Metoprolol reduces sympathetic nerve hyperactivity in patients with heart failure.
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Journal Article↗
Biomedical subjects
B Andersson
Publications and source records attributed to B Andersson.
The redox state of the plastoquinone pool controls the level of the light-harvesting chlorophyll a/b binding protein complex II (LHC II) during photoacclimation.
A cytochrome b (6) f deficient mutant of Lemna perpusilla maintains a constant and lower level of the light-harvesting chl a/b-binding protein complex II (LHC II) as compared to the wild type plants at low-light intensities. Inhibition of the plastoquinone pool reduction increases the LHC II content of the mutant at both low- and high-light intensities but only at high-light intensity in the wild type plants. Proteolytic activity against LHC II appears during high-light photoacclimation of wild type plants. However, the acclimative protease is present in the mutant at both light intensities. These and additional results suggest that the plastoquinone redox state serves as the major signal-transducing component in the photoacclimation process affecting both, synthesis and degradation of LHC II and appearance of acclimative LHC II proteolysis. The plastoquinol pool cannot be oxidized by linear electron flow in the mutant plants which are locked in a 'high light' acclimation state. The cytochrome b (6) f complex may be involved indirectly in the regulation of photoacclimation via 1) regulation of the plastoquinone redox state; 2) regulation of the redox-controlled thylakoid protein kinase allowing exposure of the dephosphorylated LHC II to acclimative proteolysis.
Journal Article↗
Comparison of ready-to-use EMDOGAIN-gel and EMDOGAIN in patients with chronic adult periodontitis.
OBJECTIVES: The aim of this multicenter trial was to compare the clinical and radiographical outcome of a ready-to-use Emdogain-gel (test) with the marketed Emdogain (control). METHODS: Subjects with bilateral infrabony defects > or =4 mm deep and > or =2 mm wide according to radiographs were selected. 88 subjects with probing pocket depth (PPD) > or =6 mm > or =1 month after supervised oral hygiene and scaling participated. At baseline plaque index, bleeding on probing, PPD and probing attachment level were recorded and reproducible radiographs for computer-based bone level measurements were taken. In each subject, 1 tooth was randomly treated with the test and 1 tooth with the control gel. Examinations were repeated 8 and 16 months post-operatively. RESULTS: After 16 months, the mean test PPD was 4.1 mm and the mean control PPD 4.2 mm. The mean gain of attachment was 2.7 mm for test and 2.9 mm for the control sites, and the radiographic measurements demonstrated a mean gain of 1 mm for both test and control sites. CONCLUSION: This series of cases demonstrated a statistically significant reduction of pocket depths and gain of attachment and bone after 8 and 16 months with no difference between the 2 preparations.
Adult↗
Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth factor rescue in recurrent aggressive NHL. High response rates and limited toxicity, but limited impact on long-term survival.
The purpose of the study was to evaluate in patients with recurrent intermediate-grade NHL, the tolerance to and efficacy of an intensive salvage regimen consisting of high doses of ifosfamide, etoposide and mitoxantrone with G-CSF support, followed by autologous stem cell transplantation and to identify prognostic factors for survival in patients with recurrent aggressive lymphoma. Patients with recurrent intermediate-grade NHL under the age of 60 years were eligible. Induction consisted of ifosfamide 10 g/m(2) and etoposide 900 mg/m(2) with G-CSF 5 microg/kg twice a day. Upon recovery, patients underwent stem cell apheresis. Patients achieving complete remission (CR) underwent autologous stem cell transplantation using BEAM conditioning. Those with partial remission (PR) received treatment with ifosfamide 10 g/m(2), mitoxantrone 20 mg/m(2) and G-CSF 5 microg/kg. Those with CR received BEAM, those with PR received cyclophosphamide 4.5 g/m(2), etoposide 1200 mg/m(2) and cisplatin 135 mg/m(2) with stem cell rescue followed by BEAM. Antibiotic prophylaxis was given with all treatment cycles. The results were compared with those obtained in a prior study that used MINE-ESHAP salvage. Forty-four patients with recurrent intermediate-grade NHL were enrolled between March 1994 and September 1996. Median age was 50 years (24-61). Eleven patients had transformed lymphoma and seven had a T cell phenotype. Response rate to the high-dose ifosfamide regimen was 77% +/- 12% after two cycles and the complete response rate was 41% +/- 14%. Myelosuppression was profound but short. Median nadir ANC was 0 and the median duration of ANC <0.5 x 10(9)/l was 6 days (range 3-12). No severe infections occurred; 55% of the patients required blood transfusion and 42% required platelet transfusions. Myelosuppression and transfusion requirements were similar after the first and second cycles. Thirty-five of the 44 patients proceeded to autologous stem cell transplantation and one transplant-related death occurred. With a median follow-up of 52 months, progression-free survival at 2 years is 38% +/- 14% and survival is 52% +/- 15%. Data from these 44 patients were pooled with data on 53 patients who had received salvage treatment with MINE-ESHAP, for a multivariate analysis of prognostic factors. In multivariate analysis, serum LDH was strongly associated with survival. The use of a more intensive salvage regimen, did not result in a significant increase in long-term outcome, despite a high response rate. In conclusion, duration of treatment, response rates, treatment-related mortality and survival compare favorably with previous salvage regimens, but recurrence remains a major problem. Long-term survival in recurrent large cell lymphoma is influenced more by disease characteristics than by the type of salvage regimen used.
Adolescent↗
Thiotepa, busulfan, cyclophosphamide (TBC) and autologous hematopoietic transplantation: an intensive regimen for the treatment of multiple myeloma.
The study was designed to evaluate the efficacy and safety of an intensive, tri-alkylator conditioning regimen, consisting of thiotepa, busulfan and cyclophosphamide (TBC), prior to autologous hematopoietic cell transplantation in patients with multiple myeloma (MM) and to analyze factors associated with outcome. One hundred and twenty patients with MM received high-dose chemotherapy with TBC followed by autologous bone marrow (n = 24) or peripheral blood stem cell (PBSC) transplantation (n = 96). Fifty-four patients had chemosensitive disease and 66 had refractory disease at the time of transplantation. The overall response rate was 81% and the complete remission (CR) rate was 26%. Patients with chemosensitive disease had a CR rate of 52% vs 5% for patients with refractory disease. Multivariable analysis determined disease status at transplant as the factor most likely associated with long survival. Estimated median survival was 48, 35 and 9 months for patients with chemosensitive, primary refractory or disease in refractory relapse, respectively. Short interval from diagnosis to transplant among patients with primary refractory disease and younger age were also favorable prognostic factors for survival. Patients with refractory disease pre-transplant who achieved remission criteria rapidly after treatment had a worse outcome than the slow responders. Treatment-related mortality with the introduction of PBSC and better supportive care was 4.8%. In conclusion, TBC is an effective and relatively well-tolerated intensive conditioning regimen in patients with MM. A more favorable outcome was observed in patients with chemosensitive disease and with early treatment for primary refractory disease. TBC merits further study in these subgroups and comparison with alternative regimens in prospective studies is warranted.
Adult↗
Decitabine with allogeneic peripheral blood stem cell transplantation in the therapy of leukemia relapse following a prior transplant: results of a phase I study.
Relapse after allogeneic progenitor cell transplant is associated with a poor prognosis for patients with advanced leukemia, with few curative options available. Use of novel chemotherapeutic agents with limited toxicity is warranted. We investigated the role of decitabine, a pyrimidine analogue with significant anti-leukemic effect and limited toxicity, in this setting. Fourteen patients with advanced acute leukemia or transformed chronic myelogenous leukemia (CML) who had failed previous allogeneic transplant were treated. Decitabine at doses of 100 mg/m2 to 150 mg/m2 given every 12 h for 5 days was followed by infusion of stem cells from the original donor 2 to 5 days after the completion of chemotherapy. Dose of decitabine was escalated in cohorts of three patients based on the modified Fibonacci scheme. The primary study end-point was assessment of the toxicity of the regimen with secondary endpoints of response and survival. Eight patients responded with either a complete remission or partial hematological remission (absence of blasts in peripheral blood and bone marrow but with platelet count <100 x 10(9)/l). Toxicity was limited with no grade 3 or 4 toxicity directly attributable to the treatment. The median survival for all patients was 190 days (range 11 to 1215+ days). Decitabine at doses of 100 mg/m2 to 150 mg/m2 given every 12 h for 5 days, followed by stem cell infusion from the original donor was well tolerated, and was associated with acceptable myelosuppression. Current response data should encourage further study of this drug, either alone or in combination with other agents, for treatment of relapsed acute leukemia after an allogeneic transplant.
Adult↗
Treatment of abdominally obese men with a serotonin reuptake inhibitor: a pilot study.
OBJECTIVE: To investigate the effects of a selective serotonin reuptake inhibitor (SSRI) on the neuroendocrine and autonomic nervous system perturbations found in abdominal obesity. DESIGN: Treatment for 6 months with citalopram and for 6 months with placebo using a double-blind, cross-over design, with a 2-month wash-out period between treatment periods. SUBJECTS: Sixteen healthy men, 45-60 years, moderately obese and with an abdominal fat distribution. MEASUREMENTS: Anthropometry, three different depression rating scales, serum lipids, testosterone, IGF-I, oral glucose tolerance test (OGTT), pituitary stimulation with corticotropin releasing hormone (CRH), arithmetic stress test, and excretion of cortisol and metoxycatecholamines in urine, collected during 24 h. RESULTS: Cortisol concentrations in the morning were low before treatment, indicating a perturbed function of the hypothalamic-pituitary-adrenal (HPA) axis. After treatment with citalopram morning cortisol concentrations rose to normal. Cortisol concentrations after stimulation with CRH or stress were elevated by citalopram treatment, but urinary cortisol excretion was unchanged. The glucose concentrations after OGTT (120 min) tended to be reduced, with unchanged insulin concentrations, whilst other metabolic values did not change during treatment. Heart rate after administration of CRH, and during laboratory stress test, decreased by treatment with citalopram. Diurnal urinary excretion of metoxycatecholamines tended to decrease. Neither body mass index nor waist/hip circumference ratio decreased. Depression scores were within normal limits before treatment and did not change. CONCLUSION: The results of this pilot study indicate improvements in the regulation of neuroendocrine-autonomic systems as well as metabolism in abdominal obesity during treatment with an SSRI.
Body Constitution↗
TGF-beta1 as a prognostic factor in the process of early osteoarthrosis in the rabbit knee.
OBJECTIVE: To assess changes in knee joint fluid concentrations of transforming growth factor-beta1 (TGF-beta1) and proteoglycan (PG) fragments during the early course of post-traumatic osteoarthrosis (OA) after meniscectomy in the rabbit knee, and to ascertain whether the concentrations of these substances shortly after operation could be used as prognostic markers for the OA process. DESIGN: In 15 rabbits with medial meniscectomy in one knee and a sham operation in the other knee, synovial lavage fluid samples were taken repeatedly, before operation, every third week post-operatively until 12 weeks, thereafter every sixth week, and at death. Five rabbits each were killed at 13, 25 and 40 weeks. Synovial lavage fluid samples from five non-operated rabbits served as controls. At death, two histological scores were formed that characterized the highest (MAX) and the overall (ALL) degree of OA changes in each joint. RESULTS: TGF-beta1 and PG fragment concentrations in synovial lavage fluid correlated highly (R=0.81, P< 0.001). Both OA scores were higher in meniscectomized than controls (P< 0.05). The synovial lavage fluid concentration of TGF-beta1 at 3 weeks, but no other time point, correlated to the histological scores (ALL, R=0.58; MAX, R=0.52;P< 0.001). CONCLUSION: Higher concentrations of TGF-beta1 in synovial lavage fluid early after surgery seemed indicative for the later development of more severe OA changes in contrast to lower concentrations. The association between TGF-beta1 and the changes found later in the cartilage was underlined by the high correlations between this substance and PG fragment concentrations in synovial lavage fluid at all time points.
Animals↗
Respiratory symptoms relate to physiological changes and inflammatory markers reflecting central but not peripheral airways. A study in 60-year-old 'healthy' smokers and never-smokers.
The aim of this study was to evaluate the relationship between respiratory symptoms, lung function and inflammatory markers in 'healthy' smokers. The study population was recruited from an epidemiological study with subjects of the same age, 60 years. Only smokers who considered themselves healthy (n=58) and a random sample of never-smokers (n=34) were investigated. All subjects underwent lung function tests--spirometry, carbon monoxide transfer (DLco) and the single-breath N2 method (N2 test)--together with high-resolution computed tomography (HRCT). A flexible bronchoscopy with a bronchoalveolar lavage (BAL) was performed in 30 smokers and 18 never-smokers. Bronchial biopsies were also taken. Smokers who reported non-specific respiratory problems, chronic bronchitis and wheezing in a symptom questionnaire had a lower forced expiratory volume in 1 sec (FEV1), FEV% and specific airway conductance (sGaw), lung function tests supposed to reflect the more central airways, than smokers without respiratory symptoms. A limited number of smokers with occasional non-specific respiratory problems also had more cytotoxic T cells (CD8) in bronchial biopsies. No differences were found in DLCO and the N2 test, lung function tests supposed to reflect the more peripheral airways including the alveoli, HRCT-diagnosed emphysema or inflammatory markers in blood and BAL between smokers with and without respiratory symptoms. It is concluded that even when smokers consider themselves 'healthy' they have mild symptoms that are related more to physiological changes and inflammatory markers that may reflect events in the central airways than to changes that may reflect events in the peripheral airways.
Biopsy↗
Neutrophil-associated activation markers in healthy smokers relates to a fall in DL(CO) and to emphysematous changes on high resolution CT.
Smoking is a risk factor for developing chronic obstructive pulmonary disease (COPD), but there are no good indicators for early identification of subjects who will develop symptomatic COPD. The aim of this study was to investigate inflammatory mechanisms related to changes in lung function and emphysematous changes on high resolution computed tomography (HRCT) in 'healthy' smokers. Subjects were 60-year-old men from a population study. Bronchoscopy was performed in 30 smokers and 18 who had never smoked. Blood tests, lung function measurements and HRCT were carried out in 58 and 34 subjects, respectively. In comparison with never-smokers, smokers had higher levels of myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein (ECP) and lysozyme in blood, higher levels of MPO, interleukin-8 (IL-8) and HNL in bronchial lavage (BL), and of IL-8, HNL and interleukin-lbeta (IL-1beta) in bronchoalveolar lavage (BAL). Smokers also had lower levels of Clara cell protein 16 (CC-16) in blood. HNL in BL and BAL showed strong correlations to other inflammatory markers (MPO, IL-8, IL-1beta). The variations in MPO in BL were explained by variations in HNL (R2 =0.69), while these variations in BAL were explained by variations in HNL and IL-1beta (R2 = 0.76). DL(CO) was the lung function variable most closely related to MPO and IL-8 in BL and BAL and to IL-1beta in BAL. In a multiple regression analysis, MPO, IL-1beta, IL-8 and CC-16 in BL and MPO in BAL contributed to the explanation of variations in DL(CO) to 41% and 22%. respectively, independent of smoking habits. In smokers with emphysematous lesions on HRCT, HNL in BAL correlated to emphysema score (r(s) = 0.71). We conclude that 'healthy' smoking men with a near normal FEV1 show signs of inflammation in the lower airways that are related to a decrease in DL(CO) and to emphysematous lesions on HRCT. This inflammation seems to be the result of both monocyte/macrophage and neutrophil activation.
Acute-Phase Proteins↗
Dose-related effects of metoprolol on heart rate and pharmacokinetics in heart failure.
BACKGROUND: The pharmacokinetics and pharmacodynamics of immediate-release (IR) metoprolol, 50 mg 3 times daily, were compared with those of different doses of controlled-release/extended-release metoprolol (CR/XL) given once daily. METHODS AND RESULTS: Fifteen patients with chronic heart failure were randomized to a 3-way crossover study to receive metoprolol IR 50 mg 3 times daily, CR/XL 100 mg once daily, and CR/XL 200 mg once daily for 7 days. On the seventh day of each treatment, serial plasma samples were drawn and standardized exercise tests and a 24-hour Holter recording were performed. Metoprolol IR 50 mg produced peak plasma levels comparable to those observed for CR/XL 200 mg (285 v 263 nmol/L). The difference in mean 24-hour heart rate between CR/XL 100 mg and IR 50 mg was 1.0 bpm (95% confidence interval [CI]), -2.9 to 4.9; NS) compared with -3.8 bpm (95% CI, -7.6 to -0.04; P = .048) between CR/XL 200 mg and IR 50 mg. Submaximal exercise heart rate was lower for patients receiving CR/XL 200 mg than those receiving IR 50 mg. No difference in tolerance or exercise performance was observed between treatment regimens. CONCLUSIONS: Peak plasma levels produced by metoprolol 200 mg CR/XL were similar to those of 50 mg IR. Metoprolol CR/XL 200 mg was associated with a more pronounced suppression of heart rate than metoprolol IR 50 mg. It is suggested that patients can safely be switched from multiple dosing of metoprolol IR 50 mg to a once-daily dose of metoprolol CR/XL.
Adrenergic beta-Antagonists↗
Procera AllCeram laminates: a clinical report.
The use of Procera AllCeram laminates for patients with discolored teeth has been described. In our experience, these laminates are simple to use and provide possibilities for excellent esthetics.
Aluminum Oxide↗
Active oxygen produced during selective excitation of photosystem I is damaging not only to photosystem I, but also to photosystem II.
With the aim to specifically study the molecular mechanisms behind photoinhibition of photosystem I, stacked spinach (Spinacia oleracea) thylakoids were irradiated at 4 degrees C with far-red light (>715 nm) exciting photosystem I, but not photosystem II. Selective excitation of photosystem I by far-red light for 130 min resulted in a 40% inactivation of photosystem I. It is surprising that this treatment also caused up to 90% damage to photosystem II. This suggests that active oxygen produced at the reducing side of photosystem I is highly damaging to photosystem II. Only a small pool of the D1-protein was degraded. However, most of the D1-protein was modified to a slightly higher molecular mass, indicative of a damage-induced conformational change. The far-red illumination was also performed using destacked and randomized thylakoids in which the distance between the photosystems is shorter. Upon 130 min of illumination, photosystem I showed an approximate 40% inactivation as in stacked thylakoids. In contrast, photosystem II only showed 40% inactivation in destacked and randomized thylakoids, less than one-half of the inactivation observed using stacked thylakoids. In accordance with this, photosystem II, but not photosystem I is more protected from photoinhibition in destacked thylakoids. Addition of active oxygen scavengers during the far-red photosystem I illumination demonstrated superoxide to be a major cause of damage to photosystem I, whereas photosystem II was damaged mainly by superoxide and hydrogen peroxide.
Cell Fractionation↗
Macrophyte development and habitat characteristics in Sweden's large lakes.
The four largest Swedish lakes, Vänern, Vättern, Hjälmaren, and Mälaren, were surveyed by means of aerial IR-color photography in the 1970s. Along small slope gradients in all lakes the emergent communities extended to a width of hundreds of meters, while the extent on steeper slopes was a few meters. Because of the fractionate shape, L. Mälaren has a very long shoreline, which promotes vegetation growth in the transition zone between land and water. Sheltered conditions are numerous and water lilies and other floating leaved and freely floating plants are abundant. Emergent as well as submerged macrophytes grow vigorously in the northernmost part of the oligotrophic lake Vättern. In L. Vänern exposed shores pre-dominate, but sheltered bays and archipelagos are overgrown with reeds. In the shallow lake Hjälmaren monospecific stands of Phragmites australis are dominant. Recurrent surveys of L. Mälaren and L. Vänern in the 1990s showed changes that could be connected to the watertable fluctuations, which have been stabilized since the first investigation. Reeds and water lilies expanded in sheltered parts of the lakes, while the distribution of reed stands growing at their deep limit decreased.
Biomass↗
The environmental consequences of alien species in the Swedish lakes Mälaren, Hjälmaren, Vänern and Vättern.
Twenty alien species have become established in the lakes Mälaren, Vänern, Vättern and Hjälmaren. Intentional introductions include fish and the signal crayfish from North America, ornamental plants, and the Canada goose. Unintentional introductions include the crayfish plague introduced with infected crayfish, the zebra mussel, and Chinese mitten crab introduced with ballast water. The introduction of pathogens and parasites, in particular the crayfish plague, to the lakes has had the greatest environmental and socioeconomic effects and has contributed to the decimation of the indigenous noble crayfish. The stocking of brown trout and salmon with origins from different biogeographical regions has contributed to the extinction of relict indigenous fish species in L. Vänern. Although major ecosystem damage caused by the introduction of alien species, with the exception of the crayfish plague, has not occurred in the four large Swedish lakes, local problems of considerable dignity occur occasionally.
Animals↗
[Asthma and allergy in schools--guidelines with strong support].
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Adolescent↗
GTP enhances the degradation of the photosystem II D1 protein irrespective of its conformational heterogeneity at the Q(B) site.
The light exposure history and/or binding of different herbicides at the Q(B) site may induce heterogeneity of photosystem II acceptor side conformation that affects D1 protein degradation under photoinhibitory conditions. GTP was recently found to stimulate the D1 protein degradation of photoinactivated photosystem II (Spetea, C. , Hundal, T., Lohmann, F., and Andersson, B. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 6547-6552). Here we report that GTP enhances the cleavage of the D1 protein D-E loop following exposure of thylakoid membranes to either high light, low light, or repetitive single turnover flashes but not to trypsin. GTP does not stimulate D1 protein degradation in the presence of herbicides known to affect the accessibility of the cleavage site to proteolysis. However, GTP stimulates degradation that can be induced even in darkness in some photosystem II conformers following binding of the PNO8 herbicide (Nakajima, Y., Yoshida, S., Inoue, Y., Yoneyama, K., and Ono, T. (1995) Biochim. Biophys. Acta 1230, 38-44). Both the PNO8- and the light-induced primary cleavage of the D1 protein occur in the grana membrane domains. The subsequent migration of photosytem II containing the D1 protein fragments to the stroma domains for secondary proteolysis is light-activated. We conclude that the GTP effect is not confined to a specific photoinactivation pathway nor to the conformational state of the photosystem II acceptor side. Consequently, GTP does not interact with the site of D1 protein cleavage but rather enhances the activity of the endogenous proteolytic system.
Binding Sites↗
A cyclophilin-regulated PP2A-like protein phosphatase in thylakoid membranes of plant chloroplasts
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Journal Article↗