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PubMed2004

Lipoic acid attenuates hypertension and improves insulin sensitivity, kallikrein activity and nitrite levels in high fructose-fed rats.

Chronic feeding of fructose to normal rats causes impaired glucose tolerance, loss of tissue sensitivity to insulin, hyperinsulinemia and hypertension. alpha-Lipoic acid (LA), a co-enzyme known for its potent antioxidant effects, stimulates insulin-mediated glucose uptake in clinical and experimental diabetes. The purpose of this study was to examine whether LA can mitigate fructose-induced insulin resistance and associated abnormalities. Male Wistar rats of body weights 150-170 g were divided into 4 groups containing 12 rats each. Control rats received a control diet containing starch and water ad libitum. Fructose rats received a fructose-enriched diet (>60% of total calories). Fructose + LA rats received a fructose diet and LA (35 mg/kg b.w.) intraperitoneally. Control + LA rats received a normal diet and LA (35 mg/kg b.w.) intraperitoneally. After the treatment period of 20 days, blood pressure (BP) was measured. Oral glucose-tolerance test, insulin-sensitivity index, urea and creatinine clearance tests, and plasma and urinary sodium and potassium levels were analysed. Kallikrein activity and nitrite content were assayed. Additionally, the activities of RBC-membrane Na(+)/K(+) ATPase and Ca(2+) ATPase enzymes were assayed. Fructose rats showed increased BP, decreased glucose tolerance, decreased insulin sensitivity and altered sodium and potassium levels and renal clearance. LA supplementation mitigated these alterations. The increase in BP was attenuated and the levels of biochemical parameters were brought close to normal. The BP-lowering effect of LA in fructose rats may be related to improvement in insulin sensitivity.

Animals↗

PubMed2005

Water turbidity affects predator-prey interactions in a fish-damselfly system.

Community structure may differ dramatically between clear-water and turbid lakes. These differences have been attributed to differences in the cascading effect of fish on prey populations, owing to the reduced efficiency of fish predation in the presence of macrophytes. However, recent theoretical ideas suggest that water turbidity may shape predator-prey interactions, and it is predicted that prey will relax its antipredation behaviour in turbid water (H1). As a result, the nature of predator-prey interactions is expected to shift from both direct and indirect in clear water to dominantly direct in turbid water (H2). We tested these ideas in a fish-damselfly predator-prey system. In a first behavioural experiment, we looked at antipredation behaviour of damselfly larvae isolated from habitats that differ in turbidity, in the presence of fish in clear and turbid water. As predicted in H1, the larvae were more active in turbid than in clear water. In a complementary enclosure experiment, we reared larvae in a clear-water pond and a turbid pond, respectively, and manipulated the origin of the larvae (clear-water, turbid pond), fish presence (absent, present), and vegetation density (sparse, abundant). In both ponds, fish had a direct negative effect on survival of the larvae, which was mitigated in the presence of vegetation. In the fish treatment, the change in average body mass tended to be higher in the turbid pond than in the clear-water pond, suggesting indirect effects of fish were mitigated in the turbid pond. This was supported by a negative effect of fish on the effective growth rate of larvae in the clear pond, but not in the turbid pond. These results are compatible with the idea that predator-prey relationships are mainly governed by direct effects in turbid water, and by direct and indirect effects in clear water.

Analysis of Variance↗

PubMed2026

Gout and allopurinol adherence in newly diagnosed patients and the risk of fractures: a nationwide cohort study.

INTRODUCTION / OBJECTIVES: The association between gout and fractures remains controversial due to the competing effects of uric acid's antioxidant properties and gout-induced chronic inflammation. Our study aimed to evaluate the risk of fractures in newly diagnosed gout patients and to analyze the impact of Allopurinol medication adherence on this risk. METHODS: This nationwide cohort study utilized the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database (2002-2019). We identified 4,107 patients newly diagnosed with gout who remained on continuous allopurinol therapy during the 24-month medication assessment period and matched them 1:3 with 12,321 non-gout controls using propensity score matching. Allopurinol adherence was assessed via the Medication Possession Ratio (MPR) over a 24-month period and categorized into three groups: MPR < 0.3, 0.3 ≤ MPR < 0.8, and MPR ≥ 0.8. Multivariable Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for fractures (vertebral, hip, and distal radius). RESULTS: Gout patients demonstrated a significantly higher risk of overall fractures compared to the non-gout group (aHR 5.52; 95% CI 4.19-7.26). A significant inverse linear relationship was observed between allopurinol adherence and fracture risk (P for trend < .001). The risk was highest in the low-adherence group (MPR < 0.3; aHR 5.91; 95% CI 4.40-7.93) and relatively lower in the high-adherence group (MPR ≥ 0.8; aHR 4.77; 95% CI 2.94-7.72). Consistent trends were observed for vertebral (aHR 5.68) and hip (aHR 4.22) fractures. These associations remained consistent across all subgroups, including age, sex, and comorbidities. CONCLUSION: Newly diagnosed gout is associated with a substantially increased risk of fractures. Higher adherence to Allopurinol therapy is correlated with a significant reduction in this risk, suggesting that consistent urate-lowering therapy may mitigate gout-related bone fragility. Key Points • Newly diagnosed gout patients have a significantly higher risk of major osteoporotic fractures compared to the non-gout population. • A significant inverse linear relationship exists between Allopurinol adherence and fracture risk, with the highest adherence group (MPR ≥ 0.8) showing a relatively lower risk. • Consistent urate-lowering therapy (ULT) may mitigate bone fragility in gout patients by reducing systemic inflammatory burden caused by urate crystal deposition.

Humans↗

PubMed2004

Drought hazard and desertification management in the drylands of Southern Africa.

Droughts have been occurring persistently in southern African dryland regions for over a century. The impacts of droughts on people, their domesticated animals, wildlife, rangelands and cropped lands have been shown to be astronomical. If left alone the rangelands often recover after the calamity, however human occupation has led to irreversible damage. Even though some communities have evolved viable and sustainable coping mechanisms, recent times have seen weakened coping strategies leading to loss of life in most of the 10 countries in southern Africa. While land degradation has many inter-related causes and effects, drought-related effects have proven most difficult to manage and/or overcome. Drought-related land degradation or desertification poses a huge threat to sustainable land and resource management in the region. The paper examines appropriate drought mitigating initiatives, linking them to land tenure and land management practices. Numerous interventions targeted at reducing poverty and improvement in resource management have failed to achieve desired effects due to rigidity and imposition, and failure of the external interveners to recognise and incorporate indigenous peoples' preferences and coping strategies. Non-governmental organisations and authorities' willingness to institute drought and desertification combating measures are reviewed, highlighting the role that community action plays in reducing adverse effects in the region. Linkages to trade patterns that perpetuate poverty and unwise use of resources are discussed. Adopting 'people centred' mitigating measures is emphasised. Success rests with both the people in the 'south' and those in the 'north'. What is required is an informed global action.

Africa, Southern↗

PubMed2006

The ecotoxicological recovery of Ely Creek and tributaries (Lee County, VA) after remediation of acid mine drainage.

The Ely Creek watershed (Lee County, VA) was determined in 1995 to be the most negatively affected by acid mine drainage (AMD) within the Virginia coalfield. This determination led the US Army Corps of Engineers to design and build passive wetland remediation systems at two major AMD seeps affecting Ely Creek. This study was undertaken to determine if ecological recovery had occurred in Ely Creek. The results indicate that remediation had a positive effect on all monitoring sites downstream of the remediated AMD seeps. At the site most impacted by AMD, mean pH was 2.93 prior to remediation and improved to 7.14 in 2004. Benthic macroinvertebrate surveys revealed that one AMD influenced site had increased taxa richness from zero taxa in 1997 to 24 in 2004. While in situ testing of Asian clams resulted in zero survival at five of seven AMD influenced sites prior to remediation, some clams survived at all sites after. Clam survival was found to be significantly less than upstream references at only two sites, both downstream of un-mitigated AMD seeps in 2004. An ecotoxicological rating (ETR) system that combined ten biotic and abiotic parameters was developed as an indicator of the ecological status for each study site. A comparison of ETRs from before and after remediation demonstrated that all sites downstream of the remediation had experienced some level of recovery. Although the remediation has improved the ecological health of Ely Creek, un-mitigated AMD discharges are still negatively impacting the watershed.

Aluminum↗

PubMed2006

The use of religion in death penalty sentencing trials.

Both prosecutors and defense attorneys have presented religious appeals and testimony about a defendant's religious activities in order to influence capital jurors' sentencing. Courts that have objected to this use of religion fear that religion will improperly influence jurors' decisions and interfere with their ability to weigh aggravators and mitigators. This study investigated the effects of both prosecution and defense appeals. Prosecution appeals did not affect verdict decisions; however, use of religion by the defense affected both verdicts and the weighing of aggravators and mitigators. These results could be due to differences in perceived sincerity and remorse that are conveyed in the various appeals.

Adolescent↗

PubMed2006

From stratospheric ozone to climate change: historical perspective on precaution and scientific responsibility.

The issue of the impact of human activities on the stratospheric ozone layer emerged in the early 1970s. But international regulations to mitigate the most serious effects were not adopted until the mid-1980s. This case holds lessons for addressing more complex environmental problems. Concepts that should inform discussion include 'latency,' 'counter-factual scenario based on the Precautionary Principle,' 'inter-generational burden sharing,' and 'estimating global costs under factual and counter-factual regulatory scenarios.' Stringent regulations were adopted when large scientific uncertainty existed, and the environmental problem would have been prevented or more rapidly mitigated, at relatively modest incremental price, but for a time delay before more rigorous Precautionary measures were implemented. Will history repeat itself in the case of climate change?

Air Pollutants↗

PubMed1994

Responsibility analysis: a methodology to study the effects of drugs in driving.

In order to study the role of drugs in driving, a responsibility analysis was developed to allow an assessment to be made of the driver's culpability or responsibility in an accident. Factors possibly mitigating drivers' responsibility in each accident were identified and scored. Factors considered were: condition of road, condition of vehicle, driving conditions, accident type, witness observations, road law obedience, difficulty of task, and level of fatigue. If a sufficient number of mitigating factors were identified a driver would be found to be either partly or totally exonerated from blameworthiness and scored either as a contributory or nonculpable driver. If drugs present in a driver contributed to accident causation, it would be expected that they would be overrepresented in culpable drivers, i.e. those drivers not exonerated from blame. A total of 341 driver fatalities occurring in Victoria were analysed for blood alcohol content (BAC). Twenty-nine percent had a BAC over .05% (the legal limit in Victoria). Alcohol-positive drivers were statistically overrepresented in the culpable group (p < .001), in single-vehicle accidents (p < .05) and those accidents in which vehicles left the road for no apparent reason (p < .001). Odds-ratio estimation of relative risk of culpable and nonculpable drivers showed that the relative risk rose disproportionately to BAC.

Accidents, Traffic↗

PubMed1984

Functional importance of coronary collateral vessels.

Angiographically demonstrable coronary collateral vessels are believed to preserve myocardial function at rest, but disagreement exists regarding the importance of collaterals in mitigating exercise-induced ischemic dysfunction. Therefore, we used radionuclide cineangiography during exercise to assess the left ventricular (LV) functional effects of collateral vessels in 125 patients with at least 1 major coronary artery that had greater than or equal to 90% diameter stenosis but without prior myocardial infarction. Regional LV function, graded on a 4-point scale, worsened during exercise by at least 1 grade in 14 of 43 regions (33%) with good collaterals, and in 70 of 98 without good collaterals (p less than 0.001). Of the 43 good collaterals, 14 were supplied by arteries with greater than or equal to 75% stenoses; 10 of 14 regions (71%) thus supplied worsened by at least 1 grade (p less than 0.01). The ischemia-mitigating effect of coronary collateral vessels also affected the magnitude of exercise-induced global dysfunction. Of 43 patients with only one greater than or equal to 90% stenotic artery, 18 had good collaterals; in these patients, average LV ejection fraction (EF) at rest was 51 +/- 8%; LVEF during exercise was 46 +/- 7%. In the 25 patients without good collaterals, LVEF at rest was 52 +/- 7%, and LVEF during exercise was 41 +/- 9% (p less than 0.005 vs good collaterals).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Quantitative evaluation of electromyogram activity in rat extensor and flexor muscles immobilized at different lengths.

Because immobilization of muscles in the "long" position mitigates the effects of inactivity and rapid wasting occurs when muscles are immobilized in the "short" position, a study was made of the EMG activity in the soleus (SOL)--an extensor muscle--and the tibialis anterior (TA)--a flexor muscle--in order to clarify the possible role of muscle function in modifying the course of disuse atrophy. EMG activity was recorded in the SOL and TA muscles in adult rats in which the ankle had been immobilized in a plaster cast either in plantar flexion or dorsiflexion. The number of action potentials per minute in samples of the EMG activity from control and immobilized muscles was assessed before, for 10 days during immobilization, and up to 9 days after removal of the cast. Immobilization in the short position (plantar flexion) led to a dramatic reduction in the EMG activity of the SOL (to 10% of the control). On the other hand, fixation of the SOL in the long position was without effect upon resting EMG activity. In the TA, EMG activity was exclusively phasic in character and corresponded to about 3% of that of the SOL. Neither the fixation of the ankle in plantar flexion nor dorsiflexion had any appreciable effect upon EMG activity in the TA. We conclude that, because immobilization in the lengthened position does not increase EMG activity in either extensor or flexor muscles, passive stretch appears to be the factor mainly responsible for mitigating the effects of disuse in this situation. On the other hand, when a typical extensor muscle (SOL) is immobilized in the shortened position and undergoes rapid wasting, an accessory role of decreased activity cannot be excluded.

Animals↗

PubMed1988

Striatal grafts provide sustained protection from kainic and quinolinic acid-induced damage.

Grafts of neonatal striatal tissue were placed into the striata of adult rats. When challenged immediately with intrastriatal injections of either kainic or quinolinic acid, excitotoxic damage was prevented. Thirty days later these same graft recipients received another injection of excitotoxin. The intrastriatal grafts continued to mitigate toxin-induced damage. It is hypothesized that the grafted cells not only survive, but that they may continue to elaborate some substance or substances that prevent excitotoxin-induced injury for at least 30 days. Previous investigations indicated that grafts of neonatal striatal tissue can protect the recipient striatum from kainic acid toxicity. In the following study it is demonstrated that such grafts also protect the striatum from quinolinic acid, an endogenous excitotoxin which induces kainate-like neuronal degeneration and has been implicated in the pathogenesis of Huntington's disease. It is postulated that the salutary effect of striatal grafting may be sufficiently long lasting to mitigate a chronic toxic insult. Such grafting may therefore represent a therapy for Huntington's disease and other neurodegenerative disorders in which an endogenous or exogenous toxin has been implicated as the pathogenetic agent.

Animals↗

PubMed1981

Ketamine: convulsant or anti-convulsant?

Ketamine hydrochloride in doses producing narcotic-cataleptic effects (50--100 mg/kg, IP) reduced the intensity of picrotoxin convulsions and eliminated seizures caused by metrazol administration. Subcataleptic doses (5--20 mg/kg) increased the duration of mitigated convulsive symptoms (abortive grand mal fits, jerks) especially those evoked by picrotoxin. Narcotic-cateleptic doses of ketamine considerably increased the duration of the period of single and multiple jerks produced by picrotoxin administration. Both convulsants transformed 1--2 Hz "ketamine complexes" into 2--4 Hz Wave spike discharges which appeared in a quasi-periodic fashion alternating with periods of relatively suppressed electrocortical activity. Electroencephalographic grand mal patterns were typically dissociated from behavioral manifestations under 50--100 mg/kg of ketamine, followed by a short period of postictal depression and a rapid recovery of preseizure electrographic patterns. Findings suggest that mechanisms involved in seizure alleviation may be responsible for sustaining mitigated convulsive phenomena. Neuro-chemical processes underlying antiepileptic ketamine potency remain unknown.

Animals↗

PubMed1996

Lessons learned from investigations of therapy misadministration events.

PURPOSE: Investigation teams composed of Idaho National Engineering Laboratory (INEL), United States Nuclear Regulatory Commission (NRC), and subcontractor personnel performed detailed investigations and analyses of seven misadministration events that were specifically selected on the basis of particular characteristics. These events were analyzed to identify the direct causes, contributing factors, actions to mitigate the event, and the consequences of these events. The INEL also sought to determine the role played by the recent Quality Management Rule. METHODS AND MATERIALS: The investigation teams were multidisciplinary and, depending on the nature of the event, included three or more team members with appropriate expertise in the areas of radiation oncology, medical physics, nuclear medicine technology, risk analysis, and human factors. The investigations focused on the general areas of causes of the event, mitigating actions, and corrective actions. Seven misadministration events were investigated by the teams during 1991 and 1992. RESULTS: Results from the events investigated indicated that (a) the institutional traditions of some licensees contributed to the potential for misadministrations, (b) many misadministrations occurred primarily due to lack of procedures or procedures that were not clearly written, (c) some licensees in this study had not effectively implemented their Quality Management programs, and (d) limited involvement on the part of the Radiation Safety Officer and Authorized Users and changes in routine and unique conditions contribute to the potential for misadministrations. CONCLUSIONS: The project shows that licensees that have experienced misadministration events appear to lack comprehensive safety cultures, where all aspects of daily operations are shaped with patient and staff safety being the primary objective of all activities.

Brachytherapy↗

PubMed1995

Effects of enalapril on T and B cell function in rats after myocardial infarction.

The cellular mechanisms following myocardial infarction remain poorly characterized. It is believed that an inflammatory and immunologic process may be involved and that the beneficial effects of enalapril on remodeling may, in part, work through an immune mechanism. To characterize the effect of enalapril on immune alterations in the late phase of ventricular remodeling after myocardial infarction, rats underwent left coronary artery ligation followed by 6 weeks of either enalapril or placebo treatment. Infarct sizes, heart weights, and volumes were compared. Peripheral and splenic leukocyte and lymphocyte subsets, along with T cell blastogenesis, were quantified in enalapril treated rats 6 weeks after coronary ligation and compared to untreated control rats. Additionally, antibody production to a de novo antigen, keyhole limpet hemocyanin, was assessed with and without treatment. Average infarct size was equivalent among enalapril-treated myocardial infarction rats and untreated infarct rats. There was, however, less left and right ventricular hypertrophy in the enalapril treated group. Enalapril completely prevented the 42% increase in white blood count, the 88% increase in neutrophils, and the 28% increase in lymphocyte count seen in untreated infarct rats. Both untreated and enalapril treated rats tended toward a decrease in T helper:suppressor ratio. All rats treated with enalapril, however, had a significant increase in the T helper:suppressor ratio versus untreated control rats (F = 3.6, P = .018). Blastogenesis was markedly increased in T cells from infarcted animals. This was mitigated by treatment with enalapril. Additionally, immunoglobulin G antibody production was significantly lessened in rats treated with enalapril. The results of this study suggest that alterations in immunoregulatory cell type and function occurs following myocardial infarction. The beneficial effects of the angiotensin-converting enzyme inhibitor enalapril may be, in part, due to its mitigating effects on immune cell release and activation following myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2005

Endothelial dysfunction induced by postprandial lipemia is neutralized by addition of proteins to the fatty meal.

BACKGROUND: Postprandial lipemia is known to reduce endothelium-dependent flow-mediated vasodilation (FMD). Because postprandial lipemia can be acutely mitigated when proteins are added to the fatty meal, we investigated whether this mitigation could neutralize the lipemia-induced endothelial dysfunction. DESIGN: Sixteen healthy students (aged 19-23, eight males and eight females) received three different test meals at intervals of 1 week between successive tests. Each meal contained whipping cream alone or whipping cream together with either caseinate or soy protein. The whipping cream contained 33% fat, and 3 ml (= 1 g fat) was given per kg body weight. The proteins added were either 50 g sodium caseinate or 50 g soy protein. FMD was assessed by two-dimensional ultrasonography of the brachial artery in the fasting state and 1, 2, 3, 4, 5, 6, 7, and 8h after the fatty meal. Blood was withdrawn at the same time-points from the other arm. Triglycerides, free fatty acids, and insulin were determined using routine methods, and both L-arginine and asymmetric dimethylarginine (ADMA) were determined by LC-MS. RESULTS: Postprandial lipemia reduced FMD, the reduction reaching a maximum of 58% after 3 h. This impairment of endothelial function was not observed when either of the test proteins had been added to the fatty meal (p < 0.01 for caseinate and p < 0.001 for soy protein). The effects of the protein addition were decreases in triglycerides and free fatty acids, increased insulin concentrations at all time-points, and an increased arginine/ADMA ratio between 1 and 5h after the meal, particularly in the case of the soy protein. CONCLUSION: We suggest that the neutralization of the lipemia-induced endothelial dysfunction is caused by direct and indirect effects of the proteins insulinotropy and, secondly, by an increased supply of L-arginine.

Adult↗

PubMed2006

Preparing for the unthinkable: emergency preparedness for the hematopoietic cell transplant program.

Emergencies come at the most inopportune times. Some are totally unexpected, others come with short warnings. Although rare, an emergency comes with the potential to wreak disaster and pose serious risk to the services provided to hematopoietic cell transplant (HCT) patients. Yet, the consequences of an emergency can be mitigated by thinking the unthinkable and having a plan for emergency preparedness in place. Each HCT center should develop a plan containing steps of mitigation, preparedness, response and recovery. This report provides the framework for a HCT-specific emergency preparedness plan that can be used by individual centers to develop customized guidelines on preparing for, responding to, and recovering from an emergency.

Disaster Planning↗

PubMed2004

Urinary adiponectin excretion is increased in patients with overt diabetic nephropathy.

Adiponectin, a novel adipose-derived adipocytokine, has beneficial effects not only on improvement of insulin sensitivity but also on mitigation of vascular damage. To evaluate whether adiponectin is implicated in the pathogenesis of diabetic nephropathy characterized by microvascular damage, we examined urinary and serum adiponectin levels in type 2 diabetic patients with different stages of nephropathy. We first confirmed adiponectin is excreted into urine through Western blot analysis, followed by measurements of urinary and serum adiponectin levels by radioimmunoassay. Interestingly, urinary adiponectin excretion levels were markedly increased in patient group with overt nephropathy relative to the groups without nephropathy and with incipient nephropathy. Surprisingly, serum adiponectin levels were also elevated in patient group with overt nephropathy. Increased urinary adiponectin excretion may result from elevations in circulating adiponectin levels and enhanced filtration of circulating adiponectin through the damaged kidney. Furthermore, adiponectin synthesis in adipose tissue and its secretion into circulating blood may be enhanced to mitigate microvascular damage in the advanced stage of diabetic nephropathy.

Adiponectin↗

PubMed2005

Fourier's law of heat transfer and its implication to cell motility.

Fourier's law of heat transfer addressing temperature differences is intrinsically selective in favoring the mitigation of the differences proceeding as fast as possible. We present an experimental demonstration of such selective behavior of material origin. When an actin filament equipped with nano-scale heat acceptors was placed under heat pulsation, it demonstrated a unidirectional movement without the presence of myosin or ATP. The prime factor for the unidirectional movement was the temperature differences between the locally heated portions on the actin filament and the cooler material bodies in the surroundings. The unidirectional movement could be enhanced in the process of mitigating the temperature differences as fast as possible.

Actin Cytoskeleton↗