Biomedical subjects

Mohamed A Fahim

Publications and source records attributed to Mohamed A Fahim.

11 recordsLinked to original sources

PubMed2007

The effect of ovariectomy on biomarkers of urogenital ageing in old versus young adult rats.

The aim of this study was to compare the effects of ageing and ovariectomy on biomarkers of urogenital ageing in old and young-adult rats. Fisher 344 rats (18- and 3-months-old, n = 6 x 2) underwent ovariectomy. Age-matched sham animals received no intervention (n = 6 x 2). One month later, biomarkers of urogenital ageing were evaluated (light microscopic count of urethral and anal canal submucosal blood vessels, Western blot analysis of urethral, and anal canal submucosal collagen I and III and cytoplasmic p27(kip1) expression in the striated urethral and anal sphincters and levator ani and gel electrophoresis of isomyosin I proportion in these muscles) and compared in all groups (n = 24). All biomarkers of urogenital ageing studied were significantly increased in old compared to young-adult sham rats. Ovariectomy significantly increased these changes further in old versus young-adult rats with either smaller or larger differential effect than ageing compared to young-adult sham animals. Ovariectomy significantly exacerbates normative urogenital ageing changes in rats.

Aging↗

PubMed2006

Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses.

Persistent exposure to inorganic lead (Pb) is known to adversely affect the immune system. In the present study, we assessed the effect of chronic Pb exposure on susceptibility to infection by the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in drinking water for approximately 16 weeks, resulting in a significant level of Pb in the blood (106.2+/-8.9 microg/dl). Pb exposure rendered mice susceptible to Salmonella infection, manifested by increased bacterial burden in target organs and heightened mortality. Flow cytometric analysis of the splenic cellular composition in normal and Pb-exposed mice revealed no gross alteration in the ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and T cells to upregulate the expression of activation antigens in response to mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a marked reduction in IFN-gamma and IL-12p40 production associated with Pb exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3- to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4 correlated with a shift in the in vivo anti-Salmonella antibody response from the protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that chronic exposure to high levels of Pb results in a state of immunodeficiency which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather is largely caused by a shift in immune responsiveness to Th2-type reactions.

Animals↗

PubMed2006

Modulation of neuronal [Ca2+]i by caffeine is altered with aging.

Voltage-dependent calcium channels play an important role in controlling many neuronal processes such as neuronal excitability and synaptic transmission. Any slight alteration in intracellular calcium concentration ([Ca2+]i) can have a considerable impact on various neuronal functions. The effects of caffeine on [Ca2+]i were studied in CA1 hippocampal neurons of young (2 months) and old (24 months) C57BL mice. Fura 2-AM fluorescence photometry was used to measure [Ca2+]i in the presence and absence of caffeine (100 microM) in response to KCl (26 mM) application. Caffeine enhanced the peak [Ca2+]i as compared to control solution in young mice (control: 325+/-8 nM, caffeine: 402+/-10 nM), but had no effect on the peak [Ca2+]i in old mice (control: 222+/-6 nM, caffeine: 223+/-7 nM). These results indicate that caffeine can impact neuronal functions through the modification of [Ca2+]i. The lack of caffeine-induced modulation of [Ca2+]i in old mice suggests that this role of caffeine has been compromised with aging.

Aging↗

PubMed2006

Estrogen and ghrelin decrease cytoplasmic expression of p27kip1, a cellular marker of ageing, in the striated anal sphincter and levator muscle of ovariectomized rats.

A study was carried out to investigate the effect of estrogen and/or ghrelin on the cellular marker of ageing, p27kip1, in pelvic floor muscles of ovariectomized rats. Virgin Wistar rats (13 months old) underwent ovariectomy followed (1 month) by 42 daily intraperitoneal 17-beta estradiol (10 microg/kg), ghrelin (2 microg/kg), both hormones, or placebo vehicle (n=6x4 groups). Six more age-matched animals underwent sham surgery without ovariectomy. Cytoplasmic expression of p27kip1 in the striated urethral and anal sphincters and levator muscle was measured by Western blot analysis in all animals (n=30). p27kip1 signal intensity significantly increased postovariectomy in all muscles compared to sham animals. In the anal sphincter and levator, signal intensity decreased to sham levels with ghrelin or estrogen and decreased further after estrogen or ghrelin and estrogen/ghrelin administration. Urethral sphincter signal intensity decreased without reaching sham levels after drug administration. Estrogen and/or ghrelin replacement reverses the ovariectomy-induced exacerbation of biochemical cellular ageing in the anal sphincter and levator muscle of middle-aged rats.

Aging↗

PubMed2005

Estrogen and ghrelin increase number of submucosal urethral and anal canal blood vessels in ovariectomized rats.

OBJECTIVES: Urinary and fecal control deteriorates after menopause, but it is not clear whether this is age or hormone related. This study investigates whether administration of estrogen and/or the anti-aging growth hormone-releasing peptide, ghrelin, improves the adverse effects of menopause/aging on urethral and anal canal submucosal blood vessel counts in middle-age rats. METHODS: Female Wistar rats (13 months old) underwent ovariectomy, followed 1 month later by intraperitoneal once-daily administration of 17-beta estradiol (10 microg/kg), ghrelin (2 microg/kg), both hormones, or vehicle (n = 6 in each of four groups) for 42 days. An age-matched sham group (n = 6) received no intervention. Submucosal blood vessels were counted by light microscopy in five randomly selected fields from five nonconsecutive sections (5 microm thick) per rat of formalin-fixed and paraffin-embedded tissue blocks of the urethra and anal canal stained with hematoxylin-eosin. The results are expressed as the mean vessel number per high power field (x400). RESULTS: Ovariectomy significantly reduced submucosal urethral and anal vascular counts below the sham values (7.41 +/- 0.98 versus 5.46 +/- 0.82, P = 0.003 and 7.16 +/- 1.11 versus 4.92 +/- 0.65, P = 0.0009, respectively). Estrogen restored the urethral counts (7.76 +/- 0.88, P = 0.5) and ghrelin or combined estrogen and ghrelin administration significantly increased the counts to greater than the sham counts (8.68 +/- 0.99, P = 0.04 and 9.72 +/- 1.21, P = 0.004, respectively). Estrogen, ghrelin, and combined estrogen and ghrelin administration also restored the anal counts to sham levels (7.26 +/- 0.97, P = 0.8; 6.56 +/- 0.78, P = 0.3; and 7.76 +/- 0.88, P = 0.3, respectively). CONCLUSIONS: Combined or individual replacement of estrogen and ghrelin produces a beneficial effect by reversing the ovariectomy-induced decrease in urethral and anal canal submucosal vessel numbers in middle-age rats.

Anal Canal↗

PubMed2004

Synaptic vesicle cycling at type-identified diaphragm neuromuscular junctions.

Differences in neuromuscular transmission and neuromuscular junction morphology exist across muscle fiber types. We hypothesized that these fiber-type differences are reflected in the size of the cycling synaptic vesicle pool. Synaptic vesicle cycling at type-identified rat diaphragm neuromuscular junctions was examined by fluorescently labeling presynaptic vesicles with FM4-64. We found that FM4-64 fluorescence uptake was higher at presynaptic terminals of type I/IIa fibers than type IIx/IIb fibers. However, no fiber-type differences in the rate of FM4-64 destaining were found with repetitive nerve stimulation. Synaptic vesicle density at active zones was examined by transmission electron microscopy. In accordance with FM4-64 uptake, synaptic vesicle density was greater at type I/IIa than IIx/IIb fibers. These results demonstrate differences in synaptic vesicle cycling across diaphragm muscle fiber types, which may underlie previously observed differences in neuromuscular transmission across diaphragm muscle fiber types. In the diaphragm, motor units comprising type I and type IIa fibers are most frequently recruited with a duty cycle of approximately 40%. Motor units comprising IIx/IIb fibers are infrequently recruited and only for short durations. The capacity for synaptic vesicle release and cycling at different muscle fiber types matches the functional requirements of these motor units. If the demand for recruitment of motor units comprising IIx/IIb fibers increases, for example, with mechanical loading, there is an increased risk for neuromuscular transmission failure that my relate to the capacity for synaptic vesicle release and cycling. Muscle fiber type-specific adaptations should be considered when examining neuromuscular disorders.

Animals↗

PubMed2004

Increased calcium influx through acetylcholine receptors in dunce neurons.

Calcium homeostasis was studied in dunce, a Drosophila mutant that is defective in learning and memory. Fura 2-AM fluorescence photometry was used to measure the intracellular calcium concentration in wild type and dunce cleavage-arrested neurons under resting conditions and in response to neurotransmitters. After acetylcholine application, the peak [Ca2+]i was greater in dunce (693 +/- 125 nM) than in wild type neurons (464 +/- 154 nM), but half decay time was shorter in dunce (66 +/- 15 s) than in wild type neurons (104 +/- 40 s). In contrast, the application of glutamate, NMDA, dopamine, and serotonin had no effect on [Ca2+]i. These results indicate that calcium influx through acetylcholine receptors is increased in dunce, compared to wild type neurons. The results also suggest that calcium extrusion to the outside and/or calcium buffering are enhanced in dunce, compared to wild type neurons. This disturbance in the homeostasis of cytosolic calcium concentration in dunce may be implicated in defective associative learning in Drosophila, and may play a role in acute and chronic neurodegenerative disorders in the mammalian brain.

Acetylcholine↗

PubMed2004

Pkc-a differentially affects rutabaga and wild-type Drosophila neuronal potassium current.

Learning and memory are defective in the Drosophila mutant rutabaga, which has a low intracellular cyclic adenosine monophosphate (cAMP) concentration. The aim of this study was to compare modulation effects of protein kinase C activator (PKC-A) on the delayed-rectifier potassium current (IKDR) in wild-type and rutabaga neurons. IKDR was measured from cultured (2 days) wild-type and rutabaga neurons. The authors examined the effects of PKC-A on IKDR in wild-type and rutabaga neurons. IKDR was measured from neurons before and after addition of PKC-A to the external solution. IKDR was smaller in rutabaga neurons (380 +/- 25 pA) than in wild-type neurons (529 +/- 44 pA). IKDR was reduced by PKC-A more in wild-type (decreasing 55 +/- 6%) than in rutabaga (decreasing 35 +/- 8%) neurons (single-cell studies). In the presence of PKC-A, there was no difference in IKDR between wild-type (229 +/- 31 pA) and rutabaga (242 +/- 26 pA) neurons (population studies). These results indicate that PKC-A differentially affects the delayed-rectifier channel in wild-type rutabaga.

Animals↗

PubMed2003

Drug effects on calcium homeostasis in mouse CA1 hippocampal neurons.

Voltage-dependent Ca2+ channels (VDCC) are important in control of neuronal excitability, synaptic transmission, and many other cellular process. Even the slightest alteration in Ca2+ currents can have a considerable impact on the neuronal function. However, it is still unknown whether Ca2+ currents are affected by neurotoxic drugs such as lead, cobalt, zinc, cadmium, thallium, lanthanum, and aluminum. We have characterized the effects of neurotoxic drugs on Ca2+ homeostasis in CA1 hippocampal C57BL mice. Fura 2-AM fluorescence photometry was used to measure intracellular Ca2+ concentration ([Ca2+]i) in the presence and absence of neurotoxic drugs (10 microM) in response to KCl application. The peak [Ca2+]i due to KCl application was reduced in the presence of lead (60%), cobalt (35%), zinc (62%), cadmium (71%), thallium (27%), and lanthanum (66%). By contrast, in the presence of aluminum the peak [Ca2+]i was either increased (46%) or it was not affected. These results indicate that neurotoxic drugs could block the entry of calcium into CA1 neurons via VDCC.

Aluminum↗

PubMed2003

Serotonin reduces potassium current in rutabaga and wild-type Drosophila neurons.

The Drosophila learning mutant rutabaga is defective in short-term memory and has a reduced intracellular cyclic adenosine monophosphate (cAMP) concentration. The delayed-rectifier potassium current (IKDR) was measured from cultured (2 days) wild-type and rutabaga neurons. IKDR was smaller in rutabaga neurons (382 +/- 41 pA) than in wild-type neurons (542 +/- 33 pA). IKDR was measured from neurons before and after addition of serotonin to the external solution. IKDR was reduced by serotonin in wild type (decreasing 37 +/- 7%) and rutabaga (decreasing 33 +/- 6%) neurons (single-cell studies). In the presence of serotonin, IKDR was smaller in rutabaga (218 +/- 24 pA) than in wild-type (426 +/- 35 pA) neurons (population studies). These results indicate that serotonin has affected IKDR so that the inherent difference between the two genotypes was preserved.

Animals↗

PubMed2003

Alpha tocopherol protects against immunosuppressive and immunotoxic effects of lead.

Chronic exposure to lead (Pb) is associated with multiorgan toxicity. The precise mechanism(s) involved, however, remains incompletely defined. The present study was undertaken to analyze the effect of Pb on the immune system and determine the ability of alpha tocopherol (AT) to reverse Pb-induced immunotoxicity. Groups of TO Mice (6 per group) were treated ip for 2 weeks with saline alone, Pb acetate alone, Pb plus AT, or with AT alone. Spleens were then analyzed for (i) cellular composition by flow cytometry, (ii) cellular response to B and T cell mitogens and (iii) production of nitric oxide (NO). Pb treatment resulted in a significant state of splenomegaly associated mainly with an influx of CD11b+ myeloid cells. Surprisingly, however, these cells exhibited no upregulation in expression of activation markers and did not produce NO. The lymphocyte mitogenic responses were inhibited by > or = 70% in Pb-treated group. Concurrent treatment with Pb and AT resulted in almost a complete reversal of Pb-induced splenic cellular influx. Despite this, however, mitogenic responses in Pb + AT treated group were approximately 50% of those observed in normal (saline-treated) controls. We conclude that (1) chronic treatment with Pb acetate induces a state of splenomegaly and decreased proliferation in response to mitogenic stimuli and (2) co-treatment with AT largely reversed the cellular influx but this was associated with only a partial improvement of the mitogenic responses. These results highlight the role of AT as a potentially effective antioxidant in the immune system.

Animals↗