Serum cortisol of Sahel goats following rumenotomy with assorted anaesthetics and sutures.

The utmost need for pragmatic combination of surgical sutures and local anaesthetic that would evoke minimal post-surgical stress response and allow uncomplicated healing is essential for successful surgeries. Fifteen Sahel goats were randomly allocated into three groups A, B and C to quantitatively assay (ELISA) serum cortisol profiles following rumenotomy, as markers of surgical stress. Diazepam at 0.2 mg/kg was administered intravenously to groups A and B with subsequent lidocaine HCl and bupivacaine inverted-L block respectively. Group C did not receive any treatment. Chromic catgut (CCG) and polyglycolic acid (PGA) sutures were used for rumen and abdominal muscles closure for groups A and B respectively and nylon for skin closure. Blood samples were taken at post anaesthetic induction (PAI) and post-surgery at 0, 5, 8, 24, 48 and 72 h. The Group A goats expressed serum cortisol that was significantly high 52.76 ± 6.12 ng/mL at 5 h post-surgery. At 8 h post-surgery serum cortisol for both groups A (72.53 ± 3.79 ng/mL) and B (61.59 ± 3.90 ng/mL) were at their peak. Serum cortisol levels compared to the baseline data were significantly different (P < 0.05) at 5, 24, and 48 h for the CCG goats. The serum cortisol levels at 72 h drastically decreased to 20.53 ± 8.74 ng/mL for groups A and 17.59 ± 2.45 ng/mL for group B and were not significantly different (p > 0.05). Cortisol responses unambiguously indicate that diazepam-bupivacaine induce less stress than Diazepam-lidocaine, hence a preferred anesthesia. Moreover, polyglycolic acid sutures are associated with less inflammatory reaction than chromic catgut.

Legionella pneumophila multiplication is enhanced by chronic AMPK signalling in mitochondrially diseased Dictyostelium cells.

Human patients with mitochondrial diseases are more susceptible to bacterial infections, particularly of the respiratory tract. To investigate the susceptibility of mitochondrially diseased cells to an intracellular bacterial respiratory pathogen, we exploited the advantages of Dictyostelium discoideum as an established model for mitochondrial disease and for Legionella pneumophila pathogenesis. Legionella infection of macrophages involves recruitment of mitochondria to the Legionella-containing phagosome. We confirm here that this also occurs in Dictyostelium and investigate the effect of mitochondrial dysfunction on host cell susceptibility to Legionella. In mitochondrially diseased Dictyostelium strains, the pathogen was taken up at normal rates, but it grew faster and reached counts that were twofold higher than in the wild-type host. We reported previously that other mitochondrial disease phenotypes for Dictyostelium are the result of the activity of an energy-sensing cellular alarm protein, AMP-activated protein kinase (AMPK). Here, we show that the increased ability of mitochondrially diseased cells to support Legionella proliferation is suppressed by antisense-inhibiting expression of the catalytic AMPKalpha subunit. Conversely, mitochondrial dysfunction is phenocopied, and intracellular Legionella growth is enhanced, by overexpressing an active form of AMPKalpha in otherwise normal cells. These results indicate that AMPK signalling in response to mitochondrial dysfunction enhances Legionella proliferation in host cells.

Diverse cytopathologies in mitochondrial disease are caused by AMP-activated protein kinase signaling.

The complex cytopathology of mitochondrial diseases is usually attributed to insufficient ATP. AMP-activated protein kinase (AMPK) is a highly sensitive cellular energy sensor that is stimulated by ATP-depleting stresses. By antisense-inhibiting chaperonin 60 expression, we produced mitochondrially diseased strains with gene dose-dependent defects in phototaxis, growth, and multicellular morphogenesis. Mitochondrial disease was phenocopied in a gene dose-dependent manner by overexpressing a constitutively active AMPK alpha subunit (AMPKalphaT). The aberrant phenotypes in mitochondrially diseased strains were suppressed completely by antisense-inhibiting AMPKalpha expression. Phagocytosis and macropinocytosis, although energy consuming, were unaffected by mitochondrial disease and AMPKalpha expression levels. Consistent with the role of AMPK in energy homeostasis, mitochondrial "mass" and ATP levels were reduced by AMPKalpha antisense inhibition and increased by AMPKalphaT overexpression, but they were near normal in mitochondrially diseased cells. We also found that 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, a pharmacological AMPK activator in mammalian cells, mimics mitochondrial disease in impairing Dictyostelium phototaxis and that AMPKalpha antisense-inhibited cells were resistant to this effect. The results show that diverse cytopathologies in Dictyostelium mitochondrial disease are caused by chronic AMPK signaling not by insufficient ATP.