Development and characterization of two GP-specific monoclonal antibodies, which synergistically protect non-human primates against Ebola lethal infection.

Ebola fever is an acute highly contagious viral disease characterized by severe course, high mortality and development of hemorrhagic syndrome (tendency to skin hemorrhage and bleeding of mucous membranes). The mortality rate of the disease 60-90%. Nowadays, there are no licensed specific therapeutic agents for Ebola in the world. Monoclonal antibodies (MAbs) having viral neutralizing activity with high specificity to the GP protein of the Ebola virus are considered as candidate highly effective antiviral drugs. In our study, for the first time a panel of mouse monoclonal antibodies specifically binding to EBOV GP protein was obtained using recombinant human adenovirus 5 serotype, expressing GP protein (Ad5-GP). The virus-neutralizing capacities of antibodies were evaluated on the Ebola virus cell infection model, as well as recombinant vesicular stomatitis virus pseudotyped by GP Ebola virus protein (rVSV-GP) cell infection model. Based on the results of virus neutralization, two most promising clones were selected, the specific and protective capacities of which were determined. The study of the protection of selected individual antibody clones, as well as their combinations on the model of lethal infection of rhesus macaques with Ebola virus showed that intravenous administration of a mixture of antibodies in the amount of 50 mg/kg 24 h after infection leads to the survival of 100% of the animals, while individual clones of antibodies possess partial protection (0-30%). The results of the study suggest the important role of antibodies in controlling replication of the Ebola virus in vivo and show the possibility of using a mixture of antibodies specific to the GP to protect against lethal infection with the Ebola virus in the post-infected mode of administration.

(+/-)-1-(2,5-Dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and serotonin-1A receptors.

Serotonergic behavioral responses, effects on motor activity and core temperature, and binding properties of the novel putative anxiolytic amphetamine derivative (+/-)1-(2,5-dimethoxy-4-ethylthio-phenyl)-2-aminopropane (ALEPH-2), were examined in rodents in order to elucidate the mechanism underlying its anxiolytic-like effect. After peripheral administration in rats, ALEPH-2 induced some symptoms of the serotonergic syndrome, e.g. forepaw treading and flat body posture. Additionally, a decrease in motor activity was observed. No significant effects on the number of head shakes were observed after injection, although high inter-subject variability was noted. Higher doses of ALEPH-2, in the range exhibiting anxiolytic properties (4mg/kg), elicited significant hypothermia in mice. The affinity of the drug for 5-HT2A/2C receptors ([3H]ketanserin sites) was in the nanomolar range (Ki = 173 nM), whereas for 5-HT1A, benzodiazepine sites, and GABAA receptors, the affinity was micromolar of lower. Based on these results the mechanism of action and the anxiolytic-like properties of ALEPH-2 are discussed.

The challenge of marketing wellness programs to small versus large firm employees.

The authors extend prior research by examining employee attitudes towards wellness programs among thirty-eight large and small companies in five states. Program components that were considered to be most desirable by workers at different sized companies are identified in a series of regression models. The results indicate that different sized firms can emphasize general wellness and aerobic exercise programs during the design phase of employee wellness programs. However, employees at large companies were more interested in early detection programs than small firm employees.

Marketing hospital wellness products to service companies.

The authors examine service firm employee attitudes towards wellness programs among twenty-three service companies in three states. Program components that were considered to be most desirable by service industry workers are identified in a regression model. The results indicate that hospital administrators need to adopt a marketing approach during the design phase of employee wellness programs.

Effect of moisture in total mixed rations on feed consumption and milk production and composition in Holstein cows.

The DM levels in total mixed rations were maintained at 62.7, 52.8, and 45.8% by incorporating 38% of the DM from alfalfa silages of twi different DM contents into the ration to determine the effect on milk production and composition when fed to lactating Holstein cows. The alfalfa silages were stored at approximately 25 and 50% DM and harvested from the same field on consecutive days either direct-cut and bagged or wilted overnight before bagging. Silages were used (minimum of 8.5 kg of Dm/d) in a total mixed ration formulated to be isonitrogenous (using cottonseed meal) and isocaloric and fed to 144 lactating cows randomly allotted into three equal groups based on days in milk (initially 33 d), lactation number, and pretrial 3.5% FCM production. Yields of 3.5% FCM were 35.3, 35.7 and 35.4 kg, respectively, for the dry, intermediate, and wet rations and were not significantly different. Consumption of DM tended to decline as DM content of the ration decreased, but the decrease was not significant. Results showed that total mixed ration moisture levels evaluated in this trial had no significant effects on consumption of DM of isonitrogenous rations or milk yield and composition.

Influence of protein percentage and degradability on performance of lactating cows during moderate temperature.

Sixty high producing Holstein cows (15/treatment) averaging 157 d postpartum were offered the following diets: high protein (18.5%), high rumen degradability (60%); high protein (18.0%), medium degradability (41%); medium protein (15.4%), high degradability (61%); medium protein (15.0%), medium degradability (46%). All diets contained 32% corn silage, 15% alfalfa haylage, and 10% whole cottonseed. Degradabilities were determined by the ficin method and were lowered by replacing soybean meal with meat and bone meal and brewers dried grains. Cows were milked three times daily and the study was conducted from May 11 to June 23 in Provo, UT during ascending day temperatures but cool nights. Milk yields were not different for the respective treatments (36.9, 35.4, 34.8, and 36.7 kg/d), but milk fat was higher at high protein degradability: 3.11, 2.89, 3.04, 2.78%, respectively, resulting in a tendency toward higher FCM. Lower acetate and propionate and acetate:propionate ratios were observed for medium degradability diets and were consistent with lower milk fat. Rumen NH3, butyrate, valerate, isovalerate, 2-methyl butyrate, and blood urea N were higher for cows on high protein diets but were not affected by degradability. Serum glucose and cortisol were not significantly affected by protein treatment, but serum triiodothyronine was lower on high protein; the interaction effect for thyroxine was significant.

Differences between consumers and psychiatrists in attitude toward advertising of psychiatric services.

Psychiatrist and consumer attitudes toward the advertising of psychiatric services are examined. The results indicate that consumers are consistently more favorable than psychiatrists toward psychiatric services advertising. Both groups felt that professional magazines are the most appropriate media for psychiatrists who advertise. The psychiatrists reported a higher level of exposure to advertising of psychiatric services than did the consumers. However, some apprehension about psychiatric services advertising also was reported. Managerial implications for advertising usage by the practicing psychiatrist are presented.

Consumer versus dentist attitudes toward dental services advertising.

The authors report the findings of a consumer survey and a dentist survey that were used to examine attitudes toward the advertising of dental services. The results clearly indicate positive consumer attitudes and negative dentist attitudes toward such advertising. Relatively few consumer demographic differences are noted, though younger dentists appear to have more positive attitudes toward dental services advertising than their older colleagues. The results suggest significant opportunities for dentists in dental services advertising.

Factors affecting rural consumers' satisfaction with medical care.

This study examines various factors which influence consumer satisfaction with medical care at a family practice office of a randomly generated sample of 259 rural households. Consumer perceptions regarding physician competence, seeing the same doctor on successive visits, and whether the physician's office is meeting the general medical needs of the community were important predictors of satisfaction. Marketing implications are suggested to increase the economic and professional viability of medical practice.