Metabolic syndrome, radiographic osteoarthritis progression and chronic pain of the knee among men and women from the general population: The Rotterdam study.

OBJECTIVE: Although a relationship between osteoarthritis and components of metabolic syndrome (MetS) has been suggested, most of the results have been cross-sectional. We, therefore, aimed to investigate the sex-specific longitudinal association of (components of) MetS with progression of radiographic osteoarthritis and chronic pain in the knee joints in a large prospective cohort. METHOD: In the large population-based Rotterdam study of up to 6,138 individuals, median follow-up time 5.7 (IQR 5.5) years, we examined the relation between MetS and its components (abdominal obesity, high triglycerides, low high-density lipoprotein, elevated blood pressure, and type 2 diabetes) with the progression of osteoarthritis using generalized estimating equations, generalized linear models and competing risk analysis. Analyses were stratified for sex. Covariates adjusted for: age, smoking, alcohol use, education, sub-cohort, baseline K/L grade, months between radiographs and BMI. RESULTS: The presence of MetS (37.6 % in men, 39 % in women) and elevated blood pressure was associated with an increased risk of knee osteoarthritis progression in both men and women. MetS was associated with an increased risk of incident chronic knee pain (CKP) in men. In addition, abdominal obesity and high triglycerides showed higher riskfor incidence of CKP in men,but not in women. The associations were attenuated and no longer significant after BMI-adjustment, except for the association of MetS and high triglycerides with incidence of CKP in men that stayed significant (OR 1.04, 95 %CI 1.00-1.07 for MetS and OR 1.04, 95 %CI 1.01-1.07 for high triglycerides). CONCLUSION: Metabolic syndrome and individual metabolic components, such as abdominal obesity and elevated blood pressure, were associated with radiographic progression of knee OA in both men and women, but not independent of BMI. Metabolic syndrome and high triglycerides were associated with incidence of CKP only in men.

Skin autofluorescence, a non-invasive biomarker of advanced glycation end products, and its relation to radiographic and MRI based osteoarthritis.

OBJECTIVES: Accumulation of advanced glycation end products (AGEs) in articular cartilage during aging has been proposed as a mechanism involved in the development of osteoarthritis (OA). Therefore, we investigated a cross-sectional relationship between skin AGEs, a biomarker for systemic AGEs accumulation, and OA. METHODS: Skin AGEs were estimated with the AGE Reader™ as skin autofluorescence (SAF). Knee and hip X-rays were scored according to Kellgren and Lawrence (KL) system. KL-sum score of all four joints was calculated per participant to assess severity of overall radiographic OA (ROA) including or excluding those with prosthesis. Knee MRI of tibiofemoral joint (TFMRI) was assessed for cartilage loss. Sex-stratified regression models were performed after testing interaction with SAF. RESULTS: 2,153 participants were included for this cross-sectional analysis. In women (n = 1,206) for one unit increase in SAF, the KL-sum score increased by 1.15 (95% confidence interval = 1.00-1.33) but excluding women with prosthesis, there was no KL-sum score increase [0.96 (0.83-1.11)]. SAF was associated with higher prevalence of prosthesis [Odds ratio, OR = 1.67 (1.10-2.54)] but not with ROA [OR = 0.83 (0.61-1.14)] when compared to women with no ROA. In men (n = 947), there was inconclusive association between SAF and KL sum score or prosthesis. For TFMRI (n = 103 women), SAF was associated with higher prevalence of cartilage loss, full-thickness [OR = 5.44 (1.27-23.38)] and partial-thickness [OR = 1.45 (0.38-5.54)], when compared to participants with no cartilage loss. CONCLUSION: Higher SAF in women was associated with higher prosthesis prevalence and a trend towards higher cartilage loss on MRI. Our data presents inconclusive results between SAF and ROA in both sexes.

Thermal behavior of food preservative sorbic acid and its derivates.

Sorbic acid and its potassium and calcium salts used as food preservatives and sorbic chloride were submitted to thermal analysis in order to characterize their thermal behavior on heating and cooling processes, using TG/DTG/DTA, TG-MS, DSC, hot stage microscopy and DRX analysis. Sorbic acid melted and decomposed under dynamic heating. Under isothermal it sublimated without decomposition before melting (T < 134 °C). The potassium salt presented a solid-solid phase transition before decomposition. Both potassium and calcium salts decomposed in temperatures higher than the acid without melting, producing the respective carbonates and oxides as final residues. Sorbic chloride evaporate without condensation, on dynamic heating.

Osteoarthritis year in review 2019: biomarkers (biochemical markers).

OBJECTIVE: To provide an insightful summary of studies on biochemical markers for osteoarthritis (OA). DESIGN: Two investigators systematically searched the electronic PubMed database for clinical studies into soluble biochemical markers for OA in humans that were published between 01-03-2018 and 01-03-2019. Data from selected publications were systematically extracted and tabulated and were summarized in a narrative review. RESULTS: Out of 1,279 publications, 124 fulfilled all selection criteria and were selected for data extraction. The majority were around knee OA, cross-sectional in design, relatively small, and/or focused on one or a few biochemical markers. Among the intervention studies, relatively many were on non-pharmacological interventions, used clinical outcomes and/or were rather short. Some leads that were provided by this year's studies pertained to less conventional inflammatory mediators, oxidative stress, acidosis, angiogenesis and/or autoantibody formation. CONCLUSIONS: This year's biochemical marker studies did provide potential leads for therapeutic targets or other biochemical marker applications that require robust and strategic follow-up research to be validated.

[Pain care in Austrian health care centers: Questionnaire study on the current status of Austrian pain clinics]. / Schmerztherapeutische Versorgung österreichischer Gesundheitszentren: Fragebogenstudie zum Istzustand österreichischer Schmerzambulanzen.

BACKGROUND: Pain clinics provide interdisciplinary therapy to treat chronic pain patients and to increase the return-to-work rate. In recent years and due to increased economic pressure in health care, a change in the management of pain in Austrian health care centers has been observed. For the analysis of the current situation, two surveys addressing all Austrian pain clinics were performed. MATERIALS AND METHODS: In total, 133 heads of Austrian Anesthesia Departments were interviewed online and personally. The data from the first interview were confirmed by an additional telephone survey that was performed by one anesthetist per Austrian state (n = 9). RESULTS: Currently, 44 Austrian pain clinics are active. During the last 5 years, 9 pain clinics closed. Adding the current active pain clinics together, they represent a total of 17.5 full-time-operated clinics. The most common reasons for closing the pain clinics were lack of personnel (47%), lack of time resources (26%), lack of space resources (11%), and financial difficulties (11%). A reduction of >50% of operating hours during the last 3 years was reported by 9 hospitals. The reasons for not running a pain clinic were lack of personnel (36%), lack of time (25%) and department too small (16%). Estimates between actual and required clinics indicate that 49.5 full-time-operating pain clinics are lacking in Austria, resulting in 74% of the Austrian chronic pain patients not receiving interdisciplinary pain management. CONCLUSION: Our survey confirmed the closure of 9 pain clinics during the last 5 years due to lack of personnel and time. Pain clinics appear to provide the simplest economic saving potential. This development is a major concern. Although running a pain clinic seems to be expensive at the first sight, it reduces pain, sick leave, complications, and potential legal issues against health care centers, while simultaneously increasing the hospital's competitiveness. Our results show that 74% of Austrian chronic pain patients do not have access to an interdisciplinary pain clinic. Because of plans to further economize resources, Austria may lose its ability to provide state-of-the-art pain therapy and management.

[Optimising pain therapy for neurological inpatients]. / Optimierung der Schmerztherapie an neurologischen Stationen.

BACKGROUND: The Department of Neurology at the Medical University Graz has implemented a multiprofessional pain management concept and evaluated the outcome by means of a patient survey. METHODS: Standard operating procedures for standardised pain measurement, documentation and therapy were developed. All engaged professional participants were trained before implementation. RESULTS: 88.7 % of the surveyed 63 patients reported pain during the hospitalisation. During the night and in the morning, the occurrence of severe pain was most likely. The position or activity most likely triggering severe pain was mobilisation (19 %). Patients with degenerative diseases of the spine without radiculopathy reported the highest levels of pain. CONCLUSIONS: Pain is an important problem for neurological inpatients. Nocturnal pain, pain induced by mobilisation, and pain therapy for patients with degenerative diseases of the spine without radiculopathy require particular attention.

[Topical pain therapy in oral mucositis: a systematic review]. / Topische Schmerztherapie bei oraler Mukositis : Eine systematische Übersicht.

BACKGROUND: The pain provoked by mucositis is often described as the most excruciating symptom of cancer treatment. It often causes reduced ingestion, malnutrition, and sometimes postponement or withdrawal of the therapy. For health care providers, adequate pain treatment is a major challenge. The aim of this article is to present an overview of studies on the topical treatment of mucositis pain. METHODS: A systematic search was performed in PubMed with the keywords "mucositis" "pain" and "topical" or "local". In addition, reference lists and relevant websites were scanned for appropriate literature. RESULTS: A total of 47 articles were included. There is only scarce evidence for the topical treatment of mucositis pain. The most convincing studies tested opioids, corticoids and benzydamine. For the other substances, too few studies were performed, the results were contradictory, or the study quality was low. CONCLUSION: Based on the information gathered in this systematic search of the literature, topical treatment of mucositis pain today is based on empiricism and not on scientific evidence.

Hydrolysis of dinucleoside phosphates - mRNA 5' cap analogues - promoted by a binuclear copper(II)-zinc(II) complex.

The hydrolysis of a 5' cap analogue, diadenosinyl-5',5'-triphosphate (ApppA), and two dinucleoside monophosphates: adenylyl(3',5')adenosine (ApA) and uridylyl(3',5')uridine (UpU) promoted by an imidazolate-bridged heterobinuclear copper(II)-zinc(II) complex, Cu(II)-diethylenetriamino-micro-imidazolato-Zn(II)- tris(aminoethyl)amine trisperchlorate (denoted as Cu,Zn-complex in the followings) has been investigated. Kinetic measurements were performed in order to explore the effects of pH, the total concentration of the Cu,Zn-complex and temperature on the cleavage rate. The catalytic activity of the Cu,Zn-complex was quantified by pseudo-first-order rate constants obtained in the excess of the cleaving agent. The results show that the Cu,Zn-complex and its deprotonated forms have phosphoesterase activity and with ApppA the metal complex promoted cleavage takes place selectively within the triphosphate bridge.

Absolute and relative-rate kinetics experiments and direct dynamics computations for the reaction of Br atoms with CH2ClBr.

Kinetics of the reaction Br + CH2ClBr <--> CHClBr + HBr (1, -1) were studied experimentally in the forward direction. The absolute reaction kinetics method of laser flash photolysis coupled with Br atom resonance fluorescence detection and three different relative-rate methods with gas-chromatographic analysis were applied to carry out the experiments. The rate constants determined were found to obey the Arrhenius law in the wide temperature range of T = 293-785 K providing the kinetic expression k1 = (2.8 +/- 0.1) x 10(13) exp[-(47.6 +/- 0.3) kJ mol(-1)/RT] cm3 mol(-1) s(-1) (the errors given refer to 1sigma precision). An ab initio direct dynamics method was used to study reaction (1, -1) theoretically. The electronic structure information including geometries, gradients, and force constants was obtained at the MP2 level of theory; and energies were improved at higher theoretical levels. Rate constants were calculated using the canonical variational transition state theory with small-curvature tunneling correction over the temperature range 200-1000 K. Theory substantially underestimates k1 compared to experiment. The agreement was found good with k(-1) reported previously predicting positive temperature dependence. The experimental kinetic parameters were utilized in thermochemical calculations yielding the recommended standard enthalpy of formation of delta(f)H degrees (298) (CHClBr) = (140 +/- 4) kJ mol(-1) (with 2sigma accuracy given).

Speciation study of an imidazolate-bridged copper(II)-zinc(II) complex in aqueous solution.

The solution equilibrium and the binding mode of the species in the five-component system containing two metal ions (copper(II) and zinc(II)) and three ligands (A=diethylenetriamine, B=imidazole, C=tris(2-aminoethyl)amine) were investigated by pH-potentiometric titration, UV-visible spectrophotometry and EPR (electron paramagnetic resonance) spectroscopic titration in aqueous solution in the 2-11 pH range. An imidazolate-bridged heterobinuclear complex (ACuBH(-1)ZnC) was found to evolve above pH=7 and was stable between pH 7 and 11. The existence of the ACuBH(-1)ZnC complex (by determination of its molecular weight) was proved by mass spectrometry (ESI-MS (electrospray ionization mass spectrometry) and MALDI (matrix-assisted laser desorption/ionization) techniques). The electrochemical behaviour and the superoxide dismutase activity of this complex were also tested by cyclic voltammetry and the Riboflavin/NBT (nitro blue tetrazolium) assay, respectively.

Secretory breast cancer in a 7.5-year old boy.

Breast cancer is extremely rare in children, and consequently no consensus has been reached on the optimal treatment modalities. The medical history and treatment plan for a 7.5-year old male breast cancer patient is described. Radical mastectomy with sentinel node biopsy was performed in October 2002. As no malignant cells were detected in the sentinel node, and no BRCA1-2 mutations were detected, no further radio- or chemotherapy was performed. A "wait-and-see" policy was decided on. Further treatment will be given if this becomes necessary with the development of metastases.

Protease-elicited TUNEL positivity of non-apoptotic fixed cells.

The appearance of free DNA ends in the chromatin is usually considered an indication of advanced apoptosis. Unexpectedly, the nuclei of non-apoptotic cells derived from mouse thymuses could be specifically labeled by terminal transferase after proteinase K treatment of the fixed, cytocentrifuged samples. Artifactual mechanical or contaminating nucleolytic factors have been ruled out as players in the generation of free DNA ends. The phenomenon was detected in both formaldehyde- and ethanol-fixed specimens, in agarose-embedded fixed cells, and in chromatin spreads. By urea-agarose gel electrophoresis, the average single-strand size of the DNA molecules carrying the free ends was found between 50 and 250 kb. We suggest that ss discontinuities preexisting in the fixed normal cells are unmasked by protease treatment eliciting TUNEL (terminal transferase-mediated nick end-labeling) positivity.

Single-strand breaks in agarose-embedded chromatin of nonapoptotic cells.

Loop-size chromatin fragmentation frequently observed upon apoptotic cell death is thought to be initiated by ss nicks. Here we show that the agarose-embedded, deproteinized chromatin of normal, non-apoptotic murine and human cells, as well as yeast protoplasts, falls apart to 50-300 kb ss fragments upon heat denaturation, as revealed by urea-TAE field-inversion agarose gel electrophoresis resolving ss and ds fragments alike. These data were in line with S1digestion experiments. The nicks (gaps) observed are best explained either by enzymatic cleavages occurring upon cell lysis instantaneously or by preexisting discontinuities becoming manifest upon heat denaturation. These discontinuities go unnoticed in the usual nondenaturaing circumstances but seem to be inevitably present in any DNA preparation. The loop-size ds DNA fragmentation in apoptosis may be based on these pre-existing or "ready-to-go" (upon cell lysis) ss discontinuities of the normal cellular chromatin.

[Thermoanalytic determination of the enantiomeric purity of selegiline]. / A selegilin enantiomertisztaságának vizsgálata termoanalitikai módszerekkel.

The thermal behaviour of Selegiline (a chiral, non racemic pharmaceutical used in the therapy of Parkinson disease) was studied by differential scanning calorimetry (DSC) for determining the enantiomeric purity (e.p.) of the bulk substance. It has been found, that (i) the binary phase diagram (melting point phase diagram) of the R/S enantiomer mixtures is characteristic to that of the true racemic compounds; (ii) the melting behaviour of the R/S binary mixtures follows the thermodynamic laws (i.e. the Schröder-Van Laar and the Prigogine-Defay equations); (iii) the e.p. of the highly purified bulk substance can be expressed as "DSC purity" (this latter is obtained from the Van't Hoff equation) and the microcalorimetric method as above gives good reproducibility; (iv) due to the minor impurities (other than the S(-) enantiomer) the obtained e.p. (expressed as DSC purity) can be higher but not lower than the actual e.p. of the investigated substance.

Synthesis of N-(phosphonoacetyl)-dipeptide derivatives and evaluation of their antihypertensive activity.

A series of N-(phosphonoacetyl)-dipeptide derivatives was synthesized for pharmacological testing as antihypertensive compounds. Several of these compounds demonstrated a moderate antihypertensive effect in Wistar spontaneous hypertensive rats (SHR) with p.o. dosing. ACE inhibition by the compounds was studied using ACE from rat plasma and lung. Inhibitors containing esterified C-termini are pro-drugs and showed activity only for plasma ACE.

[Intrauterine insemination with "washed" sperm]. / Intrauterin inseminato "mosott" spermiumokkal.

The authors have been performing intrauterine insemination with the washed sperm of the husband since 1986. Previous to the intervention husband and wife went through a very thorough infertility examination according to the principles of the WHO. The cycle of women given intrauterine insemination was monitored. The maximum value of estradiol was measured on the 12th and 13th day of the cycle and the maximum mean value of the follicles on the 13th-14th day. In cases of ovulation the mean value of serum progesterone was found to rise on the 14th-15th day of the cycle. The semen was washed and concentrated, different protein components and bacteria were eliminated and the fraction with good motility was used for insemination. Intrauterine insemination with washed human sperm was carried out with 2 groups of patients. In the series studied the authors induced with intrauterine insemination 24 pregnancies in 100 infertile marriages. Intrauterine insemination was found to be successful if the infertility was caused by the hostility or poor quality of the cervix mucus. The treatment may be successful also in cases with slighter alteration of the spermiogram, whereas no results can be expected from intrauterine insemination with spermiograms displaying more serious alteration.

Intrauterine insemination with washed sperm.

Intrauterine insemination with washed semen has been carried out in our department since the beginning of 1986. Couples are examined carefully according to the principles of WHO before entering the program. The cycles of those couples treated by intrauterine insemination were monitored. Oestradiol values showed the highest levels on days 13 and 14, such as the size of folliculi, and serum progesterone level increased on days 14 and 15 ovulatory cycle. Insemination was performed with washed sperm after cleansing from it different albumin components and bacteria; the insemination was carried out in two groups. Good results were achieved in cases where the poor quality or hostility of the cervical mucus was the cause of infertility. The treatment can be successful if the spermiogram does not show severe deviation. No success can be expected in severe deviation of the spermiogram.