Post-release survey to assess impact and potential host range expansion by Amitus hesperidum and Encarsia perplexa, two parasitoids introduced for the biological control of the citrus blackfly, Aleurocanthus woglumi in Dominica

Four years after the release of two exotic parasitoids, Amitus hesperidum Silvestri (Hymenoptera: Platygasteridae) and Encarsia perplexa Huang and Polaszek (Hymenoptera: Aphelinidae) for the classical biological control of the citrus blackfly (CBF), Aleurocanthus woglumi Ashby (Hemiptera: Aleyrodidae) in Dominica, a survey was conducted to assess establishment as well as potential nontarget effects especially on Aleyrodidae and other related taxa. CBF populations were low to non-existent in 50 of 51 field sites examined. At the site where CBF was encountered, both E. perplexa and A. hesperidum were present and CBF populations were declining. The two parasitoids were not among the several species collected on nontarget Aleryodidae and Hemiptera. It is concluded that E. perplexa and A. hesperidum have kept CBF populations under effective biological control in Dominica and there is no evidence of any nontarget effects on other Aleyrodidae or their natural enemies. Handling Editor: Dirk Babendreier.     

Electrotonic suppression of early afterdepolarizations in isolated rabbit Purkinje myocytes

Many studies suggest that early afterdepolarizations (EADs) arising from Purkinje fibers initiate triggered arrhythmias under pathological conditions. However, electrotonic interactions between Purkinje and ventricular myocytes may either facilitate or suppress EAD formation at the Purkinje-ventricular interface. To determine conditions that facilitated or suppressed EADs during Purkinje-ventricular interactions, we coupled single Purkinje myocytes and aggregates isolated from rabbit hearts to a passive model cell via an electronic circuit with junctional resistance (R(j)). The model cell had input resistance (R(m,v)) of 50 M Omega, capacitance of 39 pF, and a variable rest potential (V(rest,v)). EADs were induced in Purkinje myocytes during superfusion with 1 microM isoproterenol. Coupling at high R(j) to normally polarized V(rest,v) established a repolarizing coupling current during all phases of the Purkinje action potential. This coupling current preferentially suppressed EADs in single cells with mean membrane resistance (R(m,p)) of 297 M Omega, whereas EAD suppression in larger aggregates with mean R(m,p) of 80 M Omega required larger coupling currents. In contrast, coupling to elevated V(rest,v) established a depolarizing coupling current during late phase 2, phase 3, and phase 4 that facilitated EAD formation and induced spontaneous activity in single Purkinje myocytes and aggregates. These results have important implications for arrhythmogenesis in the infarcted heart when reduction of the ventricular mass due to scarring alters the R(m,p)-to-R(m,v) ratio and in the ischemic heart when injury currents are established during coupling between polarized Purkinje myocytes and depolarized ventricular myocytes.     

Generation of an HIV-1-resistant immune system with CD34(+) hematopoietic stem cells transduced with a triple-combination anti-HIV lentiviral vector

HIV gene therapy has the potential to offer an alternative to the use of current small-molecule antiretroviral drugs as a treatment strategy for HIV-infected individuals. Therapies designed to administer HIV-resistant stem cells to an infected patient may also provide a functional cure, as observed in a bone marrow transplant performed with hematopoietic stem cells (HSCs) homozygous for the CCR5-Δ32-bp allele. In our current studies, preclinical evaluation of a combination anti-HIV lentiviral vector was performed, in vivo, in humanized NOD-RAG1(-/-) IL2rγ(-/-) knockout mice. This combination vector, which displays strong preintegration inhibition of HIV-1 infection in vitro, contains a human/rhesus macaque TRIM5α isoform, a CCR5 short hairpin RNA (shRNA), and a TAR decoy. Multilineage hematopoiesis from anti-HIV lentiviral vector-transduced human CD34(+) HSCs was observed in the peripheral blood and in various lymphoid organs, including the thymus, spleen, and bone marrow, of engrafted mice. Anti-HIV vector-transduced CD34(+) cells displayed normal development of immune cells, including T cells, B cells, and macrophages. The anti-HIV vector-transduced cells also displayed knockdown of cell surface CCR5 due to the expression of the CCR5 shRNA. After in vivo challenge with either an R5-tropic BaL-1 or X4-tropic NL4-3 strain of HIV-1, maintenance of human CD4(+) cell levels and a selective survival advantage of anti-HIV gene-modified cells were observed in engrafted mice. The data provided from our study confirm the safety and efficacy of this combination anti-HIV lentiviral vector in a hematopoietic stem cell gene therapy setting for HIV and validates its potential application in future clinical trials.     

Variability of fibroblast lysosomal acid hydrolases with reference to the detection of enzyme deficiencies.

The ranges of variability of eight lysosomal acid hydrolases were examined in 47 cultured human skin fibroblast lines through 5 successive subcultures. No overall trend in activity values was found for any of the enzymes tested between the first and final subcultures. Similarly, no significant differences could be found between the overall ranges of fibroblast enzyme activity between 20 clinically normal children and 27 individuals being investigated for non-specific metabolic diseases. It is concluded that for diagnostic reference purposes, wide ranges of normal enzyme values must be established. Such ranges can be validly drawn from a continuation of both clinical groups irrespective of the passage number (up to 5) of the cells at the time of isolation. It is noted that in certain cell lines derived from Fabry and Gaucher patients the 'residual' activity of the expectedly deficient enzyme could not easily be distinguished from the lowest values observed in normals, whereas, as expected, the activity of cells derived from patients with GM1 and GM2 gangliosidoses was markedly reduced.     

Effects of cholestyramine on 1,2-dimethylhydrazine-induced enteric carcinoma in germfree rats.

Oral administration of 1,2-dimethylhydrazine (DMH) induced intestinal neoplasms in germfree rats. A supplement of 2% cholestyramine resin in the diet increased the frequency of DMH-induced intestinal tumors and accelerated malignant transformation. Bile acids in the cecal content were determined with and without cholestyramine in order to obtain a correlation between the bile acid metabolism and the enteric carcinogenesis.     

The Anabolic Androgenic Steroid Nandrolone Decanoate Disrupts Redox Homeostasis in Liver,Heart and Kidney of Male Wistar Rats

The abuse of anabolic androgenic steroids (AAS) may cause side effects in several tissues. Oxidative stress is linked to the pathophysiology of most of these alterations, being involved in fibrosis, cellular proliferation, tumorigenesis, amongst others. Thus, the aim of this study was to determine the impact of supraphysiological doses of nandrolone decanoate (DECA) on the redox balance of liver, heart and kidney. Wistar male rats were treated with intramuscular injections of vehicle or DECA (1 mg.100 g⁻¹ body weight) once a week for 8 weeks. The activity and mRNA levels of NADPH Oxidase (NOX), and the activity of catalase, glutathione peroxidase (GPx) and total superoxide dismutase (SOD), as well as the reduced thiol and carbonyl residue proteins, were measured in liver, heart and kidney. DECA treatment increased NOX activity in heart and liver, but NOX2 mRNA levels were only increased in heart. Liver catalase and SOD activities were decreased in the DECA-treated group, but only catalase activity was decreased in the kidney. No differences were detected in GPx activity. Thiol residues were decreased in the liver and kidney of treated animals in comparison to the control group, while carbonyl residues were increased in the kidney after the treatment. Taken together, our results show that chronically administered DECA is able to disrupt the cellular redox balance, leading to an oxidative stress state.