Background Osteoporosis affects women severely, especially in older ages after menopause. It may lead to bad drawbacks that may be prone to considerable pathological conditions, for example, fracture and sever pain.
Objective This study aims to identify the effect of antioxidant and iron chelator on metabolic bone turnover in ovariectomized rats.
Materials and methods The rats were divided into five groups: negative control, positive control, desferal-treated, vitamin E-treated, and desferal+vitamin E-treated groups. Determination of serum estrogen, ferritin, alkaline phosphatase (ALP), tumor necrosis factor-α (TNF-α), and osteocalcin was done at the end of experiment. Moreover, morphology of bone in female rats was evaluated at the end of experiment.
Results Ovariectomy led to decrease in serum estrogen level and increase in serum levels of ferritin, ALP, TNF-α, and osteocalcin. On the contrary, usage of desferal and vitamin E led to decrease in serum levels of ferritin, ALP, TNF-α, and osteocalcin. Regarding histological picture of bone, our results showed abnormal structure of the bone of the untreated group vs improved histological picture of the treated groups.
Conclusion The female rats that were subjected to ovariectomy and experienced osteoporosis showed improvement in their bone by using desferal and vitamin E alone or in combination.
Keywords: bone remodeling, desferal, ovariectomy, vitamin E
Background Amlodipine as a calcium channel blocker has anti-inflammatory effect through overaugmentation of nitric oxide production and antioxidant effect by reduced superoxide radicals and increased level of superoxide dismutase. l-carnitine has anti-inflammatory action through reaction with acyl group that is accumulated in anoxic cells and antioxidant effect through decreasing the superoxide anion production.
Aim The aim was to evaluate the possible ameliorating effect of amlodipine (AML) and L-Carnitine (L-C) combination on osteoporotic bony changes in ovariectomized (OVX) rats versus each drug separately. A total of 50 adult female albino rats (weighting 100–125 g) of local strain were chosen as an animal model for this study. The animals were randomly divided into five groups. Each group comprised ten rats: group 1, negative control; group 2, OVX rats, positive control; group 3, AML-treated OVX rats; group 4, L-C-treated OVX rats, and group 5, AML and L-C-treated OVX rats. Bony changes were examined through evaluating markers of bone turnover, such as alkaline phosphatase and osteocalcin; femoral metaphyseal histomorphology; and serum proinflammatory cytokines, such as tumor necrosis factor-α, expression.
Results alkaline phosphatase, osteocalcin, and tumor necrosis factor-α were significantly elevated in positive control group, which was associated with marked deterioration of bone microarchitecture. Treatment with AML and L-C combination significantly mitigated inflammation and histopathological osteoporotic changes compared with each of AML and L-C drugs separately.
Conclusion AML and L-C combination could have a synergistic role in management of radical osteoporosis in OVX rats over each drug separately.
Obesity has emerged as a leading cause of death in the last few decades, mainly due to associated cardiovascular diseases. Obesity, inflammation, and insulin resistance are strongly interlinked. Lisofylline (LSF), an anti-inflammatory agent, demonstrated protection against type 1 diabetes, as well as reduced obesity-induced insulin resistance and adipose tissue inflammation. However, its role in mitigating cardiac inflammation associated with obesity is not well studied. Mice were divided into 4 groups; the first group was fed regular chow diet, the second was fed regular chow diet and treated with LSF, the third was fed high fat diet (HFD), and the fourth was fed HFD and treated with LSF. Cardiac inflammation was interrogated via expression levels of TNF α, interleukins 6 and 10, phosphorylated STAT4 and lipoxygenases 12 and 12/15. Apoptosis and expression of the survival gene, AMPK, were also evaluated. We observed that LSF alleviated obesity-induced cardiac injury indirectly by improving both pancreatic β-cell function and insulin sensitivity, as well as, directly via upregulation of cardiac AMPK expression and downregulation of cardiac inflammation and apoptosis. LSF may represent an effective therapy targeting obesity-induced metabolic and cardiovascular complications.
Moxifloxacin HCl (moxi.HCl) is a fourth generation of fluoro-quinolone which has a broad spectrum and improved anti-bacterial activity over other similar quinolones. Topical gel formulations of moxi.HCl were prepared by using gel forming agents like Carbopol 934, methyl cellulose (MC), hydroxylpropylmethylcellulose (HPMC), sodium carboxymethylcellulose (Na CMC) and sodium alginate. Compatibility studies of the drug with these polymers were performed using DSC and FT-IR techniques. Physical characterizations of moxi.HCl gels including drug content, pH measurement and rheological parameter like viscosity were studied. In vitro drug release from the prepared gel and kinetics of release were evaluated. Microbiological studies of moxi.HCl gels were carried out by using agar plate method against the tested micro-organisms. Wound healing study was performed on wound of mice infected with S.aeurus and P.aeurginosa and treated with the prepared gels. Results revealed that all the used polymers in gel preparations are compatible with moxi.HCl. All the prepared gels followed non-Newtonian (shearing thinning) pseudo-plastic flow. Higher percent cumulative drug release (87.68±2.32%) was obtained from formula (F3) containing 0.1%w/w moxi.HCl and using 4% w/v HPMC as a gel base after 8 hrs. While, formula (F5) containing 0.1 %w/w moxi.HCl and using 6%w/v of sodium alginate as a gel base showed the lowest percent cumulative drug release (50.26±1.98%) after the same time. A slight decrease in the release rate of moxi.HCl was observed by increasing the concentration of the drug to 0.5%w/w in the prepared gels. The tested formulae (F1-F5) showed a higher antibacterial activity against S.aeurus and P. aeurginosa. Formula (F3) showed a higher % of wound healing reached to 100% reduction in wound area after 6 days of topical treatment to mice with S.aeurus infected wound. Hence from the overall study, it was concluded that moxi.HCl gel would be promising in the treatment of wounds.
BACKGROUND AND AIM: Thimerosal (THIM) is a mercury-containing preservative widely used in many biological and medical products including many vaccines. It has been accused of being a possible etiological factor for some neurodevelopmental disorders such as autistic spectrum disorders (ASDs). In our study, the potential therapeutic effect of montelukast, a leukotriene receptor antagonist used to treat seasonal allergies and asthma, on THIM mice model (ASDs model) was examined.
Methodology: Newborn mice were randomly distributed into three groups: (Group 1) Control (Cont.) group received saline injections. (Group 2) THIM-treated (THIM) group received THIM intramuscular (IM) at a dose of 3000 μg Hg/kg on postnatal days 7, 9, 11, and 15. (Group 3) Montelukast-treated (Monte) group received THIM followed by montelukast sodium (10 mg/kg/day) intraperitoneal (IP) for 3 weeks. Mice were evaluated for growth development, social interactions, anxiety, locomotor activity, and cognitive function. Brain histopathology, alpha 7 nicotinic acetylcholine receptors (α7nAChRs), nuclear factor kappa B p65 (NF-κB p65), apoptotic factor (Bax), and brain injury markers were evaluated as well.
Results: THIIM significantly impaired social activity and growth development. Montelukast mitigated THIM-induced social deficit probably through α7nAChRs upregulation, NF-κB p65, Bax, and brain injury markers downregulation, thus suppressing THIM-induced neuronal toxicity and inflammation.
Conclusion: Neonatal exposure to THIM can induce growth retardation and abnormal social interactions similar to those observed in ASDs. Some of these abnormalities could be ameliorated by montelukast via upregulation of α7nAChRs that inhibited NF-κB activation and significant suppression of neuronal injury and the associated apoptosis.
Background and aim: The current study investigated the effects of treatment with 300 mg/kg valproic acid on rhabdomyolysis and acute kidney injury induced by intramuscular injection of hypertonic glycerol in rats.
Methods: Four groups of male wistar rats: control and hypertonic glycerol, valproic acid and valproic acid + hypertonic glycerol treated groups were used. Blood urea nitrogen, serum creatinine, creatinine kinase (CK) and CK MB, myoglobin and renal reduced glutathione (GSH) levels were measured. Histopathological examination of the kidneys was carried out to evaluate the degree of renal injury in each group. The expression of interleukin-1 beta "IL-1β" in renal tissue was detected using immunohistochemistry.
Results: Hypertonic glycerol administration led to severe renal tubular damage with a significant elevation of blood urea nitrogen, serum creatinine, creatinine kinase, CK MB and myoglobin levels and overexpression of IL-1β compared to control group. Valproic acid administration attenuated both the muscle injury and the acute kidney injury induced by hypertonic glycerol, estimated through a significant reduction of creatinine kinase, myoglobin, and serum creatinine. Valproic acid administration caused a significant increase in GSH in the hypertonic glycerol + valproic acid group compared to the hypertonic glycerol group. A significant decrease in tubular necrosis grade, and expression of IL-1β in hypertonic glycerol + valproic acid group compared to the hypertonic glycerol group was observed.
Conclusion: This study demonstrates, for the first time to the best of our knowledge, that valproic acid could ameliorate the rhabdomyolysis and the related acute kidney injury in rats.
Glycemic fluctuations may play a critical role in the pathogenesis of diabetic complications, such as cardiovascular disease. We investigated whether the oxycarotenoid astaxanthin can reduce the detrimental effects of fluctuating glucose on vascular endothelial cells. Human umbilical venous endothelial cells were incubated for 3 days in media containing 5.5mM glucose, 22 mM glucose, or 5.5mM glucose alternating with 22 mM glucose in the absence or presence of astaxanthin or N-acetyl-L-cysteine (NAC). Constant high glucose increased reactive oxygen species (ROS) generation, but such an effect was more pronounced in fluctuating glucose. This was associated with up-regulated p22(phox) expression and down-regulated peroxisome proliferator activated receptor-γ coactivator (PGC-1α) expression. Astaxanthin inhibited ROS generation, p22(phox) up-regulation, and PGC-1α down-regulation by the stimuli of glucose fluctuation. Fluctuating glucose, but not constant high glucose, significantly decreased the endothelial nitric oxide synthase (eNOS) phosphorylation level at Ser-1177 without affecting total eNOS expression, which was prevented by astaxanthin as well as by the anti-oxidant NAC. Transferase-mediated dUTP nick end labeling (TUNEL) showed increased cell apoptosis in fluctuating glucose. Glucose fluctuation also resulted in up-regulating gene expression of pro-inflammatory mediators, interleukin-6 and intercellular adhesion molecule-1. These adverse changes were subdued by astaxanthin. The phosphorylation levels of c-Jun N-terminal kinase (JNK) and p38 were significantly increased by glucose fluctuations, and astaxanthin significantly inhibited the increase in JNK and p38 phosphorylation. Taken together, our results suggest that astaxanthin can protect vascular endothelial cells against glucose fluctuation by reducing ROS generation.
The calcium sensitizer levosimendan is used in treatment of decompensated heart failure and may also exhibit anti-inflammatory properties. We examined whether treatment with levosimendan is substantially beneficial in mice with cecal ligation and puncture–induced polymicrobial sepsis, and its arbitration mechanism was explored in the mouse macrophage cell line RAW264.7.
Laboratory and animal/cell research.
University research laboratory.
BALB/c mice (8–10 wk old) and mouse macrophage cell line RAW264.7 cells.
Levosimendan (0.5 μg/kg/min) was administered to mice through an osmotic pump that was implanted into the peritoneal cavity immediately following surgery. In RAW264.7 cells, levosimendan was added to the culture medium 30 minutes before lipopolysaccharide.
When levosimendan was continuously administered to cecal ligation and puncture–induced septic mice, a significant improvement of left ventricular function was found without any change in heart rate, and hypotension was significantly mitigated. Furthermore, levosimendan conferred substantial protection against sepsis-associated inflammation in mice, as indicated by reduced lung injury and decreased blood proinflammatory and chemotactic cytokine levels. These beneficial effects of levosimendan led to a significant improvement of survival in mice after cecal ligation and puncture. In endotoxin-stimulated RAW264.7 macrophages, treatment with levosimendan and pimobendan suppressed overproduction of proinflammatory and chemotactic cytokines. Levosimendan and pimobendan were without effect on activation of the nuclear factor-κB, mitogen-activated protein kinase, and Akt pathways. Instead, levosimendan and pimobendan prevented high mobility group box 1 release from the nucleus to the extracellular space in macrophages. This was associated with inhibition of the Rho kinase signaling pathway. The elevated serum high mobility group box 1 levels in cecal ligation and puncture–induced septic mice were also inhibited by continued administration of levosimendan and pimobendan.
We define a novel mechanism for the anti-inflammatory action of levosimendan and suggest that the pharmacological profiles of levosimendan as both an inotrope and an anti-inflammatory agent could contribute to its clinical benefit in patients with sepsis with heart problems.
hyroid nodules are common pathologies detected in thyroid gland. A thyroid nodule is the manifestation of a wide range of thyroid diseases, some benign and others malignant. Currently, the use of imaging methods has increased the diagnosis of asymptomatic nodules. Ultrasound studies of the population have reported a nodular thyroid disease rate of nearly 67% in elderly women. Most of these nodules are benign, and the incidence of malignancy is low (3–7%). Purpose To evaluate the role of vascular pattern and spectral wave forms and resistivity and pulsatility indices to differentiate between malignant and benign features. Patients and methods A total of 40 patients who were presented with thyroid nodules scheduled for surgery and preoperative fine-needle aspiration cytology were examined in a prospective way. G?ray-scale and c?olor Doppler patterns were used to rank each thyroid nodule on a scale from 0 to 4 as follows: none, solely perinodular, accompanied by per-nodular prominence, accompanied by intranodular prominence, and only intranodular, respectively. Final diagnosis (benign or malignant) was confirmed by pathological correlations. Results Value of malignancy in thyroid nodules with a mean resistivity index of 0.72±0.13 is found to be significantly higher than with benignity (0.60.0.08). Conclusion Duplex Doppler parameters are helpful in distinguishing malignant from benign thyroid nodules.
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