bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation on the Histopathological Effects of Thyroidectomy on the Seminiferous Tubules of Immature and Adult Rats
Authors: Oncu Meral , Kavaklı Duygu , Gokcımen Alpaslan , Gulle Kanat , Orhan Hikmet , Karaoz Erdal 
Published: July 2004

<i>Introduction:</i> This study aimed to investigate the histopathological effects of thyroidectomy on both immature and adult rat testes. <i>Materials and Methods:</i> Male albino Wistar rats, 4 weeks old and weighing between 45 and 55 g, were used for this study. The experimental groups were as follows: 2-week control group (group I); 2-week thyroidectomy group (group II); 4-week control group (group III); 4-week thyroidectomy group (group IV); 6-week control group (group V), and 6-week thyroidectomy group (group VI). The control groups included both sham-operated and untreated rats. In groups II, IV and VI, total thyroidectomy was performed under ether anesthesia in all rats at 4 weeks of age. The rats were killed in the 2nd, 4th and 6th weeks, respectively, following the thyroidectomy. The testes of each animal were evaluated histologically. <i>Results:</i> In group II, spermatogenesis progressed to meiosis but round spermatids were found to be decreased and pachytene spermatocytes were observed to be increased when compared to group I. Giant pachytene spermatocytes were seen. There were also many degenerated cells of intermediate origin in the seminiferous epithelium. In groups IV and VI, spermatogonia and primary spermatocytes were normal in appearance, but there was widespread degeneration of the other spermatogenic cells. In addition, some closed lumina covered by degenerated and dead cells were observed. In group II, the mean outer diameter, luminal diameter and area occupied by seminiferous epithelium decreased by 19.74, 32.18, and 28.12%, respectively. In group IV, these data decreased by 23.9, 16.52, and 48.5%, respectively, and in group VI, by 21.10, 19.76 and 40.29%, respectively, when compared with the control groups. These data were statistically significant (p < 0.001). <i>Conclusions:</i> Thyroid hormones could have a marked influence on the seminiferous tubules of both immature and adult rats, and their permanent lack results in a depression in seminiferous tubule growth as shown by the reduced outer and luminal diameters and area occupied by the seminiferous epithelium, which could give rise to degenerative changes in the spermatogenic cells of thyroidectomized rats. In addition, all these changes could also result from both the inability of Sertoli cells to support spermatogenic cells and the diminished levels of GH and FSH.
Late Recurrence of Clinical Stage I Seminoma of the Testis after 12 Years despite Adjuvant Infradiaphragmatic Irradiation
Authors: Tavolini Ivan Matteo , Mazzariol Chiara , Dal Bianco Massimo , Bassi Pierfrancesco 
Published: July 2004

A patient treated with prophylactic infradiaphragmatic radiation therapy for clinical stage I left testicular pure seminoma developed a large mass of the chest wall 12 years after primary treatment. An incisional biopsy confirmed pure seminoma. After chemotherapy, surgical removal of the residual mass and second-line chemoradiation therapy for persistent seminoma, the patient had a vertebral relapse. He died of progression 24 months after the first relapse despite further therapy.
Topical Activity of Ascorbic Acid: From in vitro Optimization to in vivo Efficacy
Authors: Raschke T. , Koop U. , Düsing H.-J. , Filbry A. , Sauermann K. , Jaspers S. , Wenck H. , Wittern K.-P. 
Published: July 2004

We present here a new cosmetic formula system containing 3% ascorbic acid based on an optimized oil-in-water (O/W) emulsion. This formulation demonstrated a good long-term stability of the active ingredient and also of the emulsion itself. It could be deduced from in vitro release studies that this O/W emulsion enabled a better release of the hydrophilic active agent than an alternative W/O emulsion. By measuring the ultraweak photon emission, which is a well-established parameter for the oxidative stress in the skin, the high in vivo antioxidant capacity of 3% ascorbic acid was demonstrated after 1 week of product application. This placebo-controlled study also proved that ascorbic acid in an O/W cream reduced oxidative stress in human skin significantly better than the derivative sodium ascorbyl-2-phosphate, a more stable vitamin C replacement commonly used in cosmetic formulations. With increasing age, the number of papillae in the epidermal-dermal junction zone in human skin are reduced. This implies a possible consequence of reduced mechanical resistance of the skin and impaired supply of the epidermis with nutrients. In a 1-month placebo-controlled study on 25 human volunteers, a significant increase in the number of dermal papillae after application of the 3% ascorbic acid cream was demonstrated, using a confocal laser scanning microscope. Fine lines and wrinkles are a characteristic sign of aged and especially photo-aged skin. Application of 3% ascorbic acid in a 12-week placebo-controlled usage study indicated a significant reduction of facial wrinkles. Altogether, 3% ascorbic acid in a cosmetic O/W emulsion has been shown to be appropriately stable and to enable a good release of the active agent in vitro as a precondition for a high efficacy in vivo. Application in vivo resulted in a significant reduction of oxidative stress in the skin, an improvement of the epidermal-dermal microstructure and a reduction of fine lines and wrinkles in aged skin. These results were received within a relatively short period of time of product application.
To Induce or Not to Induce Labor: A Macrosomic Dilemma
Authors: Simhayoff Nurit , Sheiner Eyal , Levy Amalia , Hammel Rachel D. , Mazor Moshe , Hallak Mordechai 
Published: July 2004

We assessed the effect of labor induction among parturients carrying macrosomic fetuses on the risk of a cesarean section (CS). The study population consisted of consecutive women with singleton fetuses weighing ≧4,000 g, delivered between 1988 and 1999. A comparison was made between parturients who delivered after labor induction and those who delivered without labor induction. The Mantel-Haenszel procedure was used to obtain the weighted odds ratios while controlling for confounding variables. During the study period, 4,755 women delivered macrosomic newborns in our institution. In 20% of the women (n = 951) labor was induced, while 80% of them (n = 3,804) delivered without labor induction. The women who delivered after labor induction were more likely to be nulliparous (18.0 vs. 10.0%; p < 0.001). In addition, these women had significantly higher rates of gestational diabetes (23.3 vs. 10.7%; p < 0.001), hypertensive disorders (10.1 vs. 5.3%; p < 0.001), hydramnios (17.4 vs. 9.9%; p < 0.001), and oligohydramnios (2.1 vs. 0.2%; p < 0.001). The CS rate was significantly higher among the patients who delivered after labor induction as compared with those in whom labor was not induced (17.8 vs. 11.9%; odds ratio 1.6, 95% confidence interval 1.3–1.9, p < 0.001). Stratified analysis using the Mantel-Haenszel technique was performed to control for confounders such as gestational diabetes, hypertensive disorders, previous CS, hydramnios, oligohydramnios, and nulliparity. None of these variables changed the significant association between induction of labor and CS. The induction of labor among women carrying macrosomic fetuses was found to be an independent risk factor for a CS.
Screening for Retinopathy of Prematurity: Is It Painful?
Authors: Belda Sylvia , Pallás Carmen R. , de la Cruz Javier , Tejada Pilar 
Published: July 2004

<i>Background:</i> Screening programmes for retinopathy of prematurity have shown to reduce unfavourable visual outcome and to be cost-effective. Following present recommendations, almost 1% of all newborn babies should therefore be screened and undergo at least one ophthalmologic examination. This is a skilled procedure that requires drug instillation and manipulation of the ocular globe with scleral indentation. The objective of this study is to describe the side effects of this ophthalmic exam with special focus on the occurrence of pain. <i>Methods:</i> This was an observational study with a before-after analysis where all neonates undergoing an ophthalmologic exam during a 4-month period in a third level hospital were included. CRIES pain score was determined before the exam, 5 min after and 24 h after the screening manoeuvre. Blood pressure and pulse rate were determined in addition to the mentioned measurements 30 min after the ophthalmologic examination.<i></i>Minimum oxygen saturation, apnoeas, gastrointestinal side effects (like vomiting and gastric aspirates), the need for respiratory assistance or for intensive care unit admission were recorded within 24 h before and after the procedure. <i>Results:</i> 27 preterm neonates underwent an ophthalmologic examination and were included in the study. CRIES pain score was significantly higher 5 min after and 24 h after the screening procedure than before. This difference was also observed after stratification for birth weight and gestational age. No other study variable modified this time effect. No significant changes in blood pressure and pulse rate were shown after the ophthalmic exam. Vomiting was present in 4% of the newborns, gastric aspirates in 22% and apnoeas in 41% after the examination. Ten percent of the explored preterm babies needed increased respiratory assistance and 4% had to be transferred from the intermediate care unit to the intensive care because of severe apnoeas. <i>Comments:</i> An increase in pain score was shown after retinopathy of prematurity screening examination. Physiologic variable changes do not last long enough to evaluate the impact of certain procedures. Multivariate pain scores (like CRIES) should be used in everyday practice. It seems that the ophthalmologic examination in preterm babies might be painful and further studies should identify the best strategy to prevent pain during the retinopathy of prematurity screening manoeuvre.
Diagnosis of Acute Renal Failure in Very Preterm Infants
Authors: Choker G. , Gouyon J.B. 
Published: July 2004

This study was designed to improve the definition of acute renal failure (ARF) in very preterm infants. Twenty-eight newborn infants with gestational age ≤32 weeks were prospectively studied in the first 5 days of life and made up a control group as they did not present risk factors for vasomotor renal insufficiency. Renal insufficiency was defined as an increase in daily serum creatinine concentration above the 99th interval limit obtained in this control group, i.e., 43 µmol/l on day 1 and/or 21 µmol/l on day 2 and/or 14 µmol/l/day on day 3 and/or 22 µmol/l/day on day 4. According to this definition, 20 very preterm infants with ARF were identified. As compared with the control group, the ARF group showed more prolonged oliguric episodes, lower diuresis, insufficient weight loss (in spite of a reduction in water intake) and also more episodes with natremia <130 mEq/l (35 vs. 0%; p < 0.05) and/or kalemia >6 mEq/l (40 vs. 11%; p < 0.05). Therefore, assessment of daily changes in serum creatinine concentration in very preterm infants allows the diagnosis of clinically significant reduction in glomerular filtration rate.
Dose-Response Effects of Estrogen and Tamoxifen upon Methamphetamine-Induced Behavioral Responses and Neurotoxicity of the Nigrostriatal Dopaminergic System in Female Mice
Authors: Mickley Katherine R. , Dluzen Dean E. 
Published: July 2004

In the present experiment we evaluated the dose-response effects of estrogen (estradiol benzoate; EB) and tamoxifen (TMX) in modulating the acute behavioral and chronic effects of methamphetamine (MA) upon the nigrostriatal dopaminergic (NSDA) system in ovariectomized (OVX) mice. EB over a range of doses from 1–40 µg resulted in a neuroprotective effect upon the NSDA system as defined by both a preservation of striatal dopamine (DA) concentrations and a decrease in DOPAC/DA ratios. Interestingly, the neuroprotective effect of the 1-µg EB dose occurred in the absence of any statistically significant effect upon the bioassay parameter of uterine weight. With the exception of an increase in stereotypy time as a response to the 40-µg dose, EB at any of the doses tested failed to alter any acute behavioral responses evoked by MA. In response to TMX, a statistically significant NSDA neuroprotectant response was obtained for DOPAC/DA ratios, but not DA concentrations, to doses ranging from 12.5 to 500 µg. No statistically significant effects upon uterine weights were obtained for any of the doses of TMX tested. Behaviorally, TMX at 500 µg had the effect of increasing the amount of time spent in the center of the cage. Taken together these results demonstrate: (1) EB and TMX at relatively low doses can exert a neuroprotective effect against MA; (2) these neuroprotective effects of EB and TMX can occur in the absence of an effect upon the bioassay parameter – uterine weights; (3) the parameter of DOPAC/DA ratio may indicate a more sensitive index of NSDA neuroprotection, and (4) modulatory effects of EB and TMX upon acute behavioral responses of the NSDA system to MA can be distinguished from their neuroprotective actions.
Low-Dose Sirolimus in Combination with Mycophenolate Mofetil Improves Kidney Graft Function Late after Renal Transplantation and Suggests Pharmacokinetic Interaction of Both Immunosuppressive Drugs
Authors: Renders Lutz , Steinbach Reiko , Valerius Thomas , Schöcklmann Harald O. , Kunzendorf Ulrich 
Published: July 2004

<i>Aims:</i> Chronic allograft nephropathy and/or calcineurin inhibitor toxicity are common problems after organ transplantation. The aim of this study was to examine the safety and efficacy of switching from a calcineurin inhibitor-based to a calcineurin inhibitor-free immunosuppressive regimen consisting of sirolimus and mycophenolate mofetil (MMF) late after renal transplantation. <i>Methods:</i> Kidney biopsies were performed in renal-transplanted patients with increasing serum creatinine levels at least 6 months after transplantation (mean time ± SD after renal transplantation: 76.4 ± 50.4 months). Patients with no signs of acute rejection were switched to MMF (500–2,000 mg/day) in combination with a low dose of sirolimus (1 mg/day). Renal function, serum chemistry, blood trough levels of sirolimus and MMF, and blood pressure were monitored. <i>Results:</i> 13 patients were investigated. During our observation period (mean observation time ± SD: 11.2 ± 5.9 months), an improvement in renal function was observed in 10/13 patients. In 3/13 patients, renal function deteriorated further and hemodialysis was initiated in 2 patients within the next 6 months. However, a serum creatinine concentration above 3.5 mg/dl was measured in 2 of those 3 patients prior to the switch of the immunosuppressive protocol. Administration of a low dosis of sirolimus (1 mg/day) led to relevant sirolimus (4.16 ± 1.85 ng/ml) and MMF blood trough levels (month 1: 6.8 ± 3.46; month 3: 4.67 ± 1.78 mg/l). The following adverse events were observed: borderline acute rejection (1/11 patients), anemia responding to higher dosage of erythropoietin (3/11), hyperlipidemia (1/11), and urinary tract infections (4/11). <i>Conclusions:</i> Low-dose sirolimus therapy in combination with concentration-adjusted MMF therapy leads to improvement of organ function late after renal transplantation. The follow-up of those patients should include assessments of blood cell counts, serum lipids and urinalysis to recognize the possible side effects.
Reversal of P-gp mediated multidrug resistance in-vitro and in-vivo by FG020318
Authors: Chen Li-ming , Liang Yong-ju , Ruan Ji-wu , Ding Yan , Wang Xiu-wen , Shi Zhi , Gu Lian-Quan , Yang Xiao-ping , Fu Li-wu 
Published: July 2004

Abstract
Overexpression of P-glycoprotein (P-gp) by tumours results in multidrug resistance (MDR) to structurally and functionally unrelated chemotherapeutic drugs. Combined therapy with MDR-related cytotoxins and MDR modulators is a promising strategy to overcome clinical MDR. This study was performed to explore the MDR reversal activity of a novel compound 2-[4-(2-pyridin-2-yl-vinyl) phenyl]-4,5-bis-(4-N,N-diethylaminophenyl)-1(H)-imidazole (FG020318) in-vitro and in-vivo. Tetrazolium (MTT) assay was used to evaluate the ability of FG020318 to reverse drug resistance in two P-gp-expressing tumour cell lines, KBv200 and MCF-7/adr. Intracellular doxorubicin accumulation was determined by fluorescence spectrophotometry in MCF-7/adr cell line. The effect of FG020318 on P-gp function was demonstrated by rhodamine 123 (Rh123) accumulation in KBv200 cells. KBv200 cell xenograft models were established to study the in-vivo effect of FG020318 on reversing MDR. FG020318 was not cytotoxic by itself against P-gp expressing KBv200 cells and MCF-7/adr cells and their parental drug-sensitive KB cells and MCF-7 cells. FG020318 could significantly increase the sensitivity of MDR cells to antitumour drugs including doxorubicin and vincristine in MCF-7/adr cells and KBv200 cells, respectively. It was much stronger than the positive control verapamil in reversal of MDR. FG020318 also increased the intracellular accumulation of doxorubicin in a concentration-dependent manner in MCF-7/adr cells, but did not affect the accumulation of doxorubicin in drug-sensitive MCF-7 cells. The Rh123 accumulation in resistant KBv200 cells was also increased by the addition of FG020318, but Rh123 accumulation was not affected by FG020318 in drug-sensitive KB cells. FG020318 potentiated the antitumour activity of vincristine to KBv200 xenografts and was an efficacious modulator in-vivo. Our results suggested that FG020318 was a highly potent, efficacious MDR modulator not only in-vitro but also in-vivo. The reversal of drug resistance by FG020318 was probably related to the increased anticancer drug accumulation and its inhibition of P-gp function of MDR tumour cells.
Calcium channel antagonists attenuate cross-sensitization to the rewarding and/or locomotor effects of nicotine, morphine and MK-801
Authors: Biala Grazyna , Weglinska Barbara 
Published: July 2004

Abstract
The present study focused on the evaluation of behavioural cross-sensitization, particularly in locomotor activities and conditioned rewarding effects, between nicotine and morphine, cocaine, amphetamine or MK-801. Nicotine (0.5 mg kg−1)-experienced mice manifested an enhanced locomotor response to morphine (5 mg kg−1) or MK-801 (0.3 mg kg−1). No cross-sensitization was observed between nicotine and amphetamine (2 mg kg−1) or cocaine (15 mg kg−1). Additionally, the L-type voltage-dependent calcium-channel antagonists, nimodipine and verapamil, but not diltiazem, at a dose of 20 mg kg−1 injected before morphine or MK-801 challenge, blocked the expression of this cross-sensitization. In the second test, an enhancement of morphine place conditioning in rats pre-exposed to nicotine (0.5 mg kg−1, injected daily for 5 days) was demonstrated. After two conditioning sessions, morphine (5 mg kg−1) induced a clear place preference only in animals that had previously received nicotine injections. The administration of nimodipine (10 and 20 mg kg−1), verapamil (10 and 20 mg kg−1) and diltiazem (10 and 20 mg kg−1) prior to nicotine dose-dependently prevented this sensitization to the rewarding effect of morphine produced by prior injections of nicotine. These findings support the hypothesis that similar neural calcium-dependent mechanisms are involved in the appetitive effects of nicotine and morphine and in the sensitized locomotor stimulant effects of nicotine and morphine or MK-801.
Lack of congruence between cysteine dioxygenase activity and S-carboxymethyl-l-cysteine S-oxidation activity in rat cytosol
Authors: Khan Samera , Mitchell Stephen C , Steventon Glyn B 
Published: July 2004

Abstract
The identity of the enzyme(s) responsible for the S-oxidation of the mucoactive drug S-carboxy-methyl-l-cysteine (SCMC) is unknown but the protein(s) are a susceptibility factor for a number of chronic degenerative diseases. The structural similarities between the amino acid l-cysteine and SCMC have raised the possibility that cysteine dioxygenase (CDO) may be responsible for this biotransformation reaction. Both CDO and SCMC S-oxygenase were found to require Fe2+ for enzymatic activity, and both enzyme activities were inhibited by Fe2+ and Fe3+ chelators. However, sulphydryl group modification of the enzymes resulted in the activation of the S-oxidation of SCMC but inhibition of the S-oxidation of l-cysteine. When the two enzyme activities were quantified in 20 female hepatic cytosolic fractions no linear correlation in the production of their respective metabolites was seen. The results of this investigation indicate that CDO is not responsible for the S-oxidation of SCMC in the rat.
Solid-phase synthesis and evaluation of libraries of substituted 4,5-dihydropyridazinones as vasodilator agents
Authors: Gouault Nicolas , Martin-Chouly Corinne A E , Lugnier Claire , Cupif Jean-François , Tonnelier Amaury , Feger Frédéric , Lagente Vincent , David Michèle 
Published: July 2004

Abstract
The solid-phase parallel preparation of a library of 4,5-dihydropyridazin-3(2H)-one derivatives substituted at position 6 with piperazinylmethyl or tetrahydroquinolinylmethyl groups and analogues (3) is reported. Polymer-supported γ-keto-δ-aminoesters prepared from Wang resin reacted with hydrazine or methylhydrazine to afford pyridazinones in good yields after a cyclization cleavage approach. We have evaluated these novel analogues and several compounds of other series (1, 2) for their vasorelaxant effect. Among the products tested, 3I and 3d proved to be efficacious and potent relaxant agents of the isolated rat aorta. Inhibitors of phosphodiesterase (PDE3), responsible for the breakdown of cyclic AMP in the vascular smooth muscle, are currently developed for cardiac heart failure because of their inotropic effect and coronary vasodilatation. We had expected that the vasodilatation induced by 3l, as efficient as reference PDE3 inhibitors, milrinone or CI-930, to be due to PDE3 inhibition. However 3I and 3d exhibited a low inhibitory effect against PDE3 isoenzyme activity. These compounds induced a significant vasorelaxation, which could be of therapeutic interest even if their mechanism of action remains to be determined.