Serkan Gürgül

The effect of insulin therapy on biomechanical deterioration of bone in streptozotocin (STZ)-induced type 1 diabetes mellitus in rats

AIMS To investigate the effect of insulin therapy on biomechanical properties of bone in streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) in rats. METHODS A total of 28 male Wistar-Albino rats (12-week-old; 210-300g) were divided into 4 groups (n=7 for each) including control [C; no treatment], sham [Sh; distilled water i.p., for 8 weeks], diabetes [T1DM; 65mg/kg of STZ, single i.p.] and diabetes+insulin treatment [T1DM+I; 65mg/kg of STZ, single i.p.+insulin; 2-4UI/day/rat, i.p., for 8 weeks] groups. Body weight, blood glucose levels (BGLs), bone mineral density (BMD) and geometric/mechanical properties of bone tissue were evaluated. RESULTS BGLs in diabetic rats were significantly increased compared to non-diabetic rats, while the body weights were decreased (p<0.05). Femur length and cross-sectional area of femur were significantly decreased in both T1DM and T1DM+I groups (p<0.05). The significant reduction obtained in BMD in T1DM rats compared with C and Sh (p<0.05) groups was reversed by insulin treatment (p<0.05). Displacement, absorbed energy, maximum load, ultimate stress and toughness were significantly decreased inT1DM and T1DM+I groups compared to C and Sh groups (p<0.05). CONCLUSIONS In conclusion, insulin treatment seems to be ineffective in restoration of biomechanical deterioration of bone specific to STZ-induced T1DM.

Determination of the effects of pulmonary arterial hypertension and therapy on the cardiovascular system of rats by impedance cardiography.

Aim To evaluate the effects of bosentan, sildenafil, and combined therapy on the cardiovascular system using impedance cardiography (ICG) in rats with monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Methods Seventy male Wistar-albino rats were randomized into five groups. A single dose of MCT was given to all rats, except to the control group. After 4 weeks, bosentan, sildenafil, and combined treatment was started and lasted for 3 weeks. The last group that developed PAH did not receive any medication. Echocardiographic evaluation was performed to determine the PAH development. Thoracic fluid content index (TFCI), stroke volume index (SI), heart rate (HR), cardiac index (CI), and myocardial contractility index (IC) were determined. All procedures were performed at the baseline and after 4 and 7 weeks. Results Echocardiographic parameters showed that the all MCT-injected rats developed PAH. There were no significant inter- and intra-group differences in TFCI, SI, and IC (P > 0.05), but at the 7th week, CI value in the sildenafil-treated PAH rats was significantly higher than in other groups and HR of PAH rats with combined therapy was significantly lower than in other groups. Conclusion PAH did not have an effect on LV function of rats, or if it did, the effect was compensated by physiological processes. Also, sildenafil treatment deteriorated the LV cardiac index.

N-Acetylcysteine Ameliorates γ-Radiation-Induced Deterioration of Bone Quality in the Rat Femur

This animal study evaluated the radioprotective effects of N-acetylcysteine (NAC) and amifostine on the biomechanical properties of bone in Wistar albino rats of both genders. The rats were randomly divided into four groups of eight: A control group (C); a group given a single dose of 40 Gy of g-irradiation (R); a group given γ-irradiation plus 200 mg/kg amifostine (R + amifostine); and a group given γ-irradiation plus 1000 mg/kg NAC (R + NAC). Extrinsic and intrinsic properties of bone, bone mineral density (BMD) and the cross-sectional area of the femoral shaft were determined. The cross-sectional area was significantly higher in the R + NAC and R + amifostine groups compared with the R and C groups. The BMD, maximum load and stiffness were also significantly higher in the R + NAC and R + amifostine groups than in the R group, and energy absorption capacity was higher in the R + NAC group than in the R group. These findings indicate that NAC and amifostine preserve bone quality in rats exposed to γ-irradiation.

Clinical and histopathological relationship of sildenafil and bosentan treatments in rats with monocrotaline induced pulmonary hypertension

BACKGROUND Pulmonary arterial hypertension (PAH) is a challenging disorder characterized by increasing pulmonary artery pressure, which is hard to treat. OBJECTIVE This study was aimed to investigate the effects of bosentan, sildenafil and their combination. METHODS Saline or MCT were applied to Wistar rats. By the development of PAH (4th week), MCT-given rats were treated orally with bosentan, sildenafil and combination of sildenafil and bosentan or placebo. ECHO examinations were performed. Tissues obtained from all of the rats were evaluated under an electron microscope. RESULTS Left ventricular end diastolic diameter significantly increased in sildenafil and combined groups. Sildenafil group revealed a significant decrease in RV pressure and wall thickness. Examination of lung revealed a significant amount of connective tissue formation and increase in inflammatory cells in all the groups except controls in the interalveolar septum. Examination of PA revealed an increase in connective tissue volume, hypertrophic changes and expansions in granular endoplasmic reticulum cisternaes in smooth muscle cells in active groups rather than in the controls. Unlike the controls, the examination of the RV revealed an enlargement of the sarcoplasmic reticulum cisternaes in some cells, due to the calcium increase. CONCLUSION Sildenafil and the combined therapy demonstrated to have more impact on pressure and the RV parameters in rats, with lower inflammatory findings in lung tissue (Fig. 6, Ref. 31).

Does Levetiracetam Administration Prevent Cardiac Damage in Adulthood Rats Following Neonatal Hypoxia/Ischemia-Induced Brain Injury?

Cardiovascular abnormalities are widespread when a newborn is exposed to a hypoxic-ischemic injury in the neonatal period. Although the neuroprotective effects of levetiracetam (LEV) have been reported after hypoxia, the cardioprotective effects of LEV have not been documented. Therefore, we aimed to investigate whether levetiracetam (LEV) has a protective effect on cardiac-contractility and ultrastructure of heart muscle in rats exposed to hypoxia-ischemia (HI) during the neonatal period. A total of 49 seven-day-old rat pups were separated into four groups. For HI induction, a combination of right common carotid artery ligation with 8% oxygen in seven-day-old rat pups for 2 h was performed for saline, LEV100, and LEV200 groups. Just after hypoxia, LEV100 and LEV200 groups were administered with 100 mg/kg and 200 mg/kg of LEV, respectively. The arteries of rats in the control group were only detected; no ligation or hypoxia was performed. At the end of the 16th week after HI, cardiac mechanograms were recorded, and samples of tissue were explored by electronmicroscopy.While ventricular contractility in the control group was similar to LEV100, there were significant decreases in both saline and LEV200 groups (p < 0.05). Although ventricular contractile duration of the control and saline groups was found to be similar, durations in the LEV100 and LEV200 groups were significantly higher (p < 0.05). After HI, mitochondrial damage and ultrastructural deteriorative alterations in ventricles and atriums of the LEV-administered groups were significantly less severe than the saline group. The present study showed that neonatal HI caused long-term cardiac dysfunction and ultrastructural deteriorations in cardiac muscles. LEV administration just after HI might possess some protective effects against myocardial damage and contractility.

Determination of drug activity on pulmonary arterial hypertension using frequency-domain analysis of measured ECG signals

Electrocardiography (ECG) signals and the information obtained through the analysis of these signals constitute the main source of diagnosis of many cardiovascular system diseases. Pulmonary arterial hypertension (PAH) is a disease without any known treatment and causes failure in the right side of the heart and finally death. In this study, experimentally measured ECG signals were analyzed in frequency domain to observe the effects of PAH disease as well as medications used in the treatment of PAH on ECG main waves (P wave, T wave, QRS Complex). Wavelet transform based algorithms were used for filtering raw ECG signals and feature extraction phases. Then, for each main wave, fundamental frequency values, fundamental frequency amplitudes and the full width half maximum (FWHM) values of frequency spectrum were obtained and the changes of these parameters in disease and treatment situations were examined statistically.

Rebaudioside A inhibits pentylenetetrazol-induced convulsions in rats

The safety of patients with epilepsy consuming sweetening agents, which is becoming increasingly prevalent for various reasons, is a topic that should be emphasized as sensitively as it is for other diseases. Patients with epilepsy consume sweetening agents for different reasons such being diabetic or overweight. They can occasionally be exposed to sweetening agents unrestrainedly through consuming convenience food, primarily beverages. This study aimed to investigate the effects of rebaudioside A (Reb‐A), which is a steviol glycoside produced from the herb Stevia rebaudiana (Bertoni), on epileptic seizures and convulsions induced by pentylenetetrazole (PTZ). Forty‐eight male rats were used. Twenty‐four rats were administered 35 mg/kg PTZ to trigger epileptiform activity; the remaining 24 rats were administered 70 mg/kg PTZ to trigger the convulsion model. The epileptiform activity was evaluated by spike percentage, whereas convulsion was evaluated by Racines Convulsion Scale and the onset time of the first myoclonic jerk. Statistical analysis revealed a statistically significant decrease in the Racines Convulsion Scale score and increase in the latency of first myoclonic jerk in a dose‐dependent manner for the rat groups in which PTZ epilepsy had been induced and Reb‐A had been administered. For the groups that were administered Reb‐A, the spike decrease was apparent in a dose‐dependent manner, based on the spike percentage calculation. These results indicated that Reb‐A has positive effects on PTZ‐induced convulsions.