A New Bioassay Platform Design for the Discovery of Small Molecules with Anticancer Immunotherapeutic Activity

Immunotherapy takes advantage of the immune system to prevent, control, and eliminate neoplastic cells. The research in the field has already led to major breakthroughs to treat cancer. In this work, we describe a platform that integrates in vitro bioassays to test the immune response and direct antitumor effects for the preclinical discovery of anticancer candidates. The platform relies on the use of dendritic cells that are professional antigen-presenting cells (APC) able to activate T cells and trigger a primary adaptive immune response. The experimental procedure is based on two phenotypic assays for the selection of chemical leads by both a panel of nine tumor cell lines and growth factor-dependent immature mouse dendritic cells (D1). The positive hits are then validated by a secondary test on human monocyte-derived dendritic cells (MoDCs). The aim of this approach is the selection of potential immunotherapeutic small molecules from natural extracts or chemical libraries.     

Sex reversal and growth performance in juvenile females of the freshwater crayfish <Emphasis Type="Italic">Cherax quadricarinatus</Emphasis> (Parastacidae): effect of increasing temperature and androgenic gland extract in the diet

Monosex male culture of C. quadricarinatus is proposed for increasing yields because males reach a larger size at harvest than females. An experiment was done to evaluate the effects of androgenic gland extract and temperature on sex reversal and somatic growth in early juvenile females. Females were exposed to the following experimental conditions: C: control food and temperature maintained at 26 ± 1°C; HT (high temperature): control food and temperature maintained at 28.5 ± 1°C; VHT (very high temperature): control food and temperature maintained at 31 ± 1°C; AG: food with enriched with androgenic gland (1/10 dose for each juvenile per day) and temperature maintained at (26 ± 1)°C. The juveniles were weighed, sexed, and growth increment (GI) and growth rate (GR) were calculated twice a month. The HT and AG groups differed from the C group in GI and GR indicating a greater somatic growth. At the end of the experiment, the HT and AG groups had similar weight but only the HT group had enhanced oocyte diameter, with some vitellogenic oocytes compared to the C group. In the HT group, there was significant sex reversal, as indicated by development of male and intersex male characteristics in different individuals. Both temperature and AG diet have a high potential for culture of this species because of their enhancement of somatic growth; higher temperature increases the proportion of males, a desirable characteristic of cultured populations.     

Effect of dietary protein:energy ratio on intake, growth and metabolism of juvenile green abalone Haliotis fulgens

Juvenile green abalone Haliotis rufescens were grown under laboratory conditions at 21±1 °C and fed formulated diets consisting of different protein:energy ratios (mg protein/kcal), 62, 74, 85, 100, 108, for 60 days. The level of crude protein ranged from approximately 26% to 44% while the energy content remained constant at about 4.1 kcal g⁻¹. Growth ranged from 3.63 to 12.33 mg day⁻¹. The growth of abalone fed the 100 and 108 diets was significantly greater than that of each of the other diets. Protein efficiency ratio increased as the dietary protein content increased except for the T108 diet (44% crude protein). Abalone apparently consume food to satisfy an energy requirement. Caloric expenditure due to metabolism was estimated for abalone fed diets with protein ratios of 62, 85, 100. Energy loss due to respiration did not vary appreciably among abalone fed the different diets. The proportional distribution of dietary energy into fecal, digestible, growth, and metabolic energy was estimated for abalone fed these diets. Apparent dry matter digestibility was among the lowest for abalone fed the 100 P:E diet, but growth of abalone fed this diet was significantly higher than that of each of the other treatments except the 108 diet. Unexplained energy loss to achieve balance ranged from 7% to 28.5%, some of which is probably due to differential mucus and ammonia production. Results suggest a potential for the reduction of both dietary protein and lipid without causing any adverse effects on the growth response.     

Larval traits of the Caribbean amphidromous goby Sicydium punctatum (Gobioidei: Sicydiinae) in Guadeloupe

Amphidromous fish are the biggest contributor to the diversity of fish communities in river systems of Caribbean islands. Among them, Sicydium punctatum Perugia, 1896, which is endemic to the West Indies, represents the vast majority of fish in these rivers. The otolith microstructure and the biometry of S. punctatum postlarvae from Guadeloupe were investigated to explore the dispersal modalities of this species through an appreciation of the growth pattern, the pelagic larval duration (PLD) and the size‐at‐recruitment. The study was made on one cohort of 83 recruited postlarvae, fished at the Capesterre River's mouth on 2 November 2011. The mean (±SD) size‐at‐recruitment of the postlarvae was 24.6 ± 1.3 mm (range of 20.5–28.1 mm, n = 83). We found a mean (±SD) PLD of 72.2 ± 10.5 days (range of 54–101.5 days, n = 67). The growth rate estimated from the otolith increments showed a globally decreasing pattern during the marine larval phase. Growth rates at the beginning of the larval stage were significantly different between hatching periods, suggesting a relation between the hatching period and the growth rate in S. punctatum. This study adds on to the general understanding of the life cycle of S. punctatum in Guadeloupe that will help implement strategies to manage amphidromous fish populations in the Caribbean region.     

Structure—activity relationships of organotin biocides and Ceratocystis ulmi

The effect of organotin compounds on the growth of Ceratocystis ulmi, the causative agent of Dutch elm disease, was studied in shake culture. Triphenyltin, (C₆H₅)₃SnX, tricyclohexyltin, (C₆H₁₁)₃SnX, and tributyltin, (C₄H₉)₃SnX, compounds were all effective in the inhibition of C. ulmi in vitro. The anionic group, X, did not play a major role in the inhibitory activities of these compounds, suggesting that the species involved in the inhibition is R₃Sn⁺ or the hydrated cation.     

Evaluation of an air-filtration system for preventing aerosol transmission of Porcine reproductive and respiratory syndrome virus

The purpose of this study was to evaluate the ability of a commercial air-filtration system to reduce aerosol transmission of Porcine reproductive and respiratory syndrome virus (PRRSV). The system consisted of a pre-filter and 2 filters with EU8 and EU13 ratings. In each of 4 trials, 5 PRRSV-infected donor pigs and 1 naive recipient pig (each 25 kg) were housed in opposing chambers connected by a 1.3-m-long duct. The system filtered air entering 1 recipient-pig chamber (filtered facility) from the donor-pig chamber but not a 2nd recipient-pig chamber (nonfiltered facility). The donor pigs had been experimentally infected with PRRSV MN-184, an isolate previously documented to be shed at a high frequency in contagious aerosols. On days 3 to 7 after infection of the donors, the 2 groups were housed in their respective chambers for 6 h and then in separate facilities, where samples were collected for testing by polymerase chain reaction and enzyme-linked immunosorbent assay over 14 d. Aerosol transmission was observed in 6 of the 20 replicates in the nonfiltered facility, whereas all pigs remained PRRSV-negative in the filtered facility; the difference was significant at P < 0.01. Thus, under the conditions of this study, the air-filtration system evaluated appeared to be highly effective at reducing aerosol transmission of PRRSV.     

Prophylactic use of decoquinate for infections with Cryptosporidium parvum in experimentally challenged neonatal calves

OBJECTIVE: To evaluate the effect of daily oral administration of decoquinate to neonatal calves experimentally challenged with various numbers of Cryptosporidium parvum oocysts. DESIGN: Clinical trial. ANIMALS: 75 calves. PROCEDURE: Calves were purchased from a commercial dairy during a 5-week period. Calves were housed in individual hutches and fed milk replacer with or without decoquinate (2 mg/kg [0.9 mg/lb per day]). Calves were randomly assigned to treatment and 1 of 5 challenge groups (0, 50, 100, 1000, or 10,000 C. parvum oocysts in 60 mL of saline [0.9% NaCl] solution administered p.o. on the day after arrival). Calves were maintained in the study for as long as 28 days. Calves were clinically assessed for diarrhea and dehydration. Fecal samples were submitted for oocyst enumeration 3 times each week. RESULTS: Treatment did not affect number of days to first watery feces (diarrhea), number of days to first oocyst shedding, or duration of diarrhea or oocyst shedding. Duration of oocyst shedding was significantly associated with challenge dose of oocysts administered to calves and number of days to first oocyst shedding. Duration of diarrhea and number of days to first oocyst shedding were significantly associated with week of arrival and number of days to first watery diarrhea. CONCLUSIONS AND CLINICAL RELEVANCE: Daily treatment with decoquinate at the dosage used in this study did not affect oocyst shedding or clinical signs associated with cryptosporidiosis. However, there was an indication that if the number of oocysts calves received could be reduced, then the duration of oocyst shedding and, hence, environmental loading of C. parvum oocysts could be reduced.     

Myasthenia gravis and masticatory muscle myositis in a dog

A 21-month-old, castrated male Vizsla was presented for pelvic limb weakness, difficulty opening his mouth, ptyalism, voice change, and urinary incontinence. Myasthenia gravis and masticatory myositis were diagnosed. The unusual clinical findings, diagnosis, treatment, and case outcome are described, followed by a brief discussion of myasthenia gravis and masticatory myositis.     

Tetralogy of Fallot in a 2-year-old Holstein heifer

A 2-year-old, purebred Holstein heifer with exercise intolerance and cardiovascular compromise was diagnosed at postmortem with tetralogy of Fallot, which typically results in death within a few months of life. Survival past the age of 2 was unexpected. The concurrent endocarditis of the pulmonic valve is discussed.