Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ATR”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed2002

Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning?

OBJECTIVE: We propose that ischemic preconditioning (IPC) and mitochondrial K(ATP) channel activation protect the myocardium by inhibiting mitochondrial permeability transition pore (MPTP) opening at reperfusion. METHODS: Isolated rat hearts were subjected to 35 min ischemia/120 min reperfusion and assigned to the following groups: (1) control; (2) IPC of 2x5 min each of preceding global ischemia; (3,4,5) 0.2 micromol/l cyclosporin A (CsA, which inhibits MPTP opening), 5 micromol/l FK506 (which inhibits the phosphatase calcineurin without inhibiting MPTP opening), or 20 micromol/l atractyloside (Atr, a MPTP opener) given at reperfusion; (6,7) pre-treatment with 30 micromol/l diazoxide (Diaz, a mitochondrial K(ATP) channel opener) or 200 nmol/l 2 chloro-N(6)-cyclopentyl-adenosine (CCPA, an adenosine A1 receptor agonist); (8) IPC+Atr; (9) Diaz+Atr; (10) CCPA+Atr. The effect of mitochondrial K(ATP) channel activation on calcium-induced MPTP opening in isolated calcein-loaded mitochondria was also assessed. RESULTS: IPC, CsA when given at reperfusion, and pre-treatment with diazoxide or CCPA all limited infarct size (19.9+/-2.6% in IPC; 24.6+/-1.9% in CsA, 18.0+/-1.7% in Diaz, 20.4+/-3.3% in CCPA vs. 44.7+/-2.0% in control, P<0.0001). Opening the MPTP with atractyloside at reperfusion abolished this cardio-protective effect (47.7+/-1.8% in IPC+Atr, 42.3+/-3.2% in Diaz+Atr, 51.2+/-1.6% in CCPA+Atr). Atractyloside and FK506, given at reperfusion, did not influence infarct size (45.7+/-2.1% in Atr and 43.1+/-3.6% in FK506 vs. 44.7+/-2.0% in control, P=NS). Diazoxide (30 micromol/l) was shown to reduce calcium-induced MPTP opening by 52.5+/-8.0% in calcein-loaded mitochondria. 5-Hydroxydecanoic acid (100 micromol/l) was able to abolish the cardio-protective effects of both diazoxide and IPC. CONCLUSION: One interpretation of these data is that IPC and mitochondrial K(ATP) channel activation may protect the myocardium by inhibiting MPTP opening at reperfusion.

Adenosine↗
PubMed2003

Applications of attenuated total reflection infrared spectroscopic imaging to pharmaceutical formulations.

This paper demonstrates an approach to obtain chemical images of pharmaceutical tablets using attenuated total reflection infrared (ATR-IR) spectroscopy. FT-IR images with different fields of view and spatial resolution have been obtained using a combination of different ATR accessories. FT-IR imaging with the diamond ATR accessory and micro-ATR imaging technique have been compared. With the diamond ATR imaging accessory, compaction to a tablet can be performed and the chemical image measured in situ. It has been found that the diamond ATR imaging accessory gives information on the overall distribution of different components in a tablet while the micro-ATR imaging technique provides a closer look at the tablet with 4-microm spatial resolution. Low-concentration components down to 0.5% have been detected by the micro-ATR method. Both experimental and commercial systems are studied in this paper.

Journal Article↗
PubMed2001

The effects of propofol or halothane on free radical production after tourniquet induced ischaemia-reperfusion injury during knee arthroplasty.

BACKGROUND: Ischaemia-reperfusion injury following tourniquet release is a good in vivo model for evaluating acute conditions. The aim of the study was to investigate the effects of propofol or halothane anaesthesia on oxidative stress by determining malondialdehyde (MDA) levels during knee arthroplasty. METHODS: Thirty patients undergoing orthopaedic surgery were divided into two groups. Anaesthesia was induced with either fentanyl 100 microg and propofol 2 mg kg(-1) (Group 1) or fentanyl 100 microg and thiopentone 5 mg kg(-1) (Group 2) and maintained with infusion of propofol in Group 1 or inhalation of halothane in Group 2. ECG, SpO2, EtCO2, and mean arterial pressure (MAP) were monitored. Venous and arterial blood samples were obtained at different measurement times for MDA and blood gas analyses. RESULTS: There was a significant decrease in MAP in the 1st and 5th minutes after tourniquet release (ATR) when compared with the 5th minute before tourniquet release (BTR) in both groups. Heart rate (HR) increased significantly in the 1st minute ATR in Group 1 only. EtCO2 increased significantly in the 1st and 5th minutes ATR, SpO2 decreased in the 1st minute ATR in both groups. There was a significant decrease in pH and increase in pCO2 at 1, 5 and 30 min ATR in both groups. pO2 values decreased in the 1st minute ATR in Group 1 only and returned to control values at 5 min ATR and decreased at 30 min ATR in the recovery room in both groups. The differences in SaO2 were similar to SpO2. MDA levels decreased before and after release of tourniquet when compared to baseline in both groups. However, there was a statistically significant decrease only in Group 1. CONCLUSION: Propofol may be a good choice of anaesthetic when an ischaemia-reperfusion injury is anticipated as in orthopaedic surgery requiring a tourniquet, due to its antioxidant properties, but halothane needs further study.

Aged↗
PubMed2004

Human ATP:Cob(I)alamin adenosyltransferase and its interaction with methionine synthase reductase.

The final step in the conversion of vitamin B(12) into coenzyme B(12) (adenosylcobalamin, AdoCbl) is catalyzed by ATP:cob(I)alamin adenosyltransferase (ATR). Prior studies identified the human ATR and showed that defects in its encoding gene underlie cblB methylmalonic aciduria. Here two common polymorphic variants of the ATR that are found in normal individuals are expressed in Escherichia coli, purified, and partially characterized. The specific activities of ATR variants 239K and 239M were 220 and 190 nmol min(-1) mg(-1), and their K(m) values were 6.3 and 6.9 mum for ATP and 1.2 and 1.6 mum for cob(I)alamin, respectively. These values are similar to those obtained for previously studied bacterial ATRs indicating that both human variants have sufficient activity to mediate AdoCbl synthesis in vivo. Investigations also showed that purified recombinant human methionine synthase reductase (MSR) in combination with purified ATR can convert cob(II)alamin to AdoCbl in vitro. In this system, MSR reduced cob(II)alamin to cob(I)alamin that was adenosylated to AdoCbl by ATR. The optimal stoichiometry for this reaction was approximately 4 MSR/ATR and results indicated that MSR and ATR physically interacted in such a way that the highly reactive reaction intermediate [cob(I)alamin] was sequestered. The finding that MSR reduced cob(II)alamin to cob(I)alamin for AdoCbl synthesis (in conjunction with the prior finding that MSR reduced cob(II)alamin for the activation of methionine synthase) indicates a dual physiological role for MSR.

Adenosine Triphosphate↗
PubMed2004

Ataxia telangiectasia mutated (ATM) and ATM and Rad3-related protein exhibit selective target specificities in response to different forms of DNA damage.

The ataxia telangiectasia mutated (ATM) and ATR (ATM and Rad3-related) protein kinases exert cell cycle delay, in part, by phosphorylating Checkpoint kinase (Chk) 1, Chk2, and p53. It is well established that ATR is activated following UV light-induced DNA damage such as pyrimidine dimers and the 6-(1,2)-dihydro-2-oxo-4-pyrimidinyl-5-methyl-2,4-(1H,3H)-pyrimidinediones, whereas ATM is activated in response to double strand DNA breaks. Here we clarify the activation of these kinases in cells exposed to IR, UV, and hyperoxia, a condition of chronic oxidative stress resulting in clastogenic DNA damage. Phosphorylation on Chk1(Ser-345), Chk2(Thr-68), and p53(Ser-15) following oxidative damage by IR involved both ATM and ATR. In response to ultraviolet radiation-induced stalled replication forks, phosphorylation on Chk1 and p53 required ATR, whereas Chk2 required ATM. Cells exposed to hyperoxia exhibited growth delay in G1, S, and G2 that was disrupted by wortmannin. Consistent with ATM or ATR activation, hyperoxia induced wortmannin-sensitive phosphorylation of Chk1, Chk2, and p53. By using ATM- and ATR-defective cells, phosphorylation on Chk1, Chk2, and p53 was found to be ATM-dependent, whereas ATR also contributed to Chk1 phosphorylation. These data reveal activated ATM and ATR exhibit selective substrate specificity in response to different genotoxic agents.

Androstadienes↗
PubMed2005

DNA replication stress-induced phosphorylation of cyclic AMP response element-binding protein mediated by ATM.

The DNA damage-response regulators ATM (ataxia-telangiectasia-mutated) and ATR (ATM-Rad3-related) are structurally and functionally related protein kinases that exhibit nearly identical substrate specificities in vitro. Current paradigms hold that the relative contributions of ATM and ATR to nuclear substrate phosphorylation are dictated by the type of initiating DNA lesion; ATM-dependent substrate phosphorylation is principally activated by DNA double strand breaks, whereas ATR-dependent substrate phosphorylation is induced by UV light and other forms of DNA replication stress. In this report, we employed the cyclic AMP-response element-binding (CREB) protein to provide evidence for substrate discrimination by ATM and ATR in cellulo. ATM and ATR phosphorylate CREB in vitro, and CREB is phosphorylated on Ser-121 in intact cells in response to ionizing radiation (IR), UV light, and hydroxyurea. The UV light- and hydroxyurea-induced phosphorylation of CREB was delayed in comparison to the canonical ATR substrate CHK1, suggesting potentially different mechanisms of phosphorylation. UV light-induced CREB phosphorylation temporally correlated with ATM autophosphorylation on Ser-1981, and an ATM-specific small interfering RNA suppressed CREB phosphorylation in response to this stimulus. UV light-induced CREB phosphorylation was absent in ATM-deficient cells, confirming that ATM is required for CREB phosphorylation in UV irradiation-damaged cells. Interestingly, RNA interference-mediated suppression of ATR partially inhibited CREB phosphorylation in response to UV light, which correlated with reduced phosphorylation of ATM on Ser-1981. These findings suggest that ATM is the major genotoxin-induced CREB kinase in mammalian cells and that ATR lies upstream of ATM in a UV light-induced signaling pathway.

Ataxia Telangiectasia↗
PubMed2003

Developmental atrazine exposure suppresses immune function in male, but not female Sprague-Dawley rats.

Each year, 75 million pounds of the broadleaf herbicide atrazine (ATR) are applied to crops in the United States. Despite limited solubility, ATR is common in ground and surface water, making it of regulatory concern. ATR suppresses the immunomodulatory hormones prolactin (PRL) and the thyroid hormones (THs), with developmental exposure to ATR permanently disrupting PRL regulation. We hypothesized that ATR may cause developmental immunotoxicity through its disruption of PRL or THs. To test this hypothesis, pregnant Sprague-Dawley (SD) rats were exposed to 35-mg ATR/kg/d from gestational day (GD) 10 through postnatal day (PND) 23. Separate groups were exposed to bromocryptine (BCR) at 0.2 mg/kg/2x/day to induce hypoprolactinemia or to propylthiouracil (PTU) at 2 mg/kg/day to induce hypothyroidism. After the offspring reached immunologic maturity (at least 7 weeks old), the following immune functions were evaluated: natural killer (NK) cell function; delayed-type hypersensitivity (DTH) responses; phagocytic activity of peritoneal macrophages; and antibody response to sheep erythrocytes (SRBC). ATR decreased the primary antibody and DTH responses in male offspring only. Neither PTU nor BCR caused immunosuppression in any measured variable, although PTU increased phagocytosis by peritoneal macrophages. These results demonstrate that developmental exposure to ATR produced gender-specific changes in immune function in adult rats and suggest that immune changes associated with ATR are not mediated through the suppression of PRL or THs.

Abnormalities, Drug-Induced↗
PubMed2005

Adverse effects of prenatal exposure to atrazine during a critical period of mammary gland growth.

Prenatal exposure to 100 mg/kg atrazine (ATR) delays mammary gland (MG) development in resulting female offspring of Long-Evans rats. To determine if the fetal MG was sensitive to ATR effects during specific periods of development, timed-pregnant dams (n = 8/group/block) were dosed for 3- or 7-gestation day (GD) intervals (GD 13-15, 15-17, 17-19, or 13-19) with 100 mg ATR/kg/day or vehicle (C), and their offspring were evaluated for changes. Mammary glands taken from pups prenatally exposed to ATR displayed significant delays in epithelial development as early as postnatal day (PND) 4 compared to C, with continued developmental delays at later time points that varied by time of exposure. However, the most persistent and severe delays were seen in the GD 17-19 and GD 13-19 ATR exposure groups, demonstrating statistically similar growth retardation. Because MG developmental deficits persisted into adulthood, we hypothesized that ATR-exposed animals may have had difficulties nursing their young. Females exposed prenatally to either ATR (as defined) or C (n = 4 litters/group) were bred, and the resulting F(2) offspring from GD 17-19 and GD 13-19 exposure groups were significantly smaller in body weight (BW) than C. In a separate study, it was determined that ATR (25-100 mg/kg), delivered from GD 15-19, did not decrease fetal body weights on GD 20, even though the higher doses significantly decreased weight gain of the dosed dams. These data suggest that the consequences of brief ATR exposure during a critical period of fetal MG development (GD 17-19), are both delayed MG development of the offspring and inadequate nutritional support of F2 offspring, resulting in adverse effects on pup weight gain.

Animals↗
PubMed2005

Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of AIDS Clinical Trials Group 5108 Study.

Efavirenz (EFV) is associated with hyperlipidemia when used in combination with other antiretroviral drugs. EFV is a mixed inducer/inhibitor of cytochrome P450 (CYP) 3A4 isozyme and may interact with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that are primarily metabolized via CYP3A4. To assess the drug-drug interaction of EFV used in combination with simvastatin (SIM), atorvastatin (ATR), or pravastatin (PRA), an open-label trial was conducted in 52 healthy adult HIV-seronegative subjects across AIDS Clinical Trials Group sites in the United States. Subjects received 40 mg of SIM, 10 mg of ATR, or 40 mg of PRA daily on days 0 through 3 and days 15 through 18. EFV was administered daily at a dose of 600 mg on days 4 through 18. SIM, ATR, and PRA concentrations were determined before and after EFV, and EFV concentrations were determined before and after statins. EFV reduced SIM acid exposure (area under the curve at 0 to 24 hours [AUC0-24 h]) by 58% (Wilcoxon signed rank test, P=0.003) and active HMG-CoA reductase inhibitory activity by 60% (P<0.001). EFV reduced ATR exposure by 43% (P<0.001) and the total active ATR exposure by 34% (P=0.005). EFV administration resulted in a 40% decrease in PRA exposure (P=0.005). SIM, ATR, and PRA had no effect on non-steady-state EFV concentrations. In conclusion, EFV, when administered with SIM, ATR, or PRA, can result in significant induction of statin metabolism. The reduced inhibition of HMG-CoA reductase activity during coadministration of EFV may result in diminished antilipid efficacy at usual doses of SIM, ATR, and PRA.

Adult↗
PubMed1996

Role of the acid tolerance response in virulence of Salmonella typhimurium.

During its life cycle, Salmonella typhimurium is exposed to a variety of acidic conditions. Survival in the acidic environments within the host may require the adaptive acid tolerance response (ATR), which is characterized by the induction of several Salmonella proteins upon exposure to mildly acidic conditions. These induced proteins protect the bacterium from death under severe acid challenge. The goal of this study was to examine the role of ATR in Salmonella pathogenesis. Initially, we observed that differences exist between the virulent S. typhimurium strains and the laboratory S. typhimurium strain LT2 with respect to their ATR. Mutations affecting the ATR of S. typhimurium LT2, including atrB, atrC (polA), atrD, atbR, and fur, were crossed into virulent Salmonella strains, and the resultant transductants were screened for virulence in mice and acid sensitivity. Surprisingly, with the exception of the fur mutation, none of the muatations had a major effect on acid resistance or virulence in the pathogenic strains. The fur mutants showed a 1-to 3-log increase in the 50% lethal dose; however, the magnitude of its effect was dependent on the strain background. Strains containing two or three different atr mutations were constructed, and these were also examined for acid sensitivity and virulence. The double and triple mutants that contained an atrC mutation no longer displayed an ATR. Those mutants which were more acid sensitive were also highly attenuated, suggesting a strong correlation between the ability to mount and ATR and virulence in S. typhimurium. Comparison of the ability of the various atr single, double, and triple mutants to survive within macrophages showed that strains containing an atrC mutation survived much less than the wild type in bone marrow-derived macrophages. No difference in survival within J774 macrophage like cells were detected.

Acids↗
PubMed2000

OmpR regulates the stationary-phase acid tolerance response of Salmonella enterica serovar typhimurium.

Tolerance to acidic environments is an important property of free-living and pathogenic enteric bacteria. Salmonella enterica serovar Typhimurium possesses two general forms of inducible acid tolerance. One is evident in exponentially growing cells exposed to a sudden acid shock. The other is induced when stationary-phase cells are subjected to a similar shock. These log-phase and stationary-phase acid tolerance responses (ATRs) are distinct in that genes identified as participating in log-phase ATR have little to no effect on the stationary-phase ATR (I. S. Lee, J. L. Slouczewski, and J. W. Foster, J. Bacteriol. 176:1422-1426, 1994). An insertion mutagenesis strategy designed to reveal genes associated with acid-inducible stationary-phase acid tolerance (stationary-phase ATR) yielded two insertions in the response regulator gene ompR. The ompR mutants were defective in stationary-phase ATR but not log-phase ATR. EnvZ, the known cognate sensor kinase, and the porin genes known to be controlled by OmpR, ompC and ompF, were not required for stationary-phase ATR. However, the alternate phosphodonor acetyl phosphate appears to play a crucial role in OmpR-mediated stationary-phase ATR and in the OmpR-dependent acid induction of ompC. This conclusion was based on finding that a mutant form of OmpR, which is active even though it cannot be phosphorylated, was able to suppress the acid-sensitive phenotype of an ack pta mutant lacking acetyl phosphate. The data also revealed that acid shock increases the level of ompR message and protein in stationary-phase cells. Thus, it appears that acid shock induces the production of OmpR, which in its phosphorylated state can trigger expression of genes needed for acid-induced stationary-phase acid tolerance.

Acids↗
PubMed2005

Sustained exposure to the widely used herbicide atrazine: altered function and loss of neurons in brain monoamine systems.

The widespread use of atrazine (ATR) and its persistence in the environment have resulted in documented human exposure. Alterations in hypothalamic catecholamines have been suggested as the mechanistic basis of the toxicity of ATR to hormonal systems in females and the reproductive tract in males. Because multiple catecholamine systems are present in the brain, however, ATR could have far broader effects than are currently understood. Catecholaminergic systems such as the two major long-length dopaminergic tracts of the central nervous system play key roles in mediating a wide array of critical behavioral functions. In this study we examined the hypothesis that ATR would adversely affect these brain dopaminergic systems. Male rats chronically exposed to 5 or 10 mg/kg ATR in the diet for 6 months exhibited persistent hyperactivity and altered behavioral responsivity to amphetamine. Moreover, when measured 2 weeks after the end of exposure, the levels of various monoamines and the numbers of tyrosine hydroxylase-positive (TH+) and -negative (TH-) cells measured using unbiased stereology were reduced in both dopaminergic tracts. Acute exposures to 100 or 200 mg/kg ATR given intraperitoneally to evaluate potential mechanisms reduced both basal and potassium-evoked striatal dopamine release. Collectively, these studies demonstrate that ATR can produce neurotoxicity in dopaminergic systems that are critical to the mediation of movement as well as cognition and executive function. Therefore, ATR may be an environmental risk factor contributing to dopaminergic system disorders, underscoring the need for further investigation of its mechanism(s) of action and corresponding assessment of its associated human health risks.

Amphetamine↗
PubMed1993

[Changes in corneal astigmatism with aging].

Change in physiologic corneal astigmatism due to aging was studied. A series of 868 cases (1,660 eyes) was evaluated. These eyes were divided into 6 groups by age; A) below 40 years, B) in the 40's, C) in the 50's, D) in the 60's, E) in the 70's, and F) over 80. Corneal astigmatism was examined with an autokeratometer. In Group A, 88.5% had with-the-rule astigmatism (WTR), whereas only 3.7% had against-the-rule astigmatism (ATR). The cylindrical diopter (CD) of WTR was 1.29 +/- 0.73 D, which was significantly the largest among the groups. In Group C, WTR decreased to 55.9% and ATR increased to 22.9%. The CD of WTR also decreased to 0.85 +/- 0.47 D. In Group E, WTR was 31.4% and ATR was 49.3%. The CD of ATR increased to 0.88 +/- 0.70 D. In Group F, WTR was 19.9%, whereas ATR was 65.9%. The CD of ATR was 1.48 +/- 0.88 D, which was the largest among the groups. As such, WTR was dominant at younger ages, and ATR increased with aging at older ages. The CD of WTR decreased, and ATR increased, with aging.

Adult↗
PubMed1991

A symptomatological assessment of organophosphate-induced lethality in mice: comparison of atropine and clonidine protection.

A comprehensive symptomatological observational battery in conjunction with acute toxicity testing, evaluated with the method of a hyperbolic curve relating survival time (T) to dose (D), was used to characterize quantitatively the lethal toxicities of the organophosphorus (OP) compound, sarin, in mice. The experimental data observed with sarin (0.4-4.0 mg/kg s.c.), alone or in combination with atropine (ATR) (20 mg/kg i.p.), were plotted as a graph of D/T against D, a linearizing transformation of the hyperbolic function. This linearized plot gave two straight lines, deflecting at 1.2 mg/kg, in terms of latency to whole body tremor (BT) and loss of the righting reflex (LR). At lower lethal doses of sarin (0.4-1.2 mg/kg) with ATR pretreatment, the D/T vs. D curves of BT and LR were shifted in parallel to the left, while at high lethal doses (1.6-4.0 mg/kg) these curves interpolatedly converged. The sequelae and/or severity of symptoms were also comparatively different between the range of lower and high lethal doses as noted above. It has been claimed that the protective actions of ATR and clonidine (CLD) against the lethal effects of cholinesterase inhibitors are associated with different underlying mechanisms, i.e. presynaptic versus post-synaptic cholinergic inhibition. The protective effects of a single dose of ATR (20 mg/kg) and CLD (1.0 mg/kg), after 38 and 15 min of intraperitoneal pretreatment, respectively, alone or in combination, challenged with 2 x, 4x and 8x LD50's of sarin were also comparatively evaluated. ATR resulted in a nonsignificant increase in latency to onset of BT and LR. CLD significantly delayed the onset of these symptoms against all 3 dose levels of sarin intoxication, whereas ATR plus CLD additively increased the latency to the onset of these symptoms. The present results indicate that at lower dosages of sarin (less than or equal to 4 x LD50's) its mode of action appears to be mediated mainly by a/muscarinic mechanism, whereas at high doses it is mediated by some other non-specific actions superimposed on the cholinergic actions of sarin. The present study also lends support to the hypothesis of the existence of different forms of OP intoxication on the strength of lethal exposure. The possible mechanisms of both sarin lethality and ATR- and CLD-mediated protection are briefly discussed.

Animals↗
PubMed2001

Integration of Raman microscopy, differential interference contrast microscopy, and attenuated total reflection Fourier transform infrared spectroscopy to investigate chlorhexidine spatial and temporal distribution in Candida albicans biofilms.

Two spectroscopic techniques, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and Raman microscopy (RM), were used to characterize transport of chlorhexidine digluconate (CHG) in Candida albicans (CA) biofilms. Different (volumetric) regions of the biofilm are sampled by these two vibrational spectroscopies making them complementary techniques. Simple mathematical models were developed to analyze ATR-FTIR and RM data to obtain an effective diffusion coefficient describing transport through CA biofilms. CA biofilms were composed primarily of yeast and hyphal forms, with some pseudohyphae. Upper regions of biofilms that had become confluent, (i.e., biofilms that completely covered the germanium (Ge) substratum) were composed primarily of a tangled mass of hyphae with openings between germtubes about 10 to 50 microm across. Quantitative analysis of ATR-FTIR kinetic data curves indicated that the effective diffusion coefficient for transport of CHG through confluent biofilms about 200-microm thick was reduced 0.1 to 0.3 times compared to the diffusion coefficient for CHG in water. Effective diffusion coefficients obtained from analysis of RM data were consistently higher than those indicated by ATR-FTIR data suggesting that transport is more hindered in regions near the base of the biofilm than in the outer layers. Analysis of both ATR-FTIR and RM data obtained from thicker films indicated that adsorption of CHG to biofilm components was responsible for a substantial portion of the transport limitation imposed by the biofilm. Comparison of ATR-FTIR and RM data for both types of biofilms indicated that sites of CHG adsorption were more concentrated in the interfacial region than in the bulk biofilm. Comparison of results for ATR-FTIR and RM measurements suggests that these relatively thick CA biofilms can be modeled, for purposes of predicting transport, approximately as a homogeneous thin planar sheet. Thus, these biofilms offer a relatively tractable model system for initial investigations of the relation between antimicrobial transport and kinetics of antimicrobial action.

Anti-Bacterial Agents↗
PubMed2003

Is there a natural limit of the transformation rate of oral leukoplakia?

Recent reviews described a cumulative risk of 0-38% of oral leukoplakias (OL) to transform into oral squamous cell carcinoma (OSCC). The annual transformation rate (ATR) of OL into OSCC amounted up to 6.3%. To elucidate epidemiological consequences of varying ATR. Variations of the prevalence (1-2%) and ATR (0.5-4%) of OL were used to compute the proportional incidences of OSCC developing in OL. These were compared to the actual incidences of OSCC excerpted from European cancer registries. A ratio <50% of predicted to actual incidence overall indicated a plausible ATR. With an ATR>or=3%, the predicted incidences of OSCC would exceed the reported incidences in all countries. With an ATR<or=1%, the ratio of OSCC developed in OL to OSCC overall would be always lower than 50%. Based on present data, it was concluded that the ATR of OL into OSCC should not exceed 1%.

Carcinoma, Squamous Cell↗
PubMed2003

Characterization and quantitation of aprepitant drug substance polymorphs by attenuated total reflectance fourier transform infrared spectroscopy.

In this study, we report the use of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FT-IR) for the identification and quantitation of two polymorphs of Aprepitant, a substance P antagonist for chemotherapy-induced emesis. Mixtures of the polymorph pair were prepared by weight and ATR-FT-IR spectra of the powdered samples were obtained over the wavelength range of 700-1500 cm(-1). Significant spectral differences between the two polymorphs at 1140 cm(-1) show that ATR-FT-IR can provide definitive identification of the polymorphs. To investigate the feasibility of ATR-FT-IR for quantitation of polymorphic forms of Aprepitant, a calibration plot was constructed with known mixtures of the two polymorphs by plotting the peak ratio of the second derivative of absorbance spectra against the weight percent of form II in the polymorphic mixture. Using this novel approach, 3 wt % of one crystal form could be detected in mixtures of the two polymorphs. The accuracy of ATR-FT-IR in determining polymorph purity of the drug substance was tested by comparing the results with those obtained by X-ray powder diffractometry (XRPD). Indeed, polymorphic purity results obtained by ATR-FT-IR were found to be in good agreement with the predictions made by XRPD and compared favorably with actual values in the known mixtures. The present study clearly demonstrates the potential of ATR-FT-IR as a quick, easy, and inexpensive alternative to XRPD for the determination of polymorphic identity and purity of solid drug substances. The technique is ideally suited for polymorph analysis, because it is precise, accurate, and requires minimal sample preparation.

Drug Contamination↗
PubMed2005

Investigation of the potential utility of single-bounce attenuated total reflectance Fourier transform infrared spectroscopy in the analysis of distilled liquors and wines.

A new Fourier transform infrared (FTIR) spectroscopic method based on single-bounce attenuated total reflectance (SB-ATR) spectroscopy was developed for the analysis of distilled liquors and wines. For distilled liquors, a partial least-squares (PLS) calibration was developed for alcohol determination based on the SB-ATR/FTIR spectra of mixtures of ethanol and distilled water. An independent set of 12 different distilled liquor samples was predicted from the PLS calibration, and a standard deviation of the differences for accuracy (SDD(a)) between actual and predicted values of 0.142% (v/v) was obtained. The potential utility of SB-ATR/FTIR spectroscopy for the analysis of wines was initially evaluated based on a comparison with Fourier transform near-infrared (FT-NIR) spectroscopy and FTIR spectroscopy using a flow-through transmission cell. PLS calibrations for alcohol, total reducing sugars, total acidity and pH were developed using pre-analyzed wine samples (n = 28), and for SB-ATR/FTIR spectroscopy, the SDD(a) for the leave-one-out cross-validation statistics were of the order of 0.100% (v/v), 0.707 g L(-1), 0.189 g L(-1) (H2SO4), and 0.230, respectively. Overall, the SB-ATR/FTIR results were better than those obtained using FT-NIR spectroscopy and comparable to those obtained with transmission FTIR spectroscopy. A PLS calibration based on preanalyzed wine samples (n = 72) for the prediction of 11 different components and parameters in wines by SB-ATR/FTIR spectroscopy was subsequently developed and validated using an independent sample set (n = 77). Good coefficients of correlation between the reference and predicted values for the validation set were obtained for most of the components and parameters except citric acid, volatile acids, and total SO2. The results of this study demonstrate the suitability of SB-ATR/FTIR spectroscopy for the routine analysis of distilled liquors and wines.

Alcoholic Beverages↗