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At least 289 records · Page 16Linked to original sources
PubMed2002

A direct link between annulene and porphyrin chemistry--21-vacataporphyrin.

A novel molecule, aza-deficient porphyrin 5,10,15,20-tetraaryl-21-vacataporphyrin has been synthesised by a substraction of a tellurium atom from 5,10,15,20-tetraaryl-21-telluraporphyrin under treatment of HCl. The new macrocycle is an annulene-porphyrin hybrid and at the same time is directly related to 21-heteroporphyrins but has a vacant space instead of heteroatomic bridge. The molecule preserves the fundamental structural and spectroscopic features of the parental 5,10,15,20-tetraarylporphyrin with three nitrogen atoms and two CH groups favorably prearranged for coordination.

Journal Article↗
PubMed2004

Working conditions and health among female and male employees at a call center in Sweden.

BACKGROUND: The call center industry is one of the most expansive labor market sectors in Sweden today. The purpose of this study was to investigate the working conditions and symptoms among employees at a call center in Sweden. METHODS: This study represents the cross-sectional baseline survey, which was part of a prospective cohort study. Fifty-seven call center workers were compared with a reference group of 1,459 professional computer users from other occupations. A questionnaire covered physical and psychosocial working conditions and symptoms during the last month. Structured observations in accordance with an ergonomic checklist were used to assess workstation design during the subject's ordinary work. RESULTS: The call center group had worked for a shorter time in their present tasks and spent longer continuous time in front of the computer than the reference group. There were deficiencies in workspace, keyboard- and input device placement. The subjects reported poor support from their immediate supervisor, low control and limited opportunities to influence their work. A higher proportion of the call center group reported musculoskeletal symptoms. CONCLUSION: The call center operators were exposed to working conditions that in other studies have indicated an increased risk of developing musculoskeletal disorders. The study also shows that young computer operators in the call center group with a short working career had a higher prevalence of neck- and upper extremity symptoms than older computer workers in other labor market sectors.

Adult↗
PubMed2004

Exposure to bioaerosols: allergic reactions and respiratory function in Polish hop growers.

BACKGROUND: The aim of the study was to assess the prevalence of work-related symptoms in hop growers and their relation to bioaerosols exposure. The study group comprised 69 hop growers and 58 office workers as controls. The examination included: physician-administrated questionnaire, PEF measurements, skin prick test, agar-gel precipitation test, and migration inhibition test. Microbiological air sampling was performed on all farms. RESULTS: The concentrations of total airborne microflora ranged from 2.08 to 129.6 x 10(3) CFU/m3. Airborne endotoxin and dust concentrations ranged from 26 to 6250 ng/m3 and 0.2-31.7 mg/m3, respectively. Altogether 52.2% of farmers complained of work-related symptoms. Positive skin reactions to microbial allergens were significantly more frequent in a group of hop growers with work-related respiratory symptoms compared to the rest of the farmers (18% vs 2%, P <0.05). Positive reactions in agar-gel precipitation test and in the leukocyte migration inhibition test were not correlated with the occurrence of work-related symptoms. The mean daily PEF values in farmers were lower compared to controls (469.7 +/- 127.5 vs 562.9 +/- 123.8; P <0.001). PEF (amp%mean) was higher in farmers compared to controls (9.3% vs 8.1%; P <0.05). CONCLUSION: Despite relatively lower exposure to bioaerosols, compared to farmers in other branches of agriculture, over 50% of hop growers complained of work-related symptoms. This may be partly due to the effects of microbial allergens and toxins and partly to the irritant or allergic properties of hop plant itself.

Adolescent↗
PubMed2004

Biochemical diagnosis of Antley-Bixler syndrome by steroid analysis.

Antley-Bixler syndrome (ABS, MIM 207410) is a skeletal abnormality syndrome primarily affecting head and limbs. Little is known of the origin of the condition but inactivating mutations in the fibroblast growth factor receptor (FGFR2) has been found in some patients. Genital ambiguity is seen occasionally in this condition, suggesting possible disordered steroidogenesis in early pregnancy. We report the steroid excretion of eight patients diagnosed with the syndrome and one with a related condition, a mild phenotype of the disorder since skeletal and genital abnormalities were not evident. The steroid excretion pattern was consistent and very distinctive in all nine patients. Metabolites of the two primary precursors of steroid hormones, pregnenolone and progesterone, were elevated as were the classical diagnostic metabolites for 17- and 21-hydroxylase deficiencies. Cortisol production was typically within the normal range but generally had blunted response to ACTH. Androgen metabolite excretion tends to be low in patients over 2 months of age, but may be elevated in the newborn period. The metabolome suggested attenuated steroid hydroxylation (including 17,20-lyase activity) although underlying cause is yet to be established. Mutations in CYP17 and CYP21 have not been found and currently the prime suspect is an abnormality in an essential redox partner (P450 oxidoreductase). This paper proposes use of the distinctive steroid metabolome as the primary biochemical parameter for diagnosis of ABS, at least the form not associated with FGFR2 mutations.

Abnormalities, Multiple↗
PubMed2006

Risk evaluation of carriers with chromosome reciprocal translocation t(7;13)(q34;q13) and concomitant meiotic segregation analyzed by FISH on ejaculated spermatozoa.

We performed the segregation analysis of a relatively large pedigree of t(7;13)(q34;q13) carriers together with the sperm karyotype analysis of the one carrier using a tri-color fluorescence in situ hybridization (FISH) method. The risk assessments for unfavorable pregnancy outcomes in a series of 36 pregnancies in eight reciprocal chromosome translocation (RCT) couples of carriers were estimated directly from a pedigree after ascertainment correction. The individual probability rate for unbalanced child was predicted according to Stengel-Rutkowski and co-workers. The unbalanced karyotypes in the form of monosomy 7q34-->qter and trisomy 13q13-->qter were detected among stillborn/early death newborns with holoprosencephaly (HPE), cyclopia and other malformations. Based on clinical description of unkaryotyped stillbirth progeny, it can be assumed that the phenotype distinctions were connected with the unbalanced karyotype from 2:2 segregation (monosomy 7q with trisomy 13q) and 3:1 segregation as interchange trisomy 13 (Patau syndrome). Probability rates for miscarriages, stillbirth/early death were 12.9 +/- 6% (4/31) and 29 +/- 8.2% (9/31), respectively. The results of the meiotic segregation pattern indicated the rate of unbalanced spermatozoa for about 60%, with the unusual high rate (29.4%) of 3:1 segregant (i.e., 13.4% of the tertiary segregation and 16% of the interchange segregation). Adjacent-1 segregation followed with 23.5% and adjacent-2 followed with 7.2% of analyzed spermatozoa. The high rate of unbalanced gametes in comparison to the number of stillborn/early death and miscarriages detected in pedigree suggests a strong selection against unbalanced chromosomal constitutions during fetal development. It corresponds to a very small probability rate (about 0.3%) of viable unbalanced progeny from 3:1 meiotic segregation predicted for maternal carriers. This knowledge can be used in genetic counseling of families with similar RCT ascertained in a different way.

Abortion, Spontaneous↗
PubMed2003

Synthesis, structure, and antibacterial activity of 4-imino-1, 4-dihydrocinnoline-3-carboxylic acid and 4-oxo-1, 4-dihydrocinnoline-3-carboxylic acid derivatives as isosteric analogues of quinolones.

Chemical modification of cinnoxacin was studied with the aim of improving its antibacterial activity and spectrum. A series of 4-imino-1, 4-dihydrocinnoline-3-carboxylic acid derivatives was synthesized and their in vitro antibacterial activity was evaluated. These derivatives were designed as isosteric analogues of fluoroquinolones and are characterized by the presence of an imine group instead of an oxo group at the 4-position and a nitrogen atom in position 2. The crystal structure of one analogue determined by X-ray diffraction shows the dipolar form of the compound in the solid state. The in vitro antibacterial activity of the synthesized compounds against Gram-positive and Gram-negative bacteria was examined. The MIC of the most active compounds lies in the range of the first generation of quinolones such as nalidixic acid. The compounds with dichlorobenzyl substituent show enhanced activity against Gram-positive bacteria.

4-Quinolones↗
PubMed2003

Selective inhibition of cyclooxygenase 2-generated prostaglandin E2 synthesis in rheumatoid arthritis synoviocytes by taurine chloramine.

OBJECTIVE: To investigate the effects of taurine chloramine (Tau-Cl), a chlorinated derivative of the amino acid taurine, on the expression of cyclooxygenase (COX) isoenzymes and prostaglandin E(2) (PGE(2)) synthesis in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). METHODS: FLS, isolated from the synovial tissue of RA patients, were treated in vitro with either interleukin-1beta (IL-1beta; 1 ng/ml) alone or together with 200-500 microM Tau-Cl. The expression of COX isoenzymes was evaluated at both the protein (Western blotting) and the messenger RNA (mRNA) (reverse transcriptase-polymerase chain reaction) levels. The concentration of PGE(2) was measured by competitive acetylcholinesterase enzyme immunoassay. RESULTS: Resting FLS expressed mRNA encoding both COX-1 and COX-2, but only COX-1 was present at the protein level. These cells produced negligible amounts of PGE(2). Upon stimulation with IL-1beta, elevation of COX-2, but not COX-1, mRNA and protein preceded the enhancement of PGE(2) synthesis. In the presence of 300-400 microM Tau-Cl, significant inhibition of IL-1beta-triggered COX-2 mRNA and protein, and a related decrease in PGE(2) production, was observed. In contrast, no significant changes in COX-1 mRNA and protein levels were noted. CONCLUSION: Tau-Cl inhibits IL-1beta-triggered elevation of COX-2 and generation of PGE(2) by RA FLS. These results expand the spectrum of known antiinflammatory activities of this compound.

Arthritis, Rheumatoid↗
PubMed2003

Heterogeneous requirement of IkappaB kinase 2 for inflammatory cytokine and matrix metalloproteinase production in rheumatoid arthritis: implications for therapy.

OBJECTIVE: To investigate the potential role of IkappaB kinase 1 (IKK-1) and IKK-2 in the regulation of nuclear factor kappaB (NF-kappaB) activation and the expression of tumor necrosis factor alpha (TNFalpha), as well as interleukin-1beta (IL-1beta), IL-6, IL-8, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs), in rheumatoid arthritis (RA). METHODS: Recombinant adenoviruses expressing beta-galactosidase, dominant-negative IKK-1 and IKK-2, or IkappaBalpha were used to infect ex vivo RA synovial membrane cultures and synovial fibroblasts obtained from patients with RA undergoing joint replacement surgery, or human dermal fibroblasts, human umbilical vein endothelial cells (HUVECs), and monocyte-derived macrophages from healthy volunteers. Then, their effect on the spontaneous or stimulus-induced release of inflammatory cytokines, VEGF, and MMPs from RA synovial membrane cells was examined. RESULTS: IKK-2 was not required for lipopolysaccharide (LPS)-induced NF-kappaB activation or TNFalpha, IL-6, or IL-8 production in macrophages, but was essential for this process in response to CD40 ligand, TNFalpha, and IL-1. In synovial fibroblasts, dermal fibroblasts, and HUVECs, IKK-2 was also required for LPS-induced NF-kappaB activation and IL-6 or IL-8 production. In RA synovial membrane cells, IKK-2 inhibition had no effect on spontaneous TNFalpha production but significantly reduced IL-1beta, IL-6, IL-8, VEGF, and MMPs 1, 2, 3, and 13. CONCLUSION: Our study demonstrates that IKK-2 is not essential for TNFalpha production in RA. However, because IKK-2 regulates the expression of other inflammatory cytokines (IL-1beta, IL-6, and IL-8), VEGF, and MMPs 1, 2, 3, and 13, which are involved in the inflammatory, angiogenic, and destructive processes in the RA joint, it may still be a good therapeutic target.

Arthritis, Rheumatoid↗
PubMed2003

Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis.

OBJECTIVE: To evaluate the prevalence and predictive value of anti-cyclic citrullinated peptide (anti-CCP) antibodies in individuals who subsequently developed rheumatoid arthritis (RA) and to determine the relationship to rheumatoid factor (RF) of any isotype. METHODS: A case-control study was nested within the Northern Sweden Health and Disease Study and the Maternity cohorts of Northern Sweden. Patients with RA were identified among blood donors whose samples had been taken years before the onset of symptoms. Control subjects matched for age, sex, date of sampling, and residential area were selected randomly from the same cohorts. Anti-CCP antibody and RFs were determined using enzyme immunoassays. RESULTS: Eighty-three individuals with RA were identified as having donated blood before presenting with any symptoms of joint disease (median 2.5 years [interquartile range 1.1-4.7] before RA). In samples obtained before the onset of RA, the prevalence of autoantibodies was 33.7% for anti-CCP, 16.9% for IgG-RF, 19.3% for IgM-RF, and 33.7% for IgA-RF (all highly significant compared with controls). The sensitivities for detecting these autoantibodies >1.5 years and </=1.5 years before the appearance of any RA symptoms were 25% and 52% for anti-CCP, 15% and 30% for IgM-RF, 12% and 27% for IgG-RF, and 29% and 39% for IgA-RF. In conditional logistic regression models, anti-CCP antibody and IgA-RF were found to be significant predictors of RA. CONCLUSION: Anti-CCP antibody and RFs of all isotypes predated the onset of RA by several years. The presence of anti-CCP and IgA-RF predicted the development of RA, with anti-CCP antibody having the highest predictive value. This indicates that citrullination and the production of anti-CCP and RF autoantibodies are early processes in RA.

Adult↗
PubMed2004

Platelet-activating factor-acetylhydrolase and other novel risk and protective factors for cardiovascular disease in systemic lupus erythematosus.

OBJECTIVE: There is an important inflammatory component to atherosclerosis and cardiovascular disease (CVD). It is therefore interesting that the risk of CVD is high in inflammatory diseases such as systemic lupus erythematosus (SLE). In this study, we investigated nontraditional risk factors for the development of CVD in patients with SLE. METHODS: Twenty-six women (mean age 52 years) with SLE and a history of CVD were compared with 26 age-matched women with SLE and no clinical manifestations of CVD (SLE controls) and 26 age-matched healthy women (population controls). Serum levels of several novel nontraditional risk and protective factors were determined: heat-shock protein (HSP)-related factors (Hsp60, Hsp70, anti-human Hsp60, anti-human Hsp70, and anti-mycobacterial Hsp65), platelet-activating factor-acetylhydrolase (PAF-AH) activity, secretory phospholipase A(2) GIIA (sPLA(2)), and anti-endothelial cell antibody (AECA). The intima-media thickness and the presence of plaques in the common carotid arteries were determined by B-mode ultrasound as a surrogate measure of atherosclerosis. RESULTS: Levels of PAF-AH, but not HSP-related factors, AECA, or sPLA(2), were significantly increased in SLE cases. Only PAF-AH discriminated between SLE cases and SLE controls (P = 0.005). PAF-AH was significantly associated with low-density lipoprotein (LDL) cholesterol and total cholesterol in the SLE cases (r = 0.50, P = 0.0093 and r = 0.54, P = 0.0045), but not in either control group. CONCLUSION: The increased levels of PAF-AH in SLE cases and the association between PAF-AH and LDL cholesterol adds support to the notion that PAF-AH may promote atherothrombosis in SLE. The role of HSPs in CVD is complex, since anti-Hsp65 appears to be associated with the presence of CVD, whereas Hsp70 might protect against it. In this cross-sectional study, levels of HSP-related factors, AECA, and sPLA(2) were not associated with CVD in SLE.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2005

Modulation of CD28 expression with anti-tumor necrosis factor alpha therapy in rheumatoid arthritis.

OBJECTIVE: The immune system of patients with rheumatoid arthritis (RA) is characterized by the accumulation of CD4+ T cells deficient in CD28 expression and the up-regulation of tumor necrosis factor alpha (TNFalpha). Previous in vitro studies have shown that TNFalpha induces transcriptional silencing of the CD28 gene. Because reduced expression of CD28 in T cells compromises immunocompetence, we examined whether CD28 expression is reduced in patients with RA in vivo and whether the reduction is related to TNFalpha. METHODS: Patients with RA and age-matched individuals were recruited. Peripheral blood mononuclear cells were stained for CD3, CD4, CD8, CD28, TNF receptor I (TNFRI), and TNFRII, and analyzed by quantitative flow cytometry. The number of CD28 and TNFR molecules was monitored in a subgroup of patients with RA undergoing treatment with anti-TNFalpha. RESULTS: In addition to higher frequencies of CD28null T cells, patients with RA had significantly reduced numbers of CD28 and TNFRI molecules on CD4+,CD28+ T cells. Normal expression could be restored in vitro by overnight culture, suggesting that CD28 in patients was modulated by exogenous factors. In contrast, treatment with TNFalpha in vitro resulted in further down-regulation. CD28 expression was normalized in patients undergoing TNFalpha-neutralizing therapy. CONCLUSION: Overproduction of TNFalpha in RA induces a global down-regulation of CD28 in CD4+ T cells and may cause reduced sensitivity to costimulatory signals in T cell responses.

Adolescent↗
PubMed2005

Positive effects of moderate exercise on glycosaminoglycan content in knee cartilage: a four-month, randomized, controlled trial in patients at risk of osteoarthritis.

OBJECTIVE: To evaluate the effects of moderate exercise on glycosaminoglycan (GAG) content in knee cartilage in subjects at high risk of knee osteoarthritis (OA). METHODS: Forty-five subjects (16 women, mean age 46 years, mean body mass index 26.6 kg/m(2)) who underwent partial medial meniscus resection 3-5 years previously were randomized to undergo a regimen of supervised exercise 3 times weekly for 4 months or to a nonintervention control group. Cartilage GAG content, an important aspect of the biomechanical properties of cartilage, was estimated by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), with results expressed as the change in the T1 relaxation time in the presence of Gd-DTPA (T1[Gd]). RESULTS: Thirty of 45 patients were examined by dGEMRIC at baseline and followup. The exercise group (n = 16) showed an improvement in the T1(Gd) compared with the control group (n = 14) (15 msec versus -15 msec; P = 0.036). To study the dose response, change in the T1(Gd) was assessed for correlation with self-reported change in physical activity level, and a strong correlation was found in the exercise group (n = 16, r(S) = 0.70, 95% confidence interval [95% CI] 0.31-0.89) and in the pooled group of all subjects (n = 30, r(S) = 0.74, 95% CI 0.52-0.87). CONCLUSION: This in vivo cartilage monitoring study in patients at risk of knee OA who begin exercising indicates that adult human articular cartilage has a potential to adapt to loading change. Moderate exercise may be a good treatment not only to improve joint symptoms and function, but also to improve the knee cartilage GAG content in patients at high risk of developing OA.

Cartilage, Articular↗
PubMed2006

The effect of therapeutic glucocorticoids on the adrenal response in a randomized controlled trial in patients with rheumatoid arthritis.

OBJECTIVE: To measure the effect of low-dose systemic glucocorticoid treatment on the adrenal response to adrenocorticotropic hormone (ACTH) in patients with rheumatoid arthritis (RA). METHODS: Patients with RA who took part in a randomized double-blind placebo-controlled trial of budesonide (3 mg/day and 9 mg/day) and prednisolone (7.5 mg/day) underwent a short (60-minute) test with injection of ACTH (tetracosactide hexaacetate) at baseline and the day after completing the 3-month treatment program. Plasma cortisol measurements at baseline and 3 months were compared within and between the treatment groups. Individual patients were classified as normal responders to ACTH or as abnormal responders if changes were >2 SD below the pretreatment value in the entire group of study patients. RESULTS: Short tests with ACTH injection were performed on 139 patients before beginning the study medication and on 134 patients after cessation of the medication. There were no changes in the placebo group. Mean plasma cortisol levels following treatment were reduced in all active treatment groups. In addition, mean values were significantly reduced for the 30-minute and 60-minute responses to ACTH. The maximum reduction (35%) occurred in the prednisolone group at 60 minutes. Following treatment, 34% of patients taking budesonide 9 mg and 46% of those taking prednisolone 7.5 mg failed to reach the normal maximum cortisol response to ACTH. Four patients failed to achieve the normal percentage increase in cortisol levels, but only 1 patient failed to meet both criteria. CONCLUSION: Low doses of a glucocorticoid resulted in depression of baseline and ACTH-stimulated cortisol levels after 12 weeks of therapy. Although the responsiveness of the hypothalamic-pituitary-adrenal axis in individual patients generally remained within the normal range, these changes should be investigated further.

Adrenal Glands↗
PubMed2006

Muscle strength, functional performance, and self-reported outcomes four years after arthroscopic partial meniscectomy in middle-aged patients.

OBJECTIVE: To examine thigh muscle strength, functional performance, and self-reported outcome in patients with nontraumatic meniscus tears 4 years after operation, and to study the impact of a strength deficit on self-reported outcome and evaluate the feasibility of 3 performance tests in this patient group. METHODS: The study group comprised 45 patients (36% women, mean age 46.7) who had an arthroscopic partial meniscectomy a mean of 4 years (range 1-6 years) previously. Main outcome measures included isokinetic strength of knee extensors and flexors, functional performance (1-leg hop, 1-leg rising, and square-hop tests), and a self-reported questionnaire (Knee Injury and Osteoarthritis Outcome Score). RESULTS: We found lower knee extensor strength and worse 1-leg rising capacity in the operated leg, but no difference between operated and nonoperated leg for knee flexors (P < or = 0.004 and P > 0.3, respectively). Patients with a stronger quadriceps of the operated leg compared with the nonoperated leg had less pain and better function and quality of life (r = 0.4-0.6, P < or = 0.010). We found the 1-leg rising and 1-leg hop tests to be suitable performance tests in middle-aged meniscectomy patients. CONCLUSION: Quadriceps strength is reduced in the meniscectomized leg compared with the nonoperated leg 4 years after surgery. This relative quadriceps weakness significantly affects objective and self-reported knee function, pain, and quality of life, indicating the importance of restoring muscle function after meniscectomy in middle-aged patients.

Adult↗