Exploring the relationship between chronic pain and cortisol levels in subjects with osteoarthritis: results from a systematic review of the literature.

OBJECTIVE: Several reports in the literature have identified an association between cortisol levels and the presence of chronic pain in conditions such as rheumatoid arthritis, low back pain or whiplash. In contrast, few have examined the association of cortisol and pain in people with osteoarthritis (OA). The purpose of this systematic review was to verify the association between cortisol and pain in the OA population. DESIGN: The databases MEDLINE, CINAHL, EMBASE were searched systematically for human studies written in English up to December 2018. Two researchers screened titles and abstracts against predefined inclusion criteria; a third resolved discrepancies. Articles were included if they measured the cortisol levels in adults with pain in the OA population. Methodological quality was assessed using Methodological Index for non-randomized Studies (MINORS) score. RESULTS: Seven studies reporting on 415 patients were included in this review. The MINORS scale yielded mean scores of 8.6 of 16 and 17.5 of 24, for the cohort and case-control studies respectively. In general, the studies were of poor quality. A discrepancy of noteworthy associations between cortisol level comparison and pain was found. CONCLUSIONS: This study shows that there is a discrepancy in the relationship between cortisol and pain dependent on how and when cortisol is measured. Evidence from three low-quality studies suggest increased cortisol levels in patients with pain but the conclusions have a high risk of bias. It was not possible to make a quantitative analysis comparing the relationship between cortisol and pain in the OA population.

Polycyclic Aromatic Hydrocarbons Exposure Assessment in a Refractory Brick Production.

In a refractory brick manufacturing company a qualitative and quantitative determination of the sources of occupational exposure to polycyclic aromatic hydrocarbons (PAHs) was obtained in order to validate targeted hygiene measurements. The study included the assessment of PAHs contamination of work surfaces by wipe-sampling, cutaneous exposure by hand washing, contamination of personal protective equipments (gloves) by extraction in solvent, and airborne PAHs concentration in atmospheric samples. Biomonitoring was also carried out by measurement of urinary 1-hydroxypyrene (1-OHPU) in three groups of workers (packaging, production, and controls). The surface contamination sampling was performed in production, packaging, and in other departments (external area) in theory less contaminated by PAHs. Two different areas were identified within the production, one included surfaces that were regularly cleaned (A area) and one included data from non-cleaned surfaces (B area). To confirm the source of exposure, a clear correspondence was observed between the percentage of the single compounds in the binder and those measured in wipes and air samples. As far as the wipes are concerned, the concentrations of phenanthrene, anthracene, fluoranthene, pyrene, benzo(a)pyrene (BaP), and the total PAHs mixture were higher in the B area than the A area of production. The same happened between the A area and the other two departments. According to results of the statistical analysis, these differences were significant. These results were confirmed by the hand washing data and the analysis of PPE. On the other hand, a marked difference does not exist between the packaging department and the external area. In air samples, the differences were much less evident with only higher concentrations of anthracene and total PAHs between production as a whole and the other two departments. Biological monitoring showed 1-OHPU values significantly higher in production workers than in packaging workers. In conclusion, the analysis of the wipes demonstrated that the production B area has a higher surface contamination compared to the production A area and the packaging department. In the absence of a significant difference in air concentrations of PAHs between A and B areas, this is attributable to surfaces not subject to cleaning. Results confirm that the measurement of surface contamination represents a valid tool for the assessment of sources of exposure to PAHs in the workplace.

[Refractory industrial production, chemical composition, synthesis processes and hygienical aspects in worker health protection]. / La produzione industriale di materiali refrattari, natura chimica, processi di trasformazione ed aspetti igienistici per la tutela della salute dei lavoratori.

The importance of the refractories sintering and manufacture can be better understood considering that the worldwide refractories consumption is about 2,3 kg per year/human being. The RHI Group, world leader in the refractories production, is present in Italy with the production of refractories for the steel and glass sectors in two important industrial sites, in Marone (Brescia) and in San Vito al Tagliamento (Pordenone) respectively. Describes origin, structure and characteristics of the different refractory materials, with particular focus on the different production technologies used in the manufacture of basic refractories (dolomite refractories) and mixed based on alumina, zirconia and silica. We describe the main hygienistics aspects relevant for the protection to the exposure of the workers involved in described production processes. In the production of dolomite refractories, we present the actions that have been implemented in order to reduce the exposure to the Polycyclic Aromatic Hydrocarbons (PAHs). In this process, we report the results of a decade of exposure's monitoring to polycyclic aromatic hydrocarbons in a group of refractory workers.

Food entrapped in papilla of Vater: uncommon cause of vomiting.

CASE REPORT: A 20 month old girl was admitted for intractable vomiting over several days, with no other symptoms. Family and personal history were not contributive. Clinical and neurological examination, and routine blood tests and investigations (plain abdominal x ray, upper gastrointestinal tract contrast study, abdominal ultrasonography) were normal. The upper gastrointestinal endoscopy showed a mild antral gastritis and the second portion of duodenum was occupied by a tough, fibrous mass partially embedded into the papilla of Vater. The foreign body was removed and proved to be vegetable fibre (pineapple). Symptoms subsided immediately and the child was discharged with gastroprotective therapy. After two months, on endoscopic examination, the signs of gastropathy had cleared; the papilla of Vater was undamaged, but unchomped food debris was again found in the duodenum. DISCUSSION: There are sporadic reports of foreign bodies retained into the papilla of Vater, all of them in adults. This child, though her papilla was tiny, had no jaundice or pancreatitis, unlike most of the reported cases. This is the first report of this finding in a child. The cause of the vomiting was not shown on abdominal ultrasonography or contrast study. It should be added to the list of unusual causes of vomiting.

Effects of chronic noradrenaline on the nitric oxide pathway in human endothelial cells.

Altered endothelium-dependent vasodilation has been observed in congestive heart failure (CHF), a disease characterized by a sustained adrenergic activation. The purpose of our study was to test the hypothesis that chronically elevated catecholamines influence the nitric oxide (NO) pathway in the human endothelium. Human umbilical vein endothelial cells (HUVEC) were exposed for 7 days to a concentration of noradrenaline (NA, 1 ng/mL) similar to that found in the blood of patients with CHF. Kinetics of endothelial constitutive NO synthase (ecNOS) and inducible NO synthase (iNOS) activity, measured by [3H]L-arginine to [3H]L-citrulline conversion, and protein expression of ecNOS and iNOS, assessed by Western blot analysis, were unaffected by chronic NA treatment. Furthermore, no changes in subcellular fraction-associated ecNOS were found; this indirectly shows that chronic NA did not cause phosphorylation of the enzyme. Moreover, [3H]L-arginine transport through the plasma membrane was conserved in chronically NA-treated cells. The data demonstrate that prolonged in vitro exposure to pathologic CHF-like NA does not affect the L-arginine: NO pathway in human endothelial cells.

Skeletal muscle metabolism in experimental heart failure.

We studied peripheral skeletal muscle metabolism in monocrotaline-treated rats. Two distinct groups emerged: a percentage of the animals developed ventricular hypertrophy, with no signs of heart failure (compensated group), whilst others, besides ventricular hypertrophy, developed the syndrome of congestive heart failure (CFH group). Oxidative metabolism and redox cellular state were expressed in terms of creatine phosphate, purine (ATP, ADP and AMP) and pyridine (NAD and NADH) nucleotides tissue content. Skeletal muscles with different metabolism were studied: (a) Soleus (oxidative), (b) extensor digitorium longus (glycolytic) and tibialis anterior (oxidative and glycolytic). The results showed that in CFH animals a decreased high-energy phosphates content occurs in the soleus and extensor digitorum longus, but not in the tibialis anterior. In the soleus. ATP declined from 20.31 +/- 2.5 of control group to 9.55 +/- 0.61 mumol/g dry wt. while in the extensor digitorum longus ATP declined from 30.92 +/- 2.68 to 22.7 +/- 1.54 mumol/g dry wt. In both these muscles, a shift of NAD/NADH couple towards oxidation was also observed (from 26.58 +/- 3.34 to 6.95 +/- 0.97 and from 18.88 +/- 3.43 to 10.57 +/- 1.61, respectively). These alterations were more evident in the aerobic soleus muscle. On the contrary, no major changes occurred in skeletal muscle metabolism of compensated animals. The results show that: (1) a decrease in muscle high-energy phosphates occurs in CFH; (2) this is accompanied by a decrease of NAD/NADH couple suggesting an impairment in oxygen utilization or availability.

Effects of felodipine on the ischemic heart: insight into the mechanism of cytoprotection.

To assess whether the administration of felodipine protects the myocardium in a dose-dependent manner against ischemia and reperfusion, isolated rabbit hearts were infused with three different concentrations of felodipine: 10(-10), 10(-9), and 10(-8) M. Diastolic and developed pressures were monitored; coronary effluent was collected and assayed for CPK activity and for noradrenaline concentration; mitochondria were harvested and assayed for respiratory activity; and ATP production and calcium content and tissue concentration of ATP, creatine phosphate (CP), and calcium were determined. The occurrence of oxidative stress during ischemia and reperfusion was also monitored in terms of tissue content and release of reduced (GSH) and oxidized (GSSG) glutathione. Treatment with felodipine at 10(-10) and 10(-9) M had no effect on the hearts when perfused under aerobic conditions, whilst the higher dose reduced developed pressure from 57.7 +/- 2.6 to 30.0 +/- 2.6 mmHg (p < 0.01). On reperfusion treated hearts recovered better than the untreated hearts with respect to left ventricular performance, replenishment of ATP and CP stores, and mitochondrial function. Recovery of developed pressure was 100% at 10(-8) M, 55% at 10(-9) M, and 46% at 10(-10) M. The reperfusion-induced tissue and mitochondrial calcium overload, release of CPK and noradrenaline, and oxidative stress were also significantly reduced. The effects of felodipine were dose dependent. Felodipine inhibited the initial rate of ATP-driven calcium uptake but failed to affect the initial rate of mitochondrial calcium transport. It is concluded that felodipine infusion provides dose-dependent protection of the heart against ischemia and reperfusion. Because this protection also occurred at 10(-9) M and 10(-10) M in the absence of a negative inotropic effect during normoxia and of a coronary dilatory effect during ischaemia, it cannot be attributed to an energy-sparing effect or to improvement in oxygen delivery. From our data we can envisage two other major mechanisms-(1) membrane protection and (2) reduction in oxygen toxicity. The ATP-sparing effect occurring at 10(-8) M is likely to be responsible for the further protection.

Extraction and assay of creatine phosphate, purine, and pyridine nucleotides in cardiac tissue by reversed-phase high-performance liquid chromatography.

The levels of creatine phosphate, purine, and pyridine nucleotides in tissues provide important information on energetic and oxidative cellular states. Nevertheless, technical, theoretical, and methodological difficulties in extraction and quantification procedures have so far limited our understanding of the exact role that these substances play in metabolic processes which take place in cells. The objective of our study was to find an easy and rapid method for extracting, separating, and quantifying creatine phosphate, purine, and pyridine nucleotides in solid tissues. We adapted the classic acid-extraction procedure with HClO4 for purine and oxidized pyridine nucleotides and then developed a new alkaline extraction with phenol in a phosphate buffer solution (pH 7.8) for reduced pyridine nucleotides. Biopsies of myocardial tissue were frozen and ground at -180 degrees C using the appropriate extraction procedure. The separation and quantification of the metabolites were performed using a reversed-phase 3-microns Supelchem C18 column, with the addition of tetrabutylammonium as an ion-pair agent to the buffer solution, by ultraviolet detection. The recovery of the external and internal standards always exceeded 90%. The autooxidation or interconversion processes were almost insignificant for each reduced form. This technique allowed us to avoid complex enzymatic procedures and difficulties in the selective assay of pyridine nucleotides with chemiluminescence and surface spectroscopy.

Effect of angiotensin converting enzyme inhibition with quinaprilat on the ischaemic and reperfused myocardium.

We assessed whether the local inhibition of myocardial converting enzyme by quinaprilat and captopril reduces the functional and metabolic damage caused by ischaemia and reperfusion. Quinaprilat and captopril were either subcutaneously injected (0.3 mg/kg once daily for 5-6 days) in the rabbit before isolation of the heart or delivered to the isolated hearts in the perfusate (10(-6) M) 60 min before ischaemia. Cardiac protection was evaluated in terms of left ventricular pressure recovery during reperfusion, creatine phosphokinase (CPK) release, mitochondrial function, ATP and CP tissue contents, calcium homeostasis and the occurrence of oxidative stress, established by measuring content and release of reduced and oxidized glutathione. Both drugs exerted cardioprotection. Optimal myocardial preservation is achieved when quinaprilat is prophylactically administered to the rabbit. Recovery of developed pressure on reperfusion improved from 11.3 +/- 2.7 (S.E.) to 25.4 +/- 5.4 mmHg, P < 0.01 and the release of CPK was reduced from 665.8 +/- 101.4 to 231.8 +/- 81.4 mU/min/g wet wt, P < 0.01. Peak of noradrenaline release was also attenuated, from 5.253 ng/min/g wet wt to 1.764 ng/min/g wet wt. The accumulation of tissue and mitochondrial calcium was reduced from 52.3 +/- 7.5 and 44.1 +/- 5.6 to 20.5 +/- 3.2 and 27.3 +/- 4.6 nmol/kg dry wt, respectively, P < 0.01. This resulted in significant (P < 0.01) improvement of left ventricular diastolic dysfunction during ischaemia and reperfusion and in a preservation of all indices of mitochondrial function, allowing a higher recovery of ATP and CP after reperfusion (from 4.1 +/- 0.5 and 5.2 +/- 0.5 to 11.1 +/- 1.1 and 24.8 +/- 1.0 mumol/g dry wt, respectively, P < 0.01). Reperfusion-induced myocardial accumulation and release of oxidized glutathione were reduced from 0.301 +/- 0.056 and 0.318 +/- 0.083 to 0.138 +/- 0.025 nmol/mg protein and 0.076 +/- 0.012 nmol/min/g wet wt, respectively, P < 0.01. Similar results were obtained when quinaprilat was administered to the isolated heart. These data suggest that the cardioprotective effect of quinaprilat is independent from haemodynamic changes or direct reduction of toxicity due to oxygen free-radicals but it is likely to be related to a reduction in the release of noradrenaline, maintenance of high energy phosphates and membrane integrity.

Mitochondrial energy production and cation control in myocardial ischaemia and reperfusion.

In the heart mitochondria exert two roles essential for cell survival: ATP synthesis and maintainance of Ca2+ homeostasis. These two processes are driven by the same energy source: the H+ electrochemical gradient (delta microH) which is generated by electron transport along the inner mitochondrial membrane. Under aerobic physiological condition mitochondria do not contribute to the beat to beat regulation of cytosolic Ca2+, although Ca2+ transient in mitochondrial matrix has been described. Increases in mitochondrial Ca2+ of mumolars concentration stimulate the Krebs cycle and NADH redox potential and, therefore, ATP synthesis. Under pathological conditions, however, mitochondrial Ca2+ transport and overload might cause a series of vicious cycles leading to irreversible cell damage. Mitochondrial Ca2+ accumulation causes profound alterations in permeability of the inner membrane to solutes, leading to severe mitochondrial swelling. In addition Ca2+ transport takes precedence over ATP synthesis and inhibits utilization of delta microH for energy production. These processes are important to understand the sequence of the molecular events occurring during myocardial reperfusion after prolonged ischaemia which lead to irreversible cell damage. During ischaemia an alteration of intracellular Ca2+ homeostasis occurs and mitochondria are able to buffer cytosolic Ca2+, suggesting that they retain the Ca2+ transporting capacity. Accordingly, once isolated, even after prolonged ischaemia, the majority of the mitochondria is able to use oxygen for ATP phosphorylation. When isolated after reperfusion, mitochondria are structurally altered, contain large quantities of Ca2+, produce excess of oxygen free radicals, their membrane pores are stimulated and the oxidative phosphorylation capacity is irreversibly disrupted. Most likely, reperfusion provides oxygen to reactivate mitochondrial respiration but also causes large influx of Ca2+ in the cytosol as result of sarcolemmal damage. Mitochondrial Ca2+ transport is therefore stimulated at maximal rates and, as consequence, the equilibrium between ATP synthesis and Ca2+ influx is shifted towards Ca2+ influx with loss of the ability of ATP synthesis.