IL-13 protects from C. difficile colitis.

OBJECTIVES: Clostridioides difficile infection (CDI) is the leading hospital-acquired infection in North America. We have previously discovered that antibiotic disruption of the gut microbiota decreases intestinal IL-33 and IL-25 and increases susceptibility to CDI. We further found that IL-33 promotes protection through type 2 Innate Lymphoid Cells (ILC2s), which produce IL-13. However, the contribution of IL-13 to disease has never been explored. METHODS: We used a validated model of CDI in mice, in which we neutralized via blocking antibodies, or administered recombinant protein, IL-13 to assess the role of this cytokine during infection using weight and clinical scores. Fluorescent activated cell sorting (FACS) was used to characterize myeloid cell population changes in response to IL-13 manipulation. RESULTS: We found that administration of IL-13 protected, and anti-IL-13 exacerbated CDI. Additionally, we observed alterations to the monocyte/macrophage cells following neutralization of IL-13 as early as day three post infection. We also observed elevated accumulation of myeloid cells by day four post-infection following IL-13 neutralization. Neutralization of the decoy receptor, IL-13Rα2, resulted in protection from disease, likely through increased available endogenous IL-13. CONCLUSIONS: Our data highlight the protective role of IL-13 in protecting from more severe CDI and the association of poor responses with a dysregulated monocyte-macrophage compartment. These results increase our understanding of type 2 immunity in CDI and may have implications for treating disease in patients.

Prenatal ethanol exposure has differential effects on fetal growth and skeletal ossification.

There is increasing evidence suggesting that the intrauterine environment may influence long-term bone health and the risk of developing osteoporosis in later life. Alcohol (ethanol) is one factor whose presence in the prenatal environment has long-term consequences for the offspring, including permanent growth retardation. Moreover, prenatal ethanol exposure retards both fetal and postnatal bone development. It is unknown if ethanol's effects on skeletal development result from generalized growth retardation or effects specific to skeletal development. Furthermore, the level of ethanol exposure required to produce skeletal effects is unknown. The objectives of this study were to determine (1) if ethanol exerts specific effects on fetal skeletal development that are independent from its effects on general growth, and (2) the level of prenatal ethanol exposure required to affect fetal growth and skeletal ossification. Rats were fed isocaloric diets with ethanol (15%, 25%, or 36% ethanol-derived calories (EDC), approximating low, moderate, and high exposure levels), or without ethanol (pair-fed, PF, or control, C groups), prior to and throughout 21 days of gestation. The degree of E-induced delay in development was determined by comparison of E fetuses on d21 gestation to C fetuses on d17-d21 gestation. Prenatal ethanol exposure at 36% EDC decreased fetal body weight, length, and skeletal ossification compared with PF and C fetuses on d21 gestation. Importantly, effects on ossification, but not body weight or length, were also seen at the more moderate dose of 25% EDC, and the number of bones affected and the severity of effects on ossification tended to increase with dose of ethanol. Comparison of E fetuses on d21 gestation with C fetuses from d17 to 21 gestation indicated that the ethanol-induced delay in development differed for weight and skeletal ossification, and was not uniform among skeletal sites. Taken together, these data suggest that prenatal ethanol exposure has effects on fetal skeletal development that are independent of those on overall fetal growth, and that these effects occur even at moderate levels of maternal drinking. Effects of prenatal ethanol exposure on fetal skeletal development could potentially increase the offspring's risk of osteoporosis later in life.

Target-controlled propofol requirements at induction of anaesthesia: effect of remifentanil and midazolam.

BACKGROUND AND OBJECTIVE: Target-controlled infusions of anaesthetic agents have become increasingly available. They can involve the use of propofol in combination with an opioid or a benzodiazepine. The effect site concentration of propofol infusions has been advocated as a method of estimating drug distribution. We investigated the influence of co-induction with remifentanil and midazolam on effect site propofol requirements at induction of anaesthesia using target-controlled infusions. METHODS: Sixty-six consenting adult patients were randomly allocated to three treatment groups. Each group received induction of anaesthesia with a different total intravenous technique. One group was induced with target-controlled propofol alone; another received target-controlled propofol and target-controlled remifentanil (3 ng mL-1); and the last received midazolam (0.03 mg kg-1), target-controlled remifentanil (3 ng mL-1) and target-controlled propofol. Computer simulation was used to calculate effect site concentrations. We recorded propofol dose and effect site concentration at loss of verbal response. RESULTS: The effect site concentration (Ce50) of propofol alone was 2.19 micrograms mL-1. This was reduced to 1.55 micrograms mL-1 during co-induction with remifentanil and further reduced to 0.64 microgram mL-1 with midazolam premedication (P < 0.001; ANOVA). CONCLUSIONS: We conclude that co-induction with remifentanil alone or with midazolam can be used to reduce propofol doses at induction of anaesthesia using target-controlled infusions. We believe that using effect site concentration may prove a useful tool in routine clinical practice.

Type A behavior, field dependence, and serum lipids.

Given evidence that individual differences on the cognitive style dimension of field dependence/independence are significantly related to sympathetically mediated cardiovascular functioning and lipid metabolism, a correlational study was designed to examine associations between Type A behavior, field dependence, and serum lipids. It was hypothesized that field dependent Type A individuals would exhibit higher levels of total cholesterol and triglycerides than would field independent Type A individuals. Using 82 medical students as subjects, the hypothesis was supported among both males and females for total cholesterol, with a trend in the predicted direction for triglycerides. Field dependent Type A individuals of both sexes were also found to have a higher level of low-density lipoprotein to total cholesterol, when compared to their field independent Type A counterparts. The overall pattern of findings provides suggestive evidence that field dependence is an important mediating personality factor influencing levels of autonomic arousal and coronary risk among Type A individuals. Alternative explanations as to why field dependent Type A individuals may be more chronically aroused in response to environmental stimuli are discussed.

Pharmacokinetics of althesin--comparison with lignocaine.

The plasma concentrations of alphaxalone were measured with a gas chromatographic technique in six patients following a single i.v. injection of Althesin, and in five volunteers following oral administration. A two-compartment open model was used in the pharmacokinetic analysis of the data, and the plasma clearance of alphaxalone was similar to the blood flow through the liver. A comparison with the pharmacokinetics of lignocaine was made.

Weight increase of cotton fibers during swelling in alkali as a sensitive measure of cellulose degradation in ruminal fluid.

Weight increase of cotton fiber in an 18% NaOH solution, termed "alkali-centrifuge" or "AC" value, was measured after incubation of either 1 g or 100 mg of the fiber in ruminal fluid. The AC response was a sensitive measure of cellulolytic activity. Thus, fiber incubated at 21 and 51 degrees C exhibited major AC increases even when direct weight losses of the unswollen fiber were less than 2%. Similarly, progressive additions of acetic acid to ruminal fluid progressively depressed both AC response and direct weight loss, but the former was still easily measurable when the latter was not. In tightly closed, completely filled vials with high ratio of ruminal fluid to sample, AC increased greatly and rapidly, i.e., in 6 h. This time could be further reduced to 2 h by overnight "preincubation" of the ruminal fluid with cotton fiber before starting the test incubation. Certain surfactants used to aid wetting of the fiber had a low but measurable potency in inhibiting cellulose digestion, but other surfactants were non-inhibitory. The AC response was maintained when ruminal fluid was diluted with an equal amount of McDougall's "artificial saliva" solution.

Effects of trace metals on the production of aflatoxins by Aspergillus parasiticus.

Certain metals added as salts to a defined basal culture medium influenced the level of aflatoxin production by Aspergillus parasiticus in the low micrograms-per-milliliter range of the added metal. In many cases no change or a relatively small change in mat weight and final pH of the medium accompanied this effect. With zinc at added levels of 0 to 10 mug/ml in the medium, aflatoxin increased 30-to 1,000-fold with increasing of zinc, whereas mat weight increased less than threefold. At 25 mug of added zinc per ml, aflatoxin decreased, but mat weight did not. At an added level of 25 mug or less of the metal per ml, salts of iron, manganese, cooper, cadmium, trivalent chromium, silver, and mercury partly or completelyinhibited aflatoxin production, without influencing mat weight.

Fungi that infect cottonseeds before harvest.

As a part of an investigation of aflatoxins and other mycotoxins in cottonseeds at harvest, samples of seeds collected from the 1971 crop at locations across the U.S. Cotton Belt were examined to determine the kinds of microorganisms causing internal or seed-coat infection in the field. Aspergillus flavus infection was absent from all seeds examined from most areas but was present in some samples from Arizona, California, and Texas. Fusarium spp., Alternaria sp., and A. niger caused internal infection at many locations; Colletotrichum gossypii and Rhizopus stolonifer were present in seeds from some areas but were generally much less common. Many of the infections with A. niger were in the seed coat. Bacterial infections were fairly frequent. In a series of commerical samples from Arizona. A. flavus infection was found in 61% of seeds, with fiber showing the bright, greenish-yellow (BGY) fluorescence that is diagnostic for A. flavus boll rot. Aflatoxin contamination was also concentration in the same seeds. The above findings agree with previous data showing that aflatoxin contamination of cottonseeds before harvest occurs rarely, if at all, in most parts of the U.S. Cotton Belt and that when such contamination does occur, it tends to be concentrated in seeds with the BGY fluorescence in their fiber and seed fuzz.