Taurine reduces high glucose induced leukocyte–endothelial interactions via down-regulation of ICAM-1

Taurine is a semiessential amino acid and naturally occurring antioxidant. One of its main roles is to protect tissues against attack by chlorinated oxidants particularly hypochlorous acid (HOCl). It is found in high concentrations in neutrophils and previous studies showed it possesses potent antimicrobial properties and attenuates high glucose induced endothelial cell apoptosis. In humans taurine has been shown to up-regulate constitutive nitric oxide synthase (cNOS), a known cytoprotector.
No reported studies to date have looked at the possible therapeutic role of taurine in preventing diabetic endothelial dysfunction. We therefore hypothesised that taurine would attenuate the microvascular changes associated with hyperglycaemia in an animal model through alteration of leucocyte–endothelial interactions.
Male Sprague Dawley rats were randomised into control, hyperglycaemia, and taurine + hyperglycaemia groups. Taurine was gavaged (200 mg/kg) for 5 d prior to the experiment. Hyperglycaemia was established by intravenous infusion of 50% glucose. Blood glucose reached a steady state of 3 times baseline at 30 min. Using intravital microscopy leukocyte rolling, adhesion and transendothelial migration was determined in mesenteric postcapillary venules for 3 h. Intracellular adhesion molecule-1 (ICAM-1) was immunohistochemically graded using a scoring system to determine the expression in mesenteric tissue.
Taurine pretreatment significantly attenuates leukocyte-endothelial adhesion and transendothelial migration following acute hyperglycaemia but not leukocyte rolling velocity. The mechanism by which taurine protects against these effects is in part by inhibition of ICAM-1 expression .  

      

52.

Characterization of self-reactive T cells that evade tolerance in hepatitis B e antigen transgenic mice     

David R. Milich  Florian Schdel  Darrell L. Peterson  Joyce E. Jones  Janice L. Hughes 《European journal of immunology》1995,25(6):1663-1672

Previous studies of hepatitis B e antigen (HBeAg)-expressing transgenic (Tg31e) mice have indicated that the degree of T cell tolerance was epitope specific. For example, T cells specific for residues 120–131 of HBeAg are profoundly tolerant, whereas a proportion of T cells specific for residues 129–140 escape tolerance induction in B10. S × B10-Tg31e mice. To understand the basis for differential tolerance towards two T cell sites on the same self antigen, we characterized T cell recognition of HBeAg by primary T cells and T cell hybridomas derived from HBeAg-Tg and non-Tg mice. The self-reactive T cells surviving in B10-Tg31e mice exhibited a unique fine specificity, albeit still focussed on HBeAg residues 129–140, which could be distinguished from the HBeAg-specific T cell repertoire in non-Tg B10 mice. Further, self-reactive T cells were comprised predominantly of Th2-type cells that preferentially evaded tolerance induction as compared to their Th1 counterparts. Because HBeAg may act as a tolerogen during the vertical transmission of chronic hepatitis B virus (HBV) infection, these results suggest that a predominance of HBeAg-specific Th2 cells expressing a limited repertoire may influence the initiation or the maintenance of the HBV chronic carrier state.     

53.

Ethics consultants: a self-portrait of decision makers     

Bermel J 《The Hastings Center report》1985,15(6):2-2

     

54.

Phase I and pharmacokinetic study of tiazofurin (TCAR,NSC 286193) administered by continuous infusion     

Gerald Batist  Raymond W. Klecker Jr.  Hiremagalur N. Jayaram  Jean F. Jenkins  John Grygiel  Daniel C. Ihde  Joyce L. Eddy  Robert L. Fine  Ian G. Kerr  Jerry M. Collins 《Investigational new drugs》1985,3(4):349-355

Summary Tiazofurin (2--D-ribofuranosylthiazole-4-carboxamide, TCAR) is a synthetic C-nucleoside that demonstrated significant in vivo activity against a variety of animal tumors as well as in vitro activity against human tumor-derived cell lines. Thirteen patients were treated with TCAR administered as a 5-day continuous infusion in this Phase I trial. Seventeen complete cycles were administered in three dose levels ranging from 550 to 1450 mg/M². Dose-limiting toxicities were myelosuppression and neurotoxicity including severe lethargy. Other toxicities including superficial skin peeling, myalgias, and tearing were seen at all doses. One patient had chest pain on day 4 resulting in stopping the drug, however, there was no evidence of cardiac or pericardial disease. Uric acid levels rose within one day in the absence of allopurinol treatment. There were no treatment related deaths. HPLC measurement of drug levels demonstrated steady-state plasma levels during the infusion, and a half-life following the infusion of 7.7 ± 0.6 hours. Minor abnormalities in renal function were associated with dramatic changes in pharmacokinetics and toxicity. No clinical responses were observed in this trial.Abbreviations TCAR Tiazofurin - HPLC High performance liquid chromatography - IMPD Inosine monophosphate dehydrogenase - WBC white blood cell - CPK creatine phosphokinase - C_ss steady-state concentration     

55.

Inconsistent effects of all-trans retinoic acid on different clones of chemically transformed rat liver epithelial cells   总被引：1，自引：0，他引：1  

Tsao  Ming-Sound; Blaisdell  Joyce; Chou  Barbara B.; Earp  H.Shelton; Grisham  Joe W. 《Carcinogenesis》1987,8(4):497-501

The effects of all-trans retinoic acid (RA) on the growth andbiochemical properties of five clonal strains of neoplasticallytransformed rat liver epithelial cells were studied. These cellstrains were derived clonally from a single line of normal diploidrat liver epithelial cells that had been transformed by treatmentwith N-methyl-N'-nitro-N-nitrosoguanidine. The results showthat RA induces inconsistent alterations in selected phenotypicproperties of these five different cell strains. Retinoic acideither depressed, enhanced or produced no effect on the colony-formingability in soft agar, on the activity of -glutamyl transpeptidase,on the amount of cell-associated fibronectin, and on the bindingcapacity of ¹²⁵I-epidermal growth factor (EGF). The only consistentcorrelation observed among cell strains was between the cellularability to grow in soft agar and the amount of cell-associatedfibronectin. Enhancement of anchorage-independent growth byretinoic acid was not mediated through changes in the numberof EGF receptors. Our data demonstrate that the responses toretinoic acid of clonal subpopulations of chemically transformedrat liver epithelial cells are inconsistent, even when the clonalsubpopulations are derived from a common precursor.     

56.

Biochemical and morphologic studies of heterogeneous lobe responses in hepatocarcinogenesis   总被引：1，自引：1，他引：0  

Richardson  Frank C.; Boucheron  Joyce A.; Dyroff  Martin C.; Popp  James A.; Swenberg  James A. 《Carcinogenesis》1986,7(2):247-251

Experiments have demonstrated interlobe differences in the incidenceof diethylnitrosamine (DEN)-induced hepatocellular carcinoma(HCCA), with a 100% incidence in the left and right median lobesand a 30% incidence in the right anterior lobe 20 weeks afterexposure began. These tumor data provide a model to test thehypothesis that chemically induced neoplasia can be qualitativelyand quantitatively related to promutagenic DNA damage and concurrentcell replication. Experiments were performed to measure O⁴-ethyldeoxythymidine(O⁴-EtdT) (a major pro-mutagenic lesion in hepatic DNA of ratsexposed to DEN), N7-ethylguanine, cell replication and hepatocyteinitiation using the induction of growthselected -glutamyl transferase-positive(GGT+) foci in the left and right median and right anteriorhepatic lobes following 0, 3, 7, 14 or 28 days of DEN administration.Results demonstrated that O⁴-EtdT concentrations were consistentlyhigher in the left and right median versus the right anteriorhepatic lobes, while cell replication was transiently higherin the right median and right anterior lobes. Likewise, highnumbers of GGT+ foci were observed in the left and right medianlobes in DEN-exposed rats subjected to a Cayama-Farber growthselection protocol. Following administration of [¹⁴C]DEN, thedistribution of radioactivity showed a marked left lobe preferencein 4-week-old rats that had no prior exposure to DEN and in8-week-old rats exposed to DEN for 4 weeks. This study suggeststhat interlobe differences in hepatocyte initiation and theincidence of HCCA may be due in part to differences in cellreplication and in DNA alkylation resulting from differentialDEN distribution and/or metabolism.     

57.

Measuring quality and level of care provided by family caregivers of persons with dementia: protocol for a systematic review of validated instruments     

Afeez Abiola Hazzan  Joyce O Hazzan  Mark Oremus 《AIMS Public Health》2021,8(2):206

BackgroundChanges in the quality-of-life (QoL) of family caregivers as they care for their loved ones with dementia over time may affect the quality or level of care that these caregivers provide. We do not know if validated instruments exist to directly measure this quality or level of care. The purpose of this systematic review is to identify validated instruments for measuring the quality or level of care provided by family caregivers of persons with dementia.MethodsWe will include articles containing a validated instrument or questionnaire designed to measure quality or level of care provided by the aforementioned group of caregivers. The included articles may utilize the tools in primary or secondary data analyses, or evaluate the tools'' psychometric properties. The following electronic databases will be searched from inception date to the present: Medline, CINAHL Complete, Cochrane Central, and PsycINFO. We will also search the gray literature, the reference lists of included articles, and contact experts in the field to help identify relevant instruments. Included articles will be required to report on an instrument measuring at least one of the following outcomes: quality of care, level of care, appropriateness of care, amount of time spent providing care, and caregiver performance. Two reviewers will independently screen retrieved citations, extract data, and assess the methodological quality of each included article. A narrative synthesis method will be used to describe the findings.DiscussionResults of this systematic review will show whether validated instruments exist to measure the quality or level of care provided by family caregivers of persons living with dementia. This will make it possible to develop initiatives that are targeted towards improving the quality or level of care provided by family caregivers.     

58.

Providing culturally safe care to Indigenous people living with diabetes: Identifying barriers and enablers from different perspectives     

Marie&#x;Claude Tremblay  Maude Bradette&#x;Laplante  Holly O. Witteman  Maman Joyce Dogba  Pascale Breault  Jean&#x;Sbastien Paquette  Emmanuelle Careau  Sandro Echaquan 《Health expectations》2021,24(2):296

     

59.

The implementation of an infection control bundle within a Total Care Burns Unit     

Tania Lorena Mcwilliams  Di Twigg  Joyce Hendricks  Fiona Melanie Wood  Jane Ryan  Anthony Keil 《Burns : journal of the International Society for Burn Injuries》2021,47(3):569-575

AimTo evaluate the impact of the implementation of a best practice infection prevention and control bundle on healthcare associated burn wound infections in a paediatric burns unit.BackgroundBurn patients are vulnerable to infection. For this patient population, infection is associated with increased morbidity and mortality, thereby representing a significant challenge for burns clinicians who care for them.MethodsAn interrupted time series was used to compare healthcare associated burn wound infections in paediatric burn patients before and after implementation of an infection prevention and control bundle. Prospective surveillance of healthcare associated burn wound infections was conducted from 2012 to 2014. Other potential healthcare associated infection rates were also reviewed over the study period, including urinary tract infections, pneumonia, upper respiratory tract infections and sepsis. An infection prevention and control bundle developed in collaboration between the paediatric burn unit and infection control clinicians was implemented in 2013 in addition to previous standard practice.ResultsDuring the study period a total of 626 patients were admitted to the paediatric burns unit. Healthcare associated burn wound infections reduced from 34 in 2012 to 0 in 2014 following the implementation of the infection prevention and control bundle. Pneumonia and sepsis also reduced to 0 in 2013 and 2014, however one upper respiratory tract infection occurred in 2013 and urinary tract infections persisted in 2013.ConclusionThe implementation of an infection prevention and control bundle was effective in reducing healthcare associated burn wound infections, pneumonia and sepsis within our paediatric burns unit. Urinary tract infections remain a challenge for future improvement.     

60.

Impact of donor smoking history on post heart transplant outcomes: A propensity‐matched analysis of ISHLT registry     

Zeeshan Hussain  Mingxi Yu  Amy Wozniak  Daniel Kim  Nicholas Krepostman  Max Liebo  Eugenia Raichlin  Alain Heroux  Cara Joyce  Haseeb Ilias‐Basha 《Clinical transplantation》2021,35(1):e14127

     

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Characterization of self-reactive T cells that evade tolerance in hepatitis B e antigen transgenic mice

Previous studies of hepatitis B e antigen (HBeAg)-expressing transgenic (Tg31e) mice have indicated that the degree of T cell tolerance was epitope specific. For example, T cells specific for residues 120–131 of HBeAg are profoundly tolerant, whereas a proportion of T cells specific for residues 129–140 escape tolerance induction in B10. S × B10-Tg31e mice. To understand the basis for differential tolerance towards two T cell sites on the same self antigen, we characterized T cell recognition of HBeAg by primary T cells and T cell hybridomas derived from HBeAg-Tg and non-Tg mice. The self-reactive T cells surviving in B10-Tg31e mice exhibited a unique fine specificity, albeit still focussed on HBeAg residues 129–140, which could be distinguished from the HBeAg-specific T cell repertoire in non-Tg B10 mice. Further, self-reactive T cells were comprised predominantly of Th2-type cells that preferentially evaded tolerance induction as compared to their Th1 counterparts. Because HBeAg may act as a tolerogen during the vertical transmission of chronic hepatitis B virus (HBV) infection, these results suggest that a predominance of HBeAg-specific Th2 cells expressing a limited repertoire may influence the initiation or the maintenance of the HBV chronic carrier state.     

Phase I and pharmacokinetic study of tiazofurin (TCAR,NSC 286193) administered by continuous infusion

Summary Tiazofurin (2--D-ribofuranosylthiazole-4-carboxamide, TCAR) is a synthetic C-nucleoside that demonstrated significant in vivo activity against a variety of animal tumors as well as in vitro activity against human tumor-derived cell lines. Thirteen patients were treated with TCAR administered as a 5-day continuous infusion in this Phase I trial. Seventeen complete cycles were administered in three dose levels ranging from 550 to 1450 mg/M². Dose-limiting toxicities were myelosuppression and neurotoxicity including severe lethargy. Other toxicities including superficial skin peeling, myalgias, and tearing were seen at all doses. One patient had chest pain on day 4 resulting in stopping the drug, however, there was no evidence of cardiac or pericardial disease. Uric acid levels rose within one day in the absence of allopurinol treatment. There were no treatment related deaths. HPLC measurement of drug levels demonstrated steady-state plasma levels during the infusion, and a half-life following the infusion of 7.7 ± 0.6 hours. Minor abnormalities in renal function were associated with dramatic changes in pharmacokinetics and toxicity. No clinical responses were observed in this trial.Abbreviations TCAR Tiazofurin - HPLC High performance liquid chromatography - IMPD Inosine monophosphate dehydrogenase - WBC white blood cell - CPK creatine phosphokinase - C_ss steady-state concentration     

Inconsistent effects of all-trans retinoic acid on different clones of chemically transformed rat liver epithelial cells

The effects of all-trans retinoic acid (RA) on the growth andbiochemical properties of five clonal strains of neoplasticallytransformed rat liver epithelial cells were studied. These cellstrains were derived clonally from a single line of normal diploidrat liver epithelial cells that had been transformed by treatmentwith N-methyl-N'-nitro-N-nitrosoguanidine. The results showthat RA induces inconsistent alterations in selected phenotypicproperties of these five different cell strains. Retinoic acideither depressed, enhanced or produced no effect on the colony-formingability in soft agar, on the activity of -glutamyl transpeptidase,on the amount of cell-associated fibronectin, and on the bindingcapacity of ¹²⁵I-epidermal growth factor (EGF). The only consistentcorrelation observed among cell strains was between the cellularability to grow in soft agar and the amount of cell-associatedfibronectin. Enhancement of anchorage-independent growth byretinoic acid was not mediated through changes in the numberof EGF receptors. Our data demonstrate that the responses toretinoic acid of clonal subpopulations of chemically transformedrat liver epithelial cells are inconsistent, even when the clonalsubpopulations are derived from a common precursor.     

Biochemical and morphologic studies of heterogeneous lobe responses in hepatocarcinogenesis

Experiments have demonstrated interlobe differences in the incidenceof diethylnitrosamine (DEN)-induced hepatocellular carcinoma(HCCA), with a 100% incidence in the left and right median lobesand a 30% incidence in the right anterior lobe 20 weeks afterexposure began. These tumor data provide a model to test thehypothesis that chemically induced neoplasia can be qualitativelyand quantitatively related to promutagenic DNA damage and concurrentcell replication. Experiments were performed to measure O⁴-ethyldeoxythymidine(O⁴-EtdT) (a major pro-mutagenic lesion in hepatic DNA of ratsexposed to DEN), N7-ethylguanine, cell replication and hepatocyteinitiation using the induction of growthselected -glutamyl transferase-positive(GGT+) foci in the left and right median and right anteriorhepatic lobes following 0, 3, 7, 14 or 28 days of DEN administration.Results demonstrated that O⁴-EtdT concentrations were consistentlyhigher in the left and right median versus the right anteriorhepatic lobes, while cell replication was transiently higherin the right median and right anterior lobes. Likewise, highnumbers of GGT+ foci were observed in the left and right medianlobes in DEN-exposed rats subjected to a Cayama-Farber growthselection protocol. Following administration of [¹⁴C]DEN, thedistribution of radioactivity showed a marked left lobe preferencein 4-week-old rats that had no prior exposure to DEN and in8-week-old rats exposed to DEN for 4 weeks. This study suggeststhat interlobe differences in hepatocyte initiation and theincidence of HCCA may be due in part to differences in cellreplication and in DNA alkylation resulting from differentialDEN distribution and/or metabolism.     

Measuring quality and level of care provided by family caregivers of persons with dementia: protocol for a systematic review of validated instruments

BackgroundChanges in the quality-of-life (QoL) of family caregivers as they care for their loved ones with dementia over time may affect the quality or level of care that these caregivers provide. We do not know if validated instruments exist to directly measure this quality or level of care. The purpose of this systematic review is to identify validated instruments for measuring the quality or level of care provided by family caregivers of persons with dementia.MethodsWe will include articles containing a validated instrument or questionnaire designed to measure quality or level of care provided by the aforementioned group of caregivers. The included articles may utilize the tools in primary or secondary data analyses, or evaluate the tools'' psychometric properties. The following electronic databases will be searched from inception date to the present: Medline, CINAHL Complete, Cochrane Central, and PsycINFO. We will also search the gray literature, the reference lists of included articles, and contact experts in the field to help identify relevant instruments. Included articles will be required to report on an instrument measuring at least one of the following outcomes: quality of care, level of care, appropriateness of care, amount of time spent providing care, and caregiver performance. Two reviewers will independently screen retrieved citations, extract data, and assess the methodological quality of each included article. A narrative synthesis method will be used to describe the findings.DiscussionResults of this systematic review will show whether validated instruments exist to measure the quality or level of care provided by family caregivers of persons living with dementia. This will make it possible to develop initiatives that are targeted towards improving the quality or level of care provided by family caregivers.     

The implementation of an infection control bundle within a Total Care Burns Unit

AimTo evaluate the impact of the implementation of a best practice infection prevention and control bundle on healthcare associated burn wound infections in a paediatric burns unit.BackgroundBurn patients are vulnerable to infection. For this patient population, infection is associated with increased morbidity and mortality, thereby representing a significant challenge for burns clinicians who care for them.MethodsAn interrupted time series was used to compare healthcare associated burn wound infections in paediatric burn patients before and after implementation of an infection prevention and control bundle. Prospective surveillance of healthcare associated burn wound infections was conducted from 2012 to 2014. Other potential healthcare associated infection rates were also reviewed over the study period, including urinary tract infections, pneumonia, upper respiratory tract infections and sepsis. An infection prevention and control bundle developed in collaboration between the paediatric burn unit and infection control clinicians was implemented in 2013 in addition to previous standard practice.ResultsDuring the study period a total of 626 patients were admitted to the paediatric burns unit. Healthcare associated burn wound infections reduced from 34 in 2012 to 0 in 2014 following the implementation of the infection prevention and control bundle. Pneumonia and sepsis also reduced to 0 in 2013 and 2014, however one upper respiratory tract infection occurred in 2013 and urinary tract infections persisted in 2013.ConclusionThe implementation of an infection prevention and control bundle was effective in reducing healthcare associated burn wound infections, pneumonia and sepsis within our paediatric burns unit. Urinary tract infections remain a challenge for future improvement.