The effects of chronic long-term intermittent hypobaric hypoxia on blood rheology parameters.

The effect of chronic long-term intermittent hypobaric hypoxia (CLTIHH) on blood rheology is not completely investigated. We designed this study to determine the effect of CLTIHH on blood rheology parameters. Present study was performed in 16 male Spraque-Dawley rats that divided into CLTIHH and Control groups. To obtain CLTIHH, rats were placed in a hypobaric chamber (430 mmHg; 5 hours/day, 5 days/week, 5 weeks). The control rats stayed in the same environment as the CLTIHH rats but they breathed room air. In the blood samples aspirated from the heart, hematocrit, whole blood viscosity, plasma viscosity, plasma fibrinogen concentration, erythrocyte rigidity index and oxygen delivery index were determined. The whole blood viscosity, plasma viscosity, hematocrit and fibrinogen concentration values in the CLTIHH group were found to be higher than those of the control group. However, no significant difference was found in erythrocyte rigidity index and oxygen delivery index between the groups. Our results suggested that CLTIHH elevated whole blood viscosity by increasing plasma viscosity, fibrinogen concentration and hematocrit value without effecting the erythrocyte deformability. Hence, CLTIHH that may occur in intermittent high altitude exposure and some severe obstructive sleep apnea (OSA) patients may be responsible for hemorheologic changes in those subjects.

Alterations of central hypercapnic respiratory response induced by acute central administration of serotonin re-uptake inhibitor, fluoxetine.

Long-term neurochemical changes are responsible for therapeutic actions of fluoxetine. The role of increased central concentration of serotonin by inhibiting its re-uptake via fluoxetine on the central hypercapnic ventilatory response is complex and little is known. We aimed to research the effect of acute intracerebroventricular (ICV) injection of fluoxetine on hypercapnic ventilatory response in the absence of peripheral chemoreceptor impulses and the role of 5-HT2 receptors on responses. Eighteen anesthetized albino rabbits were divided as Fluoxetine and Ketanserin groups. For ICV administration of fluoxetine and ketanserin, a cannula was placed in the left lateral ventricle by the stereotaxic method. Respiratory frequency (fR), tidal volume (V(T)) and ventilation minute volume (V(E)) were recorded in both groups. ICV fluoxetine (10.12 mmol/kg) injection during normoxia caused significant increases in V(T) and V(E) (both P < 0.01) in the fluoxetine group. When the animals were switched to hypercapnia f/min, V(T) and V(E) increased significantly. The increases in percentage values in V(T) and V(E) in Fluoxetine + Hypercapnia phase were higher than those during hypercapnia alone (P < 0.01 and P < 0.05, respectively). On blocking of 5-HT2 receptors by ketanserin (0.25 mmol/kg), the ventilatory response to Fluoxetine was abolished and the degree of increases in V(T) and V(E) in the Ketanserin + Hypercapnia phase were lower than those during hypercapnia alone (P < 0.01 and P < 0.001, respectively). We concluded that acute central fluoxetine increases normoxic ventilation and also augments the stimulatory effect of hypercapnia on respiratory neuronal network by 5-HT2 receptors in the absence of peripheral chemoreceptor impulses.

Respiratory alterations due to chronic long-term intermittent hypobaric hypoxia in rabbits: importance of peripheral chemoreceptors.

BACKGROUND: None of the studies carried out so far investigated the effect of denervation of peripheral chemoreceptors on basal ventilation and respiratory responses to acute hypoxia in subjects exposed to chronic long-term intermittent hypobaric hypoxia (CLTIHH). We aimed to research (i) the effect of CLTIHH (430 mmHg, 5 h/day, 5 days/week, 5 weeks) on basal ventilation and respiratory responses to hypoxia and (ii) the effects of CLTIHH on central respiratory mechanisms after peripheral chemodenervation. METHODS: Sixteen adult albino rabbits were divided into two groups: CLTIHH (n = 8) and control (n = 8). The tidal volume (V(T)) and respiratory frequency (f/min) were initially recorded in both groups and respiratory minute volume (V(E)) was calculated. PaO(2), PaCO(2), and pHa values were determined. RESULTS: The initial values of f/min and V(E) in CLTIHH group were significantly higher than that of control group. After exposure to hypoxic gas mixture (8% O(2)-92% N(2)), the elevations in f/min, V(T), and V(E) in CLTIHH group were significantly higher than those of control group. After denervation of peripheral chemoreceptors, the decrease in V(E) in CLTIHH group was found to be significantly less than that of control group. When the animals in control group were allowed to breathe hypoxic gas mixture, f/min, V(T,) and V(E) decreased significantly and hypoxic depression was obtained. In contrast, hypoxic depression did not occur in the CLTIHH group. CONCLUSIONS: Our results suggested that CLTIHH increases the basal ventilation and hypoxic respiratory responses and that enhanced ventilatory responses were due not only to the augmentation of peripheral chemoreceptor activity but also to the augmentation of central respiratory activity.

Analysis of HLA antigens in Turkish sarcoidosis patients.

BACKGROUND: Sarcoidosis is a systemic granulomatous disorder associated with high CD4+cell activity, without any detectable pathogen. Clustering in families occurs, and the existence of a genetic predisposition to sarcoidosis is widely accepted. There are differences among different ethnic groups. METHODS: We studied HLA polymorphisms in 64 Turkish patients with biopsy proven sarcoidosis. The control group was taken of 160 donor candidates of kidney transplantation within the same period. RESULTS: Fifty-one patients were female, and 13 were male. The mean age was 39 +/- 6.1 years. Frequency of HLA A2, A9, A24 (9), A25, A69 (28), B12, B22, B38, B49 (21), DR4, and DR14 antigens were significantly higher, and frequencies of HLA B7 and DR7 were significantly less in sarcoidosis patients. Clustering in some families were also noted in our study. CONCLUSIONS: This study implies a genetic predisposition to sarcoidosis in the Turkish population. Clustering in some families should be kept in mind.

Effects of flurbiprofen and tiaprofenic Acid on oxidative stress markers in osteoarthritis: A prospective, randomized, open-label, active- and placebo-controlled trial.

BACKGROUND: The relationship between oxidative stress and osteoarthritis (OA) has been widely investigated. Serum malondialdehyde (MDA), nitric oxide (NO), and Cu/Zn superoxide dismutase (SOD) levels are useful markers of oxidative stress. Because of the importance of oxidative stress markers in the pathogenesis of OA, treatment might involve modification of these markers to control oxidative stress. OBJECTIVE: The aim of this study was to compare the effects of 2 conventionalNSAIDs on markers of oxidative stress in patients with OA of the knee. METHODS: This 3-week, prospective, randomized, open-label, active- and placebo-controlled study was conducted at the Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. Adult patients with clinically and radiographically diagnosed moderate OA of the knee who were previously untreated were enrolled. Patients were randomly assigned to 1 of 3 treatment groups: flurbiprofen 100 mg PO (tablets) BID, tiaprofenic acid 300 mg PO (tablets) BID, or placebo tablets BID. Patients were evaluated using clinical assessment and laboratory testing before treatment (week 0; baseline) and at the end of week 3. The primary end points were the differences in serum MDA, NO, and SOD levels versus placebo. Clinical parameters-pain at rest and on motion-were evaluated using a 10-cm visual analog scale (0 = no pain to 10 = worst pain imaginable). The duration (in minutes) of morning stiffness was recorded by patients, using patient diaries. The differences between treatment groups were assessed using multivariate analysis. RESULTS: Thirty-nine patients (20 women, 19 men; mean [SD] age, 59.0 [11.3]years) were included in the study. Mean serum MDA and NO levels were significantly decreased at 3 weeks compared with baseline in the 2 active-treatment groups (all, P < 0.001); these values remained statistically similar to baseline in the placebo group. Serum SOD levels were increased significantly from baseline in the 2 active-treatment groups (both, P < 0.001), but not in the placebo group. No significant differences in serum MDA and NO levels were found between the group receiving flurbiprofen and that receiving tiaprofenic acid. Serum SOD levels were significantly higher in the flurbiprofen group compared with the tiaprofenic acid and placebo groups (both, P < 0.01). The mean (SD) score for pain at rest was significantly lower at 3 weeks compared with baseline with flurbiprofen and tiaprofenic acid (both, P < 0.001), but not with placebo. The mean score for pain on motion was significantly reduced from baseline values only with tiaprofenic acid (P < 0.001). The duration of morning stiffness was significantly shorter at 3 weeks compared with baseline in all 3 study groups (all, P < 0.001). The mean scores for pain on motion and duration of morning stiffness were significantly reduced with tiaprofenic acid compared with placebo (both, P < 0.05). The study had some limitations (ie, small sample size, no blinding, the short duration of the study, and the weak correlation between serum and synovial fluid levels of NO). CONCLUSIONS: In this comparison of the effects of 3 weeks of treatment withflurbiprofen 100 mg BID and tiaprofenic acid 300 mg BID in patients with knee OA, both treatments effectively reduced serum MDA and NO levels compared with placebo. Only tiaprofenic acid significantly improved pain at rest and on motion and duration of morning stiffness compared with placebo.

Bone mineral density in women with sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Almost any organs of the body, but mostly the lungs, are involved. Bone mineral density (BMD) can be affected directly or indirectly in chronic granulomatous systemic diseases such as sarcoidosis. The aim of our study was to evaluate BMD in premenopausal and postmenopausal sarcoidosis patients with or without prednisone treatment and to compare their BMD values with those of a control group having the same menopausal status. Thirty-five premenopausal women (18 untreated, 8 treated, and 9 controls) and 21 postmenopausal women (5 untreated, 5 treated, and 11 controls) were included in the study. All of the patients had a histologically proven diagnosis and were being followed-up at the Sarcoidosis Outpatient Clinic of our unit. BMD of the lumbar (L) spine and femoral neck was measured by dual-energy absorptiometry (DEXA). The subgroups of premenopausals and postmenopausals were compared separately. Comparison among the groups was performed by using analysis of variance. Age, duration of the disease, and body mass index were comparable in treated, untreated, and control subgroups of the pre- and postmenopausal groups, and the subgroups of postmenopausals had comparable durations since menopause. For premenopausals, BMD values at L1-4 were not significantly different among the subgroups (0.920 +/- 0.08 g/cm(2), 0.801 +/- 0.09 g/cm(2), and 0.910 +/- 0.05 g/cm(2), for untreated, treated, and controls, respectively). However, the BMD value at the femoral neck in treated patients (0.921 +/- 0.1 g/cm(2)) was significantly lower than the values in untreated patients (1.080 +/- 0.2 g/cm(2); P < 0.01) and in controls (1.028 +/- 0.17 g/cm(2); P < 0.05). For postmenopausals, the BMD value at L1-4 in controls (1.019 +/- 0.07 g/cm(2)) was significantly higher than the values in untreated patients (0.783 +/- 0.01 g/cm(2)) and in treated patients (0.751 +/- 0.08 g/cm(2); P < 0.001 for both). The BMD value at the femoral neck in controls (0.890 +/- 0.1 g/cm(2)) was higher than the values in untreated patients (0.745 +/- 0.08 g/cm(2)) and treated patients (0.747 +/- 0.1 g/cm(2)), but the difference was not statistically significant (P = 0.06). We concluded that sarcoidosis patients, especially postmenopausal patients with corticosteroid treatment, may have an increased risk of bone mineral loss. Large-scale studies are warranted in order to delineate the exact roles of the disease itself, menopausal status, and corticosteroid treatment in this bone mineral loss.