PubMed Health⌕ Search

Biomedical subjects

L Skelley

Publications and source records attributed to L Skelley.

7 recordsLinked to original sources
PubMed2006

AAV delivery of mineralocorticoid receptor shRNA prevents progression of cold-induced hypertension and attenuates renal damage.

UNLABELLED: The aim of this study was to determine the effect of RNA interference inhibition of mineralocorticoid receptor (MR) on cold-induced hypertension (CIH) and renal damage. Recombinant adeno-associated virus (AAV) carrying short hairpin small interference (si)RNA for MR (AAV.MR-shRNA) was constructed and tested for the ability to inhibit renal MR and to control CIH. Three groups of rats with CIH received AAV.MR-shRNA (1.25 x 10(9) particles/rat, intravenous), AAV carrying scrambled shRNA (AAV.Control-shRNA) (1.25 x 10(9) particles/rat, intravenous) and phosphate buffer solution (PBS), respectively. All rats were kept in a cold chamber (6.7 degrees C) throughout the experiment. Adeno-associated virus delivery of MR-shRNA prevented progression of CIH. Blood pressure (BP) of the AAV.MR-shRNA-treated group did not increase and remained at 145+/-3 mm Hg, whereas BP of the AAV.Control-shRNA-treated and PBS-treated group increased to 167+/-4 and 161+/-3 mm Hg, respectively, at 3 weeks after gene delivery. Thus, the antihypertensive effect of a single injection of AAV.MR-shRNA lasted for at least 3 weeks (length of the study). Adeno-associated virus carrying short hairpin siRNA for MR significantly increased urinary sodium excretion and decreased proteinuria. It also decreased serum creatinine and blood urea nitrogen, suggesting enhanced renal function. Both Western blot and immunohistochemical analysis showed that MR expression was decreased significantly in the kidney in the AAV.MR-shRNA-treated rats, confirming that renal MR is effectively inhibited by AAV.MR-shRNA. Adeno-associated virus carrying short hairpin siRNA for MR also significantly attenuated renal hypertrophy. In addition, AAV delivery of MR-shRNA prevented atrophy and dilation of renal tubules and abolished tubular deposition of proteinaceous material seen in CIH rats. CONCLUSIONS: (1) AAV delivery of MR-shRNA effectively silenced MR in vivo. (2) RNA interference inhibition of MR may open a new avenue for the long-term control of hypertension and renal damage.

Animals↗
PubMed1995

Effects of tumor necrosis factor blockade on interleukin 6, lactate, thromboxane, and prostacyclin responses in miniature horses given endotoxin.

A monoclonal antibody (MAB) against equine tumor necrosis factor-alpha (Eq TNF) was used to investigate the role of TNF in cytokine, eicosanoid, and metabolic responses of Miniature Horses given endotoxin. Plasma concentrations of interleukin 6 (IL-6), lactate, thromboxane A2 metabolite, and prostacyclin metabolite (6-keto-PGF1 alpha) were measured in 10 Miniature Horses given 0.25 microgram of lipopolysaccharide (LPS; Escherichia coli O55:B5)/kg of body weight. Five horses were given Eq TNF MAB and 5 were given isotype-matched MAB as control. All horses were given 1.86 mg of antibody/kg by IV infusion, 5 minutes before LPS was given IV. Blood samples were taken 20 minutes before and at multiple intervals for 24 hours after LPS was given. Interleukin 6 bioactivity in plasma was measured, using IL-6-dependent cell line (B9). Eicosanoid activities were assessed by enzyme immunoassay, and plasma lactate concentration was determined enzymatically. Data were analyzed by ANOVA and Tukey's honest significant difference test for significant (P < 0.05) effect of treatment. Horses given Eq TNF MAB had significantly (P < 0.050) lower peak mean +/- SEM IL-6 (59 +/- 29 U/ml), lactate (16 +/- 2.00 mg/dl), and 6-keto-PGF1 alpha (254 +/- 79 pg/ml) values then did horses given control MAB (880 +/- 375 U/ml for IL-6; 26 +/- 0.04 mg/dl for lactate; and 985 +/- 290 pg/ml for 6-keto-PGF1 alpha). There was no effect of anti-TNF treatment on LPS-induced thromboxane A2 metabolite production. Tumor necrosis factor mediated IL-6, lactate, and prostacyclin responses, without affecting thromboxane production in horses given LPS.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Effect of treatment with a monoclonal antibody against equine tumor necrosis factor (TNF) on clinical, hematologic, and circulating TNF responses of miniature horses given endotoxin.

Tumor necrosis factor-alpha (TNF) is an important mediator of endotoxin-induced pathologic changes. To help define the role of TNF in equids with endotoxemia, the effects of pretreatment with a murine monoclonal antibody (MAB) against equine TNF were evaluated in Miniature Horses given endotoxin. Five horses were given TNF MAB at a dosage of 1.86 mg/kg of body weight, IV, and 5 were given control MAB. Five minutes later, lipopolysaccharide (LPS; Escherichia coli O55:B5), 0.25 microgram/kg, was given to all horses by bolus IV infusion. Clinical signs of disease were monitored at intervals up to 24 hours after LPS infusion, and blood was taken for determination of WBC count, PCV, plasma total protein concentration, plasma TNF activity, and serum MAB concentration. Reduction of plasma TNF activity in anti-TNF-treated horses was highly significant (P < 0.001), compared with that in control horses. Horses given TNF MAB had significantly improved clinical abnormality score (P < 0.010), lower heart rate (P < 0.001), and higher WBC count (P < 0.001), compared with horses given control MAB. Rectal temperature, respiratory rate, PCV, and plasma total protein concentration were not significantly different between groups. Serum MAB concentration peaked at 68 micrograms/ml 30 minutes after the end of antibody infusion in both groups. Neutralization of LPS-induced TNF activity reduced the hematologic and clinical responses of horses given LPS IV.

Analysis of Variance↗
PubMed1992

Serving the needs of donor families: the role of the critical care nurse.

The humanitarian act of donating organs has tremendous benefits not only for the transplant recipients but also for the family of the donor. The opportunity to provide some hope to a grief-stricken family that something positive can result from their tragedy is an important contribution that a critical care nurse can make. The nurse's participation in recognizing the possibility of organ donation for the family of a terminal patient can drastically reduce the national shortage of transplantable organs. The consent and organ recovery process is a complex one, and a team approach by the nurse, physician, OPO coordinator, and other hospital staff members is necessary. Ultimately, the success of the effort is determined by the family's positive response to give the "Gift of Life."

Adolescent↗