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Biomedical subjects

Michael Golden

Publications and source records attributed to Michael Golden.

7 recordsLinked to original sources

Recombination in eukaryotic single stranded DNA viruses.

Although single stranded (ss) DNA viruses that infect humans and their domesticated animals do not generally cause major diseases, the arthropod borne ssDNA viruses of plants do, and as a result seriously constrain food production in most temperate regions of the world. Besides the well known plant and animal-infecting ssDNA viruses, it has recently become apparent through metagenomic surveys of ssDNA molecules that there also exist large numbers of other diverse ssDNA viruses within almost all terrestrial and aquatic environments. The host ranges of these viruses probably span the tree of life and they are likely to be important components of global ecosystems. Various lines of evidence suggest that a pivotal evolutionary process during the generation of this global ssDNA virus diversity has probably been genetic recombination. High rates of homologous recombination, non-homologous recombination and genome component reassortment are known to occur within and between various different ssDNA virus species and we look here at the various roles that these different types of recombination may play, both in the day-to-day biology, and in the longer term evolution, of these viruses. We specifically focus on the ecological, biochemical and selective factors underlying patterns of genetic exchange detectable amongst the ssDNA viruses and discuss how these should all be considered when assessing the adaptive value of recombination during ssDNA virus evolution.

Animals↗

Effects of ascorbic acid, glutathione, thiocyanate, and iodide on antimicrobial activity of acidified nitrite.

It has been hypothesized that dietary nitrite augments the antimicrobial activity of gastric acid after conversion to nitric oxide and other reactive nitrogen intermediates, thus resulting in increased resistance against gastrointestinal infection. In this study, we showed that the reducing agents ascorbic acid and glutathione reduced the activity of acidified nitrite against Yersinia enterocolitica (P < 0.001). In contrast, iodide and thiocyanate increased the antimicrobial activity (P < 0.001), whereas hydroxyacids (citrate, lactate, and tartarate) had no measurable effects.

Acids↗

Beta-cyclodextrin tetradecasulfate, a novel cyclic oligosaccharide, inhibits thrombus and neointimal formation after coronary vascular injury.

BACKGROUND: Neointimal formation is a major cause of restenosis after interventional vascular procedures. Beta-cyclodextrin tetradecasulfate (beta-CDT) has been shown to inhibit fibroblast growth factor activity and we hypothesized that beta-CDT would reduce intimal formation. DESIGN: Three studies were performed: (1) pharmacokinetics of oral and intravenous beta-CDT and determination of optimal dose, (2) determination of efficacy of oral and intravenous beta-CDT in reducing neointimal formation after balloon-overstretch injury and (3) determination of the effect of beta-CDT on cellular proliferation, factor Xa activity, activated clotting time, activated partial thromboplastin time and thrombus formation. METHODS: Pharmacokinetics were determined in eight domestic swine following administration of oral beta-CDT and intravenous beta-CDT at three doses each. In the efficacy study, balloon-overstretch injury of 37 pigs (69 arteries) was performed and randomized into three groups (n = 23 arteries/group): control, oral administration of 300 mg beta-CDT/kg per day or intravenous infusion of 100 mg beta-CDT/kg per day. Animals were sacrificed 14 days later. Cellular proliferation and mural thrombus were determined in six arteries/group at 5 days and endothelial coverage was evaluated at 5 and 14 days. RESULTS: Oral and intravenous beta-CDT reduced the intimal hyperplasia area normalized to injury index by 24 and 48%, respectively: control, 3.03 +/- 0.75 mm2, oral, 2.31 +/- 0.83 mm2 (P = 0.004) and intravenous, 1.67 +/- 0.73 mm2 (P = 0.0000002). beta-CDT reduced cellular proliferation (control, 55 +/- 18%, oral, 35 +/- 7%, P = 0.03 and intravenous, 30 +/- 12%, P = 0.01) and mural thrombus formation (control, 0.84 +/- 0.4 mm2, oral, 0.44 +/- 0.14 mm2, P = 0.04, intravenous, 0.42 +/- 0.09 mm2, P = 0.03). Endothelial coverage was increased in the experimental groups (P = 0.008, oral versus control, P < 0.0001, intravenous versus control). Factor Xa activity was inhibited 9-10 fold following intravenous administration while oral administration demonstrated no effect. CONCLUSIONS: Both oral and intravenous formation of beta-CDT reduced intimal hyperplasia with the greatest reduction in the intravenous group. We postulate that beta-CDT was effective by the combination of increasing endothelial coverage, reducing mural thrombus formation, inhibiting factor Xa activity and reducing cellular proliferation.

Animals↗

Bone formation in carotid plaques: a clinicopathological study.

BACKGROUND AND PURPOSE: Bone formation and dystrophic calcification are present in carotid endarterectomy plaques. The clinical significance of these findings is unknown. The purpose of this study was to determine whether bone formation and extensive dystrophic calcification are associated with stable plaques and protective against ischemic vascular events. METHODS: Carotid endarterectomy plaques were collected from 142 patients (94 men) with carotid stenosis. The specimens were evaluated for lamellar bone formation, dystrophic calcifications, inflammatory infiltrates, neovascularization, and histological type or grade of plaque according to a standard AHA grading system. Immunohistochemical staining was performed to identify vascular endothelial cells in neovascularization (factor VIII) and lymphocytes. Clinical data, including history of cerebrovascular and cardiovascular events, were recorded at the time of surgery. RESULTS: Patients with calcification of carotid plaques had fewer symptoms of stroke and transient ischemic attack (P=0.042) than those without calcification. Stroke and transient ischemic attack occurred less frequently in patients with plaques with large calcific granules (P=0.021). Of the patients, 13% had lamellar bone formation, which directly correlated with the presence of sheetlike calcifications (P=0.0001) and inversely correlated with ulcerated lesions (P=0.048). The presence of bone also correlated with diabetes (P<0.01) and coronary artery disease (P<0.01). Of the 20 patients with bone, 6 had a history of stoke and transient ischemic attack (P=0.5). CONCLUSIONS: The results indicate that bone formation tends to occur in heavily calcified carotid lesions devoid of ulceration and hemorrhage. Patients with extensive calcification of the carotid plaques are less likely to have symptomatic disease.

Adult↗

Electrotherapy reverses inframalleolar ischemia: a retrospective, observational study.

OBJECTIVE: To determine if high-voltage pulsed current (HVPC) augments ischemic wound healing and increases periwound perfusion. DESIGN: A 5-year, retrospective, observational study was conducted on successive patients with ischemic wounds who were poor candidates for revascularization. INTERVENTION: HVPC was applied directly to wounds at greater than 100 volts, 100 pulses per second, 1 hour per day. In addition to HVPC, patients received standard care for ischemic wounds at the study facility. Ischemic wounds for which HVPC was not clinically indicated or not available received standard care alone. MAIN OUTCOME MEASURES: Wound area measured by planimetry, wound appearance observed by digital imaging techniques, and microcirculation monitored by transcutaneous oxygen (TcPo(2)) levels. RESULTS: The group that received HVPC plus standard care showed smaller wound areas from weeks 20 though 52 after the start of treatment compared with the group that received standard care alone (P <.05; Mann-Whitney test). One year after the start of treatment, 90% of HVPC-treated wounds were healed, compared with 29% of the wounds that received only standard care (P <.05; Fisher exact test). For the HVPC group, maximum periwound TcPo(2) improved during electrotherapy (6 +/- 8 mm Hg [standard deviation; SD] at baseline improved to 26 +/- 20 SD, during HVPC, P <.05; Wilcoxon signed rank test). CONCLUSION: The results of this retrospective trial demonstrate that HVPC plus standard care improved the healing rate of high-risk ischemic wounds. A direct relationship was shown between improved healing rates and increased periwound perfusion. A prospective randomized controlled trial is needed to further support these observational, preliminary findings.

Adult↗

Electrotherapy promotes healing and microcirculation of infrapopliteal ischemic wounds: a prospective pilot study.

OBJECTIVE: To determine if high-voltage pulsed current (HVPC) electrotherapy augments ischemic wound healing and increases periwound microcirculation. DESIGN: A prospective, randomized, single-blinded, sham-controlled clinical trial was conducted on a homogenous subset of quasi-stable ischemic wounds. INTERVENTION: Active HVPC or sham HVPC was applied to wounds for a 14-week period. MAIN OUTCOME MEASURE: Wounds were monitored every 4 weeks, except 2 weeks between weeks 12 and 14, for wound area, wound appearance, and microcirculation, which was measured by transcutaneous oxygen (TcPO2) levels and laser Doppler flow. RESULTS: Ischemic wounds treated with active HVPC decreased in size, contrary to the expected increase in ischemic wound size that was observed in wounds in the control group (P <.05, Student t test; week 4). A trend toward smaller wound area occurred in wounds in the HVPC group compared with wounds in the control group (week 14). Among the HVPC group, an improvement in periwound microcirculation occurred at weeks 8 (P <.05, TcPO2; P <.01, laser Doppler) and 12 (P <.05, laser Doppler). These increases suggest that HVPC promotes arteriolar vasodilation and dermal capillary formation. HVPC was well tolerated. CONCLUSION: The results of this study demonstrate that HVPC decreased the area of ischemic wounds, reversing the expected increase in wound size, and improved microcirculation. The promising results of this pilot study require a larger Phase II study to confirm and generalize these findings. CLINICAL RELEVANCE: Electrotherapy may prove to be a relatively safe and effective complement to surgical revascularization to improve the odds of healing ischemic wounds and promoting limb salvage.

Adult↗