Examining the potential for porcine-derived islet cells to harbour viral pathogens

With an onus on safety in the potential use of porcine islet cells as a treatment for diabetes, the use of animals lacking exogenous pathogens is clearly important and multilevel screening strategies have been presented on testing animals and the product. In this study, we wished to investigate whether islet cells indeed harboured the same viral pathogens of concern in the source animal. PMBC and islet cells from both adult and neonatal source animals were directly compared and tested for PCMV, PLHV, PCV2, PPV and HEV using both molecular and serological assays. Adult PBMC were found positive for all viruses with the exception of PCV2 and HEV. Neonatal PBMC were only found positive for PCMV and HEV. All animals were found negative for HEV antibodies. Interestingly, islet cells were negative for all viruses tested regardless of status in the animal-derived PBMC. Given that other laboratories have demonstrated the lack of virus detection during the culture of islets, this study also demonstrates that the hygiene status of the herd may not reflect the status of the product. This is important for establishing guidelines for any risk evaluation and mitigation process utilised during product manufacture

Assessment of porcine endogenous retrovirus transmission across an alginate barrier used for the encapsulation of porcine islets

BACKGROUND: Subcutaneous implantation of a macroencapsulated patch containing human allogenic islets has been successfully used to alleviate type 1 diabetes mellitus (T1DM) in a human recipient without the need for immunosuppression. The use of encapsulated porcine islets to treat T1DM has also been reported. Although no evidence of pathogen transfer using this technology has been reported to date, we deemed it appropriate to determine if the encapsulation technology would prevent the release of virus, in particular, the porcine endogenous retrovirus (PERV). METHODS: HEK293 (human epithelial kidney) and swine testis (ST) cells were co-cultured with macroencapsulated pig islets embedded in an alginate patch, macroencapsulated PK15 (swine kidney epithelial) cells embedded in an alginate patch and free PK15 cells. Cells and supernatant were harvested at weekly time points from the cultures for up to 60 days and screened for evidence of PERV release using qRT-PCR to detect PERV RNA and SG-PERT to detect reverse transcriptase (RT). RESULTS: No PERV virus, or evidence of PERV replication, was detected in the culture medium of HEK293 or pig cells cultured with encapsulated porcine islets. Increased PERV activity relative to the background was not detected in ST cells cultured with encapsulated PK15 cells. However, PERV was detected in 1 of the 3 experimental replicates of HEK293 cells cultured with encapsulated PK15 cells. Both HEK293 and ST cells cultured with free PK15 cells showed an increase in RT detection. CONCLUSIONS: With the exception of 1 replicate, there does not appear to be evidence of transmission of replication competent PERV from the encapsulated islet cells or the positive control PK15 cells across the alginate barrier. The detection of PERV would suggest the alginate barrier of this replicate may have become compromised, emphasizing the importance of quality control when producing encapsulated islet patches

Blood pressure normalization by fixed perindopril/indapamide combination in hypertensive patients with or without associate metabolic syndrome: results of the OPTIMAX 2 study

The aim of the observational pharmaco-epidemiological study Optimax II was to seek whether the pre-existence of a metabolic syndrome (MS) defined by the NCEP-ATP III criteria impacts blood pressure (BP) control in hypertensive patients receiving a fixed perindopril/indapamide combination therapy. The primary objective of the study was to compare in patients with and without MS the rate of BP control defined as a systolic BP ≤140 mmHg and a diastolic BP ≤90 mmHg. Patients were prospectively included and the follow-up lasted 6 months. The study population consisted of 24,069 hypertensive patients (56% men; mean age 62 ± 11 years; 18% diabetics; mean BP at inclusion 162 ± 13/93 ± 9 mmHg). MS was found in 30.4% of the patients (n = 7322): 35.2% women and 20.1% men. Three therapeutic subgroups were constituted: Group A, previously untreated, received the combination therapy as initial treatment; Group B, previously treated but with unsatisfactory results and/or treatment intolerance, had its previous treatment switched to perindopril/indapamide; and Group C, previously treated, with good treatment tolerance but uncontrolled BP, received the study treatment in adjunction to the previous one. The normalization rate was 70.3% in group A, 68.4% in Group B, and 64.1% in Group C (p < 0.0001). The pre-existence of MS did not show any significant influence on these rates since BP lowering was −22.7 ± 13.7 (SBP) and −12.0 ± 10.0 mmHg (DBP) in patients without MS and −22.6 ± 13.3 (SBP) and −12.1 ± 9.7 (DBP) in those with MS. The results of this study show a significant effect of perindopril/indapamide treatment on systolic BP lowering, whatever the treatment status: initiation, switch, or adjunctive therapy, and independently from the presence or not of MS. This effect may be related to the specific vascular effect of the perindopril/indapamide combination, which has recently demonstrated in the ADVANCE trial its ability to reduce mortality, and cardiovascular and renal complications in diabetic patients

LEED v4 : where are we now? Critical assessment through the LCA of an office building using a low impact energy consumption mix

Various Green Building Rating Systems (GBRS) have been proposed to reduce the environmental impact of buildings. However, these GBRS, such as LEED v4, are primarily oriented towards a building`s use stage energy consumption. Their application in contexts involving a high share of renewable energy, and hence a low impact electricity mix, can result in undesirable side effects. This paper aims to investigate such effects, based on an existing office building in Quebec (Canada), where more than 95% of the electricity consumption mix is renewable. This paper compares the material impacts from a low-energy context building to material considerations in LEED v4. In addition to their contributions to the building impacts, material impacts are also defined by their potential to change impacts with different material configurations. LCA impacts were evaluated using Simapro 8.2, ecoinvent 3.1 database, and IMPACT 2002+ method. The building LCA results indicated higher environmental impact contributions from materials (> 50%) compared to those from energy consumption. This is in contrast with LEED v4 rating system, as it did not seem to be as effective in capturing such effects. The conclusions drawn from this work will help stakeholders from the buildings sector to have a better understanding of building environmental profiles, and the limitations of LEED v4 in contexts involving a low impact energy mix. In addition, this critical assessment can be used to further improve the LEED certification system