Changes in sugar-sweetened beverage purchases across the price distribution after the implementation of a tax in Mexico: a before-and-after analysis.

BACKGROUND: A tax of one-Mexican peso per liter of sugar-sweetened beverage (SSB) came into effect in January 2014 in Mexico as a national health policy to tackle the high overweight and obesity prevalence. Previous studies have shown an overall reduction in SSB purchases after the tax implementation. However, it remains unknown whether and to what extent SSB consumers switched to cheaper taxed beverages, attenuating the potential effect of the policy. Our study's objective was to estimate changes in household purchases of taxed SSBs by tertiles of SSB prices (low, middle, and high) in urban areas after the SSB tax implementation in 2014. METHODS: Based on purchase data for 2012-2015 from households living in 54 Mexican cities with a population > 50,000 inhabitants, we calculated unit-value SSB prices for the full period and sorted them on a monthly basis to create monthly price tertiles. We merged these price tertiles to household purchases and created average monthly ml/capita/day SSB purchases by price tertile at the city level. We assessed SSB purchase switching patterns before and after the tax implementation through price-tertile stratified linear models. The main variable in the models was a dummy indicator that allowed us to identify the pre-tax period (2012-13) and post-tax period (2014-15). We controlled our models for time trends and contextual economic variables. RESULTS: In the regression adjusted models, we found a statistically significant purchase reduction ranging between 10.80 and 13.79 ml/capita/day (p-value < 0.001) across taxed beverages from the middle-price SSB after the tax implementation. We observed no statistically significant reductions in purchases of low-price SSBs and high-price SSBs. CONCLUSIONS: Our findings show purchase reductions in the middle-price SSBs, which represents ≈30% of the overall SSB purchases in urban Mexico. Future studies should be conducted to test if the redesign of the current the tax, by either doubling the tax amount or taxing sugar content, might reduce more effectively purchases across all SSBs.

The effects of traffic light labelling versus cartoon labelling on food and beverage purchases in a children's hospital setting.

This study's purpose was to examine changes in healthy and unhealthy items purchased following the implementation of traffic light and cartoon labelling in a small retail food venue (Café Bay) in a children's hospital in eastern North Carolina. Between October 2015 and March 2016, daily food and beverage sales from Café Bay were obtained during baseline, traffic light labelling, a washout period, cartoon labelling (on healthy foods only) and a final washout period. Pearson chi-squared tests and multiple linear regressions were used to examine effects of labelling strategies, controlling for the holidays. In unadjusted analyses, traffic light labelling was associated with significant decreases in purchases of unhealthy items purchased, while cartoon labelling was associated with increases in unhealthy items purchased. In adjusted linear regression analysis, traffic light labelling was associated with fewer unhealthy purchases and thus may have potential to decrease the amount of unhealthy items purchased in a children's hospital food retail venue.

Defining sepsis on the wards: results of a multi-centre point-prevalence study comparing two sepsis definitions.

Our aim was to prospectively determine the predictive capabilities of SEPSIS-1 and SEPSIS-3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24-h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days. Out of the 5422 patients screened, 431 fulfilled inclusion criteria and 380 (88%) were recruited. Using the SEPSIS-1 definition, 212 patients had sepsis. When using the SEPSIS-3 definitions with Sequential Organ Failure Assessment (SOFA) score ≥ 2, there were 272 septic patients, whereas with quickSOFA score ≥ 2, 50 patients were identified. For the prediction of primary outcome, SEPSIS-1 criteria had a sensitivity (95%CI) of 65% (54-75%) and specificity of 47% (41-53%); SEPSIS-3 criteria had a sensitivity of 86% (76-92%) and specificity of 32% (27-38%). SEPSIS-3 and SEPSIS-1 definitions were associated with a hazard ratio (95%CI) 2.7 (1.5-5.6) and 1.6 (1.3-2.5), respectively. Scoring system discrimination evaluated by receiver operating characteristic curves was highest for Sequential Organ Failure Assessment score (0.69 (95%CI 0.63-0.76)), followed by NEWS (0.58 (0.51-0.66)) (p < 0.001). Systemic inflammatory response syndrome criteria (0.55 (0.49-0.61)) and quickSOFA score (0.56 (0.49-0.64)) could not predict outcome. The SEPSIS-3 definition identified patients with the highest risk. Sequential Organ Failure Assessment score and NEWS were better predictors of poor outcome. The Sequential Organ Failure Assessment score appeared to be the best tool for identifying patients with high risk of death and sepsis-induced organ dysfunction.

SSB taxes and diet quality in US preschoolers: estimated changes in the 2010 Healthy Eating Index.

BACKGROUND: Taxing sugar-sweetened beverages (SSBs) has been proposed as a strategy to combat child obesity. Yet it is unclear how a tax on SSBs might influence the overall quality of diet in preschool children. Thus, we use simulated price increases and the 2010 Healthy Eating Index (HEI-2010) to explore the relationship between SSB taxes and diet quality in preschool children. METHODS: Price and purchase data from the 2009-2012 Nielsen Homescan Panel and a two-part marginal effects model were used to estimate relative changes in purchases with a 20% increase in the price of SSBs. Demand elasticities were applied to dietary intake data for children ages 2-5 years from the National Health and Nutrition Examination Survey (2009-2010 and 2011-2012) to estimate the impact of a 20% SSB tax on dietary intake and quality (HEI-2010). RESULTS: A 20% increase in the price of SSBs was associated with lower total caloric intake (-28 kcal d-1 , p < 0.01), caloric intake from juice drinks (-20 kcal d-1 , p < 0.01), added sugars (-4.1 servings d-1 , p = 0.03), refined grains (-0.63 servings d-1 , p < 0.01) and total meat (-0.56 servings d-1 , p < 0.01). Beneficial decreases in empty calories and refined grains were offset by unfavourable changes in fatty acid profile, total protein, vegetables and fruit, such that total HEI scores (0-100 range) were not meaningfully changed with a 20% increase in SSB price (difference: -0.85, p < 0.01). CONCLUSIONS: A 20% tax on SSBs could decrease caloric intake, and intakes of added sugars and SSBs, but may not improve diet quality as an isolated intervention among US preschool children.

Ten-year beverage intake trends among US preschool children: rapid declines between 2003 and 2010 but stagnancy in recent years.

BACKGROUND: It has been previously reported that total energy intake among US preschool children (ages 2-5 years) decreased between 2003-2004 and 2009-2010. However, little is known about how intakes of beverages among US preschoolers (ages 2-5 years) changed from 2003-2004 to 2011-2012. OBJECTIVES: This paper examines changes in intakes of key beverages during this period, as well as how eating location (at home or away from home) and source (store vs. others) may have contributed to these changes. METHODS: Cross-sectional day one dietary data among children ages 2-5 years from the National Health and Nutrition Examination Survey 2003-2004, 2005-2006, 2007-2008, 2009-2010 and 2011-2012 were used. Survey-weighted mean intakes by survey year, eating location and source were computed for total sugar-sweetened beverages (SSBs), milks, 100% juice, low/no-calorie beverages, 10 key beverages, total beverages and total foods. Means were compared using two-tailed z-tests with Bonferroni corrections (α < 0.05). RESULTS: Between 2003-2004 and 2011-2012, among 2-5 year olds, total caloric intake fell by 132 kcal d(-1) , with intakes of beverages falling by 55 kcal d(-1) . Decreases in intakes of total SSBs (-57 kcal d(-1) ), fruit-flavoured or juice drinks containing <100% juice (juice drinks) (-37 kcal d(-1) ), caloric soft drinks (-13 kcal d(-1) ) and >1% fat, low-sugar milk (-42 kcal d(-1) ) were among the major changes. By eating location, total beverage intake at home fell by 73 kcal d(-1) . By source, total beverage intake from stores fell by 106 kcal d(-1) . Changes in intakes occurred primarily between 2003-2004 and 2009-2010, as there were no significant differences in beverage intakes between 2009-2010 and 2011-2012. Intakes of total calories (+49 kcal d(-1) ) and calories from foods (+53 kcal d(-1) ) trended upward between 2009-2010 and 2011-2012, but changes were not significant. CONCLUSIONS: These findings suggest improvements in the diets of preschoolers between 2003-2004 and 2009-2010, of which stores were a major contributor.

Corticosteroid adulteration in proprietary Chinese medicines: a recurring problem.

OBJECTIVES: To investigate adulteration of proprietary Chinese medicines with corticosteroids in Hong Kong. DESIGN: Case series with cross-sectional analysis. SETTING: A tertiary clinical toxicology laboratory in Hong Kong. PATIENTS: All patients using proprietary Chinese medicines adulterated with corticosteroids and referred to the authors' centre from 1 January 2008 to 31 December 2012. MAIN OUTCOME MEASURES: Patients' demographic data, clinical presentation, medical history, drug history, laboratory investigations, and analytical findings of the proprietary Chinese medicines were analysed. RESULTS: The records of 61 patients who consumed corticosteroid-adulterated proprietary Chinese medicines were reviewed. The most common corticosteroid implicated was dexamethasone. Co-adulterants such as non-steroidal anti-inflammatory drugs and histamine H1-receptor antagonists were detected in the proprietary Chinese medicine specimens. Among the patients, seven (11.5%) required intensive care, two (3.3%) died within 30 days of presentation, and 38 (62.3%) had one or more complications that were potentially attributable to exogenous corticosteroids. Of 22 (36.1%) patients who had provocative adrenal function testing performed, 17 (77.3% of those tested) had adrenal insufficiency. CONCLUSION: The present case series is the largest series of patients taking proprietary Chinese medicines adulterated with corticosteroids. Patients taking these illicit products are at risk of severe adverse effects, including potentially fatal complications. Adrenal insufficiency was very common in this series of patients. Assessment of adrenal function in these patients, however, has been inadequate and routine rather than discretionary testing of adrenal function is indicated in this group of patients. The continuing emergence of proprietary Chinese medicines adulterated with western medication indicates a persistent threat to public health.

Recipes and general herbal formulae in books: causes of herbal poisoning.

Traditional Chinese medicine is commonly used locally, not only for disease treatment but also for improving health. Many people prepare soups containing herbs or herbal decoctions according to recipes and general herbal formulae commonly available in books, magazines, and newspapers without consulting Chinese medicine practitioners. However, such practice can be dangerous. We report five cases of poisoning from 2007 to 2012 occurring as a result of inappropriate use of herbs in recipes or general herbal formulae acquired from books. Aconite poisoning due to overdose or inadequate processing accounted for three cases. The other two cases involved the use of herbs containing Strychnos alkaloids and Sophora alkaloids. These cases demonstrated that inappropriate use of Chinese medicine can result in major morbidity, and herbal formulae and recipes containing herbs available in general publications are not always safe.

The physical activity transition among adults in China: 1991-2011.

Previous studies have linked work, home production, travel activities and inactivity with weight and health outcomes. However, these focused on average physical activity (PA) over time rather than changes in PA and associated sociodemographic and economic factors and urbanicity. Using the 1991-2011 China Health and Nutrition Survey data, we estimated the metabolic equivalent of task hours per week for individuals in occupational, domestic, travel and active leisure domains and sedentary hours per week. We present the distributions among adult men and women (aged 18-60), and use quantile regression models to explore factors associated with these trends. Trend analyses on the distribution of PA show declines along the whole distribution of occupational PA for men and women and domestic PA for women in China. These patterns remain consistent after adjusting for individual- and household-level factors. Controlling for urbanicity mitigated the decrease in occupational PA, particularly for men, but not the decrease in domestic PA. Given China's rapid urbanization and its association with occupational PA declines and the strong time trend in domestic PA, there is a need to invest in interventions and policies that promote PA during leisure and travel times.

Ultra-processed products are becoming dominant in the global food system.

The relationship between the global food system and the worldwide rapid increase of obesity and related diseases is not yet well understood. A reason is that the full impact of industrialized food processing on dietary patterns, including the environments of eating and drinking, remains overlooked and underestimated. Many forms of food processing are beneficial. But what is identified and defined here as ultra-processing, a type of process that has become increasingly dominant, at first in high-income countries, and now in middle-income countries, creates attractive, hyper-palatable, cheap, ready-to-consume food products that are characteristically energy-dense, fatty, sugary or salty and generally obesogenic. In this study, the scale of change in purchase and sales of ultra-processed products is examined and the context and implications are discussed. Data come from 79 high- and middle-income countries, with special attention to Canada and Brazil. Results show that ultra-processed products dominate the food supplies of high-income countries, and that their consumption is now rapidly increasing in middle-income countries. It is proposed here that the main driving force now shaping the global food system is transnational food manufacturing, retailing and fast food service corporations whose businesses are based on very profitable, heavily promoted ultra-processed products, many in snack form.

Complexities and opportunities in monitoring and evaluating US and global changes by the food industry.

In developed nations and increasingly in the rest of the world, a large proportion of people's diets comes from manufactured food sources and food not produced at home. These types of products are constantly changing and have significant nutrition and health implications for the world's population. However, researchers, public health workers and policy makers face major complexities in understanding what these changes are and their relationships to diet and health outcomes. This paper will describe some of the complexities faced in monitoring and evaluating the nutritional composition of food products and what it means for population health. Importantly, no existing food composition database is able to keep up with the continuous reformulation and introductions and removals of packaged foods and food services. The paper will also discuss opportunities to improve and update the monitoring and evaluation of changes made by each of these key sectors of the modern food supply and how these changes can influence the nutrients purchased or consumed across the globe. The focus will be on the United States with some examples from other developed nations and a discussion of implications for low- and middle-income countries.

Trends in purchases and intake of foods and beverages containing caloric and low-calorie sweeteners over the last decade in the United States.

BACKGROUND: Current food databases might not capture rapidly occurring changes in the food supply, such as the increased use of caloric (CS) and low-calorie sweeteners (LCS) in products. OBJECTIVE: We explored trends in purchases and intake of foods and beverages containing LCS, CS or both sweeteners over the last decade in the United States, as well as household and socioeconomic status (SES) predictors of these trends. METHODS: We analyzed household purchases from Homescan 2000-2010 (n = 140 352 households; 408 458 individuals) and dietary intake from National Health And Nutrition Examination Survey (NHANES) 2003-2010 (n = 34 391 individuals). We estimated per capita purchases and intake (g or mL d(-1)) and percent of consumers of foods and beverages containing LCS, CS or both LCS + CS. We estimated change in purchases associated with SES and household composition using random-effects longitudinal models. RESULTS: From 2000 to 2010, percent of households purchasing CS products decreased, whereas that for LCS and LCS + CS products increased among all types of households and particularly among those with children. African-American, Hispanic and households with children had a higher % CS beverage purchases (+9, +4 and +3%, respectively, P < 0.001) and lower % LCS beverage purchases (-12, -5 and -2%, respectively, P < 0.001). CONCLUSIONS: During a period of declining purchases and consumption of CS products, we have documented an increasing trend in products that contain LCS and a previously unexplored trend in products with both LCS and CS, especially important among households with children.

C-terminal binding protein-2 regulates response of epithelial ovarian cancer cells to histone deacetylase inhibitors.

Ovarian cancer survival rates have stagnated in the last 20 years despite the development of novel chemotherapeutic agents. Modulators of gene expression, such as histone deacetylase (HDAC) inhibitors, are among the new agents being used in clinical trials. Predictors of sensitivity to chemotherapy have remained elusive. In this study, we show that the expression of the transcriptional corepressor C-terminal binding protein-2 (CtBP2) is elevated in human ovarian tumors. Downregulation of CtBP2 expression in ovarian cancer cell lines using short-hairpin RNA strategy suppressed the growth rate and migration of the resultant cancer cells. The knockdown cell lines also showed upregulation of HDAC activity and increased sensitivity to selected HDAC inhibitors. Conversely, forced expression of wild-type CtBP2 in the knockdown cell lines reversed HDAC activity and partially rescued cellular sensitivity to the HDAC inhibitors. We propose that CtBP2 is an ovarian cancer oncogene that regulates gene expression program by modulating HDAC activity. CtBP2 expression may be a surrogate indicator of cellular sensitivity to HDAC inhibitors.

Time use and physical activity: a shift away from movement across the globe.

Technology linked with reduced physical activity (PA) in occupational work, home/domestic work, and travel and increased sedentary activities, especially television viewing, dominates the globe. Using detailed historical data on time allocation, occupational distributions, energy expenditures data by activity, and time-varying measures of metabolic equivalents of task (MET) for activities when available, we measure historical and current MET by four major PA domains (occupation, home production, travel and active leisure) and sedentary time among adults (>18 years). Trends by domain for the United States (1965-2009), the United Kingdom (1961-2005), Brazil (2002-2007), China (1991-2009) and India (2000-2005) are presented. We also project changes in energy expenditure by domain and sedentary time (excluding sleep and personal care) to 2020 and 2030 for each of these countries. The use of previously unexplored detailed time allocation and energy expenditures and other datasets represents a useful addition to our ability to document activity and inactivity globally, but highlights the need for concerted efforts to monitor PA in a consistent manner globally, increase global PA and decrease sedentary behavior. Given the potential impact on weight gain and other cardiometabolic health risks, the differential declines in MET of activity and increases in sedentary time across the globe represent a major threat to global health.

Acute corneal hydrops mimicking full thickness perforation.

A 26-year-old Caucasian female with keratoconus presented with an acutely painful and red left eye. Visual acuity on presentation was 3/60. Slit lamp examination revealed localised Descemet's membrane break with iris partially plugging it. There was a bulging stromal cyst which would intermittently flatten and reform. The appearance when the cyst was flattened mimicked a full thickness corneal perforation. However, no obvious overlying epithelial defect was detected and an intermittent leakage through micro-perforations in the corneal epithelium was the probable cause of the variable appearance. The anterior chamber reformed and iris plug freed following an insertion of a bandage contact lens and taped eyelid. On follow-up, the Descement's membrane had healed with visual acuity improving to 6/18. Our case illustrates the importance of identifying corneal hydrops mimicking a full thickness perforation as conservative management has a greater chance of recovery.

Arthroscopic debridement of intercarpal ligament and triangular fibrocartilage complex tears.

INTRODUCTION: Wrist arthroscopy has evolved since its inception to become an essential diagnostic and therapeutic tool for the management of various wrist disorders. Our study aimed to examine the outcomes of arthroscopic debridement in the treatment of scapholunate (SL), lunotriquetral (LT) and triangular fibrocartilage complex (TFCC) tears. METHODS: We conducted a retrospective review of 68 consecutive wrist arthroscopies performed at our institution between January 2000 and July 2005. All the patients complained of wrist pain, which often interfered with their daily activities, work or sports. A standard arthroscopic technique was employed in all. Any intercarpal ligament or TFCC tears found were debrided. RESULTS: There were 42 patients with TFCC tears, 58 with SL tears and 49 with LT tears. At a mean follow-up time of 16.6 months, 85.3% of the patients reported an improvement in symptoms and 27.9% had improved range of motion. Grip strength improved by 11.8%. All except two patients returned to their original activities. Outcome following arthroscopic debridement was determined using the Mayo Modified Wrist Score. Based on the postoperative wrist scores of 47 patients, 24 were rated excellent, 17 good, four fair and two poor. By comparing the pre- and postoperative wrist scores of 31 patients, we were able to demonstrate significant improvement in patients who underwent wrist arthroscopies. CONCLUSION: Our study demonstrated that there is a definite role for arthroscopic debridement in the management of SL, LT and TFCC tears.

Drinking to our health: can beverage companies cut calories while maintaining profits?

Carbonated soft drinks and other beverages make up an increasing percentage of energy intake, and there are rising public health concerns about the links between consumption of sugar-sweetened beverages and weight gain, obesity, and other cardiometabolic problems. In response, the food and beverage industry claims to be reformulating products, reducing package or portion sizes and introducing healthier options. Comparative analysis on various changes and their potential effects on public health are needed. We conduct a case study using the two largest and most influential producers of sweetened beverages, The Coca-Cola Company and PepsiCo Inc., who together control 34% of the global soft drink market, examining their product portfolios globally and in three critical markets (the United States, Brazil and China) from 2000 to 2010. On a global basis, total revenues and energy per capita sold increased, yet the average energy density (kJ 100 mL(-1) ) sold declined slightly, suggesting a shift to lower-calorie products. In the United States, both total energy per capita and average energy density of beverages sold decreased, while the opposite was true in the developing markets of Brazil and China, with total per capita energy increasing greatly in China and, to a lesser extent, in Brazil.

Nutrition transition in the United Arab Emirates.

BACKGROUND/OBJECTIVES: The United Arab Emirates has undergone remarkable economic and social transformations over the past few decades. We present findings on the prevalence of overweight and obesity, dietary and activity patterns among Emiratis in 2009/10, and explore associated urbanization and wealth factors. SUBJECTS/METHODS: A cross-sectional study was conducted in 628 randomly selected households in all seven emirates. Sociodemographics, 24-h dietary recalls, physical activity and anthropometric data were collected from adult females (≥ 19 years), adolescents (11-18 years) and children (6-10 years) in each family via in-person interviews using validated questionnaires. RESULTS: In 2009/10, 65% of adult women, 28% of male adolescents and 40% of female adolescents, 25% of male children and 41% of female children were overweight or obese. 43% of girls and 38% of boys (6-10 years) consumed more calories than their estimated energy requirements. Snacking represents a major source of Emirati caloric intake (>20%) of total calories. In addition, caloric beverages account for 8-14% of total calories. Meanwhile, physical activity levels are low, especially among females Emiratis and those living in urban areas. CONCLUSIONS: These trends represent the potential risk for severe cardiometabolic problems in the United Arab Emirates. The significant gender differentials among children and adolescents are driven by diet and activity differences. More attention should be paid to educate the public on nutrition (for example, limit the consumption of sugared sodas, fruit drinks and whole milk, promote water and low-fat/skim milk consumption instead) and encourage physical activity from a young age, especially among females. Built environments and social support for improved lifestyle choices by individuals are needed.

The island pedicled anterolateral thigh (pALT) flap via the lateral subcutaneous tunnel for recurrent ischial ulcers.

Chronic recurrent ischial sores are an important cause of morbidity in paraplegics and geriatric patients. Compared to sacral and trochanteric ulcers, ischial sores are the most difficult to treat, with a low success rate following conservative therapy and a high recurrence rate after surgical treatment. We report the use of the pedicled anterolateral thigh (pALT) flap for reconstruction of a chronic ischial sore. The free ALT flap has an established role in reconstruction in the head and neck and extremities. However, there are few reports concerning its clinical applications for regional reconstruction. As a pedicled flap, it has been used in the primary reconstruction of the perineum, groin, anterior abdominal wall, thigh and ischium. We present the first reported case of a paraplegic man with a recurrent ischial sore treated successfully with an island pALT flap inset via a lateral subcutaneous approach. We discuss the indications and its role as a simple and reliable secondary reconstructive option in the treatment of recurrent ischial ulcers after first-line loco-regional surgical options have been exhausted.

The prevalence and trends of overweight, obesity and nutrition-related non-communicable diseases in the Arabian Gulf States.

This paper reviews studies on the prevalence of overweight, obesity and related nutrition-related non-communicable diseases in Bahrain, Kuwait, Qatar, Oman, Saudi Arabia and the UAE. Obesity is common among women; while men have an equal or higher overweight prevalence. Among adults, overweight plus obesity rates are especially high in Kuwait, Qatar and Saudi Arabia, and especially among 30-60 year olds (70-85% among men; 75-88% among women), with lower levels among younger and elderly adults. The rate of increase in obesity was pronounced in Saudi Arabia and Kuwait. Prevalence of obesity is high among Kuwaiti and Saudi pre-schoolers (8-9%), while adolescent overweight and obesity are among the highest in the world, with Kuwait having the worst estimates (40-46%); however, comparison of child data is difficult because of differing standards. Among nutrition-related non-communicable diseases, hypertension and diabetes levels are very high and increase with age, with the UAE performing the worst because of a rapid rate of increase between 1995 and 2000. Additional monitoring of the prevalence of metabolic syndrome and cancers is necessary. Nationally representative longitudinal surveys with individual, household and community-level information are needed to determine the importance of various factors that contribute to these troubling trends.

Identification of regions of the P2X(7) receptor that contribute to human and rat species differences in antagonist effects.

BACKGROUND AND PURPOSE: Several P2X(7) receptor antagonists are allosteric inhibitors and exhibit species difference in potency. Furthermore, N(2)-(3,4-difluorophenyl)-N(1)-(2-methyl-5-(1-piperazinylmethyl)phenyl)glycinamide dihydrochloride (GW791343) exhibits negative allosteric effects at the human P2X(7) receptor but is a positive allosteric modulator of the rat P2X(7) receptor. In this study we have identified several regions of the P2X(7) receptor that contribute to the species differences in antagonist effects. EXPERIMENTAL APPROACH: Chimeric human-rat P2X(7) receptors were constructed with regions of the rat receptor being inserted into the human receptor. Antagonist effects at these receptors were measured in ethidium accumulation and radioligand binding studies. KEY RESULTS: Exchanging regions of the P2X(7) receptor close to transmembrane domain 1 modified the effects of KN62, 4-(4-fluorophenyl)-2-(4-methylsulphinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580) and GW791343. Further studies, in which single amino acids were exchanged, identified amino acid 95 as being primarily responsible for the differential allosteric effects of GW791343 and, to varying degrees, the species differences in potency of SB203580 and KN62. The species selectivity of pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid was affected by multiple regions of the receptor, with potency being particularly affected by the amino acid 126 but not by amino acid 95. A further region of the rat receptor (amino acids 154-183) was identified that, when inserted into the corresponding position in the human receptor, increased ATP potency 10-fold. CONCLUSIONS: This study has identified several key residues responsible for the species differences in antagonist effects at the P2X(7) receptor and also identified a further region of the P2X(7) receptor that can significantly affect agonist potency at the P2X(7) receptor.