Biomedical subjects

Joseph J Cullen

Publications and source records attributed to Joseph J Cullen.

At least 19 recordsLinked to original sources

PubMed2006

A prospective study of outcomes, healthcare resource utilization, and costs associated with postoperative nosocomial infections.

OBJECTIVE: We evaluated 4 important outcomes associated with postoperative nosocomial infection: costs, mortality, excess length of stay, and utilization of healthcare resources. DESIGN: The outcomes for patients who underwent general, cardiothoracic, and neurosurgical operations were recorded during a previous clinical trial. Multivariable analyses including significant covariates were conducted to determine whether nosocomial infection significantly affected the outcomes. SETTING: A large tertiary care medical center and an affiliated Veterans Affairs Medical Center. PATIENTS: A total of 3,864 surgical patients. RESULTS: The overall nosocomial infection rate was 11.3%. Important covariates included age, Karnofsky score, McCabe and Jackson classification of the severity of underlying disease, National Nosocomial Infection Surveillance system risk index, and number of comorbidities. After accounting for covariates, nosocomial infection was associated with increased postoperative length of stay, increased costs, increased hospital readmission rate, and increased use of antimicrobial agents in the outpatient setting. Nosocomial infection was not associated independently with a significantly increased risk of death in this surgical population. CONCLUSION: Postoperative nosocomial infection was associated with increased costs of care and with increased utilization of medical resources. To accurately assess the effects of nosocomial infections, one must take into account important covariates. Surgeons seeking to decrease the cost of care and resource utilization must identify ways to decrease the rate of postoperative nosocomial infection.

Adult↗

PubMed2006

Mitochondrial production of reactive oxygen species mediate dicumarol-induced cytotoxicity in cancer cells.

Dicumarol is a naturally occurring anticoagulant derived from coumarin that induces cytotoxicity and oxidative stress in human pancreatic cancer cells (Cullen, J. J., Hinkhouse, M. M., Grady, M., Gaut, A. W., Liu, J., Zhang, Y., Weydert, C. J. D., Domann, F. E., and Oberley, L. W. (2003) Cancer Res. 63, 5513-5520). Although dicumarol has been used as an inhibitor of the two-electron reductase NAD(P)H:quinone oxidoreductase (NQO1), dicumarol is also thought to affect quinone-mediated electron transfer reactions in the mitochondria, leading to the production of superoxide (O2*-) and hydrogen peroxide (H(2)O(2)). We hypothesized that mitochondrial production of reactive oxygen species mediates the increased susceptibility of pancreatic cancer cells to dicumarol-induced metabolic oxidative stress. Dicumarol decreased clonogenic survival equally in both MDA-MB-468 NQO1(-) and MDA-MB-468 NQO1+ breast cancer cells. Dicumarol decreased clonogenic survival in the transformed fibroblast cell line IMRSV-90 compared with the IMR-90 cell line. Dicumarol, with the addition of mitochondrial electron transport chain blockers, decreased clonogenic cell survival in human pancreatic cancer cells and increased superoxide levels. Dicumarol with the mitochondrial electron transport chain blocker antimycin A decreased clonogenic survival and increased superoxide levels in cells with functional mitochondria but had little effect on cancer cells without functional mitochondria. Overexpression of manganese superoxide dismutase and mitochondrial-targeted catalase with adenoviral vectors reversed the dicumarol-induced cytotoxicity and reversed fluorescence of the oxidation-sensitive probe. We conclude mitochondrial production of reactive oxygen species mediates the increased susceptibility of cancer cells to dicumarol-induced cytotoxicity.

Antineoplastic Agents↗

PubMed2006

Metastatic progression of pancreatic cancer: changes in antioxidant enzymes and cell growth.

Pancreatic cancer has a dismal prognosis due to the fact that patients present late when metastatic disease is already present. Previous studies have demonstrated that pancreatic cancer cells have decreased levels of MnSOD, which correlates well with increased rates of tumor cell proliferation. Recently, we have found that nude mice injected with MIA PaCa-2 human pancreatic cancer cells in the flank occasionally develop ascites and intra-abdominal metastatic deposits. Mice that developed ascites were sacrificed and the ascites cultured. Necropsy demonstrated metastatic tumors in the retroperitoneum, which were excised, digested, and cultured. Western blots, enzyme activity and enzyme activity gels were performed for manganese superoxide dismutase (MnSOD), copper/zinc (CuZnSOD), catalase, and glutathione peroxidase (GPx) in the ascites cell line, metastatic tumor cell line, MIA PaCa-2 primary pancreatic cancer cell line, and the Capan-1, a metastatic pancreatic cancer cell line. Cell growth, plating efficiency, growth in soft agar and growth in nude mice were determined in the ascites, metastatic tumor, and MIA PaCa-2 cell lines. MnSOD, CuZnSOD, and GPx protein and activity were increased in the ascites, metastatic tumor, and Capan-1 cell lines compared to MIA PaCa-2. The ascites and metastatic tumor cell lines had decreased cell growth, plating efficiency, and growth in soft agar, but the ascites cell line had increased cell growth in 4 and 1% O(2) concentrations in vitro and more rapid growth in vivo. Metastatic disease is associated with changes in the content and activity of antioxidant enzymes with an associated change in growth characteristics depending on the O(2) concentrations.

Animals↗

PubMed2006

Suppression of the malignant phenotype in pancreatic cancer by overexpression of phospholipid hydroperoxide glutathione peroxidase.

Phospholipid glutathione peroxidase (PhGPx) reduces lipid hydroperoxides generated in biomembranes and also uses a wide range of reducing cofactors in addition to glutathione. PhGPx is synthesized as a mitochondrial PhGPx form (L-form) and as a nonmitochondrial PhGPx form (S-form). Our aims were to determine whether overexpression of PhGPx altered pancreatic tumor cell behavior. Pancreatic cancer cell lines were found by Western blotting to have diminished levels of PhGPx-immunoreactive protein compared with normal human pancreas. To normalize the levels of this protein, PhGPx was overexpressed in MIA PaCa-2 and AsPC-1 human pancreatic cancer cells by infection with an adenovirus-PhGPx L-form construct (AdPhGPx- L-form) (0-200 MOI) or with an adenovirus-PhGPx S-form construct (AdPhGPx-S-form) (0-200 MOI), and cell growth, plating efficiency, and growth in soft agar were determined. Pancreatic cancer cells were also injected subcutaneously into nude mice and tumor volume was calculated. Single direct injections of the adenoviral- PhGPx constructs were made into preestablished tumors. In vitro, AdPhGPx-S-form demonstrated 80% tumor growth inhibition, whereas AdPhGPx-L-form demonstrated 95% tumor growth inhibition. Ad- PhGPx-L-form or AdPhGPx-S-form also decreased plating efficiency and growth in soft agar. AdPhGPx-Lform decreased in vivo tumor growth to a greater extent than did AdPhGPx-S-form. Because of the growthinhibitory effects of PhGPx, lipid hydroperoxides may play an important role in the growth of pancreatic cancer.

Adenoviridae↗

PubMed2005

Efficacy of beta-lapachone in pancreatic cancer treatment: exploiting the novel, therapeutic target NQO1.

NAD(P)H:quinone oxidoreductase (NQO1) is elevated in human pancreatic cancers. We hypothesized that beta-lapachone, a novel 1,2-naphthoquinone with potential antitumor activity in cancer cells expressing elevated levels of NQO1, would induce cytotoxicity in pancreatic cancer cells, wherein this two-electron reductase was recently found elevated. beta-lapachone decreased clonogenic cell survival, metabolic cell viability, and anchorage- independent growth in soft agar. The cytotoxic in vitro effects of beta-lapachone were inhibited with coadministration of dicumarol, a specific inhibitor of NQO1. In preestablished human pancreatic tumor xenografts in nude mice, beta-lapachone demonstrated greater tumor growth inhibition when given intratumorally compared to when complexed with cyclodextrin to increase its bioavailability. Due to the poor prognosis of patients with pancreatic cancer and the limited effectiveness of surgery, chemotherapy, and radiation therapy, treatment regimens based on sound, tumor-specific rationales are desperately need for this disease.

Aged↗

PubMed2005

Targeting NAD(P)H:quinone oxidoreductase (NQO1) in pancreatic cancer.

NAD(P)H:quinone oxidoreductase (NQO1) functions as an important part of cellular antioxidant defense by detoxifying quinones, thus preventing the formation of reactive oxygen species (ROS). The aim of our study was to determine if NQO1 is elevated in pancreatic cancer specimens and pancreatic cancer cell lines and if so, would compounds previously demonstrated to redox cycle with NQO1 be effective in killing pancreatic cancer cells. Immunohistochemistry of resected pancreatic specimens demonstrated an increased immunoreactivity for NQO1 in pancreatic cancer and pancreatic intraepithelial neoplasia (PanIN) specimens versus normal human pancreas. Immunocytochemistry and Western immunoblots demonstrated increased immunoreactivity in pancreatic cancer cells when compared to a near normal immortalized human pancreatic ductal epithelial cell line and a colonic epithelial cell line. Streptonigrin, a compound known to cause redox cycling in the presence of NQO1, decreased clonogenic survival and decreased anchorage-independent growth in soft agar. Streptonigrin had little effect on cell lines with absent or reduced levels of NQO1. The effects of streptonigrin were reversed in pancreatic cancer cells pretreated with dicumarol, a known inhibitor of NQO1. NQO1 may be a therapeutic target in pancreatic cancer where survival is measured in months.

Agar↗

PubMed2004

Treatment of pancreatic cancer cells with dicumarol induces cytotoxicity and oxidative stress.

PURPOSE NAD(P)H: quinone oxidoreductase (NQO(1)) catalyzes the two-electron reduction of quinones to hydroquinones. This reaction is believed to prevent the one-electron reduction of quinones that would result in redox cycling with generation of superoxide (O(2)(.-)). We have recently demonstrated that inhibition of NQO(1) with dicumarol increases intracellular O(2)(.-) production and inhibits the in vitro malignant phenotype of pancreatic cancer cells (J. Cullen et al., Cancer Res., 63: 5513-5520, 2003). We hypothesized that inhibition of NQO(1) would increase cell killing, induce oxidative stress, and inhibit in vivo tumor growth. EXPERIMENTAL DESIGN AND RESULTS: In the human pancreatic cancer cell line MIA PaCa-2, dicumarol decreased cell viability, as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and decreased clonogenic survival. Dicumarol increased the percentage of apoptotic cells in a time-dependent and dose-dependent manner as measured by 3,3'-diaminobenzidine staining and flow cytometry, which was associated with cytochrome c release and poly(ADP-ribose) polymerase cleavage. Dicumarol also induced oxidative stress as evidenced by increased total glutathione and oxidized glutathione, as well as sensitizing to cell killing mediated by menadione. In established orthotopic pancreatic tumors in nude mice, intratumoral injections of dicumarol slowed tumor growth and extended survival. CONCLUSIONS: Inhibition of NQO(1) with dicumarol induces cell killing and oxidative stress in pancreatic cancer cells and speculate that dicumarol may prove to be useful in pancreatic cancer therapeutics.

Animals↗

PubMed2004

Inhibition of cell growth by overexpression of manganese superoxide dismutase (MnSOD) in human pancreatic carcinoma.

Manganese superoxide dismutase (MnSOD) levels have been found to be low in human pancreatic cancer [Pancreas 26, (2003), 23] and human pancreatic cancer cell lines [Cancer Res. 63, (2003), 1297] when compared to normal human pancreas. We hypothesized that stable overexpression of pancreatic cancer cells with MnSOD cDNA would alter the malignant phenotype. MIA PaCa-2 cells were stably transfected with a pcDNA3 plasmid containing sense human MnSOD cDNA or containing no MnSOD insert by using the lipofectAMINE method. G418-resistant colonies were isolated, grown and maintained. Overexpression of MnSOD was confirmed in two selected clones with a 2-4-fold increase in MnSOD immunoreactive protein. Compared with the parental and neo control cells, the MnSOD-overexpressing clones had decreased growth rates, growth in soft agar and plating efficiency in vitro, while in vivo, the MnSOD-overexpressing clones had slower growth in nude mice. These results suggest that MnSOD may be a tumor suppressor gene in human pancreatic cancer.

Agar↗

PubMed2004

Preoperative risk factors for nasal carriage of Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus nasal carriage is a risk factor for surgical-site infections (SSIs) caused by S. aureus, and eradication of carriage reduces postoperative nosocomial infections caused by it. No study has compared large groups of preoperative carriers and non-carriers to identify factors that are linked to S. aureus nasal carriage. METHODS: While conducting a clinical trial evaluating whether mupirocin prevented S. aureus SSIs, we prospectively collected data on 70 patient characteristics that might be associated with S. aureus carriage. We performed stepwise logistic regression analysis. RESULTS: Of the 4,030 patients, 891 (22%) carried S. aureus. Independent risk factors for S. aureus nasal carriage were obesity (odds ratio [OR], 1.29; 95% confidence interval [CI95], 1.11-1.50), male gender (OR, 1.29; CI95, 1.11-1.51), and a history of a cerebrovascular accident (OR, 1.53; CI95, 1.03-2.25) for all patients. Factors associated with nasal carriage varied somewhat by surgical specialty. In all groups, preoperative use of antimicrobial agents was independently associated with a lower risk of carrying S. aureus in the nares. Previously identified risk factors were not significantly associated with S. aureus nasal carriage in this large group of surgical patients. CONCLUSION: Male gender, obesity, and a history of a cerebrovascular accident were identified as risk factors for S. aureus nasal carriage. It remains to be seen whether preoperative weight loss would reduce the rate of nasal carriage. In addition, the value of screening this patient population for S. aureus nasal carriage merits further investigation.

Adult↗

PubMed2004

Redox regulation of pancreatic cancer cell growth: role of glutathione peroxidase in the suppression of the malignant phenotype.

Pancreatic cancer has low levels of antioxidant enzymes including manganese superoxide dismutase (MnSOD), which converts superoxide radical (O(2)(*-)) into hydrogen peroxide (H(2)O(2)), and glutathione peroxidase (GPx), which converts H(2)O(2) into water. Recent studies have demonstrated that overexpression of MnSOD has a tumor-suppressive effect in pancreatic cancer. However, GPx overexpression has been shown to reverse the tumor cell growth inhibition caused by MnSOD overexpression in other types of cancer. Our aims were to determine if overexpression of GPx alters in vitro pancreatic cancer cell behavior and if delivering the GPx gene directly to tumor xenografts alters growth and survival. In vitro, AdGPx slowed tumor growth by 39% and AdMnSOD slowed tumor growth by 35%. AdGPx also decreased plating efficiency and growth in soft agar. The combination of AdGPx and AdMnSOD had the greatest effect on tumor cell growth suppression with a 71% reduction in cell growth compared to controls. In vivo, either AdGPx or AdMnSOD alone slowed tumor growth by 51% and 54%, respectively, while the combination of AdGPx and AdMnSOD potentiated tumor growth suppression by 81% of controls and increased animal survival. GPx may be a tumor suppressor gene in pancreatic cancer. Delivery of the GPx gene alone or in combination with the MnSOD gene may prove beneficial for treatment of pancreatic cancer.

Adenoviridae↗

PubMed2004

Preoperative risk factors for postoperative Staphylococcus aureus nosocomial infections.

Of the 40 million patients who undergo surgery each year in the United States, 20% may develop a postoperative nosocomial infection. Staphylococcus aureus (S. aureus) is the most common organism involved, and carriage of S. aureus in the anterior nares has been identified as a risk factor for these infections. Topical mupirocin applied to the anterior nares has been successful in eliminating S. aureus and decreasing nosocomial infections due to S. aureus. Concurrent use of preoperative chlorhexidine showers may further reduce the incidence of S. aureus surgical site infections (SSIs). In addition to treating the patient, active surveillance programs to eliminate nasal colonization in hospital surgical personnel have controlled outbreaks of S. aureus SSIs. Recently, a large study identified risk factors linked to S. aureus nasal colonization, which included obesity, male gender, and a history of a cerebrovascular accident. Protective factors included older age, current smoking, and alcohol use. Thus, by modulating these variables, investigators may create interventions aimed at reducing S. aureus nasal carriage and ultimately, postoperative nosocomial infections.

Antibiotic Prophylaxis↗

PubMed2003

Dicumarol inhibition of NADPH:quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism.

NADPH:quinone oxidoreductase (NQO(1)), a homodimeric, ubiquitous, flavoprotein, catalyzes the two-electron reduction of quinones to hydroquinones. This reaction prevents the one-electron reduction of quinones by cytochrome P450 reductase and other flavoproteins that would result in oxidative cycling with generation of superoxide (O(2)(.-)). NQO(1) gene regulation may be up-regulated in some tumors to accommodate the needs of rapidly metabolizing cells to regenerate NAD(+). We hypothesized that pancreatic cancer cells would exhibit high levels of this enzyme, and inhibiting it would suppress the malignant phenotype. Reverse transcription-PCR, Western blots, and activity assays demonstrated that NQO(1) was up-regulated in the pancreatic cancer cell lines tested but present in very low amounts in the normal human pancreas. To determine whether inhibition of NQO(1) would alter the malignant phenotype, MIA PaCa-2 pancreatic cancer cells were treated with a selective inhibitor of NQO(1), dicumarol. Dicumarol increased intracellular production of O(2)(.-), as measured by hydroethidine staining, and inhibited cell growth. Both of these effects were blunted with infection of an adenoviral vector containing the cDNA for manganese superoxide dismutase. Dicumarol also inhibited cell growth, plating efficiency, and growth in soft agar. We conclude that inhibition of NQO(1) increases intracellular O(2)(.-) production and inhibits the in vitro malignant phenotype of pancreatic cancer. These mechanisms suggest that altering the intracellular redox environment of pancreatic cancer cells may inhibit growth and delineate a potential strategy directed against pancreatic cancer.

Adenocarcinoma↗

PubMed2003

The role of manganese superoxide dismutase in the growth of pancreatic adenocarcinoma.

Chronic pancreatitis, K-ras oncogene mutations, and the subsequent generation of reactive oxygen species (ROS) appear to be linked to pancreatic cancer. ROS have also been suggested to be mitogenic and capable of stimulating cell proliferation. Cells contain antioxidant enzymes to regulate steady state levels of ROS produced by products of metabolism. The aims of our study were to determine antioxidant enzyme activity in pancreatic cancer cells and correlate enzyme activity with tumor growth, as well as determine whether tumor cell growth could be altered with antioxidant gene transfection. Western blots, enzyme activity, and enzyme activity gels were performed for manganese superoxide dismutase (MnSOD), copper/zinc, catalase, and glutathione peroxidase in normal human pancreas and in the human pancreatic cancer cell lines BxPC-3, Capan-1, MIA PaCa-2, and AsPC-1. Cell population doubling times were determined and correlated with antioxidant enzyme activity. MnSOD was overexpressed in MIA PaCa-2 using an adenoviral vector, and the effect on cell growth was determined. The cell pancreatic cancer lines BxPC-3, MIA PaCa-2, and AsPC-1 had decreased levels of MnSOD immunoreactive protein as well as activity and decreases in MnSOD levels correlated well with increased rates of tumor cell proliferation as determined by cell doubling time. No correlation could be found between cell growth and levels of copper/zinc superoxide dismutase, catalase, or glutathione peroxidase. Enforced expression of MnSOD by adenovirus transfection in the rapid growing cell line MIA PaCa-2 increased MnSOD immunoreactivity and MnSOD activity and decreased growth rate. Overexpression of MnSOD may be effective in growth suppression of pancreatic cancer.

Adenocarcinoma↗

PubMed2003

Intracerebroventricular calcitonin prevents stress-induced gastric dysfunction.

BACKGROUND: Restraint stress produces gastric hypercontractility and acidity leading to stress ulceration. Intracerebroventricular (ICV) salmon calcitonin (sCT) decreases restraint injury and acidity, but its effects on restraint-induced hypercontractility are unknown. METHODS: Using stereotactic guidance, ICV catheters were placed into the lateral ventricle of adult male rats and calibrated gastric strain gauge transducers were implanted 5 days prior to restraint stress. sCT rats (n = 8) were pretreated with 5 microg of calcitonin ICV (10 microl volume), while controls (n = 10) received 10 microl of ICV saline prior to restraint for 2 h at 20 degrees C followed by 2 h at 4 degrees C. Gastric motility data were collected with AT-CODAS and analyzed with ADVANCED CODAS. Gastric volume, pH, and lesions were recorded following the stress. RESULTS: ICV calcitonin prevented gastric mucosal injury in all animals (0% vs 100%, P <.01) and elevated pH slightly (2.5 +/-.3 vs 1.6 +/-.1, P <.05). Stress caused the force of contractions to increase from 0.35 +/-.1 to 1.38 +/-.4 g in controls (P <.01), while treated animal's force fell from.42 +/-.1 to 0.2 +/-.05 g (P <.01 vs control). Stress did not affect contractions/min (3.4 +.6 vs 3.5 +.3), but sCT increased frequency (2.5 +.4 to 5.0 +.2, P <.01). Stress prolonged contraction duration (11.5 + 1 to 16.5 + 1.7 s, P <.01), but stress's effect was prevented by sCT (11.0 +.5 to 11.2 +.3, P <.01 vs control). CONCLUSIONS: Pretreatment with 5 microg central sCT prevents the increased amplitude and duration of gastric contractions produced by restraint stress for 2 h, in association with gastroprotection.

Animals↗

PubMed2003

Expression of antioxidant enzymes in diseases of the human pancreas: another link between chronic pancreatitis and pancreatic cancer.

INTRODUCTION: Chronic pancreatitis is a significant risk factor for pancreatic cancer and is associated with the generation of reactive oxygen species. Cells contain a large number of antioxidants to prevent or repair the damage caused by reactive oxygen species. There are three major types of primary intracellular antioxidant enzymes in mammalian cells: superoxide dismutase (SOD), catalase, and peroxidase, of which glutathione peroxidase is the most prominent. AIM: To determine the level of antioxidant enzymes in human pancreas from normal, chronic pancreatitis, and pancreatic cancer specimens. METHODOLOGY: Immunohistochemical analysis for manganese SOD, copper/zinc SOD, catalase, and glutathione peroxidase expression using the avidin-biotin-peroxidase complex method was performed on pancreatic specimens previously fixed in formalin and embedded in paraffin. A quantitative digital imaging methodology was used to examine antioxidant staining in the pancreatic tissue. Cytoplasmic regions of ductal and acinar cells were identified and digitized. Mean gray-level pixel values were then obtained for each of these regions. RESULTS: Cytoplasmic values of manganese SOD, catalase, and glutathione peroxidase were decreased in pancreatic cells from chronic pancreatitis specimens when compared with normal pancreas. In pancreatic carcinoma specimens, mean cytoplasmic gray-level values of all antioxidant enzymes were decreased when compared with normal pancreas. CONCLUSION: There appears to be a gradual decrease in antioxidant enzyme expression in pancreatic cells from normal pancreas to chronic pancreatitis to pancreatic cancer.

Adenocarcinoma↗

PubMed2003

Suppression of the malignant phenotype in human pancreatic cancer cells by the overexpression of manganese superoxide dismutase.

Cells contain a large number of antioxidants to prevent or repair the damage caused by reactive oxygen species. One component of the antioxidant system, manganese superoxide dismutase (MnSOD), is localized in the mitochondria, and the levels of this protein have been previously shown to inversely correlate with pancreatic cancer cell growth. The aim of the present study was to determine whether MnSOD overexpression could suppress the in vitro and in vivo malignant phenotype of a human pancreatic cancer cell line. Tumor cell behavior was determined in the pancreatic cancer cell line MIA PaCa-2 by examining cell growth, plating efficiency, and anchorage-independent growth in soft agar. MnSOD was overexpressed in the pancreatic cancer cell line MIA PaCa-2 by infection with an adenovirus-MnSOD construct. Cells were also injected s.c. in nude mice and tumor volume was calculated. Single and multiple direct injections of the adenoviral MnSOD construct (10(9) plaque-forming units) were delivered to the tumor. Increases in MnSOD immunoreactivity and activity were seen after transduction with the adenovirus-MnSOD construct. Increasing MnSOD levels correlated with increased doubling time. Cell growth, plating efficiency, and growth in soft agar decreased with increasing amounts of the adenovirus MnSOD construct. Tumors grew slower and survival was increased in nude mice injected with the adenoviral MnSOD construct compared with the parental cell line, whereas multiple injections of the adenoviral MnSOD construct further inhibited tumor cell growth and extended survival. These results suggest that MnSOD may be a tumor suppressor gene in human pancreatic cancer. Delivery of the MnSOD gene may prove beneficial for suppression of pancreatic cancer growth.

Adenoviridae↗

PubMed2003

Preventing postoperative Staphylococcus infections: an update.

Postoperative nosocomial infections are associated with increased cost, hospitalization, and morbidity. S. aureus is the most common organism that contributes to postoperative nosocomial infections, and causes up to 25% of these infections. The role of the nose as a reservoir for S. aureus and possible subsequent endogenous infections has been recognized for approximately 40 years. Elimination of nasal carriage of S. aureus may be another intervention aimed at reducing postoperative infections. Mupirocin, a topical antibiotic effective against Gram-positive organisms, was proved to be effective in reducing the rates of nasal colonization of S. aureus and decreased postoperative nosocomial infections due to S. aureus.

Anti-Bacterial Agents↗

PubMed2002

The effect of phosphodiesterase inhibition on gallbladder motility in vitro.

BACKGROUND: Coffee consumption decreases the risk of gallstone disease. The proposed motility effects of caffeine, a phosphodiesterase (PDE) inhibitor, are unknown. The aim of our study was to determine the effect of caffeine and specific PDE inhibitors on gallbladder motility in vitro. METHODS: Gallbladder muscle strips from opossums were attached to force transducers. Baseline tone, electrical field stimulation (EFS)-induced nitric oxide-mediated off responses, and changes in the cholecystokinin (CCK)-8 dose-response relationship were measured. Caffeine; vinpocetine (VIN), type I PDE inhibitor; erythro-9-[2-hydroxy-3-nonyl]adenine HCl (EHNA), type II PDE inhibitor; zarderverine (ZARD), type III/IV PDE inhibitor; Ro 20-1724, type IV PDE inhibitor; and zaprinast (ZAP), type V PDE inhibitor were added to the tissue baths. RESULTS: Caffeine and all specific PDE inhibitors decreased baseline tone. Caffeine, VIN, EHNA, ZARD, Ro 20-1724, and ZAP decreased the EFS-induced off response. Caffeine (10(-5) M) and EHNA increased the CCK-8 dose-response contractions. This effect was not inhibited by atropine. Caffeine increased the tissue levels of cyclic 3',5'-guanosine monophosphate but not cyclic 3',5'-adenosine monophosphate. Caffeine decreases baseline tone and the off response via type I-V PDE pathways. Caffeine also increases CCK-induced gallbladder contractions via type II PDE pathways. CONCLUSION: These effects may be a mechanism that contributes to the decreased gallstone formation with caffeine consumption.

Animals↗