Pharmacological effects of gemfibrozil on some isolated smooth muscle preparations of experimental animals

Background: Gemfibrozil is a member of fibrates (gemfibrozil, fenofibrate, ceprofibrate, and benzafibrate) which is employed for treatment of dyslipidemia particularly hypertriglyceridemiae through its action on peroxisome proliflator activated receptors (PPAR-). Objective: The aim of this work was to study the site of action and pharmacololgical effects of different doses of gemfibrozil on some isolated smooth muscles preparations of experimental animals. Materials and Methods: The experiments were conducted on isolated jejunum of rabbits, isolated spiral tracheal and urinary bladder strips of guinea pigs. Results: I- On isolated rabbit jejunum, gemfibrozil produced a dose-dependent reduction on the amplitude of jejunal contractions. The inhibitory effect of gemfibrozil was not abolished after complete blockade of alpha and beta adrenergic receptors, while it was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. On the other hand the stimulatory effects of nicotine small dose, acetylcholine, calcium gluconate, histamine and serotonin were not abolished after administration of gemfibrozil. II- On isolated tracheal spiral strips of ginea pigs, gemfibrozil produced a dose- dependent relaxation on the basal tone and a dose-dependent reduction on the amplitude of acetylcholine-induced tracheal contractions of the tracheal strips. The inhibitory effect of gemfibrozil was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. Gemfibrozil completely abolished also serotonin-induced contraction, while it has no effect on histamine or calcium-induced tracheal contractions. III- On isolated urinary bladder strips of guinea pigs, gemfibrozil produced a dose-dependent reduction on the amplitude of urinary bladder contractions. The inhibitory effect of gemfibrozil was not abolished after complete blockade of beta adrenergic receptors, while it was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. On the other hand the stimulatory effects of acetylcholine and serotonin were not abolished after administration of gemfibrozil. Conclusion: Gemfibrozil (antidyslipidemic, PPAR- agonist) reduced jejunal and urinary bladder contractions and has a relaxant effect on tracheal basal tone. So it has a beneficial effect in obstructive airway diseases and cases of urgency and frequency of micturation and urinary incontinence. However, it may be used cauciously in cases of ,GIT disturbances as constipation and prostatic hypertrophy

Pharmacological effects of gemfibrozil on some isolated smooth muscle preparations of experimental animals

Background: Gemfibrozil is a member of fibrates [gemfibrozil, fenofibrate, ceprofibrate, and benzafibrate] which is employed for treatment of dyslipidemia particularly hypertriglyceridemiae through its action on peroxisome proliflator activated receptors [PPAR-alpha]

Objective: The aim of this work was to study the site of action and pharmacololgical effects of different doses of gemfibrozil on some isolated smooth muscles preparations of experimental animals

Materials and Methods: The experiments were conducted on isolated jejunum of rabbits, isolated spiral tracheal and urinary bladder strips of guinea pigs

Results: I- On isolated rabbit jejunum, gemfibrozil produced a dose-dependent reduction on the amplitude of jejunal contractions. The inhibitory effect of gemfibrozil was not abolished after complete blockade of alpha and beta adrenergic receptors, while it was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. On the other hand the stimulatory effects of nicotine small dose, acetylcholine, calcium gluconate, histamine and serotonin were not abolished after administration of gemfibrozil. II- On isolated tracheal spiral strips of ginea pigs, gemfibrozil produced a dose- dependent relaxation on the basal tone and a dose-dependent reduction on the amplitude of acetylcholine-induced tracheal contractions of the tracheal strips. The inhibitory effect of gemfibrozil was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. Gemfibrozil completely abolished also serotonin-induced contraction, while it has no effect on histamine or calcium-induced tracheal contractions. III- On isolated urinary bladder strips of guinea pigs, gemfibrozil produced a dose-dependent reduction on the amplitude of urinary bladder contractions. The inhibitory effect of gemfibrozil was not abolished after complete blockade of beta adrenergic receptors, while it was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. On the other hand the stimulatory effects of acetylcholine and serotonin were not abolished after administration of gemfibrozil

Conclusion: Gemfibrozil [antidyslipidemic, PPAR-alpha agonist] reduced jejunal and urinary bladder contractions and has a relaxant effect on tracheal basal tone. So it has a beneficial effect in obstructive airway diseases and cases of urgency and frequency of micturation and urinary incontinence. However, it may be used cauciously in cases of ,GIT disturbances as constipation and prostatic hypertrophy

role of puppets' theatre in development of visual skills of children with learning disabilities

Introduction: Child's theatre represents one of the most important educational medium, tool, and art affecting all his life stages. Puppets' theatre is a modern educational means and exciting source of attraction for children in general and children with learning disabilities in particular. The current study sheds lights on the potentials of puppets theatre in attempt to utilize its potentialities in developing some sensomotor skills of children with learning disabilities

Problem: It is defined in the following inquiry What is the effectiveness of using the puppet theatre for developing some sensomotor skills among children with learning disabilities?

Significance: The current study assists those children through some programs for developing the sensomotor skills to treat and develop their potentials; through designing a collection of puppets which are attractive and enjoyable for children to develop their skills

Objectives: The study checks out the effectiveness of using the puppet theatre in developing the sensomotor skills of children with learning disabilities

Population and Sample: Thirty children [Male/ Females] are selected from mental education schools in Cairo governorate, aged [9-15] year olds, divided into two equal groups, the control and the experimental, whose 1Q ranges [70-90], with fixed socio-economic level

Type and Method: It uses the experimental method

Tools: The designed Program for measuring efficacy of participation in using puppets' theatre for developing some sensomotor skills among children with learning disabilities [By Researcher], and A Scale of measuring the sensomotor skills [By Researcher]

Results: Regarding the first hypothesis, it is not proved as there exist significant statistical differences between the average scores of the control and the experimental group, post use of the program, in favor of the experimental group, and There are no significant statistical differences between the average scores of the experimental group students due to the socio-economic level, in favor of the middle socio-economic level, so, it is not proved

Hypofractionated radiation therapy versus conventional radiation in they adjuvant setting of breast cancer; is there any difference in toxicity?

Recent studies of radiation toxicity in the treatment of breast cancer have shown that; the effects on normal tissues can constitute a significant health problem. One of these problems is skin toxicity. The aim of the current study is to compare the acute skin toxicity between two different fractionation schedules of adjuvant breast radiation: the conventional radiation [CFR] versus hypofractionated radiation [HFR]. This is a prospective randomized study done in breast cancer patients referred for adjuvant radiation therapy. Radiation therapy was given in either one of two ways: CFR [5000 cGy/ 25 fractions I 5 weeks; 200 cGy per fraction] or HFR [4005 cGy/15 fractions / 3 weeks; 267 cGy per fraction] Acute radiation reactions were graded according to the Radiation Therapy Oncology Group toxicity grading system [RTOG] [1]. A comparison was done between the incidence of these reactions and different variables as: total radiation dose, type of surgery, number of surgically dissected nodes.etc. Seventy eight patients were accrued to the study, of whom 57.7% had breast conservative surgery [BCS], while 42.3% had modified radical mastectomy [MRM]. Patients who had received HFR represented 53.8%, while those who received CFR represented 46.2% of all patients. The majority of patients [64.1%] had grade 0/II radiation reaction, and 35.9% had grade III/IV reaction. On univariate analysis, there was a statistically significant difference between the two radiation arms regarding the incidence of radiation reaction, with higher incidence [52.8%] in CFR as compared to 21.4% in HFR [p 0.004], while the other variables [type of surgery, number of surgically removed nodes, etc] were not statistically significant. On multivariate analysis; the only factor of statistical significance regarding the incidence of radiation reaction was the radiation therapy schedule, with a higher incidence in CFR [p value 0.03]. There is a statistically less incidence of acute radiation reactions in hypofractionated arm as compared to conventional fractionated arm in the adjuvant radiation of breast cancer.

ameliorating effect of vitamin [E] against the toxicity of Zineb on the testicular structure and chromosomal pattern of adult albino rats

Zineb is one of the ethylene-bis-dithiocarbamate fungicides which are widely used for the plant protection especially grains, vegetables and fruits. Potential exposure to zineb can occur in workers engaged in the production and use of the fungicide, people living in agricultural areas where the compound is sprayed and people consuming polluted products. Zineb can produce toxic effects on the testes and chromosomes. This study was performed to evaluate the possible protective role of vitamin [E] against zineb-induced toxicity on the testicular structure and chromosomal pattern of adult male albino rats. Ninety six albino rats equally divided into six groups were used; the first group was used as a negative control. The second group: each rat was given l C.C. distilled water orally once daily for 3 months and the third group: each rat was given I C.C. com oil orally once daily for 3 months were used as positive control groups. The fourth group: each rat was given 1/10 LOSO of zineb which is 5 gm/Kg. body weight once daily orally for three months. The fifth group: each rat was given vitamin [E] I 00 mg/kg once daily orally for three months. The six group: each rat was given both zineb and vitamin [E] for three months. At the end of the study [after 3 months]. The tests of zineb-treated rats [group 4] showed significant histopathological alterations in the form of distorted 1>eminiferous tubules with irregular contour. The tubules were shrunken and attain different shapes and separated from each- other by wide interstitial spaces. These changes were confirmed by electron microscope that showed marked loss of spennatogenic cells, the distorted spennatids had an irregular outline and their nuclei showed densely packed chromatin material. Their cytoplasm was poor with organoids. Leydig cells appeared with irregular outlined nuclei. The rats of group 6 [zineb and vitamin E group] showed less histopathological changes when compared with group 4 [zineb group]. Moreover, chromosomal study of zineb-treated rats showed a significant increase in the frequency of structural and numerical chromosomal aberrations when compared with groups 1, 2 and 3 and group 6 [zineb and vitamin E group]. It could be concluded that chronic zineb exposure can induce testicular and chromosomal abnormalities, while simultaneous administration of vitamin [E] can ameliorate such toxic effects, indicating that vitamin [E] can play a protective role against the toxic effects of zineb on the testis and chromosomal pattern of adult male albino rats

Effect of N- acetylcysteine and garlic against acute and chronic nephrotoxicity induced by mercuric chloride in adult albino rats

Mercuric chloride is a known human and animal nephrotoxicant. This study was conducted to evaluate the effect of N-acetylcysteine and garlic against acute and chronic nephrotoxicity induced by mercuric chloride in adult albino rats. The study included 140 adult albino rats for studying the acute and chronic toxicities of mercuric chloride. The acute toxicity study included 7 subgroups [each subgroup contains 10 rats]: subgroup I [negative control], subgroup II[positive control]:Each rat orally received 1-mLsaline in a single dose, subgroup IJI orally received mercuric chloride in a dose of 13mg/ kg body weight [1/2 Lethal Dose] in 1-mL saline as a single dose, subgroup IV [Nacetylcysteine subgroup] orally received 505mg/ kg body weight [1/10 LD[50]] in 1-mL saline, subgroup V [garlic- treated subgroup] given orally garlic in a dose of 54 mg/100 gm of body weight dissolved in 1-mL saline once daily, subgroup VI: is given mercuric chloride and N-acetylcysteine with the previous doses and subgroup VII is given mercuric chloride and garlic with the previous doses. After 24 hours urine was collected from the rats of each group to measure urinary mercuric chloride level. The rats were then sacrificed and blood samples were collected for measuring serum creatinine level. Kidney samples were subjected for histopathological examination by light microscope. The chronic mercury toxicity study included 7 Subgroups each contained 10 rats The 1[st] subgroup [negative control], 2[nd] subgroup [positive control]:Each rat orally received 1-mLsaline daily, 3[rd] subgroup orally received mercuric chloride in a dose of 2.59 mg/ kg body weight [1/10 Lethal Dose] in 1-mLsaline for each rat daily, 4th subgroup [N-acetylcysteine subgroup] orally received 505mg/ kg body weight [1/10 LD[50]] in 1-mLsaline daily, 5[th] subgroup [garlic- treated subgroup] orally given garlic in a dose of 54 mg/100 gm of body weight dissolved in 1 mL saline once daily. 6[th] subgroup given mercuric chloride and N-acetylcysteine with the previous doses and 7[th] subgroup given mercuric chloride and garlic in the previous doses all subgroups were treated for 2 months then blood samples were collected for measuring serum creatinine level then rats were sacrificed and kidney samples were taken for histopathological examination by light microscope. After 24 hours urinary mercuric chloride level was highly significantly increased in rats acutely intoxicated with mercuric chloride as compared with positive control subgroup [P < 0.001]. At the same time urinary mercuric chloride level was highly significantly increased in rats received N-acetylcysteine or garlic concomitantly with mercuric-chloride than rats received mercuric chloride alone [P < 0.001]. Serum creatinine level was highly significantly increased in rats acutely intoxicated with mercuric chloride than other groups [P < 0.001]. Histopathological findings after 24 hours in the acute toxicity study were cloudy swelling of convoluted tubular epithelium with cell necrosis. After 2 months of chronic toxicity there was a very high significant increase in serum creatinine level of the mercury intoxicated rats alone [3[rd] subgroup] when compared with rats of other subgroups [P < 0.001] and the histopathological findings were coagulative necrosis, cystic dilatation of some renal tubules, hyaline and cellular casts, thickening of Bowman's capsule with interstitial aggregation of lymphocytes. It can be concluded that. N-acetylcysteine and garlic can protect the kidney from the nephrotoxicity of mercuric chloride when concomitantly administered with it

Alterations in developing testis of albino rats induced by flunitrazepam

The use of flunitrazepam [Rohypnol], which is known in Egyptian street as Abou-Saliba, is markedly increased. So, the present study was designed to investigate its effect on the developing testes. The male off-springs of 16 pregnant rats were used. The pregnant rats were divided equally into 4 groups. The off-springs of the 1st group were used as a control. The 2nd group was the group of treated off-springs of treated mothers. The pregnant rats of this group received a single oral daily therapeutic dose 0.036 mg of flunitrazepam for the whole period of gestation up to the first ten days after delivery. Then their off-springs received a single oral daily therapeutic dose 0.0036 mg of flunitrazepam from the 10th day of postnatal life up to the 30th day. The 3rd group was the group of treated off-springs of non treated mothers. The pregnant females of this group did not receive any treatment, while their off-springs were treated similar to those of the 2nd group. The 4th group was the group of non-treated offsprings of treated mothers. The pregnant rats of this group were treated similar to those of the 2nd group, while their offsprings of this group did not receive any treatment. The testes were collected from the offsprings of all groups at day 30 of postnatal life. The specimens of all groups were prepared for light microscopic examination and the specimens of the 1st and the 2nd groups were also prepared for electron microscopic examination. Flunitrazepam induced delay spermatogenesis in all treated groups as evidenced by the small size of the seminiferous tubules which did not develop central lumena, the seminiferous cells were arranged in 3-4 rows only, the nearly absence of early spermatids and the delay differentiation of supporting cells into Sertoli cells. Flunitrazepam also induced prominent histopathological effects. These effects were severe in the testis of the 2nd group where the seminiferous cells of many tubules were deeply stained, could not be recognized and many of them were degenerated. However, the seminiferous cells of the 3rd group were moderately affected, while those of the 4th group were slightly affected. The interstitial cells of Leydig were markedly affected in all treated groups. They became singly scattered between the seminiferous tubules of the 2nd and 3rd groups or appeared as small collections in the 4th group. The ultrastructural examination of the testis of the 2nd group confirmed the previous effects and revealed that A and B spermatogonia were slightly affected, supporting cells were numerous and moderately affected, while the primary spermatocytes and the interstitial cells of Leydig were the most affected cells