Mustafa Kom

Strontium substituted hydroxyapatites: Synthesis and determination of their structural properties, in vitro and in vivo performance.

The objective of this study is to present a detailed report related to the synthesis and characterization of strontium substituted hydroxyapatites. Based on this purpose, hydroxyapatite (HAp) bioceramics with different amounts of strontium (e.g., 0, 0.45, 0.90, 1.35, 1.80 and 2.25 at.%) were prepared using a sol-gel method. The effects of Sr substitution on the structural properties and biocompatibility of the samples were studied by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) techniques, in vitro and in vivo tests. All the samples composed of the nanoparticles ranging from 21 to 27 nm. The presence of Sr at low levels influenced the crystal size, crystallinity degree, lattice parameters and volume of the unit cell of the HAp. Both in vitro conditions and soaking period in simulated body fluid (SBF) significantly affected these properties. Especially, the (Ca+Sr)/P molar ratio gradually decreases with increasing soaking period in SBF. Animal experiments revealed the bone formation and osseointegration for all samples, and as compared with other groups, more reasonable, were observed for the sample with the lowest Sr content.

Effect of carnosine, methylprednisolone and their combined application on irisin levels in the plasma and brain of rats with acute spinal cord injury

Spinal cord injury (SCI) might occur to anybody at any time and any age. In its treatment, methylprednisolone (MP) is a first choice worldwide, but there is still no significant breakthrough in truly beneficial treatment due to SCIs complex pathophysiology. We investigated the effect of carnosine, methylprednisolone (MP) and its combination on irisin levels in the plasma, brain and medulla spinalis tissues in SCI using a rat model. The rats were divided into 6 groups: I (Control, saline); II (sham animals with laminectomy without cross-clamping); III (SCI); IV (SCI treated with 150mg/kg carnosine); V (SCI treated with 30mg/kg methylprednisolone); and VI (SCI treated with a combination of carnosine and MP). The animals were given traumatic SCI after laminectomy, using 70-g closing force aneurysm clips (Yasargil FE 721). Irisin concentration was measured by ELISA. The distribution of irisin in brain and spinal cord tissues was examined by immunochemistry. Irisin was mainly expressed in the astrocytes and microglia of brain tissues, and multipolar neurones of the anterior horn of spinal cord tissue in rats of all groups, indicating that irisin is physiologically indispensable. MP and carnosine and the combination of the two, significantly increased irisin in plasma and were accompanied by a significant rise in irisin immunoreactivity of brain and spinal cord tissues of the injured rats compared with control and sham. This finding raises the possibility that methylprednisolone and carnosine regulate the brain and spinal cord tissues in SCI by inducing irisin expression, and may therefore offer a better neurological prognosis.

Comparison of the Effects of Local and Systemic Zoledronic Acid Application on Mandibular Distraction Osteogenesis

Abstract Bisphosphonates are antibone resorptive drugs that are used to prevent bone tissue resorption in several skeletal diseases. The aim of this study was to examine the effects of systemic and local applications of zoledronic acid (ZA) on newly regenerated bone in a model of experimental distraction osteogenesis (DO). To do this mandibular DO was applied to 30 adult female Sprague Dawley rats, which were randomly divided into 3 groups: control, DO only, systemic zoledronic acid (SZA), and local zoledronic acid (LZA). In the LZA group, the gap between the bone fragments was filled with a gelatin sponge soaked in 2 mg of ZA and 0.1 mL of sterile saline. In the SZA group, a single dose of 0.1 mg/kg ZA was administered systemically. After the surgery, there was a 5-day latent waiting period and 10-day distraction phase. Following a 28-day consolidation period, the rats were euthanized and their mandibles were collected. The distracted bone area was seen to be filled with newly regenerated bone tissue in all 3 groups, both histologically and histomorphometrically. In addition, amounts of new bone formation, osteoblast cella, osteoclast (OC) cells, osteopontin, and vascular endothelial growth factor in the SZA and LZA groups were found to be higher when compared with the controls. Furthermore, in the SZA group, new bone formation, osteoblast, OC, osteopontin, and vascular endothelial growth factor were detected in significant amounts compared with the LZA group. Osteoclast numbers did not differ in a statistically significant manner in the SZA group with respect to the LZA group. Based on the results of this study, systemic and local applications of ZA could increase the formation of new bone in patients of DO, and systemic application is a more effective method compared with local application.

Systemic melatonin application increases bone formation in mandibular distraction osteogenesis

This study aimed to investigate the effects of different doses of systemic melatonin application on new bone formation during mandibular distraction osteogenesis (DO) in rats. Mandibular DO was performed on 30 adult female Sprague-Dawley rats, which were randomly divided into three groups: control group (CNT), melatonin dose 1 (MLT-D1), and melatonin dose 2 (MLT-D2). A five-day latent waiting period and a ten-day distraction phase followed the surgery. After the surgery, rats from the MLT-D1 and MLT-D2 groups received 25 and 50 mg/kg melatonin, respectively, at 7, 14, 21, 28, and 35 days. The animals were euthanised 28 days after distraction, i.e. at 43 days after surgery. Histological and histomorphometric analyses revealed that the distracted bone area was completely filled with new bone formation in all three groups. The MLT-D2 group exhibited the most new bone formation, followed by MLT-D1 and CNT. The melatonin groups had more osteoclasts than the CNT (p < 0.05). The number of osteoblasts was higher in the melatonin groups than in the CNT group, and the MLT-D2 had more osteoclasts than the MLT-D1 group (p < 0.05). Finally, the osteopontin (OPN) and vascular endothelial growth factor (VEGF) levels were higher in the melatonin groups than in the CNT group, and the MLT-D2 had higher OPN and VEGF levels than the MLT-D1 (p < 0.05). This study suggests that systemic melatonin application could increase new bone formation in DO.

Dynamic renal scintigraphic estimation of deceased donor kidneys in a rat model

At present a large number of the renal transplantations are being performed from the deceased donors. The success of these transplantations depends on the viability of the deceased donor kidneys. The aim of this study was to investigate the reliability of scintigraphic estimation of function of deceased donor kidneys by comparing the histopathologic and scintigraphic findings. Ten rats were included in the study (2-3 months old, 250-300 g, all male). Control scintigraphy was performed to all the rats by injection of 37 MBq Tc-99m DTPA from the tail vein in a dynamic manner. Brain death of the rats was achieved by inflation of a Fogartys catheter in the cranial cavity. Immediately, after brain death confirmation, dynamic renal scintigraphy was performed with the same parameters of control scintigraphy. In the comparison of scintigraphies obtained in the before and just after brain death period, there was impairment of tubular functions, concentration and excretion functions in the postbrain death period. In the immediate postbrain death period, there was a significant elevation in the glomerular filtration rate and time to maximum concentration values. In the histopathological evaluation of the kidney samples in the postbrain death period, there were definitive findings of tubular impairment. Dynamic renal scintigraphy also demonstrated definite impairment of tubular system and tubular functions in the deceased donor kidneys. This could explain the reason of the increased frequency of acute tubular necrosis seen among deceased donor kidneys.

Brain death scintigraphy and pathology results in a rat model.

OBJECTIVES Brain scintigraphy with Tc-99m-labeled diethylenetriaminopenta-acetic acid is a sensitive diagnostic method showing loss of cerebral blood flow that occurs after brain death. Cerebral blood flow can be quantitatively estimated by this method. The aim of this study was to compare histopathologic changes occurring with the decrease of cerebral blood flow (as shown by Tc-99m-labeled diethylenetriaminopenta-acetic acid brain death scintigraphy) after brain death in an experimental model. MATERIALS AND METHODS The study included examination of cerebral blood flow by Tc-99m-labeled diethylenetriaminopenta-acetic acid brain scintigraphy in the 20 rats, 1 day before brain death, after producing brain death in 11 surviving rats. Tc-99m-labeled diethylenetriaminopenta-acetic acid brain scintigraphy was performed under intubation and monitored. The Mann-Whitney U test was performed to compare groups (scintigraphic quantification results before and after brain death). RESULTS In the time activity curves generated from the analysis of the scintigraphies, decreases in counts in the brain death group were obtained in the arterial phase (P < .01). Decreases of the cerebral blood flow between the first and the sixth minutes were statistically significant (P < .05). Common principal histopathologic changes of the brain death (ie, autolysis and color loss in the nerve cells, diffuse edema, petechial hemorrhage in the brain tissues) were observed in all subjects. CONCLUSIONS Quantitative findings of the brain scintigraphy by Tc-99m-labeled diethylenetriaminopenta-acetic acid was related with the histopathologic findings seen during the early brain death, with significant decreases of the cerebral blood flow. Quantification of Tc-99m-labeled diethylenetriaminopenta-acetic acid brain death scintigraphy as an easier and less-expensive scintigraphic method of cerebral blood flow might indicate a definite diagnosis of brain death and thus, potential donors can be determined earlier, leaving to increased transplant rates.