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Biomedical subjects

J Boyles

Publications and source records attributed to J Boyles.

At least 19 recordsLinked to original sources
PubMed2006

The dental caries experience of 11-year-old children in Great Britain. Surveys coordinated by the British Association for the Study of Community Dentistry in 2004 / 2005.

OBJECTIVE: This paper reports the results of standardized clinical caries examinations of 11-year-old children from across England and Wales, Scotland, Isle of Man, and Jersey in 2004/5. These co-ordinated surveys are the latest in a series which seek to monitor the dental health of children and to assess the delivery of dental services. METHOD: The criteria and conventions of the British Association for the Study of Community Dentistry were used. Representative samples were drawn from participating strategic health authorities (SHAs), primary care trusts (PCTs), health boards (HBs), and local health boards (LHBs). Caries was diagnosed at the caries into dentine threshold using a visual method without radiography or fibre-optic transillumination. RESULTS: The results again demonstrated a wide variation in disease prevalence and care strategies across Great Britain. Mean values for D3MFT within the current English strategic health authorities ranged from 0.19 in Harlow to 1.32 in North Manchester and in Salford; in Wales mean values ranged from 0.69 in Vale of Glamorgan to 2.09 in Blaenau Gwent; while in Scotland they ranged from 0.59 in Orkney to 1.77 in Western Isles. Mean D3MFT across England was 0.64 (D3T = 0.32, MT = 0.06, FT = 0.25), across Wales it was 1.09 (D3T = 0.48, MT 0.11, FT = 0.50), and across Scotland values were 1.29 (D3T = 0.52, MT = 0.17, FT = 0.60). Overall, 31.3% of children in England & Wales and 47.1% of children inspected in Scotland had evidence of caries experience in dentine (D3MFT > 0, including visual dentine caries). As in previous surveys, the distribution of caries was highly skewed. Thus the mean caries experience for those with dentinal decay in England and Wales was 2.12, as opposed to the overall mean of 0.66; in Scotland the corresponding values were 2.74 and 1.29. Trends over time demonstrate an improvement in overall mean D3MFT for England and Wales since the 2000/2001 of 12-year-olds, although part of this difference is accountable to the younger age, at examination, in this survey. The mean value for those with dentine decay experience was also marginally less at 2.12 compared with 2.35 in the previous survey. (Figures for Scotland were not included in the 2000/2001 survey.) The care index was also found to be marginally lower than previously at 41% compared with 48% but again the younger age of the children would influence this value. CONCLUSION: Dental health of 11-year-old children has been surveyed in Great Britain, Jersey, and the Isle of Man: being a slightly younger mean age than in previous BASCD surveys. Geographic variation in oral health is marked at both the local and national levels. Overall, the provision of operative care for those with dentinal decay is around 42%. While many children enjoy good oral health, sizable groups remain within the population of 11-year-old children who have a clinically significant burden of preventable dental disease.

Age Factors↗
PubMed2005

The dental caries experience of 5-year-old children in England and Wales (2003/4) and in Scotland (2002/3). Surveys co-ordinated by the British Association for the Study of Community Dentistry.

OBJECTIVE: This paper reports the results of standardized clinical caries examinations of 5 year old children from across England and Wales in 2003/4 and Scotland in 2002/3. These co-ordinated surveys are the latest in a series which seek to monitor the dental health of children and to assess the delivery of dental services. METHOD: The criteria and conventions of the British Association for the Study of Community Dentistry were used. Representative samples were drawn from participating strategic health authorities (SHAs), primary care trusts (PCTs) and health boards (HBs). Caries was diagnosed at the caries into dentine threshold using a visual method without radiography or fibre-optic transillumination. Data for Jersey and the Isle of Man are also included. RESULTS: The results again demonstrated a wide variation in disease prevalence and care strategies across Great Britain. Mean values for d3mft within the current English Strategic Health Authorities ranged from 0.47 in Maidstone Weald (South) to 3.69 in North Kirklees (North); in Wales mean values ranged from 1.48 in Flintshire (NW) to 3.73 in Merthyr (SE); while in Scotland they ranged from 1.29 in Borders to 3.67 in Argyll & Clyde. Mean d3mft across England was 1.49 (d3t = 1.12, mt = 0.19, ft = 0.18), across Wales it was 2.42 (d3t = 1.70, mt = 0.43, ft = 0.29) and across Scotland values were 2.76 (d3t = 1.87, mt = 0.65, ft = 0.24). Overall, 39.6% of children in England & Wales and 55.4% of children inspected in Scotland had evidence of caries experience in dentine (d3mft > 0, including visual dentine caries). The distribution of caries was highly skewed. Thus the mean caries experience for those with dentinal decay in England and Wales was 3.90, as opposed to the overall mean of 1.55; in Scotland the corresponding values were 4.98 and 2.76. Trends over time demonstrate virtually no change in the overall mean d3mft for England and Wales since 2001/2, although the mean value for those with dentine decay experience increased marginally from 3.83 to 3.90. In Scotland there had been deterioration in the overall mean (2.76 as compared to the 2.55 reported in 1999). The care index has also fallen (for example in England & Wales to 12% from 13.2% in 2001/2002 and 14.3% in 1999/2000). CONCLUSION: There has been no overall improvement in the dental health of 5 year old children over the last 2 years. Geographic variation in oral health is marked at both the local and national levels. Overall, the provision of operative care for those with dentinal decay has again decreased slightly. While many children enjoy good oral health, sizable groups remain within the population of 5 year old children who have a clinically significant burden of preventable dental disease.

Child, Preschool↗
PubMed2004

Development of a method for the detection and confirmation of the alpha-2 agonist amitraz and its major metabolite in horse urine.

Amitraz (N'-(2,4-dimethylphenyl)-N-[[(2,4-dimethylphenyl)imino]methyl]-N-methyl-methanimidamide) is an alpha-2 adrenergic agonist used in veterinary medicine primarily as a scabicide- or acaricide-type insecticide. As an alpha-2 adrenergic agonist, it also has sedative/tranquilizing properties and is, therefore, listed as an Association of Racing Commissioners International Class 3 Foreign Substance, indicating its potential to influence the outcome of horse races. We identified the principal equine metabolite of amitraz as N-2,4-dimethylphenyl-N'-methylformamidine by electrospray ionization(+)-mass spectrometry and developed a gas chromatographic-mass spectrometric (GC-MS) method for its detection, quantitation, and confirmation in performance horse regulation. The GC-MS method involves derivatization with t-butyldimethylsilyl groups; selected ion monitoring (SIM) of m/z 205 (quantifier ion), 278, 261, and 219 (qualifier ions); and elaboration of a calibration curve based on ion area ratios involving simultaneous SIM acquisition of an internal standard m/z 208 quantifier ion based on an in-house synthesized d(6) deuterated metabolite. The limit of detection of the method is approximately 5 ng/mL in urine and is sufficiently sensitive to detect the peak urinary metabolite at 1 h post dose, following administration of amitraz at a 75-mg/horse intravenous dose.

Adrenergic alpha-Agonists↗
PubMed2004

The dental caries experience of 14-year-old children in England and Wales. Surveys co-ordinated by the British Association for the Study of Community Dentistry in 2002/2003.

OBJECTIVE: This paper reports the results of standardised clinical caries examinations of 77,693 14-year-old children from across England, Wales, Jersey and the Isle of Man. These 2002/3 coordinated surveys are the latest in a series which seeks to monitor the dental health of children and to assess the delivery of dental services. METHOD: The criteria and conventions of the British Association for the Study of Community Dentistry were used. Representative samples were drawn from participating health authorities and boards and caries was diagnosed at the caries into dentine (D3) threshold using a visual method without radiography or fibre-optic transillumination. RESULTS: These demonstrated, once again, a wide variation in prevalence across the area surveyed, with mean values for D3MFT for the current English government offices (of the National Health Service) and the local Health Boards in Wales ranging from 0.99 in the South East to 2.10 in Wales (2.41 in the Isle of Man). The mean value for across England and Wales was 1.48 (D3T=0.56, MT=0.10, FT=0.82). Overall 49 per cent of 14-year-old children in England and Wales had evidence of dentinal caries experience (D3MFT>0), the regional/country means ranged between 37 per cent (South-East) and) and 60 percent in Wales (65 per cent, Isle of Man). The mean D3MFT for those with disease at this threshold was 3.03. Trends over time demonstrate an improvement of 4% in overall D3MFT for England and Wales, there has been only small improvement in mean MT since 1994/95, while FT and care index have fallen. The number of fillings provided in 2002/3 and thus the care index, remains low, on average across England and Wales, only 55% of the dentinal caries experience identified by survey examinations of permanent teeth was seen as fillings (range in individual areas: 28% to 83%). CONCLUSION: These findings demonstrate a modest overall improvement in oral health, but a continuing need for more effective preventive strategies and treatment services for permanent teeth in this important age group. An average of half of the 14 year old children examined being affected by dentinal decay and a mean of three permanent teeth decayed into dentine for those children affected at this level of diagnosis is a poor start to charting oral health in the 21st Century in England and Wales.

Adolescent↗
PubMed2003

The workforce of professionals complementary to dentistry in the general dental services: a survey of general dental practices in the South West.

OBJECTIVE: To describe the working patterns, training experiences, estimated size, and future training needs of the workforce of professionals complementary to dentistry in the general dental service in an English region. METHODS: Postal questionnaire of NHS dental practices in the South West of England. RESULTS: The response rate was 65%. There was an average of two whole time equivalent (wte) dentists working per practice. Dentists work a mean 0.8 wte per practice. Sixty per cent of practice time is NHS. Vacancies existed for 120 dentists (98 wte) with reported difficulties in recruitment. There was an average of 1.25 wte dental nurses per dentist with 44% of nurses working part-time. A quarter of nurses' time is on non-clinical duties. The turnover rate for nurses was between 13% and 26%, with recruitment difficulties. Approximately 50% of nurses do not have a professional qualification. There is variation between health authorities in proportions of qualified nurses. Hygienists are employed in 72% of practices, but only 20% of their work is NHS. Dentists have favourable attitudes to an expansion in the employment and training of professionals complementary to dentistry. CONCLUSIONS: There are problems with recruitment and retention of all categories of the dental workforce in the GDS, particularly in rural areas. There is a large unmet need for pre- and post-qualification training for professionals complementary to dentistry compounded by marked inequalities in access to training.

Administrative Personnel↗
PubMed2003

The dental caries experience of 5-year-old children in England and Wales. Surveys co-ordinated by the British Association for the Study of Community Dentistry in 2001/2002.

OBJECTIVE: This paper reports the results of standardised clinical caries examinations of 170,731 5-year-old children from across England and Wales. These 2001/2002 co-ordinated surveys are the latest in a series which seek to monitor the dental health of children and to assess the delivery of dental services. METHOD: The criteria and conventions of the British Association for the Study of Community Dentistry were used. Representative samples were drawn from participating health authorities and boards and caries was diagnosed at the caries into dentine threshold using a visual method without radiography or fibre-optic transillumination. RESULTS: The results again demonstrated a wide variation in prevalence across Britain, with mean values for d3mft for the current English Strategic Health Authorities (SHA) (of the National Health Service), Wales and British 'territories' ranging from 0.75 in Jersey and 0.84 in Kent & Medway to 2.73 in Gwent and 2.47 in Greater Manchester. Mean d3mft across England and Wales was 1.52 (d.t = 1.11, mt = 0.20, ft = 0.20). Overall, 40% of children had evidence of caries experience (d3mft > 0); the percentages ranged between 23% (Jersey) or 29% (Essex) and 61% (Gwent) or 54% (Greater Manchester). The distribution of caries was highly skewed. Thus the mean caries experience for those with disease in England and Wales was 3.83, as opposed to the overall mean of 1.52. Trends over time demonstrate slight increase of 3% in overall d3mft for England and Wales since 1999/2000, compared to the 4% improvement seen for the two previous years. Of the three components of dmft, d3t and mt have increased while ft has fallen. The care index has also fallen (13.2% in 2001/2002, compared to 14.3% in 1999/2000); SHA/country percentages for 2001/2002 ranged from 8-29%. This indicator has not, however, regained the levels seen in the past. CONCLUSION: There has been no improvement in the dental health of 5-year-old children. Overall, the provision of operative care for those with dentinal decay has decreased slightly; significant groups remain within the population of 5-year-old children who have dental disease and who are in need of dental care.

Catchment Area, Health↗
PubMed2001

Ropivacaine in the horse: its pharmacological responses, urinary detection and mass spectral confirmation.

This report evaluates the pharmacological responses, urinary detection and mass spectral confirmation of ropivacaine in horses. Ropivacaine, a potent local anesthetic (LA) recently introduced in human medicine, has an estimated highest no-effect dose (HNED) of about 0.4 mg/site as determined in our abaxial sesamoid block model. Apparent ropivacaine equivalents were detectable by ELISA screening using a mepivacaine ELISA test after administration of clinically effective doses. Mass spectral examination of postadministration urine samples showed no detectable parent ropivacaine, but a compound indistinguishable from authentic 3-hydroxyropivacaine was recovered from these samples. The study shows that ropivacaine is a potent LA in the horse, that clinically effective doses can be detected in postadministration samples by ELISA-based screening, and that its major post administration urinary metabolite is 3-hydroxyropivacaine.

Amides↗
PubMed2000

Direct MS-MS identification of isoxsuprine-glucuronide in post-administration equine urine.

Isoxsuprine is routinely recovered from enzymatically-hydrolyzed, post-administration urine samples as parent isoxsuprine in equine forensic science. However, the specific identity of the material in horse urine from which isoxsuprine is recovered has never been established, although it has long been assumed to be a glucuronide conjugate (or conjugates) of isoxsuprine. Using ESI/MS/MS positive mode as an analytical tool, urine samples collected 4-8 h after isoxsuprine administration yielded a major peak at m/z 554 that was absent from control samples and resisted fragmentation to daughter ions. Titration of this material with increasing concentrations of sodium acetate yielded m/z peaks consistent with the presence of monosodium and disodium isoxsuprine-glucuronide complexes, suggesting that the starting material was a dipotassium-isoxsuprine-glucuronide complex. Electrospray ionization mass spectrometry negative mode disclosed the presence of a m/z 476 peak that declined following enzymatic hydrolysis and resulted in the concomitant appearance of peaks at m/z 300 and 175. The resulting peaks were consistent with the presence of isoxsuprine (m/z 300) and a glucuronic acid residue (m/z 175). Examination of the daughter ion spectrum of this putative isoxsuprine-glucuronide m/z 476 peak showed overlap of many peaks with those of similar spectra of authentic morphine-3- and morphine-6-glucuronides, suggesting they were derived from glucuronic acid conjugation. These data suggest that isoxsuprine occurs in post-administration urine samples as an isoxsuprine-glucuronide conjugate and also, under some circumstances, as an isoxsuprine-glucuronide-dipotassium complex.

Animals↗
PubMed2000

Identification of lidocaine and its metabolites in post-administration equine urine by ELISA and MS/MS.

Lidocaine is a local anesthetic drug that is widely used in equine medicine. It has the advantage of giving good local anesthesia and a longer duration of action than procaine. Although approved for use in horses in training by the American Association of Equine Practitioners (AAEP), lidocaine is also an Association of Racing Commissioners International (ARCI) Class 2 drug and its detection in forensic samples can result in significant penalties. Lidocaine was observed as a monoprotonated ion at m/z 235 by ESI+ MS/MS (electrospray ionization-positive ion mode) analysis. The base peak ion at m/z 86, representing the postulated methylenediethylamino fragment [CH2N(CH2CH3)2]+, was characteristic of lidocaine and 3-hydroxylidocaine in both ESI+ and EI (electron impact-positive ion mode) mass spectrometry. In addition, we identified an ion at m/z 427 as the principal parent ion of the ion at m/z 86, consistent with the presence of a protonated analog of 3-hydroxylidocaine-glucuronide. We also sought to establish post-administration ELISA-based 'detection times' for lidocaine and lidocaine-related compounds in urine following single subcutaneous injections of various doses (10, 40, 400 mg). Our findings suggest relatively long ELISA based 'detection times' for lidocaine following higher doses of this drug.

Anesthetics, Local↗
PubMed1999

Mepivacaine: its pharmacological effects and their relationship to analytical findings in the horse.

Mepivacaine is a local anaesthetic drug that is widely used in equine medicine and is classified by the Association of Racing Commissioners International (ARCI) as a Class 2 foreign substance that may cause regulators to impose significant penalties if residues are identified in post-race urine samples. Therefore, an analytical/pharmacological database was developed for this agent and its metabolites. Using an abaxial sesamoid local anaesthetic model, it was determined that the highest no-effect dose (HNED) for its local anaesthetic effect was 2 mg. Using enzyme-linked immunosorbent assay (ELISA) screening, it was determined that subcutaneous (s.c.) administration of the HNED of mepivacaine to eight horses yielded a peak urinary concentration of apparent mepivacaine of 63 ng/mL 2 h after injection. The major identified metabolite recovered from equine urine after dosing with mepivacaine is 3-hydroxymepivacaine. Therefore, 3-hydroxymepivacaine was synthesized, purified and characterized, and a quantitative mass spectrometric method was developed for this metabolite as isolated from horse urine. Following subcutaneous injection of the HNED of mepivacaine, the concentration of 3-hydroxymepivacaine recovered from horse urine reached a peak of about 64.6 ng/mL at 4 h after administration as measured by GC/MS. The concentration of mepivacaine or its metabolites after administration of a HNED dose are detectable by mass spectral techniques. Within the limits of this research, the study suggests that recovery of concentrations less than about 65 ng/mL of 3-hydroxymepivacaine from post-race urine samples may not be associated with a recent LA effect of mepivacaine.

Anesthetics, Local↗
PubMed1999

Bupivacaine in the horse: relationship of local anaesthetic responses and urinary concentrations of 3-hydroxybupivacaine.

Bupivacaine is a potent local anaesthetic used in equine medicine. It is also classified as a Class 2 foreign substance by the Association of Racing Commissioners International (ARCI). The identification of residues in postrace urine samples may cause regulators to impose significant penalties. Therefore, an analytical/pharmacological database was developed for this medication. The highest no-effect dose (HNED) for the local anaesthetic effect of bupivacaine was determined to be 0.25 mg by using an abaxial sesamoid local anaesthetic model. Administration of the HNED of bupivacaine to eight horses yielded a peak urine concentration of apparent bupivacaine of 23.3 ng/mL 2 h after injection as determined with enzyme-linked immunosorbent assay (ELISA) screening. The major metabolite recovered from beta-glucuronidase-treated equine urine after dosing with bupivacaine is a hydroxybupivacaine, either 3-hydroxybupivacaine, 4-hydroxybupivacaine, or a mixture of the two. To determine which positional isomer occurs in the horse, 4-hydroxybupivacaine was obtained from Maxxam Analytics, Inc., and 3-hydroxybupivacaine was synthesized, purified, and characterized. Furthermore, a quantitative mass spectrometric method was developed for the metabolite as recovered from horse urine. Following subcutaneous injection of the HNED of bupivacaine, the concentration of the hydroxybupivacaine recovered from horse urine reached a peak of 27.4 ng/mL at 4 h after administration as measured by gas chromatography/mass spectrometry (GC/MS). It was also unequivocally demonstrated with ion chromatography that the hydroxybupivacaine metabolite found in horse urine is exclusively 3-hydroxybupivacaine and not 4-hydroxybupivacaine. The mean pH of the 4-h urine samples was 7.21; the mean urine creatinine was 209.5 mg/dL; and the mean urine specific gravity was 1.028. There was no apparent effect of pH, urine creatinine concentration, or specific gravity on the concentration of 3-hydroxybupivacaine recovered. The concentration of bupivacaine or its metabolites after administration of a HNED dose are detectable by mass spectrometric techniques. This study also suggests that recovery of concentrations less than approximately 30 ng/mL of 3-hydroxybupivacaine from postrace urine samples is unlikely to be associated with a recent local anaesthetic effect of bupivacaine.

Anesthetics, Local↗
PubMed1999

Diclazuril in the horse: its identification and detection and preliminary pharmacokinetics.

Diclazuril (4-chlorophenyl [2,6-dichloro-4-(4,5-dihydro-3H-3,5-dioxo-1,2,4-triazin-2-yl)pheny l] acetonitrile), is a benzeneacetonitrile antiprotozoal agent (Janssen Research Compound R 64433) marketed as Clinacox . Diclazuril may have clinical application in the treatment of Equine Protozoal Myeloencephalitis (EPM). To evaluate its bioavailability and preliminary pharmacokinetics in the horse we developed a sensitive quantitative high-pressure liquid chromatography (HPLC) method for diclazuril in equine biological fluids. MS/MS analysis of diclazuril in our HPLC solvent yielded mass spectral data consistent with the presence of diclazuril. After a single oral dose of diclazuril at 2.5 g/450 kg (as 500 g Clinacox), plasma samples from four horses showed good plasma concentrations of diclazuril which peaked at 1.077 +/- 0.174 microg/mL (mean +/- SEM) with an apparent plasma half-life of about 43 h. When this dose of Clinacox was administered daily for 21 days to two horses, mean steady state plasma concentrations of 7-9 microg/mL were attained. Steady-state levels in the CSF ranged between 100 and 250 ng/mL. There was no detectable parent diclazuril in the urine samples of dosed horses by HPLC or by routine postrace thin layer chromatography (TLC). These results show that diclazuril is absorbed after oral administration and attains steady-state concentrations in plasma and CSF. The steady state concentrations attained in CSF are more than sufficient to interfere with Sarcocystis neurona, whose proliferation is reportedly 95% inhibited by concentrations of diclazuril as low as 1 ng/mL. These results are therefore entirely consistent with and support the reported clinical efficacy of diclazuril in the treatment of clinical cases of EPM.

Administration, Oral↗
PubMed1998

Lidocaine in the horse: its pharmacological effects and their relationship to analytical findings.

Lidocaine is a local anaesthetic agent that is widely used in equine medicine. It is also an Association of Racing Commissioners International (ARCI) Class 2 foreign substance that may cause regulators to impose substantial penalties if residues are identified in post race urine samples. Therefore, an analytical/pharmacological database was developed for this drug. Using our abaxial sesamoid local anaesthetic model, the highest no-effect dose (HNED) for the local anaesthetic effect of lidocaine was determined to be 4 mg. Using enzyme-linked immunosorbent assay (ELISA) screening, administration of the HNED of lidocaine to eight horses yielded peak serum and urine concentrations of apparent lidocaine of 0.84 ng/mL at 30 min and 72.8 ng/mL at 60 min after injection, respectively. These concentrations of apparent lidocaine are readily detectable by routine ELISA screening tests (LIDOCAINE ELISA, Neogen, Lexington, KY). ELISA screening does not specifically identify lidocaine or its metabolites, which include 3-hydroxylidocaine, dimethylaniline, 4-hydroxydimethylaniline, monoethylglycinexylidine, 3-hydroxymonoethylglycinexylidine, and glycinexylidine. As 3-hydroxylidocaine is the major metabolite recovered from equine urine, it was synthesized, purified and characterized, and a quantitative mass spectrometric method was developed for 3-hydroxylidocaine as recovered from horse urine. Following subcutaneous (s.c.) injection of the HNED of lidocaine, the concentration of 3-hydroxylidocaine recovered from urine reached a peak of about 315 ng/mL at 1 h after administration. The mean pH of the 1 h post dosing urine samples was 7. 7, and there was no apparent effect of pH on the amount of 3-hydroxylidocaine recovered. Within the context of these experiments, the data suggests that recovery of less than 315 ng/mL of 3-hydroxylidocaine from a post race urine sample is unlikely to be associated with a recent local anaesthetic effect of lidocaine. Therefore these data may be of assistance to industry professionals in evaluating the significance of small concentrations of lidocaine or its metabolites in postrace urine samples. It should be noted that the quantitative data are based on analytical methods developed specifically for this study, and that methods used by other laboratories may yield different recoveries of urine 3-hydroxylidocaine.

Anesthetics, Local↗
PubMed1996

Regulatory significance of procaine residues in plasma and urine samples: preliminary communication.

Plasma and urinary concentrations of procaine and the duration of response to procaine after its administration as a local anaesthetic to horses were studied. Following injection of a clinical dose of procaine HCl (80 mg), the concentration of procaine in plasma was less than the lower limit of quantitation and unsuitable for threshold determination. Therefore, the urinary concentration of procaine was determined after injection of a dose of 5 mg procaine HCl, the highest no-effect dose (HNED) of this agent. Free unconjugated procaine in equine urine reached a peak concentration of 23.7 ng/mL, while total (unconjugated plus conjugated) procaine peaked at 37.9 ng/mL (mean urine pH of 8.5). Because a basic drug may concentrate substantially in acidic urine, a threshold concentration of 25 ng/mL of unconjugated procaine is a reasonable and conservative threshold for procaine at this time. Horses were administered abaxial sesamoid blocks containing 2% procaine HCl (40, 80, 160 and 320 mg) and 2% procaine HCl (40 and 320 mg) with epinephrine (1:100,000) in local anaesthetic experiments. There was a significant local anaesthetic (LA) effect for all doses of procaine HCl with the duration of effect ranging from 30 min (40 mg) to 60 min (320 mg). The addition of epinephrine significantly increased the duration of local anaesthesia to 180 min for a 40 mg dose and 420 min for a 320 mg dose. Because epinephrine may extend the duration of local anaesthesia beyond a reasonable period of confinement for horses before the starting time of a race, the increased LA effect following the addition of epinephrine to procaine has regulatory significance.

Anesthetics, Local↗
PubMed1992

Role of extracellular matrix in regulating fenestrations of sinusoidal endothelial cells isolated from normal rat liver.

Open fenestrations are a conspicuous feature of sinusoidal endothelial cells and allow free movement of plasma into the space of Disse. In hepatic fibrosis, the number of fenestrations decreases as interstitial collagen increases in the liver, a change that correlates with deposition of extracellular matrix in the space of Disse. In this study, the possibility of a causal relationship between altered fenestral morphology and perisinusoidal matrix has been examined by culturing rat sinusoidal endothelial cells on individual matrix proteins or on a native matrix consisting of human amniotic membrane with interstitial collagen (types I and III) on one side and basement membrane proteins (collagen types IV and V and laminin) on the other. Under culture conditions, individual components of the extracellular matrix failed to maintain fenestrations. A basement-membranelike gel matrix derived from the Engelbreth-Holm-Swarm tumor war similarly ineffective. Fenestral density and porosity (percentage of cell surface occupied by fenestrations) were significantly enhanced, however, when endothelial cells were cultured on the basement-membrane side of human amnion. These data suggest that support of endothelial fenestrations requires a complex matrix. In particular, physiologically derived basement membrane maintains fenestrations, whereas interstitial collagen matrix does not. The loss of fenestrations associated with hepatic fibrosis may be related in part to an accumulation of interstitial collagens in the space of Disse.

Amnion↗
PubMed1991

The influence of particle size and multiple apoprotein E-receptor interactions on the endocytic targeting of beta-VLDL in mouse peritoneal macrophages.

Low density lipoprotein (LDL) and beta-very low density lipoprotein (beta-VLDL) are internalized by the same receptor in mouse peritoneal macrophages and yet their endocytic patterns differ; beta-VLDL is targeted to both widely distributed and perinuclear vesicles, whereas LDL is targeted almost entirely to perinuclear lysosomes. This endocytic divergence may have important metabolic consequences since beta-VLDL is catabolized slower than LDL and is a more potent stimulator of acyl-CoA/cholesterol acyl transferase (ACAT) than LDL. The goal of this study was to explore the determinants of beta-VLDL responsible for its pattern of endocytic targeting. Fluorescence microscopy experiments revealed that large, intestinally derived, apoprotein (Apo) E-rich beta-VLDL was targeted mostly to widely distributed vesicles, whereas small, hepatically derived beta-VLDL was targeted more centrally (like LDL). Furthermore, the large beta-VLDL had a higher ACAT-stimulatory potential than the smaller beta-VLDL. The basis for these differences was not due to fundamental differences in the means of uptake; both large and small beta-VLDL were internalized by receptor-mediated endocytosis (i.e., not phagocytosis) involving the interaction of Apo E of the beta-VLDL with the macrophage LDL receptor. However, large beta-VLDL was much more resistant to acid-mediated release from LDL receptors than small beta-VLDL. Furthermore, partial neutralization of the multiple Apo Es on these particles by immunotitration resulted in a more perinuclear endocytic pattern, a lower ACAT-stimulatory potential, and an increased sensitivity to acid-mediated receptor release. These data are consistent with the hypothesis that the interaction of the multivalent Apo Es of large beta-VLDL with multiple macrophage LDL receptors leads to a diminished or retarded release of the beta-VLDL from its receptor in the acidic sorting endosome which, in turn, may lead to the widely distributed endocytic pattern of large beta-VLDL. These findings may represent a physiologically relevant example of a previously described laboratory phenomenon whereby receptor cross-linking by multivalent ligands leads to a change in receptor targeting.

Animals↗