Hemoglobin kinetics and the effect of organic phosphates

A kinetic model based on allosteric mechanisms of cooperativity fits the experimentally observed phosphate dependence of hemoglobin reactions. Subunit inequivalence is found to be important in analyzing hemoglobin kinetics. The observed increase in the rate of deoxygenation in the presence of organic phosphates is primarily related to the increased rate of dissociation of the second oxygen molecule.     

Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix

BCL-2 family proteins constitute a critical control point for the regulation of apoptosis. Protein interaction between BCL-2 members is a prominent mechanism of control and is mediated through the amphipathic alpha-helical BH3 segment, an essential death domain. We used a chemical strategy, termed hydrocarbon stapling, to generate BH3 peptides with improved pharmacologic properties. The stapled peptides, called "stabilized alpha-helix of BCL-2 domains" (SAHBs), proved to be helical, protease-resistant, and cell-permeable molecules that bound with increased affinity to multidomain BCL-2 member pockets. A SAHB of the BH3 domain from the BID protein specifically activated the apoptotic pathway to kill leukemia cells. In addition, SAHB effectively inhibited the growth of human leukemia xenografts in vivo. Hydrocarbon stapling of native peptides may provide a useful strategy for experimental and therapeutic modulation of protein-protein interactions in many signaling pathways.     

Tritrichomonas foetus infection in purebred cats in Germany: prevalence of clinical signs and the role of co-infection with other enteroparasites

The aim of this study was to determine the prevalence of Tritrichomonas foetus infection and associated clinical signs in purebred cats in Germany, to investigate the role of co-infection, and identify determinants of infection. Faecal specimens accompanied by epidemiological questionnaires were scored and collected from 230 purebred cats. Faeces were examined for trichomonads and other enteroparasites. The prevalence of T foetus was 15.7% among cats and 18.5% among catteries. An abnormal faecal score and history of diarrhoea were observed in 64% and 61% of T foetus-positive cats, respectively, and correlated significantly with infection. Co-infection, observed in 36% of T foetus-infected cats, was not associated with diarrhoea. Norwegian Forest cats were infected significantly more often than other breeds. No association was found with any environmental factors. This study demonstrated a high prevalence of symptomatic T foetus infections in purebred cats in Germany. Co-infection with other enteroparasites did not worsen clinical signs of trichomonosis.     

Surgical amputation of a digit and vacuum-assisted-closure (V.A.C.) management in a case of osteomyelitis and wound care in an eastern black rhinoceros (Diceros bicornis michaeli)

A 14-yr-old female eastern black rhinoceros (Diceros bicornis michaeli) presented with progressive suppurative osteomyelitis in her left hind lateral toe. beta-Hemolytic Streptococcus sp. was isolated. The animal was treated with multiple systemic antibiotics, and topical wound cleansing. Repeated debridements and nail trimmings were performed for 5 mo prior to electing amputation. The toe was surgically amputated under general anesthesia between the first and second phalanges. Analgesia was diffused into the wound topically via a catheter and elastomeric pump. The open amputation site was covered with adherent drapes and a negative-pressure wound therapy device provided vacuum-assisted closure (V.A.C.) for 72 hr. Three months later this animal developed a deep dermal ulcer on the lateral aspect of the right hind limb, at the level of the stifle. Methicillin-resistant Staphylococcus aureus was isolated. The wound was managed by initial daily lavage, followed by 1 mo of V.A.C. therapy, with 72 hr between dressing changes. Clinically, this therapy expedited the formation of healthy granulation tissue and overall healing was accelerated. The animal tolerated the machine and bandage changes well via operant conditioning. The use of negative-pressure wound therapy appeared to shorten time to resolution of slow-healing wounds in black rhinoceros.