Gerardo Pérez

Antioxidant status in patients with sleep apnoea and impact of continuous positive airway pressure treatment

The episodes of hypoxia/re-oxygenation associated with the respiratory disturbances observed in patients with obstructive sleep apnoea syndrome (OSAS) may induce the generation of oxygen free radicals. Indeed, several studies suggest that OSAS is associated with oxidative stress. The present study tested the hypothesis that patients with OSAS have an alteration in antioxidant defences. The plasma levels of total antioxidant status (TAS), glutathione peroxidase (GPX), γ-glutamyltransferase (GGT), vitamins A, E, B12 and folate, and homocysteine were determined in 47 patients with OSAS and 37 healthy subjects. Of these, 27 patients who used continuous positive airway pressure (CPAP) for >4 h·night−1 were re-examined 12 months later. Patients with OSAS had lower TAS (1.4±0.16 versus 1.50±0.10 mmol·L−1), vitamin A (64±19 versus 74±17 μg·dL−1) and vitamin E levels (1,525±499 versus 1,774±503 μg·dL−1), and increased values of GGT (42±22 versus 32±16 U·L−1) than controls. There was no difference between groups in GPX, homocysteine, vitamin B12 and folate plasma levels. CPAP treatment normalised the levels of TAS (1.50±0.13 mmol·L−1) and the activity of GGT (30±14 U·L−1) without any influence on vitamins levels. In conclusion, the results indicate that patients with obstructive sleep apnoea syndrome have a decreased antioxidant capacity that is partially reversed by continuous positive airway pressure treatment.

Increased plasma levels of asymmetric dimethylarginine and soluble CD40 ligand in patients with sleep apnea.

Background: Cardiovascular (CV) diseases are a leading cause of mortality and they are frequent in patients with the obstructive sleep apnea syndrome (OSAS). Objectives: In this study we investigated if OSAS influences CV function independently of other CV risk factors frequently present in these patients (e.g. obesity, high blood pressure). Methods: We compared plasma markers of endothelial dysfunction, asymmetric dimethylarginine (ADMA) and endothelin-1 (ET-1), and atherosclerosis progression (soluble fraction of the CD40 ligand, sCD40L) in OSAS patients with (n = 23) and without (n = 18) concurrent CV risk factors, as well as in healthy subjects (n = 23). Results: Plasma ADMA (p < 0.01) and sCD40L (p < 0.05) were abnormally increased in patients with OSAS versus healthy controls, but they were not influenced by the presence or absence of CV risk factors in OSAS. ET-1 levels were not different between the three groups of subjects studied. Conclusions: OSAS is associated with endothelial injury and atherosclerosis progression independently of other CV risk factors.

Neuroticism and cortisol: Pinning down an expected effect

BACKGROUND There are strong theoretical arguments that those high on Neuroticism (N) should normally exhibit higher prevailing levels of the stress-linked hormone cortisol (C), but findings are inconsistent, probably reflecting methodological weaknesses especially in taking account of Cs diurnal cycle. METHODS High and low N students [Total N=118; mean age=20.99years] were recruited and their salivary cortisol measured, ensuring that saliva samples were numerically adequate to assess Cs diurnal cycle over two days with objective verification of sample timing. RESULTS Cortisol secretion was approximately 20% higher in High N than low N participants in the period of 12h after awakening (p<.008), but no differences in secretion were evident during the first 0.75 of this period, when typically the Cortisol Awakening Response (CAR) rapidly takes cortisol to its daily peak. N effects were thus confined to the 0.75h-12h period (p<.007). Males had approximately 25% higher cortisol secretion levels than females, also confined to the 0.75h-12h period (p<.003). No significant differences between N groups were evident for dynamic measures of cortisol change, viz. the magnitude of CAR rise and subsequent diurnal fall. All effects were controlled for cohort date of study entry, age, smoking status, study day and time of awakening. DISCUSSION With careful control, it appears that an important theoretically predicted effect exists, and is replicated in different student intake cohorts recruited in different years. Most importantly, findings support several lines of evidence that the period of massive rise in the brief 0-0.75h CAR period should be seen as quite separate from the rest of the diurnal cycle, underpinned by different control mechanisms, and with potentially different correlates.

Circulating branched-chain amino acids in children with obstructive sleep apnea

The effects of obstructive sleep apnea (OSA) on the metabolic system are not well understood, especially in children. Recent studies have provided evidence of the modulation of insulin action by branched‐chain amino acids (BCAAs) and suggested novel mechanistic relationships between glucose and amino acid metabolic pathways. We hypothesized that plasma BCAA levels may serve as biomarkers of insulin resistance and metabolic dysfunction in children with OSA.

Assessing the improvements in the newborn screening strategy for cystic fibrosis in the Balearic Islands.

OBJECTIVES Newborn screening strategies for cystic fibrosis (CF) are run worldwide, and aim at the early detection of the disorder to significantly improve the quality of life. Elevated levels of immunoreactive trypsinogen (IRT) represent a high likelihood for the screened child to be affected with CF. However, the specificity of IRT is low. The objective of this study was to assess the screening program in the Balearic Islands during the past 14 years. DESIGN & METHODS We evaluated all results of the screening program after 14 years, by considering all changes in the protocol and assessing the number of positive samples, the mutations detected, the number of sweat tests performed, the incidence of CF and the presence of false-negative cases. RESULTS Despite a great variability among the different Balearic Islands, the global incidence of CF was 1:6059 for the 14 years assessed. The incidence in the smaller islands is about 5 times higher than in Majorca (1:2376 versus 1:10,613). After different changes in the protocol, an IRT cut-off value of 60 ng/mL was established. The two most common mutations are ΔF508 and G542X, in accordance with other geographical regions. CONCLUSIONS The changes in the protocol helped reduce the number of sweat tests performed without any increase in the false-negative rate.

A randomized controlled trial: branched‐chain amino acid levels and glucose metabolism in patients with obesity and sleep apnea

There is evidence that changes in branched‐chain amino acid (BCAA) levels may correlate with the efficacy of therapeutic interventions for affecting improvement in metabolic control. The objective of this study was to evaluate whether serum concentrations of BCAAs (leucine, isoleucine, valine) could mediate in insulin sensitivity and glucose tolerance after continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). A prospective randomized controlled trial of OSA patients with morbid obesity was conducted. Eighty patients were randomized into two groups: 38 received conservative treatment and 42 received CPAP treatment for 12 weeks. Plasma levels of BCAA, glucose tolerance and insulin resistance were evaluated at baseline and after treatment. After treatment, significant decreases of leucine levels were observed in both groups when compared with baseline levels (P < 0.005). With respect to patients with normal glucose tolerance (NGT), patients with impaired glucose tolerance (IGT) had higher baseline levels of isoleucine (78 ± 16 versus 70 ± 13 μmol L−1, P = 0.014) and valine (286 ± 36 versus 268 ± 41 μmol L−1, P = 0.049), respectively. Changes in levels of leucine and isoleucine after treatment were related negatively to changes in fasting plasma glucose and glycosylated haemoglobin values only in the conservative group (P < 0.05). In summary, we found that the treatment with CPAP for 12 weeks caused similar changes in circulating BCAAs concentrations to conservative treatment and a differential metabolic response of CPAP and conservative treatment was observed between the relationship of BCAAs and glucose homeostasis. Additional studies are needed to determine the interplay between branched‐chain amino acids and glucose metabolism in patients with sleep apnea.