Prokinetic agents in postgastrectomy patients

Postgastrectomy syndromes are uncommon but, unfortunately, frustrating for both patient and physician, because treatment with prokinetic agents is often of limited benefit. This article examines the evidence for efficacy of available prokinetic drugs in the management of these difficult disorders.     

In vivo studies of an implantable energy convertor for skeletal muscle powered cardiac assist

A device that harnesses the mechanical energy of skeletal muscle contracting in a linear configuration has been implanted in goats. This energy convertor transforms muscle work to hydraulic energy that could drive a variety of cardiac assist devices. The device is mounted with a rib clamp and plate affixed to the sternum by cortical bone screws. A transcutaneous hydraulic line carries a silicon based working fluid to an external system that controls the muscle load. In 60 to 70 kg goats, the latissimus dorsi insertion was reattached to the energy convertor. A Telectronics myostimulator with intramuscular electrodes stimulated the latissimus dorsi. In acute implants, hydraulic pressures in excess of 150 psi were obtained. Chronic implantation of the device allowed system evaluation in the conscious unanesthetized animal. Two weeks after implant, hydraulic pressures in excess of 200 psi were obtained and energy transferred to the external loading system exceeded 1 J per contraction. Six weeks after implant, the device continued to cycle freely. These initial results are very promising and suggest an implantable energy convertor is feasible. Development of an energy convertor is an important step toward tether-free skeletal muscle powered cardiac assist devices.     

Glial development in the Drosophila CNS requires concomitant activation of glial and repression of neuronal differentiation genes

Two classes of glial cells are found in the embryonic Drosophila CNS, midline glial cells and lateral glial cells. Midline glial development is triggered by EGF-receptor signalling, whereas lateral glial development is controlled by the gcm gene. Subsequent glial cell differentiation depends partly on the pointed gene. Here we describe a novel component required for all CNS glia development. The tramtrack gene encodes two zinc-finger proteins, one of which, ttkp69, is expressed in all non-neuronal CNS cells. We show that ttkp69 is downstream of gcm and can repress neuronal differentiation. Double mutant analysis and coexpression experiments indicate that glial cell differentiation may depend on a dual process, requiring the activation of glial differentiation by pointed and the concomitant repression of neuronal development by tramtrack.     

Evidence for the presence of sodium- and potassium-dependent adenosine triphosphatase alpha1 and beta1 subunit isoforms and their probable role in blastocyst expansion in the preattachment horse conceptus

Two Caribbean hair sheep breeds, the St. Croix (SC) and Barbados Blackbelly (BB), are found in the United States, and the SC has led to the development of the Katahdin (K), a synthetic breed of hair sheep. These breeds have mature ewe BW ranging from 32 to 54 kg (for BB and SC) and from 55 to 73 kg (K). Hair sheep and hair sheep crosses have lower rectal temperatures and respiration rates than wool breeds and a lower DMI and water intake. There are indications of increased resistance to internal parasites in hair sheep. Although hair sheep are seasonal breeders under U.S. photoperiodic conditions, they tend to perform better under accelerated lambing systems than traditional wool breeds. Fertility, prolificacy, and lamb survival is high in BB and SC, but hair x wool crossbred ewes tend to have a higher level of fertility than hair and wool parent breeds. Ewe productivity is also higher in hair x wool crosses than in wool crosses, particularly when adjusted for ewe BW or under accelerated lambing systems. Hair sheep have a lower ADG and intake of high-energy diets, as well as a lower gain/feed ratio, than wool breeds. Growth rates tend to be higher in SC than in BB. Differences in carcass characteristics are inconsistent between hair and wool breeds. Production characteristics of hair sheep, particularly hair x wool crosses, make them suitable for low-input, sustainable production systems that do not require high growth rates and large carcasses. There is a need to preserve the existing U.S. hair sheep germplasm base in support of such systems.     

8-epi PGF2 alpha generation during coronary reperfusion. A potential quantitative marker of oxidant stress in vivo

BACKGROUND: Myocardial reperfusion is believed to be associated with free radical injury. However, indexes of oxidative stress in vivo have been limited by their poor specificity and sensitivity. Isoprostanes are stable products of arachidonic acid formed in a nonenzymatic, free radical-catalyzed manner. We have developed a sensitive and specific assay for one of these compounds, 8-epi prostaglandin (PG) F2 alpha. METHODS AND RESULTS: To address its utility as an index of oxidative stress during coronary reperfusion, we measured urinary levels by gas chromatography/mass spectrometry in a canine model of coronary thrombolysis, in patients with acute myocardial infarction treated with thrombolytic therapy, and in patients after elective coronary artery bypass surgery. Urinary 8-epi PGF2 alpha was unchanged after circumflex artery occlusion in a canine model of coronary thrombolysis (n = 13; 437.2 +/- 56.4 versus 432.7 +/- 55.2 pmol/mmol creatinine) but increased significantly (P < .05) immediately after reperfusion (553.8 +/- 64.7 pmol/mmol). Urinary levels were increased (P < .001) in patients (n = 12) with acute myocardial infarction given lytic therapy (265.8 +/- 40.8 pmol/mmol) compared with age-matched control subjects (n = 20; 91.5 +/- 11.8 pmol/mmol) and patients with stable coronary disease (n = 20; 95.7 +/- 6.3 pmol/mmol). Preoperative levels rose from 113.2 +/- 11.8 to 248.2 +/- 86.3 pmol/mmol at 30 minutes into revascularization to 332.2 +/- 82.6 pmol/mmol by 15 minutes after global myocardial reperfusion (P < .05) and dropped to 181.2 +/- 50.4 pmol/mmol at 30 minutes and 120.2 +/- 9.9 pmol/mmol at 24 hours after bypass surgery (n = 5). Corresponding changes in spin adduct formation, found with electron paramagnetic resonance, were noted in 2 patients. CONCLUSIONS: These data support the hypothesis that free radical generation occurs during myocardial reperfusion. Measurement of isoprostane production may serve as a noninvasive index of oxidative stress.     

Scarring trachoma is associated with polymorphism in the tumor necrosis factor alpha (TNF-alpha) gene promoter and with elevated TNF-alpha levels in tear fluid

Tumor necrosis factor alpha (TNF-alpha) may play a central role in the disease pathogenesis which occurs as a consequence of chlamydial infection. To investigate the importance of TNF-alpha gene promoter polymorphisms and TNF-alpha levels in tear fluid in scarring trachoma, a large matched-pair case-control study was performed in The Gambia. The -308A allele was present in a higher proportion of patients (28.4%) than controls (18.4%), with an increasing association for homozygotes (chi2 for trend, P = 0.032; allele frequency, 0.163 in patients and 0.099 in controls; chi2, P = 0.025). For the -238A allele, the association was similar but not significant. The disease association was highly significant when the number of either -308A or -238A sites in an individual was considered (P = 0.003). TNF-alpha promoter alleles are tightly linked to some HLA class I and II alleles, but multivariate analysis confirmed that the disease associations were independent of HLA, although a class I allele, A*6802, is also associated with disease. TNF-alpha was more frequently detected in tear samples from patients (27.6%) than from controls (15.9%), increasingly so for higher levels of detectable TNF-alpha (P = 0.015). Among patients, detectable TNF-alpha in tears was highly associated with the presence of ocular chlamydial infection (P < 0.001). The results indicate that TNF-alpha plays a major role in the tissue damage and scarring which occurs as a consequence of Chlamydia trachomatis infection.     

Differential divalent cation requirements uncouple the assembly and catalytic reactions of human immunodeficiency virus type 1 integrase

Previous in vitro analyses have shown that the human immunodeficiency virus type 1 (HIV-1) integrase uses either manganese or magnesium to assemble as a stable complex on the donor substrate and to catalyze strand transfer. We now demonstrate that subsequent to assembly, catalysis of both 3' end processing and strand transfer requires a divalent cation cofactor and that the divalent cation requirements for assembly and catalysis can be functionally distinguished based on the ability to utilize calcium and cobalt, respectively. The different divalent cation requirements manifest by these processes are exploited to uncouple assembly and catalysis, thus staging the reaction. Staged 3' end processing and strand transfer assays are then used in conjunction with exonuclease III protection analysis to investigate the effects of integrase inhibitors on each step in the reaction. Analysis of a series of related inhibitors demonstrates that these types of compounds affect assembly and not either catalytic process, therefore reconciling the apparent disparate results obtained for such inhibitors in assays using isolated preintegration complexes. These studies provide evidence for a distinct role of the divalent cation cofactor in assembly and catalysis and have implications for both the identification and characterization of integrase inhibitors.