Sefa Gulturk

The effect of sildenafil on the altered thoracic aorta smooth muscle responses in rat pre-eclampsia model

The pathophysiology of pre-eclampsia is still unknown thus effective primary prevention is not possible at the stage. The present study was conducted to research the smooth muscle responses in the pre-eclampsia model with suramin treated rats and the effect of phosphodiesterase-5 (PDE5) inhibitor on these responses. Rats of three groups; control, suramin and suramin+sildenafil were given intraperitoneal injections of saline, suramin or sildenafil citrate. Suramin injections caused increased blood pressure, protein in urine and caused fetal growth retardation. The use of sildenafil citrate straightened significantly both blood pressure and average fetus weight, but did not reach to control values. At the end of pregnancy, thoracic aorta rings were exposed to contractile and relaxant agents. KCl contraction responses, sodium nitroprusside and papaverine relaxation responses were similar in three groups. Contraction responses of phenylephrine, increased significantly in suramin group. Relaxation responses of acethylcholine and bradykinin decreased in suramin group. The use of sildenafil citrate partially straightened both relaxation and contraction responses, but did not reach to control values. In all groups in the presence of L-nitromonomethylarginine (L-NAME), 1H-(1, 2, 4) oxadiazole (4, 3-a) guinoxalin-1-one (ODQ) and indomethacin decreased the relaxation responses of acetylcholine and bradykinin. The cyclic guanosine monophosphate (cGMP) content of thoracic aorta tissue was determined by radioimmunoassay technique. The content of cGMP in suramin group decreased and use of sildenafil citrate increased the cGMP content but did not reach to control values. We conclude that in pre-eclampsia, the increase of contraction responses, the decrease of relaxation responses and the decrease of cGMP content can depend on insufficiency about synthesis or release of relaxant factors which was released from the vessel endothelium. The results in this study show that in pre-eclampsia; PDE5 inhibitors enhance endothelial function and may be used for protection. Further studies are needed to clear the efficiency and safety of PDE5 inhibitors.

The effect of adenotonsillectomy on right ventricle function and pulmonary artery pressure in children with adenotonsillar hypertrophy

OBJECTIVES Adenotonsillar hypertrophy (ATH) is the most common cause of upper airway obstruction in children. Severe upper airway obstruction may have an effect on chronic alveolar hypoventilation, which consequently may lead to right ventricle (RV) dysfunction induced by hypoxemic pulmonary vasoconstriction. The investigators aimed to study RV function and mean pulmonary artery pressure (mPAP) in patients with ATH who were undergoing adenotonsillectomy by using tissue Doppler echocardiography (TDE). METHODS The study examined 27 children with ATH who had a mean age of 8 ± 2 years. The subjects were comprised 17 (63%) males and 10 (37%) females. Hypertrophy of the tonsils was graded according to the Brodsky scale. Children having either grade 3 or 4 hypertrophied adenotonsils were recruited for the study. Adenotonsillectomy was performed on all subjects in the study group and echocardiographic examination was repeated 3 months postoperatively. RESULTS Tricuspid Em significantly increased after adenotonsillectomy (17.7 ± 3.6 vs. 19.1 ± 5.5, p=0.04). The RV myocardial performance index (MPI) and mPAP significantly decreased after adenotonsillectomy (RV MPI: 0.57 ± 0.13 vs. 0.40 ± 0.12, p<0.001 and mPAP (mmHg): 31 ± 9 vs. 25 ± 7, p=0.001). CONCLUSION The results of this study, evaluated with the results of previous studies, demonstrated that adenotonsillectomy improved RV performance and reduced mPAP in children with ATH.

Effect of exposure to 50 Hz magnetic field with or without insulin on blood–brain barrier permeability in streptozotocin‐induced diabetic rats

We investigated the effect of long-term exposure to modulation magnetic field (MF), insulin, and their combination on blood-brain barrier (BBB) permeability in a diabetic rat model. Fifty-three rats were randomly assigned to one of six groups: sham, exposed to no MF; MF, exposed to MF; diabetes mellitus (DM), DM induced with streptozotocin (STZ); DM plus MF (DMMF); DM plus insulin therapy (DMI); and DM plus insulin therapy plus MF (DMIMF). All the rats underwent Evans blue (EB) measurement to evaluate the BBB 30 days after the beginning of experiments. The rats in MF, DMMF, and DMIMF groups were exposed to MF (B = 5 mT) for 165 min every day for 30 days. Mean arterial blood pressure (MABP), body mass, and serum glucose level of the study rats were recorded. The extravasation of brain EB of the MF, DM, DMMF, DMI, and DMIMF groups was higher than that of the sham group and the extravasation of right hemisphere of the DMIMF group was highest (P < 0.05). The post-procedure body mass of the sham and MF groups were significantly higher than those of the DM and DMMF groups (P < 0.05). In the DM, DMMF, DMI, and DMIMF groups, the baseline glucose was significantly lower than the post-procedure glucose (P < 0.05). DM and MF increase BBB permeability; in combination, they cause more increase in BBB permeability, and insulin decreases their effect on BBB. Improved glucose metabolism may prevent body mass loss and the hypoglycemic effect of MF. DM increases MABP but MF causes no additional effect.

Reduced uterine perfusion pressure model is not successful to mimic severe preeclampsia

The aim of the study was to investigate maternal (hemoglobin, hematocrit, and biochemical parameters of blood and urine) and fetal parameters (number and weight of alive fetus) of preeclampsia in a rat model. Placental oxidative stress markers (protein carbonyl, malondialdehyde) and placental antioxidant values (CuZn-superoxide dismutase, glutathione peroxidase) were also measured. Preeclampsia was induced experimentally in timed-pregnant Sprague-Dawley rats by using the reduced uterine perfusion pressure (RUPP) model. Placental oxidative stress that plays a key role in the pathophysiology of placenta-related disorders, most notably preeclampsia (PE) and intrauterine growth restriction (IUGR) were demonstrated by using RUPP model. On day 14 of gestation, silver clips were placed around the aorta below the renal arteries and on the left and right uterine arcade at the ovarian artery. In the RUPP model animals (n = 15), when compared with the normotensive controls (n = 15), arterial pressure on day 19 of gestation was significantly higher in the RUPP rats (151.7 ± 17.6 mmHg) than normal pregnant rats (113.9 ± 11.4 mmHg). The RUPP rats showed a significant increase in protein excretion when compared with the normal pregnant rats (0.3 ± 0.04 vs 0.47 ± 0.07 g/dL) (p < 0.05). Associated with the hypertension in RUPP rats, placental levels of malondialdehyde (2.4 ± 0.2 vs. 1.6 ± 0.2 umol/gm tissue) and protein carbonyl (1.4 ± 0.3 vs. 0.9 ± 0.3 nmol/mg protein) were increased, while superoxid dismutase (0.03 vs 0.42 U/mg protein) and glutathione peroxidase (1.04 ± 0.31 vs 0.76 ± 0.22 U/g protein) were decreased. Pup number (6.6 ± 3.1 vs. 9.93 ± 2.0) and litter weight (17.4 ± 7.7 vs. 22.9 ± 6.7 g) were lower in the preeclamptic group. None of the complete blood counts and biochemical values other than sodium and chlorine were significantly different in preeclamptic group. Our findings suggest that the RUPP model cannot mimic severe preeclampsia; however, further studies using different settings may be helpful to obtain a preeclampsia model that is capable of successfully producing severe preeclampsia findings.

Evaluation of cochlear function using transient evoked otoacoustic emission in children with Familial Mediterranean Fever

OBJECTIVE The aim of this study was to investigate cochlear functions in children with Familial Mediterranean Fever (FMF). METHODS Fifty-six FMF patients (112 ears) and 30 healthy control subjects (60 ears) were included in the study. Transient evoked otoacoustic emission (TEOAE) was investigated. Numerical measurements of TEOAE, except the correlation percentage (%), included response amplitude (dB) and signal/noise (SN) ratio. RESULTS There was no statistically significant difference in age and sex in the two groups. Mean TEOAE correlation percentage, signal/noise ratio, TEOAE amplitudes in 1, 1.5, 2, 3 and 4 Hz frequency values were not different between the two groups (p>0.05). CONCLUSIONS In this study using the TEOAE test, we found that FMF did not cause outer cell hair damage in children. In the literature, there is no study on outer cell hair damage in children or adults with FMF, so this is the first investigational study.

The evaluation of hypoxia-inducible factor 1 in N-nitro-L-arginine methyl ester preeclampsia model of pregnant rats.

Objective The objective of the study was to evaluate hypoxia-inducible factor 1 (HIF-1), which plays a major role in the stimulation of angiogenesis in placental tissues, by using immunohistochemical staining in preeclampsia model of rats, developed by N-nitro-L-arginine methyl ester (L-NAME) Methods Thirty pregnant rats were randomized into 2 groups (n = 15 in each group) on day 10 of gestation. L-NAME was given to rats in the study group by gavage. On days 0, 10, and 20 of gestation, rats were weighted, and urine protein values and blood pressures were measured. Hypoxia-inducible factor 1 expressions were assessed with immunohistochemical staining by using avidin-biotin peroxidase via selecting preparation. Results Systolic and diastolic blood pressures and urine protein value of L-NAME group on day 20 of gestation were found to be significantly higher than those obtained on days 0 and 10 of gestation in the same group and those obtained on day 20 of gestation in the sham group (P < 0.05). Maternal weight, number of fetuses, and mean fetal weight of rats in L-NAME group on day 20 of gestation were found to be significantly lower than those obtained from rats in the sham group (P < 0.05). Regarding HIF-1 expression of placental tissues, mild immunohistochemical staining was found in 2 rats (13.4%) and moderate in 13 rats (86.6%) in the L-NAME group. A significant difference was found in terms of HIF-1 positivity in the maternal placentas of both groups (P < 0.05). Conclusions L-NAME preeclampsia model of pregnant rats is consistent with human preeclampsia in terms of hypertension, proteinuria, and intrauterine growth retardation; in addition, it also shows evidence of placental hypoxia findings.

Evaluation of effects of T and N type calcium channel blockers on the electroencephalogram recordings in Wistar Albino Glaxo/Rij rats, an absence epilepsy model

Objectives: It is suggested that excessive calcium entry into neurons is the main triggering event in the initiation of epileptic discharges. We aimed to investigate the role of T and N type calcium channels in absence epilepsy experimental model. Materials and Methods: Wistar Albino Glaxo/Rij (WAG/Rij) rats (12–16 weeks old) were randomly allocated into four groups; sham, mibefradil (T type calcium channel blocker), w-Conotoxin MVIIA (N type calcium channel blocker), and mibefradil + w-Conotoxin MVIIA. Beta, alpha, theta, and delta wave ratios of EEG recordings and frequency and duration of spike wave discharges (SWDs) were analyzed and compared between groups. Results: Beta and delta recording ratios in 1 μM/5 μl mibefradil group was significantly different from basal and other dose-injected groups. Beta, alpha, and theta recordings in 0.2 μM/5 μl w-Conotoxin MVIIA group was significantly different from basal and other dose-injected groups. In w-Conotoxin MVIIA after mibefradil group, beta, alpha, and theta recording ratios were significantly different from basal and mibefradil group. Mibefradil and w-Conotoxin MVIIA significantly decreased the frequency and duration of SWDs. The decrease of frequency and duration of SWDs in mibefradil group was significantly different from w-Conotoxin MVIIA group. The frequency and duration of SWDs significantly decreased in w-Conotoxin MVIIA after mibefradil group compared with basal, mibefradil, and w-Conotoxin MVIIA groups. Conclusions: We concluded that both T and L type calcium channels play activator roles in SWDs and have positive effects on frequency and duration of these discharges. These results are related with their central effects more than peripheral effects.

ASSESSMENT OF THE OUTCOMES OF CEREBRAL BLOOD FLOW MEASUREMENTS AFTER ELECTRICAL STIMULATION OF UPPER RIGHT INCISOR TOOTH IN RABBITS

The cerebral vessels are innervated by sympathetic, parasympathetic, and sensory nerves. A sensory innervation of the cerebral vessels originating in the trigeminal ganglion has been described in a number of species by several investigations. It has been shown that the electrical stimulation of the trigeminal ganglion causes an increase of cerebral cortical blood flow (CCoBF). The aim of the present study was to determine the effects of dental electrical stimulation the CCoBF in rabbits. A stimulating electrode was located in the upper right incisor tooth of rabbits and trigeminal ganglion was stimulated orthodromically via the infraorbital nerve. Variations in the cortical CCoBF were evaluated by laser-Doppler flowmetry. In experiment group, CCoBF increased together with the beginning of electrical stimulation (5 V, 0.5-ms impulse duration, square-shaped, 10-Hz frequency). The right and left hemisphere CCoBF values of stimulation period at 15s, 30s, 45s, 60s, 75s, and 90s were significantly higher than those of baseline and 105 and 120s (p < 0.05). The maximum increase in right and left CCoBF was 15.6% and 15.1% respectively. In post-stimulation period, the right CCoBF decreased gradually and returned to the baseline values at 120 s. In experiment groups, the CCoBF values of right hemisphere were comparable that of left hemisphereL (p > 0.05). This study demonstrated that the electrical stimulation of the trigeminal nerves infraorbital branch via dental pulp increases the cortical right and left CCoBF under physiological conditions.

Delayed habituation in Behcet's disease

BACKGROUND The autonomic nervous system in Behcets patients may be affected due to various reasons. This entity may be detected with the measurement of the electrodermal activities, heart rate variability and pupillometric methods. Habituation is one of the implicit forms of learning and memory and the loss of habituation can reveal pathological changes in the synaptic regions. AIM To determine whether there is a functional decrease in the synaptic effectiveness (habituation) of the pathways to sympathetic neurons that had been repeatedly activated in Behcets. MATERIALS AND METHODS Twelve patients with Behcets disease and 12 healthy controls were included in the study. Sympathetic skin potential (SSP) records were taken at normal room temperature in a quiet place within a Faraday cage. Sixteen square wave single shock impulses (duration: 1200 ms, strength: 5 mA) were applied on each case. RESULTS After the 1st stimulus, the SSP amplitudes were lower in the patients compared to the controls (P<0.001, t value=7.69). There was no significant differences among the SSP amplitudes after the 13th impulse in the patients (P>0.05). Whereas there was no significant differences among the SSP amplitudes after the 9th impulse in the controls (P>0.05). The habituation rate of the SSP after consecutive impulses was slowest in the patients compared to controls (P<0.001, t value=12.39). CONCLUSIONS There is a delayed habituation in Behcets disease and that may due to pathologic changes with vasculitis through their peripheral nerves.

Combination of paracetamol or ketamine with meperidine enhances antinociception.

Objectives: Dealing with pain is one of the most important issues of medicine. All of the studies aim to find a drug or combination of drugs in order to have more effective analgesia and less side effects. In this study, we aimed to investigate the antinociceptive effects of combination of paracetamol or ketamine with meperidine. Methods: In this study, we evaluated the systemic antinociceptive effects of meperidine, paracetamol, and ketamine one by one with their combinations. We used 50 mice (weighing 25–30 g), which were divided into 5 groups with each group consisting of 10 mice. Meperidine was applied to animals with increasing doses and their tail flick latencies (TFL) were noted at 20, 40, 60, 90, 120, 180, and 240 min. The same protocol was repeated after the combination of meperidine with paracetamol or ketamine. Results: There was no analgesic effect on low doses of ketamine and paracetamol at TFL measurements. But the combination of low doses of these drugs with meperidine significantly increased TFL (p < 0.05). Conclusion: It was observed that meperidine + ketamine and meperidine + paracetamol combinations have potent analgesic effect.