Acute Aspirin Research Articles

Medical Outcomes of Acute Aspirin Single Substance Poisoning in Pediatric Patients.

A consensus guideline on salicylate poisoning recommends referring patients to the emergency department if they ingested 150 mg/kg of aspirin. The dose of aspirin associated with severe poisoning in pediatric patients has not been investigated. This study aims to associate medical outcomes with aspirin overdoses in patients 5 years old and younger. A retrospective review of data on pediatric patients with single substance aspirin exposures reported from poison centers across the country was conducted. The primary endpoint was to associate aspirin doses with medical outcomes. Secondary endpoints included evaluation of the signs, symptoms, and treatments of ingestion and their association with medical outcomes. There were 26 488 included exposures with aspirin exposures resulting in no effect (92.5%), minor effect (6.0%), moderate effect (1.4%), major effect (0.2%), and death (0.02%). There were 8921 cases with available weight-based dosing information. Median doses associated with no effect, minor effects, moderate effects, major effects, and death ranged between 28.4 and 40.9 mg/kg, 52.5 and 82.3 mg/kg, 132.1 and 182.3 mg/kg, 132.3 and 172.8 mg/kg, and 142.2 and 284.4 mg/kg, respectively. Minor effect and moderate effect exposures were more likely to have alkalinization documented compared to no effect exposures (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.41-2.17; OR = 1.79, 95% CI = 1.12-2.86). There was no difference in rates of alkalinization between minor and moderate exposures (OR = 1.02, 95% CI: 0.61-1.7). Reevaluation of the current recommendation of 150 mg/kg for referral to a healthcare facility is necessary for pediatric acute salicylate overdoses.

High polyphenolic cranberry beverage alters specific fecal microbiota but not gut permeability following aspirin challenge in healthy obese adults: A randomized, double-blind, crossover trial

• Polyphenol-rich cranberry beverage was consumed by healthy adults who were obese. • Fecal Faecalibacterium prausnitzii and Eggerthella lenta increased. • Gastrointestinal permeability, inflammation, and immune function were unchanged. • An intervention longer than 2 weeks may be required to observe beneficial effects. Polyphenol-rich cranberry extracts decrease intestinal inflammation, alter gut microbiota, and decrease intestinal permeability in obese mice, but the effect has not been investigated in adults who are obese. The purpose of this randomized double-blind, cross-over feeding study in obese (BMI = 37.4 ± 1.2 kg/m 2 ) but otherwise healthy adults (n = 36) 35.4 ± 1.3 years was to determine the effects of consuming 480 mL of a high polyphenolic cranberry or control beverage daily for 2 weeks on gastrointestinal permeability, markers of inflammation and immune function, and gut microbiota. An acute aspirin challenge was administered prior to assessing intestinal permeability to determine resistance to barrier function compromise. The cranberry beverage did not affect markers of gastrointestinal permeability, inflammation, or immune function. However, fecal Faecalibacterium prausnitzii and Eggerthella lenta increased with consumption of the cranberry beverage. Data suggest that the intervention impacted bacterial communities. A longer intervention may be required to observe beneficial effects on inflammation and gastrointestinal barrier function.

Activated Charcoal and Bicarbonate for Aspirin Toxicity: a Retrospective Series.

Aspirin overdose causes acid-base disturbances and organ dysfunction. Management is guided by research reported over 50years ago when chronic aspirin toxicity was common and accounted for significant morbidity. We investigate our experience of aspirin overdose and the effectiveness of charcoal and bicarbonate administration over 20years. This is a retrospective series of acute aspirin overdosefrom two toxicology units from January 2000 to September 2019. Acute aspirin ingestions > 3000mg were identified in each unit's database. Excluded were cases of chronic exposure, hospital presentation > 24 hours after ingestion, and cases without a salicylate concentration. Included in our analysis wasdemographic data, clinical effects, investigations, complications, and treatment. There were 132 presentations in 108 patients (79 females (73%)). The median age was 28years (range: 13-93years). The median dose ingested was 7750mg (IQR: 6000-14,400mg). There were 44 aspirin-only ingestions. Mild toxicity (nausea, vomiting, tinnitus or hyperventilation) occurred in 22 with a median dose of 160mg/kg. Moderate toxicity (acid-base disturbance, confusion) occurred in 16 with a median ingested dose of 297mg/kg. There were no cases of severe toxicity (coma or seizures) due to aspirin alone. The median peak salicylate concentration was 276mg/L (IQR: 175-400mg/L, range: 14-814mg/L). There was a moderate association between dose ingested and peak concentration (Pearson r = 0.58; 95% CI 0.45-0.68). Activated charcoal was administered in 36 (27%) cases, which decreased the median peak salicylate concentration (34.2 to 24.8mg/L/g (difference: 9.4, 95% CI: 1.0-13.1)). Bicarbonate was administered in 34 (26%) presentations, decreasing the median apparent elimination half-life from 13.4 to 9.3h (difference: 4.2h, 95% CI: 1.0-6.5h). Acute aspirin overdose caused only mild to moderate effects in this series. Early administration of activated charcoal decreased absorption and use ofbicarbonate enhancedelimination.

Abstract WP116: Association Between Smoking Status, Platelet Function and Clinical Outcomes of Ticagrelor versus Clopidogrel in Patients With Minor Stroke or Transient Ischemic Attack

Background: Association between smoking status, platelet function and clinical outcomes of ticagrelor versus clopidogrel in patients with minor stroke or transient ischemic stroke (TIA) remains unclear. Methods: A subgroup analysis was conducted of Platelet Reactivity in Acute Non-disabling Cerebrovascular Events (PRINCE) trial. PRINCE trial was a randomized, prospective, multicenter, open-label, active-controlled, and blind-endpoint trial, which randomized patients with acute minor stroke, or TIA, to ticagrelor plus aspirin or clopidogrel plus aspirin within 24 hours of symptoms onset. Patients who smoked at least one cigarette per day for at least one year in their lives were defined as smokers. Platelet reactivity was assessed by the VerifyNow P2Y12 assay at baseline, 7+2 days and 90±7 days. High-on-treatment platelet reactivity (HOPR) was defined as P2Y12 reaction units >208.Clinical outcomes included any stroke, composite clinical vascular events and bleeding events at 90 days. Results: Among 675 patients enrolled in the PRINCE trial, 370 patients (54.8%) were smokers. At 7+2 days, the proportion of HOPR in ticagrelor versus clopidogrel was significantly lower in smokers (5.2% versus 21.8%) and non-smokers (2.3% versus 34.4%). There were marginal significant interactions between treatment groups and smoking status for the proportion of HOPR ( P =0.058). There were significant interactions between treatment groups and carrier status of CYP2C19 LOF alleles for the proportion of HOPR among smokers ( P =0.04), but no significant interactions were found among non-smokers ( P =0.91). At 90±7 days, there were significant interactions between treatment groups and smoking status for the risk of new stroke (smokers, 7.0% versus 4.9%, hazard ratio [HR], 1.57 [95%CI, 0.65-3.79], P =0.39; non-smokers, 5.3% versus 13.5%, HR, 0.39 [95%CI, 0.17-0.91], P =0.01. P for interaction=0.02). Conclusions: Among patients with minor stroke or TIA, ticagrelor might be superior to clopidogrel in inhibiting platelet reactivity and reducing the risk of stroke, particularly in non-smokers. Carrier status of CYP2C19 LOF alleles might play a role in the impact of smoking status. Clinical Trial Registration : Clinicaltrials.gov NCT02506140.

Acute Aspirin Plus Cilostazol Dual Therapy for Noncardioembolic Stroke Patients Within 48 Hours of Symptom Onset.

BackgroundThe aim of the present study was to investigate the efficacy and safety of antiplatelet (aspirin plus cilostazol) dual therapy for patients with noncardioembolic stroke within 48 hours of symptom onset.Methods and ResultsThe ADS (Acute Aspirin Plus Cilostazol Dual Therapy for Non‐Cardiogenic Stroke Patients Within 48 Hours of Symptom Onset ) study is an investigator‐initiated, prospective, multicenter (34 hospitals in Japan), randomized, open‐label, and aspirin‐controlled trial. Acute stroke patients with noncardioembolic stroke within 48 hours of onset were studied. The subjects were randomly allocated to combination therapy with aspirin 81 to 200 mg plus cilostazol 200 mg (dual group) and single therapy with aspirin 81 to 200 mg (aspirin group) for 14 days. After the 14 days, all patients took the cilostazol 200 mg for 3 months. A primary efficacy outcome was defined as any one of the following occurring (neurological deterioration, symptomatic stroke recurrence, or transient ischemic attack) within 14 days. A primary safety outcome included intracerebral hemorrhage and subarachnoid hemorrhage. Between May 2011 and June 2017, 1201 patients (796 [66%] men; median age, 69 [61–77] years) randomized 1:1 to either the dual group or the aspirin group were analyzed. Initial National Institutes of Health Stroke Scale score was 2 (1–4) in both groups (P=0.830). A primary efficacy outcome was observed in 11% in the dual group and 11% in the aspirin group (P=0.853). A primary safety outcome occurred in 2 (0.3%) in the dual group and in 1 (0.2%) in the aspirin group (P=0.624).ConclusionsDual antiplatelet therapy using cilostazol and aspirin was safe but did not reduce the rate of short‐term neurological worsening.Clinical Trial Registration URL: umin.ac.jp/ctr/index/htm. Unique identifier: UMIN000004950.

Firefighting Induces Acute Inflammatory Responses that are not Relieved by Aspirin in Older Firefighters.

Sudden cardiac events account for 40% to 50% of firefighter line-of-duty deaths. Inflammatory proteins are strong biomarkers of cardiovascular inflammation. The present study investigated the effects of aspirin supplementation on inflammatory biomarkers following firefighting. Using a randomized, placebo-controlled, double-blind crossover design, 24 male firefighters (48.2 ± 5.9 years) were allocated into four conditions: acute (81 mg; single-dose) aspirin and placebo supplementation, and chronic (81 mg; 14 days) aspirin and placebo supplementation. Inflammatory proteins [interleukin (IL)-6, C-reactive protein (CRP), intracellular adhesion molecule (ICAM)-1, P-selectin, matrix metalloproteinase-9 (MMP-9)] and antioxidant potential [total antioxidant capacity (TAC)] were measured pre- and post-structural firefighting drills. Firefighting activities significantly increased IL-6, MMP-9, and P-Selectin; however, no changes in TAC and ICAM-1 were detected. Neither acute nor chronic aspirin supplementation attenuated this inflammatory response. Firefighting significantly increases inflammatory biomarkers and neither acute nor chronic low-dose aspirin mitigates this response.

Acute Uremia and Aspirin: A Recipe for Disaster Leading to Post-Sphincterotomy Hemorrhage

Acute Uremia and Aspirin: A Recipe for Disaster Leading to Post-Sphincterotomy Hemorrhage

Extracorporeal elimination of butalbital in acute aspirin–butalbital–caffeine–codeine (Fiorinal with Codeine) poisoning

Background: Butalbital is a small molecule (approximately 220 Da), with 26% protein binding, a 0.8 L/kg volume of distribution, and is eliminated nearly 80% unchanged in the urine. Although hemodialysis has been used to treat overdoses of other barbiturates, the extracorporeal clearance of butalbital is unknown. The objective of this case is to describe the use of extracorporeal therapy to augment elimination of butalbital after an overdose of aspirin 325 mg–butalbital 50 mg–caffeine 40 mg with codeine 30 mg (Fiorinal with Codeine).Methods: This is a case report of a single patient.Results: A 67-year-old female was admitted to the medical intensive care unit approximately 3 h after ingestion of 40 tablets of Fiorinal with Codeine. Her presentation was notable for a decline in mental status, preserved renal function and a relatively low peak salicylate concentration at 46.4 mg/dL (3.4 mmol/L). Approximately 8 h after ingestion of 2000 mg of butalbital, our patient’s serum concentration was 26.9 mg/L (normal <10 mg/L). At the end of a four-hour hemodialysis session, the total body elimination of butalbital was approximately 60% which corresponded to an intradialytic clearance of 233–300 mL/min.Conclusions: The extracorporeal clearance of butalbital observed in this case demonstrates the utility of dialysis to augment drug elimination in a Fiorinal with Codeine overdose.

Geographic variation in the treatment of non-ST-segment myocardial infarction in the English National Health Service: a cohort study.

ObjectivesTo investigate geographic variation in guideline-indicated treatments for non-ST-elevation myocardial infarction (NSTEMI) in the English National Health Service (NHS).DesignCohort study using registry data from the Myocardial Ischaemia National Audit Project.SettingAll Clinical Commissioning Groups (CCGs) (n=211) in the English NHS.Participants357 228 patients with NSTEMI between 1 January 2003 and 30 June 2013.Main outcome measureProportion of eligible NSTEMI who received all eligible guideline-indicated treatments (optimal care) according to the date of guideline publication.ResultsThe proportion of NSTEMI who received optimal care was low (48 257/357 228; 13.5%) and varied between CCGs (median 12.8%, IQR 0.7–18.1%). The greatest geographic variation was for aldosterone antagonists (16.7%, 0.0–40.0%) and least for use of an ECG (96.7%, 92.5–98.7%). The highest rates of care were for acute aspirin (median 92.8%, IQR 88.6–97.1%), and aspirin (90.1%, 85.1–93.3%) and statins (86.4%, 82.3–91.2%) at hospital discharge. The lowest rates were for smoking cessation advice (median 11.6%, IQR 8.7–16.6%), dietary advice (32.4%, 23.9–41.7%) and the prescription of P2Y12 inhibitors (39.7%, 32.4–46.9%). After adjustment for case mix, nearly all (99.6%) of the variation was due to between-hospital differences (median 64.7%, IQR 57.4–70.0%; between-hospital variance: 1.92, 95% CI 1.51 to 2.44; interclass correlation 0.996, 95% CI 0.976 to 0.999).ConclusionsAcross the English NHS, the optimal use of guideline-indicated treatments for NSTEMI was low. Variation in the use of specific treatments for NSTEMI was mostly explained by between-hospital differences in care. Performance-based commissioning may increase the use of NSTEMI treatments and, therefore, reduce premature cardiovascular deaths.Trial registration numberNCT02436187.

Effect of Aspirin Supplementation on Hemostatic Responses in Firefighters Aged 40 to 60 Years

Sudden cardiovascular events account for approximately 45% to 50% of all duty-related deaths among firefighters and a disproportionate number of these fatalities occur after strenuous fire suppression activities. The purpose of this study was to evaluate the effect of acute and chronic aspirin supplementation on hemostatic function before and after live firefighting activities in older firefighters. A double-blind, crossover design included 4 treatments: a 2-week aspirin/placebo treatment ("chronic") and a single prefirefighting aspirin/placebo treatment ("acute"). Hemostatic function was assessed in 24 male firefighters (mean age= 48.2 ± 5.9years) immediately before and after 18minutes of live-fire firefighting activity. An acute bout of firefighting activity significantly decreased platelet aggregation time and decreased activated partial thromboplastin time. Compared with placebo, acute aspirin supplementation resulted in a significant increase in epinephrine closure time, which was further augmented by chronic supplementation. Aspirin supplementation had no effect on coagulatory or fibrinolytic factors. Our findings suggest that an acute bout of firefighting leads to increased coagulatory potential in older firefighters. In conclusion, aspirin supplementation had an antiplatelet effect that decreased platelet aggregability at rest and after an acute bout of firefighting compared with placebo.

Effect of Aspirin Supplementation on Hemodynamics in Older Firefighters.

Cardiovascular events are the leading cause of line-of-duty fatality for firefighters. Aspirin reduces the risk of cardiovascular events in men and may reduce fatalities in older (>40 yr) firefighters. We hypothesized that both chronic and acute aspirin supplementation would improve vascular function after live firefighting but that chronic supplementation would also improve resting hemodynamics. Twenty-four firefighters (40-60 yr) were randomly assigned to acute or chronic aspirin supplementation or placebo in a balanced, crossover design. Arterial stiffness, brachial and central blood pressures, as well as forearm vasodilatory capacity and blood flow were measured at rest and immediately after live firefighting. Total hyperemic blood flow (area under the curve (AUC)) was increased (P < 0.001) after firefighting with no effects for aspirin supplementation or acute versus chronic administration (AUC, from 107 ± 5 to 223 ± 9 in aspirin condition and from 97 ± 5 to 216 ± 7 mL·min⁻¹ per 100-mL forearm tissue for placebo; P < 0.05 for main, and P > 0.05 for interaction). Arterial stiffness/central blood pressure increased (P < 0.04) with no effect of aspirin (from 0.0811 ± 0.001 to 0.0844 ± 0.003 m·s·mm⁻¹ Hg⁻¹ in aspirin condition versus 0.0802 ± 0.002 to 0.0858 ± 0.002 m·s⁻¹·mm Hg⁻¹ in placebo condition), whereas peripheral and central systolic and pulse pressures decreased after firefighting across conditions (P < 0.05). Live firefighting resulted in increased AUC and pressure-controlled arterial stiffness and decreased blood pressure in older firefighters, but aspirin supplementation did not affect macro- or microvascular responsiveness at rest or after firefighting.

A High Burden of Ischemic Stroke in Regions of Eastern/Central Europe is Largely Due to Modifiable Risk Factors.

Incidence and mortality of ischemic stroke in Croatia is significantly higher than in many other developed European countries. Here, we aimed to evaluate underlying conditions of this unacceptably high disease burden. An observational prospective cohort study of first-ever ischemic stroke patients identified in a population-based incidence study (N=751) (study 1, S1) and a concurrent case-control trial (215 patients, 125 controls, S2) were conducted in the county of Varazdin from 2007-2010. Atrial fibrillation (AF) was common (36.1% in S1, 40.9% in S2) and mostly (>50%) unrecognized before the index event. In a multivariate analysis, odds of stroke increased with tobacco smoking (OR=3.95, 95%CI 1.33-10.8), unhealthy diet (OR=2.12, 1.12-4.01) and AF (OR=9.40, 4.01-22.0), and decreased with higher education (OR=0.33, 0.11-0.98), moderate alcohol consumption (OR=0.48, 0.25-0.93), higher fasting HDL (OR=0.14, 0.07-0.30) and pre-stroke use of anticoagulants (OR=0.09, 0.01-0.59), antihypertensive drugs (OR=0.52, 0.27-1.00) and statins (OR=0.29, 0.12-0.69). Fourteen-day case fatality was 10.8% (S1) and 6.1% (S2) and the risk was higher with AF, cardioembolic stroke, older age, higher fasting serum glucose, and lower with acute aspirin. Among the acute phase survivors, 30.9% died over the subsequent 1-3 years (p<0.05). We conclude that the incidence of ischemic stroke in Croatia is related to conventional risk factors and largely due to a high rate of unawareness and inadequate treatment of predisposing morbidity.

Clinical Implications of Changes in Individual Platelet Reactivity to Aspirin Over Time in Acute Ischemic Stroke.

Time-dependent changes in individual platelet reactivity have been detected in patients with coronary artery disease. Therefore, we sought to evaluate the time-dependent changes in platelet reactivity to aspirin during the acute stage after ischemic stroke and the clinical implications of variable patient responses to aspirin in acute ischemic stroke. We conducted a single-center, prospective, observational study. The acute aspirin reaction unit (ARU) was measured after 3 hours of aspirin loading, with higher values indicating increased platelet reactivity despite aspirin therapy. The follow-up ARU was measured on the fifth day of consecutive aspirin intake. The numeric difference between the follow-up ARU and the acute ARU was defined as ΔARU and was stratified into quartiles. Early neurological deterioration was regarded as an early clinical outcome. Both the acute ARU (476±69 IU) and the follow-up ARU (451±68 IU) were measured in 349 patients in this study. Early neurological deterioration was observed in 72 patients (20.6%). Changes in aspirin platelet reactivity over time showed an approximately Gaussian distribution. The highest ΔARU quartile was independently associated with early neurological deterioration (odds ratio, 3.19; 95% confidence interval, 1.43-7.10; P=0.005) by multivariate logistic regression analysis. The results of our study showed that the increase in platelet reactivity to aspirin over time is independently associated with early neurological deterioration in patients with acute ischemic stroke. In addition, during the acute stage of ischemic stroke, serial platelet reactivity assays may be more useful than a single assay for identifying the clinical implications of aspirin platelet reactivity after ischemic stroke.

Abstract T P73: Overcoming Framing Bias in Stroke Neurologists’ Assessments of the Minimally Clinically Important Difference for Novel Acute Ischemic Stroke Therapies

Background: The determination of the minimally clinically important difference (MCID) worth detecting is an essential prerequisite for clinical trial sample size calculation, funding decisions by NIH and other sponsors, and drug or device approval by regulatory agency. However, prior surveys to establish expert judgment of MCID have had a cognitive framing bias by offering response options with midpoints in the 5-15% range, well above the treatment effect actually accepted in practice and national guidelines as worthwhile (1% for acute aspirin). Methods: A 5 item internet-based survey was administered to US academic stroke neurologists. Respondents were asked to indicate, for an acute neuroprotective drug free of side effects, how many patients, per 1000 treated, would need to benefit by achieving freedom from disability at 90 days (mRS 0-2) for the agent to be worthwhile to use in clinical practice? Results: Survey responses were received from 122 of 332 academic stroke neurologists. Among the participants, 38.0% were professors, 24.0% associate professors, 33.1% assistant professors, and 5.0% neurology residents or fellows. All respondents were engaged in stroke clinical care, with cerebrovascular disease accounting for more than half of practice time in over 75%. Categorized responses to the value of the MCID were: 1 per 1000 by 3.3% of respondents, 2-5 in 7.4%, 6-10 by 19.7%, 11-15 by 22.1%, 16-20 by 15.6%, and greater than 20 by 32.0%. The median MCID was 13 (IQR 8 to &gt; 20). Converted to natural base 100 values, the MCID was 1.3% (IQR 0.8% - &gt;2%). Conclusion: When assessed with framing based on clinical practice rather than convenience, vascular neurologists indicated the minimally clinical important difference for a safe agent to be worthwhile to use in acute ischemic stroke is about 1%. Drug and device agencies should consider this value to be the expert opinion MCID for acute ischemic stroke treatments when making regulatory decisions.

Apple Polyphenol Extracts Protect Against Aspirin‐induced Gastric Mucosal Damage in Rats

The protective role of two apple polyphenol extracts, Douglas-FB (FB) and Douglas-EF (EF), on gastric mucosal damage following aspirin ingestion was investigated in healthy rats. Polyphenol content of the apple extracts varied, with the EF extract having 20% w/w polyphenols and a high proportion of flavanols as epicatechin and procyanidin, whereas the FB extract comprised 12% w/w polyphenols, which were mostly flavonols as quercetin glycosides. Male Sprague-Dawley rats were allocated to control, FB and EF groups and fed the experimental diet during the 10-day trial. Control treatment rats received 1 mL of deionised water, whereas apple polyphenol treatment group rats, FB and EF received a concentration of 10(-2) m polyphenols in 1 mL deionised water daily via oral gavage. At the end of 10-day feeding period, rats were fasted overnight, and the following morning, aspirin (200 mg/kg) was given by oral gavage. Four hours after aspirin administration, the animals were euthanised, and samples taken for analysis. Both apple polyphenol extracts significantly reduced the ulcer area, ulcer lesion index and gastric injury score. The glutathione in gastric mucosa was increased significantly in rats given FB apple extract. Despite their different polyphenol compositions, FB and EF apple extracts assisted in protecting the gastric mucosa following acute aspirin administration in rats.

Urinary concentrations of physiological markers of intestinal barrier dysfunction do not increase with acute aspirin use (LB749)

Previous studies have shown that acute aspirin use causes increased intestinal permeability to ingested permeability probes. The purpose of the present studies was to determine whether acute aspirin use also increases concentrations of urinary physiological markers of intestinal barrier dysfunction. The urinary markers were: 1) D‐lactate (produced by intestinal bacteria; a marker of intestinal barrier dysfunction if increased in the plasma or urine), 2) intestinal fatty acid binding protein (I‐FABP; a marker of small intestinal enterocyte damage), and 3) claudin‐3 (an intestinal tight junction protein). Two studies were conducted and involved ingestion of aspirin (975 mg) or placebo the night before and the morning of an experiment. Eight healthy subjects participated in each study. Six hours after the morning dose of aspirin or placebo, subjects provided a urine sample. In the first study, the urine was assayed for D‐lactate. In the second study, the urine was assayed for I‐FABP and claudin‐3. No significant differences were found between aspirin and placebo experiments for D‐lactate in study 1, or for I‐FABP or claudin‐3 in study 2. These results indicate that urinary concentrations of D‐lactate, I‐FABP, and claudin‐3 do not increase with acute aspirin use.

Effect of Vitamins C &amp; E on Aspirin Induced Gastric Mucosal Damage and Oxidative Stress

The effects of Vitamins C & E on Aspirin - induced gastric mucosal damage on gastric ulcer parameters and stomach oxidative stress markers were determined in acute and sub-acute studies in Wistar rats. Aspirin produced a significant (p<0.05) increase in gastric ulcer score in both studies. Vitamins C & E conferred protection in acute and sub-acute studies with preventive indices of 54 and 60% respectively. Histologically the gastric mucosa of animals in the sub-acute study showed a severe necrosis of the epithelial cells than observed in the acute study. Acute aspirin administration did not increase the stomach tissue Malondialdehyde (MDA) but sub-acute administration significantly (p<0.05) increased MDA, while vitamins C & E caused a significant (p<0.05) decrease below the level seen in normal controls. Aspirin in both studies significantly decreased Catalase activity. While acute aspirin exposure had no effect on Superoxide Dismutase (SOD) activity, sub-acute exposure raised it significantly (p<0.05). Administration of Vitamins C and E significantly increased SOD activity only in the acute study. Aspirin significantly decreased reduced Glutathione (GSH) in both studies and was reversed by Vitamin C and E. The level of GSH reductase (GSHRD) in the acute study was significantly decreased by aspirin but sub- acutely and prior treatment with vitamins C and E had no significant effect. Combine administration of vitamins C & E prior to intake of aspirin significantly prevented aspirin-induced gastric ulceration with decrease in some oxidative stress markers.

Early management of acute ischemic stroke cases: (Acute Stroke Protocols & Guidelines/Algorithms) @ Apollo Hospitals, Hyderabad

Stroke is a medical emergency, with a mortality rate higher than most forms of cancer. It is the second leading cause of death in developed countries and is the most common cause of serious, long-term disability in adults. The incidence of stroke is increasing with the aging of populations and hence there is a major challenge to health planners.Evidence-based advances in acute stroke have included proof of the benefit of organized care in stroke units, modern brain imaging, and thrombolytic therapy, the modest benefit of acute aspirin in ischemic stroke clearly, a lack of awareness of the common symptoms of stroke remains a major educational challenge, and the urgency of stroke treatment is still poorly appreciated. Despite the proven benefit of stroke units, the majority of patients in most countries cannot access specialized stroke care.The article focuses on current treatment guidelines and new therapeutic prospects, emphasizing the importance of early intervention and the need for a multidisciplinary approach to the management of stroke patients.

Effect of Aspirin Dose on Gastrointestinal Permeability

The primary purpose of this study was to determine the aspirin dose that increases gastrointestinal (GI) permeability. A pilot study was also conducted to determine whether the menstrual cycle affects GI permeability. Both portions of the study involved 4 experimental conditions. For the aspirin portion, 8 subjects ingested 0 mg, 325 mg, 650 mg, or 975 mg of aspirin the night before and the morning of an experiment. For the menstrual cycle pilot study, 5 female subjects with regular menstrual cycles were tested for GI permeability on the same day each week for 4 weeks. GI permeability was assessed by the urinary excretion of ingested probes. Sucrose (5 g) was used to determine gastroduodenal permeability. Lactulose (5 g) and rhamnose (2 g) were used to assess small intestinal permeability via the lactulose-to-rhamnose urinary excretion ratio (L/R). The data indicated that the menstrual cycle had no effect on GI permeability. In contrast, gastroduodenal permeability was significantly (P <0.008) increased following a dose of 650 mg aspirin and small intestinal permeability (L/R) was significantly (P <0.008) increased following a dose of 975 mg aspirin. These results suggest healthy individuals should be cautious even with acute aspirin use as it may result in GI barrier dysfunction.

Effect of Acute Aspirin Dose on Gastrointestinal Permeability

Gastrointestinal (GI) permeability refers to the non-mediated diffusion of large molecules (> 150 Da) that are normally restricted from the body's internal environment by the GI barrier. Non-steroidal anti-inflammatory drugs such as aspirin are known to disrupt the GI barrier and increase GI permeability. Increased GI permeability to harmful substances can promote both local and systemic inflammatory reactions. PURPOSE: The purpose of this study was to determine the acute aspirin dose that increases GI permeability. METHODS: Eight subjects (4 male; 4 female; age = 25 ± 7.6 yrs) completed four experiments: 1) 0 mg of aspirin, 2) 325 mg of aspirin, 3) 650 mg of aspirin, and 4) 975 mg of aspirin. In a randomized, blinded study, subjects were given one of the four doses of aspirin 1 hour before bedtime and again the morning of the experiment. On the morning of the experiment, subjects then drank a solution (150 ml) containing 5 g sucrose, 5 g lactulose, and 2 g rhamnose approximately 1 hour after ingesting the pills. All urine was collected for the following 5 hours. Using high-performance liquid chromatography, urine concentrations of lactulose, rhamnose, and sucrose were determined. Gastroduodenal permeability was assessed by urinary sucrose excretion (percent of ingested dose). Small intestinal permeability was determined from the lactulose-to-rhamnose urinary excretion ratio (L/R). RESULTS: Sucrose excretion was found to be significantly greater with aspirin doses of 650 mg (median = 0.24% excreted) and 975 mg (median = 0.36% excreted) compared to the 0 mg aspirin condition (median = 0.007% excreted). In addition, the L/R showed a significant difference between a 975 mg dose of aspirin (median = 0.063) and a 0 mg dose (median = 0.038). CONCLUSION: Gastroduodenal permeability is significantly increased with an aspirin dose of 650 mg (i.e., 2 × 325 mg capsules) when taken before bedtime and the next morning. Small intestinal permeability is also increased with an aspirin dose of 975 mg (i.e., 3 × 325 mg capsules) when ingested in the same manner. Supported by the Gatorade Sports Science Institute.