Blood rheology of Weddell seals and bowhead whales

Red blood cell (RBC) aggregation and blood viscosity are important determinants of in vivo blood flow dynamics and, in marine mammals, these parameters may impact diving physiology by altering blood oxygen delivery during the diving response. Weddell seals are superb divers and exhibit age-related patterns in blood oxygen chemistry and diving ability. By contrast, bowhead whales are not long duration divers, and little is known of their blood properties relative to diving. The present study was designed to compare rheological characteristics of blood from Weddell seal pups, Weddell seal adults, and from adult bowhead whales: blood viscosity and RBC aggregation in plasma and in polymer solutions (i.e., RBC "aggregability") were measured. Salient findings included: (1) significant 4- to 8-fold greater aggregation in blood from adult seals compared with pups and human subjects; (2) 2-to 8-fold greater aggregation in bowhead whale blood compared with human blood; (3) compared to human red cells, enhanced RBC aggregability of RBC from adult seals and whales as determined by their greater aggregation in polymer solutions; (4) increasing RBC aggregation and aggregability of seal pup blood over a seven day period following birth; (5) significantly greater blood viscosity for adult seals compared with pups at both native and standardized hematocrits. These results indicate that, for both species, hemorheological parameters differ markedly from those of humans, and suggest progressive changes with seal age; the physiological implications of these differences have yet to be fully defined.     

4-Anilino-6-phenyl-quinoline inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK2)

A class of inhibitors of mitogen activated protein kinase-activated kinase 2 (MK2) was discovered via high-throughput screening. This compound class demonstrates activity against the enzyme with sub-μM IC₅₀ values, and suppresses LPS-induced TNFα levels in THP-1 cells. MK2 inhibition kinetic measurements indicated mixed binding approaching non-ATP competitive inhibition.     

The phylogeny of Mediterranean tortoises and their close relatives based on complete mitochondrial genome sequences from museum specimens

As part of an ongoing project to generate a mitochondrial database for terrestrial tortoises based on museum specimens, the complete mitochondrial genome sequences of 10 species and a approximately 14kb sequence from an eleventh species are reported. The sampling of the present study emphasizes Mediterranean tortoises (genus Testudo and their close relatives). Our new sequences are aligned, along with those of two testudinoid turtles from GenBank, Chrysemys picta and Mauremys reevesii, yielding an alignment of 14,858 positions, of which 3238 are parsimony informative. We develop a phylogenetic taxonomy for Testudo and related species based on well-supported, diagnosable clades. Several well-supported nodes are recovered, including the monophyly of a restricted Testudo, T. kleinmanni+T. marginata (the Chersus clade), and the placement of the enigmatic African pancake tortoise (Malacochersus tornieri) within the predominantly Palearctic greater Testudo group (Testudona tax. nov.). Despite the large amount of sequence reported, there is low statistical support for some nodes within Testudona and so we do not propose names for those groups. A preliminary and conservative estimation of divergence times implies a late Miocene diversification for the testudonan clade (6-10 million years ago), matching their first appearance in the fossil record. The multi-continental distribution of testudonan turtles can be explained by the establishment of permanent connections between Europe, Africa, and Asia at this time. The arrival of testudonan turtles to Africa occurred after one or more initial tortoise invasions gave rise to the diverse (>25 species) 'Geochelone complex.' Two unusual genomic features are reported for the mtDNA of one tortoise, M. tornieri: (1) nad4 has a shift of reading frame that we suggest is resolved by translational frameshifting of the mRNA on the ribosome during protein synthesis and (2) there are two copies of the control region and trnF, with the latter having experienced multiple-nucleotide substitutions in a pattern suggesting that each is being maintained by selection.     

Structure-based discovery of a new affinity ligand to pancreatic alpha-amylase

A ligand useful for affinity capture of porcine pancreatic alpha-amylase was found by virtual screening of the commercially available compound data base MDL Available Chemicals Directory. Hits from the virtual screening were investigated for binding by nuclear magnetic resonance (NMR) and surface plasmon resonance. Selected compounds were tested for inhibition of the enzyme using a NMR-based assay. One of the binders found was covalently coupled to a chromatographic resin and a column, packed with this resin, could retain alpha-amylase, which subsequently was eluted by introduction of the known inhibitor acarbose to the elution buffer.     

Effect of enhanced red blood cell aggregation on blood flow resistance in an isolated-perfused guinea pig heart preparation

The role of red blood cell (RBC) aggregation as a determinant of in vivo blood flow is still unclear. This study was designed to investigate the influence of a well-controlled enhancement of RBC aggregation on blood flow resistance in an isolated-perfused heart preparation. Guinea pig hearts were perfused through a catheter inserted into the root of the aorta using a pressure servo-controlled pump system that maintained perfusion pressures of 30 to 100 mmHg. The hearts were beating at their intrinsic rates and pumping against the perfusion pressure. RBC aggregation was increased by Pluronic (F98) coating of RBC at a concentration 0.025 mg/ml, corresponding to about a 100% increment in RBC aggregation as measured by erythrocyte sedimentation rate. Isolated heart preparations were perfused with 0.40 l/l hematocrit unmodified guinea pig blood and with Pluronic-coated RBC suspensions in autologous plasma. At high perfusion pressures there were no significant differences between the flow resistance values for the two perfusates, with differences in flow resistance only becoming significant at lower perfusion pressures. These results can be interpreted to reflect the shear dependence of RBC aggregation: higher shear forces associated with higher perfusion pressures should have dispersed RBC aggregates resulting in blood flow resistances similar to control values. Experiments repeated in preparations in which the smooth muscle tone was inhibited by pre-treatment with papaverine indicated that significant effects of enhanced RBC aggregation could be detected at higher perfusion pressures, underlining the compensatory role of vasomotor control mechanisms.     

Fatal disseminated cytomegalovirus infection in an infant with Cushing's syndrome caused by topical steroid

Corticosteroids, even in topical application, may cause immunosuppression and Cushing's syndrome. A case of disseminated fatal cytomegalovirus infection is reported in a 3-month-old girl with Cushing's syndrome caused by exogenous topical clobetasol propionate application, which might have caused immunosuppression due to prolonged use.