Orexins/Hypocretins and Cancer: A Neuropeptide as Emerging Target

Over 20 years ago, orexin neuropeptides (Orexin-A/hypocretin-1 and Orexin-B/hypocretins-2) produced from the same precursor in hypothalamus were identified. These two neurotransmitters and their receptors (OX1R and OX1R), present in the central and peripheral nervous system, play a major role in wakefulness but also in drug addiction, food consumption, homeostasis, hormone secretion, reproductive function, lipolysis and blood pressure regulation. With respect to these biological functions, orexins were involved in various pathologies encompassing narcolepsy, neurodegenerative diseases, chronic inflammations, metabolic syndrome and cancers. The expression of OX1R in various cancers including colon, pancreas and prostate cancers associated with its ability to induce a proapoptotic activity in tumor cells, suggested that the orexins/OX1R system could have a promising therapeutic role. The present review summarizes the relationship between cancers and orexins/OX1R system as an emerging target.

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Risk assessment of occupational and occupationally conditioned diseases connection to noise when exceeding maximum permissible levels

Russian Journal of Occupational Health and Industrial Ecology ◽

10.31089/1026-9428-2018-10-17-19 ◽

2019 ◽

pp. 17-19

Author(s):

Vladimir A. Fokin ◽

Dmitrii M. Shlyapnikov ◽

Svetlana V. Red’ko

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Autonomic Nervous System ◽

High Blood Pressure ◽

Noise Exposure ◽

Physical Factors ◽

Autonomic Nervous ◽

Permissible Levels ◽

The Relationship ◽

Perm Region

In accordance with the requirements of paragraph 3.2.6 of sanitary rules and norms «Sanitary and epidemiological requirements for physical factors at workplace», in the event of exceeding noise level at workplace above 80 dBA, an employer is obliged to assess the health risk of workers and confirm an acceptable risk to their health. The connection between the incidence of occupational and occupationally conditioned diseases with noise exposure exceeding the maximum permissible levels (80 dBA) was estimated. The assessment was carried out at a food industry enterprise of Perm Region. Assessing the relationship between morbidity and noise exposure is the first step in evaluation of occupational health risks for workers exposed to noise exceeding MAL. If a reliable relationship between morbidity and noise exposure is established, an assessment of occupational risk is conducted. The odds ratio (OR) for diseases characterized by high blood pressure and disorders of autonomic nervous system was <1 (confidence interval CI=0.11–1.61 and CI=0.08–2.78, respectively). The relative risk (RR) for diseases characterized by high blood pressure and disorders of autonomic nervous system was <1. The received data testify absence of connection of morbidity with exposure to industrial noise, calculation of etiological share of responses and levels of risk is not required.

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Reproductive hormone secretion and spermatogenic function in thyroidectomized rams receiving graded doses of exogenous thyroxine

Journal of Endocrinology ◽

10.1677/joe.0.1110245 ◽

1986 ◽

Vol 111 (2) ◽

pp. 245-253 ◽

Cited By ~ 17

Author(s):

Y. Chandrasekhar ◽

M. J. D'Occhio ◽

B. P. Setchell

Keyword(s):

Hormone Secretion ◽

Reproductive Function ◽

Pulse Frequency ◽

Endocrine Function ◽

Sex Hormone Binding Globulin ◽

Testosterone Levels ◽

Reproductive Endocrine ◽

Lh Release ◽

Lh Releasing Hormone ◽

The Relationship

ABSTRACT This study aimed to obtain a better understanding of the relationship between circulating thyroxine (T4) concentrations and reproductive endocrine function in the ram. Mature Merino rams were thyroidectomized and supplemented with 0, 30, 100 and 300% of normal T4 for 10 weeks. Thyroidectomy had no apparent effect on spermatogenic function but interfered with sperm maturation, the latter being returned to normal by 30% T4 replacement. Circulating testosterone levels were reduced by thyroidectomy and restored to control levels by 30% T4; when T4 levels were supranormal (300%), circulating testosterone levels were again reduced. The lowered circulating testosterone levels in thyroidectomized rams occurred as a result of suppressed testosterone secretion from the testis, observed under basal conditions and also following LH-releasing hormone (LHRH) and human chorionic gonadotrophin injection. In thyroidectomized rams, sex hormone binding globulin (SHBG) levels were depressed without changes in testosterone clearance rate (TCR), while in rams with supranormal T4 levels, TCR was increased without changes in SHBG levels. Subnormal levels of T4 also restored to normal the reduced LH pulse frequency in thyroidectomized rams. Reduced LH pulse frequency, together with diminished LH release following LHRH injection in thyroidectomized rams, suggested effects of T4 at the hypothalamo-pituitary axis. The present study demonstrates that complete lack of thyroid hormones suppresses normal reproductive endocrine function in the ram, but that this can be restored to normal by 30% T4 replacement. The results support the theory that T4 plays a permissive rather than a regulatory role in reproductive function in males. J. Endocr. (1986) 111, 245–253

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The Relationship Between Objectively Measured Physical Activity, Salivary Cortisol, and the Metabolic Syndrome Score in Girls

Pediatric Exercise Science ◽

10.1123/pes.2013-0109 ◽

2014 ◽

Vol 26 (3) ◽

pp. 221-230 ◽

Cited By ~ 8

Author(s):

Katrina D. DuBose ◽

Andrew J. McKune

Keyword(s):

Physical Activity ◽

Blood Pressure ◽

Metabolic Syndrome ◽

Waist Circumference ◽

Body Fat ◽

Salivary Cortisol ◽

Sexual Maturity ◽

Vigorous Physical Activity ◽

The Metabolic Syndrome ◽

The Relationship

The relationship between physical activity levels, salivary cortisol, and the metabolic syndrome (MetSyn) score was examined. Twenty-three girls (8.4 ± 0.9 years) had a fasting blood draw, waist circumference and blood pressure measured, and wore an ActiGraph accelerometer for 5 days. Saliva samples were collected to measure cortisol levels. Previously established cut points estimated the minutes spent in moderate, vigorous, and moderate-to-vigorous physical activity. A continuous MetSyn score was created from blood pressure, waist circumference, high-density-lipoprotein (HDL), triglyceride, and glucose values. Correlation analyses examined associations between physical activity, cortisol, the MetSyn score, and its related components. Regression analysis examined the relationship between cortisol, the MetSyn score, and its related components adjusting for physical activity, percent body fat, and sexual maturity. Vigorous physical activity was positively related with 30 min post waking cortisol values. The MetSyn score was not related with cortisol values after controlling for confounders. In contrast, HDL was negatively related with 30 min post waking cortisol. Triglyceride was positively related with 30 min post waking cortisol and area under the curve. The MetSyn score and many of its components were not related to cortisol salivary levels even after adjusting for physical activity, body fat percentage, and sexual maturity.

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Regional vascular resistance vs. conductance: which index for baroreflex responses?

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.260.2.h632 ◽

1991 ◽

Vol 260 (2) ◽

pp. H632-H637 ◽

Cited By ~ 74

Author(s):

D. S. O'Leary

Keyword(s):

Blood Pressure ◽

Cardiac Output ◽

Arterial Pressure ◽

Pressure Regulation ◽

Differential Analysis ◽

Initial Value ◽

Baseline Effect ◽

Regional Vascular Resistance ◽

Vascular Beds ◽

The Relationship

When large changes in baseline blood flow occur in regional vascular beds (i.e., in skeletal muscle between rest and dynamic exercise or in skin between normothermia and hyperthermia) opposite conclusions are often drawn regarding the magnitude of a given vasomotor response (such as baroreflex vasoconstriction during hypotension) using regional resistance versus conductance. This report analyzes the relationship between changes in regional resistance or conductance and the contribution of the responses in the maintenance of blood pressure. The main supposition is that the appropriate index of baroreflex responses should reflect the importance of the response in the maintenance of blood pressure. Through differential analysis of the relationship between changes in resistance and conductance on arterial pressure, it can be seen that in terms of resistance, the effect of a given change in resistance on arterial pressure is greatly dependent on the baseline level of resistance. For conductance, while a modest baseline effect exists when cardiac output changes markedly, at a constant cardiac output, the same change in regional conductance always causes the same change in arterial pressure regardless of the initial value of conductance. Conclusions drawn are that while neither resistance nor conductance is a perfect index of vasomotor responses, changes in conductance far better reflect the importance of the response in pressure regulation than do changes in regional resistance.

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Activation of protease‐activated receptor 2 is associated with blood pressure regulation and proteinuria reduction in metabolic syndrome

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/1440-1681.13431 ◽

2020 ◽

Vol 48 (2) ◽

pp. 211-220

Author(s):

Kana Maruyama‐Fumoto ◽

John J. McGuire ◽

David P. Fairlie ◽

Kazumasa Shinozuka ◽

Satomi Kagota

Keyword(s):

Blood Pressure ◽

Metabolic Syndrome ◽

Blood Pressure Regulation ◽

Pressure Regulation ◽

Protease Activated Receptor 2

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Contribution of BKCa channels to local metabolic coronary vasodilation: effects of metabolic syndrome

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00876.2009 ◽

2010 ◽

Vol 298 (3) ◽

pp. H966-H973 ◽

Cited By ~ 33

Author(s):

Léna Borbouse ◽

Gregory M. Dick ◽

Gregory A. Payne ◽

Brittany D. Payne ◽

Mark C. Svendsen ◽

...

Keyword(s):

Blood Pressure ◽

Metabolic Syndrome ◽

Heart Rate ◽

Atherogenic Diet ◽

Bkca Channels ◽

Selective Blockade ◽

Before And After ◽

Lactate Uptake ◽

Exercise Induced ◽

The Relationship

This investigation was designed to examine the hypothesis that impaired function of coronary microvascular large-conductance Ca2+-activated K+ (BKCa) channels in metabolic syndrome (MetS) significantly attenuates the balance between myocardial oxygen delivery and metabolism at rest and during exercise-induced increases in myocardial oxygen consumption (MV̇o2). Studies were conducted in conscious, chronically instrumented Ossabaw swine fed a normal maintenance diet (11% kcal from fat) or an excess calorie atherogenic diet (43% kcal from fat, 2% cholesterol, 20% kcal from fructose) that induces many common features of MetS. Data were collected under baseline/resting conditions and during graded treadmill exercise before and after selective blockade of BKCa channels with penitrem A (10 μg/kg iv). We found that the exercise-induced increases in blood pressure were significantly elevated in MetS swine. No differences in baseline cardiac function or heart rate were noted. Induction of MetS produced a parallel downward shift in the relationship between coronary venous Po2 and MV̇o2 ( P < 0.001) that was accompanied by a marked release of lactate (negative lactate uptake) as MV̇o2 was increased with exercise ( P < 0.005). Inhibition of BKCa channels with penitrem A did not significantly affect blood pressure, heart rate, or the relationship between coronary venous Po2 and MV̇o2 in lean or MetS swine. These data indicate that BKCa channels are not required for local metabolic control of coronary blood flow under physiological (lean) or pathophysiological (MetS) conditions. Therefore, diminished function of BKCa channels does not contribute to the impairment of myocardial oxygen-supply demand balance in MetS.

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