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Biomedical subjects

P Schwarz

Publications and source records attributed to P Schwarz.

At least 19 recordsLinked to original sources
PubMed2006

Nitric oxide and fibrinogen in polycystic ovary syndrome: associations with insulin resistance and obesity.

OBJECTIVE: Nitric oxide (NO) and fibrinogen levels, two markers of vascular disease, are associated with insulin resistance, a common trait in women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Case-control study including 31 women with PCOS and 21 age-matched women with regular, ovulatory cycles, normal androgen levels and idiopathic hirsutism (control group). Nitrite/nitrate concentration (index of endothelium-derived NO) and fibrinogen plasma levels were assessed and analysed in association with anthropometric, metabolic and hormonal variables. RESULTS: The groups were similar in terms of age, positive family history of diabetes and Ferriman-Gallwey hirsutism score. Nitrite/nitrate and fibrinogen levels were also similar in the two groups. In contrast, in PCOS patients, insulin levels and the homeostatic model assessment were negatively correlated with NO production (r=-0.39, p=0.03 and r=-0.41, p=0.02, respectively). Age, BMI, waist circumference and waist-to-hip ratio were positively correlated with fibrinogen in both groups. CONCLUSION: The present data indicate a negative, BMI-independent association between NO levels and insulin resistance in PCOS patients. Further studies are required to clarify the role of androgens on the pathogenesis of endothelial dysfunction in PCOS and investigate androgen action and/or the gene receptor modulating NO secretion.

Adult↗
PubMed2006

Effects of parathyroid hormone alone or in combination with antiresorptive therapy on bone mineral density and fracture risk--a meta-analysis.

AIM: The effects of parathyroid hormone (PTH) alone or in combination with antiresorptive therapy on changes in bone mineral density (BMD) and fracture risk were studied. MATERIALS AND METHODS: Randomised placebo controlled trials were retrieved from the PubMed, Web of Science or Embase databases. RESULTS: PTH alone or in combination with antiresorptive drugs reduced vertebral [relative risk (RR)=0.36, 95% confidence interval (CI): 0.28-0.47, 2p<0.01] and non-vertebral (RR=0.62, 95% CI: 0.48-0.82, 2p<0.01) fracture risk and increased spine BMD by 6.6% (95% CI: 5.2-8.1%, 2p<0.01) and hip BMD non-significantly by 1.0% (95% CI: -0.1 to 2.1%, 2p=0.08) during 11-36 months of follow-up (13 trials). The gain in spine and hip BMD tended to increase with the length of the PTH treatment. No significant effect of study duration on fracture risk could be demonstrated. The major adverse events were hypercalcaemia, nausea and discomfort at the injection sites. Only limited data are currently available on fracture risk reduction with PTH plus antiresorptive therapies. CONCLUSION: Although the number of studies on non-vertebral fractures is limited, our pooled analysis revealed that PTH alone or in combination with antiresorptive drugs would appear to be able to reduce the risk of vertebral and non-vertebral fractures and to increase spine and perhaps hip BMD. However, these analyses were based on cross-sectional data--i.e. based on indirect comparisons--and further studies with a direct comparison of study duration are necessary. No studies comparing PTH, PTH plus antiresorptive drugs and antiresorptive drug versus placebo in a factorial design are available; consequently, we were unable to draw any conclusions on the superiority of PTH plus antiresorptive drug versus antiresorptive drug or PTH alone with respect to BMD or fractures.

Bone Density↗
PubMed2006

The prevalence of osteoporosis in patients with chronic obstructive pulmonary disease: a cross sectional study.

Chronic obstructive pulmonary disease (COPD) is a complex disease, where the initial symptoms are often cough as a result of excessive mucus production and dyspnea. With disease progression several other symptoms may develop, and patients with moderate to severe COPD have often multiorganic disease with severely impaired respiratory dysfunction, decreased physical activity, right ventricular failure of the heart, and a decreased quality of life. In addition osteoporosis might develop possibly due to a number of factors related to the disease. We wanted to investigate the prevalence of osteoporosis in a population of patients with severe COPD as well as to correlate the use of glucocorticoid treatment to the occurrence of osteoporosis in this population. Outpatients from the respiratory unit with COPD, a history of forced expiratory volume in 1s (FEV1) less than 1.3 L, with FEV1% pred. ranging from 17.3% to 45.3% (mean 31.4%, standard deviation (sd) 7.3%). Patients between 50 and 70 years were included. Other causes of osteoporosis were excluded before inclusion. At study entry spirometry, X-ray of the spine (to evaluate presence of vertebral fractures), and bone mineral density of lumbar spine and hip were performed. Of 181 patients invited by mail, 62 patients were included (46 females and 16 males). All had symptoms of COPD such as exertional dyspnea, productive cough, limitations in physical activity etc. The mean FEV1 was 0.90 L (sd: 0.43 L) and the mean FEV1% pred. of 32.6% (sd: 14.1%). All had sufficient daily intake of calcium and vitamin D. In 15 patients, X-ray revealed compression fractures previously not diagnosed. Bone density measurements showed osteoporosis in 22 patients and osteopenia in 16. In total, 26 of the COPD patients were osteoporotic as evaluated from both X-ray and bone density determinations. Thus 68% of the participants had osteoporosis or osteopenia, but glucocorticoid use alone could not explain the increased prevalence of osteoporosis. A large fraction of these needed treatment for severe osteoporosis in order to prevent further bone loss and to reduce future risk of osteoporotic fractures. Thus, there is a significant need to screen patients with COPD to select the individuals in risk of fracture and to initiate prophylaxis or treatment for the disease.

Aged↗
PubMed2005

Reference values of NT-proBNP serum concentrations in the umbilical cord blood and in healthy neonates and children.

BACKGROUND: N-terminal brain natriuretic peptide (NT-proBNP) is a neurohormonal substance secreted mainly by the cardiac myocytes of the left ventricle and to a less degree of the left atrium. The releasing mechanism is induced by an increased wall stress on the base of volume or pressure load of the ventricle. The physiologic actions of BNP are prohibition of the sympathetic activity, vasodilatation, natriuresis, diureses and inhibition of the renin-angiotensin system. Because of its high sensitivity and specifity in relation to the left ventricular incompetence, BNP as well as NTproBNP are well accepted markers of ventricular dysfunction. It was the aim of the study to establish reference values of NT-proBNP serum concentrations throughout childhood, in particular in the newborn age group. METHODS: In a cross sectional study, serum NT-proBNP concentrations were measured by an ElectroChemiLuminescenceImmunoAssay ("ECLIA" Roche) in the umbilical cord blood of 62 healthy full-term neonates and in 222 healthy probands from birth up to the age of 18 years. RESULTS: The concentration of NT-proBNP in the cord blood samples ranged from 281 to 2595 pg/ml (mean: 818 pg/ml). There was a significant increase in the first days of life followed by a rapid decrease during the first year and a further gradual decrease throughout infancy; beyond the 10(th) year of age normal adult values were approached. CONCLUSIONS: The knowledge of the normal range of plasma NT-proBNP levels in healthy subjects during childhood serves as a non-invasive marker for differentiation of pathologic conditions such as acute myocarditis, hypertrophic or dilated cardiomyopathy, tachyarrhythmias and pulmonary hypertension.

Adolescent↗
PubMed2005

[Surgical treatment of distally located rectal carcinomas using the rendez-vous method--a laparoscopic resection in combination with T.E.M].

The aim of this work is to introduce a surgical procedure, which would make operations of distally located rectal carcinomas indicated for abdominoperineal extirpation of the rectum possible while maintaining intestinal continence and full functioning of the sphincter system. At the same time, we have aimed at the maximum use of all pros of contemporary miniinvasive surgical techniques. We have labelled our proposed surgical technique the "rendez-vous technique". The trial group includes the original group of 10 patients, who have been operated in our clinic since April 2004, using the rendez-vous technique. We are aware of the fact, that the trial group is small, however we believe that this trial group is the starting group, which will continue to enlarge and that it will bring results to the patients themselves, as well as for a valid prospective study in order to confirm or challenge the proposed method's effectiveness.

Female↗
PubMed2003

Calcium-sensing receptor induces proliferation through p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase but not extracellularly regulated kinase in a model of humoral hypercalcemia of malignancy.

Using H-500 rat Leydig cancer cells as a model of humoral hypercalcemia of malignancy (HHM), we previously showed that high Ca(2+) induces PTH-related peptide (PTHrP) secretion via the calcium-sensing receptor (CaR) and mitogen- and stress-activated kinases, e.g. MAPK kinase 1 (MEK1), p38 MAPK, and stress-activated protein kinase 1/c-Jun N-terminal kinase. Because cellular proliferation is a hallmark of malignancy, we studied the role of the CaR in regulating the proliferation of H-500 cells. Elevated Ca(2+) has a mitogenic effect on these cells that is mediated by the CaR, because the calcimimetic NPS R-467 also induced proliferation. Inhibition of phosphatidylinositol 3-kinase (PI3K) and p38 MAPK but not MEK1 abolished the mitogenic effect. Activation of PI3K by elevated Ca(2+) was documented by phosphorylation of its downstream kinase, protein kinase B. Because protein kinase B activation promotes cell survival, we speculated that elevated Ca(2+) might protect H-500 cells against apoptosis. Using terminal uridine deoxynucleotidyl nick end labeling staining, we demonstrated that high Ca(2+) (7.5 mM) and NPS R-467 indeed protect cells against apoptosis induced by serum withdrawal compared with low Ca(2+) (0.5 mM). Because the CaR induces PTHrP secretion, it is possible that the mitogenic and antiapoptotic effects of elevated Ca(2+) could be indirect and mediated via PTHrP. However, blocking the type 1 PTH receptor with PTH (7-34) peptide did not alter either high Ca(2+)-induced proliferation or protection against apoptosis. Taken together, our data show that activation of PI3K and p38 MAPK but not of MEK1/ERK by the CaR promotes proliferation of H-500 cells as well as affords protection against apoptosis. These effects are likely direct without the involvement of PTHrP in an autocrine mode.

Animals↗
PubMed2003

Calcium-sensing receptor stimulates PTHrP release by pathways dependent on PKC, p38 MAPK, JNK, and ERK1/2 in H-500 cells.

Elevated extracellular calcium ([Ca2+]o) and other agonists potentially acting via the calcium-sensing receptor (CaR) increase parathyroid hormone-related peptide (PTHrP) release from H-500 Leydig cells. Here, we provide strong evidence for the CaR's involvement by using a dominant negative CaR that attenuates high [Ca2+]o-induced PTHrP release. This effect is likely transcriptional, because high [Ca2+]o upregulates the PTHrP transcript, an effect that is abolished by actinomycin D. Regulation of PTHrP release by the CaR involves activation of PKC as well as ERK1/2, p38 MAPK, and JNK pathways. However, we show for the first time that high [Ca2+]o-induced activation of the stress-activated protein kinase SEK1 is PKC independent, because there is an additive effect of a PKC inhibitor in combination with the JNK inhibitor on [Ca2+]o-stimulated PTHrP release. Furthermore, high [Ca2+]o, in a PKC-independent fashion, induces phosphorylation of ERK1/2, SEK1, p38 MAPK, and its downstream transcription factor ATF-2. We conclude that CaR regulation of PTHrP release in H-500 cells involves activation of PKC as well as the ERK1/2, p38 MAPK, and JNK pathways.

Animals↗
PubMed2001

[SERM--selective estrogen receptor modulators].

SERM describes a category of drugs that exert their influence on estrogen-sensitive tissue and are known especially in the treatment of estrogen receptor-positive breast cancer. The development and clinical trials of new SERM in recent years seem to establish more fields of diseases, where treatment with SERM may be indicated.

Aged↗
PubMed2001

Complement facilitates early prion pathogenesis.

New-variant Creutzfeldt-Jakob disease and scrapie are typically initiated by extracerebral exposure to the causative agent, and exhibit early prion replication in lymphoid organs. In mouse scrapie, depletion of B-lymphocytes prevents neuropathogenesis after intraperitoneal inoculation, probably due to impaired lymphotoxin-dependent maturation of follicular dendritic cells (FDCs), which are a major extracerebral prion reservoir. FDCs trap immune complexes with Fc-gamma receptors and C3d/C4b-opsonized antigens with CD21/CD35 complement receptors. We examined whether these mechanisms participate in peripheral prion pathogenesis. Depletion of circulating immunoglobulins or of individual Fc-gamma receptors had no effect on scrapie pathogenesis if B-cell maturation was unaffected. However, mice deficient in C3, C1q, Bf/C2, combinations thereof or complement receptors were partially or fully protected against spongiform encephalopathy upon intraperitoneal exposure to limiting amounts of prions. Splenic accumulation of prion infectivity and PrPSc was delayed, indicating that activation of specific complement components is involved in the initial trapping of prions in lymphoreticular organs early after infection.

Animals↗
PubMed2001

Rapid suppression of S-PTH by oral calcitriol and calcium in healthy premenopausal women.

The influence of oral calcium +/- cholecalciferol or calcitriol on S-PTH and whole blood ionized calcium (B-Ca++) in the very short term has not been elucidated. B-Ca++ and S-PTH were measured after overnight fast every 5 or 15 min for 4-h in 7 healthy premenopausal women (30-45 years) in a crossover design where the subjects were studied on 4 different days. Study 1: (control), 125-ml tap water (also given in studies 2-4); study 2: 1000 mg calcium, as calcium carbonate; study 3: 1000 mg calcium and 400 IU (5 microg) cholecalciferol; and study 4: 0.5 microg calcitriol plus 1000 mg calcium. Calcium plus 1,25(OH)2 vitamin D3 induced a rapid and significant fall in S-PTH compared to the control period (p < 0.02). Calcium alone or calcium plus cholecalciferol did not change the PTH levels significantly compared to control (water). B-Ca++ increased significantly after calcium plus 1,25(OH)2 vitamin D3 (p<0.01) and calcium plus cholecalciferol (p<0.05) compared to the control period. The B-Ca++ elevation was significantly higher after calcium plus 1,25 vitamin D3 than after calcium plus cholecalciferol (p<0.05). In conclusion, oral calcitriol plus calcium causes a rapid elevation in B-Ca++ and suppression of the PTH secretion also in the short term (hours).

Adult↗
PubMed2001

Serum levels of parathyroid hormone and markers of bone metabolism in patients with rheumatoid arthritis. Relationship to disease activity and glucocorticoid treatment.

OBJECTIVE: To evaluate the influence of inflammatory activity and glucocorticoid (GC) treatment on serum parathyroid hormone (s-PTH) and bone metabolism in patients with rheumatoid arthritis (RA). Furthermore, in patients with active RA, to examine the PTH secretion and Ca2+ set point before and after treatment with GC. METHODS: A range of biochemical markers of bone metabolism and calcium homeostasis were measured in 95 patients with definite RA stratified into groups according to disease activity and GC treatment. In a subgroup of 12 patients with active disease, initiating slow-acting-anti-rheumatic-drugs (SAARDs) +/- GC, the PTH secretion and calcium set point were evaluated by use of the Cica clamp technique before and after 1 month of treatment. RESULTS: S-osteocalcin, s-total alkaline phosphatase (s-TAP) and s-carboxyterminal cross-linked telopeptide of type I collagen (s-ICTP) were elevated in all groups. The levels of urine pyridinoline (Pyr) and s-albumin-corrected calcium (s-AlbCorrCa2+) were elevated in patients with active disease and patients treated with GC. S-PTH and s-phosphate were within normal ranges. S-TAP, s-ICTP, Pyr and s-AlbCorrCa2+ correlated positively with indices of disease activity. In the subgroups undergoing the Cica clamp technique, no difference in PTH responsiveness of B-Ca2+ was unveiled. CONCLUSION: Neither active disease nor GC therapy appears to induce secondary hyperparathyroidism, nor is there an alteration in PTH responsiveness of B-Ca2+ in patients with RA. The increased levels of markers of type I collagen metabolism (s-ICTP, Pyr) and s-AlbCorrCa2+ in patients with active disease and patients treated with GC may be a result of increased degradation in synovium, cartilage and bone due to the inflammatory process.

Anti-Inflammatory Agents↗
PubMed2001

Efficient lymphoreticular prion propagation requires PrP(c) in stromal and hematopoietic cells.

In most prion diseases, infectivity accumulates in lymphoreticular organs early after infection. Defects in hematopoietic compartments, such as impaired B-cell maturation, or in stromal compartments, such as abrogation of follicular dendritic cells, can delay or prevent lymphoreticular prion colonization. However, the nature of the compartment in which prion replication takes place is controversial, and it is unclear whether this compartment coincides with that expressing the normal prion protein (PrP(c)). Here we studied the distribution of infectivity in splenic fractions of wild-type and fetal liver chimeric mice carrying the gene that encodes PrP(c) (Prnp) solely on hematopoietic or on stromal cells. We fractionated spleens at various times after intraperitoneal challenge with prions and assayed infectivity by bioassay. Upon high-dose challenge, chimeras carrying PrP(c) on hematopoietic cells accumulated prions in stroma and in purified splenocytes. In contrast, after low-dose challenge ablation of Prnp in either compartment prevented splenic accumulation of infectivity, indicating that optimal prion replication requires PrP(c) expression by both stromal and hematopoietic compartments.

Animals↗
PubMed2001

Transmission of scrapie by steel-surface-bound prions.

BACKGROUND: Prions are unusually resistant to conventional disinfection procedures. An electrode used intracerebrally on a Creutzfeldt-Jakob disease (CJD) patient transmitted the disease to two patients in succession and finally to a chimpanzee, despite attempted disinfection. Concerns that surgical instruments may transmit variant CJD have been raised by the finding of PrP(Sc), a surrogate marker for infectivity, in various tissues other than brain. MATERIALS AND METHODS: Stainless steel wire was exposed to scrapie-infected brain or brain homogenate, washed exhaustively and inserted into the brain of indicator mice to measure infectivity. RESULTS: A contact time of 5 min with scrapie-infected mouse brain suffices to render steel wire highly infectious and insertion of infectious wire into the brain of an indicator mouse for 30 min suffices to cause disease. Infectivity bound to wires persists far longer in the brain than when injected as homogenate, which can explain the extraordinary efficiency of wire-mediated infection. No detectable amounts of PrP could be eluted with NaOH, however the presence of PrP on infectious wires was demonstrated by chemiluminescence. Several recommended sterilisation procedures inactivated wire-bound mouse prions, but exposure to 10% formaldehyde was insufficient. CONCLUSIONS: Prions are readily and tightly bound to stainless steel surfaces and can transmit scrapie to recipient mice after short exposure times. This system mimics contaminated surgical instruments and will allow an assessment of sterilisation procedures.

Animals↗
PubMed2000

New diarylmethylpiperazines as potent and selective nonpeptidic delta opioid receptor agonists with increased In vitro metabolic stability.

Nonpeptide delta opioid agonists are analgesics with a potentially improved side-effect and abuse liability profile, compared to classical opioids. Andrews analysis of the NIH nonpeptide lead SNC-80 suggested the removal of substituents not predicted to contribute to binding. This approach led to a simplified lead, N, N-diethyl-4-[phenyl(1-piperazinyl)methyl]benzamide (1), which retained potent binding affinity and selectivity to the human delta receptor (IC(50) = 11 nM, mu/delta = 740, kappa/delta > 900) and potency as a full agonist (EC(50) = 36 nM) but had a markedly reduced molecular weight, only one chiral center, and increased in vitro metabolic stability. From this lead, the key pharmacophore groups for delta receptor affinity and activation were more clearly defined by SAR and mutagenesis studies. Further structural modifications on the basis of 1 confirmed the importance of the N, N-diethylbenzamide group and the piperazine lower basic nitrogen for delta binding, in agreement with mutagenesis data. A number of piperazine N-alkyl substituents were tolerated. In contrast, modifications of the phenyl group led to the discovery of a series of diarylmethylpiperazines exemplified by N, N-diethyl-4-[1-piperazinyl(8-quinolinyl)methyl]benzamide (56) which had an improved in vitro binding profile (IC(50) = 0.5 nM, mu/delta = 1239, EC(50) = 3.6 nM) and increased in vitro metabolic stability compared to SNC-80.

Animals↗
PubMed2000

[Severe neonatal hyperparathyroidism in a family with familial hypocalciuric hypercalcemia].

Familial hypocalciuric hypocalcaemia (FHH) is a rare disorder, inherited in an autosomal dominant manner. It has earlier been believed that neonatal severe hyperparathyroidism (NSHPT) is the homozygous form of FHH, but in this case story we show that it is not always like that. We describe a girl who presents with a calcium metabolic disorder from birth. Genetic examination of the girl and her family shows a single abnormal allele in the calcium ion sensitive receptor. We discuss why some heterozygotic inactivating calcium receptor mutations cause NSHPT, while the majority of other mutations only cause mild, asymptomatic hypercalcaemia as in FHH.

Alleles↗