Salivary cortisol and α-amylase: subclinical indicators of stress as cardiometabolic risk.

Currently, the potential for cardiovascular (CV) stress-induced risk is primarily based on the theoretical (obvious) side effects of stress on the CV system. Salivary cortisol and α-amylase, produced respectively by the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adrenomedullary (SAM) system during stress response, are still not included in the routine evaluation of CV risk and require additional and definitive validation. Therefore, this article overviews studies published between 2010 and 2015, in which salivary cortisol and α-amylase were measured as stress biomarkers to examine their associations with CV/CMR (cardiometabolic risk) clinical and subclinical indicators. A comprehensive search of PubMed, Web of Science and Scopus electronic databases was performed, and 54 key articles related to the use of salivary cortisol and α-amylase as subclinical indicators of stress and CV/CMR factors, including studies that emphasized methodological biases that could influence the accuracy of study outcomes, were ultimately identified. Overall, the biological impact of stress measured by salivary cortisol and α-amylase was associated with CV/CMR factors. Results supported the use of salivary cortisol and α-amylase as potential diagnostic tools for detecting stress-induced cardiac diseases and especially to describe the mechanisms by which stress potentially contributes to the pathogenesis and outcomes of CV diseases.

Salivary α-amylase and cortisol after exercise in menopause: influence of long-term HRT.

OBJECTIVES: This observational prospective study analyzed the effect of an incremental cardiopulmonary exercise test (CPET) on the secretion of salivary biomarkers of the adrenergic nervous system and hypothalamus-pituitary-adrenal (HPA) axis activity by measuring salivary α-amylase and cortisol diurnal trajectories in the setting of long-term hormone replacement therapy (HRT). METHODS: Fifteen healthy sedentary postmenopausal women who were current HRT users and 15 women who had never used HRT were consecutively recruited. α-Amylase and cortisol were measured in salivary samples collected on the CPET day and on a rest day. Cardiovascular and respiratory fitness parameters were recorded during the CPET challenge. RESULTS: The participants had very homogeneous somatic characteristics, and they were all in generally good health. The postmenopausal never-HRT users presented an abnormal diurnal pattern of α-amylase at baseline and a flattened response to CPET. In contrast, women on HRT had a physiological α-amylase diurnal pattern and increased salivary α-amylase production during the CPET-induced challenge. The CPET challenge physiologically activated the HPA axis activity, as shown by the increase in the concentration of salivary cortisol during the effort test. HPA axis activity was not affected by long-term HRT. Postmenopausal women using HRT exhibited a cardiorespiratory functional capacity that was significantly (p < 0.05) higher than that of non-users. CONCLUSIONS: Our findings show that healthy postmenopausal women present an asymmetry between adrenergic nervous system and HPA axis activities under both basal and stress conditions. HRT was able to modify the abnormal adrenergic nervous system activity, most likely by reducing the sympathetic hyperactivity that characterizes menopause.

Diurnal trajectories of salivary cortisol, salivary α-amylase and psychological profiles in oral lichen planus patients.

Although many reports have been published on the link between oral lichen planus (OLP) and the stress-related neuro-psycho-endocrine clinical features of the disease over the last 20 years, the data still remain controversial. Therefore, the aim of this study was to explore the personality traits of OLP subjects and assess the subjects' capability of coping with stress challenges. Cortisol and alpha-amylase were measured as reliable markers of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) activities in salivary samples collected by the participants at their home during the sampling day (07:30, 12:00, and 19:30). Compared with the healthy controls, the OLP patients demonstrated a less effective coping ability, had higher scores in stress perception and loneliness, and had no significant variation in their anxiety and depressive symptoms. The OLP patients also showed dysregulation of the HPA axis activity with a significant reduction of diurnal salivary cortisol production, which was particularly significant in the morning hours. No significant variation was found in the OLP salivary alpha-amylase diurnal fluctuation and production, which was measured at the same time point as that for cortisol. In conclusion, we report that OLP subjects had a reduced capability of coping with stress events and presented a dysregulation of HPA axis activity with hypocortisolism detected in the morning hours.

Serum testosterone and depressive symptoms in severe OSA patients.

Obstructive sleep apnoea (OSA), also characterised by hypoxia-related sleep- fragmentation, has been studied in relation to depression and serum testosterone deficit. In middle-aged men, it has been reported the association between depressive mood and low serum testosterone level; however, no data are available about this association in OSA patients. Therefore, the aim of this study was to investigate in adult obese males, affected by severe OSA, the relationship between serum testosterone concentration and depressive symptoms, in order to identify among all measured parameters (serum testosterone morning concentration, polysomnography parameters, body mass index, Epworth Sleepiness Scale) those predictors for OSA-related depression. Forty patients diagnosed with severe OSA and forty subjects for the control-matched group were enroled in the study. The results indicated that the serum testosterone in OSA group was significantly lower than in controls. In addition, the OSA group presented a level of depression although moderate, yet significantly higher than controls. Furthermore, a statistically significant inverse correlation has been found between serum testosterone level and depressive symptoms. Among all variables, serum testosterone level was shown to be the only independent variable significantly predictor for depression in OSA patients.

In vivo biocompatibility evaluation of some Bidens tripartita extracts in rats.

UNLABELLED: Adaptogens represent a class of herbs frequently used as a unique and natural alternative medicine and herbal remedy for treating the many forms of stress and different other pathological conditions. Bidens tripartite, a flowering plant from the genus Bidens, family Compositae, subfamily Asteroideae was widely used in traditional medicine for its antiseptic, anti-inflammatory, antioxidant, astringent, diuretic, febrifuge, narcotic and sedative effects. Phytochemical analysis of this plant has revealed the presence of flavonoids, xanthophylls, volatile oil, acetylene and polyacetylene, sterols, aurones, chalcones, caffeine and tannins. AIM: The in vivo biocompatibility evaluation of two extracts from Bidens tripartita plant in rats. MATERIAL AND METHODS: The vegetable product used for the study was obtained after maceration and extraction in alcohol. Flower powder was dissolved in absolute chloroform, re-extracted and filtered. After a complete dryness the product was extracted by the addition of ethanol then evaporated. The chemical composition of the extracts was determined. The administered dose of Bidens tripartita retained was 1/20 of lethal dose 50 (LD50). The experiment was carried out on white male Wistar rats (200-250g) divided into 3 groups of 7 animals each treated intraperitoneally as follows: Group I (Control): distilled water 0.1ml/10g weight; Group II (coded BT-alcoholic): 200mg/kbw alcoholic Bidens tripartita extract; Group III (coded BT-aqueous): 250mg/kbw aqueous Bidens tripartita extract. The biocompatibility properties of alcoholic and aqueous extracts from Bidens tritartita were studied by assessing their effects on blood count and serum biochemical tests. The following immune parameters: phagocytic capacity of peripheral neutrophils (NBT test) and serum complement activity were also evaluated. The data were presented as +/- SD and significance was tested by SPSS for Windows version 13.0 and ANOVA method. Experimental protocol was implemented according to the recommendations of the University Committee for Research and Ethical Issues and guidelines of IASP Committee for Research and Ethical Issue. RESULTS: Laboratory analysis did not show significant differences on leucocyte formula (GOT, GPT and LDH) or immune parameters (phagocytic capacity of peripheral neutrophils and serum complement activity) between alcoholic and aqueous B. tripartita extracts and distilled water, elements suggesting a good in vivo biocompatibility. CONCLUSIONS: In our experimental conditions, the alcoholic extract and aqueous extract from B. tripartita determined similar immune responses as distilled water following intraperitoneal administration in rats, indicative of good in vivo biocompatibility.

Experimental researches on acute toxicity of a Bidens tripartita extract in mice - preliminary investigations.

UNLABELLED: Plants take up an important place in traditional medicine and scientific research confirmed properties about their use as alternative therapy. Bidens tripartita, commonly known as Three-lobe Beggarticks, Three-part Beggarticks, Trifid Bur-marigold, is a flowering plant in the genus Bidens, family Compositae, subfamily Asteroideae. Evaluation of the chemical composition of this plant has revealed the presence of flavonoids, xanthophylls, volatile oil, acetylene and polyacetylene, sterols, aurones, chalcones, caffeine and tannins. AIM: Theoretical data investigation regarding Bidens tripartita plant and experimental researches on acute toxicity of an original extract in mice. MATERIAL AND METHODS: The vegetal product of Bidens tripartita used for study was obtained by maceration and extraction in alcohol, and its chemical composition was determined. Acute toxicity of the alcoholic extract of Bidens tripartita was assessed by median lethal dose (LD50) calculation, using a limit dose test of up- and- down procedure at a limit dose of 2000mg/kbw after intraperitoneal administration in mice. RESULTS: In the alcoholic extract of Bidens tripartita different active principles were identified: tannins, anthracene derivatives, triterpenes, coumarins, antocyanosides. The toxicity of plant product was evaluated by different characteristic signs for the mouse which can be retained as toxicity elements of the extract. Using the intraperitoneal route, the animals showed dose-dependent signs of toxicity, ranging from lack of appetite, depression, immobility and respiratory distress to death. Single-dose intraperitoneal LD50 value of the alcoholic Bidens tripartita extract in mice was 4038 mg/kg. No macroscopic changes were seen in the organs of mice that died following extract administration. Histopathological lesions were not found in all examined organs. CONCLUSIONS: The obtained LD50 value classifies the study plant extract as slightly toxic according to Hodge and Sterner toxicity scale. We determined the low toxic dose at a rate of 4038 mg of body weight for the alcoholic extract of this medicinal plant. These results suggest that the alcoholic extract of Bidens tripartita is relatively safe toxicologically when administered intraperitoneally, and this product could be used with some degree of safety to continue the investigation for in vivo biocompatibility evaluation.

Predictive value of animal models for human cytochrome P450 (CYP)-mediated metabolism: a comparative study in vitro.

One major challenge in drug development is defining of the optimal animal species to serve as a model of metabolism in man. The study compared the hepatic drug metabolism characteristics of humans and six widely used experimental animal species. Classical in vitro model enzyme assays with known human cytochrome P450 (CYP) enzyme selectivity were employed and optimized to target human hepatic CYP forms. The profile of CYP activities best resembling the human was seen in mouse followed by monkey, minipig, and dog liver microsomes, with rats displaying the most divergent. The widest interindividual variability was found in CYP3A-mediated midazolam -hydroxylase, and omeprazole sulphoxidase activities in human and monkey liver microsomes. These data demonstrate that if hepatic xenobiotic-metabolizing characteristics were to be the sole reason for the selection of animal species for toxicity studies, then the rat might not be the most appropriate model to mimic human CYP activity patterns.

[Immunosuppressive effects of a new phenothiazine derivative]. / Les effets immunosuppresseurs d'un nouveau dérivé de la phénothiazine.

An original phenothiazine, CPTZ, was tested for its effects on the mouse immune system. Serum opsonic capacity, phagocyte and bactericidal activity of peritoneal macrophages, counts of splenic cells forming hemolysis plaques, and the number of survivors after experimental infection were recorded. The effects observed were compared with those produced by levamisole (a non-selective immunomodulator) and indometacin (an antiinflammatory drug with selective immunomodulator properties). The effects of CPTZ might be useful for the development of a new class of immunosuppressor drugs.

[Prognosis and treatment of membranous glomerulonephritis-a 5-year prospective study]. / Prognosticul si tratamentul glomerulonefritei membranoase: studiu prospectiv pe 5 ani.

UNLABELLED: The aims of the study were to describe the clinical, pathological and biological features of membranous GN and to prospectively evaluate the relationships between individual negative prognostic factors--type of therapy and outcome. Between 1993-1998, 13/150 (8.7%) consecutive patients with renal biopsy had membranous GN (M = 62%, age = 42.5 +/- 14.5 years). Main (major) findings in these patients were: asymptomatic proteinuria--23.1%, heavy proteinuria (> 10 g/day)--33.3%, microscopic hematuria--53.8%, increased plasma creatinine levels--33.3%, hypertension--23.1% cases. 60% of the patients with nephrotic proteinuria had an underlying cause (infection, malignancy, immune-mediated systemic diseases). 40% of the patients with nephrotic proteinuria had 0 or less than 2 negative prognostic factors (without any of the recognized severe morphological changes). The following differentiated treatment protocols were applied: no treatment for asymptomatic proteinuria (group A), i.v. methyl-prednisolone boluses + prednisone 1 mg/kgc/day 3 months for those patients with few negative prognostic factors (group B), and steroids (as above) + cyclophosphamide (2 mg/kgc/day 3 months) or the Ponticelli regime in patients with important risk factors (group C). Outcome after a median follow-up period of 24 months was: complete remission in all cases from groups A + B (with only one exception were the underlying cause was breast malignancy); in group C in 75% of the subjects a complete or partial remission (proteinuria < 1 g/day) was obtained. Only one case progressed to chronic renal failure. There were no secondary effects from corticoids or immunosuppressive therapy. CONCLUSIONS: In membranous GN treatment should be tailored to the presence and type of negative prognostic factors. Even in high-risk patients combined steroids and immunosuppressive therapy determines a favorable outcome in 75% of the cases, without severe adverse effects.