Publications by authors named "Deniz Unal"

40 Publications

3D Hyaluronic Acid Hydrogels for Modeling Oligodendrocyte Progenitor Cell Behavior as a Function of Matrix Stiffness.

Biomacromolecules 2020 12 28;21(12):4962-4971. Epub 2020 Oct 28.

Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22903, United States.

The lack of regenerative solutions for demyelination within the central nervous system motivates the development of strategies to expand and drive the bioactivity of the cells, including oligodendrocyte progenitor cells (OPCs), that ultimately give rise to myelination. In this work, we introduce a 3D hyaluronic acid (HA) hydrogel system to study the effects of microenvironmental mechanical properties on the behavior of OPCs. We tuned the stiffness of the hydrogels to match the brain tissue (storage modulus 200-2000 Pa) and studied the effects of stiffness on metabolic activity, proliferation, and cell morphology of OPCs over a 7 day period. Although hydrogel mesh size decreased with increasing stiffness, all hydrogel groups facilitated OPC proliferation and mitochondrial metabolic activity to similar degrees. However, OPCs in the two lower stiffness hydrogel groups (170 ± 42 and 794 ± 203 Pa) supported greater adenosine triphosphate levels per cell than the highest stiffness hydrogels (2179 ± 127 Pa). Lower stiffness hydrogels also supported higher levels of cell viability and larger cell spheroid formation compared to the highest stiffness hydrogels. Together, these data suggest that 3D HA hydrogels are a useful platform for studying OPC behavior and that OPC growth/metabolic health may be favored in lower stiffness microenvironments mimicking brain tissue mechanics.
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http://dx.doi.org/10.1021/acs.biomac.0c01164DOI Listing
December 2020

Engineering biomaterial microenvironments to promote myelination in the central nervous system.

Brain Res Bull 2019 10 12;152:159-174. Epub 2019 Jul 12.

Department of Chemical Engineering, University of Virginia, Charlottesville, VA 22903, United States. Electronic address:

Promoting remyelination and/or minimizing demyelination are key therapeutic strategies under investigation for diseases and injuries like multiple sclerosis (MS), spinal cord injury, stroke, and virus-induced encephalopathy. Myelination is essential for efficacious neuronal signaling. This myelination process is originated by oligodendrocyte progenitor cells (OPCs) in the central nervous system (CNS). Resident OPCs are capable of both proliferation and differentiation, and also migration to demyelinated injury sites. OPCs can then engage with these unmyelinated or demyelinated axons and differentiate into myelin-forming oligodendrocytes (OLs). However this process is frequently incomplete and often does not occur at all. Biomaterial strategies can now be used to guide OPC and OL development with the goal of regenerating healthy myelin sheaths in formerly damaged CNS tissue. Growth and neurotrophic factors delivered from such materials can promote proliferation of OPCs or differentiation into OLs. While cell transplantation techniques have been used to replace damaged cells in wound sites, they have also resulted in poor transplant cell viability, uncontrollable differentiation, and poor integration into the host. Biomaterial scaffolds made from extracellular matrix (ECM) mimics that are naturally or synthetically derived can improve transplanted cell survival, support both transplanted and endogenous cell populations, and direct their fate. In particular, stiffness and degradability of these scaffolds are two parameters that can influence the fate of OPCs and OLs. The future outlook for biomaterials research includes 3D in vitro models of myelination / remyelination / demyelination to better mimic and study these processes. These models should provide simple relationships of myelination to microenvironmental biophysical and biochemical properties to inform improved therapeutic approaches.
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http://dx.doi.org/10.1016/j.brainresbull.2019.07.013DOI Listing
October 2019

Protective effects of amifostine, curcumin and caffeic acid phenethyl ester against cisplatin-induced testis tissue damage in rats.

Exp Ther Med 2018 Apr 31;15(4):3404-3412. Epub 2018 Jan 31.

Department of Medical Microbiology, Faculty of Medicine, Recep Tayyip Erdoğan University, Rize 53010, Turkey.

Cisplatin is an effective antineoplastic drug that is usually used to treat a number of different types of cancer in the clinic. One of the most notable side effects of cisplatin use is infertility. The present study was designed to determine the non-oxidative testicular effects caused by the use of cisplatin in rats. The rats were randomly allocated to the experimental groups. The untreated rats represented the control group (group I) and the treatment groups were as follows: cisplatin alone (group II), cisplatin+amifostine (group III), cisplatin+curcumin (group IV), and cisplatin+caffeic acid phenethyl ester (CAPE; group V). The present study observed that following cisplatin administration, the expression of nuclear factor-κB (NF-κβ)/p65, caspase-3 and 8-deoxyguanosine (8-OHdG) increased in germinal epithelium and Leydig cells. However, the expression of these markers decreased in groups III-V, most notably in the group treated with amifostine. cisplatin induced-damage was countered by amifostine and curcumin. The results revealed that the activation of NF-κB, caspase-3 and 8-OHdG had a significant role in cisplatin-induced testicular toxicity. Thus, amifostine, curcumin and, to a lesser extent, CAPE have the potential for use as therapeutic adjuvants in cisplatin-induced testis injury.
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http://dx.doi.org/10.3892/etm.2018.5819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840930PMC
April 2018

Liver 5-HT7 receptors: A novel regulator target of fibrosis and inflammation-induced chronic liver injury in vivo and in vitro.

Int Immunopharmacol 2017 Feb 30;43:227-235. Epub 2016 Dec 30.

Ataturk University, Faculty of Medicine, Department of Embryology and Histology, 25240 Erzurum, Turkey.

Background And Aim: Hepatocellular cancer (HCC) is the sixth most common cancer and liver fibrosis is strongly associated with HCC. Treatment options are limited, and preventive strategies should be developed. An important step in the beginning of liver fibrosis is a strong inflammatory response. 5-HT7 is the last recognized member of the serotonin receptor family and is expressed in both central nerve system and peripheral system and have a lot of functions like learning, memory, smooth muscular relaxation, in the control of circadian rhythms and thermoregulation, pain and migraine, schizophrenia, anxiety, cognitive disturbances, and even inflammation.

Methods: We therefore examined the biochemical, histopathological and molecular effects of the 5-HT7 receptor agonist and antagonist on inflammatory liver fibrogenesis in animal models of progressive cirrhosis: a mouse model induced by carbon tetrachloride (CCl4) and in Hep3b cells.

Results: 5-HT7 expression was observed in the liver in vivo and in vitro in CCl4-induced damage. 5-HT7 receptor agonist but not the antagonist reduced liver markers in mice and in Hep3b cells in carbon tetrachloride (CCl4) induced damage. 5-HT7 agonist, but not antagonist, protected liver tissue from oxidative stress in fibrosis. 5-HT7 agonist but not antagonist induces anti-inflammatory, anti-fibrinotic and anti-cytokine features in liver fibrosis in vivo and in vitro.

Conclusions: 5-HT7 receptors have modulatory function and are an up-and-coming pharmacological target in the inflammatory fibrotic process. 5-HT7 receptor agonist LP-44 showed significant hepatoprotective effects against liver fibrosis, and LP-44 might become a useful therapeutic target for chronic liver inflammation and fibrosis.
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http://dx.doi.org/10.1016/j.intimp.2016.12.023DOI Listing
February 2017

Protective effects of estrogen and bortezomib in kidney tissue of post-menopausal rats: an ultrastructural study.

Ren Fail 2016 Aug 19;38(7):1129-35. Epub 2016 May 19.

b Department of Histology and Embryology, Faculty of Medicine , Ataturk University , Erzurum , Turkey ;

Purpose: Symptoms and disorders related to menopause and its associated estrogen deficiency have become a considerable health concern worldwide. Ovarian hormone depletion/estrogen deficiency can be usefully studied using animal models after removal of the ovaries [ovariectomy (Ovx)]. This study assessed renal changes after Ovx-induced estrogen deficiency in a rat model.

Methods: Rats were randomly allotted into one control group (group I, healthy) and three study groups (group II, Ovx group; group III, Ovx +17β-estradiol group; and group IV, Ovx + bortezomib group).

Results: In the Ovx group (group II), thickening of glomerular capillary walls, narrowing of Bowman's capsular space, glomerular hypertrophy, atrophic tubules, and loss of the basal membranes of the tubules were observed. Mesangial cell proliferation was observed, particularly in the glomerulus. Immunohistochemical (IHC) staining studies in this group showed dense staining in the mesangial cells, tubular cell Nf-KB/p65, and caspase-3. Groups III and IV (Ovx +17β-estradiol and Ovx + bortezomib) showed decreased NF-kB/p65 and caspase-3 expression compared with the Ovx group (p < 0.05).

Conclusion: In renal failure related to estrogen deficiency caused by Ovx, 17β-estradiol and bortezomib have a protective effect on renal tissue.
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http://dx.doi.org/10.1080/0886022X.2016.1184958DOI Listing
August 2016

Inhalation of mercury vapor can cause the toxic effects on rat kidney.

Ren Fail 2016 18;38(3):465-73. Epub 2016 Feb 18.

d Department of Oral Diagnosis and Radiology, School of Dentistry , Atatürk University , Erzurum , Turkey.

Dental amalgam has been used in dentistry as a filling material. The filler comprises mercury (Hg). It is considered one of the most important and widespread environmental pollutants, which poses a serious potential threat for the humans and animals. However, mercury deposition affects the nervous, cardiovascular, pulmonary, gastrointestinal, and especially renal systems. In most animals' species and humans, the kidney is one of the main sites of deposition of mercury and target organ for its toxicity. In this study, the effects of mercury intake on kidney in rats were searched. For the this purpose; we used 24 adult female Wistar albino rats (200 g in weight) obtained from Experimental Research and Application Center of Atatürk University with ethical approval. Besides, they were placed into a specially designed glass cage. Along this experiment for 45 days, subjects were exposed to (1 mg/m(3)/day) mercury vapor. However, no application was used for the control subjects. At the end of the experiment, kidney samples were obtained from all subjects and processed for routine light microscopic level and stereological aspect were assessed. Finally, according to our results, mercury affects the histological features of the kidney. That means, the severe effects of mercury has been shown using stereological approach, which is one of the ideal quantitative methods in the current literature. In this study, it was detected that chronic exposure to mercury vapor may lead to renal damage and diseases in an experimental rat model.
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http://dx.doi.org/10.3109/0886022X.2016.1138832DOI Listing
December 2016

Morphological and antioxidant impairments in the spinal cord of male offspring rats following exposure to a continuous 900MHz electromagnetic field during early and mid-adolescence.

J Chem Neuroanat 2016 09 17;75(Pt B):99-104. Epub 2015 Dec 17.

Department of Histology and Embryology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey. Electronic address:

The effects of devices emitting electromagnetic field (EMF) on human health have become the subject of intense research among scientists due to the rapid increase in their use. Children and adolescents are particularly attracted to the use of devices emitting EMF, such as mobile phones. The aim of this study was therefore to investigate changes in the spinal cords of male rat pups exposed to the effect of 900MHz EMF. The study began with 24 Sprague-Dawley male rats aged 3 weeks. Three groups containing equal numbers of rats were established-control group (CG), sham group (SG) and EMF group (EMFG). EMFG rats were placed inside an EMF cage every day between postnatal days (PD) 21 and 46 and exposed to the effect of 900MHz EMF for 1h. SG rats were kept in the EMF cage for 1h without being exposed to the effect of EMF. At the end of the study, the spinal cords in the upper thoracic region of all rats were removed. Tissues were collected for biochemistry, light microscopy (LM) and transmission electron microscopic (TEM) examination. Biochemistry results revealed significantly increased malondialdehyde and glutathione levels in EMFG compared to CG and SG, while SG and EMFG catalase and superoxide dismutase levels were significantly higher than those in CG. In EMFG, LM revealed atrophy in the spinal cord, vacuolization, myelin thickening and irregularities in the perikarya. TEM revealed marked loss of myelin sheath integrity and invagination into the axon and broad vacuoles in axoplasm. The study results show that biochemical alterations and pathological changes may occur in the spinal cords of male rats following exposure to 900MHz EMF for 1h a day on PD 21-46.
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http://dx.doi.org/10.1016/j.jchemneu.2015.11.006DOI Listing
September 2016

Protective effects of beta glucan in brain tissues of post-menopausal rats: a histochemical and ultra-structural study.

Gynecol Endocrinol 2016 16;32(3):234-9. Epub 2015 Nov 16.

a Department of Histology and Embryology , Faculty of Medicine, Ataturk University , Erzurum , Turkey and.

Decline of estrogen during menopause has been associated with numerous significant changes that have been linked to many pathophysiological complications. In addition, ovarian hormone deficiency increases the production of reactive oxygen radicals which could result in oxidative stress and cell damage. While estrogen therapy is often considered to overcome the behavioral and physiological shortcomings, antioxidants are gaining popularity for their beneficial property. For this purpose, in the present study, utilizing the antioxidant properties of beta glucan has been examined in treatment of menopause induced oxidative stress in cerebral neurons. Four groups of female Wistar rats were used: control, ovariectomy, ovariectomy + estrogen treated and ovariectomy + beta glucan treated. We observed a significant increase in neural degeneration in ovariectomized rats as compared to controls. Moreover, increased oxidative stress in the brains of the ovariectomized rats has been detected by performing immunohistochemical analysis. A large number of immuno-positive cerebral neurons have been observed in ovariectomy group rat brains. Interestingly, providing beta glucan treatment to ovariectomized rats reduced the number of degenerated neurons. Our study is the first to examine light and electron microscopic examination and immunohistochemical and stereological analysis of estrogen depletion in rats and to test protective role of beta glucan in the experimental study.
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http://dx.doi.org/10.3109/09513590.2015.1110139DOI Listing
December 2016

Astrocyte/neuron ratio and its importance on glutamate toxicity: an in vitro voltammetric study.

Cytotechnology 2016 Aug 6;68(4):1425-33. Epub 2015 Oct 6.

Department of Medical Pharmacology, Faculty of Medicine, Erzincan University, Erzincan, Turkey.

The purpose of this study was to clarify the relationship between neuron cells and astrocyte cells in regulating glutamate toxicity on the 10th and 20th day in vitro. A mixed primary culture system from newborn rats that contain cerebral cortex neurons cells was employed to investigate the glutamate toxicity. All cultures were incubated with various glutamate concentrations, then viability tests and histological analyses were performed. The activities of glutamate transporters were determined by using in vitro voltammetry technique. Viable cell number was decreased significantly on the 10th day at 10(-7) M and at 10(-6) M glutamate applications, however, viable cell number was not decreased at 20th day. Astrocyte number was increased nearly six times on the 20th day as compared to the 10th day. The peak point of glutamate reuptake capacity was about 2 × 10(-4) M on the 10th day and 10(-3) M on the 20th day. According to our results, we suggested that astrocyte age was important to maintain neuronal survival against glutamate toxicity. Thus, we revealed activation or a trigger point of glutamate transporters on astrocytes due to time since more glutamate was taken up by astrocytes when glutamate transporters on the astrocyte were triggered with high exogenous glutamate concentrations. In conclusion, the present investigation is the first voltammetric study on the reuptake parameters of glutamate in vitro.
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http://dx.doi.org/10.1007/s10616-015-9902-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960189PMC
August 2016

Effects of Administration of Amlodipine and Lacidipine on Inflammation-Induced Bone Loss in the Ovariectomized Rat.

Inflammation 2016 Feb;39(1):336-346

Department of Histology and Embryology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.

This study was performed to evaluate the possible protective effect of two calcium channel blocker's "lacidipine (LAC) and amlodipine (AML)" on bone metabolism in an experimental ovariectomized and inflammation-induced osteoporosis rat model (OVXinf). For the purpose of this study, the rats were divided into eight groups, each containing eight rats: sham-operated control (group 1, SH), sham + inflammation (group 2, SHinf), ovariectomy (group 3, OVX), ovariectomy + inflammation (group 4, OVXinf), ovariectomy + LAC 4 mg/kg (group 5, OVX + LAC), ovariectomy + inflammation + LAC 4 mg/kg (group 6, OVXinf + LAC), ovariectomy + AML 5 mg/kg (group 7, OVX + AML), ovariectomy + inflammation + AML 5 mg/kg (group 8, OVXinf + AML). The levels of osteocalcin and osteopontin decreased in OVXinf + LAC and OVXinf + AML groups. The serum levels of TNF-α, IL-1β, and IL-6 were increased significantly in the OVXinf rats compared with the SH group. Gene expression levels of the osteogenic factor runt-related transcription factor 2 (Runx2) and type I collagen 1A1 (Col1A1) significantly decreased in the OVXinf group, when compared with the control group. AML or LAC administrations increased the levels of Runx2 and Col1A1. These results suggest that amlodipine and lacidipine may be a novel therapeutic target for radical osteoporosis treatment in hypertensive patients.
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http://dx.doi.org/10.1007/s10753-015-0254-6DOI Listing
February 2016

The protective effects of beta-carotene against ischemia/reperfusion injury in rat ovarian tissue.

Acta Histochem 2015 Oct 6;117(8):790-7. Epub 2015 Aug 6.

Ataturk University, Medical Faculty, Department of Anatomy, 25240 Erzurum, Turkey.

Introduction: Beta-carotene is a well-known antioxidant and precursor of Vitamin A that has a preventative role in the oxidative damage process. Our aim was to investigate the possible preventive effects of beta-carotene on oxidative damage via experimental ischemia and ischemia-reperfusion models in rat ovaries.

Materials And Methods: A traumatic vascular clamps were used for 3h to induce ischemia (Group 2, 3, 4, 5, 6, 7). The clamps were then removed to allow reperfusion for 3h (Group 3, 6, 7). Sham-operated rats (Group 1) underwent laparotomy without the induction of ischemia/reperfusion injury. Real-Time-PCR was performed to determine IL-1-beta, IL-6 and iNOS expression levels. Histopathological (H&E) and immunohistochemical staining (NF-kβ p65) processes were then performed. Finally, SOD, GSH, and MDA levels were determined.

Results: Intense hemorrhagic areas were observed in both the ischemia and ischemia/reperfusion groups, whereas minimal hemorrhage was observed in the treatment groups. The ischemia and ischemia/reperfusion groups exhibited extreme immunoreactivity, detected by NF-kβ p65 staining; this reactivity decreased after the application of beta-carotene. The expression of IL-1-beta, IL-6, and iNOS in the injury groups increased significantly, whereas a dose-dependent improvement was observed in the treatment groups. Finally, MDA levels increased significantly and SOD and GSH levels decreased drastically in the injury groups. However, these values obtained from I/R groups were normalized after beta-carotene treatment.

Discussion: In this study, we demonstrated via molecular and biochemical parameters the protective effect of beta-carotene, which is a potent antioxidant, on the experimental ischemia-reperfusion model.
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http://dx.doi.org/10.1016/j.acthis.2015.07.006DOI Listing
October 2015

Protective effect of L-carnitine in a rat model of retinopathy of prematurity.

Turk J Med Sci 2014 ;44(3):471-5

Department of Ophthalmology, Atatürk University, Erzurum, Turkey.

Aim: To investigate the effects of L-carnitine (LC) on rats with oxygen-induced retinopathy.

Materials And Methods: The study was conducted on 40 Sprague Dawley rat pups. The rat pups were randomly divided into 4 groups: group 1 (n = 10) the healthy control group with intraperitoneal 0.1 mL/day physiological saline injection; group 2 (n = 10), exposed to hyperoxygen, did not receive LC but received 0.1 mL/day physiological saline intraperitoneally; group 3 (n = 10), exposed to hyperoxygen and received 100 mg/kg/day LC intraperitoneally; group 4 (n = 10), exposed to hyperoxygen and received 200 mg/kg/ day LC intraperitoneally. After postnatal day 20, the rat pups were killed and an histological examination was performed on the eyes, in addition to the detection of plasma malondialdehyde (MDA) levels.

Results: The retinal and choroidal histopathological changes due to hyperoxygen were less in group 3 and minimal in group 4 compared with group 2. Compared with the healthy control group, the increase in the MDA levels in group 2 was significant (P <0.05). Compared with group 2 there was a significant (P < 0.05) decrease in the MDA levels in groups 3 and 4.

Conclusion: LC has beneficial effects on oxygen-induced retinopathy in rats in terms of histopathological changes and MDA levels.
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http://dx.doi.org/10.3906/sag-1301-9DOI Listing
March 2015

The effects of prenatal exposure to a 900-MHz electromagnetic field on the 21-day-old male rat heart.

Electromagn Biol Med 2015 28;34(4):390-7. Epub 2014 Aug 28.

a Department of Histology and Embryology, Faculty of Medicine , Karadeniz Technical University , Trabzon , Turkey .

The growing spread of mobile phone use is raising concerns about the effect on human health of the electromagnetic field (EMF) these devices emit. The purpose of this study was to investigate the effects on rat pup heart tissue of prenatal exposure to a 900 megahertz (MHz) EMF. For this purpose, pregnant rats were divided into experimental and control groups. Experimental group rats were exposed to a 900 MHz EMF (1 h/d) on days 13-21 of pregnancy. Measurements were performed with rats inside the exposure box in order to determine the distribution of EMF intensity. Our measurements showed that pregnant experimental group rats were exposed to a mean electrical field intensity of 13.77 V/m inside the box (0.50 W/m(2)). This study continued with male rat pups obtained from both groups. Pups were sacrificed on postnatal day 21, and the heart tissues were extracted. Malondialdehyde, superoxide dismutase and catalase values were significantly higher in the experimental group rats, while glutathione values were lower. Light microscopy revealed irregularities in heart muscle fibers and apoptotic changes in the experimental group. Electron microscopy revealed crista loss and swelling in the mitochondria, degeneration in myofibrils and structural impairments in Z bands. Our study results suggest that exposure to EMF in the prenatal period causes oxidative stress and histopathological changes in male rat pup heart tissue.
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http://dx.doi.org/10.3109/15368378.2014.952742DOI Listing
September 2016

Investigation of the effect of telmisartan on experimentally induced peripheral nerve injury in rats.

Int J Neurosci 2015 Jun 26;125(6):464-73. Epub 2014 Aug 26.

1Department of Pharmacology.

Aim: The aim of this study was to investigate the effects of telmisartan on nerve healing in a rat peripheral nerve injury model.

Material And Method: Thirty adult male Wistar albino rats were divided into five groups: healthy, axonotmesis, anastomosis, axonotmesis+10 mg/kg telmisartan and anastomosis+10 mg/kg telmisartan. Walking track analyses were performed 4 weeks after the surgery. The right sciatic nerves of all the animals were examined histopathologically, stereologically and molecularly.

Results: Many badly damaged axons were detected in the axonotmesis group, in addition to enlarged spaces between the axons. In the anastomosis group, both ir- regular and degenerated axons at different severities were observed. The sections of the telmisartan group after the axonotmesis were similar to those of the healthy group. The sections of the telmisartan group after the anastomosis were similar to those of the healthy group and the telmisartan group after the axonotmesis. Interleukin-1 beta (IL-1β) gene expression increased in both the axonotmesis and the anastomosis groups when compared with the healthy group. Telmisartan had a significant down-regulatory effect on IL-1β expression. Caspase-3 mRNA expression was significantly increased in the anastomosis group, and the administration of telmisartan in this group significantly decreased this rise in caspase-3 mRNA expression. As a functional outcome, telmisartan also increased the walking distance of the rats after axonotmesis and anastomosis.

Conclusion: The histopathological, stereological, functional and molecular data suggest that telmisartan improves nerve regeneration in peripheral nerve injuries by inhibiting inflammatory cytokine IL-1β and apoptotic caspase-3.
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http://dx.doi.org/10.3109/00207454.2014.948115DOI Listing
June 2015

Ultra-structural changes and apoptotic activity in cerebellum of post-menopausal-diabetic rats: a histochemical and ultra-structural study.

Gynecol Endocrinol 2014 Mar 7;30(3):226-31. Epub 2014 Jan 7.

Department of Histology and Embryology, Faculty of Veterinary Medicine .

Diabetes mellitus (DM) is one of the most common and chronic diseases, especially in post-menopausal periods. Neuro-degeneration occurs more frequently in post-menopausal diabetics. Therefore, we investigated ovariectomized rats cerebellar cortex response to the estradiol deficiency and hyperglycemia. For the ovariectomy, the rats were bilaterally ovariectomized, and then DM induced by a single dose of Alloxan monohydrate injection in ovariectomy or/and diabetic groups. During light and electron microscopic examination, degenerated Purkinje cells membrane, swollen organelles, degenerated mitochondria, edema formation and vacuolization were seen in the ovariectomy and ovariectomy-diabetic groups sections. In addition, increased apoptotic activity was observed in the ovariectomy and ovariectomy-diabetic groups compared to the control group. We demonstrated that estradiol and insulin deficiency can affect the cerebellar cortex, which support the hypothesis that the execution of neuronal damages in post-menopausal diabetics. Also, diabetes and menopause are major risks factors for many disorders including nervous system and the number of post-menopausal-diabetics are increasing world-wide.
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http://dx.doi.org/10.3109/09513590.2013.864270DOI Listing
March 2014

Effects of intraocular rifampicin on retinal ganglion cell structure: a stereological and histopathological study.

Int J Ophthalmol 2013 18;6(5):596-9. Epub 2013 Oct 18.

Department of Ophthalmology, Erzurum Research and Education Hospital, Erzurum 25100, Turkey.

Aim: To determine the histopathological changes of rifampicin applied intravitreally on retinal ganglion cells by means of stereological and histopathological methods.

Methods: For this study twenty-four New Zealand adult rabbits were divided into four groups (n=6 for each group). 50µg/0.1mL (group 1), 100µg/0.1mL (group 2), 150µg/0.1mL (group 3) and 200µg/0.1mL (group 4), rifampicin were injected into the vitreous of the right eyes of animals, their left eyes were used as control (group 5). After the 28(th) day of application, animals were anesthetised with xylazine (8mg/kg, IM) and then their eyes were enucleated immediately. Patterns were taken away and eyes were prepared for both stereological and electromicroscopic observation.

Results: Depending on the high dose of rifampicin, some histopathological changes such as cytoplasmic dilatation and damaged membrane were observed on the electromicroscopic level. Using quantitative examination, which was done at the light microscopic level, it was shown that the number of neurons decreased linearly as rifampicin dose increased when compared with the control group.

Conclusion: Based on these findings, low-dose rifampicin (50µg/0.1mL) may be useful for treatment of the ocular diseases.
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http://dx.doi.org/10.3980/j.issn.2222-3959.2013.05.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3808904PMC
November 2013

Inflammation and peripheral 5-HT7 receptors: the role of 5-HT7 receptors in carrageenan induced inflammation in rats.

Eur J Pharmacol 2013 Sep 3;715(1-3):270-9. Epub 2013 Jun 3.

Ataturk University, Faculty of Medicine, Department of Pharmacology, Erzurum, Turkey.

The aim of this study was: (1) to investigate possible role for 5-HT7 receptors in carrageenan induced inflammatory paw oedema in rats; (2) to determine the presence of 5-HT7 receptors in rat paw tissue; (3) to observe the effects of 5-HT7 receptor agonist and antagonist administration on inflammation; and (4) to determine a unique mechanism for inflammatory processes via 5-HT7 receptors. Effects of 5-HT7 receptor agonist, antagonist and indomethacin were investigated in carrageenan induced paw oedema in rats. Blood and tissue samples were collected and evaluated biochemically for serum cytokine levels, tissue oxidant-antioxidant balance and histopathologically for inflammatory cell accumulation. We performed Real Time PCR analyses for tissue 5-HT7 receptor and COX mRNA expressions. The 5-HT7 receptor agonist AS-19 exerted significant anti-inflammatory effect both alone and in combination with indomethacin. Antagonist, SB269970, did not affect inflammation alone but decreased the effects of agonist when co-administered. 5-HT7 mRNA levels were higher in the carrageenan group than healthy control. Carrageenan+indometacin group decreased the mRNA expression of 5-HT7 when compared to carrageenan group. While agonist administration decreased 5-HT7 mRNA expression when compared to carrageenan group. Agonist decreased paw COX expression. Agonist also decreased serum cytokine levels and tissue oxidative stress. In conclusion, this study demonstrated for the first time that 5-HT7 receptors are expressed in rat paw tissue and that this expression responds to inflammatory stimuli. The 5-HT7 receptor may be a promising new therapeutic target for prevention of inflammation and inflammatory disorders and may also provide a new glimpse into inflammation pathophysiology.
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http://dx.doi.org/10.1016/j.ejphar.2013.05.010DOI Listing
September 2013

Peripheral 5-HT7 receptors as a new target for prevention of lung injury and mortality in septic rats.

Immunobiology 2013 Oct 27;218(10):1271-83. Epub 2013 Apr 27.

Atatürk University, Faculty of Pharmacy, Department of Pharmacology, Erzurum, Turkey.

Sepsis is a complex pathophysiological event involving metabolic acidosis, systemic inflammatory response syndrome, tissue damage and multiple organ dysfunction syndrome. Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Presence of 5-HT7 receptors in immune tissues prompted us to hypothesize that these receptors have roles in inflammation and sepsis. We investigated the effects of 5-HT7 receptor agonists and antagonists on serum cytokine levels, lung oxidative stress, lung histopathology, nuclear factor κB (NF-κB) positivity and lung 5-HT7 receptor density in cecal ligation and puncture (CLP) induced sepsis model of rats. Agonist administration to septic rats increased survival time; decreased serum cytokine response against CLP; decreased oxidative stress and increased antioxidant system in lungs; decreased the tissue NF-κB immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. In septic rats, as a result of high inflammatory response, 5-HT7 receptor expression in lungs increased significantly and agonist administration, which decreased inflammatory response and related mortality, decreased the 5-HT7 receptor expression. In conclusion, all these data suggest that stimulation of 5-HT7 receptors may be a new therapeutic target for prevention of impaired inflammatory response related lung injury and mortality.
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http://dx.doi.org/10.1016/j.imbio.2013.04.012DOI Listing
October 2013

The protective effect of amiodarone in lung tissue of cecal ligation and puncture-induced septic rats: a perspective from inflammatory cytokine release and oxidative stress.

Naunyn Schmiedebergs Arch Pharmacol 2013 Jul 12;386(7):635-43. Epub 2013 Apr 12.

Department of Pharmacology, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.

Sepsis is a serious medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. Amiodarone is a class III antiarrhythmic agent, a multichannel blocker (Ca++, Na+, and K+), and a noncompetitive α- and β-adrenergic blocker in cardiac cells. The present study aimed to determine whether amiodarone was protective against experimentally induced cecal ligation and puncture sepsis in rat lung tissue. The relationship between its probable protective effect and antioxidant/anticytokine action biochemically and histopathologically was also examined. Five groups of rats were used, each composed of 20 rats: (1) the sham-operated control group; (2) the CLP group; (3) the 25-mg/kg amiodarone-treated control healthy group; (4) the 50-mg/kg amiodarone-treated CLP group; and (5) the 50-mg/kg amiodarone-treated CLP group. A CLP polymicrobial sepsis model was applied to the rats. All groups were sacrificed 16 h later, and lung and blood samples were analyzed histopathologically and biochemically. Twenty-five and 50 mg/kg amiodarone decreased the level of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in serum and 8-iso-prostaglandin F2α level in lung tissue. They increased the activities of superoxide dismutase and levels of total glutathione in lung tissues of rats. Histopathological scores and examinations were in accordance with the biochemical results. Histopathological analysis revealed significant differences in inflammation scores between the sepsis group and the other groups. The CLP + amiodarone 50 mg/kg group had the lowest inflammation score among CLP groups. Our results indicate that administration of amiodarone prevented oxidative stress and cytokine action and protected lung tissue during sepsis cascade.
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http://dx.doi.org/10.1007/s00210-013-0862-3DOI Listing
July 2013

Protective effects of lithium: a new look at an old drug with potential antioxidative and anti-inflammatory effects in an animal model of sepsis.

Int Immunopharmacol 2013 May 29;16(1):35-40. Epub 2013 Mar 29.

Department of Pharmacology, Ataturk University Faculty of Medicine, Erzurum, Turkey.

Sepsis is the systemic response of an organism against microorganisms and toxins. Lithium is a therapeutic agent used for bipolar disorder and neurodegenerative disease, and it exerts pleiotropic effects on various cellular processes. The present study aimed to determine the effect of lithium on cecal ligation and puncture (CLP)-induced tissue injury in the lungs, by inhibiting the pro-inflammatory cytokine response, and the generation of reactive oxygen species (ROS) triggered by polymicrobial sepsis. Five groups of 20 rats each were used: 1) sham-operated control group; 2) CLP group; 3) 50mg/kg lithium-treated control healthy group; 4) 25 mg/kg lithium-treated CLP group; and 5) 50 mg/kg lithium-treated CLP group. A CLP polymicrobial sepsis model was applied to the rats. All rat groups were killed 16 h later, and lung and blood samples were analyzed histopathologically and biochemically. The 25 and 50 mg/kg of lithium decreased the level of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and the tumor necrosis factor-α (TNF-α) in the serum, and the 8-iso-prostaglandin F2α (8-ISO) level in lung tissue. The lithium also increased the activity of superoxide dismutase (SOD) and the total levels of glutathione (GSH) in the lung tissues of rats. The histopathological scores and examinations were in accordance with the biochemical results, and revealed significant differences in the inflammation scores between the sepsis group and the other groups. The CLP+lithium 50mg/kg group had the lowest inflammation score among the CLP groups. Our results indicated that the therapeutic administration of lithium prevented oxidative stress changes and cytokine changes, and also protected vital tissues.
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http://dx.doi.org/10.1016/j.intimp.2013.03.018DOI Listing
May 2013

Bilateral ovariectomy in young rats: what happens in their livers during cecal ligation and puncture induced sepsis?

J Pediatr Adolesc Gynecol 2012 Dec 22;25(6):371-9. Epub 2012 Oct 22.

Department of Pediatric Surgery, Ataturk University Faculty of Medicine, Erzurum, Turkey.

Study Objective: Pediatric ovarian masses comprise a heterogeneous group of benign and malignant lesions. Surgical methods consist of emergency or programmed surgery with tumoral resection and uni/bilateral oophorectomy or salpingo-oophorectomy. We examined whether bilateral ovariectomy (OVX) worsens liver injury during the onset of cecal ligation and puncture (CLP)-induced sepsis in rats.

Design: The rat groups were: sham, bilateral-OVX, sepsis, and OVX-sepsis.

Settings: After OVX operation, rats were allowed to recover for 12 weeks. At the end of recovery, CLP was applied 16 hours after sepsis induction.

Main Outcome: There was a significant difference in the numerical density of hepatocytes only between the sepsis and the OVX-sepsis groups. Serum ALT and AST were increased significantly in the OVX-sepsis group. NF-κB activation after OVX increased after induction of sepsis. OVX-sepsis group showed marked thrombosis in portal vein branches and the central vein, degeneration in the bile ducts, and widespread ischemic areas in liver sections. Intra-inflammatory cell invasion was observed in both the portal and intrasinusoidal areas.

Discussion: This study indicates that increases in liver NF-κB activity in ovariectomized rats following CLP-induced sepsis correlates with elevated levels of serum ALT and AST and with histopathologic changes in rat liver. Bilateral OVX therefore appears to play a role in the activation of NF-κB or in production of cytokines in liver cells. Thus, we provided novel insight into the effects of OVX on liver injury following CLP-induced sepsis.
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http://dx.doi.org/10.1016/j.jpag.2012.07.002DOI Listing
December 2012

Beneficial pharmacological effects of levosimendan on antioxidant status of acute inflammation induced in paw of rat: involvement in inflammatory mediators.

Basic Clin Pharmacol Toxicol 2013 Mar 17;112(3):156-63. Epub 2012 Oct 17.

Department of Pharmacology and Toxicology, Ataturk University School of Veterinary, Erzurum, Turkey.

Levosimendan (LEVO) is a new calcium sensitizer with positive inotropic and vasodilating properties that represents a new pharmacological class of inotropic drugs that stimulate elevated cardiac output. The purpose of this study was to examine anti-inflammatory effect and antioxidant activity of LEVO in a carrageenan (CAR)-induced inflammatory paw oedema rat model. The CAR-induced rat groups received LEVO 1, 2 and 3 mg/kg by intraperitonally and indomethacin (IND) 25 mg/kg by oral gavage. LEVO inhibited CAR-induced paw oedema and suppressed the production of TNF-α, IL-1 and IL-6 at doses of 2 and 3 mg/kg. In contrast to CAR-injected paws, 2 and 3 mg/kg doses of LEVO and IND increased superoxide dismutase (SOD) activity and also both doses of LEVO, and IND decreased the 8-isoprostaglandin F2α (8-ISO) level. A 2 mg/kg dose of LEVO produced 39%, 46%, 61% and 64.7% anti-inflammatory effects (p < 0.0001) for the 1st, 2nd, 3rd and 4th hours, respectively. Other results of our current study have shown that SOD and glutathione for CAR-injected groups were lower, and 8-ISO level was higher than those for the healthy rat group. LEVO may be provided as a pharmacological agent in the prevention or treatment of diseases in which acute or chronic inflammation occurs based on a pathogenic factor.
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http://dx.doi.org/10.1111/bcpt.12004DOI Listing
March 2013

Self-assembly of doublets from flattened polymer colloids.

Langmuir 2012 Mar 24;28(9):4086-94. Epub 2012 Feb 24.

Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.

Bottom-up fabrication methods are used to assemble strong yet flexible colloidal doublets. Part of a spherical particle is flattened, increasing the effective interaction area with another particle having a flat region. In the presence of a moderate ionic strength, the flat region on one particle will preferentially "bond" to a flat region on another particle in a deep (≥10 kT) secondary energy minimum. No external field is applied during the assembly process. Under the right conditions, the flat-flat bonding strength is ≥10× that of a sphere-sphere interaction. Not only can flat-flat bonds be quite strong, but they are expected to remain freely rotatable and flexible, with negligible energy barriers for rotation because particles reside in a deep secondary energy minimum with a ~20-30 nm layer of fluid between the ~1 μm radius particles. We present a controlled technique to flatten the particles at room temperature, the modeling of the interparticle forces for flattened spheres, and the experimental data for the self-assembly of flat-flat doublets.
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http://dx.doi.org/10.1021/la204584zDOI Listing
March 2012

A case of bacillary angiomatosis developed at a burn site.

Indian J Dermatol Venereol Leprol 2012 Jan-Feb;78(1):121

Department of Infectious Diseases, Erzurum Region Education and Research Hospital, Erzurum, Turkey.

Bacillary Angiomatosis (BA) is frequently seen in patients with human immunodeficiency virus (HIV)-induced immunodeficiency. Our patient was a case that developed granuloma-like lesions in the area of a burn, 8 days after being burnt on the upper right arm by scalding water. No indication of immune deficiency was observed and no history of direct contact with cats was evident. By the sixth day of the patient's admission to our clinic, some of the lesions had reached a diameter of 2.5 cm. An excision biopsy was carried out from the lesions present on the patient. Electron microscopy revealed solitary bacilli located close to the capillary wall. Oral erythromycin treatment was implemented at 250 mg, 4 times a day for 2.5 months. Within this period of treatment, the lesions regressed completely, and a complete cure was achieved. This case demonstrates that BA must be considered in the differential diagnosis of both HIV-infected and immunocompetent patients.
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http://dx.doi.org/10.4103/0378-6323.90970DOI Listing
April 2016

Diffractaic acid, a novel proapoptotic agent, induces with olive oil both apoptosis and antioxidative systems in Ti-implanted rabbits.

Eur J Pharmacol 2012 Jan 19;674(2-3):171-8. Epub 2011 Nov 19.

Ataturk Univ., Faculty of Pharmacy, Dep. of Biochemistry, Türkiye.

Usnea longissima Ach., a lichen species, is a traditional herbal medicine with anti-detrimental effects. We evaluated the in vivo effects of a major constituent of U. longissima, diffractaic acid, and the main fatty component of the Mediterranean diet, olive oil, against apoptosis, including various caspase activations and oxidative injury in surrounding tissues after titanium implantation in rabbit femurs. Furthermore, we evaluated the underlying molecular mechanisms. In this study, this lichen metabolite and olive oil activated caspase-dependent cell death with apoptotic morphology, which is distinctly different from necrosis. Both orally and locally administered olive oil and diffractaic acid exerted pro-apoptotic induction in tissues surrounding the implants in titanium-implanted rabbits through the activation of initiator caspases (Cas-2, -8 and -9) and executioner caspase (Cas-3). In addition, they displayed strong myeloperoxidase and inducible nitric oxide synthase activities, providing an alleviating effect. Furthermore, administrations of diffractaic acid and olive oil attenuated the Ti-alloy implantation, and decreased superoxide dismutase activity and total glutathione level in peri-implant tissues. These results demonstrate that diffractaic acid and olive oil are involved in the induction of apoptotic cell death both through caspase-dependent cell death and as an antioxidant. Thus, the data suggest that both diffractaic acid and olive oil could be developed as effective proapoptotic agents in various disorders treatments.
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http://dx.doi.org/10.1016/j.ejphar.2011.11.019DOI Listing
January 2012

The effects of testosterone on intestinal ischemia/reperfusion in rats.

J Invest Surg 2011 ;24(6):283-91

Department of Surgery, Education and Research Hospital, Yildizkent, Erzurum, Turkey.

ABSTRACT Ischemic injury to the gut is believed to occur in many serious clinical conditions. Our aim was to investigate the postischemia/reperfusion (I/R) effects of exogenously administered testosterone on the intestines of normal and orchiectomized rats.Forty-eight rats were divided into eight groups of six animals: (1) Sham-operated control group; (2) Sham-operated + testosterone-treated group; (3) I/R group: Rats were subjected to the surgical procedures and underwent intestinal ischemia for 60 min followed by reperfusion for 60 min; (4) I/R + testosterone-treated group: Rats were subjected to the surgical procedures and received testosterone 100 mg/kg (i.p.); (5) I/R + orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (6) orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (7) orchiectomy + testosterone-treated group: Rats were subjected to the surgical procedures as well as orchiectomy and received testosterone 100 mg/kg (i.p.); and (8) I/R + orchiectomy + testosterone-treated group. The histological findings of this study paralleled the observed degree of lipid peroxidation (LPO) and protein oxidation. Intestinal mucosal injury was extensive in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups, but was less in the I/R + testosterone group. Histopathological injury also paralleled the degree of oxidative stress. Apoptotic enterocytes were more numerous in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups. Administration of testosterone in the presence of testes significantly protected intestinal tissue against I/R mucosal injuries, while administration of testosterone in the absence of testes did not significantly protect intestinal tissue against I/R mucosal injuries.
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http://dx.doi.org/10.3109/08941939.2011.591894DOI Listing
March 2012

A new hypothesis about neuronal degeneration appeared after a rat model of menopause.

Neurodegener Dis 2012 26;9(1):25-30. Epub 2011 Aug 26.

Departments of Histology and Embryology, Ataturk University School of Medicine, Erzurum, Turkey.

Objective: Estrogen is suggested to be one of the most important regulators of neuronal function, including neuronal proliferation, survival and plasticity. There is a broad consensus that the loss of ovarian hormones is associated with neurodegeneration in the hippocampus that leads to cognitive impairment.

Methods: A total of 8 female rats which were subjected to bilateral ovariectomy were included in this study. After ovariectomy, the rats were housed for 123 days in a standard laboratory. At the end of the 123 days, the rats were euthanized and the brain sections were investigated by conventional light microscopic and electron microscopic techniques.

Results: The regular structure of almost all axon extensions was lost. The majority of these extensions had a sawtooth-like appearance in longitudinal section profiles. Especially in transfer section profiles of myelinated axons, some morphological changes were shown which may be matched up with light microscopic findings.

Conclusions: Deficiency of estrogen will initially affect microtubule organization. When this organization breaks down, it will physically cause the distribution of the normal structure of axonal plasmalemma. This in turn will lead to the distribution of physical organizations of estrogen and other different types of receptors which are placed in both the membrane and microtubules in the axon.
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http://dx.doi.org/10.1159/000329721DOI Listing
March 2012

Effects of diabetes mellitus on the rat liver during the postmenopausal period.

J Mol Histol 2011 Jun 21;42(3):273-87. Epub 2011 May 21.

Department of Histology and Embryology, Ataturk University, Faculty of Medicine, 25240 Erzurum, Turkey.

The present study investigated whether diabetes worsened the onset of liver injury/damage during the ovariectomized (OVX)-induced postmenopausal period in rats. Diabetes results in severe complications in humans, such as liver failure. Estrogen and its derivatives are medically acceptable, powerful antioxidant agents that can enable liver and other important organs to defend themselves against oxidative related injury. Estrogen deficiency, which occurs in the postmenopausal period and in individuals with diabetes, may play a significant role in the progression of liver failure. In the present study, rats were divided into four groups: control (Group I), diabetic (Group II), ovariectomy (Group III) and ovariectomy plus diabetes (Group IV). After the experiments, quantitative histopathological and immunohistochemical changes in liver were detected using light microscopy and modern stereological systems. Histopathological examinations showed that there were many necrotic and apoptotic hepatocytes in the lobules of Group II. In addition, there were a larger number of necrotic cells in Group III than Group II. In contrast to Group II, there were also apoptotic cells in the portal areas in Group III. Moreover, evidence of liver injury was higher in the sections of Group IV compared with all other groups. In biochemical findings, there were statistically significant differences between all the groups (P < 0.001) for catalase (CAT), glutathione peroxidase (GSH) and myeloperoxidase (MPx) activity. In addition, the amount of lipid peroxidation (LPO) was significantly different between groups. In stereological results, there were significant differences between Groups I and II and Groups II and IV. The present study provided novel insight into the pernicious effects of ovariectomy on liver injury following the onset of diabetes. Indeed, the present study found that increases in liver oxidative activity in OVX rats following the onset of diabetes correlates with elevated MPx, LPO and histopathological changes in rat liver.
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http://dx.doi.org/10.1007/s10735-011-9331-9DOI Listing
June 2011

A stereological assessment method for estimating the surface area of cycloids.

Eurasian J Med 2010 Aug;42(2):66-73

Ataturk University, Faculty of Medicine, Department of Histology and Embryology, Erzurum, Turkey.

Objective: In this study, we sought to determine differences in estimations of surface area made by classical vertical uniform random (VUR) section series and vertical section series obtained perpendicular to a fixed horizontal plane.

Materials And Methods: One volunteer subject (male, 25 years of age) with no neurological deficit was chosen at random from a bank of controls in the magnetic resonance (MR) image data library of the Department of Radiology. First, a soccer ball with known geometrical features (radius: 9.75 cm) was imaged using a T1-weighted MR scanner at 5-mm thickness (total 40 sections) to test the validity and reliability of surface area and volume measurements obtained via stereological methods. Second, T1-weighted MR section profiles were obtained from a volunteer individual. Surface area and volume estimation procedures were carried out using the Stereo Investigator 6, MicroBright-Field, Inc., USA.

Conclusions: We determined that there are no differences in either surface area or volume estimations made using VUR sections and direct vertical sections. We have performed an exhaustive series analysis with a variety of objects.
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http://dx.doi.org/10.5152/eajm.2010.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261337PMC
August 2010

The effects of polymicrobial sepsis with diabetes mellitus on kidney tissues in ovariectomized rats.

Ren Fail 2010 Jun;32(5):592-602

Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Ataturk University, 25240, Erzurum, Turkey.

Objectives: Sepsis model was used to understand the role of sustained hyperglycemia and ovariectomy, either separately or concomitantly, on the response of the activity of the nuclear factor kappa B (NF-kappaB) and the oxidative response in kidney.

Subjects: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Diabetes was induced in female rats using administration of alloxan. The rats were divided into five groups: sham control (group 1), ovariectomy (group 2), ovariectomy + sepsis (group 3), ovariectomy + diabetes (group 4), and ovariectomy + diabetic + sepsis (group 5).

Results: In kidney tissues, the levels of lipid peroxidation (LPO) and glutathione (GSH) and the activity of catalase (CAT) were higher for groups 3, 4, 5 than the control groups. Superoxide dismutase (SOD) activity was lower for groups 3, 4, 5 than the control groups. We determined that CLP produced injury evident in the kidneys of rats when compared to the control group, whereas the severity of the injury was higher in the diabetes + ovariectomy + CLP group when compared to the CLP group. In immunohistochemical staining, we determined that CLP operation increased NF-kappaB activation. In the ovariectomized, septic, and diabetic group, NF-kappaB activation was significantly higher than other groups.

Conclusions: Hyperglycemia and ovariectomy severely increased NF-kappaB activation and oxidant levels with the stages of our sepsis model. Ovariectomy resulted in general changes in metabolism, which are seen in the kidney with diabetes under sepsis conditions.
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http://dx.doi.org/10.3109/08860221003759478DOI Listing
June 2010