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1.
Public Health ; 160: 33-40, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29729530

ABSTRACT

OBJECTIVES: To determine whether multiple viewings of one's ultraviolet (UV) facial photo differentially affects subsequent sun protection behaviors relative to a single viewing. STUDY DESIGN: Pretest-posttest control group. METHODS: Southern California college students (N = 151) were randomly assigned to be shown their UV facial photo one time, multiple times over the course of 2 weeks, or not at all. Emotional reactions, perceived susceptibility to skin damage, and sun protection intentions were assessed immediately, and sun protection behaviors were assessed during a surprise telephonic follow-up 1 month later. RESULTS: Immediately after viewing a UV photo of their face, participants reported significantly greater perceived susceptibility to skin damage, greater intentions to engage in future sun protection, and more negative emotions than those who had not seen a UV photo. Moreover, 1 month later, those who had viewed their UV photo were less likely to report having sunbathed and reported significantly greater sun protection than did controls. There were no differences in sun protection behaviors between those who had been shown their UV photo only once during the initial intervention session and those who had been sent their UV photo several times thereafter. However, among those who had been sent their UV photo several times, those who reported having viewed their photo on additional occasions reported significantly greater sun protection behaviors than those who had not. CONCLUSIONS: Being randomly assigned to view a UV facial photo multiple times generally neither strengthened nor weakened effects on subsequent sun protection behaviors relative to being shown the photo just once. However, among those who were sent their photo and thus had the option of viewing it more often than they had been assigned to, those who chose to view their photo more frequently also engaged in more sun protection behaviors.


Subject(s)
Face/radiation effects , Health Behavior , Photography/statistics & numerical data , Students/psychology , Ultraviolet Rays/adverse effects , Adolescent , Adult , California , Female , Follow-Up Studies , Humans , Intention , Male , Middle Aged , Students/statistics & numerical data , Young Adult
2.
PDA J Pharm Sci Technol ; 70(3): 191-207, 2016.
Article in English | MEDLINE | ID: mdl-26865679

ABSTRACT

Dual-chamber systems can offer self-administration and home care use for lyophilized biologics. Only a few products have been launched in dual-chamber systems so far-presumably due to dual-chamber systems' complex and costly drug product manufacturing process. Within this paper, two improved processes (both based on tray filling technology) for freeze-drying pharmaceuticals in dual-chamber systems are described. Challenges with regards to heat transfer were tackled by (1) performing the freeze-drying step in a needle-down orientation in combination with an aluminum block, or (2) freeze-drying the drug product "externally" in a metal cartridge with subsequent filling of the lyophilized cake into the dual-chamber system. Metal-mediated heat transfer was shown to be efficient in both cases and batch (unit-to-unit) homogeneity with regards to sublimation rate was increased. It was difficult to influence ice crystal size using different methods when in use with an aluminum block due to its heat capacity. Using such a metal carrier implies a large heat capacity leading to relatively small ice crystals. Compared to the established process, drying times were reduced by half using the new processes. The drying time was, however, longer for syringes compared to vials due to the syringe design (long and slim). The differences in drying times were less pronounced for aggressive drying cycles. The proposed processes may help to considerably decrease investment costs into dual-chamber system fill-finish equipment. LAY ABSTRACT: Dual-chamber syringes offer self-administration and home care use for freeze-dried pharmaceuticals. Only a few products have been launched in dual-chamber syringes so far-presumably due to their complex and costly drug product manufacturing process. In this paper two improved processes for freeze-drying pharmaceuticals in dual-chamber syringes are described. The major challenge of freeze-drying is to transfer heat through a vacuum. The proposed processes cope with this challenge by (1) freeze-drying the drug product in the syringe in an orientation in which the product is closest to the heat source, or (2) freeze-drying the drug product outside the syringe in a metal tube. The latter requires filling the freeze-dried product subsequently into the dual-chamber syringe. Both processes were very efficient and promised to achieve similar freeze-drying conditions for all dual-chamber syringes within one production run. The proposed processes may help to considerably decrease investment costs into dual-chamber syringe fill-finish equipment.


Subject(s)
Biological Products/chemistry , Biological Products/standards , Glass/standards , Syringes/standards , Technology, Pharmaceutical/methods , Freeze Drying/methods , Freeze Drying/trends , Pharmaceutical Preparations/chemistry , Pharmaceutical Preparations/standards , Technology, Pharmaceutical/trends
3.
Int J Sports Med ; 37(1): 6-11, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26528944

ABSTRACT

Assessing an individual's physical fitness can usually be achieved through evaluating lactate or ventilatory thresholds. Unfortunately, the detection of ventilatory thresholds still requires uncomfortable mass flow sensors and a laboratory setting. Therefore, this study aimed to evaluate a ventilatory inflection point (VIP) derived from thorax expansion as a useful surrogate to assess an individual's physical fitness under field conditions. 348 and 107 ramp tests have been selected respectively to examine validity and retest variability of VIP. The individual anaerobic threshold (IAT) determined by means of blood lactate sampling was used as reliable rationale for evaluation. Calibrated respiratory inductance plethysmography (RIP) was utilized to derive ventilation from thorax expansion during the ramp test. An automated software routine was applied to detect the VIP. Speed, heart rate and ventilation at the VIP correlated significantly to corresponding values at IAT (r=0.840, 0.876, 0.933). Non-systematic differences between repeated testing ranged within ±1.15 km·h(-1), ±8.74 b·min(-1) and ±12.69 l·min(-1) (±1.96 SD). The timing of VIP is not solely dependent on the aerobic capacity and might instead quantify an individual's physical fitness in terms of the efficiency of the compensative and supportive ventilatory response during increased exercise intensities.


Subject(s)
Exercise Test/methods , Physical Fitness/physiology , Respiration , Thorax/physiology , Adult , Anaerobic Threshold/physiology , Female , Heart Rate/physiology , Humans , Lactic Acid/blood , Male , Movement , Plethysmography , Pulmonary Gas Exchange , Reproducibility of Results
4.
Pharm Res ; 32(10): 3201-12, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25893328

ABSTRACT

PURPOSE: Antimicrobial preservatives are known to interact with proteins and potentially affect their stability in aqueous solutions. In this systematic study, the interactions of a model peptide with three commonly used preservatives, benzyl alcohol, phenol and m-cresol, were evaluated. METHODS: The impact on peptide oligomerization was studied using GC-MALS, SEC-MALS and DLS, antimicrobial efficiency of different formulations were studied using the Ph. Eur. antimicrobial efficacy test, and the molecular adsorption of preservative molecules on reversible peptide oligomers was monitored using NMR. RESULTS: The hydrodynamic radius and molar mass of the peptide oligomers was shown to clearly increase in the presence of m-cresol but less significantly with phenol and benzyl alcohol. The increase in size was most likely caused by peptide self-interactions becoming more attractive, leading to reversible oligomerization. On the other hand, increasing the concentration of peptide in multi-dose formulations led to reduced molecular mobility and decreased antimicrobial efficacy of all preservatives. CONCLUSIONS: Peptide-preservative interactions not only affect peptide self-interactions, but also antimicrobial efficiency of the preservatives and are thus of significant relevance. Adsorption of preservatives on oligomeric states of peptides is proposed as a mechanism to explain this reduced antimicrobial efficacy.


Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Bacteria/drug effects , Peptides/chemistry , Peptides/pharmacology , Preservatives, Pharmaceutical/chemistry , Adsorption , Chemistry, Pharmaceutical/methods , Cresols/chemistry , Excipients/chemistry
5.
Fortschr Neurol Psychiatr ; 83(4): 221-31, 2015 Apr.
Article in German | MEDLINE | ID: mdl-25893495

ABSTRACT

Among the new psychoactive substances (NPS), most frequently synthetic cannabinoids (SCBs) have been found in Europe. These are sold as active compounds in e. g. so-called "herbal blends". When inhaled or ingested, besides intoxication symptoms, as they occur with heavy cannabis use (e. g., tachycardia, myocardial infarction, confusion, hallucinations, panic attacks, and paranoia), harmful effects (severe agitation, coma, catatonic stupor, hypertension, cardiac arrhythmia, dyspnoea, seizures, myoclonus, rhabdomyolysis, hyperthermia, diaphoresis, acute kidney injury, vomiting, headache, and hypokalemia) arise, which are mostly unusual about cannabis use. In addition, the first cases of addiction and death related to SCBs have been reported. Taking into account the newest literature and using an algorithm with two main criteria (addiction potential, toxicity), the authors made a first attempt to rank the personal health hazard of SCBs in comparison to that of other psychoactive drugs. Accordingly, the relative health hazard of SCBs is found to be somewhat higher than that of cannabis and lower than that of synthetic cathinones ("bath salts"). However, the toxicity of SCBs, is significantly greater than the toxicity of cannabis, thus being similar to that of synthetic cathinones and benzodiazepines. The addiction potential appears to be lower than that of synthetic cathinones, benzodiazepines, or cannabis. Due to the fluctuation of substances and the availability in internet resources, legislation is facing a serious "hare-hedgehog" problem to control the manufacture, trade and possession of SCBs.


Subject(s)
Cannabinoids/adverse effects , Marijuana Abuse/epidemiology , Alkaloids/adverse effects , Cannabinoids/pharmacology , Cannabinoids/toxicity , Designer Drugs , Europe/epidemiology , Humans , Illicit Drugs , Marijuana Abuse/complications , Marijuana Abuse/physiopathology , Marijuana Abuse/psychology , Receptors, Cannabinoid/drug effects
6.
Int J Sports Med ; 36(1): 29-34, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25254900

ABSTRACT

The between-days variability in ascertained gain factors for calibration of a wearable respiratory inductance plethysmograph (RIP) and validity thereof for the repeated use during exercise were examined. Consecutive 5-min periods of standing still, slow running at 8 km·h(-1), fast running at 14 km·h(-1) (male) or 12 km·h(-1) (female) and recovery were repeated by 10 healthy subjects on 5 days. Breath-by-breath data were recorded simultaneously by flow meter and RIP. Gain factors were determined individually for each trial (CALIND) via least square regression. Reliability and variability in gain factors were quantified respectively by intraclass correlation coefficients (ICC) and limits of agreement. Within a predefined error range of ±20% the amount of RIP-derived tidal volumes after CALIND was compared to corresponding amounts when gain factors of the first trial were applied on the following 4 trials (CALFIRST). ICC ranged within 0.96 and 0.98. The variability in gain factors (up to ± 24.06%) was reduced compensatively by their sum. Amounts of breaths within the predefined error range did not differ between CALIND and (CALFIRST) (P>0.32). The between-days variability of gain factors for a wearable RIP-device does not show impaired reliability in further derived tidal volumes.


Subject(s)
Monitoring, Physiologic/instrumentation , Plethysmography/instrumentation , Respiration , Running/physiology , Adult , Anthropometry , Calibration , Female , Humans , Male , Middle Aged , Monitoring, Physiologic/standards , Plethysmography/standards , Reproducibility of Results , Tidal Volume , Young Adult
8.
Thalamus Relat Syst ; 3(2): 89-113, 2005 Jun 01.
Article in English | MEDLINE | ID: mdl-19305519

ABSTRACT

Thalamic relay neurons have homogeneous, adult-like firing properties and similar morphology by 12 days postnatally (PN 12). Parafascicular (Pf) neurons have a different morphology compared with typical thalamic relay neurons, but the development of their electrophysiological properties is not well studied. Intracellular recordings in PN 12-50 Pf neurons revealed several heterogeneous firing patterns different from those in thalamic relay neurons. Two types of cells were identified: Type I cells displayed a fast afterhyperpolarization (AHP) followed by a large-amplitude, slow AHP; whereas Type II cells had only a fast AHP. These cell types had overlapping membrane properties but differences in excitability. Some properties of Pf neurons were adult-like by PN 12, but, unlike thalamic relay neurons, there were significant maturational changes thereafter, including decreased action potential (AP) duration, increased fast AHP amplitude and increased excitability. Pf neurons did not exhibit rhythmic bursting and generally lacked low-threshold spike (LTS) responses that characterize thalamic relay neurons. Pf neurons exhibited nonlinear I-V relationships, and only a third of the cells expressed the time and voltage-dependent hyperpolarization activated (Ih) current, which declined with age. These results indicate that the morphological differences between Pf neurons and typical thalamic relay neurons are paralleled by electrophysiological differences, and that Pf membrane properties change during postnatal development.

9.
Article in English | MEDLINE | ID: mdl-12726850

ABSTRACT

Kavain metabolism in humans was the target of this current investigation. In the present study a high-performance liquid chromatographic (HPLC-DAD) assay method for the simultaneous determination of kavain and its main metabolites (p-hydroxykavain, p-hydroxy-5,6-dehydrokavain and p-hydroxy-7,8-dihydrokavain) in serum and urine was developed and validated. The metabolites were mainly excreted in the form of their conjugates. All kavain metabolites were detectable in serum and urine, except for p-hydroxy-7,8-dihydrokavain, which was found in urine only. Confirmation of the results and identification of the metabolites were performed by LC-MS or LC-MS-MS. Kinetics of kavain and its metabolites in serum were investigated after administration of a single oral dose (800 mg kavain). Within 1 and 4 h after uptake, the serum concentrations ranged between 40 and 10 ng/ml for kavain, 300 and 125 ng/ml for p-hydroxykavain, 90 and 40 ng/ml for o-desmethyl-hydroxy-5,6-dehydrokavain, and 50 and 30 ng/ml for 5,6-dehydrokavain.


Subject(s)
Chromatography, High Pressure Liquid/methods , Pyrones/pharmacokinetics , Administration, Oral , Biotransformation , Humans , Pyrones/administration & dosage , Pyrones/blood , Pyrones/urine , Reference Standards , Reproducibility of Results
10.
Forensic Sci Int ; 121(1-2): 126-33, 2001 Sep 15.
Article in English | MEDLINE | ID: mdl-11516897

ABSTRACT

Gas chromatography with nitrogen/phosphorus sensitive detection (GC/PND) and electron impact mass spectrometry (GC/MS) with selected ion monitoring provides a simple, rapid and sensitive method for the determination of organophosphate pesticides (OPs). A selective single-step extraction of 23 different OPs in urine, blood, serum and food samples (baby food, soft drinks and instant soups suspected of contamination from a blackmailing scare) is described. The OPs were extracted with 1ml toluene (with and without addition of mevinphos as internal standard), using a 0.7ml aliquot of urine, blood or serum sample. Food samples (0.2g) were homogenised with water (0.5ml) before extraction. An amount of 1microl of the toluene phase (extraction supernatant) was analysed directly by GC/PND and GC/MS.The method was validated using spiked human serum. The OPs were mixed with serum containing 10mg/ml disodium ethane diamine tetraacetic acid disodium salt (EDTA disodium salt) and stored up to 10 days at 4 and -20 degrees C, respectively. The recovery rates of OPs in freshly spiked human plasma ranged between 50% (dimethoate) and 133% (dialifos). OPs in plasma proved to be stable at -20 degrees C. Their levels decreased only slightly after storage at 4 degrees C.


Subject(s)
Food Contamination/analysis , Gas Chromatography-Mass Spectrometry/methods , Insecticides/blood , Organophosphorus Compounds , Animals , Humans , Insecticides/analysis , Insecticides/urine , Rats
11.
Mutat Res ; 461(4): 289-99, 2001 Jan 05.
Article in English | MEDLINE | ID: mdl-11104905

ABSTRACT

Like hydroxyl radicals, alkoxyl radicals have been implicated in the generation of cellular oxidative DNA damage under physiological conditions; however, their genotoxic potential has not yet been established. We have analyzed the DNA damage induced by a photochemical source of tert-butoxyl radicals, the water soluble peroxy ester [4-(tert-butyldioxycarbonyl)benzyl]triethylammonium chloride (BCBT), using various repair endonucleases as probes. The irradiation (UV(360)) of BCBT in the presence of bacteriophage PM2 DNA was found to generate a DNA damage profile that consisted mostly of base modifications sensitive to the repair endonuclease Fpg protein. Approximately 90% of the modifications were identified as 7,8-dihydro-8-oxoguanine (8-oxoGua) residues by HPLC/ECD analysis. Oxidative pyrimidine modifications (sensitive to endonuclease III), sites of base loss (AP sites) and single-strand breaks were only minor modifications. Experiments with various scavengers and quenchers indicated that the DNA damage by BCBT+UV(360) was caused by tert-butoxyl radicals as the ultimate reactive species. The mutagenicity associated with the induced damage was analyzed in the gpt gene of plasmid pSV2gpt, which was exposed to BCBT+UV(360) and subsequently transfected into Escherichia coli. The results were in agreement with the specific generation of 8-oxoGua. Nearly all point mutations (20 out of 21) were found to be GC-->TA transversions known to be characteristic for 8-oxoGua. In conclusion, alkoxyl radicals generated from BCBT+UV(360) induce 8-oxoGua in DNA with a higher selectivity than any other reactive oxygen species analyzed so far.


Subject(s)
Alcohols/pharmacology , DNA Damage , DNA, Viral/metabolism , Guanine/analogs & derivatives , Guanine/metabolism , Mutagenesis , Proteins , Alcohols/metabolism , Bacterial Proteins/genetics , Base Sequence , Corticoviridae/genetics , DNA, Viral/drug effects , DNA, Viral/radiation effects , Escherichia coli Proteins , Molecular Sequence Data , Pentosyltransferases , Plasmids/genetics , Quaternary Ammonium Compounds/pharmacology , Ultraviolet Rays
12.
Mutat Res ; 461(2): 145-56, 2000 Oct 16.
Article in English | MEDLINE | ID: mdl-11018587

ABSTRACT

We have analyzed the recognition by various repair endonucleases of DNA base modifications induced by three oxidants, viz. [4-(tert-butyldioxycarbonyl)benzyl]triethylammonium chloride (BCBT), a photochemical source of tert-butoxyl radicals, disodium salt of 1,4-etheno-2,3-benzodioxin-1,4-dipropanoic acid (NDPO(2)), a chemical source of singlet oxygen, and riboflavin, a type-I photosensitizer. The base modifications induced by BCBT, which were previously shown to be mostly 7,8-dihydro-8-oxoguanine (8-oxoGua) residues, were recognized by Fpg and Ogg1 proteins, but not by endonuclease IIII, Ntg1 and Ntg2 proteins. In the case of singlet oxygen induced damage, 8-oxoGua accounted for only 35% of the base modifications recognized by Fpg protein. The remaining Fpg-sensitive modifications were not recognized by Ogg1 protein and relatively poor by endonuclease III, but they were relatively good substrates of Ntg1 and Ntg2. In the case of the damage induced by photoexcited riboflavin, the fraction of Fpg-sensitive base modifications identified as 8-oxoGua was only 23%. In contrast to the damage induced by singlet oxygen, the remaining lesions were not only recognized by Ntg1 and Ntg2 proteins and (relatively poor) by endonuclease III, but also by Ogg1 protein. The analysis of the mutations observed after transfection of modified plasmid pSV2gpt into Escherichia coli revealed that all agents induced near exclusively GC-->TA and GC-->CG transversions, the numbers of which were correlated with the numbers of 8-oxoGua residues and Ntg-sensitive modifications, respectively. In conclusion, both singlet oxygen and the type-I photosensitizer riboflavin induce predominantly oxidative guanine modifications other than 8-oxoGua, which most probably give rise to GC-->CG transversions and in which eukaryotic cells are substrates of Ntg1 and Ntg2 proteins.


Subject(s)
DNA Damage , DNA, Viral/metabolism , Endonucleases/metabolism , Guanine/analogs & derivatives , Oxygen/metabolism , Proteins , Riboflavin/physiology , Bacterial Proteins/genetics , Base Sequence , Corticoviridae/genetics , DNA Ligases/metabolism , DNA, Viral/radiation effects , Escherichia coli Proteins , Guanine/metabolism , Light , Molecular Sequence Data , Mutation/radiation effects , Oxidation-Reduction , Pentosyltransferases , Substrate Specificity
13.
Mutat Res ; 435(1): 89-101, 1999 Sep 13.
Article in English | MEDLINE | ID: mdl-10526220

ABSTRACT

The oxidative DNA damage induced by the polar photosensitizer Ro19-8022 in the presence of light was studied and correlated with the associated mutagenicity. Both in isolated DNA and AS52 Chinese hamster ovary cells, photoexcited Ro19-8022 gave rise to a DNA damage profile that was similar to that caused by singlet oxygen: base modifications sensitive to the repair endonuclease Fpg protein, which according to high-performance liquid chromatography (HPLC) analysis were predominantly 8-hydroxyguanine (8-oxoG) residues, were generated in much higher yield than single-strand breaks, sites of base loss (AP sites) and oxidative pyrimidine modifications sensitive to endonuclease III. Fifty percent of the Fpg-sensitive modifications were repaired within 2 h. Under conditions that induced 10 Fpg-sensitive modifications per 10(6) bp (six 8-oxoG residues per 10(6) bp), approximately 60 mutations per 10(6) cells were induced in the gpt locus of the AS52 cells. A rather similar mutation frequency was observed when a plasmid carrying the gpt gene was exposed to Ro19-8022 plus light under cell-free conditions and subsequently replicated in bacteria. Sequence analysis revealed that GC-->TA and GC-->CG transversions accounted for 90% of the base substitutions. A significant generation of micronuclei was detectable in AS52 cells exposed to the photosensitizer plus light as well.


Subject(s)
DNA Damage , Mutation , Oxidative Stress , Photosensitizing Agents/pharmacology , Pyrrolidines/pharmacology , Quinolizines/pharmacology , Animals , Base Sequence , CHO Cells , Cell-Free System , Cricetinae , DNA, Viral/drug effects , Molecular Sequence Data
14.
J Cardiopulm Rehabil ; 19(3): 170-7, 1999.
Article in English | MEDLINE | ID: mdl-10361648

ABSTRACT

BACKGROUND: This study evaluated the relative effects on compliance with recommended lifestyle changes of two experimental videotapes that involved different approaches for preparing coronary artery bypass graft (CABG) patients for the posthospital recovery period. The tapes differed in the extent to which they portrayed the recovery period as a steady, forward progression versus a series of "ups and downs." METHODS: Two hundred sixteen male and female CABG patients were assigned randomly either to view one of the two videotapes before discharge from the hospital or to receive only the standard discharge preparation provided by the hospital. All patients completed measures of anxiety and self-efficacy at discharge, 1 month and 3 months after discharge from the hospital. Patients also completed measures of dietary fat consumption and activity level 1 and 3 months after discharge. RESULTS: Relative to controls, patients who viewed either of the videotapes before hospital release reported higher self-efficacy for adhering to the recommended low-fat diet both at discharge and 1 month after surgery. Viewing either of the videotapes also resulted in significantly less dietary fat intake 1 month after hospital release compared with controls. Patients who viewed the tape that portrayed the recovery period as consisting of ups and downs also reported significantly more frequent moderate exercise at 1 month and more frequent strenuous exercise 3 months after discharge. CONCLUSIONS: The experimental videotapes proved to be an effective method for increasing dietary and exercise compliance during the first 3 months after CABG.


Subject(s)
Coronary Artery Bypass , Coronary Disease/rehabilitation , Diet, Fat-Restricted , Exercise Therapy , Patient Discharge , Patient Education as Topic/methods , Video Recording , Adult , Aged , Coronary Disease/diet therapy , Coronary Disease/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Patient Compliance , Treatment Outcome
15.
Carcinogenesis ; 20(2): 333-7, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10069473

ABSTRACT

The effects of thiols, ascorbic acid and thermal stress on the basal (steady-state) levels of oxidative DNA base modifications were studied. In various types of untreated cultured mammalian cells, the levels of total glutathione were found to be inversely correlated with the levels of DNA base modifications sensitive to the repair endonuclease Fpg protein, which include 8-hydroxyguanine (8-oxoG). A depletion of glutathione by treatment with buthionine sulphoximine increased the steady-state level in AS52 Chinese hamster cells by approximately 50%. However, additional thiols in the culture medium did not reduce the level of Fpg-sensitive base modifications: 0-10 mM N-acetylcysteine had no effect, whereas cysteine ethylester even increased the oxidative DNA damage at concentrations >0.1 mM. Similarly, ascorbic acid (0-20 mM) failed to reduce the steady-state levels. When AS52 cells were grown at elevated temperature (41 degrees C), the steady-state level of the oxidative DNA modifications increased by 40%, in spite of a concomitant 1.6-fold increase of the cellular level of total glutathione. Depletion of glutathione at 41 degrees C nearly doubled the already elevated level of oxidative damage. A constitutive expression of the heat-shock protein Hsp27 in L929 mouse fibrosarcoma cells at 37 degrees C increased the glutathione level by 60%, but had little effect on the level of oxidative DNA damage.


Subject(s)
DNA Damage , Glutathione/metabolism , N-Glycosyl Hydrolases/metabolism , Oxidative Stress , Animals , Buthionine Sulfoximine/pharmacology , Cell Line , Cricetinae , DNA-Formamidopyrimidine Glycosylase , Enzyme Inhibitors/pharmacology , Glutathione/drug effects , HeLa Cells , Heat-Shock Proteins/metabolism , Hot Temperature , Humans , Mice , Oxidative Stress/drug effects , Tumor Cells, Cultured
16.
Ann Behav Med ; 20(1): 39-46, 1998.
Article in English | MEDLINE | ID: mdl-9755351

ABSTRACT

This study evaluated the relative effects of three experimental videotapes that involved different approaches for preparing coronary artery bypass graft (CABG) patients for surgery and the inhospital recovery period. One of the tapes conveyed information via a health care expert only. The other two featured the same health care expert and also included clips of interviews with patient models. These latter two tapes differed in the extent to which they portrayed the recovery period as a steady, forward progression or as consisting of "ups and downs". Two hundred fifty-eight male CABG patients were randomly assigned to view one of the three videotapes on the evening prior to surgery or to a control condition. Overall, patients who viewed any of the videotapes felt significantly better prepared for the recovery period, reported higher self-efficacy for using the incentive spirometer and for speeding their recovery, performed more repetitions with their incentive spirometer each time they used it postoperatively, had shorter intensive care unit stays, and were released from the hospital more quickly than patients in the control condition. There was also evidence that patients' self-efficacy beliefs for speeding recovery directly mediated the effects of the videotapes on length of stay both in the intensive care unit and in the hospital.


Subject(s)
Coronary Artery Bypass/psychology , Patient Education as Topic , Self Efficacy , Videotape Recording , Adult , Aged , Aged, 80 and over , Coronary Artery Bypass/rehabilitation , Health Behavior , Humans , Male , Middle Aged , Patient Compliance/psychology , Self Care/psychology
17.
Eur J Cancer ; 34(5): 694-8, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9713276

ABSTRACT

The success of treatment for children with cancer has resulted in a growing population of adult survivors, yet these individuals may be at risk of serious long-term health problems as a result of the treatment they have received. This study explores the pattern of morbidity within a population of 290 adult survivors of cancer in childhood assessed at a median of over 15 years from diagnosis. Acute lymphoblastic leukaemia (33%) and Hodgkin's disease (15%) were the most common primary diagnoses represented. 85% of the whole group had received treatment with chemotherapy, 81% with radiotherapy, 48% with significant surgery and 28% with all three modalities. Overall, 58% of the survivors had at least one 'chronic medical problem' and 32%, two or more. Infertility (14%), nephrectomy (11%), thyroid hormone deficiency (9%), visual handicap (9%), sex hormone (7%) and growth hormone (7%) replacement therapy were the most common problems. Compliance with long term follow-up was good and an audit of an unselected sub group of all the survivors in the study showed that 84% had attended for surveillance over a period of 1 year, accounting for 222 visits of follow up clinics: 15% were also attending other specialist follow-up including psychiatry, orthopaedic, endocrine, dental and cardiac clinics. In conclusion, survivors of cancer in childhood experience actual or potential threats to future health. More than half have at least one chronic medical problem and demonstrate a significant use of medical resources. These data support the need for the continuing follow-up of survivors of cancer in childhood into adult life and the provision of the resources to do so. Optimal patterns of care and future approaches to the reduction of sequelae in future generations of survivors are discussed.


Subject(s)
Health Status , Neoplasms/mortality , Survivors , Adolescent , Adult , Age of Onset , Child , Child, Preschool , Chronic Disease , England/epidemiology , Female , Follow-Up Studies , Hodgkin Disease/mortality , Hodgkin Disease/therapy , Hospitalization/statistics & numerical data , Humans , Infant , Infant, Newborn , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy
18.
Free Radic Res ; 29(6): 585-94, 1998 Dec.
Article in English | MEDLINE | ID: mdl-10098463

ABSTRACT

Purified repair endonucleases such as Fpg protein, endonuclease III and IV allow a very sensitive quantification of various types of oxidative DNA modifications in mammalian cells. By means of these assays, the numbers of base modifications sensitive to Fpg protein, which include 8-hydroxyguanine (8-oxoG), were determined to be less than 0.3 per 10(6) bp in several types of untreated cultured mammalian cells and human lymphocytes and less than 10 per 10(6) bp in mitochondrial DNA from rat and porcine liver. Oxidative 5,6-dihydropyrimidine derivatives sensitive to endonuclease III and sites of base loss sensitive to endonuclease IV or exonuclease III were much less frequent than Fpg-sensitive modifications. Here, we summarize our indications that all Fpg-sensitive modifications are recognized under the assay conditions and that on the other hand there is no artifactual generation of oxidative damage during the analysis. In addition, we show that the steady-state levels of Fpg-sensitive modifications in human lymphocytes and in two mammalian cell lines were higher in proliferating than in resting (confluent) cells. Only some of the Fpg-sensitive base modifications induced by various oxidants are 8-oxoG residues, as demonstrated for the damage under cell-free conditions. The percentage was dependent on the species ultimately responsible for the DNA damage and was approx. 40% in the case of hydroxyl radicals and peroxynitrite, 75% for type II photosensitizers (reacting via singlet oxygen) and only 20-30% in the case of type I photosensitizers such as riboflavin and acridine orange, which are assumed to react directly with the DNA.


Subject(s)
Biochemistry/methods , Chromatography, High Pressure Liquid/methods , DNA Repair , DNA/metabolism , Deoxyribonuclease (Pyrimidine Dimer) , Escherichia coli Proteins , N-Glycosyl Hydrolases/metabolism , Animals , Base Pairing/drug effects , CHO Cells/cytology , CHO Cells/drug effects , CHO Cells/metabolism , Carbon-Oxygen Lyases/chemistry , Carbon-Oxygen Lyases/metabolism , Cell Division , Cricetinae , DNA-(Apurinic or Apyrimidinic Site) Lyase , DNA-Formamidopyrimidine Glycosylase , Deferoxamine/chemistry , Deoxyribonuclease IV (Phage T4-Induced) , Dimethyl Sulfoxide/chemistry , Endodeoxyribonucleases/chemistry , Endodeoxyribonucleases/metabolism , Guanosine/analogs & derivatives , Guanosine/analysis , Guanosine/metabolism , HeLa Cells/drug effects , HeLa Cells/metabolism , Humans , Mammals , N-Glycosyl Hydrolases/chemistry , Oxidants/pharmacology , Oxidation-Reduction , Photosensitizing Agents/pharmacology
19.
Biochem Biophys Res Commun ; 237(1): 68-73, 1997 Aug 08.
Article in English | MEDLINE | ID: mdl-9266831

ABSTRACT

Intracellular recording techniques were used to study the effects of the cholesterol oxide, 25-hydroxycholesterol (25-OH-Chol), on gamma-aminobutyric acid (GABA) receptor-mediated inhibitory postsynaptic potentials (IPSPs) in brain slices of the rat lateral septum. Superfusion of 25-OH-Chol increased the peak amplitude of the GABAa IPSP in more than half of the neurons tested, many of which exhibited a similar increase in the GABAb IPSP. However, some neurons exhibited a gradual decrease in input resistance and a selective reduction or blockade of the GABAb IPSP during prolonged exposure. Cholesterol partly mimicked the effects of 25-OH-Chol. These findings indicate that 25-OH-Chol can selectively reduce or block metabotropic GABAb while sparing ionotropic GABAa receptor-mediated synaptic inhibition. Our results indicate that brain slices can be used to study the effects of short term alterations in cholesterol on the excitability and synaptic integration properties of neurons.


Subject(s)
Brain/physiology , Hydroxycholesterols/pharmacology , Neurons/physiology , Receptors, GABA-A/physiology , Receptors, GABA-B/physiology , Synapses/physiology , Synaptic Transmission/drug effects , Animals , In Vitro Techniques , Neurons/drug effects , Rats , Rats, Sprague-Dawley , Receptors, GABA-A/drug effects , Receptors, GABA-B/drug effects , Synapses/drug effects
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