Comparison of the local effects of different intracameral cefuroxime solutions on rabbit cornea.

PURPOSE: We aimed to compare the local effects of intracameral cefuroxime diluted in normal saline (SF groups) against those of cefuroxime in balanced salt solution (BSS group) on the cornea of rabbits. MATERIALS AND METHODS: Fourteen New Zealand albino rabbits were randomised into two groups. The right eyes of the rabbits in the SF group I were injected intracamerally with 1 mg cefuroxime diluted with 0.1 mL normal saline (n = 7), whereas the right eyes of the BSS group II were injected with 1 mg intracameral cefuroxime diluted with 0.1 mL with balance salt solution, and the left eyes of all rabbits received no treatment group III (control group). Corneal thickness was measured with pachymetry before and 1 week after the injection. Corneal samples were evaluated with light, specular and electron microscopy. RESULTS: Mean endothelial cell count was lower in the SF than in the BSS and control groups. Although an increase in corneal thickness was found in both treatment groups, this was not the case for the control group. The corneal endothelium preserved its hexagonal structure in all groups. Although both treatment groups showed a loss of endothelial microvilli, this was more prevalent in the SF group. However, microvilli were preserved in the control group. Dissolution of tight junctions in corneal endothelium was observed in the SF group only. Mitochondrial swelling, coarsening of endoplasmic reticulum, cytoplasmic vacuolisation, and increased endothelial cell sizes were the same in both treatment groups but was not observed in the control group. Thicker and more oedematous corneal stroma were observed in the SF group compared with the BSS and control groups. CONCLUSION: Dilution of intracameral cefuroxime in BSS yielded superior results compared with dilution in normal saline owing to toxicity to the endothelial cells and decline in the endothelial cell number, resulting in intracellular and intercellular morphological changes. BSS or any other solution with proven safety should be used in clinical studies.

Beneficial effects of ursodeoxycholic acid via inhibition of airway remodelling, apoptosis of airway epithelial cells, and Th2 immune response in murine model of chronic asthma.

BACKGROUND AND AIMS: In previous studies, anti-inflammatory, anti-apoptotic and immunomodulatory effects of ursodeoxycholic acid (UDCA) on liver diseases have been shown. In this study, we aimed to investigate the effects of UDCA on airway remodelling, epithelial apoptosis, and T Helper (Th)-2 derived cytokine levels in a murine model of chronic asthma. METHODS: Twenty-seven BALB/c mice were divided into five groups; PBS-Control, OVA-Placebo, OVA-50mg/kg UDCA, OVA-150mg/kg UDCA, OVA-Dexamethasone. Mice in groups OVA-50mg/kg UDCA, OVA-150mg/kg UDCA, OVA-Dexamethasone received the UDCA (50mg/kg), UDCA (150mg/kg), and dexamethasone, respectively. Epithelium thickness, sub-epithelial smooth muscle thickness, number of mast and goblet cells of samples isolated from the lung were measured. Immunohistochemical scorings of the lung tissue for matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEG-F), transforming growth factor-beta (TGF-ß), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases (caspase)-3 were determined. IL-4, IL-5, IL-13, Nitric oxide, ovalbumin-specific immunoglobulin (Ig) E levels were quantified. RESULTS: The dose of 150mg/kg UDCA treatment led to lower epithelial thickness, sub-epithelial smooth muscle thickness, goblet and mast cell numbers compared to placebo. Except for MMP-9 and TUNEL all immunohistochemical scores were similar in both UDCA treated groups and the placebo. All cytokine levels were significantly lower in group IV compared to the placebo. CONCLUSIONS: These findings suggested that the dose of 150mg/kg UDCA improved all histopathological changes of airway remodelling and its beneficial effects might be related to modulating Th-2 derived cytokines and the inhibition of apoptosis of airway epithelial cells.

Role of vascular endothelial growth factor antagonism on airway remodeling in asthma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is an important mediator of the neoangiogenesis component of remodeling in asthma. OBJECTIVE: To evaluate the influence of VEGF blockage on airway remodeling, specifically epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness, in a mouse model of chronic asthma. METHODS: We used 30 BALB/c mice. The control group was not exposed to ovalbumin or any medication (group 1). Other groups were exposed to intraperitoneal and inhaled ovalbumin to achieve chronic asthma. Each of these groups received intraperitoneal saline (group 2), intraperitoneal dexamethasone (group 3), or intraperitoneal bevacizumab (group 4). Histomorphologic examination for epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness was performed from the middle zone of the left lung. RESULTS: Treatment with anti-VEGF caused significant reduction in epithelial, subepithelial muscle, and basement membrane thickness compared with untreated asthmatic mice (P = .001, P = .03, and P = .009, respectively). Goblet and mast cell numbers were significantly lower in mice treated with anti-VEGF than in untreated mice (P = .02 and P = .007, respectively). Dexamethasone treatment resulted in improvement of all histomorphologic markers, except goblet cell number. Influences of dexamethasone and anti-VEGF on epithelial and basement membrane thickness and mast and goblet cell numbers did not differ (P > .05), but subepithelial muscle layer was thinner in the former (P = .003). CONCLUSION: VEGF blockage may provide adjunctive therapeutic options as steroid-sparing agents for more effective treatment of remodeling in asthma.

Effects of lipoic acid in an experimentally induced hypertensive and diabetic rat model.

In this study, experimental diabetes and nephrectomy have been applied separately and together in order to investigate the possible therapeutic effects of lipoic acid (LA) on hypertensive and diabetic rat kidneys. Wistar rats were divided into eight groups: control, diabetes mellitus (DM), 5/6 nephrectomy, DM + 5/6 nephrectomy, LA administration, DM + LA treated, 5/6 nephrectomy + LA treated, and DM + 5/6 nephrectomy + LA-treated groups, respectively. Renal damage was evaluated histomorphometrically, ultrastructurally, and biochemically. Our findings supported that diabetes and hypertension together increased the rate of renal injury, and LA had therapeutic effects on hypertensive and diabetic rat kidneys.

[Experimental oral candidiasis in healthy and immunocompromised BALB/c mice]. / Saglikli ve Immün Sistemi Baskilanmis BALB/c Farelerde Deneysel Oral Kandidiyaz.

Oral candidiasis which is the most common type of Candida infections affecting humans, is most frequently caused by C.albicans. Immune response of the host, as well as a variety of virulence factors of the causative agent, play important roles in the development of Candida infections. The colonization rate of Candida in the oral cavity of healthy individuals, is between 25-30%, however, this rate is reported to be increased in immunosuppressive subjects. In our study, we established an oral candidiasis model with C.albicans in healthy and experimentally immunocompromised mice and aimed to compare Candida colonization rates and histopathological changes occurred in the tongue and esophagus tissues of the animal groups. A total of 21 BALB/c mice were grouped as control (Group 1; n= 7), healthy (Group 2; n= 7) and immunocompromised (Group 3; n= 7) groups. Immunosuppression in mice was performed by subcutaneous injection of prednisolone. For experimental oral candidiasis, cotton swab impregnated with C.albicans strains which did not have acid proteinase and phospholipase enzyme activity, no biofilm production, and sensitive to fluconazole and amphotericin B, were used. In the control group, physiological saline solution was used instead of C.albicans strain. In the forth day of experimental oral candidiasis model swab samples taken from the dorsal tongue surface of mice were evaluated by quantitative cultivation method. No yeast colonies were detected in Group 1 while more significant number of yeast colonies were observed in Group 3 compared to Group 2 (p= 0.002). Tongue and esophagus tissues of mice were stained with hematoxylin-eosin and periodic acid schiff staining and evaluated in terms of inflammatory response, abscess formation, vascular congestion, vasodilation and for the presence of yeast and hyphae. When the inflammation in esophagus was considered, statistically significant difference was determined between group 1 and group 3 (p= 0.023), however, no difference was detected between group 2 and 3 (p= 0.107). The level of inflammation in tongue tissue exhibited no difference between groups 2 and 3 (p= 0.317) while the difference was significant when these groups were compared to the control group (p= 0.00, p= 0.002, respectively). Similarly, the level of congestion in tongue tissue exhibited no difference between groups 2 and 3, however, the difference was significant when compared to the control group. To enlighten the relation between host immune status and oral candidiasis caused by C. albicans, further larger-scale studies also concerning the various virulence factors of the infectious agent, should be conducted by the use of experimental animal models which may successfully guide us in this regard.

Proteome profiling of neuron-derived exosomes in Alzheimer's disease reveals hemoglobin as a potential biomarker.

Alzheimer's disease is a chronic and progressive neurodegenerative disorder, which is the most common cause of dementia worldwide. Although amyloid plaques and neurofibrillary tangles are identified as the hallmarks of the disease, the only valid diagnostic method yet is post-mortem imaging of these molecules in brain sections. Exosome is a type of extracellular vesicles secreted into extracellular space and plays fundamental roles in healthy and pathological conditions, including cell-to-cell communication. In this study, we aimed to investigate the proteomic contents of neuron-derived exosomes (NDEs) from AD patients and healthy controls (HCs) to identify a possible marker for AD diagnosis. We identified alpha-globin, beta-globin, and delta-globin increase in neuron-derived exosomes of AD patients compared to HCs with LC-MS/MS proteomics analysis. Then, we confirmed the high hemoglobin (Hb) level in NDEs of AD patients with ELISA. We found the area under the curve of hemoglobin level as 0.6913 with ROC analysis. Cargo proteins of NDEs may be useful diagnostic biomarker for AD.

Anatomical evaluation of the superficial veins of the upper extremity as graft donor source in microvascular reconstructions: a cadaveric study.

OBJECTIVE: The aim of study was to investigate the features and resources for vein grafts suitable for upper extremity arteries. METHODS: Sixteen upper extremities of 8 cadavers were investigated. Anatomic localizations, diameters, wall thickness and valve types of the superficial veins of the upper extremity were counted and evaluated. RESULTS: Average diameter of the brachial artery was 3.96 mm, the radial artery 2.54 mm, the ulnar artery 2.12 mm, the proper palmar digital artery 3 0.85 mm, the cephalic vein of the arm 1.81 mm, the basilic vein of the arm 3.20 mm, the cephalic vein of the forearm 2.04 mm, the basilic vein of the forearm 1.35 mm, and the dorsal venous network of the hand 1.27 mm. Three different types of valves were determined. The most frequent valve types were the Type 3 in the cephalic and basilica veins at 86.5% and 90.7%, respectively. CONCLUSION: Data obtained on the superficial veins of the upper extremity may be helpful to surgeons in microsurgical reconstructions.

Comparison of TNF antagonism by etanercept and dexamethasone on airway epithelium and remodeling in an experimental model of asthma.

BACKGROUND: The aim of the study was to compare the influence of TNF antagonism and corticosteroid treatment on epithelial, smooth muscle and basement membrane component of airway remodeling in an experimental murine model of chronic asthma. METHODS: We used 30 BALB/c mice. Group 1 not exposed to ovalbumin or any medication was designated as control group. Chronic asthma model was achieved in the other three groups with intraperitoneal (IP) and inhaled ovalbumin. Then, Group 2 received IP saline, Group 3 received IP dexamethasone and Group 4 received IP etanercept. Epithelial, subepithelial smooth muscle and basement membrane thickness as well as goblet cells and mast cells were examined on samples isolated from left lung. RESULTS: Etanercept treatment led to thinner epithelial and basement membrane layer and lower goblet and mast cell number than untreated asthmatic mice (p<0.001, p=0.001, p=0.005 and p=0.03 respectively). Neither epithelial and basement membrane thickness nor mast cell number was different among mice treated with etanercept and dexamethasone (p=0.38, p=0.79 and p=0.51 respectively). However, etanercept group was associated with thicker subepithelial muscle layer but lower goblet cell number (p<0.001 and p=0.04 respectively) than dexamethasone group. CONCLUSIONS: Corticosteroids are more effective in decreasing smooth muscle mass while TNF antagonists in reducing goblet cell number in animal model of asthma. Therefore, further research is needed to assess the synergistic use of TNF antagonism and dexamethasone for more rational remodeling control.

Effect of Hedera helix on lung histopathology in chronic asthma.

Hedera helix is widely used to treat bronchial asthma for many years. However, effects of this herb on lung histopathology is still far from clear. We aimed to determine the effect of oral administration of Hedera helix on lung histopathology in a murine model of chronic asthma.BALB/c mice were divided into four groups; I (Placebo), II (Hedera helix), III (Dexamethasone) and IV (Control). All mice except controls were sensitized and challenged with ovalbumin. Then, mice in group I received saline, group II 100 mg/kg Hedera helix and group III 1 mg/kg dexamethasone via orogastic gavage once daily for one week. Airway histopathology was evaluated by using light and electron microscopy in all groups.Goblet cell numbers and thicknesses of basement membrane were found significantly lower in group II, but there was no statistically significant difference in terms of number of mast cells, thicknesses of epithelium and subepithelial smooth muscle layers between group I and II. When Hedera helix and dexamethasone groups were compared with each other, thickness of epithelium, subepithelial muscle layers, number of mast cells and goblet cells of group III were significantly ameliorated when compared with the group II. Although Hedera helix administration reduced only goblet cell counts and the thicknesses of basement membrane in the asthmatic airways, dexamethasone ameliorated all histopathologic parameters except thickness of basement membrane better than Hedera helix.

Protective effect of erythropoietin pretreatment in testicular ischemia-reperfusion injury in rats.

BACKGROUND/PURPOSE: This study was designed to investigate the effects of recombinant erythropoietin (EPO), a hormone widely used for treatment of uremic anemia, in rats subjected to testicular ischemia and reperfusion (I/R). METHODS: Thirty-five male rats were divided into the following: control, sham operated, ischemia (I), I/R, and I/R + EPO groups. In the I group, 2 hours of left unilateral testicular torsion were performed, and in the I/R and I/R + EPO groups, an additional 2 hours of testicular detorsions were performed. The I/R + EPO group was pretreated intraperitoneally with EPO (500 IU/kg) before reperfusion. Testicular tissue samples were examined for biochemical and histopathologic parameters. Apoptotic cells in all testes were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling technique and caspase 3 immunohistochemistry. RESULTS: At histopathologic examination, ischemic changes in primary spermatocytes were noted in all torted testes. Cellular damage and apoptosis were more severe in ischemic groups than the EPO-pretreated group. There were statistically significant differences in tissue biochemical parameters in the I and I/R groups compared with the I/R + EPO group. CONCLUSIONS: The results of the present study suggest that EPO exerts protective effects against I/R injury via the modulation of free radical scavenger's activities, which decreases lipid peroxidation levels and attenuation of apoptosis.

Ginseng ameliorates chronic histopathologic changes in a murine model of asthma.

Currently, asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. This study aimed to determine the efficacy of oral administration of ginseng on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: control, placebo, ginseng, and dexamethasone. All mice except those in the control group were sensitized and challenged with ovalbumin. Then, mice in the ginseng group were given 2 gr/kg per day of ginseng and mice in the dexamethasone group received 1 mg/kg per day of dexamethasone via orogastic gavage once daily for 1 week. Lung histopathology was evaluated by using light and electron microscopy in all groups. All of the chronic changes of airways in the ginseng group were significantly ameliorated when compared with the placebo group. When compared with the dexamethasone group, the ginseng group had significantly lower numbers of mast cell count. Thicknesses of basement membrane, epithelium, and subepithelial smooth muscle were not statistically different between the ginseng and dexamethasone groups. Goblet cell numbers were much more reduced in the dexamethasone group. Ginseng is effective in resolving the established chronic histopathological changes of the lungs in the murine model of asthma.

The only effects of recombinant follicle-stimulating hormone for ovulation induction in the pre-implantation period of rats.

OBJECTIVE: The aim of this study was to evaluate the changes in follicular development, serum hormonal levels, and endometrium in the pre-implantation period of rats by using recombinant FSH (rFSH) without human chorionic gonadotropin (hCG). METHODS: Thirty female rats were studied in six groups of five specimens. Two groups determined as controls (groups 1 and 2). Two groups received constant doses of rFSH (groups 3 and 4) and other two decreasing doses (groups 5 and 6). One of the paired groups was mated. Uterus, ovaries, and blood samples were taken from non-mated groups (groups 1, 3, and 5) at the proestrus period and from mated groups (groups 2, 4, and 6) in the pre-implantation period. RESULTS: In non-mated groups antral follicles and corpus luteum periodicum and in mated groups antral follicles, corpus luteum periodicum, and corpus luteum graviditatis were increased in rFSH groups, especially in decreasing dose groups. Estradiol (E2) levels were increased and progesterone (P)/E2 ratio was significantly decreased in decreasing dose groups. Endometrium surface epithelium was columnar, irregular, and folded in rFSH groups. Endometrium glandular epithelium was cuboidal in all groups. In decreasing dose groups endometrial stroma was smooth and fibroblastic. Mitotic indices of endometrium surface, glandular epithelium, and stroma were significantly decreased in rFSH groups. Primary follicles and P levels showed no change. CONCLUSION: It seems likely that decreasing doses of rFSH might be used in order to improve follicular development, although it has negative effects with E2 on endometrium in the pre-implantation period of rats.