Effect of atorvastatin on phenytoin-induced osteoporosis in adult albino rats: a pharmacological and light and electron microscopic study

Phenytoin, an antiepileptic drug [AED], might affect bone structure and mineralization. Epileptic patients who take AEDs are at increased risk for falls and fractures. Therefore, there is a need for a new approach to increase bone health in these patients. This study was conducted to assess the efficacy of statins in preventing bone loss associated with AEDs. Thirty male adult albino rats were divided into five equal groups. The animals, which received daily treatment by gastric gavage for 5 weeks, were classified into: group I [the control group]; group II, in which the rats were given phenytoin 20 mg/kg bw; group III, in which rats received phenytoin as in group II with atorvastatin 5 mg/kg bw; group IV, in which rats were given phenytoin along with atorvastatin 10 mg/kg bw; and group V, in which they were given phenytoin along with atorvastatin 20 mg/kg bw. Biochemical assays, assessment of bone mineral density, light [LM] and scanning electron microscopic studies [SME], as well as morphometric and statistical studies were carried out. The present work demonstrated that atorvastatin in a dose-dependent manner significantly [P<0.001] prevented the decrease in serum and bone calcium and phosphorus and bone-specific alkaline phosphatase due to phenytoin administration. There was also a graded improvement in osteocalcin [a marker for osteoblastic activity] and TRAP [a marker for osteoclastic activity] levels. Moreover, atorvastatin significantly inhibited the loss in bone weight, volume, and density. On LM and SEM examination, atorvastatin showed a gradual improvement of the tibia bone with higher doses as there was a significant increase [P<0.05] in trabecular and cortical bone thickness and a significant decrease [P<0.05] in osteoclast numbers per area of bone surface in the metaphysis; compared with the phenytoin-only-treated group, an improvement was seen in the growth of the epiphyseal plate. Atorvastatin could be considered a beneficial drug for treatment of osteoporosis in epileptic patients on phenytoin

possible protective role of aminoguanidine in gentamicin-induced ototoxicity in guinea pig: a histological and immunohistochemical study

Introduction: Gentamicin is an ototoxic drug affecting both auditory and vestibular cells. Reactive oxygen species might play important role in the molecular pathway of this ototoxicity. Aminoguanidine is one of the guanidine derivatives and is considered as an antioxidant therapy

Aim of the work: to investigate the possible protective effect of aminoguanidine on ototoxicity induced by gentamicin in guinea pig

Materials and methods: Twenty one adult male guinea pigs were used. They were divided into three groups, seven animals each. Group I: served as a control group. Group II: I.M. injection of gentamicin [80 mg/kg/day] was used for 14 days. Group III: animals received gentamicin in the same way as group II and then followed by aminoguanidine [100 mg/kg/ day] administration using a gastric tube for 14 days. At the end of experiment, the cochlea was excised and prepared for light [LM] and scanning electron microscope [SME] examination. Immunohistochemichal technique was done to detect iNOS. Morphometric and statistical studies were also done

Results: By LM and SME examination, the present study showed that aminoguanidine protected the structure of organ of Corti in the cochlea by decreasing the degeneration of hair cells and other supporting cells. It also showed a significant decrease in the iNOS immune-reactivity in organ of Corti, stria vascularis and bipolar cells in spiral ganglia compared to group II

Conclusion: Aminoguanidine is a promising and successful antioxidant therapy for ototoxicity

Prognostic value of plasma brain natriuretic peptide in patients with stable chronic obstructive pulmonary disease

Early detection of pulmonary hypertension or cor pulmonale could be beneficial in managing patients with chronic obstructive pulmonary disease [COPD] because the prognosis of these conditions is poor. Plasma brain natriuretic peptide [BNP] levels are elevated in patients with PH secondary to chronic lung diseases. The aim of the present study was to investigate the use of plasma BNP levels as a prognostic marker in patients with stable COPD. Plasma BNP was measured in controls and patients with stable COPD stage II, III and IV [according to the Global Initiative for Chronic Obstructive Lung Disease classification]. Echocardiography, arterial blood gas analysis, and spirometry were also performed for COPD patients. The study included 57 male patients with stable COPD; 19 had stage II COPD, 21 had stage III COPD, and 17 had stage IV COPD. Twenty age-matched healthy male smokers were enrolled as a control group. The plasma BNP levels were significantly higher in COPD patients compared to controls. The plasma BNP levels in COPD patients increased with disease severity. Plasma BNP levels significantly correlated with FEV1%, PaCO2, PaO2 and pulmonary artery systolic pressure. Plasma BNP levels increased significantly with disease severity, progression of chronic respiratory failure, and secondary pulmonary hypertension in patients with stable COPD. These results suggest that plasma BNP can be a useful prognostic marker to monitor COPD progression and identify cases of secondary pulmonary hypertension in patients with stable COPD

Comparative study on the effects of grape seed extract and telmisartan on doxorubicin-induced cardiotoxicity in adult male rats: light and electron microscopic study

Doxorubicin [DOXO] is a chemotherapeutic agent used effectively for the treatment of several malignancies. The major side effect of DOXO is oxidative injury-related cardiotoxicity, which has markedly hindered its usage. Grape seed extract [GSE] has been reported to exert protective effects on DOXO -induced cardiotoxicity. However, studies have suggested that the angiotensin receptor blocker [telmisartan] may also play a protective role in DOXO -induced cardiotoxicity. The aim of this work was to determine the effect of DOXO on rats' hearts and to compare the effects of GSE and telmisartan against DOXO -induced cardiotoxicity. Thirty adult male albino rats were used. They were divided into six groups of five animals each. Group I served as a control. Group II was administered a single intraperitoneal injection of DOXO [20mg/kg]. Group III received GSE, which was administered daily by a gavage at a dose of 100mg/kg for 12 days and DOXO was administered on the seventh day as in group II. Group IV received telmisartan, which was administered daily by a gavage at a dose of 10mg/kg for 12 days and DOXO was administered on the seventh day as in group II. Group IV received telmisartan, which was administered on the seventh day as in group II. Group V received GSE alone for 12 days. Group VI received telmisartan alone for 12 days. At the end of the experiment, the heart was prepared for histological examination and morphometric studies were carried out. It was found that DOXO exerted deleterious effects on the heart structure. GSE and telmisartan exerted a protective effect against DOXO-induced heart damage. The present study indicated that DOXO affected the structure of the rat's heart, which could be protected by GSE and telmisartan. However, the protective effect of GSE on DOXO-induced cardiac injury needs further researches for a longer duration of time to obtain more definitive results

Stem cells: new different sources and applications in regenerative medicine

Recently, basic biology and clinical application of mesenchymal stem cells have become one of the most major subjects of scientific interest. Stem cell-based therapies for regeneration of various tissues allow an alternative therapeutic solution for a number of diseases. Many researches are concerned with the application of adipose tissue-derived stem cells, which share almost similar characteristics with bone marrow mesenchymal stem cells. Another new population of stem cells from human gingiva, namely, gingiva-derived mesenchymal stem cells is recently applied instead of bone marrow mesenchymal stem cells in the repair of injured organs

Effect of omega-3 versus omega-6 fatty acids on induced ulcerative colitis in male albino rat. Light and electron microscopic study

Ulcerative colitis [UC] is an inflammatory bowel disease [IBD] well known by its exacerbated immune response. At present, a specific causal treatment for IBD is not available. The drugs currently used for management of IBD unfortunately are not devoid of potentially serious side effects. Polyunsaturated fatty acids [PUFAS] as omega-3 and omega-6 were reported to have immunomodulatory activities. Hence, may be of benefit in treating UC. The goal of this study was to illustrate the effect of omega-3 and omega-6 fatty acids on ulcerative colitis induced in male albino rat. Thirty adult male albino rats were used in the study. They were divided into four groups; Group I served as a control group. Group II was used as a model of ulcerative colitis. Rats of this group were subjected to intracolonic enema injection of 1 ml of 2% acetic acid for three consecutive days. Group III and group IV were subjected to colitis induction and on the fourth day, daily oral administration of omega-3 and omega-6 was done respectively for 14 days. All rats were sacrificed on day 17 from the beginning of the experiment. Colon specimens were collected and processed for light microscopic, scanning and transmission electron microscopic examination. Ulcerative colitis induction showed mucosal injury. There were patchy areas with loss of crypt architecture, inflammatory cell infiltrate and ulcerated mucosa. Scanning electron microscopic study revealed areas of ulceration, whereas other areas showed alteration of the columnar absorptive cells. Transmission electron microscopic study revealed loss of apical microvilli of enterocytes with signs of degeneration. Administration of omega-3 completely treated the colonic structure, while omega-6 was by far less efficient in treating induced ulcerative colitis. Omega-6 fatty acids partially improved the colon against ulcer induction. Meanwhile, omega-3 fatty acid proved to be a more effective dietary management of ulcerative colitis without the adverse effects of either surgery or medications

Comparative study on the effect of retinoic acid, glycolic acid and salicylic acid on the thin skin of adult female guinea pig. light and electron microscopic study

Many products had been used as chemical peeling agents to renew thin skin. Retinoic, Glycolic and Salicylic acids were used in many dermatological diseases with hypdrkeratinization and/or hyperpigmentation. To evaluate and compare the effects of these acids on the thin skin of adult female guinea pig. Twenty animals were used and were divided into four equal groups. Group I served as the control group, whereas the other treated groups were topically applicated daily on shaved area of back skin with Retinoic [0.05%], Glycolic [12%] and Salicylic [10%] acids in Groups II, III and IV, respectively. Thin skin specimens were processed for light and transmission electron microscopic studies. Morphometric and statistical studies were done. Groups II, III and IV showed high significant increase in mean thickness of epidermal nucleated keratinocytes as compared to Control group. Group II showed proliferation hyperkeratosis and acanthosis and shrinkage of the sebaceous glands with decreased sebum production. Group III showed skin peeling by removing superficial layers of epidermis, cytoplasmic and nuclear degeneration with disruption of intercellular junctions and degeneration in melanocytes with marked decrease of melanin. Both Retinoic and Glycolic acids apparently increased the production of collagen and elastic fibers as compared to control. Group IV showed skin peeling mainly by direct action on intercellular cement substance and partially by inducing proliferation hyperkertosis. Both Retinoic and Glycolic acids showed complementary actions in treatment of hyperpigmentation and as chemical peeling agents. Salicylic acid also is a peeling agent, but its effects could be covered by either Retinoic or Glycolic acids. It is recommended to use combination of both Retinoic and Glycolic acids to give better effects on various skin disorders with hyperkeratinization and hyperpigmentation

comparative study of the effect of Budesonide versus prednisolone on adrenal gland of the male rabbit

Although oral glucocorticoids are the treatment of choice for moderate to severe pancolitis, their systemic side effects and adrenal suppression account for considerable morbidity. Budesonide is a new intestinal topical active glucocorticoid which displays high therapeutic efficacy and high systemic tolerability. To deliver the active drug to ileal and ileocecal area, Budesonide has been formulated into enterocapsule preparation. Several studies compared the efficacy of Budesonide with that of Prednisolone. However, few determined the extent of adrenocortical suppression occurring with both drugs on histological basis. In this work, fifteen adult male New Zealand albino rabbits were used. They were classified into three equal groups. Group I served as control. Group II included animals that received intragastrically one tablet of 5 mg prednisolone daily for four weeks. Group III included animals that received orally one capsule of entocort containing 3 mg budesonide every other day for four weeks. The adrenals were processed for histological and immunohistochemical study. In the present comparative study, evidence of adrenal suppression was significantly greater in the prednisolone group than in budesonide treated animals. Light microscopic examination of H and E stained sections of prednisolone group, revealed an apparent decrease in the size of zona fasciulata cells which was proved significant by morphometric study. Moreover, Oil red stained sections of group II demonstrated a relative decrease in cytoplasmic lipid content of both zona glomerulosa and fasciculata. Using chromaffin reaction, it was noticed that there was a relative increase in the number of nor-epinephrine cells than in group III. Immunohistochemical study showed that most of the nuclei of cells in zona fasciculata in group II were negatively stained for proliferating cell nuclear antigen [PCNA] which was further proved significant morphometrically using the PCNA index. Thus it was concluded that, the budesonide preparation is associated with much less impairment of adrenal axis function. Therefore, budesonide offers a useful advance in treatment of inflammatory bowel disease

Modified vaginal smear cytology the determination of the rat estrous cycle phases, versus ordinary papanning electron microscopic examination of the endometrium

The short length of the rat estrous cycle makes them ideal for investigation of changes occurring during the reproductive cycle. The estrous cycle lasts for 4 days and is characterized as proestrus, estrus, metestrus and diestrus, The present study tried to modify a rapid cytological technique for analysis of the vaginal smear and compared it to the routine gynaecological stain [Papanicolaou, in an attempt to provide Fesearchers with a fast and practical way for the determination of the rat estrous cycle phases. Vaginal smears of 20 albino rats were collected. Half of the sin ears were stained by technique. A [using Methylene blue] while the other half was stained by technique B [Papamzicolaou stain]. The results were further verified by both light and scanning electron microscopic examination of the endometrium. The present study realized that staining of vaginal smear by the Papanicolaou stain [technique B] relatively took longer time, while Methylene blue stain [technique A] was less time consuming, and could be easily applied in daily settings; requiring only slides, one stain and a microscope. Based on scanning electron microscopic examination of the endometrial surface, the morphologic changes peaked at estrus and diestrus phases. During estrus phase, the cells showed smooth membrane projections and depressions, hence giving the cell surface an uinblicated appearance. The so called "Pinopodes" which were considered as accurate markers for endometrial receptivity and their detection might be of high clinical utility in the preparation of endomnetrium before embryo transfer. On the other hand, during diestrus phase, the endomnetrial surface appeared flat and structurless with only some clusters of detaching apoptotic cells. In conclusion, SEM appeared to be a precious tool not only for estrous stage determination, and quantification of apoptosis but also, for monitoring endometrial maturation and timing for embryo transfer. Moreover, the present study proved that, vaginal smears stained with Methylene blue could be a good rapid method for assuring endometrial phases

High dose versus low dose streptokinase infusion in patients with submassive pulmonary embolism and echocardiographic right ventricular dysfunction

Pulmonary embolism [PE] remains a major cause of morbidity and mortality in the general population, the established treatment for PE is anticoagulation. It has previously been demonstrated that thrombolytic therapy can be lifesaving in patients with massive PE [haemodynamic instability and right heart failure]. However, the use of thrombolytic therapy in patients with submassive PE [haemodynamically stable] remains a controversial topic. Recent clinical studies, however, support evidence that thrombolysis may favorably affect the outcomes in a wider spectrum of high risk PE patients presenting with right ventricular dysfunction [RVD] as evidenced by decreased right ventricular end diastolic diameter [RVEDD], disappearance of paradoxical septal motion [PSM], and tricuspid regurge [TR] as well as decrease in the pulmonary artery pressure. The aim of this study was to evaluate the effect high dose streptokinase [SK] in 1 hour versus low dose SK in 24 hours in patients with submassive PE and RVD. The study included 50 patients [25 males and 25 females, mean age 45.5 y] with submassive PE [positive spiral CT chest] and RVD [proved by echocardiography]. Those without contraindications to SK were randomly assigned to receive either high dose [group 1] or low dose [group 2] of SK. Those with contraindication [s] to SK received anticoagulation [group 3]. Echocardiography was done before and 72 h after treatment. Right ventricular dysfunction [RVEDD, PSM, and TR] and mean pulmonary artery pressure [PAP] improved significantly 72 h after treatment in group 1 and 2, while a slight improvement in PAP was observed after treatment in group 3. No significant difference was noticed between group 1 and 2 regarding the effect of treatment on RVD or PAP. No significant difference was found between group 1 and 2 regarding the complications of SK. No significant difference was found between the 3 groups regarding the mortality. These data suggest that SK can rapidly reverse the pulmonary hypertension and RVD in contrast to anticoagulation. Both protocols of SK are equieffective in rapid reversal of RVD and pulmonary hypertension. Both protocols were safe as proved by absence of difference in mortality over anticoagulant group

Light and electron microscopic study on the protective role of corneal epithelium against the effect of "UVB" radiation on rabbit cornea

The human eye might be subjected to repeated exposure to ultraviolet radiation [UVR] either during a single day or over a longer period of time. It is known that the cortical epithelium strongly absorbs UVR. The aim of this study was to evaluate the protective role of corneal epithelium against the effect of UVB radiation on corneas of albino rabbits in comparison with that on de-epithelialized corneas. Sixteen adult female New Zealand albino rabbits [3-3.5 Kg] were divided into 4 groups, 4 rabbits each. Group I served as control. Group II served also as control, but their corneas underwent manual de-. In group III, corneas were exposed to UVB irradiation, peaked at 3l2nm as a single dose [3.12J/cm2] for 30 minutes. In group IV corneas underwent manual de-epithelialization. 5 minutes prior to UVB exposure. All animals were sacrificed after 48 hours, and the corneas were removed and processed for histological and transmission electron microscopic study. The histological results of group III revealed that the corneas had slight edema and the keratocytes in the outer stroma appeared to be affected. Ultrastructural evaluation of this group showed affected epithelial cells and the keratocytes revealed early apoptotic changes like chromatin condensation. Results of group IV showed that the stromal damage was deeper and more extensive. The keratocytes had been markedly affected in the entire thickness and there was thinning out of Descemet's membrane. Ultrastructurally, the keratocytes showed chromatin condensation, fragmentation and cell shrinkage. Disorganized collagen lamellae were also seen. It was concluded that the removal of the corneal epithelium makes the underlying ocular structures-more susceptible to damage by UVB in the 312nm range. Further studies are needed to investigate whether the corneal epithelium has protective properties against UVB at other wavelengths

Dipole moment of human hemoglobin in normal working condition and leukemic cases

The human hemoglobin dipole moments are measured in working conditions for normal and leukemic cases. Use is made of Rizk-Elanwar and Kirkwood's equations to calculate the dipole moment at 37 degree. The concentration of the used dilute aqueous solutions of hemoglobin are ranged from:-0.685 X 10[-5] to 5.48 X 10[-5] mole/liter. The obtained results are discussed and correlated to the molecular structure

Effect of prostaglandins on catecholamine induced changes in the free fatty acids of plasma in the rabbit

Prostaglandins E[1], E[2], E[3] and F[1] alpha were given intravenously to anesthetize rabbits during continuous infusion of norepinephrine. PGE[2] and PGE[3] in doses of 5 micrograms all significantly reduced the arterial concentration of free fatty acids of plasma [FFA], while the same dose of PGF[1] alpha had no significant effect. Continuous intraarterial infusions of PGE[1] during continuous infusion of norepinephrine had a more pronounced effect on FFA than continuous intravenous infusion. Infusion of PGE[1], almost completely blocked the usual increase of FFA caused by epinephrine, PGE[1]diminished the plasma glucose response to epinephrine only slightly. Studies on the turnover rate of FFA with labeled albumin bound palmitate showed that PGE[1]completely blocked the norepinephrine induced stimulation of lipid mobilization. Infusion of PGE[1]during continous infusion of norepinephrine also decreased the elevated plasma glycerol concentration