Drug interactions between phenytoin and rosuvastatin on lipid profile, liver functions and oxidative stress biomarkers in irradiated rats

Phenytoin is one of the most commonly used anticonvulsants for treating generalized tonic-clonic seizures and status epileptics. Rosuvastatin is a new generation HMG-CoA reductase inhibitor. This enzyme converts HMG-CoA to mevalonic acid in the cholesterol biosynthetic pathway which is the rate limiting step in cholesterol synthesis. This study was aimed to investigate the possible interactions between phenytoin and rosuvastatin when used together in irradiated rats. The experiments were carried out to investigate the acute effect of each drug individually and in combination with radiation on lipid profile [Total cholesterol, Triacylglycerols, High density lipoproteins, Low density lipoproteins and Very low density lipoproteins, Risk factor, Atherogenic Index], liver function tests [AST and ALT] and oxidative stress biomarkers [MDA, NO and SOD]. Data revealed that, phenytoin in irradiated rats significantly increased serum total cholesterol compared to normal control. Rosuvastatin significantly decreased serum total cholesterol compared to irradiated control. Combination of two drugs significantly increased serum total cholesterol; triacylglycerols and serum VLDL-c levels compared to normal and irradiated rats and significantly increased Atherogenic Index and Risk factor compared to normal control. Phenytoin significantly increased serum ALT level compared to normal and irradiated rats and significantly increased serum MDA and serum NO levels compared to normal rats. But phenytoin significantly decreased MDA and NO levels and significantly increased SOD activity compared to irradiated rats. Rosuvastatin significantly increased serum ALT level compared to normal control but it significantly decreased MDA and significantly increased SOD activity compared to irradiated rats. Combination phenytoin and rosuvastatin in irradiated rats significantly increased serum ALT level compared to normal and irradiated rats and it significantly increased MDA, NO levels but it significantly decreased SOD activity compared to normal control. It could be concluded that administration of phenytoin concurrently with rosuvastatin not recommended in patients receiving radiotherapy as dangerous side effects may be occurred

Protective effects of onion oil and selenium against cisplatin-induced nephrotoxicity and oxidative stress in rats

Nephrotoxicity is an inherent of certain anticancer drugs. This study aimed to assess the protective effect of onion oil and selenium against cisplatin-induced nephrotoxicity in male rats. Cisplatin [5 mg/kg, i.p.] caused significant increases in serum sodium, blood urea nitrogen, serum creatinine, total sodium and potassium excreted in urine, urine volume and lipid peroxides measured as the malondialdehyde content of kidney, with significant decreases in serum total protein, creatinine clearance, reduced glutathione content of kidney and kidney superoxide dismutase activity as compared to the control group. On the other hand, administration of onion oil [100 mg/kg, p.o.] or selenium [1 mg/kg, p.o.] for 14 days with a single cisplatin dose on the 10[th] day ameliorated the cisplatin-induced nephrotoxicity as indicated by the restoration of kidney function and oxidative stress biomarkers. Onion oil and selenium showed protective effects against cisplatin-induced nephrotoxicity

Uterine sarcoma. Clinico-pathological characteristics and outcome

To investigate the clinical and histopathological characteristics, with the prognostic factors, treatment outcome, pattern of relapse, and survival analysis of uterine sarcoma patients. All patients with histologically proven uterine sarcoma were identified using the database at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between January 2000 and December 2012. A total of 36 patients with uterine sarcoma were reviewed. The median age of all patients was 57 years, and the mean age was 57.72 +/- 13.17 years. Carcinosarcoma was reported in 21 patients [58%], leiomyosarcoma in 7 [19%], undifferentiated endometrial sarcoma in 6 [17%], and rhabdomyosarcoma in 2 [6%]. Approximately half of the patients were stages III and IV [28% and 25%], while 15 patients [41%] were stage I; only 2 patients [6%] were stage II. The surgical treatment was hysterectomy and bilateral salpingoophorectomy [H+BSO] plus staging in 18 patients [50%], while in 4 patients [19%], H+BSO plus debulking was performed. Adjuvant chemotherapy was given in 24 [69%] and adjuvant radiotherapy in 5 [14%] cases, At a median follow-up period of 13.5 months, 8 patients [22%] relapsed. The 2-year disease-free survival [DFS] rate was 22% and the 5-year was 14%. In the multivariate analysis, the advanced stages [p=0.015] and lymph vascular invasion [p=0.0001] were associated with poor DFS, while the use of chemotherapy significantly improved the DFS [p=0.027]. The poor outcome of high-grade uterine sarcoma patients was identified, and only one third of patients [30%] survived for 2 years. This finding necessitates the need for more aggressive tools to fight this disease

Treatment planning for high dose rate brachytherapy of cervical cancer based on total dose constraints

To compare the inverse planning optimization based on total dose constraints versus conventional treatment plan [point A planning method] for cervical carcinoma, and evaluate the benefit of CT-based image-guided brachytherapy. We prospectively analyzed data of 10 consecutive patients with cervical cancer treated with external beam radiotherapy to the whole pelvis [45 Gy in 25 fractions] followed by high-dose-rate [HDR] brachytherapy [21 Gy in 3 fractions]. For treatment planning of HDR brachytherapy, the basic equations of the linear-quadratic model were used to calculate the physical dose for each brachytherapy fraction needed to achieve a given total iso-effective dose for the whole treatment. Specific dosimetric parameters are evaluated for high risk [HR CTV], intermediate risk [IR CTV] clinical target volumes, and organs at risk [OARs]. In conventional plans, the HR CTV was well covered in only 15/31, and the IR CTV in 7/31 of the brachytherapy implants, while dose constraints of OARs bladder and rectum were respected in 28/31 and 14/31 implants. After optimization, the HR CTV and IR CTV dose constraints were respected in all the implants, and the bladder and rectum of cases dose constraints were respected in 25/31 and 17/31 of cases. Point A is a poor surrogate of target dose. Significant differences between point doses and dose volume histogram parameters indicate the need for inverse planning in image-guided brachytherapy of cervical cancer

Molecular characterization of rotavirus infection among Egyptian children

Rotavirus is the major etiologic agent of severe diarrhea in children world wide. To study the incidence of rotavirus genotypes circulating in Egypt, one hundred fecal specimens were collected from hospitalized children's with acute diarrhea during Feb.2009 to Jan.2010. Using semi nested multiplex RT-PCR for both 0 and P typing. Rotavirus prevalence was 19% [19/100]. Seasonal distribution of rotavirus was 32% [8/25], 28% [7/25], 12% [3/25], and 4% [1/25] in winter, summer, autumn and spring, respectively. G I-genotype was the most predominant and frequent in all samples, followed by G4 and [19. This study revealed that P-genotypes were rare [5/100]. The detected P-genotypes were restricted to p[l I], p[4], and p[8J. A total of 881bp PCR fragments were sequenced and compared to sequences derived from the corresponding rotavirus genome deposited in GenBank. Phylogenetic tree of Rotavirus segment 9 isolated confirmed that the isolated virus sequencing was most closely related to the previously published sequences from different localities all over the world especially that isolated from Russia, South Africa and, Italy with 97-99% homology. A marked seasonal occurrence of rotavirus, during summer and winter season. G1-genotype was the most predominant and frequent in all samples while P-genotypes were restricted to P[l1], P[8]and P[4]

Protective effects of amlodipine, coenzyme Q10 and their combination on myocardial ischemia/reperfusion injury in rats

Ischemia/reperfusion [I/R] injury is of major clinical relevance during ischemic heart diseases, percutaneous transluminal angioplasty, coronary artery bypass and heart transplantation. Amlodipine, a calcium channel blocker, exhibits antioxidant and antiproliferative activities as well as eNOS activation that could help in cardioprotection following I/R insult. Coenzyme Q10 [CoQ], a mitochondrial coenzyme involved in oxidative phosphorylation, possesses strong antioxidant and lipid peroxyl neutralizing functions. The current study demonstrated the possible cardioprotection of amlodipine [15 mg/kg/day] and CoQ [200 mg/kg/day] alone or in combination against myocardial I/R-induced functional, metabolic and cellular changes. Drugs were administered orally for one week. Rats were then subjected to myocardial I/R [35min/10min]. Heart rates and incidence of ventricular arrhythmias were recorded during l/R progress. At the end of reperfusion, blood samples were collected for estimation of plasma creatine kinase [CK] activity. The left ventricle homogenates were used for determination of lactate, ATP, thiobarbituric acid reactive substances [TBARS], reduced glutathione [GSH] and total nitrate/nitrite [NOx] contents as well as myeloperoxidase [MPO] activity. Finally, histological examination was performed to visualize the possible cellular effects of the drugs. Amlodipine, CoQ and their combination significantly protected against reperfusion-induced tachycardia and decreased the incidence and severity of arrhythmias. Amlodipine afforded a significant degree of protection against plasma CK elevation and myocardial GSH depletion, while it completely protected against myocardial MPO, lactate and TBARS elevation. On the other hand, it failed to defend against ATP depletion and NOx elevation. CoQ provided a significant degree of protection against plasma CK, myocardial MPO, NOx elevation and ATP depletion. It completely protected against GSH depletion, lactate and TBARS elevation. Combination therapy provided significant increase in myocardial ATP and GSH contents and significant decrease in plasma CK activity in comparison with amlodipine monotherapy. It could be concluded that adding CoQ to amlodipine therapy offered remarkable improvement in the cardioprotective effect of amlodipine

Teenage cigarette smokers with schistosoma mansoni: Effect of multifacet management on hepatic and bronchio-alveolar disposition

Schitosomiasis and cigarette smoking are among the common health hazards in young Egyptians worthy of concern. The present study aims to investigate the influence of cigarette smoking and management strategy on serum and branchioalveolar lavage [BAL] parameters in teenage male cases with and without S.mansoni. Certain indices of immuno-inflammatory response, oxidative stress, lipid peroxidation, vasoactive mechanisms and anti-oxidant defense capacity would be evaluated. The study included forty selected cigarette smoker male cases [mean age 15.9 +/- 2.6 years] who were sub-classified equally into two groups involving cases with S.mansoni [G I] and without S.mansoni [G II]. Ten age-matched non Schistosomal individuals non-smokers were included as a control [G Ill]. Biochemical assessment of serum and BAL included the evaluation of cotinine, total thiols, ceruloplasmin, uric acid, lipid peroxidation product, interleukin-5, eotaxin, RANTES, surfactant proteins A and D, procollagen Ill, trace elements and hepatocyte growth factor. Management strategy was evaluated after six months of quitting smoking and treatment with praziquantel, Nigella sativa, Garlic extract and antioxidants. The result showed that alterations in assessed parameters were greatly influenced by cigarette smoking more profoundly in cases with S mansoni. The management strategy identified the alleviation of reactive oxygen species [ROS] determinants on immuno-inflammatory response with beneficial outcome in assessed parameters. In conclusion, the proposed strategy for management of smoking in teenagers especially those with liver disposition was effective and identified the greater benefits of early intervention alongside smoking cessation

Antioxidative, hypolipidemic and hormonal modulating activity of green tea in iron overloaded rats

Objective: to study the efficacy of green tea extract against iron-induced oxidative stress, dyslipidemia and hormonal changes in rats compared with those of silymarin

Subjects: 54 adult male albino rats were divided into nine groups. The first three groups were considered as control groups [negative control C[1], silymarin control group C[2] and green tea control group C[3]]. The other three groups were treated with i.p. injection of ferrous sulphate [30 mg/ Kg/day]. The fourth group was considered as positive control [T[4]] while the fifth and sixth groups [T[5]andT[6]] received daily oral dose of silymarin [20 mg/kg/day] and green tea [2ml/rat/day], respectively, for ten consecutive days. The last three groups were fed the control diet for seven days, where the eighth and ninth groups were given daily oral dose of silymarin and green tea, respectively. On the seventh day, these groups were injected with a single i.p. dose of ferrous sulphate [300mg/Kg]. The seventh group was considered as positive control [T[7]] while the eighth and ninth groups [T[8]andT[9]] were continuously treated with the daily oral dose of silymarin and green tea. respectively for other three days. The experiment lasted for ten days

Methods: at the end of the experimental period, the blood samples were collected from all groups and blood hemoglobin level was estimated. Serum iron and total iron binding capacity [TIBC] were determined by spectrophotometric analysis and serum ferritin level was estimated using ELISA technique. Serum vitamin A and E as well as serum thiobarbituric acid reactive species [TBARS] levels were assayed. Serum total cholesterol, triacylglycerols [TAG] and HDL-Ch levels were also estimated. Serum creatine kinase MB [CK-ME] activity and troponin I levels were also determined. Plasma corticosterone and serum leptin levels were estimated using ELISA

Results: administration of green tea extract [GTE] to iron overloaded rats effectively decreased lipid peroxides to the same degree as silymarin. It significantly increased serum alpha-tocopherol level which was not changed by silymarin. Green tea extract decreased serum iron, ferrtin and hemoglobin as silymarin did when both agents were compared to the untreated iron overloaded rats. Regarding the lipid profile, administration of GTE to normal rats significantly decreased serum TAG compared to the control rats. For iron injected rats; GTE decreased TAG by 22.5%, while HDL-Ch level showed significant increase by GTE compared to untreated iron overloaded rats. Iron overload produced significant increase in creatine kinase MB [CK-MB] and slight increase in troponin I TnI s GTE administration, significantly decreased CK-MB and normalized TnI approximately to the same degree as silymarin. With respect to hormonal patterns, administration of GTE to iron overloaded rats like silymarin, induced slight decrease in corticosterone level compared to untreated rats. Although GTE caused no change in serum leptin for iron overloaded rats, it significantly decreased its level in normal rats [C3] compared to that of the control rats [C1]

Conclusion: in conclusion, green tea may exert its therapeutic role against oxidative stress produced by iron overload via its antioxidant properties , metal chelating activity, hypolipidemic action and hormone modulating capacity. Thus green tea extract possesses multifunctional manifestations

Sternalis: an anatomic variant of chest wall musculature

To study the prevalence of sternalis muscle in the Kingdom of Saudi Arabia [KSA] and resolve the question of its genesis by studying the innervation of this uncommon variant of anterior chest wall musculature. A morphological study of 75 adult cadavers of both sexes was carried out over a 5-year period by macroscopic dissection. We also retrospectively studied the medical records of 1580 adult females who had undergone screening and diagnostic mammographic imaging at King Khalid University Hospital, Riyadh, KSA, from 1997 to 2001. Out of 75 cadavers studied, 3 cases of sternalis muscle were observed. Two adult male cadavers had well developed bilateral sternalis muscles whereas one female cadaver exhibited right sided unilateral sternalis. All 5 sternalis muscles were positioned vertically, in a parasternal position superficial to the medial part of pectoralis major and innervated by branches of intercostal nerves. None of the 1580 women, however, who had undergone mammographic imaging were found to be sternalis positive. Consistent with other geographic populations of the world, the frequency of sternalis in KSA is approximately 4%; however, its innervation by the intercostal nerves, as observed in our study is not common. This study highlights the need for familiarity with sternalis, which may mimic a focal density in medial breast craniocaudal mammograms and may be encountered during reconstructive surgery of breast and chest wall

Mummification to plastination. revisited

A brief summary of the history of anatomy is presented with particular focus on important scientists who contributed significantly to the development of anatomical education and recognition of anatomy as a discipline of science. An attempt has been made to review the history of preservation of human cadavers from earliest mummification methodology used by ancient Egyptians to the most modern technique of embalming and plastination of human cadavers, developed by Von Hagens during the period from 1979 to 1987. The need for use of modern teaching aids for instruction of topographic anatomy is also highlighted

Detection of an early marker of atherosclerosis among non-insulin dependent-diabetic patients

An early marker of subclinical arteriosclerosis, the increased intimal-medial thickness [IMT] of the common carotid artery was measured by B-mode ultrasound in twenty non-diabetic and thirty non- insulin- dependent diabetic patients [ten newly diagnosed and twenty well established diabetics]. This marker was compared in non- diabetic and diabetic subjects to evaluate its correlation with some cardiovascular risk factors, and duration of diabetes. In addition, body mass index [BMI], waist to hip ratio [WHR], blood pressure, glycosylated hemoglobin [HbAic] and fasting concentrations of plasma glucose, serum lipids and serum insulin were measured in all subjects. In conclusion, diabetes is characterized by a greater thickness of the carotid artery, which lead to increased risk of arteriosclerosis. Also, central adiposity is considered as a predictor of IMT in non- diabetic individuals

effect of diazepam on the hypotensive action of captopril in anasthetized normotensive rats-the role of prostaglandins and angiotensin I converting enzyme

The effects of acute administration of captopril [1 mg/kg] and/or diazepam [5 mg/kg] on blood pressure and heart rate of normotensive and indomethacin pretreated rats as well as the dose-response curves of angiotensin I and II were investigated. The subacute administration of captopril and/or diazepam on blood pressure and heart rate were also studied. In the acute study diazepam prolonged the duration of the captopril-induced hypotension, while captopril abolished the diazepam-induced bradycardia. These actions have not been affected by pretreatment with indomethacin. The dose-response curve of angiotensin II was not affected by administration of captopril and/or diazepam, while that of angiotensin I was shifted to the right in response to captopril and/or diazepam in synergetic manner. Subacute administration of captopril significantly reduced blood pressure and heart rate. Similarly, subacute treatment with diazepam induced slight reduction in blood pressure and heart rate and reduced the hypertensive action of captopril. Captopril abolished the diazepam-induced bradycardia. The present study revealed that diazepam prolongs the hypotensive action of captopril, possibly by a synergetic inhibitory effect on angiotensin I converting enzyme with no saralasin-like or prostaglandin-synthesis modulating action

Histopathological and morphometric study of liver cell dysplasia in comparison with other chronic hepatic lesions

27 cases of cirrhosis with liver cell dysplasia [LCD] were evaluated and the results were compared with 11 cases of cirrhosis without LCD, 12 cases of chronic hepatitis, 15 cases of hepatocellular carcinoma and 5 cases of normal control. The morphometric study showed that the nuclear-cytoplasmic, nucleolar cytoplasmic and nucleolar-nuclear ratios were significantly higher in LCD than that observed in non neoplastic group while, the nuclear-cytoplasmic and nucleolar cytoplasmic ratios of hepaocellular carcinoma were significantly higher than those in LCD but the latter had nucleolar-nuclear ratio similar to that of neoplastic cells. These results suggested the pre- malignant nature of LCD and of important clinical appliction in regular follow up of the patients with LCD

Evaluation of antileprotic drugs in the treatment of rhinoscleroma

This study has been conducted on 30 patients suffering from rhinoscleroma. All patients have been given antileprotic drugs [dapson 100 mg every day and lamprene 100 mg every other day] for 3 months to estimate the effect of these drugs on this resistant disease. Histopathological examination of biopsy specimens taken before and after the treatment period was done to confirm the clinical results. Antileprotics showed very encouraging results in the treatment of rhinoscleroma where 26 out of 30 patients [86.67%] showed both clinical and histopathological improvement after treatment with antileprotic drugs for 3 months

Continuous epidural infusion of fentanyl for post operative pain relief

The effects of a continuous epidural administration of fentanyl on pain and ventilation were studied in 20 patients scheduled for upper abdominal surgery. In each subject epidural fentanyl was given by a bolus dose of 1 mug/kg followed by a continuous infusion of 1 mug/kg/h over 18 hours. Adequate pain relief was achieved in all patients during fentanyl administration. No significant change in ventilation was noted. These results suggested that a continuous infusion of fentanyl is a technique of analgesia that can provide adequate pain relief without ventilatory depression

Management of chronic pain of knee with acupuncture [MEA]

Acupuncture was performed in 40 patients with chronic pain of the knee joint more than 6 months due to arthralgia of the knee, from both sexes [10 males and 30 females] and different ages to relief pain and to assess the degree of articular mobility of knee joint. All patients were assessed as regards analgesia, articular mobility, pulse, BP, respiratory rate and levels of cortisol, while sugar and serum potassium were estimated. It was found that acupuncture produced significant analgesic effect with improvement of articular mobility. Regarding pulse rate, BP and respiratory rate, there were no effects observed. Serum cortisol level showed significant decrease following acupuncture therapy, glucose and serum potassium showed insignificant changes

Clinical assessment of laryngeal mask airway in intra-ocular ophthalmic surgery in comparison with tracheal intubation

Clinical studies were performed on 20 patients from both sexes and different ages [55 - 65 years] to compare between the effects of laryngeal mask airway and tracheal intubation on the intraocular ophthalmic surgery under general anesthesia. All patients were assessed as regards the changes on B.P., H.R. and intraocular pressure before induction of anesthesia, after induction of anesthesia and after insertion of the laryngeal mask or tracheal intubation. The development of coughing, straining or breath holding at the termination of anesthesia was recorded. Any postoperative sorethroat in both groups was recorded. Patients with raised intraocular pressure, history of reflux or hiatus hernia and patients with decreased lung compliance or increased airway resistance were excluded from the study. The changes in intraocular pressure, heart rate and mean arterial pressure after the insertion of the laryngeal mask airway or the tracheal tube were not significantly different. However, at the end of surgery, a significantly higher percentage of patients with a tracheal tube coughed [80%] react to head movement [70%] and suffered breath-holding [40%], in addition, significantly more patients in tracheal tube group complain of sorethroat [30%] [P < 0.05]

Lumbar epidural fentanyl infusion versus intravenous for post thoracotomy pain relief

Fifty patients undergoing thoracic surgery were randomly allocated to receive either a continuous lumbar epidural infusion of fentanyl or intravenous infusion fentanyl for postoperative analgesia. The infusion rate was adjusted to optimize analgesia. Quality of analgesia was assessed by the total dose of fentanyl administered VAS and VRS in comparison between the two groups. It was found that both lumbar epidural and I.V. fentanyl provide satisfactory analgesia, but fentanyl requirements were less when given via the epidural route, [1882 +/- 3, 2596 +/- 791, ug], [P < 0.05]. This suggests a direct spinal cord site of action for lumbar epidural fentanyl