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PubMed2026

Reported exposure to news portrayals about mental health problems and their impact: Findings from the 2025 National Survey of Stigma and Discrimination.

OBJECTIVE: Media portrayals of people with mental illness have the power to mitigate or perpetuate stigma related to mental health. This study aimed to investigate reported real-world exposure to news media portrayals about people with mental health problems in the past 12 months and the impact of these. METHODS: Data were from a nationally representative survey of 6032 Australians exploring attitudes towards people with mental health problems. Participants were asked about their exposure to positive news stories about a person with a mental health problem, as well as negative portrayals, in which someone was harmed by a person with a mental health problem. Further questions covered the sources (traditional or social media) and impact of these exposures. RESULTS: Regression models were used to explore sociodemographic predictors of impact. Most participants reported exposure to negative news portrayals (68.4%, 95% confidence interval = [66.9, 69.8]), while fewer reported exposure to positive news stories (33.7%, 95% confidence interval = [32.3, 35.2]). Most people exposed to the negative news stories reported a negative impact (69.0%, 95% confidence interval = [67.2, 70.7]), and most exposed to positive news stories reported a positive impact (80.2%, 95% confidence interval = [77.6, 82.5]). Age and gender were associated with reported impact but not lived experience of mental illness. CONCLUSIONS: Exposure to negative news stories about mental health problems was prevalent. Given their impact on news audiences broadly, negative news stories need to be accurate and responsible to mitigate negative impacts. A renewed focus on generating and promoting positive and stigma-challenging news stories is needed to increase subsequent positive impacts.

Humans↗
PubMedDate not supplied

Antioxidant supplementation with or without B-group vitamins after acute ischemic stroke: a randomized controlled trial.

BACKGROUND: Evidence shows that there is a rapid increase in the production of markers of oxidative damage immediately after acute ischemic stroke and that endogenous antioxidant defenses are rapidly depleted, thus permitting further tissue damage. Several studies point to an antioxidant effect of B-group vitamins and a pro-oxidant effect of elevated total plasma homocysteine (tHcy). METHODS: To test whether supplementary antioxidants with or without B-group vitamins during this critical period enhance antioxidant capacity or mitigate oxidative damage, ninety-six acute ischemic stroke patients within 12 hours of symptom onset were randomly assigned to receive either daily oral 800 IU (727 mg) vitamin E and 500 mg vitamin C (n = 24), or B-group vitamins (5 mg folic acid, 5 mg vitamin B(2), 50 mg vitamin B(6), and 0.4 mg of vitamin B(12); n = 24), both vitamins together (n = 24), or no supplementation (n = 24) for 14 days. Treatment groups and controls were matched for stroke subtype and age. Blood was obtained before treatment, at day 7, and day 14 for measurements of plasma or blood vitamin status, plasma total antioxidant capacity (TAOC), malondialdehyde (MDA), tHcy and C-reactive protein (CRP). RESULTS: Supplementation with antioxidant vitamins and B-group vitamins separately or together significantly increased the plasma concentration of vitamin C, E, pyridoxal phosphate (B(6) status), red blood cell folate, and improved a measure of B(2) status (red cell glutathione reductase activation coefficient [EGRAC]), compared with the control group. Plasma TAOC increased significantly in the antioxidant treatment groups compared with the nonsignificant decline seen in the control group. tHcy concentrations decreased in subjects who received B-group vitamins and the control group compared with the rise seen in those who received antioxidants alone. There was a significant reduction in plasma MDA concentration in the 3 treatment groups, in contrast to the increase seen in the control group; however, the changes were most evident in antioxidant groups. CRP concentrations (a marker of tissue inflammation) were significantly lower in the 3 treatment groups compared with the control group. There were no additive or synergistic effects of antioxidants and B-group vitamins together on any outcome measure. CONCLUSIONS: Antioxidants supplementation with or without B-group vitamins enhances antioxidant capacity, mitigates oxidative damage, and may have an anti-inflammatory effect immediately postinfarct in stroke disease.

Aged↗
PubMedDate not supplied

Engineering risk analysis of a hospital oxygen supply system.

Reports from the Food and Drug Administration (FDA) and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) have emphasized the potential for injury to patients caused by failures in oxygen supply systems. This article presents a model of patient risk related to the process of supplying oxygen at a single university hospital. One of the goals of the article is to illustrate how probabilistic risk analysis (PRA) can be used by hospitals to assess and mitigate risk and, therefore, to meet JCAHO requirements. PRA techniques are useful to 1) model the reliability of a complex system and 2) assess the cost-effectiveness of different risk mitigation measures. The authors focus on the risk estimation step, describing in detail their modeling of the oxygen supply system and analysis of the results. For the hospital that the authors study (20,000 admissions yearly), the total expected number of fatalities from oxygen system failure is 44 over a 30-year time horizon. The greatest contribution to the risk (94% of the expected number of fatalities) comes from problems that involve the supply network (e.g., damage to structure and poisoning) as opposed to incidents that occur inside patient rooms. Although the threat to patient safety is not dramatic, health care organizations should be concerned about potential failures of their oxygen system because improving this system could avoid low-probability, high-consequence failures at a low cost.

California↗
PubMed2001

The role of AIDS volunteers in developing community-based care for people with AIDS in Thailand.

The present study analyses the effectiveness of AIDS volunteers in mitigating the stigma attached to People With AIDS (PWAs) within the context of developing community-based care (CBC) in Thailand. A total of 86 trained village health volunteers (T-VHVs) and 99 non-trained village health volunteers (N-VHVs) were enrolled in the study. In addition, 58 villagers in the T-VHV's intervention area and 72 villagers in the non-intervention area were also enrolled. Both T-VHVs and N-VHVs as well as villagers were assessed to determine their level of knowledge with respect to HIV/AIDS and attitudes toward PWAs. Furthermore, we also determined the village health volunteers' level of activity in distributing knowledge of HIV/AIDS in order to prevent and reduce stigma in the community. Although T-VHVs showed a greater depth of knowledge of HIV/AIDS than N-VHVs (p < 0.05), positive attitudes toward PWAs and the level of practice of village health volunteers did not differ significantly between T-VHVs and N-VHVs. While the level of health knowledge of villagers did not differ significantly between the T-VHV's intervention and control areas, a significant difference was observed between the two areas in terms of the villagers' attitudes towards PWAs (p < 0.01). Villagers in the intervention area attached less stigma to PWAs; therefore, T-VHVs played a role in providing basic information on AIDS to the villagers and in mitigating the stigma attached to PWAs. However, these volunteers need to undergo further training through a well-organized training programme in order to obtain a greater depth of knowledge. This is essential for the development of community-based care for PWAs.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Effects of prevalence and testing by enzyme-linked immunosorbent assay and fecal culture on the risk of introduction of Mycobacterium avium subsp. paratuberculosis-infected cows into dairy herds.

A stochastic simulation model was developed to assess the risk of introduction of Mycobacterium avium subsp. paratuberculosis infection into a dairy herd through purchase of female replacement cattle. The effects of infection prevalence in the source herd(s), number of females purchased, and testing by enzyme-linked immunosorbent assay (ELISA) alone or ELISA and fecal culture as risk mitigation strategies were evaluated. Decisions about negative test results were made on a lot and individual basis. A hypothetical dairy herd, free from M. a. paratuberculosis, which replaced 1 lot (10, 30, or 100) of cows per year, was considered. Probability distributions were specified for the sensitivities and specificities of ELISA and fecal culture, the proportion of infected herds and within-herd prevalence for randomly selected replacement source herds (high prevalence) and herds in level 2 (medium prevalence) and level 3 (low prevalence) of the Voluntary Johne's Disease Herd Status Program (VJDHSP). Simulation results predicted that 1-56% of the lots had at least 1 M. a. paratuberculosis-infected cow. Assuming that ELISA sensitivity was 25%, simulation results showed on a lot basis that between 0.4% and 18% and between 0.1% and 9% were predicted to have at least 1 infected cow not detected by ELISA and by a combination of ELISA and fecal culture, respectively. On an individual cow basis, between 0.1% and 8.3% of ELISA-negative cattle in ELISA-positive lots were estimated to be infected. In both the lot and individual analyses, the probability of nondetection increased with larger lot sizes and greater prevalence. Sensitivity analysis indicated that the effect of a lower ELISA sensitivity (10%) was a variable decrease in mean detection probabilities for all combinations of prevalence and lot size. The benefit of testing introduced cattle with ELISA alone or in combination with fecal culture was found to be minimal if cows were purchased from known, low-prevalence (level 3) herds. The value of testing by ELISA alone or in combination with fecal culture was greatest in high-prevalence herds for all lot sizes. Testing of random-source cattle, bought as herd replacements, can partially mitigate the risk of introduction of M. a. paratuberculosis but not as well as by using low-prevalence source herds (level-3 VJDHSP), with or without testing.

Animals↗
PubMedDate not supplied

Collaborative research, participatory solutions: research on asbestos in Kuruman, South Africa.

The 1998 South African National Asbestos Summit proposed a post-apartheid asbestos policy for the country. In the areas of environmental rehabilitation, health care, and compensation, it envisioned connecting asbestos mitigation to participatory development. In 2001, the Asbestos Collaborative, an international and interdisciplinary team, conducted follow-up research on the recommendations of the 1998 Summit, researching environmental, health, and compensation issues through consultation of documents and interviews with officials in urban areas and with people in Kuruman, a former crocidolite-mining site with high rates of asbestos-related disease. In Kuruman, local opinion supported the recommendations of the Asbestos Summit, insisting that policies to mitigate the problem of asbestos must also address poverty. In the wake of the 2001 research, a new organization, the Asbestos Interest Group (AIG), has been founded to facilitate grassroots participation in asbestos issues. One success of the AIG has been the settlement of a lawsuit by former workers against the former mining company in Kuruman.

Asbestos↗
PubMed2003

Bacterial contamination of blood components: risks, strategies, and regulation: joint ASH and AABB educational session in transfusion medicine.

Bacterial contamination of transfusion products, especially platelets, is a longstanding problem that has been partially controlled through modern phlebotomy practices, refrigeration of red cells, freezing of plasma and improved materials for transfusion product collection and storage. Bacterial contamination of platelet products has been acknowledged as the most frequent infectious risk from transfusion occurring in approximately 1 of 2000-3000 whole-blood derived, random donor platelets, and apheresis-derived, single donor platelets. In the US, bacterial contamination is considered the second most common cause of death overall from transfusion (after clerical errors) with mortality rates ranging from 1:20000 to 1:85000 donor exposures. Estimates of severe morbidity and mortality range from 100 to 150 transfused individuals each year. Concern over the magnitude and clinical relevance of this issue culminated in an open letter calling for the "blood collection community to immediately initiate a program for detecting the presence of bacteria in units of platelets." Thereafter, the American Association of Blood Banks (AABB) proposed new standards to help mitigate transfusion of units that were contaminated with bacteria. Adopted with a final implementation date of March 1, 2004, the AABB Standard reads "The blood bank or transfusion service shall have methods to limit and detect bacterial contamination in all platelet components." This Joint ASH and AABB Educational Session reviews the risks, testing strategies, and regulatory approaches regarding bacterial contamination of blood components to aid in preparing practitioners of hematology and transfusion medicine in understanding the background and clinical relevance of this clinically important issue and in considering the approaches currently available for its mitigation, as well as their implementation. In this chapter, Drs. Hillyer and Josephson review the background and significance of bacterial contamination, as well as address the definitions, conceptions and limitations of the terms risk, safe and safety. They then describe current transfusion risks including non-infectious serious hazards of transfusion, and current and emerging viral risks. In the body of the text, Dr. Blajchman reviews the prevalence of bacterial contamination in cellular blood components in detail with current references to a variety of important studies. He then describes the signs and symptoms of transfusion-associated sepsis and the sources of the bacterial contamination for cellular blood products including donor bacteremia, and contamination during whole blood collection and of the collection pack. This is followed by strategies to decrease the transfusion-associated morbidity/mortality risk of contaminated cellular blood products including improving donor skin disinfection, removal of first aliquot of donor blood, pre-transfusion detection of bacteria, reducing recipient exposure, and pathogen reduction/inactivation. In the final sections, Drs. Vostal, Epstein and Goodman describe the regulations and regulatory approaches critical to the appropriate implementation of a bacterial contamination screening and limitation program including their and/or the FDA's input on prevention of bacterial contamination, bacterial proliferation, and detection of bacteria in transfusion products. This is followed by a discussion of sampling strategy for detection of bacteria in a transfusion product, as well as the current approval process for bacterial detection devices, trials recommended under "actual clinical use" conditions, pathogen reduction technologies, and bacterial detection and the extension of platelet storage.

Bacterial Infections↗
PubMed2002

The promise of e-Health - a Canadian perspective.

Canadians value their health care system above any other social program. Canada's system of health care faces significant financial and population pressures, relating to cost, access, quality, accountability, and the integration of information and communication technologies (ICTs). The health-system also faces certain unique challenges that include care delivery within a highly decentralised system of financing and accountability, and care delivery to a significant portion of the population sparsely distributed across a landmass of 10 million square kilometres, in areas of extreme climatic conditions. All of these challenges are significant catalysts in the development of technologies that aim to significantly mitigate or eliminate these selfsame challenges.The system is undergoing widespread review, nationally, and within each province and territory, where the bulk of care provision is financed and managed. The challenges are being addressed by national, regional and provincial initiatives in the public, private and not-for-profit sectors.The promise of e-Health lies in the manner and degree to which it can mitigate or resolve these challenges to the health system and build on advancements in ICTs supporting the development of a health infostructure. Canada is actively developing and implementing technological solutions to deliver health information and health care services across the country. These solutions, while exciting and promising, also present new challenges, particularly in regard to acceptable standards, choice of technologies, overcoming traditional jurisdictional boundaries, up-front investment, and privacy and confidentially.Many organisations and governments are working to address these challenges. The Canadian Institute for Health Information (CIHI) will play an increasingly significant role in these initiatives, as the management of health information becomes a more crucial factor in the successful delivery of health care services in the new millennium.

Journal Article↗
PubMed2025

Genome-wide identification, characterization, and expression pattern analysis of the glyoxalase gene family in Phyllostachys pubescens during abiotic stresses.

BACKGROUND: The glyoxalase pathway comprising of three enzymes i.e., glyoxalase I (GLYI), glyoxalase II (GLYII), and glyoxalase III (GLYIII), which play vital role in mitigating abiotic stresses by detoxifying the stress induced cytotoxic metabolite methylglyoxal (MG). Phyllostachys pubescens an ecologically and economically important forest species, plays vital roles in carbon sequestration and climate change mitigation. A genome-wide study was conducted to identify and characterize GLYI, GLYII, and unique DJ-1/GLYIII gene candidates in P. pubescens. The identified members were evaluated based on phylogenetic analysis, gene structure, chromosomal distribution, gene duplication, presence of conserved domain(s) and cis regulatory region. RESULTS: A total of 19 GLYI, 18 GLYII, and 15 GLYIII members were identified, each featuring characteristic domains: glyoxalase, metallo-&#x3b2;-lactamase, and DJ-1/PfpI, respectively. The presence of different cis-elements in the promoter region of the glyoxalase genes gives insights into their role and regulation under hormonal response, developmental processes and stress adaptation. Besides this, stress responsive transcription factors binding sites also dominated the promoter regions of glyoxalase genes. Expression analysis of various glyoxalase genes demonstrated significant variability under different stress conditions, underscoring their potential roles in stress modulation. Significant upregulation of all of the PhGLYI, PhGLYII, and PhGLYIII were observed under cold, drought, heavy metal and salinity stress suggesting their involvement in oxidative stress management, osmotic regulation and remodelling cellular redox homeostasis. Among the glyoxalase genes, PhGLYI-15, PhGLYII-9, and PhGLYIII-3 showed consistent upregulation under various abiotic stresses. CONCLUSIONS: Our findings reveal that glyoxalase genes crucially contribute towards the improvement of cellular osmotic potential in moso bamboo under different abiotic stresses. This study enhances our understanding of glyoxalase genes' evolution and functional roles in plants and opens new avenues for developing stress resilient crop varieties for sustainable agriculture.

Lactoylglutathione Lyase↗
PubMed2025

Altered ruminal microbiome tryptophan metabolism and their derived 3-indoleacetic acid inhibit ruminal inflammation in subacute ruminal acidosis goats.

BACKGROUND: Subacute ruminal acidosis (SARA) is a digestive disorder that often severely jeopardizes the health and lactation performance of ruminants fed a high-energy diet. Different dairy ruminants exhibit varying degrees of inflammation accompanied by variations in the rumen microbiota when SARA occurs. Our understanding of the occurrence of SARA and varying degrees of rumen epithelial inflammation is lacking. Hence, we performed rumen metagenomic, metagenome-assembled genome and metabolomic analyses, with transcriptome and single-nucleus RNA sequence analyses, to explore the microbial mechanism of SARA occurrence and different degrees of inflammation. RESULTS: A total of 36 goats fed two diets with gradually increasing levels of rumen-degradable starch (RDS) were included in this study, and SARA goats fed 70% concentrate diets supplemented with whole corn (HGW-SARA) and SARA goats fed 70% concentrate diets supplemented with crushed corn (HGC-SARA) were identified. Moreover, 11 goats fed a control basal diet, named LGW-CON, were also included. Compared with those in the LGW-CON group, the rumen fermentation capacity was enhanced, accompanied by ruminal epithelial and systemic inflammation, in goats from HGW-SARA and HGC-SARA. Between them, HGC-SARA goats presented less inflammation. Notably, the ruminal inflammation-related pathways were increased only in the HGW-SARA group but not in the HGC-SARA group. Metagenomic analysis revealed that the &#x3b2; diversity of SARA goats was significantly different from that of LGW-CON goats. Ruminococcus significantly increased in both SARA groups, whereas Prevotella and Bacteroidales significantly decreased, which was accompanied by a decrease in cellulose and hemicellulose enzymes and an increase in lysozymes and lipopolysaccharide synthesis enzymes. Multi-omics analysis of the ruminal contents and tissues suggested that epithelial inflammation was caused by disturbed ruminal microbiome-induced Th17 cell differentiation and IL-17 signalling pathway activation. Comparative analyses between the HGW-SARA and HGC-SARA groups highlighted the importance of Selenomonas and Bifidobacterium, as well as bacterial tryptophan metabolism, in the production of 3-indoleacetic acid, which mitigated ruminal epithelial inflammation by modulating Th17 cells and inhibiting IL-17 signalling. Ruminal microbiota transplantation from HGW-SARA goats to healthy dairy goats and mice revealed the role of microbes in epithelial inflammation. Additionally, 3-indoleacetic acid supplementation reduced rumen inflammation and the IL-17 concentration in the serum, improved VFAs absorption, and enhanced milk production. CONCLUSIONS: This study unveiled that after SARA was induced by high-concentrate feeding, the rumen homeostasis was disrupted, and rumen fiber degradation capacity of dairy goats decreased, but the LPS synthesis capacity increased, and inflammation of the rumen epithelium was observed. However, the ruminal microbial species from the Bifidobacterium and Selenomonas genera and bacterial 3-indole acetic acid are pivotal in mitigating ruminal epithelial inflammation during SARA in dairy goats. This could potentially be attributed to the modulation of ruminal Th17 cell proportions and the inhibition of IL-17 signalling pathways. Video Abstract.

Rumen↗
PubMed2005

NEO impact projections.

The concept of a near-Earth object (NEO) impact projection metric (PM) based on the ratio of the observation time to the impact time, rho(t), for a projected NEO impact is developed. The PM can assist NEO mitigation decision-making that is based on the discontinuously changing cumulative impact probability and help mitigate false alarms of NEO impact with Earth that have undermined public perception toward the veracity of predicting NEO threats.

Journal Article↗
PubMed2006

Improving surge capacity for biothreats: experience from Taiwan.

This article discusses Taiwan's experience in managing surge needs based on recent events, including the 1999 earthquake, severe acute respiratory syndrome in 2003, airliner crashes in 1998 and 2001, and yearly typhoons and floods. Management techniques are compared and contrasted with U.S. approaches. The authors discuss Taiwan's practices of sending doctors to the scene of an event and immediately recalling off-duty hospital personnel, managing volunteers, designating specialty hospitals, and use of incident management systems. The key differences in bioevents, including the mathematical myths regarding individual versus population care, division of stockpiles, the Maginot line, and multi-jurisdictional responses, are highlighted. Several recent initiatives aimed at mitigating biothreats have begun in Taiwan, but their efficacy has not yet been tested. These include the integration of the emergency medical services and health-facility medical systems with other response systems; the use of the hospital emergency incident command system; crisis risk-communications approaches; and the use of practical, hands-on training programs. Other countries may gain valuable insights for mitigating and managing biothreats by studying Taiwan's experiences in augmenting surge capacity.

Bioterrorism↗
PubMed1996

Displacement of T4 from transthyretin by the synthetic flavonoid EMD 21388 results in increased production of T3 from T4 in rat dams and fetuses.

EMD 21388 displaces T4 from circulating transthyretin, is a potent in vitro inhibitor of outer-ring deiodination (5'D) of T4 and affects thyroid hormone secretion. To study its extrathyroidal effects on the thyroid hormone status of pregnant dams and their fetuses, we treated the dams with methimazole and infused them with T4 and with either 2.5 mg EMD 21388/rat per day [(EMD(+)], or placebo solution [EMD(-)]. EMD reduced total T4 and T3 in the maternal circulation, but free T4 increased and free T3 decreased. The total amount of T3 generated from T4 in the maternal compartment increased. Placental T3 also increased in EMD(+) animals, T4 remaining the same. EMD also reached the fetal circulation. The total fetal extrathyroidal T4 pool decreased to half that of EMD(-) fetuses, whereas T3 increased 1.8-fold, thus mitigating fetal T3 deficiency, especially in the lung. Thus, if the maternal supply of T4 is kept constant, EMD mitigates the T3 deficiency of many tissues of the hypothyroid fetus. Most of the effects of this dose of EMD could result from the displacement of T4 from circulating transthyretin. Liver 5'D-I activity did not decrease, but actually increased by 40% in dams and fetuses. The enhanced transfer of T4 into tissues would also increase the amount of substrate available to 5'D-I, leading to an increased amount of T3 in maternal and fetal pools. This had not been anticipated from the changes in circulating T4 and T3, whether maternal or fetal, total or free.

Adipose Tissue, Brown↗
PubMed1991

Postischemic seizures and necrotizing ischemic brain damage: neuroprotective effect of postischemic diazepam and insulin.

Insulin has recently been shown experimentally to modify ischemic brain damage when administered either before or after the episode of ischemia. In controlled studies in the rat, high doses of insulin (greater than or equal to 8 IU/kg) result in seizures and early death. The present study was undertaken to determine whether diazepam, a potent, centrally penetrating GABAmimetic, alone or in combination with insulin, could mitigate postischemic seizures or regional selective neuronal necrosis and infarction. Forebrain ischemia was induced in rats for 10 1/2 minutes by carotid clamping and hypotension. The animals were observed clinically until elective perfusion-fixation and quantitative pathologic examination at 1-week recovery. Diazepam, either alone or with insulin, reduced regional brain necrosis and reduced the seizure rate. Insulin alone also led to reduced regional necrosis. However, the combination of diazepam plus insulin yielded the greatest proportion of undamaged brains in the hippocampus, thalamus, and midbrain. In the neocortex, the diazepam-only group showed the greatest number of normal hemispheres. Hypothalamic infarction was eliminated by all three treatments. Seizures per se were associated with increased damage in the cerebral cortex, thalamus, and brainstem, irrespective of treatment group. The findings indicate that ischemic brain necrosis can be mitigated by diazepam and insulin treatment begun in the immediate postischemic period.

Animals↗
PubMed2000

Hypoxia, hyperoxia, ischemia, and brain necrosis.

BACKGROUND: Human brains show widespread necrosis when death occurs after coma due to cardiac arrest, but not after hypoxic coma. It is unclear whether hypoxia alone can cause brain damage without ischemia. The relationship of blood oxygenation and vascular occlusion to brain necrosis is also incompletely defined. METHODS: We used physiologically monitored Wistar rats to explore the relationship among arterial blood oxygen levels, ischemia, and brain necrosis. Hypoxia alone (PaO2 = 25 mm Hg), even at a blood pressure (BP) of 30 mm Hg for 15 minutes, yielded no necrotic neurons. Ischemia alone (unilateral carotid ligation) caused necrosis in 4 of 12 rats, despite a PaO2 > 100 mm Hg. To reveal interactive effects of hypoxia and ischemia, groups were studied with finely graded levels of hypoxia at a fixed BP, and with controlled variation in BP at fixed PaO2. In separate series, focal ischemic stroke was mimicked with transient middle cerebral artery (MCA) occlusion, and the effect of low, normal, and high PaO2 was studied. RESULTS: Quantitated neuropathology worsened with every 10 mm Hg decrement in BP, but the effect of altering PaO2 by 10 mm Hg was not as great, nor as consistent. Autoradiographic study of cerebral blood flow with 14C-iodoantipyrine revealed no hypoxic vasodilatation during ischemia. In the MCA occlusion model, milder hypoxia than in the first series (PaO2 = 46.5 +/- 1.4 mm Hg) exacerbated necrosis to 24.3 +/- 4.7% of the hemisphere from 16.6 +/- 7.0% with normoxia (PaO2 = 120.5 +/- 4.1 mm Hg), whereas hyperoxia (PaO2 = 213.9 +/- 5.8 mm Hg) mitigated hemispheric damage to 7.50 +/- 1.86%. Cortical damage was strikingly sensitive to arterial PaO2, being 12.8 +/- 3.1% of the hemisphere with hypoxia, 7.97 +/-4.63% with normoxia, and only 0.3 +/- 0.2% of the hemisphere with hyperoxia (p < 0.01), and necrosis being eliminated completely in 8 of 10 animals. CONCLUSIONS: Hypoxia without ischemia does not cause brain necrosis but hypoxia exacerbates ischemic necrosis. Hyperoxia potently mitigates brain damage in this MCA occlusion model, especially in neocortex.

Animals↗
PubMed2003

The pharmacokinetics and pharmacodynamics of propofol in a modified cyclodextrin formulation (Captisol) versus propofol in a lipid formulation (Diprivan): an electroencephalographic and hemodynamic study in a porcine model.

UNLABELLED: The currently marketed propofol formulation has a number of undesirable properties that are in part a function of the lipid emulsion formulation, including pain on injection, serious allergic reactions, and the support of microbial growth. A modified cyclodextrin-based formulation of propofol (sulfobutyl ether-beta-cyclodextrin) has been developed that may mitigate some of these formulation-dependent problems. However, reformulation may alter propofol's pharmacologic behavior. Our aim in this study was to compare the pharmacokinetics and pharmacodynamics of propofol in the currently marketed lipid-based formulation with those of the novel cyclodextrin formulation. We hypothesized that the pharmacokinetics and pharmacodynamics of the propofol in cyclodextrin would be substantially similar to those of the propofol in lipid. Thirty-two isoflurane-anesthetized animals were instrumented with pulmonary artery, arterial, and IV catheters and were randomly assigned to receive either propofol in lipid or propofol in cyclodextrin by continuous infusion. Arterial blood samples for propofol assay were collected. The processed electroencephalogram, heart rate, mean arterial blood pressure, and cardiac output were measured continuously. The propofol formulations were compared by using model-independent analysis techniques. Combined kinetic/dynamic models were also constructed for simulation purposes. There were no significant differences in the pharmacokinetics or pharmacodynamics of the two propofol formulations. The simulations based on the combined pharmacokinetic/pharmacodynamic models confirmed the substantial similarity of the two formulations. The hypothesis that the propofol-in-cyclodextrin formulation would exhibit pharmacokinetic and pharmacodynamic behavior that was substantially similar to the propofol-in-lipid formulation was confirmed. IMPLICATIONS: A modified cyclodextrin-based formulation of propofol has been developed that may mitigate some of the problems associated with propofol in lipid emulsion. However, reformulation of propofol may change its clinical characteristics. This study in a pig model showed that the novel propofol formulation was substantially similar to the lipid emulsion propofol formulation.

Anesthetics, Intravenous↗
PubMed2007

Stereotactic radiosurgery: adjacent tissue injury and response after high-dose single fraction radiation: Part I--Histology, imaging, and molecular events.

Radiosurgery is now the preferred treatment modality for many intracranial disease processes. Although almost 50 years have passed since it was introduced as a tool to treat neurological disease, investigations into its effects on normal tissues of the central nervous system are still ongoing. The need for these continuing studies must be underscored. A fundamental understanding of the brain parenchymal response to radiosurgery would permit development of strategies that would enhance and potentiate the radiosurgical treatment effects on diseased tissue while mitigating injury to normal structures. To date, most studies on the response of the central nervous system to radiosurgery have been performed on brain tissue in the absence of pathological lesions, such as benign tumors or metastases. Although instructive, these investigations fail to emulate the majority of clinical scenarios that involve radiosurgical treatment of specific lesions surrounded by normal brain parenchyma. This article is the first in a two-part series that addresses the brain parenchyma's response to radiosurgery. This first article analyzes the histological, radiographic, and molecular data gathered regarding the brain parenchymal response to radiosurgery and aims to suggest future studies that could enhance our understanding of the topic. The second article in the series begins by discussing strategies for radiosurgical therapeutic enhancement. It concludes by focusing on strategies for mitigation and repair of radiation-induced brain injury.

Animals↗
PubMed2000

Effect of midodrine on chlorpromazine-induced orthostatic hypotension in rabbits: comparison with amezinium, etilefrine and droxidopa.

Orthostatic hypotension was produced in urethane-anesthetized rabbit by a combination of chlorpromazine (0.1 mg/kg, i.v.) and 45 degrees head-up tilt. The effect of midodrine (1 and 3 mg/kg, i.d.) was investigated in comparison with amezinium (10 and 30 mg/kg, i.d.), etilefrine (10 and 30 mg/kg, i.d.) and droxidopa (30 and 100 mg/kg, i.d.). The higher doses of each drug significantly mitigated the chlorpromazine-induced orthostatic hypotension, while none of the lower doses caused a significant effect. The effect of midodrine developed most rapidly; a significant effect was observed 25 min after administration. The order of onset time was midodrine < etilefrine < amezinium < droxidopa. The effect of droxidopa was significant only at 130 to 160 min after administration. The amplitude of effect was in the following order; midodrine = droxidopa > or = etilefrine > amezinium. Midodrine (3 mg/kg, i.d.) mitigated orthostatic hypotension induced by prazosin (0.1 mg/kg, i.v.), but not by pentolinium (0.6 mg/kg, i.v.). It is suggested that midodrine competes with chlorpromazine at alpha1-adrenoceptors and subsequently recovers reflex vasoconstriction. Midodrine may be useful to protect patients with impaired baroreflex activity from accidental orthostatic hypotension during treatment with neuroleptics.

Adrenergic alpha-Agonists↗