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Biomedical subjects

M Friedman

Publications and source records attributed to M Friedman.

At least 19 recordsLinked to original sources
PubMed2006

Acrylamide, an in vivo thyroid carcinogenic agent, induces DNA damage in rat thyroid cell lines and primary cultures.

Chronic treatment of rats with acrylamide induces various tumors among which thyroid tumors are the most frequent. The aim of the present study was to develop an in vitro model of acrylamide action on thyroid cells to allow the investigation of the mechanism of this tumorigenic action. The first part of the study considered as targets, characteristics of thyroid metabolism, which could explain the thyroid specificity of acrylamide action: the cAMP mitogenic effect and the important H2O2 generation by thyroid cells. However, acrylamide did not modulate H2O2 or cAMP generation in the thyroid cell models studied. No effect on thyroid cell proliferation was observed in the rat thyroid cell line FRTL5. On the other hand, as shown by the comet assay, acrylamide induced DNA damage, as the positive control H2O2 in the PC Cl3 and FRTL5 rat thyroid cell lines, as well as in thyroid cell primary cultures. The absence of effect of acrylamide on H2AX histone phosphorylation suggests that this effect does not reflect the induction of DNA double strand breaks. DNA damage leads to the generation of mutations. It is proposed that such mutations could play a role in the carcinogenic effect of acrylamide. The mechanism of this effect can now be studied in this in vitro model.

Acrylamide↗
PubMed2006

In vitro assessment of antimicrobial peptides as potential agents against several oral bacteria.

BACKGROUND: Antimicrobial peptides are components of the innate immunity that play an important role in systemic and oral health. OBJECTIVES: The antibacterial activity of the amphibian-derived K4 -S4(1-15)a antimicrobial peptide was tested against oral pathogens associated with caries and periodontitis and compared with the activities of the human-derived antimicrobial peptides LL-37 and dhvar4a. METHODS: Growth inhibition of planktonic bacteria was tested using standard microdilution assays. Live/Dead staining followed by confocal scanning laser microscopy (CSLM) was used to determine the bactericidal effect of K4 -S4(1-15)a on Streptococcus mutans attached to a glass surface or grown as biofilm. RESULTS: The cariogenic species S. mutans, Streptococcus sobrinus, Lactobacillus paracasei and Actinomyces viscosus were resistant to LL-37 found in the oral cavity. Porphyromonas gingivalis was the species most resistant to the three tested peptides. K4 -S4(1-15)a demonstrated the highest activity against the tested planktonic bacteria. In addition, K4 -S4(1-15)a was bactericidal to surface-attached S. mutans as well as to S. mutans biofilms grown in vitro. However, surface attachment increased S. mutans resistance to the antimicrobial peptide. CONCLUSIONS: Our results support growing evidence suggesting the use of antimicrobial peptides for prevention and treatment of oral disease.

Anti-Bacterial Agents↗
PubMed2006

Boys with high body masses have an increased risk of developing asthma: findings from the National Longitudinal Survey of Youth (NLSY).

OBJECTIVE: To determine the relation between body mass index and the development of asthma in children. DESIGN: Prospective study of 4393 asthma-free children followed for up to 14 years. SETTING: Children of participants in the National Longitudinal Survey of Youth. METHODS: Analysis was limited to children who were followed from birth and were asthma-free during the first 24 months of life. The outcome was the development of asthma during follow-up (incident asthma). Body mass index (BMI) was our main predictor of interest. Survival analyses, using time to development of asthma as the main endpoint, were stratified by sex and controlled for race/ethnicity, poverty status, and prenatal maternal smoking. RESULTS: Asthma developed in 218 (5.0 %) children during the follow-up period. The relation between BMI and incident asthma varied by sex. A BMI > or =85th percentile at age 2-3 years was a risk factor for subsequent asthma development in boys (hazard ratio (HR) 1.6 95% confidence interval (CI) 1.1, 2.4) but not girls (HR 0.8, 95% CI 0.5, 1.4). Similarly, boys with BMIs always > or =85th percentile were at increased risk for subsequent asthma development (HR 2.4, 95% CI 1.4, 4.4) but not girls (HR 1.5, 95% CI 0.7, 2.9). CONCLUSION: Boys with high body masses may be at an increased risk for developing asthma.

Asthma↗
PubMed2006

Patterns of use of antithrombotic therapy and quality of anticoagulation among patients with non-valvular atrial fibrillation in clinical practice.

We conducted a retrospective cohort study of thromboprophylaxis rates and the quality of anticoagulation control among patients with atrial fibrillation (AF) using a large, geographically diverse database of electronic medical records. The study population consisted of 13,709 AF patients treated in US outpatient physician practices. Approximately two-thirds were prescribed warfarin alone or in combination with another drug. Older patients, males, and those with congestive heart failure (CHF) or prior stroke were more likely to receive antithrombotic therapy. Among 6454 patients treated with warfarin who had at least two valid prothrombin time/international normalised ratio test results, approximately half of study days were spent in target range. Female sex, CHF and residence in the Northeast were associated with more time out of range. Our study confirms that, in routine medical practice, warfarin is not prescribed for substantial numbers of eligible patients, and anticoagulation control with warfarin is suboptimal for many of those at risk for thromboembolism.

Anticoagulants↗
PubMed2006

Cost-effectiveness of migraine prevention: the case of topiramate in the UK.

The aim of this study was to assess the cost-effectiveness of topiramate vs. no preventive treatment in the UK. Model inputs included baseline migraine frequency, treatment discontinuation and response, preventive and acute medical cost per attack [2005 GBP ( pound)] and gain in health utility. Outcomes included monthly migraines averted, acute and preventive treatment costs and cost per quality-adjusted life year (QALY). Topiramate was associated with 1.8 fewer monthly migraines and a QALY gain of 0.0384. The incremental cost of topiramate vs. no preventive treatment was about 10 UK pounds per migraine averted and 5700 UK pounds per QALY. Results are sensitive to baseline monthly migraine frequency, triptan use rate and the gain in utility. Incorporating savings from reduced work loss (about 36 UK pounds per month) suggests that topiramate would be cost saving compared with no preventive treatment. This analysis suggests that topiramate is a cost-effective treatment for migraine prevention compared with no preventive treatment.

Adult↗
PubMed2004

Stimulation of unidirectional pulses in excitable systems.

Using a judicious spatial shape of input current pulses (and electrodes), responses of an excitable system (FitzHugh-Nagumo) appear as unidirectional pulses (UDP's) instead of bidirectional ones (in one dimension) or circular ones (in two dimensions). The importance of the UDP's for a possible mechanism for pinpointing the reentry cycle position and for a possible use in tachycardia suppression is discussed.

Action Potentials↗
PubMed2003

Evaluation of cetylpyridinium chloride for infection control in storage solution.

Storage solution is used in in vitro experimental studies to prevent dehydration of teeth collected immediately after extraction and to prevent bacterial and fungal growth in the storage media. The chemical nature of the storing agent may affect the tooth structure and material properties at the tested interface. The aim of this study was to evaluate the use of 0.1% cetylpyridinium chloride (CPC) as a new storage solution and to assess the possible effect of 0.1% thymol on microleakage and bond strength. Forty extracted human teeth were collected from 10 different dental clinics. Immediately after extraction, the teeth were randomly divided and immersed in four different storage solutions. Two test solutions of 0.1% CPC (group C) and 0.1% thymol (group T) were compared with phosphate-buffered saline (Group S - positive control) and to 3% H2O2 (group H - negative control). Bond strength test and dye penetration evaluation were then carried out. The findings suggest that the use of 0.1% CPC as storage solution does not affect bond strength to enamel. However, it may increase dye penetration at the cervical margin. The effect of 0.1% thymol on shear bond strength and dye penetration is similar to the effect of phosphate-buffered saline.

Anti-Infective Agents, Local↗
PubMed2003

Relationship of asthma to irritant gas exposures in pulp and paper mills.

The potential of chronic or acute irritant gas exposures to cause asthma or a variant condition, reactive airways dysfunction syndrome (RADS) was investigated by observing asthma incidence in a large working population, using person-years at risk (P-YR) to compute relative rates (RR). Health data came from employee examinations at 62 pulp and paper plants. The 39122 workers who denied asthma beginning before the observation period included: 19326 denying irritant exposures, with no gassing exposures; 19349 with self-reported irritant exposures, and no gassing; and 447 with documented gassings. Asthma was defined as self-reported asthma beginning after the start of observation. P-YR accrued from September 29, 1986, for the nonexposed and exposed workers, and from date of first gassing for gassed workers, and ended with disease onset in any who developed asthma. RR of asthma with 95% confidence intervals (CI95) were calculated for the exposed and gassed groups, relative to the nonexposed. Exposed (nongassed) workers had an elevated asthma rate, RR=1.48, CI95=1.17-1.86, after adjustment for effects of gender and number of examinations. The rate in gassed workers was not significantly elevated: RR=1.95, CI95=0.75-5.08. Of the five asthma cases occurring after gassings, none conformed to diagnostic criteria for RADS. Chronic exposures were associated with increased rate of asthma onset, which must be interpreted with caution because self-reported data defined both exposure category and disease. Documented gassings were not associated with significantly increased rate, and none of 447 gassed persons developed RADS.

Adult↗
PubMed2001

Event-related potentials in schizophrenia during tonal and phonetic oddball tasks: relations to diagnostic subtype, symptom features and verbal memory.

BACKGROUND: This study compares event-related potentials for paranoid patients (n = 13) versus matched undifferentiated patients and unmedicated patients (n = 14) versus matched healthy adults. METHODS: Event-related potentials of right-handed patients and control subjects were recorded from 30 electrodes during oddball tasks using consonant-vowel syllables or complex tones. Patients were also assessed using the Positive and Negative Syndrome Scale, the Thought Disorder Index, and the Wechsler Memory Scale. RESULTS: Paranoid patients did not differ from undifferentiated patients in N1 or P3 amplitude but showed larger N2 at frontocentral sites to phonetic stimuli, as well as larger N2 over left than right hemisphere. Unmedicated patients showed reduced N2, but not N1 or P3, compared to control subjects. CONCLUSIONS: The N2 findings are consistent with neuropsychological evidence of greater verbal abilities and left hemisphere dominance in paranoid than nonparanoid schizophrenia. The findings also confirm the relationship of P3 to total Brief Psychiatric Rating Scale score, negative symptoms, and verbal associative memory.

Adult↗
PubMed2001

Sensory nerves promote ozone-induced lung inflammation in mice.

Genetically manipulated mice exhibiting altered innervation of the airways were used to examine the role of sensory nerves in ozone-induced lung inflammation. Transgenic mice expressing nerve growth factor (NGF) from the lung-specific Clara cell secretory protein (CCSP) promoter exhibit hyperinnervation of the airways by sympathetic and tachykinin-containing sensory nerve fibers. Mice carrying a mutation in the low-affinity NGF receptor (NGFR) gene possess deficits in sensory innervation. CCSP-NGF transgenic mice exhibited a twofold increase in the number of lung lavage neutrophil level whereas NGFR knockout mice exhibited a nearly 50% decrease in neutrophilic inflammation compared with wild-type mice 18 h after ozone inhalation. Treatment with neurokinin receptor antagonists reduced the level of neutrophilic inflammation in both wild-type and CCSP-NGF mice. Examination of lavage fluid cytokine concentrations revealed that 4 h after ozone exposure CCSP-NGF mice produced significantly higher amounts of the chemokine KC than wild-type mice exposed to ozone. The results of this study indicate that sensory nerves are important mediators of ozone-induced inflammation in mice.

Animals↗
PubMed2001

Role of LPS and receptor subtypes in the uptake of TNF by the murine lung.

Tumor necrosis factor alpha (TNF) is an important mediator in lung injury. The kinetics of TNF uptake by the lung are not completely understood. In this study, we evaluated the role that lipopolysaccharide (LPS) and the two types of TNF receptor (p55 and p75) play in the uptake of circulating murine TNF by the murine lung. TNF radioactively labeled with 125I (I-mTNF) was administered intravenously (2 x 10(6) cpm/mouse) to mice with both receptors (wild-type) or to mice missing one (p55-/- or p75-/-) or both (p55-/- and p75-/-) TNF receptors. Blood to lung non-reversible sequestration (Ki) and reversible uptake (Vi) were measured with multiple-time regression analysis. Uptake by lung of I-mTNF in wild-type mice had reversible and non-reversible components. This uptake was decreased by intratracheal, but not by intravenous, LPS, suggesting modulation by local, rather than systemic, inflammation. The p75-/- deficient mice retained the Ki (saturable, non-reversible) component of TNF uptake, whereas p55-/- deficient mice retained the Vi (saturable, reversible) component of TNF uptake. Both Ki and Vi components of TNF uptake were absent in the lungs of p55-/- p75-/- deficient mice. These studies show that local inflammation inhibits the uptake of circulating I-mTNF by lung and that uptake consists of two distinguishable compartments: reversible uptake mediated by the p75 receptor and non-reversible sequestration mediated by the p55 receptor.

Animals↗
PubMed2001

Preclinical evaluation of pharmacokinetic-pharmacodynamic rationale for oral CR metformin formulation.

We examined the pharmacokinetic (PK) and pharmacodynamic (PD) rationales to develop controlled release (CR) formulations of metformin. Unrestrained diabetic rats received the drug as intravenous bolus (i.v.), oral solution (p.o.), intra-duodenal bolus, 4-h infusion, or intra-colonic bolus. In addition, we developed two CR-gastroretentive dosage forms (CR-GRDF) that released the drug over 3 or 6 h (in vitro), and retained in the rats' stomach for 8-10 h. Metformin exhibited flip-flop PK. The colonic absorption was low but sustained and was associated with highly variable glucose-lowering effects, thus providing a PK rationale to develop CR-GRDF. In addition, the glucose-lowering effect was greater following p.o. vs. i.v. administration, despite equivalent AUC, indicating a first pass PD effect, thus, adding a PD rationale to develop metformin CR-GRDF. When administered to the diabetic rats, CR-GRDFs produced bioavailability and extent of glucose-lowering effects that were similar to those of the duodenal infusion and p.o. metformin administration. These findings are attributed to the adsorption of metformin to the intestine that yields slow and prolonged absorption even following p.o. administration of drug solution. The data indicates that unless the CR formulation could significantly extend the absorption period, it is not likely to improve glucose-lowering efficacy.

Administration, Oral↗
PubMed2001

Improved intestinal absorption of sulpiride in rats with synchronized oral delivery systems.

The goals of this study were to examine whether formulations, capable of releasing sulpiride (SP) in synchrony with the p-Glycoprotein (P-gp) inhibitors, verapamil (Ver) or quinidine (Qn) can increase SP relative bioavailability and to suggest a rationale approach for oral administration of SP. Jejunum of anesthetized rats was perfused with 200 or 400 microg/ml of SP either alone or together with 98 microg/ml of Ver. It was observed that while an increasing SP concentration did not cause an increase in SP blood levels, the addition of Ver or Qn to the perfusion solution caused a profound increase in SP absorption. Erodible matrix tablets, exhibiting a range of erosion rates, were prepared by manipulating the ratios of hydroxypropylmethylcellulose (HPMC) in the matrices. The tablets were designed to release the low water soluble SP and the highly water soluble Qn concomitantly over 1, 2 or 4 h. In all cases, the synchronous release increased SP bioavailability after intra-intestinal administration. The increase varied from 2.6- to 3.9-fold for the fast and the slow release formulations, respectively (compared with a control administration of a powdered mixture of SP and Qn). It is speculated that the poor oral bioavailability of SP was caused by brush border P-gp efflux. Synchronous release delivery systems of SP containing also the P-gp inhibitor Qn were able to increase SP bioavailability after intestinal administration in the rat. It is concluded that oral bioavailability of poorly absorbed drugs, in which absorption is restricted by gut wall secretory transport, may be improved by formulating them with functional adjuvants in synchronous release drug carriers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Prognostic significance of Bcl-2 and p53 expression in advanced laryngeal squamous cell carcinoma.

BACKGROUND: Proteins regulating the cell cycle and cell death are frequently abnormally expressed in cancer. Several of these, particularly p53 and Bcl-2, have been widely suggested as possible prognostic markers in diverse human malignancies. Their role in predicting outcome in squamous cell carcinomas of the head and neck is unclear and may depend on the location, stage, and treatment of the tumor. METHODS: To assess this question specifically for advanced squamous cell carcinoma of the larynx, we studied 69 patients with stage III or IV tumors, all but 6 of whom were treated with surgery plus postoperative irradiation by a single physician. We studied the patients retrospectively to test the association between expression of Bcl-2 and p53, as assessed by immunohistochemistry, with treatment outcome and survival. RESULTS: Twenty of the 69 patients died from their tumor (poor outcome); the rest were alive and tumor free at the last follow-up or died of unrelated causes without clinical tumor recurrence (good outcome). Fourteen tumors had detectable Bcl-2 expression, including 8 scored as overexpressors. Thirty-nine tumors overexpressed p53. Expression of neither Bcl-2 nor p53 was associated with outcome, overall survival, or disease-free survival. Only tumor stage was significantly associated with outcome and disease-free survival. CONCLUSION: These data indicate that assessing expression of p53 or Bcl-2 is unlikely to be prognostically useful for surgically treated advanced laryngeal carcinoma.

Adult↗
PubMed2001

Type A behavior and coronary atherosclerosis.

OBJECTIVES: To evaluate whether the pathogenesis of type A behavior may involve the premature development of coronary atherosclerosis. BACKGROUND: Type A or coronary-prone behavior is considered a possible risk factor for the development of coronary heart disease. Premature development of coronary atherosclerosis is suspected to play a role. Utilizing electron beam computed tomography, one can accurately determine the degree of coronary artery calcification, which is reflective of coronary atherosclerosis. METHODS: We performed a study of 35 men who had no clinical evidence of coronary heart disease. Twenty exhibited severe type A behavior and 15 exhibited type B behavior. All subjects were given an Electron Beam Computed Tomography scan of their coronary arteries and a treadmill electrocardiogram. RESULTS: Eight of the 20 (40%) type A subjects were found to have coronary calcification compared to none of the type B subjects (P=0.005). The correlation coefficient between type A score and coronary calcium score was 0.39 (P=0.09). CONCLUSIONS: The pathophysiology by which type A behavior increases the risk for coronary heart disease may involve the premature development of coronary atherosclerosis.

Calcinosis↗
PubMed2001

Antibacterial effect of parabens against planktonic and biofilm Streptococcus sobrinus.

Tooth decay is an infectious disease caused by bacteria immobilized on the tooth surfaces. Eradication of these bacteria, for example Streptococcus sobrinus (S. sobrinus), from the oral cavity is essential in the prevention and treatment of tooth decay. We have tested the antimicrobial effect of several paraben derivatives such as methyl (MP), ethyl (EP), propyl (PP) and butyl (BP) against immobilized and planktonic S. sobrinus. The antibacterial effect was as follows: MP>EP>PP=BP on immobilized bacteria and MP>EP=PP>BP on planktonic bacteria. An antibacterial synergistic effect was found between several combinations of parabens on immobilized and planktonic S. sobrinus. Our results indicate that parabens are potential antibacterial agents against immobilized or planktonic bacteria found in the oral cavity.

Anti-Bacterial Agents↗
PubMed2001

Tracer studies on the incorporation of [2-14C]-DL-mevalonate into chlorophylls a and b, alpha-chaconine, and alpha-solanine of potato sprouts.

Chlorophyll and glycoalkaloids are synthesized in different parts of the potato plant including leaves, tubers, and sprouts. Although light stimulates the biosynthesis of both constituents, the question of whether the two biosynthetic pathways are under the same genetic control has not been resolved. This study investigated the dynamics of incorporation of labeled [2-(14)C]-DL-mavalonate into chlorophyll a, chlorophyll b, and the glycoalkaloids alpha-chaconine and alpha-solanine in potato sprouts after 7 and 14 days of storage in the light and in the dark. No chlorophyll synthesis occurred in the dark. Fractionation of the "glycoalkaloid" extract followed by high-performance liquid chromatography produced four peaks. The fractions were collected and analyzed for radioactivity. About 80% of the radioactivity resided in fraction 1, the composition of which is unknown. Two of the fractions, with 1-14% of the original label, were alpha-chaconine and alpha-solanine. The radioactivity derived from mevalonate largely resides in unidentified compound(s) eluting as a single peak on the HPLC column before the peaks associated with the glycoalkaloids. The specific radioactivity of alpha-chaconine and alpha-solanine increased approximately 2-fold in going from 7 to 14 days of exposure in the light and in the dark. These and additional observations point to the near identity of the dynamics of biosynthesis of the two glycoalkaloids. These data also implicate a non-mevalonate pathway for the synthesis of both chlorophylls and the glycoalkaloids and are consistent with independent genetic control of the concurrent formation of the two classes of compounds during greening of potatoes.

Carbon Radioisotopes↗