A comparative study for determining Covid-19 risk levels by unsupervised machine learning methods.

The restrictions have been preferred by governments to reduce the spread of Covid-19 and to protect people's health according to regional risk levels. The risk levels of locations are determined due to threshold values ​​based on the number of cases per 100,000 people without environmental variables. The purpose of our study is to apply unsupervised machine learning techniques to determine the cities with similar risk levels by using the number of cases and environmental parameters. Hierarchical, partitional, soft, and gray relational clustering algorithms were applied to different datasets created with weekly the number of cases, population densities, average ages, and air pollution levels. Comparisons of the clustering algorithms were performed by using internal validation indexes, and the most successful method was identified. In the study, it was revealed that the most successful method in clustering based on the number of cases is Gray Relational Clustering. The results show that using the environmental variables for restrictions requires more clusters than 4 for healthier decisions and Gray Relational Clustering gives stable results, unlike other algorithms.

Assessment of genetic diversity and differentiation among four indigenous Turkish sheep breeds using microsatellites.

Conservation and breeding programmes of livestock species depend on determination of genetic diversity. Today in livestock species, microsatellite markers are commonly used to reveal population structure and genetic diversity in both breeds and varieties. In this study, population structure, genetic diversity, and differentiation among four native Turkish sheep breeds including Güney Karaman, Kangal, Norduz, and Karakas were assessed by using 21 microsatellite loci. By genotyping 120 individuals belonging to four sheep breeds, a total of 275 different alleles, 37 of which were private alleles, were observed across all loci. The mean number of alleles per breed ranged from 7.28 (Güney Karaman) to 8.09 (Karakas), while allelic richness ranged from 7.22 (Güney Karaman) to 7.87 (Karakas). Mean observed heterozygosity varied from 0.60 (Kangal) to 0.66 (Norduz and Karakas). The lowest pairwise F ST value (0.084) was between Kangal and Karakas populations, while the highest pairwise F ST value (0.142) was between Norduz and Karakas populations. Polymorphic information content (PIC) values, ranging from 0.71 (ETH10) to 0.91 (OarFCB304), were highly polymorphic (PIC  >  0.5) and informative in studied populations. In the present study, the results of phylogenetic analysis were of importance, since all studied populations have been accepted as Akkaraman varieties till today. However, factorial correspondence and structure analysis, pairwise F ST values, and an unweighted pair group method with arithmetic mean analysis (UPGMA) dendrogram revealed that Güney Karaman and Norduz populations have became genetically different from the Akkaraman breed due being raised in different parts of Turkey under different climatic conditions together with their breeding practices. Therefore, we recommend that more comprehensive molecular studies should be conducted to clarify genetic differentiation of Akkaraman sheep varieties.

The protective effect of avocado soybean unsaponifilables on brain ischemia/reperfusion injury in rat prefrontal cortex.

OBJECT: We investigated the protective effects of avocado/soybean unsaponifiables (ASU) on the prefrontal cortex (PFC) after global brain ischemia/reperfusion (I/R) injury in rats. METHODS: Rats were randomly divided into three experimental groups as follows: Group I was control rats, Group II was ischemia rats, Group III was Isch + ASU rats. Brain ischemia was produced via four-vessel occlusion model. These processes followed by reperfusion for 30 min for both II and III groups. Rats were sacrificed and their brains were removed immediately. Malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in left PFC, levels of TNF-α concentration were measured in the plasma. The number of apoptotic neurons was assayed in histological samples of the right PFC. RESULTS: MDA and TNF-α levels as well as the number of apoptotic neurons were observed to have decreased significantly in Group III compared to Group II, while SOD activities have been found to have increased significantly in Group III in comparison to Group II, significantly. CONCLUSIONS: We think that ASU might have an antioxidant and neuroprotective effects in brain I/R injured rats.

Incidence of epilepsy in a defined area of Central Anatolia, Turkey, after 15 years of age.

BACKGROUND: The aim of this study was to establish the incidence rate, incidence-related characteristics, and epidemiological profile of epilepsy in Eskisehir, Turkey. METHODS: Cases were prospectively recorded by utilizing multiple data sources, including case records obtained through the Hospital Information System, files kept by family physicians, and files kept by private neurologists. Patients diagnosed with epilepsy between July 1, 2007, and June 30, 2008, and above the age of 15 years were included in the study. RESULTS: 219 new cases were diagnosed with epilepsy. The adjusted incidence rate was 33.51/100,000 cases in males and 42.22/ 100,000 cases in females, for a total of 37.59/100,000 persons. The incidence rates according to age were found to be highest in the 15-19-year age group and in the ≥70-year age group. Partial seizures were observed more than generalized seizures after the age of 40. Unknown etiology accounted for 77.2% of the epilepsies. Stroke was the most common etiological cause of epilepsy among the symptomatic group. CONCLUSIONS: The incidence rate of epilepsy in Eskisehir was comparable with the rates reported for developed countries.

Does dexmedetomidine reduce secondary damage after spinal cord injury? An experimental study.

The aim of this experimental study was to investigate the possible protective effect of dexmedetomidine (DEX) on traumatic spinal cord injury (SCI). Twenty-two New Zealand rabbits were divided into three groups: sham (no drug or operation, n = 6), Control [SCI + single dose of 1 mL saline intraperitoneally (i.p), after trauma; n = 8] and DEX (SCI + 1 microg/kg dexmedetomidine in 1 mL, i.p, after trauma, n = 8). Laminectomy was performed at T10 and balloon angioplasty catheter was applied extradurally. Four and 24 h after surgery, rabbits were evaluated by an independent observer according to the Tarlov scoring system. Blood, cerebrospinal fluid (CSF), tissue samples from spinal cord were taken for biochemical and histopathological evaluations. After 4 h of SCI, all animals in control or DEX treated groups became paraparesic. On the other hand, 24 h after SCI, partial improvements were observed in both control and DEX treated groups. Traumatic SCI leads to increase in the lipid peroxidation and decreases enzymatic or nonenzymatic endogenous antioxidative defense systems. Again, SCI leads to apoptosis in spinal cord. DEX treatment slightly prevented lipid peroxidation and augmented endogenous antioxidative defense systems in CSF or spinal cord tissue, but failed to prevent apoptosis or neurodeficit after traumatic SCI. Therefore, it could be suggested that treatment with dexmedetomidine does not produce beneficial results in SCI.

The neuroprotective effect of dexmedetomidine in the hippocampus of rabbits after subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage is a serious condition, often accompanied by cerebral vasospasm, which may lead to brain ischemia and neurologic deterioration. We evaluated if dexmedetomidine has neuroprotective effects in the hippocampus of vasospastic SAH rabbits or not. MATERIALS AND METHODS: Eighteen New Zealand rabbits were taken. An experimental SAH model was formed by injecting 0.9 mL of autologous arterial blood per 1 kg of body weight to the cisterna magna of 12 rabbits. Craniotomy was performed in the control group (n = 6) except performing experimental SAH. Rabbits in the SAH-alone (n = 6) group were infused with 5 mL.kg(-1).h(-1) 0.9% sodium chloride, and rabbits (n = 6) in the SAH-dexmedetomidine group were infused with 5 microg.kg(-1).h(-1) dexmedetomidine for 2 hours, 48 hours after SAH was established. Rabbits of all groups were sacrificed via penthotal 24 hours after dexmedetomidine administration. Brains were removed immediately, and hippocampal tissues were blocked from the right hemisphere for histopathologic study. In addition to this, hippocampal tissues of left hemispheres were dissected for biochemical analyses to evaluate MDA levels, activity of XO, and SOD. RESULTS: The histopathologic study showed that dexmedetomidine may have a neuroprotective effect in SAH-induced hippocampal injuries. The biochemical parameters support the neuroprotective effect of dexmedetomidine (P < .05). CONCLUSION: Our study showed that dexmedetomidine may have a neuroprotective effect in the hippocampus of vasospastic SAH rabbits.

The protective effect of fish n-3 fatty acids on cerebral ischemia in rat prefrontal cortex.

This study presents neuroprotective effects of fish n-3 EFA on the prefrontal cortex after cerebral ischemia and reperfusion. Eighteen rats divided into three groups. Group A rats were used as control. Cerebral ischemia and reperfusion was produced in rats either on a standard diet (Group B) or a standard diet plus fish n-3 EFA for 14 days (Group C). The malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD) and catalase (CAT) were measured and the number of apoptotic neurons was counted. The levels of MDA and activities of SOD increased in Group B rats as compared to Group A rats, and decreased in Group C rats as compared to Group B rats. The activities of CAT increased in Group C as compared to Group B rats. The number of apoptotic neurons in the prefrontal cortex was lower in Group C as compared to Group B rats.

The influence of dexmedetomidine on ischemic rat hippocampus.

In our study, we evaluated the neuroprotective effects of dexmedetomidine on oxidant-antioxidant systems, pro-inflammatory cytokine TNF-alpha and number of apoptotic neurons on hippocampus and dentate gyrus after transient global cerebral I/R injury. Eighteen rats divided into 3 groups, equally. Group I rats were used as shams. For group II and III rats, they were prepared for transient global cerebral ischemia using a four-vessel-occlusion model. 5 mL/kg/h 0.9% sodium chloride was infused to the Group II and 3 microg/kg/h/5 ml dexmedetomidine was infused to the Group III for 2 h after I/R injury. The levels of MDA and NO and activities of SOD and CAT were measured in the left hippocampus tissue. The levels of TNF-alpha concentration were measured in the plasma. The number of apoptotic neurons was counted by TUNNEL method in histological samples of right hippocampus tissue. MDA and NO levels increased in Group II compared with Group I rats (p=0.002, p=0.002, respectively). In group III, MDA and NO levels decreased as compared to Group II (p=0.015, p=0.002, respectively). SOD and CAT activities increased in Group III as compared to Group II rats (p=0.002, p=0.002, respectively). The decrease in TNF-alpha levels of group III was significant as compared to group II (p=0.016). The number of apoptotic neurons in group III was lower than Group II rats. Our study showed that dexmedetomidine has a neuroprotective effect on hippocampus and dentate gyrus of rats after transient global cerebral I/R injury.

Influence of atropine therapy on fenthion-induced pancreatitis.

OBJECTIVE: We searched the influence of dose and timing of atropine therapy in fenthion-induced pancreatitis model. METHODS: All rats were intoxicated with fenthion except the control group. Two milligrams of atropine was administered for 24 hours in a high dose atropine group while a low dose atropine group received 100 micrograms of atropine for 24 hours. One group received 2 milligrams of atropine in the first four hours of intoxication while the other group received 2 milligrams of atropine in the last four hours before sacrifice. All rats were sacrificed 24 hours after intoxication. Pseudo-cholinesterase and lipase concentrations and histopathological markers of pancreatitis were studied. RESULTS: None of the models in this study completely prevented pancreatitis, however high dose atropine that is administered for 24 hours or the first four hours after intoxication prevented severe pancreatitis. CONCLUSION: Atropine administration influence on fenthion-induced pancreatitis should be studied for other organophosphates in animals and humans.

Technetium-99m diethylenetriaminepentaacetic acid radioaerosol scintigraphy in organophosphate induced pulmonary toxicity: experimental study.

BACKGROUND: The aim of this experimental study was to investigate pathological signs of lung damages caused by acute organophosphate (OP) poisoning by using Tc-99m DTPA radioaerosol scintigraphy and histopathological investigation. MATERIAL AND METHOD: Fourteen rabbits were divided into two equal groups (n = 7). Group 1 (control group) received normal saline (same volume of fenthion, 2 ml/kg) via orogastric tube. Group 2 (OP toxicity group) received 150 mg/kg of fenthion (diluted fenthion, 2 ml/kg) via orogastric tube. Six hours later, Tc-99m-DTPA aerosol inhalation lung scintigraphy was performed in both groups. Then all rabbits were anesthetized with ketamine hydrochloride (35 mg/kg, i.p.) and xysilazine (5 mg/kg, i.p.), and sacrificed by intracardiac blood discharge. The lungs were then removed. RESULTS: There was a significant difference in T1/2 values of Tc-99m DTPA clearance between control group and OP toxicity group (p = 0.04). Intraparenchymal vascular congestion and thrombosis, intraparenchymal hemorrhage, respiratory epithelial proliferation, number of macrophages in the alveolar, and bronchial lumen, alveolar destruction, emphysematous changes, and bronchoalveolar hemorrhage scores were significantly higher in the rabbits exposed to OP compared with the control group (p < 0.05). CONCLUSION: This study showed that OP toxicity caused a decrease in the alveolar clearance. Tc-99m DTPA radioaerosol inhalation lung scintigraphy was found to be a sensitive determination of acute lung damage in OP poisoning.

Oedema risk of endotracheal intubation in rabbits with cessation of steroid therapy.

Rebound oedema of tissues is a well defined complication of cessation of steroid therapy. Tapering of systemic corticosteroid regimens in short course steroid therapy is considered unnecessary in most circumstances in acute exacerbation of chronic obstructive pulmonary diseases, presence of laryngeal rebound edema is obscure in this situation. We studied whether or not laryngeal oedema increases after intubation when intubation is established after cessation of steroid therapy. Thirty-six rabbits were randomly divided into six groups. We administered 1 mg/kg methyl prednisolone intraperitoneally to four steroid groups for ten days. Another group received serum physiologic for ten days and last group was sham control that was intubated only. Rabbits that received steroid therapy were intubated and separated into groups one day, one week, two weeks, and a month after the cessation of steroid therapy. Airway area and percentage of cross sectional area of larynx lumen to their own larynx tissues surrounded by thyroid cartilage and oesophagus were studied by stereological methods. Larynx lumen area of one week steroid group was significantly narrower and percentage of cross sectional area of larynx lumen to their own larynx tissues surrounded by thyroid cartilage and oesophagus was significantly larger than sham control. Rebound oedema forms in larynx with abrupt cessation of steroid therapy in rabbits. Clinical safe time for intubation after abrupt cessation of steroid therapy is also defined with our study. These results suggest that one week after the cessation of steroid therapy may be a hazardous time for tracheal intubation.

Caffeic acid phenethyl ester reduces mortality and sepsis-induced lung injury in rats.

OBJECTIVE: Sepsis and ensuing multiorgan failure continue to be the major causes of mortality in intensive care units. Nuclear factor (NF)-kappaB activation is supposed to be one of the targets in the treatment of sepsis. We studied the effectiveness of caffeic phenethyl ester (CAPE), a known NF-kappaB inhibitor, in cecal ligation and puncture (CLP)-induced sepsis and lung injury. DESIGN: Randomized, controlled animal study. SETTING: Research laboratory of an academic institution. SUBJECTS: Female Sprague-Dawley rats. INTERVENTIONS: CLP was performed in all rats except the rats in control and sham+CAPE groups. CAPE was administered to rats at the time of operation in sham+CAPE and CAPE+sepsis 0 groups. CAPE was administered to rats in the CAPE+sepsis12 group 12 hrs after CLP. Eight rats from each group were killed 24 hrs after CLP. Blood was taken for assessment of interleukin-1, interleukin-6, interleukin-10, and tumor necrosis factor-alpha; the right lung was removed for histopathologic examination and the left lung for biochemical examination. Apoptosis, inducible nitric oxide synthase, heat shock protein 70, malondialdehyde, catalase, superoxide dismutase, and glutathione peroxidase were studied. The rest of the rats were observed for mortality. MEASUREMENTS AND MAIN RESULTS: Mortality was significantly decreased in groups that received CAPE compared with the sepsis group. All cytokine levels were similar to control levels only in the CAPE+sepsis12 group. Apoptosis, inducible nitric oxide synthase, and heat shock protein 70 evaluation were significantly changed between all groups in the following order: control < sham+CAPE< CAPE+sepsis12 < CAPE+sepsis 0 < sepsis. Malondialdehyde and catalase were increased in the sepsis group. CONCLUSIONS: CAPE reduced mortality in sepsis and improved histopathologic variables best when it was administered after the onset of sepsis.

Stepwise rising CO2 insufflation as an ischemic preconditioning method.

BACKGROUND: The pneumoperitoneum (Pp) is associated with ischemia and reperfusion (I/R) injury and oxidative stress. Various ischemic-preconditioning (IP) methods were used to reduce ischemic injury in intra-abdominal organs. In this experimental, randomized, controlled trial with a blind assessment of the outcome, we evaluated the effects of a new IP method, stepwise rising CO(2) insufflation, on oxidative stress and inflammatory cytokine response. METHODS: Twenty-one rats were divided into three groups. Rats in the control group were subjected to general anesthesia for only 60 minutes. The stepwise group was subjected to 5 mm Hg for 10 minutes, 10 mm Hg for 10 minutes, and 15 mm Hg of CO(2) insufflation for 60 minutes without deflation. In the Pp15 group, the pressure of CO(2) insufflation was fixed at 15 mm Hg for 60 minutes without deflation. Liver and blood samples were examined to determine malondialdehyde (MDA), the antioxidant, superoxide dismutase (SOD), and inflammatory cytokine (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6]) levels. Histopathologic scores of liver tissue were examined in all groups. RESULTS: The highest plasma and liver MDA, TNF-alpha, and IL-6 values were in the Pp15 group, followed by the stepwise and control groups. However, plasma and liver SOD levels determined in the control group were significantly higher, compared to stepwise and Pp15 groups. The lowest plasma and liver levels of SOD were in the Pp15 group, followed by the stepwise and control groups. Significantly higher histopathologic scores were found in the Pp15 group, followed by the stepwise and control groups, as well as MDA and inflammatory cytokine (TNF-alpha, IL-6) levels. CONCLUSIONS: We concluded that the stepwise rising CO(2) insufflation method may be an alternative IP method that may lead to a reduction in I/R injury.

Oral administration of avocado soybean unsaponifiables (ASU) reduces ischemic damage in the rat hippocampus.

BACKGROUND: The beneficial effects of avocado/soybean unsaponifiables (ASU) are known as an antiarthritic agent. This experimental study presents the effects of ASU on oxidant/antioxidant systems and the number of apoptotic neurons of hippocampal formation after ischemia and reperfusion. METHODS: Eighteen rats were divided into three equal groups: group I rats were used as controls; group II rats were fed with standard diet and group III rats were fed with standard diet plus ASU pills for 10 days. One day after electrocauterization of bilateral vertebral arteries for groups II and III, bilateral common carotid arteries were occluded for 30 min and then reperfused for 30 min. After these procedures, rats of all groups were sacrificed. The levels of malondialdehyde (MDA) and nitric oxide (NO) and activities of superoxide dismutase (SOD) and catalase (CAT) were measured in the left hippocampus. The number of apoptotic neurons was counted by Tunel method in histological samples of right hippocampus. RESULTS: MDA and NO levels increased in group II compared with group I rats (p = 0.002, p = 0.015). In group III, MDA and NO levels decreased as compared to group II (p = 0.041, p = 0.002). SOD and CAT activities increased in group III as compared to group II rats (p = 0.002, p = 0.002). The number of apoptotic neurons was lower in group III as compared to group II rats. CONCLUSIONS: The present findings suggest that ASU could decrease oxidative stress and apoptotic changes in ischemic rat hippocampus. Dietary supplementation of ASU may be beneficial to prevent or ameliorate ischemic cerebral vascular disease.

Influence of different atropine therapy strategies on fenthion-induced organ dysfunction in rats.

We studied the influence of dose and timing of atropine therapy on fenthion-induced organ dysfunction. Thirty-six rats were randomized into six groups. All rats in the five groups except the control group were intoxicated with fenthion. The high-dose atropine group received 2 mg/kg of atropine, whereas the low-dose group received 100 microg/kg of atropine every hour for 24 hr. One group received 2 mg/kg of atropine in the first 4 hr of intoxication while the other group received 2 mg/kg of atropine in the last 4 hr before killed, which for all rats was 24 hr after intoxication. Pseudocholinesterase and aspartate aminotransferase and alanine aminotransferase levels and histopathological markers of lung, brain and liver were studied. None of our atropine therapy strategies in this study totally prevented harm on the three organs. Although the high dose of atropine administered for 24 hr had the least harmful markers for lung, it also had the most harmful markers for brain and liver. We did not succeed in finding a unique therapy strategy in our models beneficial for all studied organs in fenthion intoxication in rats. Atropine administration strategy should be oriented for the most affected organ pathology in fenthion intoxication.

The protective effect of fish n-3 fatty acids on cerebral ischemia in rat hippocampus.

Reactive oxygen species (ROS) have been implicated in the pathogenesis of cerebral injury after ischemia-reperfusion (I/R). Fish n-3 essential fatty acids (EFA), contain eicosapentaenoic acids (EPA) and docosahexoenoic acids (DHA), exhibit antioxidant properties. DHA is an important component of brain membrane phospholipids and is necessary for the continuity of neuronal functions. EPA prevents platelet aggregation and inhibits the conversion of arachidonic acid into thromboxane A(2) and prostaglandins. They have been suggested to be protective agents against neurological and neuropsychiatric disorders. In this study, the neuroprotective effects of fish n-3 EFA on oxidant-antioxidant systems and number of apoptotic neurons of the hippocampal formation (HF) subjected to cerebral I/R injury was investigated in Sprague-Dawley rats. Six rats were used as control (Group I). Cerebral ischemia was produced by occlusion of both the common carotid arteries combined with hypotension for 45 min, followed by reperfusion for 30 min, in rats either on a standard diet (Group II) or a standard diet plus fish n-3 EFA (Marincap((R)), 0.4 g/kg/day, by gavage) for 14 days (Group III). At the end of procedures, the rats were sacrificed and their brains were removed immediately. The levels of malonedialdehyde (MDA) and nitric oxide (NO) and activities of superoxide dismutase (SOD) and catalase (CAT) were measured in left HF. In addition, the number of apoptotic neurons was counted by terminal transferase dUTP nick end labelling (TUNEL) assay in histological samples of the right HF. We found that SOD activities and MDA levels increased in Group III rats compared with Group II rats. On the other hand, CAT activities and NO levels were found to be decreased in Group III rats compared with Group II rats. Additionally, the number of apoptotic neurons was lower in Group III in comparison with Group II rats. The present findings suggest that fish n-3 EFA could decrease the oxidative status and apoptotic changes in ischemic rat hippocampal formation. Dietary supplementation of n-3 EFA may be beneficial to preserve or ameliorate ischemic cerebral vascular disease.

Effect of shed blood retransfusion on pulmonary perfusion after total knee arthroplasty: a prospective controlled study.

Postoperative shed blood retransfusion (autotransfusion) is a commonly used salvage method following major surgical operations, such as total knee arthroplasty (TKA). The systemic effects of shed blood are still unclear. We studied the effect of residual substances in the retransfused shed blood, on lung perfusion after TKA. Fifteen unilateral and one bilateral TKAs were performed with autotransfusion (the study group) and 15 unilateral and three bilateral TKAs were performed in a control group. Lung X-rays, arterial blood gases (ABG), D-dimer values, and lung perfusion scintigraphies were performed preoperatively and postoperatively. A mean of 300.0 +/- 335.6 ml of bank blood was needed in the autotransfusion group and a mean of 685.7 +/- 365.5 ml of bank blood was needed in the control group (p=0.001). There was a postoperative segmental perfusion defect at the lateral segment of the superior lobe of the left lung in one patient of the control group and he also had risk factors for thrombosis. Although both groups had a decrease in lung perfusion postoperatively, there were no significant differences among the groups regarding the lung perfusion scintigraphy, chest X-rays, ABG, and D-dimer values. In conclusion, although pulmonary perfusion diminishes following TKA, shed blood retransfusion does not add any risk to pulmonary perfusion.

Tonsillar lipoma causing difficult intubation: a case report.

A 63-year-old woman with confusion and disorientation was referred to the Pulmonary Medicine Department of Afyon Kocatepe University. She was uncooperative and her peripheral oxygen saturation was 75%. She was on diuretic therapy for heart failure. An emergency intubation was planned due to the development of respiratory acidosis and hypoxemia, but the patient could not be intubated. After several attempts, intubation was successful only by digital manipulation of a lateral pharyngeal mass noticed incidentally. She was inadvertently extubated on the third day of intubation and an emergency tracheotomy was performed. Otolaryngological examination revealed a mass originating from the right palatine tonsil, and a computed tomography scan showed a hypodense mass extending from the uvula to the epiglottis. Under general anesthesia, the patient underwent a right tonsillectomy and a lipomatous mass (3.6x3.2x2.2 cm) and the palatine tonsil (3.5x1.1x0.8 cm) were resected. Microscopically, the tumor consisted of mature adipocytes with thin fibrous septae. It should be borne in mind that patients may be unaware of a tonsillar mass that may lead to serious dyspnea and difficult intubation.

The Evaluation of Protective Effects of FK-506 on Neural Ischemic-Reperfusion Injury: an Experimental Study.

OBJECTIVE: In this study, we aimed to delineate the mode of neuroprotective action of FK-506, and demonstrated that FK-506 could decrease oxidative stress and apoptotic cell death in an in vivo rat model of neural ischemia-reperfusion after hemorrhagic shock. METHODS: Thirty rats were used as experimental subjects and divided into five equal groups. Group A rats (sham group, n = 6) were anesthetized and craniotomies were performed for collecting brain tissue samples. In group B ischemia-reperfusion (I/R + 1 h, n = 6), group C (I/R + 24 h, n = 6), group D (I/ R + 1 h FK-506, n = 6) and group E (I/R + 24 h FK-506, n = 6), systolic blood pressure of the rats decreased to 40-50% of the normal level via bleeding from the femoral vein. Thus, a hemorrhagic shock and ischemic neural tissue model was formed. The bloodwas retained and given to the remaining animals in groups B, C,Dand E via femoral vein for reperfusion 20 min after the procedure. In group D and E, 1 mg/kg FK-506 in 0.5 ml isotonic solution was administered to the rats 5 min before reperfusion. Group B and D rats were sacrificed after 1 h and group Cand E rats were sacrificed 24 h after reperfusion; the rats were sacrificed via bleeding associated with intracardiac puncture. Craniotomy was also performed in groups B, C, D and E and brain tissue samples were fixed using neutral buffered 10% formaldehyde solution for immunohistopathological examination as in group A. Brain tissue superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels, tissue myeloperoxydase (MPO) activities and apoptotic cell analyses with Apo 2.7 immunohistochemically were also performed in all groups. RESULTS: The result of the study revealed that the SOD activities were lower for groups B (I/R + 1 h) and C (I/ R + 24 h) than for group A (sham group) (p < 0.05). In addition, SOD activities were higher in groups D (I/ R + 1 h FK-506) and E (I/R + 24 h FK-506) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). MDA levels, MPO activities and the number of apoptotic cells were lower in group A (sham group) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). In addition to these MDA levels, MPO activities and the number of apoptotic cells were higher in groups B (I/R + 1 h) and C (I/R + 24 h) as compared to groups D (I/R + 1 h FK-506) and E (I/R + 24 h FK-506) (p < 0.05). CONCLUSION: The results suggest that the prophylactic use of FK-506 in an in situ ischemic neural tissue may prevent reperfusion injury.