Influence of saliva on the results of global laboratory coagulation tests.

BACKGROUND: Oral wounds inevitably come into contact with saliva which can affect the time needed for bleeding to stop. The influence of saliva can be non-specific, related to dilution of blood, and/or mediated by salivary factors that affect haemostasis directly. The aim of this study was to assess if mixing blood with an individual's saliva would affect the rate of its coagulation measured by global coagulation tests, prothrombin time (PT) and activated partial thromboplastin time (APTT). METHODS: The study included 30 healthy non-smoking volunteers. Paired blood and unstimulated saliva samples were obtained from each participant and PT and APTT were determined in blood, blood + saliva and blood + water mixtures. Coagulation tests were performed using the mechanical clot detection method. RESULTS: PT was significantly longer in both blood + saliva and blood + water mixtures compared to blood alone. APTT was significantly longer only in blood + water mixture compared to blood. CONCLUSIONS: Similarly prolonged PT in both mixtures suggests that both saliva and water prolong coagulation evenly due to their non-specific effect of blood dilution. The finding that APTT was significantly prolonged only when blood was mixed with water could indicate presence of tissue factor in saliva, however, in a concentration too low to influence the results of PT.

Changes in salivary oxidative status, salivary cortisol, and clinical symptoms in female patients with temporomandibular disorders during occlusal splint therapy: a 3-month follow up.

BACKGROUND: Differences in the expression of oxidative stress (OS) markers between female patients with temporomandibular disorders (TMD) and healthy individuals indicate that OS plays a role in the pathogenesis of TMD. Because chronic exposure to stress generates oxidative damage during continuous stimulation of the hypothalamic-pituitary-adrenal axis, we expected that higher levels of cortisol might be associated with higher oxidative damage. Our aim was to test the association between OS markers, stress perception, and salivary cortisol (SC) in chronic, female TMD patients. We tracked changes in OS markers and SC during occlusal splint therapy in order to evaluate the influence of treatment on oxidative status. We hypothesized that the effects of TMD therapy would differ among individuals depending on the source and intensity of pain. METHODS: Sixteen female patients were recruited, and 12 finished the study. Clinical assessment and saliva sampling were performed at the baseline and follow-up appointments. Repeated measures analysis of variance and Pearson's correlation were used for analyzing the data. RESULTS: After 3 months, a significant reduction in afternoon total antioxidant capacity (TAC) was observed (p < 0.05). A significant reduction in afternoon malondialdehyde (MDA) (p = 0.021) and a decrease in afternoon MDA to superoxide dismutase ratios (p = 0.017) were present in high-intensity pain patients. At baseline, higher levels of perceived stress were significantly associated with higher morning cortisol (ρ = 0.67). At the end of the therapy,  reduced  perceived stress was positively correlated with morning SC changes when considering all TMD patients, but the association between perceived stress with OS markers was present only in myofascial pain (MP) group. The effect of treatment on the self-perceived quality of life was more pronounced in female MP patients while the reduction of spontaneous pain was significantly greater in high-intensity pain patients. CONCLUSION: Our data indicate that occlusal splint therapy in female TMD patients contributes to increasing their capacity to remove free radicals. The question remains whether or not TAC decreases in this process as a result of avoiding unnecessary processes, once the increase in antioxidants effectively compensates for OS. The intensity and the source of pain should be considered important factors in future investigations evaluating salivary OS markers and their association with perceived stress and SC in TMD patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03029494 . Registered on 2017-01-19.

"Daisy-like" crystals: A rare and unknown type of urinary crystal.

BACKGROUND: Crystals are well known structures of urinary sediment, most of which are identified by the combined knowledge of crystal morphology, birefringence features at polarized light, and urine pH. In this paper, we report on a cohort of subjects whose urine contained a very rare type of crystal, which we first described in 2004 and which, based on its peculiar morphology, we define as "daisy-like crystal" (DLcr). METHODS: Reports on DLcr were spontaneously sent to our laboratory over a 10.5-year period by different laboratory professionals and by one veterinary clinician who, in their everyday work, had come across DLcr. After the examination of DLcr images submitted, a number of other information were requested and partly obtained. RESULTS: DLcr were found in 9 human beings in 7 different laboratories, located in 4 countries (Italy, Belgium, Croatia, France). DLcr were found mostly in female (8/9), at all ages (3.5 to 93years), mostly in alkaline urine (pH6.0 to 7.5), at variable specific gravity values (1.010 to 1.030), either as isolated particles (2/8) or in association with other crystals (5/8) and/or leucocytes or bacteria (3/8). In addition, DLcr were found in the urine of a 1-year-old dog, examined in a veterinary clinic of Czech Republic. In 3 cases, DLcr were identified by manual microscopy, while in 7 cases by automated urine sediment analyzers. CONCLUSIONS: This paper confirms the possible presence in the urine of DLcr. However, further cases are needed to clarify their frequency, clinical meaning, and composition.

Polychlorinated biphenyl (PCB) and dioxin concentrations in residential dust of pregnant women.

Polychlorinated biphenyls (PCBs) and dioxins are well known for their persistence in the environment. PCBs can be found in the residential environment long after the use of these chemicals in domestic products and industrial processes has ceased. Dioxins have been assessed in Australia as being of very low concentrations. Despite concerns about residential dust as a source of human exposure to persistent chemicals, there has been limited testing of PCBs and dioxins in dust in Australia. As part of an assessment of maternal exposure to a variety of persistent toxic substances, we analysed 30 residential dust samples from a variety of geographical settings for their dioxin and PCB concentrations. PCBs were found in most samples, the median and range concentrations (pg g(-1)) of dominant congeners of PCB were as follows: PCB118 (315; <35.0-29 000), PCB105 (130; 14.0-16 000) and PCB156 (440; <5.00-2800). Dioxin concentrations were generally low with median concentrations for the total sum of dioxin-like polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) of 3.75 pg g(-1) each. There was a very high percentage of non-detects. Concentrations of both PCBs and dioxins were low compared with most studies reporting residential dust concentrations internationally. Age of dwelling was the only factor observed to influence both PCB congener concentrations and dioxin isomers in multivariate regression analyses. No other housing or sociodemographic variables, including proximity to industry, were important predictors in multivariate linear regression models.

TSH prevents bone resorption and with calcitriol synergistically stimulates bone formation in rats with low levels of calciotropic hormones.

Thyroid-stimulating hormone exerts both antiresorptive and anabolic effects on bone remodeling in aged ovariectomized rats and thyroid stimulating hormone-receptor null mice, supported by clinical results demonstrating that low thyroid-stimulating hormone level is associated with increased bone loss. To further explore the effect of thyroid-stimulating hormone on bone metabolism we introduced here a rat model with removed thyroid and parathyroid glands to obtain low serum concentrations of thyroid and parathyroid hormone, calcitonin and 1,25(OH)2D3. Surgery resulted in hypocalcemia, low parathyroid and thyroid hormone, 1,25(OH)2D3, C-telopeptide, and osteocalcin serum level. Intermittent administration of thyroid-stimulating hormone resulted in a further decrease of serum calcium and decreased level of serum C-telopeptide due to the suppression of bone resorption, while in the same animals osteocalcin in serum was higher indicating an increased bone formation rate. A combination of thyroid-stimulating hormone and 1,25(OH)2D3 significantly increased the serum Ca2+, C-telopeptide and serum osteocalcin values. MicroCT analyses of the distal femur and proximal tibia showed that rats treated with 1,25(OH)2D3 alone or in a combination with thyroid-stimulating hormone had an increased trabecular bone volume, and enhanced trabecular bone quality. Biomechanical testing of the trabecular bone showed an increased maximal load for 105% and 235%, respectively, in rats treated with 1,25(OH)2D3 alone, or in a combination with thyroid-stimulating hormone. We suggest that thyroid-stimulating hormone independently of calciotropic hormones suppressed bone resorption and stimulated bone formation, while in combination with 1,25(OH)2D3 acted synergistically on bone formation resulting in an increased bone volume.

Effect of L-arginine dietary supplementation on salivary urea concentration and pH in physically active individuals.

BACKGROUND: The aim of this study was to assess if the consumption of 3 g of a commercially available L-arginine dietary supplement causes a postabsorptive rise in urea concentration or pH of unstimulated saliva in a group of physically active individuals. METHODS: Salivary urea and pH were determined for 117 participants in a randomized double-blinded placebo-controlled study. Samples were collected by 'spitting' method in fasting conditions. One hour prior to their second visit, participants consumed three tablets of L-arginine or placebo. RESULTS: Urea concentration was significantly lower at second measurement for both the study and control group. The magnitude of the change was not significant between the groups. pH was higher for both groups at second measurement, but only significant for the study group. The magnitude of the change was significant between the groups. Participants who intermittently ingested protein dietary supplements and those with a Body Mass Index (BMI) higher than 25 had significantly higher basal urea concentration. CONCLUSIONS: The results of this study did not confirm the hypothesis. Further studies are needed to determine the effects of different doses of L-arginine supplements on the biochemical composition of saliva and the influence of their long-term consumption on the risk of developing dental diseases.

Role of EP2 and EP4 receptor-selective agonists of prostaglandin E(2) in acute and chronic kidney failure.

We tested the efficacy of three selective agonists of prostaglandin E(2) (PGE(2)) receptor, EP2 (CP-536,745-01), EP2/4 (CP-043,305-02), and EP4 (CP-044,519-02), in two models of acute and chronic kidney failure. In the nephrotoxic mercury chloride (HgCl(2)) rat model of acute kidney failure systemically administered EP4 agonist reduced the serum creatinine values and increased the survival rate. Although the EP2 or the EP2/4 agonist did not change the serum creatinine values, the EP2 receptor agonist increased the survival rate. Histological evaluation of kidneys from EP4-treated rats indicated less proximal tubular necrosis and less apoptotic cells. In a rat model of chronic renal failure, the three receptor agonists decreased the serum creatinine and increased the glomerular filtration rate at 9 weeks following therapy. Kidneys treated with the EP4 agonist had less glomerular sclerosis, better preservation of proximal and distal tubules and blood vessels, increased convoluted epithelium proliferation and less apoptotic cells. Nephrectomy had no influence on the expression of the EP4 receptor, whereas EP2 receptor expression was reduced by 50% and then corrected following treatment with EP2 and EP2/4 receptor agonists. These findings suggest that PGE(2) has an important role in acute kidney failure via the EP4 receptor, whereas in chronic kidney failure both EP2 and EP4 receptors are equally important in preserving the progression of chronic kidney failure. Thus, agonism of EP2 and EP4 receptors may provide a basis for treating acute and chronic kidney failure.

Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury after ischemic acute renal failure in rat.

We have shown that osteogenic protein-1 (OP-1) (bone morphogenetic protein-7) is responsible for the induction of nephrogenic mesenchyme during embryonic kidney development. Gene knock-out studies showed that OP-1 null mutant mice die of renal failure within the first day of postnatal life. In the present study, we evaluated the effect of recombinant human OP-1 for the treatment of acute renal failure after 60 min bilateral renal artery occlusion in rats. Bioavailability studies in normal rats indicate that approximately 1.4 microg OP-1/ml is available in the circulation 1 min after intravenous administration of 250 microg/kg, which then declines steadily with a half life of 30 min. About 0.5% of the administered OP-1 dose/g tissue is targeted for OP-1 receptors in the kidney. We show that OP-1 preserves kidney function, as determined by reduced blood urea nitrogen and serum creatinine, and increased survival rate when administered 10 min before or 1 or 16 h after ischemia, and then at 24-h intervals up to 72 h after reperfusion. Histochemical and molecular analyses demonstrate that OP-1: (a) minimizes infarction and cell necrosis, and decreases the number of plugged tubules; (b) suppresses inflammation by downregulating the expression of intercellular adhesive molecule, and prevents the accumulation and activity of neutrophils; (c) maintains the expression of the vascular smooth muscle cell phenotype in pericellular capillaries; and (d) reduces programmed cell death during the recovery. Collectively, these data suggest that OP-1 prevents the loss of kidney function associated with ischemic injury and may provide a basis for the treatment of acute renal failure.

Analysis of the in vitro secretory activity of human pituitary adenomas: modification of corticotropin release from adenoma tissue explant cultures by addition of a human plasma ultrafiltrate bioactive fraction.

The lack of control of tumour behaviour is manifested in different ways, depending primarily on the type of tumour. This results in numerous problems of tumour diagnosis and therapy. In the case of "benign" tumours, like pituitary adenomas, in vitro studies are often used for evaluation of the tumour. The use of tissue explant cultures of human pituitary adenomas and the comparison of the feature of cultured tumours with their behaviour in vivo showed that corticotropin is released not only from the tumours associated with Cushing's disease, but also from clinically non-functioning tumours. Hence, it was supposed that the release of corticotropin in vivo from non-secreting tumours is probably under the influence of certain neuroendocrine and/or systemic humoral factors. To test this possibility, samples of 22 tumours were cultured in plain culture medium or in the presence of the "human plasma ultrafiltrate bioactive fraction" (tentatively termed as TBP) prepared by anion-exchange chromatography. In the presence of TBP the release of corticotropin was strongly inhibited in adenomas showing relatively high spontaneous secreting activity in vitro (> 200 ng/l in 24 hours), while immunohistochemistry of these tumours indicated accumulation of corticotropin inside the cells. In contrast, TBP stimulated corticotropin release from tumours that showed relatively low basic corticotropin release (< 200 ng/l in 24 hours), with no obvious change in cellular corticotropin immunoreactivity. Such a dual activity of TBP was not observed for 8 samples of adenomas cultured in the presence of surrounding pituitary tissue, probably because TBP did not affect corticotropin secretion by the normal pituitary cells (as indicated by immunohistochemistry). From these results, it appears that TBP could be one of the humoral factors involved in the regulation of corticotropin release from pituitary adenoma tissue. Its possible involvement in the regulation of corticotropin release from normal pituitary tissue, however, is uncertain.