The incidence of hypoxemia in dogs recovering from general anesthesia detected with pulse-oximetry and related risk factors.

The postoperative period is critical for the development of complications, including hypoxemia. To detect hypoxemia early and provide appropriate care, continuous monitoring of saturation is necessary: pulse oximetry is an easily accessible and simple method for this purpose. However, a SpO2 cut-off value to detect hypoxemia in dogs recovering from general anesthesia is lacking in the veterinary literature. The objectives of this clinical study are to validate the room air SpO2 test (SpAT), to identify a cut-off value to discriminate hypoxemia (Phase 1), and to apply the SpAT to study the incidence of transient postoperative hypoxemia (TPH) (Phase 2) in dogs with healthy lungs recovering from general anesthesia. Phase 1: 87 dogs recovering from general anesthesia with an arterial line were included. After extubation, SpAT was performed simultaneously with arterial blood sampling. A PaO2 < 80 mmHg was considered hypoxemia. Phase 2: 654 dogs were enrolled. They underwent general anesthesia with different ventilation settings for different procedures. After extubation, dogs were classified as hypoxemic if the SpO2 was lower than the cut-off obtained in phase 1. Phase 1 showed that the SpO2 cut-off is < 95% (sensitivity 100%, specificity 97.4%; area under the curve, AUC = 0.996; 95% Confidence Interval = 0.944-1; P<0.0001). In Phase 2, 169 dogs were hypoxemic. Body Condition Score (BCS) > 3/5, dorsal recumbency, FiO2 1, absence of Positive End-Expiratory Pressure (PEEP) had a significant odds ratio to induce TPH (5.8, 1.9, 3.7, 1.7, respectively). These results showed that SpO2 < 95% indicates PaO2 < 80 mmHg in dogs and TPH occurs in up to 28% of cases. Identification of associated risks could be useful to prevent and to increase awareness for monitoring and treatment.

Non-dioxin-like organic toxicant PCB153 modulates sphingolipid metabolism in liver progenitor cells: its role in Cx43-formed gap junction impairment.

The non-dioxin-like environmental toxicant 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153), member of a group of persistent organic pollutants wide-spread throughout the environment, reduces gap junction intercellular communication (GJIC), an event possibly associated with tumor promotion. Since very few studies have investigated the signaling effectors and mode(s) of action of PCB153, and it is known that the gap junction (GJ) protein Cx43 can be regulated by the bioactive sphingolipid (SL) sphingosine 1-phosphate (S1P), this in vitro study mainly addresses whether SL metabolism is affected by PCB153 in rat liver epithelial WB-F344 cells. PCB153 treatment obtained significant changes in the S1P/ceramide (Cer) ratio, known to be crucial in determining cell fate. In particular, an increase in S1P at 30 min and a decrease of the bioactive lipid at 3 h were observed, whereas Cer level increased at 1 h and 24 h. Notably, a time-dependent modulation of sphingosine kinase (SphK), the enzyme responsible for S1P synthesis, and of its regulators, ERK1/2 and protein phosphatase PP2A, supports the involvement of these signaling effectors in PCB153 toxicity. Electrophysiological analyses, furthermore, indicated that the lipophilic environmental toxicant significantly reduced GJ biophysical properties, affecting both voltage-dependent (such as those formed by Cx43 and/or Cx32) and voltage-independent channels, thereby demonstrating that PCB153 may act differently on GJs formed by distinct Cx isoforms. SphK down-regulation alone induced GJIC impairment, and, when combined with PCB153, the acute effect on GJ suppression was additive. Moreover, after enzyme-specific gene silencing, the SphK1 isoform appears to be responsible for down-regulating Cx43 expression, while being the target of PCB153 at short-term exposure. In conclusion, we provide the first evidence of novel effectors in PCB153 toxic action in rat liver stem-like cells, leading us to consider SLs as potential markers for preventing GJIC deregulation and, thus, the tumorigenic action elicited by this environmental toxicant.

Clinical correlates of human leucocyte antigen (HLA)-G in systemic sclerosis.

Human leucocyte antigen (HLA)-G has a tolerogenic function and could play a role in the pathogenesis of immune-mediated diseases, including systemic sclerosis (SSc). The aim of this study was to evaluate HLA-G serum expression (sHLA-G) and the HLA-G gene 14 base pairs (bp) insertion/deletion (del(-)/del(+)) polymorphism in patients with Ssc, to search for possible associations with clinical and laboratory variables. sHLA-G was measured by enzyme-linked immunosorbent assay (ELISA) in sera from 77 patients with SSc and 32 healthy donors (HD); the 14 bp del(-)/del(+) polymorphism was evaluated by polymerase chain reaction (PCR) amplification of peripheral blood mononuclear cells (PBMC) genomic DNA. Receiver operating characteristics (ROC) analysis identified the HLA-G cut-off that best discriminated dichotomized clinical and serological variables, that was subsequently employed to subdivide SSc patients into HLA-G high (HLA-G(+)) and low (HLA-G(-)) profile groups. sHLA-G were not statistically different between SSc patients and HD, nor between distinct SSc autoantibody subsets. Subdividing SSc patients by HLA-G positivity or negativity yielded significant differences for the modified Rodnan skin score (mRss) (P = 0.032), 'general' (P = 0.031) and 'kidney' (P = 0.028) Medsger severity scores (MSS) and disease activity index, and especially Δ heart/lung (P = 0.005). A worse 'general' MSS (P = 0.002) and Δ heart/lung (P = 0.011) were more frequent in the low sHLA-G group. These two variables and mRss were associated with sHLA-G levels at logistic regression analysis. Treatment had no influence on sHLA-G. Moreover, a higher frequency of scleredema was detected in the del(+)/del(+) than the del(-)/del(+) group (P = 0.04). These data suggest modulatory effects of sHLA-G on SSc. Prospective studies are needed to investigate a role in predicting the disease course.