A clinical study to evaluate the cardiopulmonary characteristics of two different anaesthetic protocols (tiletamine/zolazepam +/- medetomidine) and to evaluate their suitability for the immobilisation of healthy chimpanzees

Objective: To characterise the cardiopulmonary characteristics of two different anaesthetic protocols (tiletamine/zolazepam +/- medetomidine) and their suitability for the immobilisation of healthy chimpanzees undergoing cardiac assessment. Study design: Prospective, clinical, longitudinal study Animals: Six chimpanzees (Pan troglodytes) aged 4 - 16 years weighing 19.5 - 78.5 kg were anaesthetized on two occasions Methods: Anaesthesia was induced with tiletamine/zolazepam (TZ) (3-4 mg kg-1) or tiletamine/zolazepam (2 mg kg-1) and medetomidine (0.02 mg kg-1) (TZM) via blow dart (IM) and maintained with intermittent boluses of ketamine (IV) or zolazepam/tiletamine (IM) as required. The overall quality of the anaesthesia was quantified based on scores given for: quality of induction, degree of muscle relaxation and ease of intubation. The time to achieve a light plane of anaesthesia, number of supplemental boluses needed and recovery characteristics were also recorded. Chimpanzees were continuously monitored and heart rate (HR), pulse rate (PR), respiratory rate (fR) oxygen saturation of heamoglobin (SpO2), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), rectal temperature, mucous membrane colour and capillary refill time recorded. During the first procedure (TZ) animals underwent a 12 channel ECG, hematology, biochemistry and cardiac biomarker assessment to rule out the presence of pre-existing cardiovascular disease. A detailed echocardiographic examination was carried out by the same blinded observer during both procedures. Data were compared using Student’s paired t-test or Wilcoxon rank tests as appropriate. Results: There was a significant difference for the area under the curves between anaesthetic protocols for HR, SAP, MAP and fR. No significant differences in the echocardiographic measurements were evident. Quality of anaesthesia was significantly better with TZM and no additional boluses were required. The TZ protocol required multiple supplemental boluses. Conclusions and clinical relevance: Both combinations are suitable for immobilization and cardiovascular evaluation of healthy chimpanzees. Further work is required to evaluate the effect of medetomidine in cardiovascular disease

New insights from 3D geological models at analogue CO2 storage sites in Lincolnshire and eastern Scotland, UK

SUMMARY: Subsurface 3D geological models of aquifer and seal rock systems from two contrasting analogue sites have been created as the first step in an investigation into methodologies for geological storage of carbon dioxide in saline aquifers. Development of the models illustrates the utility of an integrated approach using digital techniques and expert geological knowledge to further geological understanding. The models visualize a faulted, gently dipping Permo-Triassic succession in Lincolnshire and a complex faulted and folded Devono-Carboniferous succession in eastern Scotland. The Permo-Triassic is present in the Lincolnshire model to depths of 2 km OD, and includes the aquifers of the Sherwood Sandstone and Rotliegendes groups. Model-derived thickness maps test and refine Permian palaeogeography, such as the location of a carbonate reef and its associated seaward slope, and the identification of aeolian dunes. Analysis of borehole core samples established average 2D porosity values for the Rotliegendes (16%) and Sherwood Sandstone (20%) groups, and the Zechstein (5%) and Mercia Mudstone (<10%) groups, which are favourable for aquifer and seal units respectively. Core sample analysis has revealed a complex but well understood diagenetic history. Re-interpretation of newly reprocessed seismic data in eastern Scotland has significantly reduced interpretative uncertainty of aquifer and seal units at depths of up to 6 km OD in a complex faulted and folded Devonian-Carboniferous succession. Synthesis of diverse data in the 3D geological model defines a set of growth folds and faults indicative of active Viséan to Westphalian dextral-strike slip, with no major changes in structural style throughout the Carboniferous, in contrast to some published tectonic models. Average 2D porosity values are 14-17% in aquifer units and <2% in the seal unit, with a ferroan dolomite cement occluding porosity at depth

Maraviroc (UK-427,857), a Potent, Orally Bioavailable, and Selective Small-Molecule Inhibitor of Chemokine Receptor CCR5 with Broad-Spectrum Anti-Human Immunodeficiency Virus Type 1 Activity

Maraviroc (UK-427,857) is a selective CCR5 antagonist with potent anti-human immunodeficiency virus type 1 (HIV-1) activity and favorable pharmacological properties. Maraviroc is the product of a medicinal chemistry effort initiated following identification of an imidazopyridine CCR5 ligand from a high-throughput screen of the Pfizer compound file. Maraviroc demonstrated potent antiviral activity against all CCR5-tropic HIV-1 viruses tested, including 43 primary isolates from various clades and diverse geographic origin (geometric mean 90% inhibitory concentration of 2.0 nM). Maraviroc was active against 200 clinically derived HIV-1 envelope-recombinant pseudoviruses, 100 of which were derived from viruses resistant to existing drug classes. There was little difference in the sensitivity of the 200 viruses to maraviroc, as illustrated by the biological cutoff in this assay (= geometric mean plus two standard deviations [SD] of 1.7-fold). The mechanism of action of maraviroc was established using cell-based assays, where it blocked binding of viral envelope, gp120, to CCR5 to prevent the membrane fusion events necessary for viral entry. Maraviroc did not affect CCR5 cell surface levels or associated intracellular signaling, confirming it as a functional antagonist of CCR5. Maraviroc has no detectable in vitro cytotoxicity and is highly selective for CCR5, as confirmed against a wide range of receptors and enzymes, including the hERG ion channel (50% inhibitory concentration, >10 μM), indicating potential for an excellent clinical safety profile. Studies in preclinical in vitro and in vivo models predicted maraviroc to have human pharmacokinetics consistent with once- or twice-daily dosing following oral administration. Clinical trials are ongoing to further investigate the potential of using maraviroc for the treatment of HIV-1 infection and AIDS

Dengue Fever, Hawaii, 2001–2002

Autochthonous dengue infections were last reported in Hawaii in 1944. In September 2001, the Hawaii Department of Health was notified of an unusual febrile illness in a resident with no travel history; dengue fever was confirmed. During the investigation, 1,644 persons with locally acquired denguelike illness were evaluated, and 122 (7%) laboratory-positive dengue infections were identified; dengue virus serotype 1 was isolated from 15 patients. No cases of dengue hemorrhagic fever or shock syndrome were reported. In 3 instances autochthonous infections were linked to a person who reported denguelike illness after travel to French Polynesia. Phylogenetic analyses showed the Hawaiian isolates were closely associated with contemporaneous isolates from Tahiti. Aedes albopictus was present in all communities surveyed on Oahu, Maui, Molokai, and Kauai; no Ae. aegypti were found. This outbreak underscores the importance of maintaining surveillance and control of potential disease vectors even in the absence of an imminent disease threat