Pharmacokinetics and efficacy of a novel long-acting bupivacaine formulation for cornual nerve block in calves.

Local anesthetics are commonly used in farm animals to provide analgesia for painful procedures but can cause adverse effects at high systemic concentrations. The pharmacokinetics and efficacy of a long-acting sucrose acetate isobutyrate (SAIB) bupivacaine formulation following cornual nerve block in calves were compared to lidocaine. Fourteen calves were randomly assigned to one of the treatment groups (i) 5% Bupivacaine-SAIB (BUP-SAIB), n = 7; or (ii) 2% lidocaine (LID), n = 7. Cornual nerve block was performed, and duration of effective analgesia was evaluated by nociceptive threshold testing using a hand-held pressure algometer. Blood samples were collected at various time points and plasma concentrations were analyzed by HPLC. Pharmacokinetic parameters were calculated using a non-compartmental model. The mechanical nociceptive thresholds showed that the novel formulation could desensitize the skin around the horn bud for 18.77 ± 8.88 h (range 8-36 h), compared to 0.79 ± 0.34 h (range 0.5-1.5 h) with lidocaine. The mean maximum plasma concentration (Cmax) of bupivacaine was 152.03 (SD 37.34) ng/mL and its Tmax was 0.39 (SD 0.13) h. The half-life of elimination was 32.79 ± 11.00 h and the rate of clearance was 0.12 ± 0.03 L h-1. No toxicity signs were seen after treatment in either group. The novel formulation produced long-lasting analgesia of several times greater duration than that produced by lidocaine. This study showed that the safety and efficacy of the SAIB formulation justifies further studies in a larger population of animals.

Environmental Influences on the Behavioural and Emotional Outcomes of Children: A Network Analysis.

BACKGROUND: Intellectual developmental disorders are a serious source of health morbidity with negative consequences for adults as well as children. However, there is limited evidence on the environmental, trace element, behavioural, and emotional outcomes in children. Here, we investigated whether there is any association between child behaviour and emotional outcomes and micronutrients using network analysis. METHODS: A cross-sectional study was conducted in 9-year-old children within a Pacific Island Families study birth cohort. Elemental concentration was determined in children's toenails after acid digestion and analysed using inductively coupled plasma mass spectrometry. We used network analysis to identify closely associated trace elements and tested the directions and strength of these trace elements. MANCOVA were used to identify the significant associations between individual elements and the behavioural/emotional function of the children using the children behaviour checklist (CBCL). At the final step, quantile regression analysis was used to assess and quantify the identified associations between CBCL function scores and manganese, adjusted by sex, ethnicity, and standardized BMI. RESULTS: Three major nutrient networks were identified. In the Mn network, Mn was strongly positively associated with Al (0.63) and Fe (r = 0.65) and moderately associated with Pb (r = 0.45) and Sb (r = 0.42). Al was also strongly associated with Fe (r = 0.9). Children in the second or third clinical group, with an elevated externalized CBCL score, had a much higher mean and median level of Mn as compared to the normal range group. The aggression score was significantly associated with Mn concentration and sex. Higher Mn concentrations were associated with a higher aggression score. A 1 ug/g unit increase in Mn was associated with a 2.44-fold increase (95% confidence interval: 1.55-4.21) in aggression score, and boys had higher median aggression score than girls (difference: 1.7, 95% CI: 0.9-2.8). Attention and rule breaking scores were both significantly associated with Mn concentration. Higher Mn concentrations were associated with higher attention behaviour problem and rule breaking scores. A 1 ug/g unit increase in Mn was found to be associated with a 1.80-fold increase (95% confidence interval: 1.37-2.82) in attention score, and a 1.46-fold increase (95% confidence interval: 1.01-1.74) in the rule breaking score. Thought score was not significantly associated with Mn concentration (p = 0.13) but was significantly lower in boys (p = 0.004). CONCLUSIONS: Exceeding Mn levels is potentially toxic and has been identified to be associated with worse externalized children's behavioural health and emotional well-being. Future studies are necessary to find the exposure paths so that advice shall be provided to family and care providers in public health and environmental protection.

Evaluating the Behavioural Responses of Healthy Newborn Calves to a Thoracic Squeeze.

A thoracic squeeze has been observed to cause low-vigour neonates of various farmed mammal species, including calves, to enter a state of reduced responsiveness. The removal of the squeeze causes rapid recovery and the expression of normal, healthy behaviours. However, the responses of healthy calves to a thoracic squeeze have not yet been characterized. The responses of 16 healthy newborn calves to a thoracic squeeze are described, along with the effect of the squeeze's application method on the response. Calves aged between 12 and 36 h were subjected to the squeeze using a rope (n = 8) or an inflation cuff (n = 8). In total, 13 of the 16 calves were induced into a state of reduced responsiveness, though neural reflexes persisted in nearly all of them. The squeeze was discontinued for nearly half of those induced before the end of the 10-min period, either due to spontaneous arousal or physiological instability. Both methods of application were equally effective at inducing reduced responsiveness, though responses to the cuff appeared to be more rapid than those to the rope. These findings support previous research on piglets and foals, and suggest that the behavioural responses to a thoracic squeeze are generalised across neonates of precocial farmed mammals; the findings provide a foundation for further research exploring the mechanisms underlying the response and the benefits that its application may bring for the performance of husbandry procedures.

Characterisation of the Behavioural Effects of a Thoracic Squeeze in Healthy Newborn Piglets.

A thoracic squeeze has been observed to cause both healthy and low vigour neonatal foals to enter a 'less-responsive state', characterised by loss of posture, eye closure and cessation of movement, from which they rapidly recover to express normal healthy behaviours when the squeeze is released. To date, there have been no systematic studies characterising the responses of healthy neonates of other mammalian species to a thoracic squeeze. We describe the responses of healthy newborn piglets (n = 17) to a standardised application of the thoracic squeeze and evaluate the effect of the method of squeeze application on the response. Neonatal piglets were squeezed around the chest with either a soft fabric rope as has been used in foals (n = 8) or a novel purpose-made inflation cuff (n = 9). Both methods were effective at inducing a less-responsive behavioural state in all piglets, with neural reflexes reduced or absent in over half of them. The inflation cuff appeared to induce the less-responsive state faster than the rope, and more piglets squeezed with the cuff remained in this state for the full 10-min squeeze. These findings suggest that the behavioural response of foals to thoracic squeezing can be generalised to neonates of other precocial mammalian species. This initial study provides a foundation for further research using the inflation cuff to explore mechanisms underlying the thoracic squeeze and ways in which it may be applied whilst performing husbandry procedures.

The COVID University Challenge: A Hazard Analysis of Critical Control Points Assessment of the Return of Students to Higher Education Establishments.

The COVID-19 pandemic has disrupted economies and societies throughout the world since early 2020. Education is especially affected, with schools and universities widely closed for long periods. People under 25 years have the lowest risk of severe disease but their activities can be key to persistent ongoing community transmission. A challenge arose for how to provide education, including university level, without the activities of students increasing wider community SARS-CoV-2 infections. We used a Hazard Analysis of Critical Control Points (HACCP) framework to assess the risks associated with university student activity and recommend how to mitigate these risks. This tool appealed because it relies on multiagency collaboration and interdisciplinary expertise and yet is low cost, allowing rapid generation of evidence-based recommendations. We identified key critical control points associated with university student' activities, lifestyle, and interaction patterns both on-and-off campus. Unacceptable contact thresholds and the most up-to-date guidance were used to identify levels of risk for potential SARS-CoV-2 transmission, as well as recommendations based on existing research and emerging evidence for strategies that can reduce the risks of transmission. Employing the preventative measures we suggest can reduce the risks of SARS-CoV-2 transmission among and from university students. Reduction of infectious disease transmission in this demographic will reduce overall community transmission, lower demands on health services and reduce risk of harm to clinically vulnerable individuals while allowing vital education activity to continue. HACCP assessment proved a flexible tool for risk analysis in a specific setting in response to an emerging infectious disease threat. Systematic approaches to assessing hazards and risk critical control points (#HACCP) enable robust strategies for protecting students and staff in HE settings during #COVID19 pandemic.

Investigation of the uptake of molybdenum by plants from Argentinean groundwater.

Some regions of Argentina are affected by high concentrations of molybdenum, arsenic and vanadium from natural sources in their groundwater. In particular, Mo levels in groundwater from Eduardo Castex (La Pampa, Argentina) typically exceed the guidelines for drinking water formerly established by WHO at 70 µg/L. Therefore, this study investigated the uptake of Mo in plants, using cress (Lepidium sativum L.) as a model using hydroponic experiments with synthetic solutions and groundwater from La Pampa. Cress grown from control experiments (150 µg/L Mo, pH 7) presented an average Mo concentration of 35.2 mg/kg (dry weight, d.w.), higher than the typical total plant range (0.7-2.5 mg/kg d.w.) in the literature. Using pooled groundwater samples (65.0-92.5 µg/L Mo) from wells of La Pampa (Argentina) as growth solutions resulted in significantly lower cress Mo levels (1.89-4.59 mg/kg d.w.) than were obtained for synthetic solutions of equivalent Mo concentration. This may be due to the high levels in these groundwater samples of As, V, Fe and Mn which are known to be associated with volcanic deposits. This research addressed the hitherto scarcity of data about the effect of various physicochemical parameters on the uptake of Mo in plants.

Use of human teardrop fluid for the determination of trace elements in healthy individuals and diabetic patients.

BACKGROUND: The use of unconventional biological materials in human trace element studies has increased in terms of published research studies. The aim of present study was to develop and validate the use of teardrop fluid for determining trace element levels in the human body. No study has been published in this area yet. This is a new non-invasive approach in the possible early diagnosis of the pathogenesis of type 2 diabetes. MATERIALS AND METHODS: Human teardrop fluid samples were obtained from Karbala (Iraq) (n = 111) healthy individuals and with type 2 diabetes (n = 44); and London (UK) healthy individuals (n = 18). The levels of V, Cr, Mn, Fe, Cu, Zn, As, Sr and Cd were determined using an inductively coupled plasma mass equipped with collision cell technology for polyatomic ion correction (ICP-MS). STATISTICAL ANALYSIS: Discriminate function analysis (DFA) was carried out to determine the set of variables that discriminated between the trace elements in teardrop fluid samples from healthy individuals and diabetic patients. RESULTS: The trace element levels of human teardrop fluid are similar for many elements to that reported for human blood serum in the literature. This is interesting since they have different physiological functions, although overall they are mainly water containing electrolytes (∼ 90 %) and solids (antibodies, hormones, etc). In general, for the study groups in Karbala, Iraq, significantly higher teardrop fluid levels of Mn and Sr were found in type 2 diabetic patients when compared with healthy individuals (evaluated using an F-test and a two-tailed t-test). The levels of V, Cu and As were found to be significantly higher (P < 0.05) in healthy individuals than type 2 diabetic patients. Although the levels of Fe and Zn were slightly higher in type 2 diabetic patients than healthy cases, the differences were not statistically significant (P > 0.05). Cr and Cd were found to have similar levels for both study groups. Significantly higher teardrop fluid levels of V, Cr, Mn, Fe, Zn, As and Sr were found in healthy individuals from Karbala (Iraq) when compared with those from London (UK). In contrast, the levels of Cd observed to be significantly higher in London (UK) than Karbala. No statistical difference was found for Cu between the two healthy groups. STATISTICAL ANALYSIS: Discriminate analysis showed that human teardrop fluid V, Mn, Zn, As, Sr and Cd levels could be used to discriminate between healthy and type 2 diabetes study groups in Karbala, Iraq (83 % of cases correctly classified). CONCLUSION: The use of human teardrop fluid for determining the trace element levels of human health conditions has been evaluated. Trace elemental levels are like that for blood serum which is widely used as an invasive method for assessing human health conditions. Sample collection for teardrop fluid is non-invasive and the application has potential for determining the trace element levels in healthy individuals and disorder conditions (like type 2 diabetes) in countries where cultural and gender sensitivity are issues with respect to the collection methods used for other body fluid samples.

Pharmacokinetics, efficacy and convulsive dose of articaine hydrochloride in goat kids.

OBJECTIVE: To investigate the pharmacokinetics, efficacy and convulsive dose of articaine hydrochloride in goat kids. STUDY DESIGN: Experimental prospective study. ANIMALS: A total of 18 (n = 6 animals per experiment) male Saanen goat kids (2-4 weeks old). METHODS: The study consisted of three experiments. The first determined the pharmacokinetics of articaine following intravenous administration of articaine hydrochloride (8 mg kg-1). The second experiment investigated the anaesthetic efficacy and pharmacokinetics following cornual nerve block using 1.5% articaine hydrochloride. Anaesthesia of horn buds was evaluated using the response to pinprick test. Non-compartmental analysis was used. The final experiment determined the convulsive dose of articaine and its corresponding plasma concentration following intravenous infusion of articaine hydrochloride (4 mg kg-1 minute-1). Data are shown as mean ± standard deviation. RESULTS: The mean terminal half-life (t1/2λz), mean volume of distribution at steady state (Vdss) and mean plasma clearance (CL) of articaine following intravenous administration were 0.66 hour, 3.81 L kg-1 and 5.33 L hour-1 kg-1, respectively. After cornual nerve block, the mean maximum plasma concentration of articaine was 587 ng mL-1 at 0.22 hour and its mean t1/2λz was 1.26 hours. Anaesthesia of horn buds was observed within 4 minutes following cornual nerve block. The mean dose required to produce convulsions was 16.24 mg kg-1 and mean convulsive plasma concentrations of articaine and articainic acid were 9905 and 1517 ng mL-1, respectively. CONCLUSIONS: Intravenous administration of 8 mg kg-1 of articaine hydrochloride did not cause any adverse effects. Pharmacokinetic data suggest that articaine was rapidly eliminated and cleared. Cornual nerve block using 1.5% articaine hydrochloride alleviated the response to the acute nociceptive stimulus during disbudding. CLINICAL RELEVANCE: Articaine hydrochloride appears to be a safe and effective local anaesthetic for disbudding in goat kids.

The Noninvasive Ventilation Outcomes (NIVO) score: prediction of in-hospital mortality in exacerbations of COPD requiring assisted ventilation.

INTRODUCTION: Acute exacerbations of COPD (AECOPD) complicated by acute (acidaemic) hypercapnic respiratory failure (AHRF) requiring ventilation are common. When applied appropriately, ventilation substantially reduces mortality. Despite this, there is evidence of poor practice and prognostic pessimism. A clinical prediction tool could improve decision making regarding ventilation, but none is routinely used. METHODS: Consecutive patients admitted with AECOPD and AHRF treated with assisted ventilation (principally noninvasive ventilation) were identified in two hospitals serving differing populations. Known and potential prognostic indices were identified a priori. A prediction tool for in-hospital death was derived using multivariable regression analysis. Prospective, external validation was performed in a temporally separate, geographically diverse 10-centre study. The trial methodology adhered to TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) recommendations. RESULTS: Derivation cohort: n=489, in-hospital mortality 25.4%; validation cohort: n=733, in-hospital mortality 20.1%. Using six simple categorised variables (extended Medical Research Council Dyspnoea score 1-4/5a/5b, time from admission to acidaemia >12 h, pH <7.25, presence of atrial fibrillation, Glasgow coma scale ≤14 and chest radiograph consolidation), a simple scoring system with strong prediction of in-hospital mortality is achieved. The resultant Noninvasive Ventilation Outcomes (NIVO) score had area under the receiver operating curve of 0.79 and offers good calibration and discrimination across stratified risk groups in its validation cohort. DISCUSSION: The NIVO score outperformed pre-specified comparator scores. It is validated in a generalisable cohort and works despite the heterogeneity inherent to both this patient group and this intervention. Potential applications include informing discussions with patients and their families, aiding treatment escalation decisions, challenging pessimism and comparing risk-adjusted outcomes across centres.

Chemical Composition and Bioactive Properties of Commercial and Non-Commercial Purple and White Açaí Berries.

Chemical composition analysis of açaí extracts revealed higher levels of total polyphenol content in purple açaí samples for both commercial (4.3-44.7 gallic acid equivalents mg/g) and non-commercial samples (30.2-42.0 mg/g) compared to white (8.2-11.9 mg/g) and oil samples (0.8-4.6 mg/g). The major anthocyanin compounds found in purple açaí samples were cyanidin-3-glucoside and cyanidin-3-rutinoside with total concentrations in the range of 3.6-14.3 cyanidin-3-glucoside equivalents mg/g. The oligomeric proanthocyanidins were quantified in the range of 1.5-6.1 procyanidin B1 equivalents mg/g. Moreover, açaí presented significant levels of calcium, magnesium, manganese, iron, zinc and copper, essential minor and trace elements, in comparison with other berries. All of the açaí extracts at 50 µg/mL potently inhibited the release of reactive oxygen species in lipopolysaccharide-stimulated RAW 264.7 murine macrophage cells, but none inhibited the release of nitric oxide. Furthermore, all the açaí samples demonstrated potential as wound healing agents due to the high levels of migration activity in human fibroblast cells.

Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study.

BACKGROUND: Over 30% of adult patients with pleural infection either die and/or require surgery. There is no robust means of predicting at baseline presentation which patients will suffer a poor clinical outcome. A validated risk prediction score would allow early identification of high-risk patients, potentially directing more aggressive treatment thereafter. OBJECTIVES: To prospectively assess a previously described risk score (the RAPID (Renal (urea), Age, fluid Purulence, Infection source, Dietary (albumin)) score) in adults with pleural infection. METHODS: Prospective observational cohort study that recruited patients undergoing treatment for pleural infection. RAPID score and risk category were calculated at baseline presentation. The primary outcome was mortality at 3 months; secondary outcomes were mortality at 12 months, length of hospital stay, need for thoracic surgery, failure of medical treatment and lung function at 3 months. RESULTS: Mortality data were available in 542 out of 546 patients recruited (99.3%). Overall mortality was 10% at 3 months (54 out of 542) and 19% at 12 months (102 out of 542). The RAPID risk category predicted mortality at 3 months. Low-risk mortality (RAPID score 0-2): five out of 222 (2.3%, 95% CI 0.9 to 5.7%); medium-risk mortality (RAPID score 3-4): 21 out of 228 (9.2%, 95% CI 6.0 to 13.7%); and high-risk mortality (RAPID score 5-7): 27 out of 92 (29.3%, 95% CI 21.0 to 39.2%). C-statistics for the scores at 3 months and 12 months were 0.78 (95% CI 0.71-0.83) and 0.77 (95% CI 0.72-0.82), respectively. CONCLUSIONS: The RAPID score stratifies adults with pleural infection according to increasing risk of mortality and should inform future research directed at improving outcomes in this patient population.

Exposure to Toenail Heavy Metals and Child Behavior Problems in Nine-Year-Old Children: A Cross-Sectional Study.

Behavioral problems are multifactorial and includes perinatal, maternal, family, parenting, socio-economic and personal risk factors, but less is known about the association of postnatal heavy metals on children's behavioral problems in Pacific Island children. METHODS: A cohort of eligible nine-year-old children within a Pacific Island Families longitudinal study were recruited for a cross-sectional study. Child behavior problems were assessed using the child behavior checklist. Heavy metals (including Ni, Cu, Pb, Al, Cr and Cd) were determined in toenails, after acid digestion and analyzed using inductively coupled plasma mass spectrometry. Other factors such as lifestyle (smoking in pregnancy), health outcomes (obesity, health status), demographics (gender, ethnicity, parents' marital status) and socioeconomic status (household income levels) were also collected. The statistical analysis included t-tests for independent sample and Mann-Whitney U-test, and chi-square or Fisher's exact tests of independence for comparisons of the proportions. Regression models tested the hypothesized risk factors for behavior outcomes. RESULTS: This observational study enrolled 278 eligible Pacific Island children living in Auckland, New Zealand. The prevalence of behavioral problems in the clinical range was high (22%) but there was no significant association between heavy metals in toenails and adverse behavioral outcomes. CONCLUSION: Regular monitoring and assessments of children for environmental risk factors, as well as social and lifestyle factors for behavior problems, continues. Alternative indicators of exposure to heavy metal should be evaluated.

Phenolic content, anti-inflammatory properties, and dermal wound repair properties of industrially processed and non-processed acai from the Brazilian Amazon.

Acai fruit is recognized for its health promoting properties. However, there is still a need to address the effects of industrial processing on this fruit. In this study, phenolic content, anti-inflammatory properties and dermal wound repair properties of 20 acai samples, before and after industrial processing, from various Amazon regions were investigated. Acai pulp was rich in total phenolics (18.9-58.8 mg g-1) and proanthocyanins (9.8-43.1 mg g-1), but contained trace anthocyanins (up to 0.1 mg g-1). Industrially processed samples lost substantial amounts of proanthocyanidins (up to 83.2%), while the anthocyanins inherently present were greatly enriched after processing (20-fold higher). Non-processed acai pulp extracts protected against early inflammation response which was correlated with proanthocyanidins, by significantly inhibiting nitric oxide production and suppressing pro-inflammatory gene expression including interleukin-1ß, cyclooxygenase-2, nitric oxide synthase, and interleukin-6. The promotion of dermal wound repair of acai seed and pulp extracts was mainly contributed by anthocyanins and other bioactive compounds. The anti-inflammatory effect was diminished but wound healing effect was retained after pulp processing, suggesting the processing technology needs to be improved to maintain biological properties of acai fruit.

Considering the Fetus as Messenger.

The author characterizes the Pope's position on the sanctity of fetal life as less a moral proposition than an observation about the unborn child's function as an essential messenger, through the mother's pregnancy to the child's birth and to the child's role in defining the family. He considers the Pope's suggestion as a means of lowering the heat surrounding the abortion issue by distancing that dialogue from ingrained dogma. However, in proposing this point to a friend who is a firm pro-choice partisan, the author finds her skeptical of the Pope's frankness in thus framing the issue, and that she views the Pope's apparent concessions as merely tactical.

Household Smoking Status and Heavy Metal Concentrations in Toenails of Children.

There is limited evidence on the distribution of heavy metals and its association with secondhand smoking (SHS) within Pacific Island children living in New Zealand. Certain heavy metals such as cadmium (Cd), lead (Pb), and aluminum (Al) bioaccumulates in the body and can deteriorate health in both children and adults. Others, such as chromium (Cr) and nickel (Ni) in trace amounts are necessary but become toxic at high levels. Exposure routes of these elements include food, water, and air. The purpose of this study was to identify the distribution of toxic metal concentrations and its possible correlation with SHS within the Pacific Island children. A sub-sample of children within Pacific Island families longitudinal study, at the nine-year phase, who were living in the New Zealand city of Auckland were invited to participate, (n = 278). Toenails were used as a biomarker to determine Cr, Pb, Cd, Cu, Ni, and Al concentration using inductively coupled plasma mass spectrometry. Reliable and validated questionnaires were used for demographics, lifestyle, and health outcome variables. Significant differences between household smoking status and ethnicity, as well as parents' marital status, were observed (p < 0.05). There was no statistical difference in heavy metal concentrations in smoking versus non-smoking households. However, Cr, Pb, Cd, Cu, and Ni concentrations were all higher than the required optimal health value in both groups. A high concentration of heavy metals was observed in these children that exceeded the value required for optimal health, although no significant difference in heavy metals with regards to secondhand smoking was observed. SHS was associated with children's ethnicity and parental marital status, but not with household income levels or maternal education.

Mercury Exposure in Mother-Children Pairs in A Seafood Eating Population: Body Burden and Related Factors.

Background: Mercury is a neurotoxin that affects neurodevelopment in children; however, its association at the lowest concentration is not clear. The main objective of this study is to measure and evaluate mercury concentrations in mother-child pairs and its association demographics, lifestyle, and dietary factors within the Pacific Island Families living in Auckland, New Zealand. Methods: Mercury exposure was assessed in a sub-sample of mother-child pairs who were a part of the Pacific Island Families birth cohort, in Auckland, New Zealand at the 6-year phase. Hair samples were collected from both mothers and their children to determine mercury concentrations. Total mercury was measured using inductively coupled plasma mass spectrometry for hair samples. An interviewer-based reliable food frequency questionnaire (FFQ) examined the frequency of seafood by all the participants. Other variables such as sociodemographic (ethnicity and gender), lifestyle factors (income, education, and smoking status) and health outcomes (child behaviour and obesity) were also collected. Results: In this study, 41% of both mothers and their children had mercury concentrations above the US Environmental Protection Agency (EPA) recommended value of 1 µg/g. Most of the participants ate fish 3 or more times a week. A significant correlation was observed between mother and child hair mercury concentrations (Spearman Rho 0.79 (95% confidence interval (CI): 0.65, 0.88)). Conclusions: Mercury levels in children can be affected by their mothers' levels due to similar eating patterns.

Comparison of electroencephalographic changes in response to acute electrical and thermal stimuli with the tail flick and hot plate test in rats administered with opiorphin.

BACKGROUND: The objective of this study was to compare the changes in the electroencephalogram (EEG) in response to noxious stimuli with tail flick and hot plate responses of rats administered opiorphin. METHODS: Female Sprague -Dawley rats (n = 8 per group) randomly received intravenous (IV) injection of morphine (1 mg/kg,) or opiorphin (2 mg/kg,) or saline (0.5 ml,) in each of the three testing methods (EEG, tail flick and hot plate). Each type of test (n = 24 per test) was conducted in different population of rats on separate occasions. The tail flick and hot plate latencies were recorded until 5 min after test drug administration to conscious rats. The EEG was recorded in anaesthetised rats subjected to noxious thermal and electrical stimuli after test drug administration. At the end of 5 min in each of the testing methods rats were administered naloxone subcutaneously (SC) (1 mg/kg) and the test procedure was repeated. RESULTS: There was no significant increase in the median frequency and spectral edge frequency (F50 & F95) of EEG, indicators of nociception, of morphine and opiorphin groups after noxious stimulation. Noxious stimuli caused a significant increase in both F50 and F95 of the saline group. An injection of naloxone significantly increased the F50, thus blocking the action of both opiorphin and morphine. There was a significant increase in the tail flick latency after administration of opiorphin and morphine as compared to the baseline values. Rats of morphine group spent significantly longer on the hot plate when compared to those of the opiorphin and saline groups. There was no significant difference in the hot plate latencies of opiorphin and saline groups. CONCLUSION: The results of this study suggest that the analgesic effect of opiorphin occurs at the spinal level and it is not as effective as morphine at supraspinal level. It may be due to rapid degradation of opiorphin or limited ability of opiorphin to cross the blood brain barrier or a higher dose of opiorphin is required for its action in the brain. Pharmacokinetic/pharmacodynamics studies along with in vivo penetration of opiorphin in the cerebrospinal fluid are required for further evaluation of opiorphin analgesia.

Status and interrelationship of toenail elements in Pacific children.

OBJECTIVE: Elemental deficiencies or in excess effects growth and development. Pacific population are at a disadvantage due to food insecurity as compared to New Zealand European households. This study aims to evaluate the status and interrelationship of elements (essential, non-essential and toxic) in nine-year-old Pacific children who were part of the Pacific Island Families Study living in New Zealand. MATERIALS AND METHODS: This observational study included 278 eligible nine-year-old children. Essential elements (including calcium, chromium, cobalt, copper, iodine, iron, magnesium, manganese, selenium, zinc, molybdenum), non-essential and toxic elements (arsenic, aluminum, antimony, boron, cadmium, lead, mercury, nickel,) were determined in toenails and after acid digestion, analysed using inductively coupled plasma mass spectrometry. Principal component analysis and multivariate analysis of covariance was used to identify differences in the groups of elements and the inter-correlations between elements. RESULTS: The mean calcium (868µg/g Ca), selenium (0.35µg/g Se) and zinc (129µg/g Zn) concentrations were lower while the mean cadmium (0.21µg/g Cd) lead (0.86µg/g Pb) and mercury (0.72µg/g Hg) concentrations were higher than the optimal health requirements. Ethnic differences in relation to toenail elemental concentrations were observed for aluminium and iron. Gender differences were observed for aluminium, antimony, arsenic and lead. Selenium and molybdenum were inversely associated with mercury. Manganese, zinc and calcium were positively associated. CONCLUSIONS: This research contributes to the understanding of the elemental concentrations for Pacific children by using tissue samples from toenails, which improves the completeness of sampling than other tissues and provides a longer exposure time frame. The study also reports several inter-correlations between essential, non-essential and toxic elements in Pacific Island population.

Effect of food preparation using naturally-contaminated groundwater from La Pampa, Argentina: Estimation of elemental dietary intake from rice and drinking water.

Water from La Pampa, Argentina, was used for washing and cooking rice to examine the in-situ impact of using naturally-contaminated water for food preparation on the elemental dietary intake. Whilst washing with the control tap water (28 µg/L As) reduced the concentration of As in rice by 23%, the use of different well waters (281-1144 µg/L) increased As levels significantly (48-227%) in comparison with the original concentration in the rice (0.056 µg/g). Cooking the rice at a low water-to-rice ratio (2:1) using modern methods increased the levels of As in the cooked samples by 2-3 orders of magnitude for both pre-washed and un-washed rice. Similar trends were observed for vanadium. Although the levels of manganese, iron, copper, zinc and molybdenum in rice were reduced during washing and cooking for most water samples, the molybdenum concentration in the cooked rice doubled (2.2-2.9 µg/g) when using water containing >1 mg/L Mo.

Domain specific effects of postnatal toenail methylmercury exposure on child behaviour.

OBJECTIVE: Very little is known about the relationship between postnatal methylmercury concentrations (via toenails as bioindicator) and behavioural characteristics of Pacific Island children living in New Zealand. The aim of this study was to explore the association between total mercury exposure and different domains of behavioural problems in Pacific children. MATERIALS AND METHODS: A sample of nine-year-old Pacific Island children resident in Auckland, New Zealand participated in this study. Total mercury was determined in biological samples (toenail clippings) on behavioural problems as identified by mothers (using the child behaviour checklist). Specific behavioural domains, particularly aggression, rule breaking, attention and social problems were studied in relation to mercury exposure using toenails. The determination of mercury concentration in toenail clippings, after acid digestion was carried out using inductively coupled plasma mass spectrometry. RESULTS: The observational study was conducted between July 2010 and July 2011 in which 278 eligible nine-year-old Pacific Island children were enrolled (Girls n=58%; boys n=42%). FINDINGS: showed that 21% of the children had total toenail mercury concentrations (1.5µg/g to 6µg/g) higher than the United State Environmental Protection Agency recommended levels (RfD; 1µg/g Hg) for optimal health in children. Aggressive behaviour was associated with total toenail mercury exposure after adjusting for gender, ethnicity and income levels (OR: 2.15 95% CI 1.45, 3.18 p-value <0.05; OR 1.38 95% CI 0.83, 1.2 p value <0.05, respectively). CONCLUSIONS: Overall, this research contributes to the understanding of total toenail mercury concentrations for Pacific people in New Zealand using toenail clippings as biomarkers in terms of associations with child behavioural problems. Mercury in toenails demonstrated a moderate association with a specific behavioural domain - aggressive behaviour.