bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioactivation of nitroglycerin to nitric oxide (NO) and S‐nitrosothiols in the rat liver and evaluation of the coexisting hypotensive effect
Authors: Sokołowska Maria , Bednarski Marek , Kwiecień Inga , Filipek Barbara , Włodek Lidia 
Published: September 2004

AbstractThe aim of the present study was to investigate nitroglycerin (NTG) bioactivation pathways in the liver after various periods of its administration. We also attempted to elucidate the relationship between nitric oxide (NO) and S‐nitrosothiol (SNT) levels, and concentration of nonprotein thiols (NPSH) and intensity of peroxidative processes. Intravenous injections of NTG cause an increase in NO and SNT levels in the rat liver. The same intravenous NTG injections in the rats pretreated with 5‐day i.p. NTG administrations lead to a drop in the levels of the biologically active NO, SNT and NPSH, with no concomitant changes in the rate of lipid peroxidation. This indicates that after such period of nitroglycerin pretreatment, levels of pharmacologically active NO and SNT decrease. However, during longer periods of NTG administration (for 10 and 17 days) NO, SNT and NPSH concentrations remain at the control level in spite of a considerably enhanced lipid peroxidation, which indicates that tolerance did not develop. Effects of NTG bioactivation in the liver, i.e. the levels of NO and SNT released from it, after different periods of drug administration correspond with hypotensive effects, which are known to be dependent on NTG biodegradation in vascular endothelial cells. The changes in NO and SNT levels observed in the rat liver after different periods of NTG administration parallel alterations in the hypotensive effect. In conclusion, NTG treatment for 10 and 17 days does not lead to tolerance, however, a transient loss of its pharmacological activity occurs after 5‐day NTG pretreatment.
Conjugation with taurine prevents side‐chain desaturation of ursodeoxycholic and β‐muricholic acids in bile fistula rats
Authors: Guitaoui Mustapha , Parquet Michel , Aubert Claude , Montet Anne‐Marie , Montet Jean‐Claude 
Published: September 2004

AbstractThe metabolism of intravenously infused bile salts, tauroursodeoxycholate, tauro‐β‐muricholate and their corresponding unconjugated forms in the liver was investigated in bile salt‐depleted bile fistula rats. The biliary bile salt composition was determined by gas chromatography–mass spectrometry using chemical positive ionization and electron‐impact methods. For an infusion rate of 2 μmol/min/kg, all bile salts were efficiently secreted in bile, inducing similar choleresis. Only tauroconjugated bile salts were recovered; no glucuronide or glyco derivatives were detected. The infusion of free ursodeoxycholate led to the appearance of a metabolite identified as a Δ22 derivative (12%). A similar biotransformation rate (11%) was observed following free β‐muricholate infusion. In contrast, no metabolite was observed after infusion of the tauroconjugated form of ursodeoxycholate and β‐muricholate. The unsaturation process probably depends on the availability of the carboxyl group for the starting step of the β‐oxidation mechanism. In conclusion, the current in vivo study demonstrates a hepatic origin for Δ22 bile salts. It also shows that free bile salts were sensitive to Δ22 formation while conjugation with taurine totally prevented the side‐chain oxidation of the two 7β‐hydroxylated bile salts.
Differential time effect profiles of amlodipine, as compared to valsartan, revealed by ambulatory blood pressure monitoring, self blood pressure measurements and dose omission protocol
Authors: Radauceanu Anca , Boivin Jean‐Marc , Bernaud Corine , Fay Renaud , Zannad Faiez ,   the CIC General Practitioners Investigators’ Group
Published: September 2004

AbstractAmlodipine and valsartan are once‐daily antihypertensive agents. To date, no comparison between these agents given as monotherapies was reported. This study was aimed to evaluate the therapeutic coverage and safety of amlodipine and valsartan in mild‐to‐moderate hypertensive patients. Multicenter, double‐blind, randomized, comparative study. After a 4‐week placebo wash‐out period, 246 outpatients with office diastolic blood pressure 95 ≤ DBP ≤110 mmHg and systolic blood pressure (SBP) < 180 mmHg, in addition to a mean daytime SBP and/or DBP > 135/85 mmHg on 24‐h ambulatory blood pressure monitoring (ABPM), were randomly allocated to once‐daily amlodipine 5–10 mg or valsartan 40–80 mg, for 12 weeks. In a subgroup of patients, 48‐h ABPM were performed at the end of the treatment period. Dose omission was simulated by a single‐blind placebo dosing. The primary efficacy end‐point was the 24‐h trough office BP after 12 weeks of active therapy. The reductions in 24‐h trough BP were more pronounced in amlodipine compared with valsartan group as well in office [SBP: −17.8 ± 10.9 vs. −14.6 ± 11.2, P = 0.025, DBP: −12.7 ± 7.2 vs. −10.9 ± 7.8 mmHg, P = 0.06) as in ambulatory BP (SBP/DBP: −13.0 ± 13.7/−10.8 ± 9.1 vs. −7.2 ± 19.4/−4.9 ± 13.4 mmHg, P < 0.05). Forty‐eight hours after the last active dose, the slope of the morning BP surge (4–9 h) was less steep with amlodipine vs. valsartan [DBP (P < 0.04), SBP (n.s.)]. Ankle edema were more often reported in amlodipine group. These results suggest a superior BP lowering and a longer duration of action with amlodipine compared with valsartan.
New metabolic and pharmacokinetic characteristics of thiocolchicoside and its active metabolite in healthy humans
Authors: Trellu M. , Filali‐Ansary A. , Françon D. , Adam R. , Lluel P. , Dubruc C. , Thénot J.P. 
Published: September 2004

AbstractThiocolchicoside (TCC) has been prescribed for several years as a muscle relaxant drug, but its pharmacokinetic (PK) profile and metabolism still remain largely unknown. Therefore, we re‐investigated its metabolism and PK, and we assessed the muscle relaxant properties of its metabolites. After oral administration of 8 mg (a therapeutic dose) of 14C‐labelled TCC to healthy volunteers, we found no detectable TCC in plasma, urine or faeces. On the other hand, the aglycone derivative obtained after de‐glycosylation of TCC (M2) was observed and, in addition, we identified, as the major circulating metabolic entity, 3‐O‐glucuronidated aglycone (M1) obtained after glucuro‐conjugation of M2. One hour after oral administration, M1 plus M2 accounted for more than 75% of the circulating total radioactivity. The pharmacological activity of these metabolites was assessed using a rat model, the muscle relaxant activity of M1 was similar to that of TCC whereas M2 was devoid of any activity. Subsequently, to investigate the PK profile of TCC in human PK studies, we developed and validated a specific bioanalytical method that combines liquid chromatography and ultraviolet detection to assay both active entities. After oral administration, TCC was not quantifiable with an lower limit of quantification set at 1 ng/mL, whereas its active metabolite M1 was detected. M1 appeared rapidly in plasma (tmax = 1 h) and was eliminated with an apparent terminal half‐life of 7.3 h. In contrast, after intramuscular administration both active entities (TCC and M1) were present; TCC was rapidly absorbed (tmax = 0.4 h) and eliminated with an apparent terminal half‐life of 1.5 h. M1 concentration peaked at 5 h and this metabolite was eliminated with an apparent terminal half‐life of 8.6 h. As TCC and M1 present an equipotent pharmacological activity, the relative oral pharmacological bioavailability of TCC vs. intramuscular administration was calculated and represented 25%. Therefore, to correctly investigate the PK and bioequivalence of TCC, the biological samples obtained must be assayed with a bioanalytical method able to specifically analyse TCC and its active metabolite M1.
Intraoperative Extracorporeal Irradiation for Limb Sparing in 13 Dogs
Authors: Liptak Julius M. , Dernell William S. , Lascelles B. Duncan X. , Larue Susan M. , Jameson Vicki J. , Powers Barbara E. , Huber Douglas J. , Withrow Stephen J. 
Published: September 2004

Objective— To evaluate extracorporeal intraoperative radiation therapy (IORT) as a treatment method for limb and joint sparing in dogs with appendicular sarcomas in sites other than the distal aspect of the radius.Study Design— Retrospective study.Animals— Thirteen client‐owned dogs.Methods— The bone tumor database and medical records (1998–2002) were reviewed for dogs with primary appendicular bone tumors treated with IORT limb‐sparing surgery and adjuvant chemotherapy. The segment of bone containing the tumor was isolated from adjacent soft tissue and an osteotomy performed distant to the tumor. The bone segment was exteriorized, irradiated (70 Gy single fraction), and then stabilized with internal fixation. Adjuvant chemotherapy was administered. Lameness was graded and local and distant tumor control was determined. Associations between intra‐ and postoperative variables with complications and Kaplan–Meier survival analysis for median disease‐free interval and survival time were calculated.Results— Limb function was good or excellent in 10 dogs (77%). Postoperative complications (9 dogs, 69%) included deep infection, fracture of the irradiated bone, and implant failure. Surgical failure was more likely if a single implant was used to stabilize the osteotomized bone and if deep infection developed postoperatively. In 3 dogs, tumors recurred locally within bone in the radiation field. The disease‐free and overall success rates of extracorporeal IORT for limb and joint preservation were 46% and 54%, respectively.Conclusions— Extracorporeal IORT provides a novel alternative to traditional techniques for preservation of joint and limb function in dogs with primary appendicular sarcomas. A minimum of 2 implants and intramedullary bone cement should be used to stabilize the osteotomized bone to minimize postoperative complications. Extracorporeal IORT should be used with caution in dogs with tumors of the distal tibia because of a high complication rate. Dogs with tumors in areas of good soft‐tissue coverage, such as the humerus and femur, may be good candidates for limb and joint‐sparing surgery using extracorporeal IORT.Clinical Relevance— Extracorporeal IORT is a surgical technique that can be used for limb and joint salvage in dogs with primary appendicular sarcomas in sites usually not amenable to traditional limb‐sparing techniques.
Evaluation of Primary Critical Ischemia Time for the Deep Circumflex Iliac Cutaneous Flap in Cats
Authors: Teunissen Brian D. , Walshaw Richard , Hauptman Joe G. , Degner Daniel A. , Jackson Andrew H. 
Published: September 2004

Objective—To evaluate the primary critical ischemia time for the deep circumflex iliac (DCI) cutaneous flap in cats.Study Design—In vivo model.Animals—Thirteen young adult female cats.Methods—An island skin flap was created on the right side of each cat based on the angiosome of the ventral branches of the DCI vessels. The cats were randomly assigned to a flap ischemia time ranging from 1 to 3 hours in 10‐minute intervals. Microvascular clamps were used to occlude the artery and vein for the designated time. Flaps were sutured into position after the ischemic period. On day 3, fluorescein dye was administered and the flaps were evaluated under ultraviolet light to assess percent area of perfusion. On days 7 and 14, the percent area of survival was determined for each flap based on cutaneous morphometry.Results—All flaps had 100 percent area of survival throughout the study. On day 3, all flaps fluoresced uniformly compared with the surrounding skin. On days 7 and 14, all flaps were uniformly viable as confirmed by skin color, consistency, bleeding, and hair re‐growth.Conclusion—The DCI cutaneous flap in cats can withstand up to 3 hours of ischemia with predictable survival.Clinical Relevance—In a clinical setting, high success rates can be expected with microvascular transfer of the DCI cutaneous flap in cats when the ischemia time is <3 hours and precise surgical technique is used.
Evaluation of Arthrocentesis Site Bacterial Flora before and after 4 Methods of Preparation in Horses with and without Evidence of Skin Contamination
Authors: Zubrod Chad J. , Farnsworth Kelly D. , Oaks J. Lindsay 
Published: September 2004

Objective—To evaluate the effectiveness of four methods of povidone–iodine preparation on skin bacterial flora of arthrocentesis sites, in horses, with and without evidence of skin contamination.Study Design—Prospective randomized study.Animals—Twenty‐four adult horses.Methods—Horses were assigned to either the clean or contaminated group based on housing environment and visual evidence of contamination. Using a moist sterile swab, microbial culture samples were obtained from the skin over the distal interphalangeal joints immediately before and after preparation. Each site was aseptically prepared with 1 of 4 povidone–iodine techniques: 10‐minutes scrub, 5‐minutes scrub, three 30‐second scrubs, or commercial one‐step iodophor surgical solution. Colony forming units (CFUs) were determined for each sample, 24 hours after inoculation, on blood agar plates.Results—Mean (±SD) pre‐scrub CFUs/mL was significantly higher in the contaminated group (9588.33±1223.65) compared with the clean group (4489.00±3842.03) (P<.01). After preparation of the arthrocentesis sites, there were no significant differences in post‐scrub CFUs/mL among the 10 minutes (mean clean, 46.00±64.36; mean contaminated, 28.67±18.04), 5 minutes (mean clean, 84.17±109.80; mean contaminated, 40.33±44.52), three 30 seconds povidone–iodine scrubs (mean clean, 95.50±172.29; mean contaminated, 46.67±56.94), or application of a commercial one‐step iodophor surgical solution (mean clean, 102.17±161.78; mean contaminated 117.67±143.78); or between the clean (81.96±131.69) and contaminated groups (58.33±85.90) (P<.01).Conclusions—Preparation of the distal interphalangeal joint arthrocentesis site with each of these techniques significantly reduces the bacterial flora to a similar level for arthrocentesis in horses with and without evidence of skin contamination.Clinical Relevance—Aseptic preparation of the skin over the distal interphalangeal joint may be accomplished with any of these techniques.
An In Vitro Study to Determine the Effectiveness of a Patellar Ligament/Fascia Lata Graft and New Tibial Suture Anchor Points for Extracapsular Stabilization of the Cranial Cruciate Ligament–Deficient Stifle in the Dog
Authors: Harper Tisha A. M. , Martin Robert A. , Ward Daniel L. , Grant J. Wallace 
Published: September 2004

Objective—(1) To determine whether an extracapsular patellar ligament/fascia lata graft would provide stability in the cranial cruciate ligament (CrCL)‐deficient stifle comparable with that of the intact stifle. (2) To determine if different tibial anchor points would enhance stability of the CrCLdeficient stifle when compared with the standard fabellar‐tibial suture (FTS) placement.Study Design—Experimental.Animals—Twenty‐eight canine cadaver hind limbs.Methods—Stifles were mounted in a jig and tested between loads of −65 and 80 N. After testing the intact CrCL, 4 stabilization techniques were tested after CrCL transection: lateral graft technique (LGT) and 3 FTS with different tibial anchor points.Results—There were no significant differences in displacement between the LGT and standard FTS, between the LGT and the intact CrCL, or between the FTS and the intact CrCL, in either the Securos™ or the Screw–washer experiments. Stiffness of the intact CrCL was significantly greater than that of any stabilization technique and the cut CrCL. The standard FTS showed the least displacement of all suture stabilization techniques. Differences in stiffness were not significant between the suture stabilization techniques.Conclusions—Securely anchored, the LGT results in a reduction in drawer motion similar to that of the intact CrCL and the standard FTS. Altering the tibial anchor point for the FTS does not improve stiffness or enhance stabilization of the CrCL‐deficient stifle.Clinical Relevance—The LGT could be used for the treatment of CrCL ruptures in the dog. A clinical study is recommended.
Accuracy and reproducibility of two manual periodontal probes
Authors: Buduneli Eralp , Aksoy Okay , Köse Timur , Atilla Gül 
Published: September 2004

AbstractBackground: Periodontal probe is the standard instrument for assessment of probing pocket depth and clinical attachment level. However, probing measurements have inherent measurement errors from a wide range of sources, such as instrument, patient, examiner and disease status.Aim: The purpose of the present study was to create an in vitro model simulating gingival sulcus/pocket and investigate the accuracy and reproducibility of two different manual probes.Methods: Thirty‐three aluminium blocks with dimensions of 2 × 2 cm and thickness ranging from 2.00 to 10.00 mm were constructed. Holes with a diameter of 1.00 mm were made in the blocks through the whole thickness. These 33 aluminium blocks were then carefully stucked together so that the probing faces would be on the same level. A plastic material, which shows deformation with forces >45 g was placed at the base of the blocks. Two conventional manual probes (Williams and WHO probes) were used in the present study. Seventeen periodontists were selected to perform duplicate measurements on the blocks over two visits using both of the probes. The intra‐ and inter‐examiner percentage accuracy (with regard to 0.25 mm) and reproducibility for each of the duplicate measurements was calculated and analysed using repeated measure analysis of variance (anova) (three factor experiments with repeated measure on two factors; probe and probing session).Results: anova showed statistically significant differences between the examiners (p=0.000) and between the two readings of each probe (p=0.002), while the differences between the two probes were not statistically significant (p=0.098). The overall percentage of accuracy was higher with WHO probe compared with Williams probe. Kappa analysis revealed better reproducibility percentages for WHO probe in comparison with Williams probe.Conclusions: This in vitro study, using a metal construction and a plastic material with a deformation coefficient similar to that of gingival pocket, may be suggested as a good model to test intra‐ and inter‐examiner differences in periodontal probing. Our findings emphasise the importance of inter‐examiner calibration for probing, particularly in longitudinal studies.
The influence of reactivation of the telomerase in tumour tissue on the prognosis of squamous cell carcinomas in the head and neck
Authors: Koscielny S. , Eggeling F. v. , Dahse R. , Fiedler W. 
Published: September 2004

Background:  The reactivation of the telomerase seems to be an important step in the carcinogenesis of most human cancer types. Cell clones, which express this enzyme, get the ability of indefinite proliferation, means become immortal.Methods:  In this study, 80 patients with squamous cell carcinomas (SSC) in oral cavity, oropharynx, hypopharynx and larynx were recorded prospectively concerning a possible correlation of telomerase activity and clinical and prognostic factors. Telomerase activity was analysed by a modified telomeric repeat amplification protocol (TRAP) assay.Results:  In 75% of the tumour tissues the telomerase was demonstrated independently of the localization of the tumour. The known clinical prognostic factors did not show any correlation to the expression rate of the telomerase activity in the tumour tissues. Also, reactivated telomerase did not affect the tumour‐dependent survival. Only the number of lymph node metastases was in tendency higher in patients with telomerase‐positive tumours. The number and timeframe of local and regional recurrences was not influenced by the telomerase status.Conclusions:  Although telomerase seems to be an important part of the carcinogenesis of SCC our data show that the reactivation of telomerase in tumour tissue did not have any prognostic significance for these tumours. The tendency that tumours with active telomerase developed lymph node metastases in a higher number should be evaluated by further enlarged studies for its clinical relevance.
Health Care Cost Implications of Sildenafil Citrate
Authors: Miner Martin 
Published: September 2004

ABSTRACT

Introduction
As prescription drug expenditures increase, third-party payors are increasingly scrutinizing costs and reimbursement guidelines, such as for medications that treat chronic conditions that are not necessarily directly life threatening (i.e., obesity, nicotine addiction, and erectile dysfunction).

Aim
To review the costs and consequences of pharmacy benefit reimbursement policies related to erectile dysfunction therapies, using sildenafil citrate as the case study.

Methods
Data and references were found through searches of PubMed and Google.

Results and Conclusions
To meet the varied health needs of a defined population under reasonable resource constraints requires analysis of cost and of the economic and non-economic consequences of a treatment. Based on analysis of sildenafil data, oral therapy of erectile dysfunction provides substantial cost savings when compared with other treatment options and contributes insignificant overall costs to health plans. Regardless, health plans impose controls to limit reimbursement. Because erectile dysfunction is often a precursor to other conditions, such limitations could compromise detection and management of underlying disease (e.g., depressive, cardiovascular, and urogenital). Reimbursement restrictions may also decrease membership satisfaction and re-enrollment rates.
Duration of Action of Sildenafil Citrate in Men with Erectile Dysfunction
Authors: Gingell Clive , Sultana Stefan R. , Wulff Maria B. , Gepi-Attee Sam 
Published: September 2004

ABSTRACT

Introduction
Viagra® (sildenafil citrate) has a rapid onset of action for the treatment of erectile dysfunction (ED). However, its duration of action has not been thoroughly investigated. Practical knowledge of the time window available for sexual intercourse would be valuable for couples planning sexual activity.

Aim
We investigated the duration of action of sildenafil in men with ED.

Methods
This was a double-blind, randomized, placebo-controlled, four-way crossover study of 16 men, mean age of 55 years (range, 36–68 years) with ED of no known organic cause. Participants received oral sildenafil (100 mg) or placebo 1, 8, or 12 hours before visual sexual stimulation (VSS). Measurements included the duration of erections of ≥ 60% rigidity, assessed by penile plethysmography (RigiScan®), and the proportion of sildenafil responders, defined as patients with erections of ≥ 60% rigidity for ≥ 4 minutes and ≥ 50% improvement over erections achieved in their placebo arm. Self-assessed duration of grade 3 (hard enough for penetration) or grade 4 (fully hard) erections was also recorded.

Results
At 1, 8, and 12 hours after dosing with sildenafil, the mean duration of erections with ≥ 60% rigidity was 26, 11, and 8 minutes, respectively, compared with only 3 minutes after placebo dosing (P &lt; 0.05). However, the mean duration of self-assessed erections was 33, 23, and 16 minutes, respectively, compared with 7 minutes after placebo dosing (P &lt; 0.05), and was greater than that assessed by RigiScan. Of the 69% sildenafil responders at 1 hour, 82% responded at 8 hours and 45% responded at 12 hours after sildenafil administration.

Conclusion
Sildenafil improved objective and self-assessed erectile function in men with ED, and the duration of action of sildenafil was longer than that previously reported. These data suggest that sildenafil may be effective in a significant proportion of men with ED up to 12 hours after being taken.