from fluoride.     

Associations of Drug Use,Violence, and Depressive Symptoms with Sexual Risk Behaviors Among Women with Alcohol Misuse

Background

Alcohol misuse is associated with increased human immunodeficiency virus sexual risk behaviors by women. Drug use, intimate partner violence (IPV), and depressive symptoms frequently co-occur, are well-recognized alcohol misuse comorbidities, and may interact to increase risk behaviors. Using a syndemic framework we examined associations between drug use, IPV, and depressive symptoms and sexual risk behaviors by 400 women with alcohol misuse attending an urban sexually transmitted infections clinic.

The Patient Reported Outcomes as a Clinical Tool (PROACT) Pilot Study: What Can be Gained by Sharing Computerized Patient-Reported Mental Health and Substance Use Symptoms with Providers in HIV Care?

AIDS and Behavior - Substance use and mental health (SU/MH) disorders are insufficiently recognized in HIV care. We examined whether conveying SU/MH screening results to patients and providers...     

The hemostatic defect of chronic liver disease. Kinetic studies using 75Se-selenomethionine.

With the use of cohort labeling with 75Se-selenomethionine, simultaneous platelet, fibrinogen, and plasminogen survival studies were carried out in 8 patients with chronic alcoholic liver disease and in 5 normal subjects. Clinical features, liver function tests, coagulation and fibrinolytic system activities, and platelet function were also assessed. On the basis of platelet survival, the patients could be divided into two groups. Three patients had shortened platelet survival; they were all thrombocytopenic and had greater prolongation of the prothrombin time (PT) and activated partial thromboplastin time (PTT) than the other 5 patients. However, platelet turnover was decreased in all the patients, and there was no difference between the two groups with regard to fibrinogen or plasminogen survival nor in the in vitro evidence of disseminated intravascular coagulation (DIC). Fibrinogen survival was increased in 5 of the 8 patients. Plasminogen survival was normal in 6 patients and prolonged in 2 patients with very low plasminogen levels. The absence of increased fibrinogen turnover in the patients studied indicates that the abnormalities in coagulation tests were not due to consumption coagulopathy. The authors' studies suggest that, at least for patients with chronic stable alcoholic liver disease, the concept that the coagulopathy of liver disease is due to increased utilization of clotting factors should be revised with caution.     

Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients

The molecular characterization of the mutations in hemophilia A patients is hampered by the large size of the factor VIII gene and the great heterogeneity of mutations. In this study, we have performed a protocol involving multiplex polymerase chain reaction in which 19 exons were amplified in four different combinations followed by nonradioactive single-strand conformational polymorphism (SSCP) to screen for mutations. Southern blotting was used to detect inversion of the factor VIII gene resulting from recombination between copies of the gene A (F8A) located in intron 22 of the factor VIII gene and two copies close telomeric region of X chromosome. Forty-two hemophilia A patients (21 with severe and 21 with mild-to-moderate disease) were studied. The inversion of factor VIII occurred in 13 of 21 patients affected by severe hemophilia A. One patient showed a large extra band in addition to the three bands observed after Southern blotting with the F8A probe. An abnormal electrophoretic pattern of SSCP was detected in 85% and 50% of the patients affected by mild-to-moderate and severe disease, respectively. Sixteen different mutations were identified. Eleven mutations were novel and comprised 9 point mutations and 2 small deletions. This study shows that the methodology used is safe and rapid and has potential for detecting almost all of the genetic defects of the studied hemophilia A patients.     

Effect of metoclopramide on interdigestive myoelectric activity in the conscious dog

The effect of two-hour infusions of metoclopramide at five different doses on interdigestive intestinal electrical activity was studied in four conscious fasting dogs. Spike activity during the infusions was quantitatively compared with activity during preceding and following periods of saline infusion. The effect of the drug was the enhancement of spike activity during migrating myoelectric complexes (MMC) without disruption of the fasting pattern; the effect was most marked in the proximal small intestine and diminished distally. As in other published studies with metoclopramide, its effects were variable and not dose dependent. The enhancement of the MMC by an exogenous stimulus, not previously reported, provides indirect evidence for cholinergic mediation of cyclical motor activity, and also suggests a rational basis for therapy.This work was undertaken with the support of the Wellcome Trust, the Medical Research Council and the University of London Central Research Fund.     

Effects of soluble copper and copper oxide nanoparticle exposure on the immune system of mussels,Mytilus galloprovincialis

Copper and copper oxide nanomaterials (nCuO) can enter the marine environment negatively impacting mussels, an environmental and commercially relevant organism. We analyzed the effects on the immune system of adult mussels exposed to soluble copper (CuSO₄, 20‐50 μg/L) or nCuO (100‐450 μg/L). CuSO₄ caused significant copper accumulation in gills and cell‐free hemolymph, while nCuO caused cell damage to gills and significant copper accumulation in hemocytes, the most abundant cells in the hemolymph. Both sources of copper caused cellular toxicity in hemocytes by increasing reactive oxygen species production and lysosome abundance, and decreasing multi‐drug resistance transporter activity. Though hemocyte abundance was not affected, their in‐vitro phagocytic activity decreased, explaining the slight (but not statistically significant) increase in bacterial proliferation in mussels exposed to the pathogenic bacteria Vibrio tubiashii following copper exposure. Thus, exposure to non‐lethal concentrations of CuSO₄ or nCuO can potentially increase mussel susceptibility to bacterial infections.