Efficacy of Copper and New Bactericides for Managing Olive Knot in California.

Baseline sensitivities were established for kasugamycin and oxytetracycline for 147 strains of Pseudomonas savastanoi pv. savastanoi collected from olive knots throughout California. Minimum inhibitory concentrations for ≥95% growth inhibition ranged from 1.86 to 11.52 and 0.13 to 0.40 µg/ml for kasugamycin and oxytetracycline, respectively. In copper sensitivity evaluations, 95.3% of the strains collected grew at concentrations of metallic copper equivalent (MCE) of <20 µg/ml, 2.7% grew at MCE between 20 and 30 µg/ml (moderately sensitive), and 2% grew at MCE of 150 µg/ml (resistant). Copper resistance was never reported previously in the olive knot pathogen, and pathogenicity studies confirmed a high virulence of the copper-resistant strains. In comparative field studies, kasugamycin at 200 µg/ml performed equally to the standard copper hydroxide treatment (MCE of 1,260 µg/ml) for reducing knot development on lateral wounds of Arbequina and Manzanillo olive inoculated with a copper-sensitive strain and was better than copper using a highly copper-resistant strain. Oxytetracycline at 200 µg/ml was not as effective as copper or kasugamycin but significantly reduced the disease as compared with the untreated control. Field studies on application timings of copper, kasugamycin, and copper-kasugamycin mixtures to inoculated wounds indicated that treatments within 24 h of inoculation resulted in higher disease control than applications at later times. In greenhouse trials, copper or copper-kasugamycin applied to wounds 7 days before inoculation persisted and reduced knot incidence by >50%. Our findings indicate that kasugamycin is an effective bactericide for controlling olive knot and that the time of any bactericide application after inoculation is critical in managing the disease.

Quaternary Ammonium Compounds as New Sanitizers for Reducing the Spread of the Olive Knot Pathogen on Orchard Equipment.

Olive knot, caused by the wound pathogen Pseudomonas savastanoi pv. savastanoi, is a serious bacterial disease that can be disseminated by orchard equipment. Greenhouse studies confirmed that cutting tools contaminated during contact with olive knots are able to spread the pathogen to healthy olive tissue. Quaternary ammonium compounds (QACs) were assessed as sanitizing agents for contaminated equipment as a disease management strategy. In laboratory in vitro tests, QACs exhibited high toxicity against the bacterium over a broad pH range from 6 to 9 using short exposure periods (15 to 60 s) and low concentrations (5 µg/ml). QACs applied to contaminated hard surfaces in the presence of an organic load reduced bacterial recovery by ≥3.6 log10 CFU/ml. In field trials, sanitation of hedging equipment that was contaminated with the pathogen (2 × 107 CFU/ml) and used to prune olives, was successful and sometimes completely prevented new infections from occurring. Application of additional foliar spray treatments of copper or copper-kasugamycin mixtures after hedging significantly improved disease control. In laboratory and field studies, sodium hypochlorite was significantly less effective than QAC compounds in the presence of organic matter. A nonphenolic QAC formulation, however, was ineffective as a preventative treatment when applied prior to inoculation of olive wounds, whereas a copper hydroxide application was highly effective. Based on data from this research, a QAC formulation was registered for field use as a sanitizer for olive equipment in California in 2015.

Pattern of distribution of Prevotella species/phylotypes associated with healthy gingiva and periodontal disease.

The purpose of the present study was to obtain diverse profiles of Prevotella species associated with gingival sites in an isolated Aboriginal and an urban community by phylogenetic analysis and to establish patterns of association of identified Prevotella species in gingival sites. Species/phylotypes identified from the phylogenetic analysis of near full-length Bacteroidetes 16S rRNA gene sequences cloned from subgingival plaque samples obtained from an Aboriginal community were compared with those from an ethnically diverse urban metropolitan population suffering from periodontal disease. Specific primer sets were designed and validated for 22 distinct Prevotella species from the 24 species/phylotypes identified from both populations. Within the isolated Aboriginal community, gingival sites in adults were colonised by a mean of 15 different Prevotella species. Prevotella sp. oral clone P4PB24, Prevotella intermedia, Prevotella oralis, Prevotella denticola and Prevotella sp. strain P4P62 had the highest association with increasing probing depth in diseased sites (p < 0.05). P. intermedia and Prevotella sp. oral clone P4PB24, the Prevotella species significantly associated with increasing probing depth in diseased gingival sites and also strongly associated with P. gingivalis load (p < 0.05) in diseased gingival sites, showed significant correlation for co-colonisation (r = 0.6). Prevotella sp. oral clone B31FD, showing strong association with P. gingivalis load (p < 0.05) in diseased gingival sites, showed no significant correlation for co-colonisation with any other Prevotella species. This study provides a comprehensive analysis of Prevotella species associated with gingival sites for the informative evaluation of the epidemiology of infection by this genus.

Effective Dose Measurements of the Latest-Generation Angiographic System in Patients with Acute Stroke: A Comparison with the Newest Multidetector CT Generation.

BACKGROUND AND PURPOSE: Patients with acute ischemic stroke are increasingly triaged with one-stop management approaches, resulting in baseline imaging with a flat detector CT scanner. This study aimed to estimate the effective dose to a patient of a novel cervical and intracranial flat detector CT angiography and a flat detector CT perfusion protocol and to compare it with the effective dose of analogous multidetector row CT protocols. MATERIALS AND METHODS: We estimated the effective dose to the patient according to the International Commission on Radiological Protection 103 using an anthropomorphic phantom with metal oxide semiconductor field effect transistor dosimeters. Placement was according to the organ map provided by the phantom manufacturer. We used 100 measurement points within the phantom, and 18 metal oxide semiconductor field effect transistor dosimeters were placed on the surface of the phantom. All protocols followed the manufacturer's specifications, and patient positioning and collimation were performed as in routine clinical practice. Measurements were obtained on the latest-generation angiography and multidetector row CT systems with identical placement of the metal oxide semiconductor field effect transistor dosimeters. RESULTS: The estimated effective doses of the investigated perfusion protocols were 4.52 mSv (flat detector CT perfusion without collimation), 2.88 mSv (flat detector CT perfusion with collimation), and 2.17 mSv (multidetector row CT perfusion). A novel protocol called portrait flat detector CT angiography that has a z-axis coverage area comparable with that of multidetector row CT angiography had an estimated effective dose of 0.91 mSv, while the dose from multidetector row CT was 1.35 mSv. CONCLUSIONS: The estimated effective dose to the patient for flat detector CT perfusion and angiography on a modern biplane angiography system does not deviate substantially from that of analogous multidetector row CT protocols.

Breakdown of B cell tolerance in a mouse model of systemic lupus erythematosus.

Anti-DNA antibodies, specifically those that stain nuclei in a homogenous nuclear (HN) fashion, are diagnostic of systemic lupus erythematosus (SLE) and the MRL-lpr/lpr SLE murine model. We have used a heavy chain transgene that increases the frequency of anti-HN antibodies to address whether their production in SLE is the consequence of a defect in B cell tolerance. Anti-HN B cells were undetectable in nonautoimmune-prone transgenic mice, but in MRL-lpr/lpr transgenic mice their Ig was evident in the sera and they were readily retrievable as hybridomas. We conclude that nonautoimmune animals actively delete anti-HN-specific B cells, and that MRL-lpr/lpr mice are defective in this process possibly because of the lpr defect in the fas gene.

Adverse events related to ibuprofen treatment for patent ductus arteriosus in premature neonates.

OBJECTIVE: Our study aimed to review adverse drug reactions (ADRs) associated with ibuprofen treatment of patent ductus arteriosus (PDA) in premature neonates. METHOD: We retrospectively evaluated electronic patient records from neonates treated with ibuprofen for PDA during 5 years in a French neonatal intensive care unit. Full chart review and targeted triggers were used to detect ADRs. The causality between suspected ADRs and medication was evaluated using the WHO causality assessment method by pharmacovigilance experts. Categorical variables were compared using chi-square tests or Fisher's test. Quantitative variables were compared using the Student t test. We explored the risk factors associated with ADR using univariate model analysis. RESULT: Of 227 infants with a mean gestational age (GA) of 27 weeks (24-33), 12 (5%) developed intestinal perforation and seven, necrotizing enterocolitis (3%). The perforation occurred less frequently in infants older than 27 weeks GA (OR=0.14; 95% CI=0.03-0.66, P=0.01). Other observed ADRs were acute renal failure (25 infants, 11%) and thrombocytopenia (five infants, 2%). CONCLUSION: Gastrointestinal complications observed in infants treated with ibuprofen for PDA including gastrointestinal perforations occur in less mature infants. Active chart review of the patient's medical file with a trigger tool should be evaluated for routine ADR monitoring.

[Active drug monitoring of adverse drug reactions in pediatric emergency department]. / Recueil systématique et actif des évènements indésirables médicamenteux chez les enfants admis aux urgences pédiatriques.

OBJECTIVES: The aim of this study was to systematically evaluate adverse drug reactions (ADRs) in children consulting at the pediatric emergency unit during a 6-month period. METHOD: The regional pharmacovigilance center (CRPV) and the department of clinical pharmacology prospectively and systematically recorded all potential ADRs among patients younger than 18 years of age in the pediatric emergency unit reported at the daily staff meetings. All cases were then screened and validated by the CRPV. For validated cases, preventability, seriousness, and off-label use were evaluated. RESULTS: During the study period, from 1 March to 1 September 2005, 90 children presented potential adverse drug events. ADRs were confirmed in 43 patients, 19 females and 24 males. Thirty-four patients (79%) were under the age of 5. According to the European definition, 14 patients (33%) had serious ADRs. One anaphylactic shock after amoxicillin injection; antimalarial prophylaxis misuse leading to convulsive status epilepticus, convulsion, and coma after hepatitis B and MMR vaccines were deemed life-threatening. Three ADRs were considered avoidable. Antibiotics and vaccines were the most common possible cause of ADRs (76%). Skin reactions (n=27), fever (n=8), and gastric disorders (n=5) were the most common clinical manifestations. CONCLUSIONS: Because ADRs were reported by clinicians on a voluntary basis, serious ADRs were probably reported more systematically. Compared to a similar period without active monitoring, active drug monitoring of ADRs doubled the number of confirmed cases 43 vs 17, p<0.001. Close collaboration between the pharmacovigilance center, pharmacologists, and clinicians is necessary and seems feasible for improving the monitoring of ADRs in children.

Postsurgery analgesic and sedative drug use in a French neonatal intensive care unit: A single-center retrospective cohort study.

OBJECTIVE: To describe pain assessment, the pattern of analgesic and sedative drug use, and adverse drug reactions in a neonatal intensive care unit (NICU) during the postsurgery phase. METHOD: Demographic characteristics, pain scores, and drug use were extracted and analyzed from electronic patient medical files for infants after surgery, admitted consecutively between January 2012 and June 2013. RESULT: One hundred and sixty-eight infants were included. Acute (DAN score) and prolonged (EDIN score) pain assessment scores were used in 79% and 64% of infants, respectively, on the 1st day. This percentage decreased over the 7 days following surgery. The weekly average scores postsurgery were 2/15 (±2.2) for the EDIN score and 1.6/10 (±2.0) for the DAN score. The rates of pain control were 88% for the EDIN and 72% for the DAN. The most prescribed opiate drug was fentanyl (98 patients; 58%) with an average dose of 1.8 (±0.6) µg/kg/h. Midazolam was used in 95 patients (56%), with an average dose of 35 (±14) µg/kg/h. A bolus was administered in 7% (±7.4) of the total dose for fentanyl and 8% (±9.3) for midazolam. Similar doses were used in term and preterm neonates. Of 118 patients receiving fentanyl and/or midazolam, 40% presented urinary retention, 28% a weaning syndrome. Paracetamol (155 patients; 92%) and nalbuphine (55 patients; 33%) were the other medications most often prescribed. CONCLUSION: The off-label use of fentanyl and midazolam was necessary to treat pain after surgery. Pain assessment should be conducted for all neonates in order to optimize their treatment. Research on analgesic and sedative medicine in vulnerable neonates seems necessary to standardize practices and reduce adverse drug reactions.

Macrophages Promote Growth of Squamous Cancer Independent of T cells.

Oral cancers, primarily squamous cell carcinomas (SCCs), progress either slowly or aggressively. Here we assessed the role of macrophages in SCC behavior. We used mouse SCC cells derived from tumors harboring a KrasG12D activation mutation and Smad4 deletion in keratin 15-positive stem cells and a human oral SCC cell line, FaDu, which has NRAS amplification and SMAD4 deletion. SCC cells were transplanted into immune-compromised or immune-competent (syngeneic) recipients. After tumors were established, we used clodronate liposomes to ablate macrophages. We found that the number of tumor-associated macrophages (TAMs) was not affected by the presence of T cells but differed considerably among tumors derived from different SCC lines. Clodronate significantly reduced TAMs and splenic macrophages, resulting in reduced SCC volumes. Tumors with clodronate treatment did not show decreased proliferation but did exhibit increased apoptosis and reduced vascular density. FLIP (Fas-associated via death domain-like interleukin 1ß-converting enzyme inhibitory protein), an apoptosis inhibitor abundantly produced in tumor cells and TAMs, was reduced in tumor cells of clodronate-treated mice. Reduced FLIP levels correlated with reductions in phosphorylated nuclear NFκB p65 and NFκB inhibitor attenuated FLIP protein levels in SCC cells. Furthermore, TGFß1 serum levels and pSmad3 were reduced in clodronate-treated mice, but their reductions were insufficient to reverse epithelial-mesenchymal transition or TGFß-mediated angiogenesis in endothelial cells. Consequently, metastasis was not significantly reduced by macrophage reduction. However, reduced pSmad3 correlated with reduction of its transcriptional target, vascular endothelial growth factor A, in clodronate-treated tumor cells, which correlated with reduced vascular density in clodronate-treated tumors. Taken together, our study revealed that macrophages contribute to SCC expansion through interactions with tumor cells but are dispensable for SCC metastasis. Our study provides novel insights into understanding the contributions and limitations of TAMs in SCC progression.

Genetic Diversity of Pseudomonas savastanoi pv. savastanoi in California and Characterization of Epidemiological Factors for Olive Knot Development.

Olive knot, caused by Pseudomonas savastanoi pv. savastanoi, is a limiting disease in the production of table and oil olives in California. The genetic variability among 152 strains from major production areas of California was determined using BOX, ERIC, and REP primers in repetitive element sequence-based polymerase chain reaction. Overall genetic variability was low, and strains shared at least 82% similarity. Phenetic analyses identified several genotypes but most strains belonged to one of two major groups. Three copper-resistant strains had two fingerprints that were distinct from any of the sensitive strains, indicating that they may have been introduced from other production areas or hosts. In inoculations, two copper-resistant strains were mostly equally as virulent as two copper-sensitive strains. Inoculum was exuded at high levels (>108 CFU/g of knot tissue) within 10 min from hydrated olive knots, and concentrations were 2- to 3-log higher than the minimum needed to induce knot formation. Arbequina olive was significantly more susceptible to infection and developed a higher incidence of knots on leaf scar and lateral wounds (59.7 to 80.6% incidence) than Manzanillo (47.4 to 68.2% incidence). In wound-healing studies, both types of wounds were less susceptible to infection ≥10 days after injury, indicating a critical period for infection and application of bactericides during favorable environments.

Prospective research on infants with mild encephalopathy: the PRIME study.

OBJECTIVE: To determine short-term outcomes of infants with evidence of hypoxia-ischemia at birth and classified as mild neonatal encephalopathy (NE) at <6 h of age. STUDY DESIGN: Prospective multicenter study. Mild NE was defined as ⩾1 abnormal category in modified Sarnat score. Primary outcome was any abnormality on early amplitude integrated electroencephalogram (aEEG) or seizures, abnormal brain magnetic resonance imaging (MRI) or neurological exam at discharge. RESULTS: A total of 54/63 (86%) of enrolled infants had data on components of the primary outcome, which was abnormal in 28/54 (52%): discontinuous aEEG (n=4), MRI (n=9) and discharge exam (n=22). Abnormal tone and/or incomplete Moro were the most common findings. MRI abnormalities were confined to cerebral cortex but two infants had basal ganglia and/or thalamus involvement. The 18 to 24 months follow-up is ongoing. CONCLUSIONS: A larger than expected proportion of mild NE infants with abnormal outcomes was observed. Future research should evaluate safety and efficacy of neuroprotection for mild NE.

The 86-kD subunit of Ku autoantigen mediates homotypic and heterotypic adhesion of multiple myeloma cells.

Previous studies have shown that triggering multiple myeloma (MM) cells via CD40 induces IL-6-mediated autocrine growth as well as increased expression of cell surface adhesion molecules including CD11a, CD11b, CD11c, and CD18. In this study, we generated the 5E2 mAb which targets an antigen that is induced upon CD40 ligand (CD40L) activation of MM cells. Immunofluorescence, immunoprecipitation, and protein sequencing studies identified the target antigen of 5E2 mAb as the 86-kD subunit of the Ku autoantigen. We demonstrate that increased cell surface expression of Ku on CD40L-treated cells is due to migration of Ku from the cytoplasm to the cell surface membrane. Moreover, cell surface Ku on CD40L-treated MM cells mediates homotypic adhesion of tumor cells, as well as heterotypic adhesion of tumor cells to bone marrow stromal cells and to human fibronectin; and 5E2 mAb abrogates IL-6 secretion triggered by tumor cell adherence to bone marrow stromal cells. These data suggest that CD40L treatment induces a shift of Ku from the cytoplasm to the cell surface, and are the first to show that Ku functions as an adhesion molecule. They further suggest that cell surface Ku may play a role in both autocrine and paracrine IL-6-mediated MM cell growth and survival.

Knowledge of Rabies Prevention in Vietnamese Public Health and Animal Health Workers.

Rabies is an invariably fatal, but preventable zoonotic disease. Despite a national programme for its prevention and control, the number of rabies associated deaths in Vietnam has increased in recent years. A cross-sectional survey was undertaken in 2012 to assess and compare the knowledge, awareness and practices of 189 public health workers (PHW) and animal health workers (AHW) attending a joint training course for professionals from provinces in northern Vietnam with the highest number of deaths from rabies. Questionnaires facilitating self-evaluation were provided, and total knowledge scores were calculated (maximum 38 points) and categorized into: 'high' (>30 points), 'moderate' (21-30) and 'low' (<21). The response rate was 100%, and among the 189 participants, 56% were PHW compared to 44% who were AHW. Although most respondents knew rabies could be transmitted through the bite of an animal, most commonly a dog, and that rabies is a preventable disease, significant differences between groups were identified. Major areas included poor knowledge of common rabies reservoirs, wound management and guidance on post-exposure prophylaxis. Overall, the total mean knowledge scores for PHW was significantly higher (P = 0.011) compared to those for AHW, but both scores fell within the 'moderate' knowledge range. However, proportionately more PHW than AHW achieved 'high' knowledge scores (P = 0.0098). To our knowledge this is the first published study to simultaneously assess the knowledge and awareness of animal health and public health professionals attending joint training activities aimed at strengthening rabies prevention and control. To ensure effective prevention and control of rabies requires that AHW and PHW not only coordinate and collaborate, but have a common knowledge and understanding of rabies prevention and control measures. This study provides important baseline data in a relatively unexplored area of research that can focus future interventions and research.

Oral drug dosage forms administered to hospitalized children: Analysis of 117,665 oral administrations in a French paediatric hospital over a 1-year period.

Selecting the most appropriate dosage form, that ensures safe administration and adherence of medications, is a major issue for children. Marketed drugs, however, have rarely been tested for their use in children. There is a need for more data on drug formulations administered to children to identify unmet needs, and drive future paediatric research. We observed, over a 12-month follow-up, 117,665 oral drug administrations to 1998 hospitalized children. Nine-tenths belonged to five Anatomical Therapeutic Chemical classes: Alimentary tract & metabolism, Nervous system, Cardiovascular system, Anti-infectives for systemic use and Blood & blood forming organs, one third of drug doses administered to school-age children and adolescents were liquids, and extemporaneous capsules were commonly used in younger children. Our study shows that despite the advantages of solid dosage forms and recent evidence from randomized controlled trials showing their acceptability in infants, they are seldom used in paediatric practice.

CD28/B7 costimulation: a review.

The current model of T cell activation requires two signals. The first signal is specific, requiring T cell receptor recognition and binding to MHC/Antigen presented by an antigen-presenting cell. The second signal is nonspecific, resulting from the binding of B7 ligand on the antigen-presenting cell with its receptor, CD28, on the T cell. If both signals are provided, the T cell will proliferate and secrete cytokines. Recently, it has been shown that CTLA4, another receptor for B7 that is upregulated following T cell after activation, can deliver an inhibitory signal, downregulating T cell proliferation. The B7 family of ligands has two family members, B7-1 and B7-2. They both bind to CD28 and CTLA4, but they differ in their binding affinity, structure, and temporal expression. Considerable research has been done on the CD28/B7 costimulatory pathway. Different ways of manipulating this pathway could provide insights into the mechanism and treatment of opposing pathological states. Blocking the CD28/B7 pathway could result in immunosuppression, with implications for the treatment of autoimmune diseases, organ transplantation, and graft vs. host disease. Activating the CD28/B7 pathway could be useful for including the immune system to recognize and eliminate tumors that evade the immune system. Finally, the CD28/B7 pathway could be involved with maintaining immune tolerance, as recent studies suggest the preferential binding of the B7-CTLA4 pathway results in the down-regulation of the responding T cells. Thus, the B7/CD28/CTLA4 pathway has the ability to both positively and negatively regulate immune responses.

A Dual Role for P2X7 Receptor during Porphyromonas gingivalis Infection.

Emerging evidence suggests a role for purinergic signaling in the activation of multiprotein intracellular complexes called inflammasomes, which control the release of potent inflammatory cytokines, such as interleukin (IL) -1ß and -18. Porphyromonas gingivalis is intimately associated with periodontitis and is currently considered one of the pathogens that can subvert the immune system by limiting the activation of the NLRP3 inflammasome. We recently showed that P. gingivalis can dampen eATP-induced IL-1ß secretion by means of its fimbriae in a purinergic P2X7 receptor-dependent manner. Here, we further explore the role of this purinergic receptor during eATP-induced IL-1ß processing and secretion by P. gingivalis-infected macrophages. We found that NLRP3 was necessary for eATP-induced IL-1ß secretion as well as for caspase 1 activation irrespective of P. gingivalis fimbriae. Additionally, although the secretion of IL-1ß from P. gingivalis-infected macrophages was dependent on NLRP3, its adaptor protein ASC, or caspase 1, the cleavage of intracellular pro-IL-1ß to the mature form was found to occur independently of NLRP3, its adaptor protein ASC, or caspase 1. Our in vitro findings revealed that P2X7 receptor has a dual role, being critical not only for eATP-induced IL-1ß secretion but also for intracellular pro-IL-1ß processing. These results were relevant in vivo since P2X7 receptor expression was upregulated in a P. gingivalis oral infection model, and reduced IFN-γ and IL-17 were detected in draining lymph node cells from P2rx7(-/-) mice. Furthermore, we demonstrated that P2X7 receptor and NLRP3 transcription were modulated in human chronic periodontitis. Overall, we conclude that the P2X7 receptor has a role in periodontal immunopathogenesis and suggest that targeting of the P2X7/NLRP3 pathway should be considered in future therapeutic interventions in periodontitis.

Self-reactive B cells in nonautoimmune and autoimmune mice.

The defining feature of autoimmune disease is the presence of specific autoreactive lymphocytes. Systemic lupus erythematosus (SLE), for example, is characterized by a discrete set of antibodies directed to nuclear antigens; these include autoantibodies to DNA and snRNPs that are diagnostic for SLE. The murine model of SLE, the MRL-lpr/lpr mouse, likewise, has a similar autoantibody profile. To understand how SLE-associated autoantibodies are regulated in healthy individuals and to identify mechanisms underlying their expression in autoimmunity, we have developed a transgenic (tg) model system using multiple sets of tgs. The development of B cells bearing these tgs has been studied in BALB/c and MRL-lpr/lpr autoimmune backgrounds, and the relative fates of anti-ssDNA and anti-dsDNA tg B cells when they are a part of a diverse as well as monoclonal B cell repertoire have been evaluated.

The PPAR activator docosahexaenoic acid prevents acetaminophen hepatotoxicity in male CD-1 mice.

Acetaminophen (APAP)-induced hepatocellular necrosis can be prevented by treatment with peroxisome proliferators. This protection is associated with lowered protein arylation and glutathione depletion in mice. Peroxisome proliferators have been shown to activate nuclear receptors. These receptors, termed peroxisome proliferator activated receptors (PPARs), can also be activated by free fatty acids. This study was designed to determine if treatment with the PPAR activator docosahexaenoic acid (DHA) would also lower APAP toxicity. Male CD-1 mice received 250 mg DHA/kg or 500 mg clofibrate (CFB)/kg, i.p., for 5 d. Controls received corn oil vehicle, i.p. After overnight fasting, mice received 800 mg APAP/kg, p.o. At 24 h after APAP, hepatotoxicity was evident in control mice by elevated plasma sorbitol dehydrogenase activity (SDH) and histologic evidence of hepatic degeneration and necrosis. As expected, CFB pretreatment significantly decreased this. Similarly, DHA protected against APAP-induced hepatotoxicity at 24 h after challenge. However, treatment with DHA did not increase hepatic glutathione prior to APAP, as previously shown with CFB. Interestingly, DHA did not increase palmitoyl coenzyme A (CoA) oxidase activity or other biochemical parameters associated with peroxisome proliferation after 5 d of treatment at 250 mg/kg. No significant alterations in microsomal APAP glucuronidation or cytochrome P-450-mediated bioactivation were detected either. Collectively, these results show that DHA also prevents APAP-induced hepatotoxicity at 24 h after challenge. However, the association between resistance against APAP-induced liver injury, PPAR activation, and peroxisome proliferation is not clearly understood.

Phagocytic and bactericidal properties of bovine macrophages from non-lactating mammary glands.

Macrophages were isolated from the mammary glands of non-lactating (dry) cows and their ability to phagocytose and kill staphylococci in vitro assessed. Normal bovine serum enhanced the uptake of staphylococci and was required for optimal killing in the bactericidal test. Dry gland secretion interfered with uptake. Secretions taken progressively into the dry period became more inhibitory. The phagocytic ability of macrophages was significantly less than that of neutrophils present in the same gland preparation when tested in the presence of dry gland secretion. A marked variation in the antibacterial activity of macrophages from different cows was noted.