Residence time distribution in holding tubes using generalized convection model and numerical convolution for non-ideal tracer detection

A procedure is proposed for the determination of the residence time distribution (RTD) of curved tubes taking into account the non-ideal detection of the tracer. The procedure was applied to two holding tubes used for milk pasteurization in laboratory scale. Experimental data was obtained using an ionic tracer. The signal distortion caused by the detection system was considerable because of the short residence time. Four RTD models, namely axial dispersion, extended tanks in series, generalized convection and PER + CSTR association, were adjusted after convolution with the E-curve of the detection system. The generalized convection model provided the best fit because it could better represent the tail on the tracer concentration curve that is Caused by the laminar velocity profile and the recirculation regions. Adjusted model parameters were well cot-related with the now rate. (C) 2010 Elsevier Ltd. All rights reserved.

Increase of core temperature induced by corticotropin-releasing factor and urocortin: A comparative study

This study compared the ability of CRF and UCN1 to induce a thermoregulatory response when centrally injected into rats. The effects of antipyretic drugs and CRF receptor antagonists (CRF(1) and CRF(2)) on the temperature (T) changes induced by these peptides were also investigated. Rectal (rT) and tail skin (T(sk)) temperatures were measured with a thermistor probe while body (bT) temperature was measured with a battery-operated biotelemetry transmitter in male Wistar rats (200 g) every 30 min over a period of 6 h, after intracerebroventricular (i.c.v.) injection of 1 nmol of either CRF or UCN1. Rats were pre-treated with indomethacin (2 mg kg(-1), i.p.) or celecoxib (5 mg kg(-1), p.o.), dexamethasone (0.5 mg kg(-1), s.c.), astressin (a CRF(1)/CRF(2) antagonist, 7 nmol, icy.) or antalarmin (a CRF(1) antagonist, 20 mg kg 1, i.p.). The increase in body temperature induced by CRF was accompanied by a reduction in T(sk) while the response induced by UCN1 was accompanied by an elevation in T(sk). Indomethacin or celecoxib did not change the increases in rT caused by either CRF or UCN1. Although dexamethasone attenuated the increase in rectal temperature in response to CRF, dexamethasone did not modify the response induced by UCN1. Astressin blocked the UCN1-induced hyperthermia and reduced CRF-induced fever. Antalarmin did not modify the hyperthermia in response to UCN1, but reduced the fever evoked by CRF. This study demonstrated that CRF by acting on the CRF(1) receptor induces a prostaglandin-independent fever which seems to depend, at least in part, on the synthesis of other mediators while UCN1 acts on the CRF(2) receptor, promoting a hyperthermic response which seems to be independent on synthesis/release of any mediator. (C) 2010 Elsevier B.V. All rights reserved.

Antinociceptive and anti-inflammatory properties of 7-hydroxycoumarin in experimental animal models: potential therapeutic for the control of inflammatory chronic pain

Objectives In the present study we investigated the anti nociceptive, anti-inflammatory and antipyretic effects of 7-hydroxycoumarin (7-HC) in animal models. Methods The effects of oral 7-HC were tested against acetic acid-induced writhing, formalin test, tail flick test, complete Freund`s adjuvant (CFA)-induced hypemociception, carrageenan-induced paw oedema, lipopolysaccharide-induced fever and the rota rod test. Key findings 7-HC (3-60 mg/kg) produced a dose-related antinociception against acetic acid-induced writhing in mice and in the formalin test. In contrast, treatment with 7-HC did not prevent thermal nociception in the tail flick test. A single treatment with 7-HC, 60 mg/kg, produced a long-lasting antinociceptive effect against CFA-induced hypernociception, a chronic inflammatory pain stimulus. Notably, at 60 mg/kg per day over 4 days the administration of 7-HC produced a continuous antinociceptive effect against CFA-induced hypernociception. 7-HC (30-120 mg/kg) produced anti-inflammatory and antipyretic effects against carrageenan-induced inflammation and lipopolysaccharide-induced fever, respectively. Moreover, 7-HC was found to be safe with respect to ulcer induction. In the rota rod test, 7-HC-treated mice did not show any motor performance alterations. Conclusions The prolonged antinociceptive and anti-inflammatory effects of 7-HC, in association with its low ulcerogenic activity, indicate that this molecule might be a good candidate for development of new drugs for the control of chronic inflammatory pain and fever.

Endogenous cannabinoids induce fever through the activation of CB(1) receptors

Background and purpose: The effects of centrally administered cannabinoids on body core temperature (Tc) and the contribution of endogenous cannabinoids to thermoregulation and fever induced by lipopolysaccharide (LPS) (Sigma Chem. Co., St. Louis, MO, USA) were investigated. Experimental approach: Drug-induced changes in Tc of male Wistar rats were recorded over 6 h using a thermistor probe (Yellow Springs Instruments 402, Dayton, OH, USA) inserted into the rectum. Key results: Injection of anandamide [(arachidonoylethanolamide (AEA); Tocris, Ellisville, MO, USA], 0.01-1 mu g i.c.v. or 0.1-100 ng intra-hypothalamic (i.h.), induced graded increases in Tc (peaks 1.5 and 1.6 degrees C at 4 h after 1 mu g i.c.v. or 10 ng i.h.). The effect of AEA (1 mu g, i.c.v.) was preceded by decreases in tail skin temperature and heat loss index (values at 1.5 h: vehicle 0.62, AEA 0.48). Bell-shaped curves were obtained for the increase in Tc induced by the fatty acid amide hydrolase inhibitor [3-(3-carbamoylphenyl)phenyl] N-cyclohexylcarbamate (Cayman Chemical Co., Ann Arbor, MI, USA) (0.001-1 ng i.c.v.; peak 1.9 degrees C at 5 h after 0.1 ng) and arachidonyl-2-chloroethylamide (ACEA; Tocris) (selective CB(1) agonist; 0.001-1 mu g i.c.v.; peak 1.4 degrees C 5 h after 0.01 mu g), but (R,S)-(+)-(2-Iodo-5-nitrobenzoyl)-[1-(1-methyl-piperidin-2-ylmethyl)-1H-indole-3-yl] methanone (Tocris) (selective CB(2) agonist) had no effect on Tc. AEA-induced fever was unaffected by i.c.v. pretreatment with 6-Iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indole-3-yl](4-methoxyphenyl) methanone (Tocris) (selective CB(2) antagonist), but reduced by i.c.v. pretreatment with N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251; Tocris) (selective CB(1) antagonist). AM251 also reduced the fever induced by ACEA or LPS. Conclusions and implications: The endogenous cannabinoid AEA induces an integrated febrile response through activation of CB(1) receptors. Endocannabinoids participate in the development of the febrile response to LPS constituting a target for antipyretic therapy.

Effects of methylmercury on male reproductive functions in Wistar rats

In this study we investigated the effects of subacute exposure to methylmercury (MeHg) on male reproductive functions in rats by means of determination of alterations in structural and functional parameters. Adult male Wistar rats received 0, 0.5, 1.0 or 3.0 mg/kg/body weight/day orally, daily MeHg for 14 days. Sperm motility, the relative sperm count and transit time in the caput/corpus epididymis, were all reduced at all doses. The lowest dose increased the number of sperm head abnormalities; daily sperm production was elevated at the intermediate dose; while at the highest dose there was a decrease in serum testosterone levels and a rise in mercury (Hg) content in reproductive organs, liver and kidneys. In conclusion, MeHg exposure produced damages on male reproductive functions which may be attributed, at least in part, to the reduction in serum testosterone levels. These consequences could potentially result in infertility in rats. (C) 2011 Elsevier Inc. All rights reserved.

Reduction of enantioselectivity in the kinetic disposition and metabolism of verapamil in rats exposed to toluene

Toluene and verapamil are subject to extensive oxidative metabolism mediated by CYP enzymes, and their interaction can be stereoselective. In the present study we investigated the influence of toluene inhalation on the enantioselective kinetic disposition of verapamil and its metabolite, norverapamil, in rats. Male Wistar rats (n = 6 per group) received a single dose of racemic verapamil (10 mg/kg) orally at the fifth day of nose-only toluene or air (control group) inhalation for 6 h/day (25, 50, and 100 ppm). Serial blood samples were collected from the tail up to 6 h after verapamil administration. The plasma concentrations of verapamil and norverapamil enantiomers were analyzed by LC-MS/MS by using a Chiralpak AD column. Toluene inhalation did not influence the kinetic disposition of verapamil or norverapamil enantiomers (p > 0.05, Kruskal-Wallis test) in rats. The pharmacokinetics of verapamil was enantioselective in the control group, with a higher plasma proportion of the S-verapamil (AUC 250.8 versus 120.4 ng.h.mL(-1); p <= 0.05, Wilcoxon test) and S-norverapamil (AUC 72.3 versus 52.3 ng.h.mL(-1); p <= 0.05, Wilcoxon test). Nose-only exposure to toluene at 25, 50, or 100 ppm resulted in a lack of enantioselectivity for both verapamil and norverapamil. The study demonstrates the importance of the application of enantioselective methods in studies on the interaction between solvents and chiral drugs.

Evaluation of curcumin and cisplatin-induced DNA damage in PC12 cells by the alkaline comet assay

A very appropriate method for antigenotoxicity evaluation of antioxidants is the comet assay, since this analytical method detects initial DNA lesions that are still subject to repair; in other words, lesions that are very associated to damages resulting from the generation and subsequent action of reactive species. However, a solid evaluation should be developed in order to avoid inexact interpretations. In our study, besides the association of curcumin with cisplatin, curcumin and cisplatin agents were also tested separately. Classical genotoxic compounds, when tested by the comet assay, present an increase in the nucleoid tail; however, the cisplatin treatment has resulted in a decrease of DNA migration. This was an expected effect, as the cross-links between cisplatin and DNA decrease the DNA electrophoretic mobility. A similar effect was observed with the curcumin treatment, which decreased the nucleoid tail. Such effect was not expected and reinforced the necessity of including in the study, separate treatment groups with potentially antigenotoxic substances. The comet assay results have been analyzed using specific software for image analysis, as well as the classical visual analysis, and we have observed that the effect of decrease in DNA electrophoretic mobility was more easily observed when the data were analyzed by the software.

Investigation of the antinociceptive efficacy and relative potency of extended duration injectable 3-acylmorphine-6-sulfate prodrugs in rats

This investigation was designed to examine the antinociceptive activity in rats of 3-O-acyl prodrugs of M6S relative to the parent drug, after intravenous and intramuscular injection, using the tail flick latency test of antinociception. M6S, 3-acetylmorphine-6-sulfate (3AcM6S), 3-propionylmorphine-6-sulfate (3PrM6S), 3-butanoylmorphine-6-sulfate (3BuM6S) and 3-heptanoylmorphine-6-sulfate (3HpM6S) were administered by the IV route in a dose of 4.10 mu mol/kg. Relatively high levels of antinociception (>40% Maximum Possible Effect) were achieved following administration of M6S, 3AcM6S and 3PrM6S, whereas insignificant antinociception (<20%MPE) was achieved following administration of 3BuM6S or 3HpM6S. Although the mean duration of action for 3AcM6S (6 h) was longer than for M6S or 3PrM6S (4 h), the mean area (+/- S.E.M.) under the degree of antinociception versus time curve (AUG) for 3AcM6S (151.6 +/- 6.9%MPE h) was not significantly different (p <0.05) from that for M6S (120.8 +/- 32.7%MPE h) or for 3PrM6S (106.0 +/- 21.3%MPE h). The mean ED50 (range) doses for M6S, 3AcM6S and 3PrM6S were calculated to be 4.16 (3.61-4.48), 4.32 (3.55-5.09) and 4.54 (4.21-4.79) mu mol/kg, respectively. Preliminary studies were conducted on potential long-acting formulations containing 8 x ED50 doses of M6S and the 3-acetyl and 3-propionyl esters suspended in soybean oil. These showed that 3PrM6S gave a greater AUC (mean + S.E.M.) (1087.4 +/- 97.4%MPE h) and longer duration of action (20 h) than did M6S (613.1 +/- 155.9%MPE h; 10 h duration) or 3AcM6S (379.3 + 114.2%MPE h: 8 h duration). Further studies are needed to more fully investigate these findings. (C) 1998 Elsevier Science B.V. All rights reserved.

Apparent insensitivity of the hotplate latency test for detection of antinociception following intraperitoneal, intravenous or intracerebroventricular M6G administration to rats

Although morphine-6-glucuronide (M6G) has been shown to be analgesically active, the relative involvement of spinal and supraspinal structures in mediating M6G's pain-relieving effects following central and systemic administration to rats is unclear. As the tail flick and hotplate latency tests are reported to quantify antinociception mediated primarily by spinal and supraspinal mechanisms respectively, these methods were used to determine the comparative apparent levels of antinociception (expressed as percentage maximum possible effect, % MPE) achieved after M6G or morphine administration. Following i.v. or i.p. M6G (1.9-5.4 mu mol) dosing or i.p. morphine (10 mu mol) dosing, high levels of antinociception (>50% MPE) were achieved using the tail flick test whereas base-line levels of antinociception were observed 30 sec later in the same rats using the hotplate test. By contrast, antinociception evoked by i.v. morphine (10 mu mol) exceeded 50% MPE using both the hotplate and tail flick tests although the apparent potency was approximately 2.5 times greater using the tail flick test. After i.c.v. dosing, M6G (0.22-3.3 nmol) was significantly (P < .05) more potent when assessed using the tail flick compared with the hotplate test. Taken together, these data strongly indicate that following central and systemic administration, M6G's antinociceptive effects are mediated primarily by spinal structures whereas both spinal and supraspinal mechanisms contribute to systemic morphine's antinociceptive effects.

H-ras activation is an early event in the ptaquiloside-induced carcinogenesis: Comparison of acute and chronic toxicity in rats

Bracken fern (Pteridium spp.) produces cancer of the urinary bladder and oesophagus in grazing animals and is a suspected human carcinogen, The carcinogenic principle ptaquiloside (PT), when activated to a dienone (APT), forms DNA adducts which eventually leads to tumor. Two groups of female Sprague-Dawley rats were given a chronic dose of 3 mg APT weekly for 10 weeks either by intravenous (iv) tail vein or by intragastric (ig) route, A third group was given a weekly dose of 6 mg of APT for 3 weeks by the ig route corresponding to acute dosing. Both chronic iv and ig dosed animals showed ischemic tubular necrosis in the kidney but only iv dosed animals developed adenocarcinomas of the mammary glands. Acutely dosed ig animals produced apoptotic bodies in the liver, necrosis of blood cell precursors in the bone marrow and ischemic tubular necrosis in the kidney but they did not develop tumors, No mutations were found in the H-ras and p53 genes in the mammary glands of either the ig rats or the tumor-bearing iv rats. However, the mammary glands of a fourth group of rats, which received APT by iv and killed before tumor development, carried Pu to Pu and Pu to Py double mutations in codons 58 and 59 of H-ras. This study indicates that the route of administration plays a role in the nature of the disease expression from ptaquiloside exposure. In addition to confirming the role of APT in the PT-induced carcinogenesis our finding suggests that activation of H-ras is an early event in the PT-carcinogenesis model. (C) 1998 Academic Press.

NMR structure of C-terminally tagged gramicidin channels

A biotin group was covalently attached to the C terminus of gramicidin A (gA) through a linker arm comprising a glycine residue with either one (gAXB) or two caproyl groups (gAXXB). High-resolution two-dimensional NMR spectroscopy was used to determine the structure of these modified gA analogues and [Lys(16)]gramicidin A (gA-Lys) in sodium dodecyl-d(25) sulphate micelles. Gated gA ion channels based on linking a receptor group to these gA analogues have been used recently as a component in a sensing device. The conformations of the gA backbones and amino acid side chains of lysinated gA and biotinylated gA in detergent micelles were found to be almost identical to that of native gA, i.e. that of an N-terminal to N-terminal (head to head) dimer formed by two right-handed, single-stranded beta(6.3) helices. The biotin tail of the gAXB and gAXXB and the lysine extremity of gA-Lys appeared to lie outside the micelle. Thus it appears that the covalent attachment of functional groups to the C terminus of gA does not disrupt the peptide's helical configuration. Further, single channel measurements of all three gA analogues showed that functioning ion channels were preserved within a membrane environment. (C) 1999 Elsevier Science B.V. All rights reserved.

Women drivers' behaviour, socio-demographic characteristics and accidents

The purpose of this study was to examine factors which affect driving behaviour and accident rates in women in Australia. Two groups of women (aged 18-23 and 45-50 years) participating in the Australian Longitudinal Study on Women's Health, completed a mailed questionnaire on driver behaviour and road accidents. Self reported accident rates in the last 3 years were 1.87 per 100 000 km for the young drivers (n = 1199) and 0.59 per 100 000 km for the mid-age drivers (n = 1564); most accidents involved damage only, not injury. Mean scores for lapses obtained using the Driver Behaviour Questionnaire, were similar in the two age groups and similar to those found in other studies. In contrast, scores for errors and violations for the young women were higher than for the mid-age group and previous reports using the same instruments. Riskier driving behaviour among young women was associated with stress and habitual alcohol consumption. In the mid-age group, poorer driver behaviour scores were related to higher levels of education, feeling rushed, higher habitual alcohol consumption and lower life satisfaction scores. Accident rates in both groups were significantly related to lapses. Women born in non-English speaking countries had significantly higher risk of accidents compared to Australian-born women: relative risk = 3.40, 95% confidence interval (1.93, 5.98) for the young drivers; relative risk = 1.77, 95% confidence interval (1.11, 2.83) for mid-age drivers. These findings support the need for road safety campaigns targeted at young women to reduce dangerous driving practices, such as speeding,'tail gating' and overtaking on the inside. There is also a need for further research to understand how lifestyle characteristics are associated with higher risk of accidents and to explore factors which might account for the higher risk for women drivers who were born overseas. (C) 1999 Elsevier Science Ltd. All rights reserved.

Inhibition of settlement and metamorphosis of the ascidian Herdmania curvata by non-geniculate coralline algae

The surfaces of non-geniculate coralline algae (NCA) are known to induce the settlement and metamorphosis of disparate marine taxa. In this study we investigate the responsiveness of larvae of Herdmania curvata (Ascidiacea: Stolidobranchia) to three species of NCA (Neo-goniolithon brassica-florida, Hydrolithon onkodes, and Lithothamnium prolifer) that cohabit the slope and crest of Heron Reef, Great Barrier Reef. H. curvata larvae were first exposed to these NCA at or within 2 h of hatching, which is 1 to 2 h prior to attaining competence, and then cultured continuously with the NCA for 12 to 14 h. Rates of settlement and metamorphosis of H, curvata cultured in laboratory chambers in the presence of the different NCA were significantly lower than spontaneous rates in seawater. The limited settlement in treatments containing NCA were confined entirely to the chamber periphery, and settlement never occurred on the surface of the NCA. The inhibitory effect was dose-dependent and was stronger in H. brassica-florida and H. onkodes than in L. prolifer. Larvae that did not settle in treatments with NCA had rounded anterior trunks and, in extreme cases, kinked tails with rounded and dissociated tail muscle cells. In some individuals, we observed the anterior chemosensory papillae being sloughed off the larval body. Morphological analysis of trunk ectodermal and mesenchymal nuclei of larvae cultured in the presence of the NCA revealed that general necrotic cell death was occurring. Importantly, H. curvata larvae that were exposed to NCA could not subsequently be induced to metamorphose in KCl-elevated seawater, whereas larvae not exposed to NCA metamorphosed at high rates in KCl-elevated seawater.

Gender and age-at-first-admission for schizophrenia: Data from Australia and Brazil

In order to examine whether different populations show the same pattern of onset in the Southern Hemisphere, we examined the age-at-first-admission distribution for schizophrenia based on mental health registers from Australia and Brazil. Data on age-at-first-admission for individuals with schizophrenia were extracted from two names-linked registers, (1) the Queensland Mental Health Statistics System, Australia (N=7651, F= 3293, M=4358), and (2) a psychiatric hospital register in Pelotas, Brazil (N=4428, F=2220, M=2208). Age distributions were derived for males and females for both datasets. The general population structure tbr both countries was also obtained. There were significantly more males in the Queensland dataset (gz = 56.9, df3, p < 0.0001 ). Both dataset distributions were skewed to the right. Onset rose steeply after puberty to reach a modal age group of 20-29 for men and women, with a more gradual tail toward the older age groups. In Queensland 68% of women with schizophrenia had their first admissions after age 30, while the proportion from Brazil was 58%. Compared to the Australian dataset, the Brazilian dataset had a slightly greater proportion of first admissions under the age 30 and a slightly smaller proportion over the age of 60 years. This reflects the underlying age distributions of the two populations. This study confirms the wide age range and gender differences in age-at-first-admission distributions for schizophrenia and identified a significant difference in the gender ratio between the two datasets. Given widely differing health services, cultural practices, ethic variability, and the different underlying population distributions, the age-at-first-admission in Queensland and Brazil showed more similarities than differences. Acknowledgments: The Stanley Foundation supported this project.

The Fornax spectroscopic survey I. Survey strategy and preliminary results on the redshift distribution of a complete sample of stars and galaxies

The Fornax Spectroscopic Survey will use the Two degree Field spectrograph (2dF) of the Angle-Australian Telescope to obtain spectra for a complete sample of all 14000 objects with 16.5 less than or equal to b(j) less than or equal to 19.7 in a 12 square degree area centred on the Fornax Cluster. The aims of this project include the study of dwarf galaxies in the cluster (both known low surface brightness objects and putative normal surface brightness dwarfs) and a comparison sample of background field galaxies. We will also measure quasars and other active galaxies, any previously unrecognised compact galaxies and a large sample of Galactic stars. By selecting all objects-both stars and galaxies-independent of morphology, we cover a much larger range of surface brightness and scale size than previous surveys. In this paper we first describe the design of the survey. Our targets are selected from UK Schmidt Telescope sky survey plates digitised by the Automated Plate Measuring (APM) facility. We then describe the photometric and astrometric calibration of these data and show that the APM astrometry is accurate enough for use with the 2dF. We also describe a general approach to object identification using cross-correlations which allows us to identify and classify both stellar and galaxy spectra. We present results from the first 2dF field. Redshift distributions and velocity structures are shown for all observed objects in the direction of Fornax, including Galactic stars? galaxies in and around the Fornax Cluster, and for the background galaxy population. The velocity data for the stars show the contributions from the different Galactic components, plus a small tail to high velocities. We find no galaxies in the foreground to the cluster in our 2dF field. The Fornax Cluster is clearly defined kinematically. The mean velocity from the 26 cluster members having reliable redshifts is 1560 +/- 80 km s(-1). They show a velocity dispersion of 380 +/- 50 km s(-1). Large-scale structure can be traced behind the cluster to a redshift beyond z = 0.3. Background compact galaxies and low surface brightness galaxies are found to follow the general galaxy distribution.