Gaber Ramadan
UAE University, Biology, Faculty Member
Breast cancer continues to be the leading cause of cancer-related deaths among women worldwide. The most aggressive type of breast cancer is triple-negative breast cancer (TNBC). Indeed, not only does TNBC not respond well to several... more
Breast cancer continues to be the leading cause of cancer-related deaths among women worldwide. The most aggressive type of breast cancer is triple-negative breast cancer (TNBC). Indeed, not only does TNBC not respond well to several chemotherapeutic agents, but it also frequently develops resistance to various anti-cancer drugs, including taxane mitotic inhibitors. This necessitates the search for newer, more efficacious drugs. In this study, we synthesized two novel chromene derivatives (C1 and C2) and tested their efficacy against a battery of luminal type A and TNBC cell lines. Our results show that C1 and C2 significantly and specifically inhibited TNBC cell viability but had no effect on the luminal A cell type. In addition, these novel compounds induced mitotic arrest, cell multinucleation leading to senescence, and apoptotic cell death through the activation of the extrinsic pathway. We also showed that the underlying mechanisms for these actions of C1 and C2 involved inhibi...
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<p>Hypothetic model illustrating the differential effect of carnosol in MDA-MB-231 breast cancer cells.</p
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<p>(<b>A</b>) Carnosol induced apoptosis in the MDA-MB-231 cells. Annexin V binding was carried out using Annexin V & Dead Cell kit (Millipore). Cells were treated with DMSO or various concentration of carnosol for... more
<p>(<b>A</b>) Carnosol induced apoptosis in the MDA-MB-231 cells. Annexin V binding was carried out using Annexin V & Dead Cell kit (Millipore). Cells were treated with DMSO or various concentration of carnosol for 24 h. Detached and adherent cells were collected and stained with Annexin V and 7-AAD and then the events for early and late apoptotic cells were counted with the Muse Cell Analyzer as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109630#s2" target="_blank">Materials and Methods</a>. (<b>B</b>) Western blot analysis of caspase 3, -9, and -8 activation, PARP cleavage and Bcl1 and Bax expression in MDA-MB-231 cells were treated with increasing concentrations of carnosol (25, 50 and 100 µM) for 24 h. (<b>C</b>) Carnosol induces the depolarization of mitochondrial membrane. Mitochondrial membrane potential (MMP) was assessed with the Muse Cell Analyzer using the Muse MitoPotential kit as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109630#s2" target="_blank">Materials and Methods</a>. Data represent the mean ±SEM of at least 3 independent experiments. Student's t test was performed to determine the significance (*<i>p</i><0.05, **<i>p</i><0.01 and ***<i>p</i><0.005).</p
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Mangrove (Avicennia marina) is a “green lung” tree growing along the Arabian Gulf coastline in the United Arab Emirates. Here, we aimed to determine the impact of the application of a commercial seaweed extract (SWE) biostimulant and... more
Mangrove (Avicennia marina) is a “green lung” tree growing along the Arabian Gulf coastline in the United Arab Emirates. Here, we aimed to determine the impact of the application of a commercial seaweed extract (SWE) biostimulant and endophytic actinobacterial isolates on growth performance and endogenous hormonal levels of mangroves. Therefore, we isolated endophytic plant growth-promoting (PGP) actinobacteria (PGPA) from mangrove roots and evaluated their potential as biological inoculants on mangrove seedlings under greenhouse and open-field nursery conditions. Seven salt-tolerant isolates had the ability to produce different levels of in vitro plant growth regulators (PGRs) and 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase (ACCD) and to solubilize phosphorus. Accordingly, only one isolate, Streptomyces tubercidicus UAE1 (St), was selected based on its relative superiority in displaying multiple modes of action and in successfully colonizing mangrove tissues for 15 weeks....
<p>(<b>A</b>) Carnosol induces ROS generation in MDA-MB-231 cells. Cells were treated with indicated concentrations of carnosol for 24 h and ROS production was analyzed, as described in <a... more
<p>(<b>A</b>) Carnosol induces ROS generation in MDA-MB-231 cells. Cells were treated with indicated concentrations of carnosol for 24 h and ROS production was analyzed, as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109630#s2" target="_blank">Material and Methods</a>, using DCFDA fluorescence stain. (<b>B</b>) time-course measurement of ROS generation in carnosol-treated MDA-MB-231 cells. Cells were treated with 100 µM carnosol and ROS generation was examined at different time-point (1, 3 and 6 h). (<b>C–D</b>) Concentration and time-dependent accumulation of γH2AX, marker of DNA damage, in carnosol-treated cells. DNA damage was evaluated by measuring, by Western blotting, the level γH2AX accumulation using anti-phospho-H2AX (ser 139) antibody.</p
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<p>(<b>A</b>) Micrograph of MDA-MB-231 cells, after 6 h incubation with various concentrations of carnosol. (<b>B</b>) Representative electron micrographs of untreated MDA-MB-231 cells (a) and MDA-MB-231... more
<p>(<b>A</b>) Micrograph of MDA-MB-231 cells, after 6 h incubation with various concentrations of carnosol. (<b>B</b>) Representative electron micrographs of untreated MDA-MB-231 cells (a) and MDA-MB-231 cells treated with 25 (b), 50 (c) and 100 (d) µM carnosol for 24 h.</p
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<p>(<b>A</b>) Carnosol induces the formation of autophagic vacuoles MDA-MB 231 cells observed after 24 h post treatment. MDA-MB-231 cells were seeded at a density of 5×10<sup>4</sup> cells per well into... more
<p>(<b>A</b>) Carnosol induces the formation of autophagic vacuoles MDA-MB 231 cells observed after 24 h post treatment. MDA-MB-231 cells were seeded at a density of 5×10<sup>4</sup> cells per well into 12-well plate followed by treatment with DMSO (vehicle) or 50 and 100 µM carnosol. Following treatment cells were washed and stained for autophagic vacuoles using the autophagy detection kit according to manufacturer's instructions. Fluorescent autophagic vacuoles were examined under Nikon Ti U fluorescence microscope. (<b>B</b>) Western blotting analysis of LC3II, p62(SQSTM1), Beclin-1 and pERK1/2 in carnosol-treated MD-MB 231 cells. Cells were treated with DMSO or increasing concentration of carnosol for 24 h, then whole cell proteins were extracted and subjected to Western blot analysis, as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109630#s2" target="_blank">Materials and Methods</a>, for LC3II, 62(SQSTM1), Beclin1, pERK1/2 and β-actin (loading control) proteins. (<b>C</b>) carnosol induced autophagy is independent of Beclin1. MDA-MB-231 cells were transiently transfected with siRNA against Beclin1 for 72 hours followed by exposure to carnosol (50 µM) for 24 hours. Whole cell lysates were then probed for LC3II. (<b>D</b>) Time-course analysis, by Western blotting, of PARP cleavage and LC3II accumulation in carnosol-treated MDA-MB-231 cells. Cells were treated with 100 µM carnosol and proteins were extracted at the indicated time-point (3, 6, 24 and 48 h) as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109630#s2" target="_blank">Materials and Methods</a>.</p
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Thirty-one endophytic streptomycete and non-streptomycete actinobacteria were isolated from healthy date palm root tissues. In vitro screening revealed that the antifungal action of isolate #16 was associated with the production of... more
Thirty-one endophytic streptomycete and non-streptomycete actinobacteria were isolated from healthy date palm root tissues. In vitro screening revealed that the antifungal action of isolate #16 was associated with the production of cell-wall degrading enzymes, whereas with diffusible antifungal metabolites in isolate #28, albeit their production of volatile antifungal compounds. According to the 16S rRNA gene sequencing, isolates #16 and #28 were identified as Streptomyces polychromogenes UAE2 (Sp; GenBank Accession #: OK560620) and Streptomyces coeruleoprunus UAE1 (Sc; OK560621), respectively. The two antagonists were recovered from root tissues until 12 weeks after inoculation, efficiently colonized root cortex and xylem vessels, indicating that the date palm roots are a suitable habitat for these endophytic isolates. At the end of the greenhouse experiments, the development of sudden decline syndrome (SDS) was markedly suppressed by 53% with the application of Sp and 86% with Sc,...
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Mangrove forests in the Arabian Gulf are under continuous threat. To increase plantations of gray mangrove (Avicennia marina) in the United Arab Emirates (UAE), 27 endophytic actinobacterial isolates obtained from mangrove roots were in... more
Mangrove forests in the Arabian Gulf are under continuous threat. To increase plantations of gray mangrove (Avicennia marina) in the United Arab Emirates (UAE), 27 endophytic actinobacterial isolates obtained from mangrove roots were in vitro pre-screened to detect the polyamines (PAs) [putrescine (Put), spermidine (Spd), and spermine (Spm)]. We also determined the abilities of the endophytic PA-producing actinobacterial isolates in enhancing the growth of A. marina under greenhouse conditions. Although three highly PA-producing isolates were recovered from inside mangrove root tissues, Streptomyces mutabilis UAE1 constantly colonized root and stem inner tissues for 12 weeks, suggesting an endophytic association between this actinobacterial isolate and mangrove seedlings. When roots were inoculated with S. mutabilis, mangrove growth was remarkably enhanced under gnotobiotic and greenhouse conditions. This was evident from the significant (P < 0.05) increases in dry weight and len...
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Research Interests: Engineering, Physics, Chemistry, Breast Cancer, Biology, and 15 moreMembrane Proteins, Mitochondria, Autophagy, DNA damage, Apoptosis, Medicine, Multidisciplinary, Cancer treatment, Humans, Female, Phosphorylation, Mitogen Activated Protein Kinase, Cell Proliferation, Carnosol, and Autophagic cell death
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The aim of this study was to investigate the protective action of licorice in diabetic nephropathy in male rats. Diabetes was induced in male Wistar rats by using streptozotocin (60 mg/kg body weight). Daily oral ingestion (1 g/kg body... more
The aim of this study was to investigate the protective action of licorice in diabetic nephropathy in male rats. Diabetes was induced in male Wistar rats by using streptozotocin (60 mg/kg body weight). Daily oral ingestion (1 g/kg body weight) of licorice extract for 60 days after the onset of diabetes reversed the adverse effect of diabetes on rats. Licorice extract alleviated blood glucose levels, restored renal function, and attenuated body-weight loss. In addition, licorice extract modulated the adverse effect of diabetes on renal malondialdehyde, glutathione, superoxide dismutase, and catalase activity. Further, licorice extract restored the total antioxidant capacity of diabetic rat kidneys. The biochemical analyses were reinforced by histologic investigations, where focal segmental glomerulosclerosis, tubular damage, and hyperemic kidney were the histologic changes seen in diabetic, but not in treated, rats. In conclusion, the biochemical analysis and the histologic investigations of diabetic rat kidneys treated with licorice extract revealed that licorice may have a potential therapeutic effect for diabetes due to its antioxidant and -hyperglycemic properties.
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The purpose of this study is to test the effect of four different powdered food such as Rice (R), Wheat (W), Chickpeas/Hummus (C), Spirulina (S) and a mixture of the previous feed (R+W+C/H+S) on parthenogenesis and resting eggs (ephippia)... more
The purpose of this study is to test the effect of four different powdered food such as Rice (R), Wheat (W), Chickpeas/Hummus (C), Spirulina (S) and a mixture of the previous feed (R+W+C/H+S) on parthenogenesis and resting eggs (ephippia) production in Daphnia carinata (King,1853) hatched from the desert of Abu Dhabi, UAE. The study continued for 21-days at temperature 19°C ± 2°C and under 12:12 hours light/dark conditions. The analysis of the experimental results has shown that test animals fed on a mixture of food resulted in significant (p 0.05) production in parthenogenesis in comparison to other food. Meanwhile, Chickpeas/Hummus and Wheat respond similarly and produce nearly the same number (p>0.05) of ephippia and parthenogenesis eggs in comparison to the Spirulina powder. However, the least number of resting eggs and parthenogenesis (p<0.05) has produced by Daphnia carinata fed on Rice powder. Therefore, we concluded that a mixture of highly nutritive feeds strongly ind...
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To investigate phagocytosis, a class of undergraduate students isolated, cultured and fixed the mouse peritoneal cells. We concluded that the mouse immune system has high efficiency to eliminate pathogens. Educational research has shown... more
To investigate phagocytosis, a class of undergraduate students isolated, cultured and fixed the mouse peritoneal cells. We concluded that the mouse immune system has high efficiency to eliminate pathogens. Educational research has shown many advantages of using “hands-on” experiments which will help students carry out different experimental techniques and ultimately gain laboratory research skills. Skills that include preparing tissue culture media, handling animals and cell culture techniques, staining, and utilizing microscopes, will develop the knowledge needed to work in a laboratory, to produce a plan to undertake and test scientific hypotheses, and to emphasize future employability skills and attitudes. Key words: Active-learning strategies, peritoneal cells,phagocytosis, microscopy, mouse Introduction Many science education reports have shown that traditional lectures accompanied with “ready recipe” labs do not serve the needs of the student during his/her educational develop...
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To manage stem canker disease on royal poinciana, actinobacterial isolates were used as biological control agents (BCAs) based on their strong in vitro inhibitory effects against Neoscytalidium dimidiatum. Streptomyces griseorubens UAE2... more
To manage stem canker disease on royal poinciana, actinobacterial isolates were used as biological control agents (BCAs) based on their strong in vitro inhibitory effects against Neoscytalidium dimidiatum. Streptomyces griseorubens UAE2 and Streptomyces wuyuanensis UAE1 had the ability to produce antifungal compounds and cell-wall-degrading enzymes (CWDEs). Only S. griseorubens, however, restored the activity of 1-aminocyclopropane-1-carboxylate (ACC) deaminase (ACCD). In vivo apple
fruit bioassay showed that lesion development was successfully constrained by either isolates on fruits inoculated with N. dimidiatum. In our greenhouse and container nursery experiments, S. griseorubens showed almost complete suppression of disease symptoms. This was evident when the preventive treatment of S. griseorubens significantly (p < 0.05) reduced the numbers of conidia of N. dimidiatum
and defoliated leaves of royal poinciana seedlings to lesser levels than when S. wuyuanensis was applied, but comparable to control treatments (no pathogen). The disease management of stem canker was also associated with significant (p < 0.05) decreases in ACC levels in royal poinciana stems when S. griseorubens was applied compared to the non-ACCD-producing S. wuyuanensis. This study is the first to report the superiority of antagonistic actinobacteria to enhance their effectiveness
as BCAs not only for producing antifungal metabolites and CWDEs but also for secreting ACCD.
fruit bioassay showed that lesion development was successfully constrained by either isolates on fruits inoculated with N. dimidiatum. In our greenhouse and container nursery experiments, S. griseorubens showed almost complete suppression of disease symptoms. This was evident when the preventive treatment of S. griseorubens significantly (p < 0.05) reduced the numbers of conidia of N. dimidiatum
and defoliated leaves of royal poinciana seedlings to lesser levels than when S. wuyuanensis was applied, but comparable to control treatments (no pathogen). The disease management of stem canker was also associated with significant (p < 0.05) decreases in ACC levels in royal poinciana stems when S. griseorubens was applied compared to the non-ACCD-producing S. wuyuanensis. This study is the first to report the superiority of antagonistic actinobacteria to enhance their effectiveness
as BCAs not only for producing antifungal metabolites and CWDEs but also for secreting ACCD.
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Toxoplasma gondii isolates are categorized into three major genotypes I, II, III which are remarkably different in severity and geographical distribution. Exposure of camels to toxoplasmosis is mainly through ingesting the oocysts from... more
Toxoplasma gondii isolates are categorized into three major genotypes I, II, III which are remarkably different in severity and geographical distribution. Exposure of camels to toxoplasmosis is mainly through ingesting the oocysts from the environment and therefore genotyping of T. gondii in camels is a good indicator of prevalent genotypes of T. gondii in their environment. Corresponding meat and blood samples were collected from AlKhazna Tannery in Abu Dhabi from 58 camels. Serological diagnosis was done using the modified agglutination test (MAT) and P30 ELISA, DNA extraction from meat of serologically positive camels and genotyping of isolates was done by nested PCR at the SAG2 locus followed by restriction fragment length polymorphism (RFLP). Thirteen sera samples were found positive in both serological tests, whereas 8 only by MAT and 3 only by P30 ELISA. Therefore, the toxoplasma gondii ser-positive rate among slaughtered camels from Abu Dhabi ranged between 22.4 to 41.4%. Su...
Diabetic Mellitus induced cardiac muscle infarction, nephropathy and liver pathology has been widely investigated by using different techniques and models. In this paper we are comparing histological features of chronic diabetic albino... more
Diabetic Mellitus induced cardiac muscle infarction, nephropathy and liver pathology has been widely investigated by using different techniques and models. In this paper we are comparing histological features of chronic diabetic albino rat tissues with that of normal ones under light microscope. We observed the sign of diabetic cardio infarction, nephropathy and liver damage in chronic diabetic albino rats induced by injecting a single dose of streptozotocin (60 mg per kg). The nephropathy of diabetes mellitus was confined to the kidney glomeruli, renal tubules, interstitial tissue and the renal artioles, specially in the cortical region. Diabetic nephropathy include, thickening of the glomerular basement membrane, expansion of the mesangium, glomerular sclerosis, interstitial and tubular fibrosis, and heart infarction. The infarcted area showed hemorrhage, edema, loss of striation, pyknosis and karyolysis. Where as liver tissues of these chronic diabetic rats demonstrates the sympt...
Overproduction of reactive oxygen species by the mitochondrial electron transport chain in diabetic patient is responsible for the devastated symptoms of this disease. Among several diabetic complexities, nephropathy is the most damaging... more
Overproduction of reactive oxygen species by the mitochondrial electron transport chain in diabetic patient is responsible for the devastated symptoms of this disease. Among several diabetic complexities, nephropathy is the most damaging among other microvascular associated disoders. However, several pathways were suggested as a mechanism by which diabetes cause microvascular deterioration. All these pathways are linked directly or indirectly to hyperglycemia-mediated superoxide overproduction. Mlatonin is hormone that is released from the pineal gland and known to have antioxidant potentials. In the present study, diabetes was induced in male Wistar rats using streptozotocin (60mg/kg body weight) and the effect of daily dose of melatonin for 30 days was studied. Diabetic rats exhibit not only the symptoms of diabetes such as the loss of body weight, hyperglycemia, polyuria and polydipsia but also renal enlargement and renal dysfunction. Daily ingestion of 200 mg/kg of body weight o...
The effect of long-term treatment of chloroquine (CAS 54-05-7) (20 mg/kg body weight) on serum lipid components and its relation to to the retinotoxic effect was studied in albino rats. Chloroquine was found to form lamellar lysosome-like... more
The effect of long-term treatment of chloroquine (CAS 54-05-7) (20 mg/kg body weight) on serum lipid components and its relation to to the retinotoxic effect was studied in albino rats. Chloroquine was found to form lamellar lysosome-like structures within the photoreceptive layer, as well as the pigment epithelium and neurooretinal layers. Biochemically, hypolipidemia in the serum was observed mainly due to the decrease in phospholipid portion. It was hypothesized that due to the inhibition of the degradation process in the defective lysosomes, the retinal cells were denied the re-use of their own phospholipids, and thereby resort to their uptake from the serum.
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Mangrove forests in the Arabian Gulf are under continuous threat. To increase plantations of gray mangrove (Avicennia marina) in the United Arab Emirates (UAE), 27 endophytic actinobacterial isolates obtained from mangrove roots were in... more
Mangrove forests in the Arabian Gulf are under continuous threat. To increase plantations of gray mangrove (Avicennia marina) in the United Arab Emirates (UAE), 27 endophytic actinobacterial isolates obtained from mangrove roots were in vitro pre-screened to detect the polyamines (PAs) [putrescine (Put), spermidine (Spd), and spermine (Spm)]. We also determined the abilities of the endophytic PA-producing actinobacterial isolates in enhancing the growth of A. marina under greenhouse conditions. Although three highly PA-producing isolates were recovered from inside mangrove root tissues, Streptomyces mutabilis UAE1 constantly colonized root and stem inner tissues for 12 weeks, suggesting an endophytic association between this actinobacterial isolate and mangrove seedlings. When roots were inoculated with
S. mutabilis, mangrove growth was remarkably enhanced under gnotobiotic and greenhouse conditions. This was evident from the significant (P < 0.05) increases in dry weight and length of root (66.7 and 65.5%, respectively) and shoot (64.8 and 58.0%, respectively), number of branches (64.3%), total leaf area (40.2%), and photosynthetic pigments (54.5% chlorophyll a; 40.0% chlorophyll b; and 53.1% carotenoids) of mangrove compared to the PA-non-producing Streptomyces sp. or control treatment. Growth promotion in plants treated with S. mutabilis was also supported by significant (P < 0.05) elevations in the contents of mangrove in planta PAs, auxins, and cytokinins, accompanied by a decrease in abscisic acid levels. No difference was, however, detected in growth and amounts of PAs or any plant growth regulators (PGRs) in plants treated with or without the PA-non-producing isolate. Our findings indicate that plant growth parameters can be enhanced as a consequence of secretion of Put, Spd, and Spm by S. mutabilis resulting in regulation of endogenous PAs and other PGRs in mangrove tissues. This study is the first record that aims to improve sustainable agricultural management practices using plant growth promoting (PGP)
actinobacteria, endophytic in mangrove tissues to promote mangrove growth under greenhouse conditions. Such research may allow this region to be a model to study the synergistic S. mutabilis–mangrove interactions and the future impacts on mangrove reforestation in the Arabian Gulf and elsewhere where mangrove forests are in threat.
S. mutabilis, mangrove growth was remarkably enhanced under gnotobiotic and greenhouse conditions. This was evident from the significant (P < 0.05) increases in dry weight and length of root (66.7 and 65.5%, respectively) and shoot (64.8 and 58.0%, respectively), number of branches (64.3%), total leaf area (40.2%), and photosynthetic pigments (54.5% chlorophyll a; 40.0% chlorophyll b; and 53.1% carotenoids) of mangrove compared to the PA-non-producing Streptomyces sp. or control treatment. Growth promotion in plants treated with S. mutabilis was also supported by significant (P < 0.05) elevations in the contents of mangrove in planta PAs, auxins, and cytokinins, accompanied by a decrease in abscisic acid levels. No difference was, however, detected in growth and amounts of PAs or any plant growth regulators (PGRs) in plants treated with or without the PA-non-producing isolate. Our findings indicate that plant growth parameters can be enhanced as a consequence of secretion of Put, Spd, and Spm by S. mutabilis resulting in regulation of endogenous PAs and other PGRs in mangrove tissues. This study is the first record that aims to improve sustainable agricultural management practices using plant growth promoting (PGP)
actinobacteria, endophytic in mangrove tissues to promote mangrove growth under greenhouse conditions. Such research may allow this region to be a model to study the synergistic S. mutabilis–mangrove interactions and the future impacts on mangrove reforestation in the Arabian Gulf and elsewhere where mangrove forests are in threat.
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Research Interests: Analytical Chemistry, Carbon Dioxide, Pharmacokinetics, Differential scanning calorimetry, Pharmaceutical, and 17 moreAnimals, Male, Temperature, Dissolution, Bioavailability, Solubility, Pressure, In Vivo, Supercritical carbon dioxide, Chemical Precipitation, Rats, Wistar Rats, Itraconazole, Supercritical Fluid Chromatography, Excipients, Drug Compounding, and Biological Availability
We compare the effects of estrogen and/or ghrelin on vascular counts and collagen I/III ratio of urethral and anal canal submucosa in old vs young-adult ovariectomized rats. Ovariectomized Fisher 344 rats (18 and 3 months old, n = 24 × 2)... more
We compare the effects of estrogen and/or ghrelin on vascular counts and collagen I/III ratio of urethral and anal canal submucosa in old vs young-adult ovariectomized rats. Ovariectomized Fisher 344 rats (18 and 3 months old, n = 24 × 2) received 42 daily intraperitoneal 17-ß estradiol (10 μg/kg), ghrelin (2 μg/kg), both, or vehicle (n = 6 × 4 per group). Blood vessel counts and collagen I/III ratio were measured, respectively, by light microscopy and Western blot analysis with immunohistochemistry of ghrelin receptors. Estrogen significantly increased urethral and anal vascular counts and collagen I/III ratio in young-adult rats. In old rats, only combined estrogen/ghrelin administration significantly increased both variables. This was not observed with estrogen or ghrelin separately. Ghrelin receptors were immunostained in urethral and anal submucosa of all samples. Combined estrogen/ghrelin administration restored postovariectomy urethral and anal canal submucosal vessel number and collagen I/III ratio in old rats suggesting independent ageing effect.