Evidence for oxidative stress at elevated plasma thiol levels in chronic exposure to carbon disulfide (CS2) and coronary heart disease

ObjectivesOxidative stress in plasma may be promoted by plasma thiols such as homocysteine. However, other thiols such as glutathione may also exert antioxidant effects in vitro and in vivo. To further investigate whether plasma thiols act as prooxidants or antioxidants, we compared plasma oxidative status in patients with coronary heart disease (CHD) and in subjects occupationally exposed to carbon disulfide (CS₂).MethodsFifty-five subjects chronically exposed to CS₂, 53 CHD patients, and 52 healthy controls were examined. To assess plasma oxidative status, concentrations of thiobarbituric reactive substances (TBARS) and total antioxidative capacity (TAC), as well as ferritin and ceruloplasmin were determined. Antioxidative reserve was assessed by the determination of vitamine E, uric acid, superoxide dismutase, catalase, and glutathion peroxidase. In addition, protein and non-protein plasma thiol levels were measured.ResultsPatients in both groups had increased levels of plasma thiols as compared to controls: CS₂-exposed subjects presented with increased levels of thiols associated with plasma proteins, whereas CHD patients presented with elevated total homocysteine and cysteine levels. TBARS were significantly increased and TAC was significantly decreased both in CS₂-exposed subjects and in CHD patients. In addition decreased activity of glutathione peroxidase, an antioxidative enzyme inhibited by thiol-containing compounds, was noted in both groups.ConclusionThese results demonstrate that regardless of their metabolic origin increased thiols are associated with increased oxidative stress in plasma.     

Relationship of salivary adipocytokines,diet quality,physical activity,and nutrition status in adult Emirati females in United Arab Emirates

AimsThe United Arab Emirates (UAE) ranks as the fifth most obese country with increasing cardio-metabolic risks. In this paper, relationships of salivary adipocytokines (markers of cardio-metabolic syndrome), diet quality and physical activity in 90 normal-weight, overweight and obese (30 subjects in each group) Emirati adult females were investigated.MethodsA cross-sectional research design was adopted. Anthropometric measurements, diet quality and physical activity questionnaires were administered. Overnight fasting saliva was collected to determine levels of adiponectin, interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α).ResultsSalivary adiponectin was significantly lower, while TNF-α was higher in obese than normal-weight subjects. IL-10 displayed a lower trend in obese subjects. Though diet quality and physical activity did not exhibit significant differences among the three groups, better diet quality and higher physical activity level were reported among normal-weight subjects. Salivary TNF-α correlated positively with body mass index (BMI) (r = 0.37; p < 0.001) and waist circumference (r = 0.31; p < 0.001), while adiponectin correlated negatively with BMI (r = −0.28; p < 0.05). IL-10 showed negative trend in correlation with obesity measures. Correlations were not observed between diet quality and physical activity with salivary adipocytokines. Interestingly, a significant negative correlation emerged between diet quality and neck circumference (r = −0.24; p < 0.05).ConclusionOur findings demonstrate that salivary adipocytokines correlate with obesity measures and can serve as convenient adjunct method in predicting cardio-metabolic risks in the population.     

Protein thiols and thiobarbituric acid reactive substance status in colon cancer patients

Objective. Colon cancer is the most common malignancy found in the developed countries. Cancer initiation and progression is known to be associated with the formation of reactive oxygen species, formed in excess in the gastrointestinal tract. The aim of the study was to assess the levels of protein thiols and thiobarbituric acid reactive substances (TBARS) in patients with colon cancer. Material and methods. Serum samples were obtained from 60 subjects (M and F, mean age 50±15 years), 30 of which were from colon cancer patients and 30 from healthy individuals. All the serum samples were analyzed for carcinoembryonic antigen (CEA), protein thiols and TBARS. Results. The levels of protein thiols were significantly lower in colon cancer patients (p<0.001) than in the healthy controls. The TBARS levels in colon cancer patients were moderately high (p<0.05) in comparison with those of the controls. Conclusions. Low levels of protein thiols and elevated TBARS of colon cancer patients support the hypothesis that colon cancer is associated with reactive oxygen species. Therefore protein thiols and TBARS may serve as additive non-invasive biochemical markers of oxidative stress in colon cancer and this hypothesis needs to be further investigated.     

Assessment of the platelet parameters and serum butyrylcholinesterase activity in type 1 diabetes patients with ketoacidosis

The potential roles of serum butyrylcholinesterase (BChE) activity and platelet indices in type 1 diabetes (T1D) remain uncertain. We aimed to investigate the correlation among the platelet indices, serum BChE activity, and diabetic ketoacidosis (DKA). Sixty-one T1D patients, 29 patients with DKA, and 30 age- and sex-matched controls were enrolled. Mean platelet volume (MPV), platelet distribution width (PDW), and serum BChE activity were measured and evaluated at admission and after the treatment. The serum BChE activity was significantly lower in patients with DKA at admission to the hospital compared with non-DKA and control subjects; however, plasma glucose level, HbA1c level, MPV and PDW were significantly higher. Serum BChE activity, variables related to glycemic control, and platelet parameters were higher in non-DKA patients than in controls. Serum BChE activity was correlated with the serum HCO₃ level (r?=?0.375, p?<?0.05) and plasma glucose level (r?=??0.387, p?<?0.05). Receiver operating characteristic curve analyses showed no difference between serum BChE activity and the platelet parameters with respect to the ability to reflect DKA. Logistic regression showed that increased PDW can act as a risk marker for the presence of DKA. Serum BChE activity and the platelet parameters returned to normal along with the plasma glucose levels when metabolic acidosis was well controlled. Serum BChE activity and the platelet parameters were significantly correlated with DKA. Measurement of PDW can provide complementary information and a risk biomarker reflecting the presence of DKA.     

Salivary eicosanoid concentration in patients with Sj?gren's syndrome.

OBJECTIVE: To investigate eicosanoid concentrations in the saliva of patients with primary Sjögren's syndrome (SS). METHODS: Whole mixed saliva of 36 subjects was assayed for eicosanoid concentrations using a radioimmunoassay. Patients with primary SS having positive lip biopsy served as the study group; their results were compared with data from patients with dry mouth and negative lip biopsy (dry mouth group), and with a group of normal healthy controls. RESULTS: Concentrations of thromboxane B2 were significantly (p < 0.01) increased in 18 patients with primary SS compared with 10 patients with dry mouth and eight healthy normal controls (1.95 (SD 0.51) ng/ml saliva compared with 0.52 (0.1) ng/ml and 0.3 (0.1) ng/ml, respectively). Similarly, prostaglandin E2 concentrations were also significantly increased (p < 0.01) in 11 patients with primary SS compared with five patients with dry mouth and eight normal controls (3.75 (0.82) ng/ml saliva compared with 0.32 (0.1) ng/ml and 0.41 (0.1) ng/ml, respectively). CONCLUSION: Salivary concentrations of eicosanoids are significantly increased in patients with primary SS, and this may prove helpful in the diagnosis of this disease.     

Alterations in cyclic nucleotide phosphodiesterase activities in omental and subcutaneous adipose tissues in human obesity

Objective: To elucidate the activity and expression of cyclic nucleotide phosphodiesterase (PDE) families in omental (OM) and subcutaneous (SC) adipose tissue and adipocytes, and to study alterations in their activity in human obesity.Design: Cross-sectional, translational research study.Patients: In total, 25 obese and 9 non-obese subjects undergoing gastrointestinal surgery participated in the study.Results: Inverse correlations between PDE activities and body mass index (BMI) were seen in both SC and OM adipose tissue. Inverse correlations between total PDE and PDE3 activity and BMI were seen in OM adipocytes but not in SC adipocytes. In both SC and OM adipose tissue of obese patients, total PDE and PDE3 activities were decreased compared with the controls. In SC adipose tissue of Type 2 diabetes (T2D) patients, the PDE activity not inhibitable by PDE3 or PDE4 inhibitors (PDEn) was increased compared with obese non-diabetic patients. In addition to PDE3 and 4 isoforms, PDE7B, PDE9A and PDE10A proteins were also detected in adipose tissue or adipocytes.Conclusions: Multiple PDE families are present in human adipose tissue and their activities are differentially affected by obesity and T2D.     

Periodontal disease and type 2 diabetes: effects on salivary enzyme activities

There has been correlation between type 2 diabetes and periodontal disease and numerous markers in saliva, such as intracellular enzymes, which have been proposed as diagnostic tests for periodontal diseases. The present study estimates the activities of some salivary enzymes as possible means of diagnosis and treatment monitoring of periodontal disease patients with type 2 diabetes. A total of 320 subjects, of both sexes, aged 28–81 years were included in the study and divided into four groups of 80 subjects each. The groups were non-diabetics with periodontal disease, type 2 diabetics with periodontal disease, type 2 diabetics without periodontal disease and apparently healthy non-diabetics (controls). The activities of the enzymes, acid phosphatase (ACP), alkaline phosphatase (ALP), alanine transmainase (ALT), aspartate transaminase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were determined in saliva of the subjects using standard spectrophotometric methods. For data analysis, paired students t-test was done using SPSS computer software and the results are presented as mean±SD. The enzyme activities (U/L) investigated showed significant differences (P?<?0.001) in the enzymes studied in non-diabetics with periodontal disease and diabetics with periodontal disease, whereas only ALT was significant in diabetics without periodontal disease, compared with controls. A comparison of non-diabetics and the type 2 diabetics with periodontal disease showed significant increases in all the enzymes except ALP and CK in diabetics. Type 2 diabetes and periodontal disease leads to significant increases in salivary enzyme activities, with higher activity in co-occurrence. Salivary enzyme activities can be useful in diagnosis, treatment and management of the two conditions.     

Salivary cortisol measurement in normal-weight, obese and anorexic women: comparison with plasma cortisol.

OBJECTIVE: To compare salivary, plasma and urinary free cortisol (UFC) measurements in patients with anorexia nervosa, in whom an overdrive of the hypothalamic-pituitary-adrenal (HPA) axis is well established but information on salivary cortisol is lacking, in viscerally obese patients in whom subtle abnormalities of cortisol secretion and metabolism are postulated, and in normal-weight healthy women. PARTICIPANTS AND EXPERIMENTAL DESIGN: Measurement of salivary cortisol offers a convenient way to assess the concentrations of free, biologically active cortisol in plasma in different physiopathological settings. Forty-seven drug-free, newly diagnosed women with active restrictive anorexia nervosa, 30 restrictive anorexic women undergoing chronic psychopharmacological treatment, 47 women with mild-to-moderate visceral obesity, 103 women with severe central obesity and 63 normal-weight healthy women entered the study. Salivary and blood samples were collected at 0800 h, 1700 h and 2400 h, together with three consecutive 24-h urine specimens for UFC determination. In controls and patients with anorexia nervosa (n=83), salivary and plasma cortisol were also measured after a 1-mg overnight dexamethasone suppression test (DST). In patients with anorexia nervosa, mood was rated by the Hamilton scale for anxiety and depression. RESULTS: Untreated patients with anorexia nervosa showed increased plasma and salivary cortisol and UFC concentrations (all P<0.001 compared with controls), and decreased cortisol suppression after DST in plasma and saliva (P<0.0001 and P<0.005 respectively compared with controls). These alterations were less pronounced, although still statistically significant, in treated patients with anorexia nervosa. Salivary cortisol was highly correlated with paired plasma cortisol in the whole population and after splitting the participants by group (P<0.0001). However, for plasma cortisol values greater than 500 nmol/l (the corticosteroid-binding globulin saturation point), this parallelism was lost. Taking plasma cortisol as a reference, the level of agreement for post-dexamethasone salivary and plasma cortisol was 58.9% among suppressors and 77.8% among non-suppressors (chi2 test: P<0.01). Decreased 0800 h/2400 h cortisol ratios were observed in plasma and saliva in drug-free patients with anorexia nervosa (P<0.005 and P<0.05 respectively compared with controls), and in saliva in severely obese patients (P<0.05 compared with controls). Depression and anxiety scores were unrelated to cortisol concentrations in any compartment. CONCLUSIONS: Salivary cortisol measurement is a valuable and convenient alternative to plasma cortisol measurement. It enables demonstration of the overdrive of the HPA axis in anorexia nervosa and subtle perturbations of the cortisol diurnal rhythm in women with visceral obesity. With the establishment of more specific and widely acceptable cut-off values for dynamic testing, measurement of salivary cortisol could largely replace plasma cortisol measurement.     

Spontaneous diabetic BB rat: studies of cyclic adenosine 3',5'-monophosphate phosphodiesterase and calmodulin

Uncontrolled diabetes in man is associated with increased plasma and tissue levels of cAMP and decreased cAMP phosphodiesterase (PDE) activity. Spontaneously diabetic BB rats (SDR) were used in these experiments. Specific tissues (i.e. liver and epididymal fat) were studied without therapeutic insulin. Another group of normal animals were rendered diabetic by streptozotocin (STZ) and killed without benefit of insulin therapy. Calmodulin (CM), a small molecular weight protein essential for activation of specific cAMP PDE was assayed. STZ diabetes is associated with a decrease (58%) in CM biological activity and in immunoreactive CM in fat (69%) and liver (13%) tissues. Similarly, SDR rats and the nondiabetic genetic controls (NDR) demonstrate decreased CM bioactivity in fat (76% and 56%, respectively) and decreased CM immunoreactivity in liver (68% and 74%, respectively) compared to normal control rats. In addition, maximum velocity (Vmax) of the low Michaelis-Menten constant (Km) cAMP PDE is decreased in SDR animals, as compared to controls in both fat (42%) and liver (39%) tissues. Similar data are presented for NDR animals. STZ diabetes is also associated with a reduction in Vmax of the low Km cAMP PDE in both liver (70%) and fat (70%) tissues. These changes found in the NDR animals suggests that the diabetic defect may be under dual regulation: genetic and environmental.     

A joint detection of CEA and CA-50 levels in saliva and serum of patients with tumors in oral region and salivary gland

Objective  To detect the levels of carcinoembryonic antigen (CEA) and carcinoma associated antigen CA-50 in the patients with oral or salivary malignant tumors. Methods  The concentrations of salivary CEA and CA-50 were assayed in 80 patients of oral and salivary malignant tumors, 40 patients of benign tumors and 80 health controls. In 80 patients with malignant tumors, serum CEA and CA-50 were also assayed by enzyme-linked immunoabsorbent assay and immunoradiometric analysis, respectively. Results  Salivary CEA and CA-50 levels were significantly higher in malignant tumors than in benign tumors and in health controls, respectively (P < 0.001). Only 7 cases and 3 cases of 80 patients with malignant tumors were found having increased serum CEA and CA-50 levels, respectively. Conclusions  The measurement of CEA and CA-50 levels in saliva were more sensitive than in serum. This may be more useful as prognostic indicators in early diagnosis of oral and salivary malignant tumors.     

Evaluation of oxidative stress,enzymatic and non-enzymatic antioxidants and metabolic thyroid hormone status in patients with diabetes mellitus

AimsOxidative stress is currently suggested as mechanism underlying diabetes and diabetic complications. The aim of the study was to evaluate the magnitude of oxidative stress in patients with diabetes by measuring the lipid peroxidation as well as the status of the antioxidant defense system, thyroid hormones status and other biochemical variables.MethodsThe study population consisted of 100 subjects divided into two groups viz. diabetic (n = 50) and healthy controls (n = 50).ResultsThe level of thiobarbituric acid reactive substances (TBARS) was found to be increased significantly in diabetic patients compared to healthy controls. On the other hand, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), reduced glutathione (GSH), vitamin A, vitamin E and vitamin C were found to be decreased significantly in diabetics when compared to control subjects. The level of TSH was significantly decreased whereas the levels of T4 and FT4 were significantly increased in diabetic patients than the control subjects. However, the T3 and FT3 levels did not differ significantly between groups.ConclusionOur findings indicate that changes in oxidant and antioxidant equilibrium will have biological and possibly pathological role in the development of secondary complications. The study has shown a high incidence of abnormal thyroid hormone status among the diabetics. In our findings demonstrate that detection of thyroid hormone status in the early stage of the disease will help the patients to improve quality of life and reduce the morbidity rate.     

Levels of cathepsins in acute myocardial infarction

Aims/objectiveOver expression of matrix degrading enzymes have been implicated in plaque destabilisation and rupture. Cathepsins associated with extracellular matrix breakdown make them intriguing suspects. The aim of the study was to analyse peripheral levels of cathepsin B and cathepsin K and their inhibitor cystatin C during acute myocardial infarction (AMI).Materials and methodsStudy population included AMI patients at acute event (AMI group, n=48), stable angina patients (stable angina group n = 17), and healthy individuals (Control group, n=31). Cathepsin B, cathepsin K, cystatin C, and matrix metalloproteinases (MMP)-9 were analysed by enzyme-linked immunosorbent assay (ELISA) method.ResultsCathepsin B (45.9%) and cathepsin K (92.31%) at acute event of myocardial infarction (AMI group) increased (P=0.001) while cystatin C decreased marginally (12.5%) as compared to controls. Stable angina group, demonstrated only marginal reduction in all the parameters studied as compared to controls.ConclusionCathepsin B and cathepsin K can be further evaluated as biomarkers in identifying high-risk individuals for AMI.     

A phosphodiesterase 3 inhibitor, K-134, improves hindlimb skeletal muscle circulation in rat models of peripheral arterial disease

ObjectiveCilostazol is a phosphodiesterase (PDE)3 inhibitor used to treat peripheral arterial disease with intermittent claudication, as there is clinical evidence that it improves treadmill exercise capacity. However, details of the mechanism underlying this enhanced walking capacity remain to be elucidated.MethodsBased on the hypothesis that PDE3 inhibitors improve peripheral microcirculation in the hindlimbs via vascular smooth muscle relaxation and antiplatelet effects, we examined the effects of a more potent and selective PDE3 inhibitor, K-134, in rat models of peripheral arterial disease (PAD).ResultsIn a hindlimb ischemia model established by bilateral femoral artery occlusion, oral administration of K-134 for 27 days significantly increased blood flow in hindlimb skeletal muscle after exercise induced by electrical stimulation of the sciatic nerve. Moreover, K-134 enlarged the luminal area of intramuscular arteries and prevented rarefaction of capillary density in the gastrocnemius muscle. These effects were observed without pre-administration on the day following the last administration, suggesting that vasodilatory, antiplatelet and angiogenic activities of K-134 were indirectly responsible for the long-term beneficial effects. In fact, K-134 dose-dependently induced relaxation of rat femoral arteries in vitro, and inhibited rat platelet aggregation ex vivo. Interestingly, in a laurate-induced peripheral vascular injury model, oral administration of K-134 for 6 days prevented progression of hindlimb necrosis.ConclusionThese findings suggest that the beneficial effects of PDE3 inhibitors on walking capacity are due to increased hindlimb skeletal muscle blood flow via intramuscular artery enlargement, and that K-134 is a promising drug for PAD associated with platelet hyperaggregability.     

Correlation between salivary epidermal growth factor levels and refractory intraoral manifestations in patients with Sjögren's syndrome

Abstract

Objective. To assess changes in salivary epidermal growth factor (EGF) levels and the correlation between these levels and the severity of intraoral manifestations in Sjögren's syndrome (SS).

Methods. Forty SS patients and 23 controls were enrolled. Salivary EGF concentration was measured using an enzyme-linked immunosorbent assay, and intraoral manifestations were evaluated using a short version of the Oral Health Impact Profile (OHIP-14). The associations among salivary flow rate, EGF levels and the severity of intraoral manifestations were analyzed.

Results. The total salivary EGF output was significantly decreased in the SS patients compared with the controls (9237.6 ± 8447.0 vs. 13296.9 ± 7907.1 pg/10 min, respectively, p = 0.033). In the SS patients, total EGF output and salivary flow rate showed a strong positive correlation (r_s = 0.824, p = 0.0005), while total EGF output and disease duration showed a negative correlation (r_s = ?0.484, p = 0.008). Further, total EGF output was significantly correlated with the OHIP-14 score (r_s = ?0.721, p = 0.012).

Conclusions. The salivary flow rate and EGF levels are decreased in SS, and this deterioration in saliva quality causes refractory intraoral manifestations. Our findings have provided new therapeutic targets for SS.     

Salivary gland involvement and oxidative stress in juvenile idiopathic arthritis: novel observation in oligoarticular-type patients

OBJECTIVE: The salivary glands may become affected in various collagen diseases, but their involvement in juvenile idiopathic arthritis (JIA) has received little attention. We studied the salivary composition and the antioxidant profile in patients with JIA, as well as their serum antioxidant status. METHODS: Twenty-two children with JIA according to the American College of Rheumatology criteria (10 oligoarticular, 7 polyarticular, and 5 systemic-type) and 15 healthy controls were studied. Serum and saliva samples were obtained simultaneously and analyzed. RESULTS: Significantly raised levels of antioxidant enzyme activity were observed in the patients with JIA, in both saliva and serum. The salivary peroxidase activity was significantly higher in the total group of patients with JIA by 8.5% (p < 0.01) as compared to controls (0.76 vs 0.70 mU/ml). Salivary superoxide dismutase was found to be significantly increased mainly in the patients with systemic JIA (by 74%; p < 0.02). Significantly higher levels of peroxidase activity were observed in serum of patients with JIA, particularly of the polyarticular group, by 17% (p < 0.05). Major changes in saliva composition were observed in patients with oligoarticular disease compared to controls: the patients had a lower salivary flow by 33%, less acidic saliva, and significantly lower salivary levels of magnesium by 44% (p < 0.01), total protein by 44% (p < 0.02), amylase by 34% (p < 0.02), and lactate dehydrogenase by 62% (p < 0.02). CONCLUSION: Children with JIA exhibited a major increase in antioxidant enzyme activity, both in serum and in saliva. Patients with oligoarticular JIA displayed indications of significant and specific damage to the salivary glands, a novel observation.     

Plasma protein oxidation and total antioxidant power in premenstrual syndrome

ObjectiveTo explore whether oxidative stress has any role in premenstrual syndrome (PMS).MethodsFemale volunteers suffering from PMS, in the age group of 20–24 years were compared to their asymptomatic normomennorhoeic counterparts in follicular phase and late luteal phase for ferric reducing antioxidant power of plasma (FRAP), plasma protein thiols (PPT) and protein carbonyls (PPC) levels.ResultsThere was no significant change in FRAP and PPC levels in controls and PMS groups but PPT decreased significantly in luteal phase of PMS (P<0.05) when compared to follicular phase.ConclusionsEstrogen and progesterone, might be responsible for a healthy antioxidant profile in PMS. However, a marked decrease in PPT in luteal phase of PMS group may be due to pro-oxidant nature of estrogen-active in this phase of PMS leading to consumption of the sacrificial antioxidant-protein thiol.     

Phosphodiesterase type-5 inhibitors for erectile dysfunction following nerve-sparing radical prostatectomy: A network meta-analysis

Background:To verify which phosphodiesterase type 5 inhibitors (PDE5is) strategy is better for erectile dysfunction (ED) following nerve-sparing radical prostatectomy (NSRP).Methods:This systematic literature search was conducted in MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials database to identify eligible studies from the startup of these databases to 1 November, 2019. The ED recovery rate was the main outcome. Traditional pair-wise meta-analysis and multivariate random-effects network meta-analysis (NMA) were performed to explore direct and indirect comparisons, respectively. The surface under the cumulative ranking (SUCRA) probabilities was used to evaluate the efficacy of treatments.Results:A total of 14 randomized controlled trials with four kinds of PDE5is were included. Further pooled evidence suggested that PDE5is followed by NSRP had a benefit for penile rehabilitation compared to placebo using traditional pair-wise meta-analyses. Our NMA showed that Avanafil 200 mg on demand might be most likely to be the best treatment option according to the first rank of SUCRA both in NMA (SUCRA 83.5) and sensitivity analysis (SUCRA 90.2).Conclusion:Avanafil 200 mg on demand has the highest probability of being the best intervention among PDE5is in treating ED following NSRP. However, more randomized controlled trials are needed to validate this in consideration of the published data regarding Avanafil is relatively small scale.     

Diurnal variations in salivary protein carbonyl levels in normal and cognitively impaired human subjects

Oxidative stress has been documented in tissues and biofluids of subjects with sporadic Alzheimer disease (AD) and mild cognitive impairment (MCI). The aim of this study was to determine whether (a) salivary protein carbonyls are elevated in AD and MCI subjects, (b) salivary protein carbonyl contents in these groups exhibit diurnal variation, and (c) apolipoprotein E ɛ4 (apoE ɛ4) carrier status impacts salivary carbonyl concentrations or rhythmicity in the AD and MCI cohorts. Unstimulated saliva was collected at fixed intervals between 8 AM and 10 PM from 15 AD subject , 21 MCI subjects, and 30 cognitively-intact controls. Salivary protein carbonyl concentrations were measured by ELISA. ApoE genotyping was performed on the AD and MCI individuals. For all groups, mean protein carbonyl contents were significantly elevated at 2 PM relative to other time points surveyed. Mean salivary protein carbonyl concentrations did not differ among the diagnostic groups. ApoE ɛ4 carriers exhibited less temporal variation in salivary protein carbonyls relative to noncarriers. Thus, protein carbonyl content exhibits diurnal variation in adult human saliva. ApoE ɛ4 carrier status may impact oropharyngeal disease expression by attenuating the inherent diurnal variability in salivary redox homeostasis. Salivary protein carbonyls do not differentiate AD and MCI from normal individuals. In conclusion, oxidative stress has been documented in tissues and biofluids of subjects with sporadic AD and MCI. This article demonstrates that levels of protein carbonyls, a marker of oxidative stress, exhibit robust diurnal variation in the saliva of normal elderly, MCI, and AD subjects. Apolipoprotein E ɛ4 allele carrier status may attenuate this temporal variability in salivary redox homeostasis and thereby impact the natural history of oropharyngeal diseases.     

A biochemical and functional assessment of monocyte phosphodiesterase activity in healthy and asthmatic subjects

The aim of this study was to investigate whether cyclic adenosine 3'5-monophosphate (cAMP) phosphodiesterase (PDE) activity is altered in monocytes from mild asthmatic subjects. Total cAMP PDE activity (pmol/min per mg protein) was significantly greater in homogenates prepared from monocytes from asthmatic subjects (68.3 +/- 7.0, n=9) compared to healthy individuals (46.3 +/- 3.3, n=14, P<0.05). The PDE inhibitors siguazodan (PDE3-selective), rolipram (PDE4-selective) and theophylline (non-selective) produced a concentration-dependent inhibition of cAMP PDE activity in homogenates from monocytes from normal and asthmatic subjects. However, siguazodan produced significantly greater (P<0.05), and rolipram significantly less (P<0.05), inhibition of total cAMP PDE activity in monocytes from asthmatics (n=4) than from healthy individuals (n=5). cAMP PDE activity was inhibited with equal potency by theophylline in monocytes from healthy and asthmatic subjects. We also investigated the functional consequences of the changes in PDE activity in mononuclear cells obtained from asthmatic subjects. There was no significant difference in the ability of PDE4 inhibitors to attenuate TNF alpha release from monocytes obtained from asthmatic compared with healthy subjects (P>0.05). Despite a significant increase in the biochemical activity of PDE3 in monocytes from asthmatic subjects, the PDE3 inhibitor siguazodan, failed to significantly reduce TNF alpha release from human monocytes. Thus, total cAMP PDE activity is increased in monocytes taken from mild asymptomatic asthmatics compared to healthy subjects and is reflected by an increase in the proportion of PDE3 and a decrease in the proportion of PDE4. This augmented enzyme activity was not associated with an alteration in the ability of PDE4 inhibitors to attenuate mononuclear cell function from asthmatics compared to healthy individuals.