In vitro elution of gentamicin, amikacin, and ceftiofur from polymethylmethacrylate and hydroxyapatite cement

OBJECTIVE: To compare the elution characteristics of ceftiofur and liquid and powdered gentamicin and amikacin from polymethylmethacrylate (PMMA) and from hydroxyapatite cement (HAC). METHODS: PMMA and HAC beads in triplicate were impregnated with various amounts and formulations of antibiotics. Beads were immersed in 5 mL of phosphate buffered saline that was replaced at 1, 3, 6, and 12 hours, and 1, 2, 3, 5, 7, 10, 14, 18, 22, 26, and 30 days. The eluent was stored at -70 degrees C until assayed within 2 weeks by microbiological assay (gentamicin and amikacin) or capillary electrophoresis (ceftiofur). RESULTS: Rate of elution for all beads was greatest within the first 24 hours. Cumulative release of total antibiotic dose from beads over 30 days was significantly greater from HAC than PMMA. Antibiotic elution was directly related to the amount of antibiotic incorporated into the cement. Powdered and liquid forms of gentamicin had similar elution rates from PMMA. Elution of amikacin from PMMA beads was greater when the powdered form was used compared with liquid amikacin. Eluent concentrations of ceftiofur were similar to those of the aminoglycosides during the first 3 to 7 days but then decreased precipitously by comparison. CONCLUSIONS: Elution of antibiotics from HAC was greater than from PMMA. Gentamicin- and amikacin-impregnated PMMA and HAC released bactericidal concentrations of antibiotic for at least 30 days. Ceftiofur-impregnated PMMA or HAC is unlikely to provide long-term bactericidal concentrations. CLINICAL RELEVANCE: Gentamicin and amikacin elute effectively from PMMA and HAC.     

Potent analgesic effects of GDNF in neuropathic pain states

Neuropathic pain arises as a debilitating consequence of nerve injury. The etiology of such pain is poorly understood, and existing treatment is largely ineffective. We demonstrate here that glial cell line-derived neurotrophic factor (GDNF) both prevented and reversed sensory abnormalities that developed in neuropathic pain models, without affecting pain-related behavior in normal animals. GDNF reduces ectopic discharges within sensory neurons after nerve injury. This may arise as a consequence of the reversal by GDNF of the injury-induced plasticity of several sodium channel subunits. Together these findings provide a rational basis for the use of GDNF as a therapeutic treatment for neuropathic pain states.     

Activation of integrin alphaIIbbeta3 by modulation of transmembrane helix associations

Transmembrane helices of integrin alpha and beta subunits have been implicated in the regulation of integrin activity. Two mutations, glycine-708 to asparagine-708 (G708N)and methionine-701 to asparagine-701, in the transmembrane helix of the beta3 subunit enabled integrin alphaIIbbeta3 to constitutively bind soluble fibrinogen. Further characterization of the G708N mutant revealed that it induced alphaIIbbeta3 clustering and constitutive phosphorylation of focal adhesion kinase. This mutation also enhanced the tendency of the transmembrane helix to form homotrimers. These results suggest that homomeric associations involving transmembrane domains provide a driving force for integrin activation. They also suggest a structural basis for the coincidence of integrin activation and clustering.     

Permeability and structure of junctional membranes at an electrotonic synapse

The dye Procion Yellow M4RS crosses junctional membranes from cytoplasm to cytoplasm at electrotonic synapses between segments of the crayfish septate axon. The dye does not enter the cells from extracellular space. Thus permeability of junctional membranes is qualitatively different from that of nonjunctional membranes. Electron microscopy after fixation in the presence of lanthanum hydroxide indicates that these synapses are "gap junctions" and that there is a network of channels continuous with extracellular space between apposed junctional membranes. These channels must be interlaced with intercytoplasmic channels that are not open to extracellular space.     

A survey to identify economic opportunities for smallholder dairy farms in Bangladesh

Identified economic opportunities for planning interventions greatly increase farmers’ compliance with an extension programme. We investigated opportunities for interventions to increase dairy farmers’ income in four areas of Bangladesh, including the districts of Mymensingh, Khulna-Satkhira, Sirajgonj-Pabna and Chittagong. The data were collected from 1440 dairy farms at a one-day visit and were summarized as the difference between management targets and each herd’s calculated management indices. The average number of lactating cows, feed cost as a percentage of income from milk, milk sold as percentage of milk produced, lactating cows as a percentage of mature cows, and lactating cows as a percentage of total cattle varied from 1.5 to 3.4, from 52.5% to 92.1%, from 78.7% to 92.6%, from 81.9% to 86.7% and from 34.3% to 37.7%, respectively. The average age at first calving, calf production interval, lactation length, and milk production were 35.0–44.3 months, 14.0–17.6 months, 249–286 days and 3.5–7.2 litres, respectively, depending on the locality. The average cost for producing 100 litres of milk was 18.9–35.1 US dollars. The production cost increased when daily milk production per cow decreased (r² = 0.43–0.55). Management improvements directed towards increasing average milk production per cow per day, increasing lactation length, decreasing age to first calving, and decreasing calf production interval could expect to yield an average income increase up to a range of 676.3–1730.6 US dollars depending on the milk-producing area.