Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037315 (sleep apnea)
 8,000 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is an increased mortality among patients with sleep related breathing disorders. This fact is largely ascribed to arterial hypertension and its associated cardiovascular risk with which sleep apnoea is interlinked, as is known from epidemiological and clinical studies. The present study was based on 20 males suffering from arterial hypertension and sleep apnoea, measuring the blood pressure changes 4 hours before and 4 hours after waking up, in each case without therapy and after 8 weeks' treatment with a combination preparation made up from verapamil and a potassium-saving diuretic. Besides the usual polysomnographic measurements in the sleep laboratory blood pressure was measured intra-arterially and continually, each time on two consecutive days. The average age was 53 (39-70) years, and the average of Broca's index was 129 (109-158). It was found that blood pressure values rise already 2-3 hours before waking up and maximum is attained subsequent to waking. Under therapy the minimal systolic values before waking dropped from 132.8 mmHg (+/- 22.8) to 119.4 mmHg (+/- 11.9) (p < 0.01) and the maximal values after awakening were reduced with 149.8 mmHg (+/- 27.7) vs 132.7 mmHg (+/- 25.4) (p < 0.01) without dropping to hypotensive levels. Under therapy there was a less marked and also slower rise in blood pressure with time. Besides pointing to the fact that endogenous mechanisms also influence blood pressure patterns in addition to the well-known exogenous influences, the study proved the favourable therapeutic action of treatment with an antihypertensive drug that is effective for a period of 24 hours.
 ...
PMID:[Hypertension at awakening in sleep apnea]. 849 78

Insulin resistance appears to be a common feature and a possible contributing factor to several frequent health problems, including type 2 diabetes mellitus, polycystic ovary disease, dyslipidemia, hypertension, cardiovascular disease, sleep apnea, certain hormone-sensitive cancers, and obesity. Modifiable factors thought to contribute to insulin resistance include diet, exercise, smoking, and stress. Lifestyle intervention to address these factors appears to be a critical component of any therapeutic approach. The role of nutritional and botanical substances in the management of insulin resistance requires further elaboration; however, available information suggests some substances are capable of positively influencing insulin resistance. Minerals such as magnesium, calcium, potassium, zinc, chromium, and vanadium appear to have associations with insulin resistance or its management. Amino acids, including L-carnitine, taurine, and L-arginine, might also play a role in the reversal of insulin resistance. Other nutrients, including glutathione, coenzyme Q10, and lipoic acid, also appear to have therapeutic potential. Research on herbal medicines for the treatment of insulin resistance is limited; however, silymarin produced positive results in diabetic patients with alcoholic cirrhosis, and Inula racemosa potentiated insulin sensitivity in an animal model.
 ...
PMID:Insulin resistance: lifestyle and nutritional interventions. 1076 68

In excitable cells, small-conductance Ca2+-activated potassium channels (SK channels) are responsible for the slow after-hyperpolarization that often follows an action potential. Three SK channel subunits have been molecularly characterized. The SK3 gene was targeted by homologous recombination for the insertion of a gene switch that permitted experimental regulation of SK3 expression while retaining normal SK3 promoter function. An absence of SK3 did not present overt phenotypic consequences. However, SK3 overexpression induced abnormal respiratory responses to hypoxia and compromised parturition. Both conditions were corrected by silencing the gene. The results implicate SK3 channels as potential therapeutic targets for disorders such as sleep apnea or sudden infant death syndrome and for regulating uterine contractions during labor.
 ...
PMID:Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3. 1098 76

Humans encounter hypoxia throughout their lives. This occurs by destiny in utero, through disease, and by desire, in our quest for altitude. Hypoxic pulmonary vasoconstriction (HPV) is a widely conserved, homeostatic, vasomotor response of resistance pulmonary arteries to alveolar hypoxia. HPV mediates ventilation-perfusion matching and, by reducing shunt fraction, optimizes systemic Po(2). HPV is intrinsic to the lung, and, although modulated by the endothelium, the core mechanism is in the smooth muscle cell (SMC). The Redox Theory for the mechanism of HPV proposes the coordinated action of a redox sensor (the proximal mitochondrial electron transport chain) that generates a diffusible mediator [a reactive O(2) species (ROS)] that regulates an effector protein [voltage-gated potassium (K(v)) and calcium channels]. A similar mechanism for regulating O(2) uptake/distribution is partially recapitulated in simpler organisms and in the other specialized mammalian O(2)-sensitive tissues, including the carotid body and ductus arteriosus. Inhibition of O(2)-sensitive K(v) channels, particularly K(v)1.5 and K(v)2.1, depolarizes pulmonary artery SMCs, activating voltage-gated Ca(2+) channels and causing Ca(2+) influx and vasoconstriction. Downstream of this pathway, there is important regulation of the contractile apparatus' sensitivity to calcium by rho kinase. Controversy remains as to whether hypoxia decreases or increases ROS and which electron transport chain complex generates the ROS (I and/or III). Possible roles for cyclic adenosine diphosphate ribose and an unidentified endothelial constricting factor are also proposed by some groups. Modulation of HPV has therapeutic relevance to cor pulmonale, high-altitude pulmonary edema, and sleep apnea. HPV is clinically exploited in single-lung anesthesia, and its mechanisms intersect with those of pulmonary arterial hypertension.
 ...
PMID:Hypoxic pulmonary vasoconstriction. 1559 9

Resistant hypertension affects approximately 10% of the hypertensive patient population. It should be differentiated from white-coat hypertension and pseudo-resistant hypertension. Non-compliance to anti-hypertensive therapy remains the most common cause of resistant hypertension. Primary hyperaldosteronism is not as uncommon as previously thought, but its prevalence depends on the selected population. Low-renin resistant hypertension responds to aldosterone blockade when other drugs are apparently inadequately effective. Sleep apnea syndrome can also contribute to the development of resistant hypertension by stimulating aldosterone secretion, which leads to vascular damage and may promote scarring through more direct actions. Normal blood levels of potassium in resistant hypertension do not exclude the possible presence of hyperaldosteronism.
 ...
PMID:Resistant hypertension: a methodological approach to diagnosis and treatment. 1767 42

Sleep apnea associated with chronic intermittent hypoxia (IH) impairs hippocampal functions but the pathogenic mechanisms involving dysfunction of nitric oxide (NO) and ionic channels remain unclear. We examined the hypothesis that hippocampal NO deficit impairs the activity of large conductance calcium-activated potassium (BK) channels in rats with chronic IH, mimicking conditions in patients with sleep apnea. A patch-clamp study was performed on hippocampal CA1 neurons acutely dissociated from IH and control rats. The levels of endogenous NO and intracellular calcium in the CA1 region of the hippocampal slices were measured respectively by electrochemical microsensors and spectrofluorometry. We found that the open probability of BK channels remarkably decreased in the CA1 pyramidal neurons in a time-dependent manner with the IH treatment, without changes in the unitary conductance and reversal potential. NO donors, SNP or DETA/NO, significantly restored the activity of BK channels in the IH neurons, which was prevented by blockade of S-nitrosylation with NEM or MTSES but not by inhibition of the cGMP pathway with ODQ or 8-bromo-cGMP. Endogenous NO levels were substantially lowered in the IH hippocampus during resting and hypoxia. Also, the level of protein expression of neuronal NO synthase was markedly lessened in the IH neurons with decreased intracellular calcium response to hypoxia. Collectively, the results suggest that the IH-induced NO deficit mediated by a down-regulation of the expression of neuronal NO synthase plays a causative role in the impaired activity of BK channels, which could account for the hippocampal injury in patients with sleep apnea.
 ...
PMID:Nitric oxide deficit in chronic intermittent hypoxia impairs large conductance calcium-activated potassium channel activity in rat hippocampal neurons. 1799 5

Recent studies revealed that unstable ventilation control is one of mechanisms underlying the occurrence of sleep apnea. Thus, we investigated whether TASK-1, an acid-sensitive potassium channel, plays a role in the occurrence of sleep apnea. First, the expression of TASK-1 transcriptions on brainstem was checked by in situ hybridization. Then, the correlation between the central apneic episodes and protein contents of TASK-1 measured by western blot was analyzed from 27 male rats. Results showed that TASK-1 mRNAs were widely distributed on the putative central chemoreceptors such as locus coeruleus, nucleus tractus solitarius and medullary raphe, etc. Both the total spontaneous apnea index (TSAI) and spontaneous apnea index in NREM sleep (NSAI) were positively correlated with TASK-1 protein contents (r=0.547 and 0.601, respectively, p<0.01). However, the post-sigh sleep apnea index (PAI) had no relationship with TASK-1 protein. Thus, we concluded that TASK-1 channels may function as central chemoreceptors that play a role in spontaneous sleep apneas in rats.
 ...
PMID:Expression of TASK-1 in brainstem and the occurrence of central sleep apnea in rats. 1827 37

Primary aldosteronism (PA) is associated with vascular end organ damage. The aim of the study was to evaluate differences regarding comorbidities depending on tumor size in patients with aldosterone producing adenoma (APA). The retrospective cross-sectional study was done by collection from 6 German centers (German Conn's registry) between 1990 and 2007. Among the 640 registered patients with PA, 60 operated patients with APA were analyzed. The main outcome of measures was the comorbidities depending on tumor size. Thirty-one patients (17 men, 14 women) had an adenoma size <20 mm, and 29 patients (10 men, 19 women) had an adenoma size>/=20 mm. There was no difference in age, preoperative potassium, aldosterone, or creatinine levels, preoperative systolic and diastolic blood pressure, or duration of hypertension between the two groups. In the group with APA <20 mm, cerebrovascular events occurred with a prevalence of 12.9%, cardiac events 16.1%, peripheral vascular events 25.8%, renal insufficiency 16.1%, and sleep apnea 6.4%, respectively. There was no significant difference in comorbidities compared to the group with APA>/=20 mm. Subgroup analysis (n=22) of follow-up data on post-operative systolic and diastolic blood pressure showed no significant difference between these subgroups with regard to potassium, aldosterone or creatinine levels, blood pressure, duration of hypertension, or comorbidities. Our data indicate a high prevalence of comorbidities in patients with APA. However, adenoma size was not correlated with cardio- and cerebrovascular comorbidities, and does not seem to be a prognostic factor for blood pressure outcome.
 ...
PMID:Tumor size of Conn's adenoma and comorbidities. 1954 84

Aldosterone is present and active all along the cardiovascular continuum. Excessive tissue production occurs in cardiovascular diseases including myocardial infarction (MI) and heart failure, resulting in a multitude of adverse effects in the cardiovascular system necessitating pharmacologic blockade of this neurohormone. Both human and animal studies have consistently proven the beneficial effects of antialdosteronics in the improvement of: 1) endothelial function, 2) modulation of inflammatory mechanisms between blood and the vascular wall and 3) reduction of tissue proliferation and cardiovascular remodeling leading to different severities of cardiovascular damage. These basic mechanisms of anti-aldosterone therapy strongly support the promising data observed in major clinical trials with aldosterone blockers in cardiovascular diseases, specially in heart failure patients. Whereas aldosterone receptor blockers were initially viewed as potassium-sparing diuretics there has been a clear change of concept in the past 10 years, mainly following the positive results of RALES with spironolactone in chronic heart failure, followed by EPHESUS using eplerenone in patients with systolic dysfunction post MI. The significant positive results in both studies were a clear support for the inclusion of this pharmacologic intervention as first line treatment in most international guidelines for the management of heart failure. More recent and ongoing studies are exploring the usefulness of this type of intervention in preventing vascular and myocardial hypertrophy and remodeling in refractory hypertensive and some hyperfibrotic syndromes. There are also provocative studies investigating in the possibility of inhibiting atherosclerosis. More recently, some studies are suggesting the benefit of aldosterone blockade in sleep apnea. In addition, two large multicentric trials, TOPCAT and EMPHASIS are analyzing the potential use of antialdosteronics in patients with cardiac insufficiency and preserved systolic function and the possibility of extending their indication in systolic heart failure to Phase II respectively. New compounds, blocking the synthesis of aldosterone instead of blocking its receptor are being developed, and initial Phase 2 studies are positive. All of the above results are very interesting, show an optimistic future and are consolidating and enlarging the spectrum of aldosterone blockade in cardiovascular disorders every day.
 ...
PMID:Aldosterone inhibition and cardiovascular protection: more important than it once appeared. 2067 26

Cushing's syndrome is a condition caused by high levels of glucocorticoids, or most commonly as a result of prolonged exposure to exogenous steroids. Clinical features include diabetes, hypertension, obesity, skin atrophy, immune suppression and delayed wound healing. We report a patient with iatrogenic Cushing's syndrome, in whom long-term topical steroid therapy was used to treat varicose eczema, which contributed to the development of type 2 diabetes, morbid obesity, sleep apnoea and chronic wound sepsis. In this case, repeated hospital admissions and systemic antibiotics were associated with considerable comorbidity. Aggressive local treatment, consisting of potassium permanganate soaks and irrigating gels, was highly effective in reducing the amount of exudate, pain and preventing from further deterioration of the patient's legs.
 ...
PMID:Cushing's syndrome and chronic venous ulceration--a clinical challenge. 2107 30


1 2 3 Next >>