bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the effects of desloratadine 5‐mg daily and placebo on nasal airflow and seasonal allergic rhinitis symptoms induced by grass pollen exposure
Authors: Horak F. , Stübner P. , Zieglmeyer R. , Harris A. G.
Published: May 2003

Background: Nasal congestion is a chronic symptom of seasonal allergic rhinitis (SAR) that is often difficult to treat with antihistamines. Desloratadine, a new, potent, H1‐receptor antagonist has been shown to decrease nasal congestion in clinical trials and to maintain nasal airflow in response to grass pollen exposure. We compared the effects of desloratadine 5 mg and placebo on nasal airflow, nasal secretion weights and SAR symptoms, including nasal congestion, in patients exposed to grass pollen in an environmental exposure unit.

Methods: Forty‐six grass pollen allergic SAR patients received desloratadine or placebo for 7 days, followed by a 10‐day washout, and then crossed over to the other treatment for 7 days. A 6‐h allergen exposure was performed at the end of each treatment period.

Results: Desloratadine was significantly superior to placebo in maintaining nasal airflow (P≤ 0.014) and lessening the increase in nasal secretion weights (P < 0.001) throughout allergen exposure. SAR symptom scores, including nasal congestion, were significantly less with desloratadine than placebo (P≤ 0.001). Desloratadine was well tolerated.

Conclusions: This study confirms that, compared with placebo, desloratadine can maintain nasal airflow and reduce nasal secretion weights and the severity of SAR symptoms, including nasal congestion, in SAR patients exposed to grass pollen allergen.
Accumulation of CCR4‐expressing CD4+ T cells and high concentration of its ligands (TARC and MDC) in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia
Authors: Katoh S. , Fukushima K. , Matsumoto N. , Matsumoto K. , Abe K. , Onai N. , Matsushima K. , Matsukura S.
Published: May 2003

Background: Th2 cells are thought to be involved in eosinophilic inflammation of the lung. CC chemokine receptor 4 (CCR4) has been identified as a specific receptor for both thymus and activation‐regulated chemokine (TARC) and macrophage‐derived chemokine (MDC), and is preferentially expressed on Th2 cells.

Objective: Our aim was to evaluate the role of Th2 cells in the lung of patients with eosinophilic pneumonia (EP).

Methods: The concentrations of TARC, MDC, and interleukin (IL)‐5 were measured in bronchoalveolar lavage fluid (BALF) by ELISA. Proportion of CCR4‐expressing CD4+ T cells (CCR4+ CD4+ T cells) was determined by flow cytometry.

Results: TARC and MDC concentrations in BALF were higher in patients with EP than in normal subjects. The proportion of CCR4‐expressing cells among CD4+ T cells was higher in BALF than in peripheral blood of patients with EP. There was a significant correlation between the number of CCR4+ CD4+ T cells and the levels of TARC, MDC, and IL‐5 in BALF of patients with EP.

Conclusions: Our data suggest that Th2 cells, which express CCR4 and its ligands (TARC and MDC), contribute to the pathogenesis of EP in the lung.
A dual long‐term effect of breastfeeding on atopy in relation to heredity in children at 4 years of age
Authors: Siltanen M. , Kajosaari M. , Poussa T. , Saarinen K.M. , Savilahti E.
Published: May 2003

Background: The long‐term effect of early feeding on atopic sensitization is still unsolved. The aim of this study was to evaluate the long‐term effect of breastfeeding on atopy in groups of 4‐year‐old children stratified by atopic heredity.

Methods: We collected four groups of 4‐year‐old children from a birth cohort: two groups with differing backgrounds of atopic heredity, all exclusively breast‐fed for at least 3 months; and two groups with differing atopic heredity, but all fed with cow's milk‐based formula during their first weeks. The data were collected with a questionnaire, skin prick testing, and measurement of serum total and allergen‐specific IgE levels.

Results: Breastfeeding significantly decreased the risk of allergic rhino‐conjunctivitis [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.18–0.95] and sensitization to furred pets, as measured by skin prick results, in children with atopic heredity, whereas in children without atopic heredity, breastfeeding was related to an increased risk of symptomatic atopy (OR 2.57, 95% CI 1.16–5.70), and high serum IgE values. A significant interaction was found between heredity and breastfeeding.

Conclusions: The long‐term effect of breastfeeding was dual: in children with atopic heredity, breastfeeding protected against atopy, whereas in children without atopic heredity, it increased the risk of atopy.
Combined skin prick and patch testing enhances identification of peanut‐allergic patients with atopic dermatitis
Authors: Seidenari S. , Giusti F. , Bertoni L. , Mantovani L.
Published: May 2003

Background:  Food atopy patch tests (APTs) are considered a useful tool for the diagnosis of food allergy. Hypersensitivity to peanuts has not been investigated by means of APTs so far.

Methods:  APTs and skin prick tests (SPTs) with peanuts were performed in 136 atopic dermatitis (AD) patients. Relevance of positive and negative responses to these tests was assessed by repeated open challenges with peanuts.

Results:  Nine percent of our AD patients reacted to the challenge. Positive responses to APTs were recorded in 19% of the patients, whereas in 12% positive SPTs were observed. APTs were more frequently positive in subjects with eczematous responses after challenge with respect to those with urticarial reactions. SPT reactivity proved to be higher in patients above 12 years of age, whereas APT positivity was more frequent in children under 6 years. APT sensitivity proved significantly higher than SPT sensitivity, in particular in children under 12 years of age. On the contrary, SPT specificity and positive predictive value were significantly higher with respect to those of APT in the age group of subjects under 6 years of age.

Conclusions:  Our data suggest that APTs with peanuts may represent a useful integration to standard testing modalities employed for the diagnosis of peanut allergy in AD patients.
Epidermal growth factor receptor – but not histamine receptor – is upregulated in seasonal allergic rhinitis
Authors: Matovinovic E. , Solberg O. , Shusterman D.
Published: May 2003

Background: We were interested in exploring the molecular mechanisms underlying the observed difference in histamine (H) responsiveness between seasonal allergic rhinitic (SAR) and nonrhinitic (NR) subjects. We hypothesized that SAR subjects express higher nasal mucosal histamine receptor 1 (H1R) and 2 (H2R) levels than do NR subjects. In addition, we examined expression of genes involved in regulating the glandular response, including epidermal growth factor (EGF), EGF receptor (EGFR), and mucins (Muc5Ac and Muc5B).

Methods: Fourteen subjects, seven SAR and seven NR, were provoked during pollen season with doubling doses of H (0.125–8.0 mg/ml). Nasal airway resistance (NAR) was measured by active posterior rhinomanometry. Provocation was halted when NAR exceeded 150% of baseline. Prior to provocation, nasal scrapings were obtained and mRNA quantified using two‐step real‐time PCR.

Results: The mean PD50 (concentration of H producing a 50% increase in NAR) was significantly lower in the SAR than NR group (0.36 vs 1.32 mg/ml; P < 0.05). The ratio of relative gene copy numbers between the SAR and NR groups were as follows: H1R, 0.85 (P = 0.52); H2R, 0.67 (P = 0.35); EGF, 1.02 (P = 0.93), and EGFR, 103.5 (P < 0.05).

Conclusions: There were no significant differences in H1R or H2R mRNA levels between SAR and NR subjects in‐season, despite observed differences in H reactivity. SAR subjects, however, did show a significant elevation in EGFR expression, consistent with the observation of mucus hypersecretion in allergic rhinitis.
Nasal blockage and urinary leukotriene E4 concentration in patients with seasonal allergic rhinitis
Authors: Higashi N. , Taniguchi M. , Mita H. , Ishii T. , Akiyama K.
Published: May 2003

Background: Cysteinyl‐leukotrienes have been reported to have a primary role in the induction of nasal blockage of allergic rhinitis. However, there has been little experimental evidence that substantiates the relationship between nasal blockage severity and urinary leukotriene E4 (U‐LTE4) concentration in patients with seasonal allergic rhinitis (SAR).

Methods: The concentrations of urinary mediators in 20 SAR patients were measured using an enzyme immunoassay to determine the relationship between nasal blockage severity and U‐LTE4 concentration in patients with SAR.

Results: The basal U‐LTE4 concentration was significantly higher in SAR patients with severe nasal blockage than in those with mild nasal blockage and in healthy control subjects. Although U‐LTE4 concentrationwas significantly higher in patients with both asthma and SAR than in SAR patients with mild nasal blockage, no significant difference in the U‐LTE4 concentration between patients with both asthma and SAR and SAR patients with severe nasal blockage was found. There was a significant correlation between U‐LTE4 and urinary 9α11β‐prostoglandin F2 (9α11βPGF2) concentrations (rs = 0.51, P = 0.02) in SAR patients.

Conclusions: Although specific sites and cells of cysteinyl‐leukotriene biosynthesis could not be determined in this study, severe nasal blockage is associated with the increased excretion level of U‐LTE4.
Cross‐reactivity between the major Parietaria allergen and rotavirus VP4 protein
Authors: Di Somma C. , Fiore L. , Di Lonardo A. , Ridolfi B. , Garzillo C. , Chersi A. , Buono C. , Menna T. , Ruffilli A.
Published: May 2003

Background: The present study investigates immunological cross‐reactivity between Par o 1, the major pollen allergen of Parietaria, and the VP4 protein of rotavirus, a microorganism that is world‐wide the main etiological agent of gastroenteritis in children.

Methods: IgG and IgE cross‐reactivity was assessed by direct binding and competitive inhibition assays (ELISA and DARIA), using recombinant VP4 from rhesus infectious rotavirus (RR), synthetic peptides and Par o 1‐specific antibodies affinity purified from pooled and individual human sera.

Results: Antibodies specifically binding Par o 1, affinity purified from the sera of 35 individuals with skin test positivity to Parietaria and from 14 pools, were extensively cross‐reactive with RRVP4. Cross‐reactive binding was specifically inhibited by synthetic peptides derived from the C‐terminal sequences of the VP4 proteins from human and rhesus infectious rotavirus.

Conclusions: This study reports the first evidence of cross‐reactivity between an allergen and a viral antigen.
Enhanced cough response to hyperpnea with cold air challenge in chronic cough patients showing increased cough sensitivity to inhaled capsaicin
Authors: Cho Y. S. , Park S. Y. , Lee C.‐K. , Lee E. Y. , Shin J.‐H. , Yoo B. , Moon H.‐B.
Published: May 2003

Background: Although many chronic cough patients have complained of an induced cough by cold air contact, the clinical relevance of cold air to inducing a cough and the diagnostic value of a hyperpnea with cold air (HCA) challenge to detect a hyperreactive cough reflex have not yet been investigated.

Methods: Recordings of cough counts after a 2‐min HCA challenge were performed in 49 chronic cough patients and 15 healthy controls. Capsaicin cough provocation tests, which determine the threshold concentration of capsaicin that induces five or more consecutive coughs (C5), were also administered.

Results: After comparing the results from the capsaicin cough provocation tests of the patients and the controls, the chronic cough patients were divided into two groups: an increased cough sensitivity (ICS) group (n = 28) (C5 < 32 μmol/l) and a normal cough sensitivity (NCS) group (n = 21) (C5 ≥ 32 μmol/l). The median value of induced cough counts after a HCA challenge was 11 coughs in patients with ICS and was a significantly enhanced cough response compared to that of the patients with NCS and healthy controls (four coughs, respectively).

Conclusions: A simple cough provocation test using a HCA challenge may be useful for detecting ICS. It also suggests that hyperreactive cough reflexes may be one of the mechanisms of inducing chronic cough.
The effect of calcineurin inhibitors on endothelial function in renal transplant recipients
Authors: Oflaz Huseyin , Turkmen Aydin , Kazancioglu Rumeyza , Kayacan Seyit M , Bunyak Banu , Genchallac Hakan , Erol Bulent , Mercanoglu Fehmi , Umman Sabahattin , Sever Mehmet S
Published: May 2003

Abstract:  Endothelial dysfunction is of vital importance, as it may cause ischemia and dysfunction in various organs. Despite, this problem has been well documented in patients with end‐stage renal disease (ESRD), there is not enough data considering this issue following renal transplantation. One of the potential causes of endothelial dysfunction in renal transplant recipients may be administration of calcineurin inhibitors. The aim of this study is to evaluate the effects of two different calcineurin inhibitors [cyclosporin A (CsA) and tacrolimus (FK506)] on endothelial function in renal transplant patients. Forty‐four renal transplant recipients [22 on FK506 (group I) and 22 on CsA (group II)] were studied. Endothelial functions of the brachial artery were evaluated by using high resolution vascular ultrasound. Endothelium‐dependent and ‐independent vasodilations were assessed by establishing reactive hyperemia and using sublingual nitroglycerine (NTG), respectively. Results are presented as percentage change from baseline values. Significant endothelial dysfunction was noted in renal transplant patients treated with CsA. While endothelium‐dependent vasodilation was 12.1 ± 5.1% in group I and it was 6.5 ± 3.7% in group II (p < 0.001). The increase in brachial artery diameter after sublingual NTG was 20.1 ± 6.3 and 12.7 ± 5.6% in groups I and II, respectively. This indicates that the endothelium‐dependent and ‐independent vasodilation of the patients on FK506 is better preserved than the patients on CsA therapy. Besides, blood flow volume (BFV) increase was 51.2 ± 39.4 and 43.9 ± 24.3%, in groups I and II, respectively, in reactive hyperemia period (p > 0.05). Post‐transplant course of renal transplant recipients is complicated by endothelial dysfunction. This problem is more prominent in patients on CsA therapy, which can predispose these patients to more frequent cardiac complications.
The effect of ATG on cytokine and cytotoxic T‐lymphocyte gene expression in renal allograft recipients during the early post‐transplant period
Authors: Simon Tania , Opelz Gerhard , Weimer Rolf , Wiesel Manfred , Feustel Andreas , Ott Ralf C , Süsal Caner
Published: May 2003

Abstract: Background: Despite the long history of ATG use, the exact in vivo mechanism of action remains unclear. In the present study, we analyzed the effect of ATG‐induction therapy on expression of 10 immunologically relevant genes in the early post‐transplant period.

Methods: Eight renal allograft recipients received post‐transplant prophylactic ATG treatment on 10 consecutive days and an additional three patients received treatment on 5, 6, or 7 consecutive days, respectively. Gene expression was measured at the beginning and the end of therapy and normalized to a control gene using Taqman real‐time PCR methodology. Results were compared with those of matched control patients. No patients were diagnosed with rejection.

Results: ATG‐treated patients showed decreases in the expression of cytotoxic T cell genes perforin (−56%, p = 0.03) and granzyme B (−45%, p = 0.01) and cytokine gene IFN‐γ (−75%, p = 0.005), and significant increases in the expression of cytokine genes IL‐7 (550%, p = 0.04), IL‐10 (275%, p = 0.01), IL‐15 (417%, p = 0.03), TNF‐α (615%, p = 0.01), and TGF‐β (235%, p = 0.02). No significant changes were observed in the control group, with the exception of a decrease in IL‐10 expression (−42%, p = 0.01). There were no significant changes in IL‐12 or Fas‐L expression in either group.

Conclusion: ATG‐induced decreases in the expression of IFN‐γ, perforin, and granzyme B and increases in IL‐10 and TGF‐β might be considered beneficial to the recipient, whereas increases in the expression of IL‐7, IL‐15, and TNF‐α genes might be involved in immunological processes not effected by ATG that may harm the transplant in the long term.
Cyclosporine and its metabolites before and 2 h post‐dose: comparative measurements of a monoclonal and a polyclonal immunoassay
Authors: Vyzantiadis T , Belechri AM , Memmos D , Axiotou M , Vyzantiadis A , Papadimitriou M
Published: May 2003

Abstract:  The aim of the study was to investigate the better accuracy of the 2‐h post‐dose (C2) levels of cyclosporine (CyA), compared with the pre‐dose (C0) levels and to evaluate the results measured by a monoclonal or a polyclonal immunoassay. The parent compound of CyA in C2 (monoclonal2) was measured in 53 kidney transplant patients by the monoclonal fluorescence polarization method, as well as the parent compound plus metabolites (polyclonal2) by the polyclonal fluorescence polarization method. Also, the parent compound was measured in 21 of the patients for the C0 (monoclonal0), whereas the parent compound plus metabolites in 36, for the C0 (polyclonal0). As level of metabolites was considered the difference between polyclonal and monoclonal values (polyclonal–monoclonal), either in C0 (metabolites0) or in C2 (metabolites2). The ratio polyclonal2/monoclonal2 gave a mean value of 1.7±0.2 (mean±SD), whereas the mean value of the ratio polyclonal0/monoclonal0 was 2.3±0.6, with almost double variation. The mean value of the ratio metabolites2/monoclonal2 was 0.7±0.2 and of the ratio metabolites0/monoclonal0 was 1.3±0.6. The difference between the two ratios is very significant (p = 0.000001) and they are not correlated with each other (r = 0.18, p = 0.44). The measurements of monoclonal0 and polyclonal0 or monoclonal2 and polyclonal2 are very significantly correlated (r = 0.94, p = 0.000001 and r = 0.97, p = 0.000001, respectively). In C0 the proportion of metabolites is higher than in C2, with a double variation, as the degree of metabolism is diverse. Consecutively, in monoclonal methods, as cross‐reactions occur with metabolites, it is more accurate to use the C2 measurement for the evaluation of CyA. The application of both methods, the polyclonal and the monoclonal, could be a useful tool as it gives an estimation of metabolites whose degree of contribution to the immunosuppressive result is difficult to ascertain. Finally, if for reasons of clinical experience, the polyclonal method is used, then the mean therapeutic levels of polyclonal2 are 1.5–1.7 compared with monoclonal2.
Chronic rejection with or without transplant vasculopathy
Authors: Sijpkens Yvo WJ , Doxiadis Ilias IN , Van Kemenade Folkert J , Zwinderman Aeilko H , De Fijter Johan W , Claas Frans HJ , Bruijn Jan A , Paul Leendert C
Published: May 2003

Abstract: Background: Chronic allograft nephropathy (CAN) is defined and graded in the Banff ’97 scheme by the severity of interstitial fibrosis and tubular atrophy. It has been denoted that chronic rejection can be diagnosed if the typical vascular lesions are seen, consisting of fibrointimal thickening. We observed several patients who developed CAN without vascular changes or signs of cyclosporine toxicity. Therefore, we assessed the risk factor profiles of CAN with and without transplant vasculopathy.

Methods: A cohort of 654 cadaveric renal transplants performed between 1983 and 1997 that functioned for more than 6 months was studied. Fifty‐four transplants had CAN defined by a significant decline in renal function together with interstitial fibrosis and tubular atrophy without signs of cyclosporine nephrotoxicity or recurrent disease. Using the Banff chronic vascular (CV) score, 23 of 54 cases (43%) had a chronic vasculopathy score of 0 or 1 whereas 31 cases (57%) had a CV score of 2 or 3. Applying multivariate logistic regression, predictor variables of the two groups were compared with 231 transplants with a stable function for at least 5 yr.

Results: Graft histology was obtained at a mean of 2.4 and 2.9 yr after transplantation in the group with or without vasculopathy, respectively. Acute rejection episodes (AREs) after 3 months post‐transplantation were the strongest risk factor for both forms of CAN, odds ratio (OR) 14.7 (6.0–36.0). CAN with vasculopathy was also associated with transplants performed in the 1980s, OR 4.95 (1.65–14.9) and with creatinine clearance at 6 months, OR 0.58 (0.44–0.75) per 10 mL/min increase. In contrast, young recipient age, OR 0.69 (0.47–0.99) per 10‐yr increase, and the presence of panel reactive antibodies at the time of transplantation, OR 1.26 (1.08–1.47) per 10% increase, were independent risk factors for CAN without vasculopathy.

Conclusions: After exclusion of cyclosporine toxicity or recurrent disease CAN occurred without moderate or severe transplant vasculopathy in 43% of the cases. The correlation with young recipient age, sensitization and late ARE suggest an immune pathogenesis, consistent with chronic rejection.
Cost‐effective and safe ambulatory long‐term immunoprophylaxis with intramuscular instead of intravenous hepatitis B immunoglobulin to prevent reinfection after orthotopic liver transplantation
Authors: Faust Dominik , Rabenau Holger F , Allwinn Regina , Caspary Wolfgang F , Zeuzem Stefan
Published: May 2003

Abstract: Background: Hepatitis B (HBV)‐infected patients receive an anti‐HBs immunoprophylaxis [hepatitis B immunoglobulin (HBIG) titre of more than 100 IU/L] in combination with lamivudine to prevent reinfection after orthotopic liver transplantation (OLT). In comparison with intramuscular (i.m.) HBIG, costs for intravenous (i.v.) HBIG are found to be extremely high. We therefore studied patients' outcome (i) after a switch from i.v. to i.m. HBIG and (ii) the outcome after the patients were initially treated with i.m. HBIG after discharge from the hospital.

Methods: (i) Six outpatients were switched from 2000 IU i.v. HBIG (Hepatect®) administered every 2 wk to 2000 IU i.m. HBIG (Hepatitis‐B‐Immunglobulin Behring®) given once a month. (ii) Six other outpatients were directly treated with i.m. HBIG every 4 wk after OLT. All patients also received 100 mg lamivudine/d.

Results: Patients switched from i.v. to i.m. HBIG had stable anti‐HBs titres (i.v. HBIG: 180 ± 37 IU/L vs. i.m. HBIG: 173 ± 23 IU/L). Patients directly treated with i.m. HBIG also had sufficient anti‐HBs titres (176 ± 31 IU/L). Intramuscular application of HBIG was well tolerated by all patients and no side‐effects were observed in patients receiving i.m. HBIG. In comparison with the protocol using i.v. HBIG, the costs of i.m. treatment were 60% lower.

Conclusion: Long‐term administration of i.m. HBIG saves up to 60% of the usual costs for i.v. prophylaxis of HBV reinfection in patients after OLT. In combination with lamivudine, long‐term i.m. HBIG therapy is as efficient as i.v. HBIG treatment, but its lower costs clearly favour its use in preventing HBV reinfection after OLT.
Hyperparathyroidism and long‐term bone loss after renal transplantation
Authors: Heaf James , Tvedegaard Erling , Kanstrup Inge‐Lis , Fogh‐Andersen Niels
Published: May 2003

Abstract: Background:  While early bone loss after renal transplantation (RT) is well described, factors affecting the long‐term fate of bone have received less attention.

Methods:  Whole body (WB), lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) was measured using dual energy X‐ray absorptionometry in 126 stable RT patients and repeated in 114 survivors after 3 yr. Percentage change per year (%/yr) was correlated to clinical and biochemical markers of bone metabolism.

Results:  Low bone mass was a marker of increased mortality (FN < 80% normal 6.3%/yr; >80% 2.2%/yr). Percent change was WB −0.7 ± 1.5 (p < 0.01); LS −0.3 ± 2.6; FN −1.0 ± 3.0 (p < 0.01) and, corrected for expected loss for age and sex: WB −0.5 (p < 0.01); LS 0.0; FN −0.8 (p < 0.05). Factors associated with increased loss rates were (LS%): short RT duration [<2 yr: −3.1 (p < 0.01)], high prednisone dose [>9 mg/d: −1.9 (p < 0.01)], high cyclosporine trough concentration [>175 ng/L: −1.9 (p < 0.05)], high hyperparathyroidism (PTH) [>150 ng/L: −1.5 (p < 0.05)], high alkaline phosphatase [>275 U/L: −1.6 (p < 0.05)], high osteocalcin [>75 μg/L: −1.6 (p < 0.05)]. Marginal detrimental effects of uremia, hypoalbuminemia and hyperphosphatemia were noted. Thiazide treatment seemed to protect against, and furosemide to exacerbate, bone loss, but this may have been related to associated uremia. Patients treated with vitamin D gained bone, while untreated patients with low initial 1,25‐dihydroxyvitamin D lost bone [FN%−2.1 (p < 0.05)]. The prevalence of PTH (52%) and hypercalcemia (22%) remained unchanged. There was no effect of sex hormone levels, calcium and phosphate excretion, or serum calcium.

Conclusion:  While LS BMD stabilizes after RT, there is a continuing loss of WB and FN BMD. The major causes of bone loss are steroid therapy and continuing PTH, with no tendency towards spontaneous resolution. Increased vitamin D and calcium therapy should be considered for this patient group, and more aggressive therapy, e.g. parathyroidectomy given for patients with resistant PTH of >150 ng/L.
Diagnostic efficiency of rejection monitoring after heart transplantation with cardiac troponin T is improved in specific patient subgroups
Authors: Gleissner Christian A , Klingenberg Roland , Nottmeyer Winfried , Zipfel Stephan , Sack Falk‐Udo , Schnabel Philipp A , Haass Markus , Dengler Thomas J
Published: May 2003

Abstract: Cardiac troponin T (cTnT) is a cardio‐specific myofibrillar protein known to be elevated early after heart transplantation and during cardiac allograft rejection. cTnT determination in heart allograft recipients showed elevated levels in patients with higher degrees of graft rejection (International Society for Heart and Lung Transplantation grades ≥3A−4). Subgroup analyses revealed demographic patient characteristics markedly improving the diagnostic efficiency of cTnT measurement for rejection monitoring, including male recipient gender, recipient age <60 yr, female donor gender and donor age ≥ 33 yr. The clinical utility of these parameters was confirmed by longitudinal patient data and may help to select recipients most likely to benefit from cTnT rejection surveillance.
Improving oral health: current considerations
Authors: Ciancio S.
Published: May 2003

The high incidence of periodontal disease among adults in the Western world indicates that in most cases, routine dental care could be considerably improved. The progressive effect of the disease suggests that improvements in oral cleanliness are mandatory if large numbers of adults are to retain their teeth into old age. Data show that periodontal disease can be minimized through effective plaque control, and that a combination of brushing, interdental cleaning, and chemotherapeutic agents (e.g. mouthwash) is beneficial to patients with plaque control problems. The vast majority of adults do not follow an adequate home‐care routine. Average brushing times are low, and only a minority of patients regularly floss. In addition, in those patients who do regularly brush and floss, a deterioration of plaque control occurs over time, suggesting that compliance is a major issue. The principal challenge for dental professionals is to identify how best to elicit an improvement.
Penetrating the plaque biofilm: impact of essential oil mouthwash
Authors: Ouhayoun J.‐P.
Published: May 2003

The interaction between saliva‐coated tooth surfaces and pathogenic bacteria is partly governed by electrostatic and hydrophobic interactions, providing a solid rationale for using chemical agents as part of a plaque‐control routine. Chlorhexidine works in several ways. For example, it binds to salivary mucins on the bacterial cell membrane, and penetrates the plaque biofilm. Essential oil (EO) mouthwashes kill micro‐organisms by disrupting their cell walls and inhibiting their enzymic activity. They prevent bacterial aggregation, slow multiplication and extract endotoxins. Recent studies have shown that bacterial phenotypes are altered when organisms change from a planktonic to a sessile state. This suggests that an effective mouthwash must also penetrate the plaque biofilm. Two studies have demonstrated the ability of an EO mouthwash to penetrate the plaque biofilm.
Management of oral malodour
Authors: Quirynen M.
Published: May 2003

Halitosis is a common problem. Its aetiology is multifactorial, but oral malodour is usually caused by microbial metabolism from the tongue, saliva or dental plaque. Mouthwashes are only effective against halitosis caused by intraoral factors. The principal causative agents of oral malodour are volatile sulphide compounds (VSCs), including hydrogen sulphide, methyl mercaptan and dimethyl sulphide. Data suggest that oral VSC levels correlate with the depth of periodontal pockets. Trials have shown that both mechanical oral care and mouthwash use can reduce halitosis levels. The majority of studies involving mouthwashes have investigated chlorhexidine and essential oil mouthwashes, although comparative studies are sparse.
Effects of maxillary sinus floor elevation surgery on maxillary sinus physiology
Authors: Timmenga Nicolaas M. , Raghoebar Gerry M. , Liem Robert S. B. , Van Weissenbruch Ranny , Manson Willem L. , Vissink Arjan
Published: May 2003

In a prospective study, the effects of elevation surgery of the maxillary sinus floor on maxillary sinus physiology were assessed. Seventeen consecutive patients without preoperative anamnestic, clinical and radiological signs of maxillary sinusitis underwent sinus floor elevation surgery with iliac crest bone grafts. All patients were subjected to unilateral endoscopic examination of the maxillary sinus, taking of a biopsy specimen from the sinus floor mucosa, and collection of a sinus lavage‐fluid aspirate. This triad of evaluations was performed immediately preceding the elevation procedure, and 3 months (at implant insertion) and 9 months (at uncovering of implants) postoperatively. All procedures were performed under general anesthesia. Preoperatively, three out of 17 patients showed pre‐existing mucosal pathology endoscopically, while the 3‐ and 9‐month results revealed the presence of mucosal pathology in four and two patients, respectively. The 3‐month microbiological evaluation showed a significant increase in cultures with bacterial growth, while the 9‐month culture results were comparable to the preoperative status of the maxillary sinus. Morphologically, neither fibrosis nor an altered inflammatory response or thickening of the epithelium and lamina propria was observed postoperatively. The number of goblet cells in the epithelial layer was increased. From this study it is concluded that the effect of maxillary sinus floor elevation surgery with autogenous bone grafts does not appear to have clinical consequences in patients without signs of pre‐existing maxillary sinusitis.
Elevated levels of collagen cross‐link residues in gingival tissues and crevicular fluid of teeth with periodontal disease
Authors: Jepsen Søren , Springer Ingo N. G. , Buschmann Andreas , Hedderich Jürgen , Açil Yahya
Published: May 2003

Lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) are collagen cross‐link residues. Lysylpyridinoline is present in most tissues, whereas LP is present mainly in mineralized tissue. Both are elevated in tissue with increased collagen resorption. The purpose of this investigation was to assess if the concentrations of LP and HP are elevated in gingiva and gingival crevicular fluid (GCF) of teeth with advanced periodontitis (AP). We investigated human gingival biopsies of healthy teeth (n = 19) and teeth with AP (n = 43) in 49 individuals. Samples of GCF from 54 teeth with AP were collected in seven patients and compared with samples from 11 patients with experimentally induced gingivitis. Levels of LP and HP were measured by HPLC and fluorescence detection. Gingival concentrations of HP but not LP around teeth with advanced periodontitis were significantly elevated compared with teeth with healthy periodontium. While significant amounts of HP and LP were measurable in the GCF of teeth with AP, no HP and LP was identified 3 months following non‐surgical periodontal therapy of the teeth or in fluid from teeth subjected to experimentally induced gingivitis. Elevated concentrations of HP and LP in GCF may serve as indicators of ongoing destruction of periodontal tissues and alveolar bone in advanced periodontitis.
Serum‐mediated release of leukotoxin from the cell surface of the periodontal pathogen Actinobacillus actinomycetemcomitans
Authors: Johansson A. , Claesson R. , Hänström L. , Kalfas S.
Published: May 2003

The leukotoxin of the periodontopathogen Actinobacillus actinomycetemcomitans is an important virulence factor that lyses human neutrophils and monocytes and thus, it may enable the bacterium to evade the local host defense. The toxin also induces degranulation of neutrophils and cytokine release in monocytes. To trigger these biological activities, leukotoxin has to be released from the bacterium and diffuse into the periodontal tissues. To date, the conditions found to cause toxin release have been artificial and have included high ion concentration and alkaline conditions. To study the release of the toxin under conditions mimicking the natural environment of the periodontium the ability of human serum to enable leukotoxin release from the bacterial surface was examined. Suspensions of leukotoxic A. actinomycetemcomitans strains were incubated with various concentrations of human serum or serum albumin. The suspensions were centrifuged and the leukotoxin in the supernatants or the cell pellets was detected by gel electrophoresis and immunoblotting. Serum was found to cause the rapid release of leukotoxin from the bacteria in a concentration‐dependent manner. Pure albumin exhibited a similar effect. The leukotoxin released was active against human neutrophils. Only a minor proportion of it was associated with membranous vesicles produced by the bacteria. The results indicate that serum, a fluid closely related to the exudate in inflamed periodontal pockets, releases leukotoxin from the cell surface of A. actinomycetemcomitans. The process may enable the diffusion of the toxin from the bacterial biofilm into the surrounding tissues, where it can exert its biological effect.
Erosion‐inhibiting effect of sodium fluoride and titanium tetrafluoride treatment in vitro
Authors: Van Rijkom Hans , Ruben Jan , Vieira Ana , Huysmans Marie Charlotte , Truin Gert‐Jan , Mulder Jan
Published: May 2003

The prevention of dental erosion with fluoride is still largely unknown territory. It was the aim of this study to determine the erosion‐inhibiting effect of topical neutral 1% sodium fluoride (NaF) application and an application of a 4% titanium tetrafluoride (TiF4) solution compared with no treatment. Ten bovine incisors were selected and three enamel samples prepared from each tooth. One sample from each tooth was assigned to one of three experimental groups. The experimental treatments were: no fluoride application (control); 4 min application of neutral 1% NaF gel; and 4 min application of 4% TiF4 solution. All of the specimens were repeatedly exposed to 50 mm citric acid solution containing 0.4 mm CaCl2, and 2.2 mm KH2PO4 at pH 3.0 over four consecutive days. The acid exposure was performed in intervals and the intensity was increased over the days of the experiment. Enamel dissolution was determined by calcium content measurement of the acid solution after exposure, using atomic absorption spectroscopy. A statistically significant erosion‐inhibiting effect was found for both NaF and TiF4 treatments compared with the control group from an erosion exposure time of 3 min. The reduction of calcium loss, however, was higher for the TiF4‐treated specimens than the NaF‐treated. From 16 min of erosion exposure, the erosion‐inhibiting effect was significantly stronger in the TiF4 than the NaF group. The relative reduction of calcium loss compared with the control group remained stable for the TiF4 group, whereas for the NaF group the relative reduction decreased with cumulative erosion time. It is concluded that topical TiF4 application provides a potential treatment option in erosion prevention.
The effects of a triclosan/copolymer dentifrice on oral bacteria including those producing hydrogen sulfide
Authors: Sreenivasan Prem
Published: May 2003

A clinical procedure was developed to examine the effects of short‐term and extended use of a triclosan/copolymer dentifrice and a commercial fluoride dentifrice on oral bacteria, including those producing hydrogen sulfide. Healthy adults volunteered for this double‐blind, crossover design clinical study and provided saliva samples for culturing on enriched and indicator media to enumerate all salivary bacteria and those producing hydrogen sulfide (odorigenic), respectively. Subjects brushed with an assigned dentifrice for 7 d and were sampled on day 8 to assess the long‐term effects on bacteria. Extended use of the triclosan/copolymer dentifrice resulted in a 49% and 66% reduction of salivary and odorigenic bacteria, respectively, compared with the fluoride dentifrice. To examine short‐term effects, subjects subsequently brushed with their assigned dentifrice and were sampled at 2 h and 4 h post‐brushing. At 2 h and 4 h post‐brushing, the triclosan/copolymer dentifrice resulted in a 62% and 52% decrease for salivary bacteria and 79% and 72% decrease for odorigenic bacteria, respectively, vs. the fluoride dentifrice. The results indicate a significant decrease of all salivary bacteria and hydrogen sulfide‐producing odorigenic bacteria following use of the triclosan/copolymer dentifrice and explain previous results on the efficacy of this dentifrice on oral malodor.
Human enamel dissolution in citric acid as a function of pH in the range 2.30≤pH≤6.30 – a nanoindentation study
Authors: Barbour Michele E. , Parker David M. , Allen Geoff C. , Jandt Klaus D.
Published: May 2003

The objective of this study was to investigate the dissolution of human enamel in citric acid solutions over a wide range of pH. The in vitro conditions are considered to be relevant to soft drink‐induced enamel erosion. Nanoindentation was used to investigate changes in the nanomechanical properties of polished enamel surfaces after exposure to citric acid solutions. Solutions used had 38.1 mmol l−1 citric acid and pH greater than 2.3 but less than 6.3 (2.30  pH  6.30). Samples were exposed to rapidly stirred, constant composition solutions for 120 s. Statistically significant changes in enamel hardness and reduced elastic modulus were observed after exposure to all solutions. There was an approximately linear dependence of enamel hardness on solution pH for 2.90  pH  6.30. Below pH 2.90, enamel is thought to have reached the lowest possible hardness value. The reduction in enamel dissolution caused by an increase in pH of a soft drink is likely to be small. Product modification to reduce the erosive potential of drinks may require additional methods such as addition of calcium salts.
Salivary IgA in response to periodontal treatment
Authors: Hägewald Stefan J. , Fishel Daniel L. W. , Christan Claudia E. B. , Bernimoulin Jean‐Pierre , Kage Andreas
Published: May 2003

There is evidence that the quantity of antigen load is crucial for the activation of IgA immune responses. In order to investigate the relevance of these findings in aggressive periodontitis, salivary antibody responses were measured during non‐surgical and antibiotic treatment. Twenty‐one patients with generalized aggressive periodontitis were monitored for total salivary IgA and IgA reactive to Porphyromonas gingivalis in resting and stimulated whole saliva. Non‐surgical treatment included full‐mouth professional tooth cleaning and subgingival scaling and root planing (SRP) under local anesthesia. Patients were recalled at 3 months and 6 months following systemic antibiotic treatment. Non‐parametric statistics showed significant improvements in the clinical parameters in all patients. Between baseline and 4 wk following SRP, median concentrations of total IgA decreased both in resting (−46%) and in stimulated (−33%) saliva. The P. gingivalis‐specific IgA activity showed a twofold increase at 4 wk after SRP. In addition to these changes, periodontal treatment of aggressive periodontitis did not appear to affect salivary IgA, and there were no significant correlations of IgA to the clinical parameters. In conclusion, salivary IgA responses during periodontal treatment were not found to have a diagnostic or prognostic significance.
Melatonin protects hepatic mitochondrial respiratory chain activity in senescence‐accelerated mice
Authors: Okatani Yuji , Wakatsuki Akihiko , Reiter Russel J.
Published: May 2003

Mitochondrial oxidative damage from free radicals may be a factor underlying aging, and melatonin, a powerful free radical scavenger, may participate in mitochondrial metabolism. We measured respiratory chain complex I and IV activities in liver mitochondria from a strain of senescence‐accelerated prone mice (SAMP8) and a strain of senescence‐accelerated resistant mice (SAMR1) at age 3, 6, and 12 months. No age‐associated effects were found in either complex I and IV activities, thiobarbituric acid‐reactive substances (TBARS), or glutathione peroxidase (GPx) activity in SAMR1. In contrast, SAMP8 showed significant age‐associated decreases in complex I and IV activities. While no age effect was found in TBARS in SAMP8, TBARS levels in SAMP8 were significantly more abundant than in SAMR1. GPx activity in SAMP8 decreased significantly by 12 months. Daily oral melatonin administration (2 μg/mL of drinking fluid) beginning when the mice were 7 months old significantly increased complex I and IV activity, decreased TBARS, and increased GPx activities in both SAMR1 and SAMP8 at 12 months. The implication of the findings is that melatonin may be beneficial during aging as it reduced the deteriorative oxidative changes in mitochondria and other portions of the cell associated with advanced age.
The protection of long chain polyunsaturated fatty acids by melatonin during nonenzymatic lipid peroxidation of rat liver microsomes
Authors: Leaden P. , Barrionuevo J. , Catalá A.
Published: May 2003

The in vivo and in vitro effects of melatonin (N‐acetyl‐ 5‐methoxytryptamine) on lipid peroxidation of long chain polyunsaturated fatty acids (PUFA) located in rat liver microsomes were determined. The effect of intraperitoneal administration of melatonin (10 mg/kg weight/24 hr) on ascorbate‐Fe++ induced lipid peroxidation of isolated rat liver microsomes was first examined. The ascorbate induced light emission in hepatic microsomes was inhibited by melatonin treatment [control group: 10.714 ± 0.894; melatonin group: 3.162 ± 0.515, counts per minute (cpm) × 10–5]. Significant differences in the content of arachidonic C20:4 n‐6 and docosahexaenoic acid C22:6 n‐3 were observed when control microsomes were lipid peroxidized in the presence of ascorbic acid. These changes were less pronounced in liver microsomes isolated from melatonin treated rats. In vitro assays showed that after incubation of rat liver microsomes in an ascorbate‐Fe++ system, at 37°C for 210 min, the total cpm originated from light emission (chemiluminescence) was found to be lower in those membranes incubated in the presence of melatonin. The fatty acid composition of total lipids isolated from rat liver microsomes was substantially modified when subjected to nonenzymatic lipid peroxidation with a considerable decrease of docosahexaenoic acid 22:6 n‐3 and arachidonic acid 20:4 n‐6. The inhibition of the lipid peroxidation process evaluated as chemiluminescence (total cpm at selected times) was melatonin concentration dependent. Melatonin, at a concentration 1.2 mM, inhibited almost completely the lipid peroxidation process. Arachidonic and docosahexaenoic acids were more affected than docosapentaenoic acid during the lipid peroxidation process. Not all fatty acids were equally protected after the addition of melatonin to the incubation medium. Our results indicate that melatonin may act in vivo and in vitro as an antioxidant protecting long chain PUFA present in rat liver microsomes from the deleterious effect by a selective mechanism that reduces the loss of docosahexaenoic and arachidonic acids.
The neuroprotective activities of melatonin against the Alzheimer β‐protein are not mediated by melatonin membrane receptors
Authors: Pappolla Miguel A. , Simovich Marcia J. , Bryant‐Thomas Tara , Chyan Yau‐Jan , Poeggeler Burkhard , Dubocovich Margarita , Bick Roger , Perry George , Cruz‐Sanchez Felix , Smith Mark A.
Published: May 2003

Exposure of neuronal cells to the Alzheimer's amyloidβprotein (Aβ) results in extensive oxidative damage of bio‐molecules that are profoundly harmful to neuronal homeostasis. It has been demonstrated that melatonin protects neurons against Aβ‐mediated neurotoxicity, including cell death and a spectrum of oxidative lesions. We undertook the current study to determine whether melatonin membrane receptors are involved in the mechanism of neuroprotection against Aβneurotoxicity. For this purpose, we characterized the free‐radical scavenging potency of several compounds exhibiting various affinities for melatonin membrane receptors (MLT 1a and 1b). Aβ‐mediated neurotoxicity was assessed in human neuroblastoma cells and in primary hippocampal neurons. In sharp contrast with melatonin, no neuroprotection against Aβtoxicity was observed when we used melatonin membrane receptor agonists that were devoid of antioxidant activity. In contrast, the cells were fully protected in parallel control experiments when either melatonin, or the structurally unrelated free‐radical scavenger phenyl‐N‐t‐butyl nitrone (PBN), were added to Aβ‐containing culture media. This study demonstrates that the neuroprotective properties of melatonin against Aβ‐mediated toxicity does not require binding of melatonin to a membrane receptor and is likely the result of the antioxidant and antiamyloidogenic features of the agent.
Melatonin blocks rat hippocampal neuronal apoptosis induced by amyloid beta‐peptide 25–35
Authors: Shen Yu‐Xian , Xu Shu‐Yun , Wei Wei , Wang Xue‐Long , Wang H , Sun X
Published: May 2003

To investigate whether melatonin protects neurons from apoptosis, we used amyloid beta‐peptide 25–35 (Aβ25–35) to induce apoptosis in cultured hippocampal neurons, and monitored the apoptotic activity of the neurons with or without melatonin treatment. Present study shows that melatonin at concentrations of 1 × 10−6and 1 × 10−5 mol/L prevents neuronal morphological changes induced by apoptosis, as characterized by the shrunken and rounded morphology caused by condensed chromatin and fragmented DNA. Melatonin further exhibited the ability to inhibit apoptotic internucleosomal DNA degradation. Moreover, flow cytometric analysis of cell cycle demonstrated that melatonin abolished the Aβ25–35‐induced apoptotic peak. Our results suggest that melatonin may play an important role to protect neurons from Aβ25–35‐induced apoptosis.