bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Triamcinolone Acetonide on Adult Human Lung Fibroblasts: Decrease in Proliferation, Surface Molecule Expression and Mediator Release
Authors: Oddera S. , Cagnoni F. , Mangraviti S. , Giron-Michel J. , Popova O. , Canonica G.W. 
Published: April 2003

<i>Background:</i> Lung fibroblasts may have a pivotal role in airway inflammation as they are involved in continuous cycles of mediator secretion, proliferation, activation and cross-talk with recruited inflammatory cells. The role of fibroblasts as intermediate participants in the inflammatory network suggests that they could represent an important target for drugs commonly used in asthma; thus, we investigated the effects of triamcinolone acetonide (TAA) on primary human lung fibroblasts. <i>Methods:</i> The in vitro activity of increasing concentrations (10<sup>–9</sup> to 10<sup>–7</sup> <i>M</i>) of TAA in fibroblast cultures was evaluated as regards the following parameters: proliferation, extracellular matrix (ECM) release, cytokine/chemokine secretion and surface antigen expression. <i>Results:</i> All concentrations of TAA decreased fetal calf serum (FCS)-induced fibroblast proliferation, whereas in the presence of FCS plus basic fibroblast growth factor TAA was only effective at 10<sup>–8</sup> and 10<sup>–7</sup><i>M</i>. TAA failed to decrease ECM, whereas at 10<sup>–8</sup> and 10<sup>–7</sup><i>M</i> it decreased IL-6 and IL-8 secretion to different extents. In the presence of IFN-γ the drug was able to reduce VCAM-1 expression at all of the tested concentrations; on the other hand, in TGF-β<sub>1</sub>-driven cultures a decrease in CD54 expression was detected with TAA at 10<sup>–8</sup> and 10<sup>–7</sup><i>M</i>. <i>Conclusions:</i> TAA acts on some functional properties of human lung fibroblasts that make these cells active participants in the inflammatory network. The ability of TAA to inhibit lung fibroblast proliferation may prevent or even reverse some of the histological changes that characterize airway remodeling in chronic inflammatory diseases; moreover, IL-6, IL-8 and surface molecule decreases by TAA may suggest a direct anti-inflammatory effect of the drug by suppression of resident lung cell function.
Altered Control of the Hypothalamo-Pituitary-Adrenal Axis in Adult Male Rats Exposed Perinatally to Food Deprivation and/or Dehydration
Authors: Sebaai Naima , Lesage Jean , Vieau Didier , Alaoui Abdelilah , Dupouy Jean Paul , Deloof Sylvie 
Published: April 2003

Dehydration, a classic homeostatic stressor in rats, leads to a series of well characterized endocrine responses including stimulation of the hypothalamo-pituitary-adrenal (HPA) axis. In this study, the hypothesis to be tested was that a 50% maternal food restriction (FR50) in late gestation and lactation may have long-term repercussions on HPA axis responsiveness to dehydration in offspring. For this purpose, we studied HPA axis activity in 4-month-old control (C) and perinatally malnourished male rats after a 72-hour water deprivation period. Furthermore, we investigated the long-lasting effects of perinatal maternal malnutrition on the basal activity of the HPA axis. Under basal conditions, rats exposed to perinatal malnutrition showed reduced body weight, enhanced mineralocorticoid receptor (MR) mRNA levels in CA2 and CA3 hippocampal areas, but decreased glucocorticoid receptor (GR) mRNA levels in CA1, CA3 and dentate gyrus (DG) areas. In contrast, the levels of corticotropin-releasing hormone (CRH) and vasopressin (VP) mRNAs in the hypothalamic paraventricular nucleus (PVN) as well as of VP mRNA in the supraoptic nucleus (SON) were unaffected by maternal undernutrition. Expression of proopiomelanocortin (POMC) in the adenohypophysis was significantly enhanced, whereas prohormone convertase-1 (PC1) was not affected. Perinatal malnutrition reduced absolute adrenal weight but did not affect circulating levels of adrenocorticotropin (ACTH), corticosterone and free corticosterone as well as corticosteroid-binding globulin (CBG) binding capacity. Seventy-two hours of dehydration induced a decrease in body weight and CRH mRNA levels in PVN of controls as well as of FR50 rats, but also led to a rise in plasma corticosterone and free corticosterone without changing CBG binding capacity. Dehydration also induced an increase in adenopituitary POMC (C) and PC1 (FR50), PVN and SON VP (C) and GR in CA1 hippocampal area (FR50) mRNA levels and plasma ACTH (C), but a decrease in MR in DG (C) and GR in CA3 and DG (C) mRNA levels. We conclude that maternal food restriction during the perinatal period affects (1) the adult basal activity of the HPA axis with mainly opposite effects on hippocampal MR and GR gene expression and an increase in adenopituitary POMC gene expression, and (2) the responsiveness to water deprivation in adults. In the latter case, the rise in plasma ACTH levels, adenopituitary POMC gene expression, hypothalamic VP gene expression, and the decrease in hippocampal MR gene expression in DG and GR gene expression in CA3 and DG observed in controls are lacking in FR50 rats. In contrast, drastic adenopituitary PC1 gene expression occurred in FR50 rats but not in control animals.
Effect of Chlorhexidine Varnish and Gel on Mutans Streptococci in Margins of Restorations in Adults
Authors: Wallman C. , Birkhed D. 
Published: April 2003

The aim of this study was to compare the effect of two different chlorhexidine regimens, varnish and gel, on mutans streptococci (MS) in the margins of restorations and in saliva. Eighteen subjects (mean age 44 years) with >250,000 MS/ml saliva and with many restored teeth were assigned to three groups, each comprising 6 individuals. They were treated with: (1) Cervitec<sup>®</sup> varnish, containing 1% chlorhexidine and 1% thymol; (2) placebo varnish, or (3) Corsodyl<sup>®</sup> gel, containing 1% chlorhexidine. The varnish was applied on two separate occasions to all tooth surfaces at an interval of 3–4 days. The gel was applied for 3×5 min in individual applicators on 2 consecutive days. Plaque samples from 8–9 margins of restorations per subject, mainly in the premolar and molar region, and stimulated saliva samples were collected at baseline and after 1, 4, 8 and 12 weeks. The general finding was that the Corsodyl gel gave the most pronounced reduction of MS followed by the Cervitec varnish. According to repeated measures ANOVA, no significant differences could be demonstrated either for MS in margins or in saliva among the three groups (p = 0.06 for margins and p = 0.07 for saliva). However, within the groups, the reduction of MS over time was statistically significant, both in margins and in saliva (p < 0.001 and p < 0.05, respectively). Student-Newman-Keuls test showed that MS in margins were significantly reduced at most sampling occasions in both chlorhexidine groups: the reduction was more pronounced in the Corsodyl gel group. The conclusion from this study is that the 1% chlorhexidine gel Corsodyl, administered 6 times during 2 days, is more effective in suppressing MS in the margins of restorations and in saliva than the 1% chlorhexidine varnish Cervitec, administered twice within 3–4 days.
Comparative Histologic Effects of Daily Topical Application of Creams Containing All-<i>trans</i>-Retinoic Acid or All-<i>trans</i>-Retinoyl β-Glucuronide on Pig Skin
Authors: Gunning Desiree B. , Barua Arun B. , Myers Ronald K. , Ueltschy Amanda , Romans David , Olson James A. 
Published: April 2003

The efficacy of all-<i>trans</i>-retinoic acid (tRA) and all-<i>trans</i>-retinoyl β-glucuronide (RAG), a water-soluble metabolite of vitamin A, in the topical treatment of acne is comparable. However, whereas 3.3 m<i>M</i> tRA shows side effects, 3.3 m<i>M</i> RAG does not. To assess the relative toxic and histologic effects (dermal and epidermal changes) of long-term (24-week) daily applications of tRA and RAG on the skin, separate skin patches were measured and marked dorsally on the skin of six 21-day-old, castrated male pigs. Each skin patch area was treated daily with a cream formulation containing either 3.3 m<i>M </i>RAG, 16.5 m<i>M</i> RAG, 33 m<i>M</i> RAG, 3.3 m<i>M</i> tRA, 16.5 m<i>M</i> tRA or blank cream. To serve as controls, one patch received no treatment, one patch received blank cream only and for 5.3 weeks one ‘washed’ patch was given daily application of 33 m<i>M</i> RAG with routine cleansing using a mild soap typical of skin care. The amount of cream used per square centimeter remained the same during the course of the study. Biopsy tissue was collected at –1, 0, 2, 4, 8, 12 and 24 weeks from 7 test patches. The ‘washed’ patch was biopsied once at the 5.3-week mark. Topically applied RAG cream (3.3 m<i>M</i>) resulted in significantly lower histologic scores when compared with scores from tissue treated with an equimolar concentration of tRA. The highest concentration of RAG tested (33.3 m<i>M</i>) resulted in a response comparable to that observed in the lowest tRA (3.3 m<i>M</i>) treated patch area. Daily cleansing of the test area receiving 33.3 m<i>M</i> RAG completely eliminated any clinical signs or negative histologic changes. In conclusion, long-term topical tRA treatment in young pigs, as in humans, showed dose-dependent adverse effects on the skin, whereas RAG treatment had significantly lower histologic changes and less irritation and/or inflammation.
Stratum corneum pH: Formation and Function of the ‘Acid Mantle’
Authors: Fluhr Joachim W. , Elias Peter M. 
Published: April 2003

Although the acidic surface pH of the skin has been known for over a century, the stratum corneum (SC) pH gradient has been discovered only recently. After removal of SC layers with sequential tape strips, in humans, surface pH starts at 4.5–5.3, increasing by about 2–3 units until it reaches 6.8 in the lower SC. Both exogenous [free fatty acids (FFA) from sebaceous lipid, microbial metabolites, lactic acid from eccrine glands] and endogenous epidermal (enzymatic; membrane antiporters/pumps) mechanisms have been hypothesized to contribute to SC acidification. Three endogenous mechanisms have been identified to date that not only could influence SC pH, but also regulate one or more key SC functions: (1) the histidine-to-urocanic-acid pathway; (2) the phospholipid-to-FFA pathway, and (3) the sodium proton antiporter (NHE1). Additional factors that influence human surface pH have been detected. Endogenous factors, unrelated to pathological features, such as racial differences, topographical variation, gender differences, developmental and age-related changes have been reported. In contrast to adults, human newborn SC displays a near-neutral surface pH, which declines rapidly over the first postnatal month. Furthermore, endogenous factors have been described, as in atopic dermatitis, seborrheic dermatitis, diabetes, renal insufficiency and ichthyosis associated with an increased pH. Exogenous factors, like the use of detergents and cleansing products as well as SC hydration, can modify the surface pH. The consequences of SC acidification for several key SC functions are becoming clear, including (1) the role of an acidic pH for SC permeability barrier homeostasis, (2) the pH dependence of extracellular lipid processing and (3) SC integrity/cohesion. Integrity is defined as a measure of resistance to dissociation of adjacent corneocytes by tape stripping (cohesion is a related index defined as the amount of protein removed per stripping). (4) Proteolytic processes leading to desquamation are pH dependent, and (5) an acidic pH provides important antimicrobial resistance.
Influence of Tacalcitol on Cell Cycle Kinetics of Human Keratinocytes following Standardized Injury
Authors: Mommers J.M. , ter Meulen A.C. , van Erp P.E.J. , van de Kerkhof P.C.M. 
Published: April 2003

In the last few years, tacalcitol (1α,24-dihydroxy vitamin D<sub>3</sub>, TV-02) has become widely available for the topical treatment of psoriasis. Several studies documented its effect on epidermal differentiation, inflammation and proliferation. Especially the effect on epidermal proliferation has shown to be most substantial. This finding strongly suggests that the antipsoriatic effect of tacalcitol may be mediated by the normalization of epidermal cell cycle kinetics. Aim of the present study was to investigate the effect of tacalcitol ointment (4 µg/g) compared with the ointment base on epidermal proliferation following tape stripping. In particular, we addressed the question to what extent tacalcitol influences the recruitment of G&#8320; cells after standardized injury. In 15 healthy volunteers, Sellotape<sup>TM</sup> stripping of the epidermis was performed at two places on the lower back. Then, tacalcitol ointment (4 µg/g) and the ointment base were applied on the lesions and covered by a semiocclusive dressing. Punch biopsies of the lesions were obtained at 24, 32, 38, 44, 50, and 56 h after tape stripping. Using a flow cytometric staining procedure with parameters for epidermal proliferation (DNA content), differentiation (keratin 10 expression) and nonmesenchymal cells (vimentin expression), quantitative data were obtained. There was a statistically significant difference between the time intervals for tacalcitol and placebo with respect to the percentage of recruited basal cells in S phase: The peak of recruited basal cells in S phase was seen at 38 h for the placebo-treated lesions, whereas this peak was seen at 50 h for the tacalcitol-treated lesions. There was no significant difference in the total number of recruited cells between tacalcitol and placebo. The influence of tacalcitol on epidermal keratinization and on the percentage of nonkeratinocytes did not show any significance compared to placebo. We concluded that the mode of action of tacalcitol on proliferation is mainly through an extension of the cell cycle time of keratinocytes and/or an extension of the duration of the recruitment process of cycling cells, whereas the ability to suppress recruitment of resting keratinocytes is not different from placebo. Moreover, because of the limited effect of tacalcitol on epidermal keratinization, combination treatments with agents which interfere with keratinization and/or inflammation may be attractive.
The Effect of the Base on the Kinetics of Action of the Capsaicinoid Nonivamide: Evaluation with a Hyperemic Test
Authors: Stücker M. , Reuther T. , Hoffmann K. , Aicher B. , Altmeyer P. 
Published: April 2003

Because of their selective receptor-mediated action on cutaneous nociceptive C-fibers, the interest in capsaicinoids as topical analgetic drugs has been constantly growing over the past years. Knowledge of the pharmacokinetics seems particularly important for potential future clinical applications. Therefore, the aim of the present study was to investigate the influence of the type of preparation on the time course of action of the capsaicinoid nonivamide monitored by the axon-reflex-induced hyperemic action and area of erythema. Sixteen healthy subjects were included in the study. The hyperemic responses after application of nonivamide in an oil-in-water (O/W) emulsion and in a water-free ointment were assessed both by laser Doppler perfusion imaging and planimetry after 0, 15, 30, 45, 60, 120 and 240 min. They were compared with the reaction after application of the nicotinic ester nicoboxil and a combination of nonivamide and nicoboxil in the same preparations. Applied as a water-free ointment, nonivamide showed a slow onset of hyperemic action, reaching its maximum 45 min after application. When applied as an O/W emulsion, however, the increase in effect was high, reaching its maximum already after 30 min. Application of the nicoboxil preparations revealed a clearly lesser influence of the base regarding the onset of maximum effect. The combination of both substances showed an additive effect for both bases, and a maximum effect was found already after 15 min with both the water-free ointment and the O/W emulsion base. In conclusion, the results of the present study show that there appears to be a strong influence of the vehicle on the kinetics of action of capsaicinoids, and that the hyperemic test used in this paper is very useful for the quantitative determination of the pharmacokinetic properties of capsaicinoids. Moreover, the C-fiber-stimulating effect of capsaicinoids can, at least in part, be enhanced by combination with a nicotinic ester, even though these substances have no direct effect on the C-fibers.
European Audit of Current Practice in Diagnosis and Treatment of Childhood Growth Hormone Deficiency
Authors: Juul Anders , Bernasconi Sergio , Clayton Peter E. , Kiess Wieland , DeMuinck-Keizer Schrama Sabine 
Published: April 2003

<i>Background:</i> The present survey among members of the ESPE on current practice in diagnosis and treatment of growth hormone (GH) deficiency (GHD) is of great clinical relevance and importance in the light of the recently published guidelines for diagnosis and treatment of GHD by the Growth Hormone Research Society. We have found much conformity but also numerous discrepancies between the recommendations of the Growth Hormone Research Society and the current practice in Europe. <i>Results:</i> We found that 80% of the pediatric endocrinologists included insulin-like growth factor I (IGF-I) in their initial evaluation of a short child suspected of having GHD, whereas only 22% used GH provocative testing alone in the initial evaluation of a short child. Sixty-eight percent confirmed the diagnosis of GHD using two separate provocative tests. In the present survey cutoff values for GH provocative testing clustered around two values; 10 ng/ml and 20 mU/l. Interestingly, these two values, differing by a factor of 2, were also the most prevalent cutoff values among those who reported their assay to be calibrated against the WHO International Reference Preparation 80/505 where the conversion factor between milligrams and milliunits is 2.6. This suggests that the selection of cutoff values is based on tradition rather than on specific GH assay characteristics. In addition, only 63% of the respondents actually knew what GH assay they were using, and only 57% knew how their GH assay was calibrated. Dosing of GH at the start of treatment was reported according to body surface by 39%, whereas 59% were dosing according to body weight. GH dose adjustment was primarily based on growth response and height during auxological assessment every 3–4 months (height velocity, change in height velocity or change in height standard deviation scores) as indicated by almost 70% of the respondents. However, dose adjustment according to body surface (38%) and body weight (44%) was also quite common. Sixty-five percent measures IGF-I regularly (at least once a year) during GH therapy in children, and to our surprise 17% reported that they adjust the GH dose according to the IGF-I levels. <i>Summary:</i> In summary, we have found large heterogeneity in the current practice of diagnosis and treatment of childhood GHD among European pediatric endocrinologists. Especially standardizations of GH assays and cutoff values are urgently required to ensure a uniform and correct diagnosis and therapy of GHD in the future.
Some Aspects of Hemostasis in CAPD Patients Treated with Erythropoietin
Authors: Małyszko Jolanta , Suchowierska Ewa , Małyszko Jacek S. , Myśliwiec Michał 
Published: April 2003

<i>Background:</i> Bleeding diathesis and simultaneous thrombotic complications may be seen in dialyzed patients. Erythropoietin may shift the precarious balance of the hemostatic system towards thrombosis. Thrombin activatable fibrinolysis inhibitor (TAFI) is a key protein linking coagulation and fibrinolysis. <i>Methods:</i> The effects of 3-month erythropoietin treatment on some hemostatic parameters – TAFI, fibrinolytic activity index (FAI), markers of ongoing coagulation (thrombin-antithrombin complexes and prothrombin fragments 1 + 2), marker of ongoing fibrinolysis (plasmin-antiplasmin complexes) and marker of endothelial cell injury (thrombomodulin) – were studied in 17 patients on continuous ambulatory peritoneal dialysis (CAPD). Patients on CAPD not treated with rHuEPO were also studied. Healthy volunteers served as a control group. 2,000 U erythropoietin was given subcutaneously three times a week. Commercially available kits were used to determine hemostatic parameters. <i>Results:</i> All the hemostatic parameters studied were significantly higher in CAPD patients when compared to the control group. All these hemostatic parameters except the plasmin-antiplasmin complexes did not differ significantly between patients before rHuEPO therapy and patients without rHuEPO. Erythropoietin therapy resulted in a significant decrease in plasmin-antiplasmin complexes, a significant rise in FAI after 3 months of drug administration, and a tendency to decrease the TAFI concentration and activity (after 1 month, p = 0.11 and p = 0.10, respectively; after 3 months p = 0.07 and p = 0.06, respectively). Treatment with erythropoietin did not affect platelet count, prothrombin time, activated partial thromboplastin time, cholesterol, triglycerides, fibrinogen, total protein, albumin, serum iron, ferritin, fibronectin, pH, bicarbonates, creatinine, and urea. Hemoglobin and hematocrit increased significantly after 1 month of the therapy. <i>Conclusion:</i> Short-term treatment with erythropoietin seems to minimally affect hemostasis in CAPD patients.
Heterotopic Pregnancy: Successful Management with Aspiration of Cornual/Interstitial Gestational Sac and Instillation of Small Dose of Methotrexate
Authors: Oyawoye Seye , Chander Bina , Pavlovic Biserka , Hunter Jocelyn , Abdel Gadir Ahmed 
Published: April 2003

<i>Objectives:</i> Terminating a corneal pregnancy without jeopardizing a coexistent intrauterine pregnancy. <i>Methods:</i> A 29-year-old woman with a 4-year history of primary infertility became pregnant after in-vitro fertilization and embryo transfer. A heterotopic pregnancy with a left cornual and intrauterine sacs was confirmed by early transvaginal scan examinations. The ectopic sac was aspirated under ultrasound guidance followed by local injection of 12.5 mg methotrexate. This was followed by serial ultrasound scans and serum βhCG assays. <i>Results:</i> The fetal pole in the ectopic pregnancy disappeared following the procedure. She had no significant vaginal bleeding or any other unusual symptoms. The intrauterine pregnancy progressed satisfactorily until spontaneous onset of labour and vacuum extraction delivery at 39 weeks. The baby weighed 2.9 kg. <i>Conclusions:</i> Local injection of low-dose methotrexate following aspiration of a cornual pregnancy proved effective in halting the ectopic trophoblasts’ growth without adversely affecting a coexistent intrauterine pregnancy. The injected ectopic trophoblasts resolved quickly despite the small dose of methotrexate used. This technique avoided a more costly surgical treatment with its associated risks in subsequent pregnancies.