Hepatitis B virus variants in an HIV-HBV co-infected patient at different periods of antiretroviral treatment with and without lamivudine

Background  

Lamivudine inhibits replication of both human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and is commonly used as part of antiretroviral therapy. The main limitation in the use of lamivudine is resistant mutation selection. Most of these mutations affect the YMDD motif of the HBV DNA polymerase. The resistance occurs through M550V or M550I aminoacid replacements. The M550V variation may be accompanied by L526M mutation, notably in HIV-HBV co-infected patients. The aim of this study was to investigate mutations associated with lamivudine resistance in a hemodialysis patient chronically co-infected with HIV-1 and HBV, who was submitted to several antiretroviral treatments.     

Development of an improved dosimetry system for the workers at the Mayak Production Association

Databases are being created that contain verified and updated dosimetry and worker history information for workers at the Mayak Production Association. Many workers had significant external and internal exposures, particularly during the early years (1948-1952) of operation. These dosimetric and worker history data are to be used in companion epidemiology studies of stochastic and deterministic effects. The database contains both external and internal dose information and is being constructed from other databases that include radiochemical analyses of tissues, bioassay data, air sampling data, whole body counting data, and occupational and worker histories. The procedures, models, methods, and operational uncertainties will be documented and included in the database, technical reports, and publications. The cohort of the stochastic epidemiological study is expected to include about 19,000 persons while the cohort for the deterministic epidemiological study is expected to include about 600 persons. For external dosimetry, workplace gamma, beta, and neutron doses are being reconstructed. The models used for this incorporate issues such as known isotopes, composition, shielding, further analysis of film badge sensitivities, and records of direct measurements. Organ doses from external exposures are also being calculated. Methods for calculating dose uncertainties are being developed. For internal dosimetry, the organ doses have been calculated using the established FIB-1 biokinetic model. A new biokinetic model is being developed that includes more information of the solubility and biokinetics of the different chemical forms and particulate sizes of plutonium that were in the workplace. In addition, updated worker histories will be used to estimate doses to some workers where direct measurements were not made. A rigorous quality control procedure is being implemented to ensure that the correct dosimetry data is entering the various databases being used by the epidemiologists.     

Lack of effects of typical and atypical antipsychotics in DARPP-32 and NCS-1 levels in PC12 cells overexpressing NCS-1

Background

Schizophrenia is the major psychiatry disorder, which the exact cause remains unknown. However, it is well known that dopamine-mediated neurotransmission imbalance is associated with this pathology and the main target of antipsychotics is the dopamine receptor D₂. Recently, it was described alteration in levels of two dopamine signaling related proteins in schizophrenic prefrontal cortex (PFC): Neuronal Calcium Sensor-1 (NCS-1) and DARPP-32. NCS-1, which is upregulated in PFC of schizophrenics, inhibits D₂ internalization. DARPP-32, which is decreased in PFC of schizophrenics, is a key downstream effector in transducing dopamine signaling. We previously demonstrated that antipsychotics do not change levels of both proteins in rat's brain. However, since NCS-1 and DARPP-32 levels are not altered in wild type rats, we treated wild type PC12 cells (PC12 WT) and PC12 cells stably overexpressing NCS-1 (PC12 Clone) with antipsychotics to investigate if NCS-1 upregulation modulates DARPP-32 expression in response to antipsychotics treatment.

Results

We chronically treated both PC12 WT and PC12 Clone cells with typical (Haloperidol) or atypical (Clozapine and Risperidone) antipsychotics for 14 days. Using western blot technique we observed that there is no change in NCS-1 and DARPP-32 protein levels in both PC12 WT and PC12 Clone cells after typical and atypical antipsychotic treatments.

Conclusions

Because we observed no alteration in NCS-1 and DARPP-32 levels in both PC12 WT and Clone cells treated with typical or atypical antipsychotics, we suggest that the alteration in levels of both proteins in schizophrenic's PFC is related to psychopathology but not with antipsychotic treatment.     

Nifekalant versus lidocaine for in-hospital shock-resistant ventricular fibrillation or tachycardia

Objective

To compare the efficacy and safety of nifekalant, a pure class III anti-arrhythmic drug, and lidocaine in patients with shock-resistant in-hospital ventricular fibrillation (VF) or ventricular tachycardia (VT).

Patients and methods

Between August 2005 and March 2008, we conducted a prospective, two-arm, cluster observational study, in which participating hospitals were pre-registered either to the nifekalant arm or the lidocaine arm. Patients were enrolled if they had in-hospital VF or VT resistant to at least two defibrillation shocks. Congenital or drug-induced long QT syndrome was excluded. The primary end-point was termination of VF or VT with/without additional shock. The secondary end-points were return of spontaneous circulation (ROSC), 1-month survival and survival to hospital discharge. We also assessed the frequency of adverse events, including asystole, pulseless electrical activity and torsade de pointes.

Results

In total, 55 patients were enrolled. After nifekalant, 22 of 27 patients showed termination of VF or VT, as compared with 15 of 28 patients treated with lidocaine with/without additional shock (odds ratio (OR): 3.8; 95% confidence interval (CI): 1.1-13.0; P = 0.03). Twenty-three of 27 patients given nifekalant showed ROSC, as compared with 15 of 28 patients given lidocaine (OR: 5.0; 95% CI: 1.4-18.2; P = 0.01). There was no difference in 1-month survival or survival to hospital discharge between the nifekalant and lidocaine arms. There was a higher incidence of asystole with lidocaine (7 of 28 patients) than with nifekalant (0 of 27 patients) (P = 0.005). Torsade de pointes was not observed.

Conclusion

Nifekalant was more effective than lidocaine for termination of arrhythmia and for ROSC in patients with shock-resistant in-hospital VF or VT (umin-CTR No. UMIN 000001781).     

Exposure of human CD34+ cells to human immunodeficiency virus type 1 does not influence their expansion and proliferation of hematopoietic progenitors in vitro

The susceptibility of highly purified human CD34+ cells to monocytotropic (Ba-L) and lymphotropic (A018-post) strains of human immunodeficiency virus-1 (HIV-1) was examined. Liquid cultures initiated with fresh immunomagnetically purified CD34+ cells using the K6.1 CD34 monoclonal antibody (MoAb) (K6.1/CD34+) were positive for HIV expression 2 weeks after exposure to HIV-1 Ba-L. These cells were initially greater than 90% CD34+ and had undetectable monocyte contamination by flow-cytometric staining and side-scatter analyses, respectively, and undetectable T-cell contamination by CD3 polymerase chain reaction (PCR) analysis. However, secondary CD34+ liquid cultures reselected from the primary liquid cultures 24 hours after HIV exposure by panning with the ICH3 CD34 MoAb (ICH3/CD34+) and maintained for an additional 14 days were negative for HIV expression. The ICH3-unbound cells were positive for both spliced and unspliced HIV RNA when exposed to HIV-1 Ba-L, and were DNA PCR positive when exposed to either monocytotropic or lymphotropic HIV-1. To further test that CD34+ cells were not infectible by HIV-1, we exposed K6.1/CD34+ cells continuously to HIV-1 in a culture system capable of maintaining and expanding primitive CD34+ cells. HIV-exposed K6.1/CD34+ cells proliferated and expanded as efficiently as uninfected cultures. However, when reselected magnetically using the K6.1 CD34 MoAb after expansion for 7 days, bound K6.1/CD34+ cells were again negative for HIV-1 expression, whereas unbound cells were positive for HIV-1 expression. These findings suggest that a sequential CD34+ cell-selection process, in which the two selections are separated by a brief culture period, can yield a population of CD34+ cells that are not infected with HIV-1. This process may be useful in the design of stem or progenitor cell- based transplantation therapies for HIV infection.     

238Pu: a review of the biokinetics, dosimetry, and implications for human exposures

Plutonium-238 (238Pu) has a half-life of about 87.7 y and thus a higher specific activity than 239Pu. It is used in radioisotope thermoelectric generators and is a substantial source of plutonium alpha-radiation in spent nuclear fuels. Early animal studies demonstrated differences in the biokinetics of inhaled oxides of 238Pu and 239Pu with 238Pu having a substantially more rapid translocation from the lungs to the systemic organs, particularly the skeleton. This resulted in the predominant occurrence of skeletal cancers in animals exposed to 238Pu oxides but lung cancers in those with exposures to 239Pu oxides. The anatomical distribution of osteogenic sarcomas seen in animal studies was similar to that observed with 239Pu and also in plutonium workers but differed from naturally occurring tumors. The in vivo "solubility" of 238Pu has been associated with the relative amounts of 238Pu/239Pu in the particles and calcination temperatures during the preparation of the dioxides. There is experimental evidence of in vivo 238Pu particle fragmentation attributed to nuclear recoil during radioactive decay. The resulting conversion of microparticles to nanoparticles may alter their interactions with macrophages and transport across epithelial barriers. There are few documented cases of human exposures, but the biokinetics appeared to depend on the chemical and physical nature of the aerosols. Robust human biokinetic and dosimetric models have not been developed, due in part to the lack of data. With the acceleration of nuclear technologies and the greater demand for reprocessing and/or disposal of spent nuclear fuels, the potential for human exposure to 238Pu will likely increase in the future.     

Vitamin E (α-tocopherol) supplementation in diabetic rats: effects on the proximal colon

Background  

Neuropathy is one of the complications caused by diabetes mellitus which is directly related to the gastrointestinal manifestations of the disease. Antioxidant substances, such as vitamin E, may play an important role in the reduction of the neurological damage caused by diabetes mellitus. The aim of the present study was to determine whether vitamin E (α-tocopherol) at different concentrations induces any effects on the morphology of the intestinal wall and intrinsic innervation in the proximal colon of diabetic rats.