Study of electroencephalography in people with generalized epilepsy in a Saudi population.

BACKGROUND: Electroencephalography (EEG) remains a vital tool in the diagnostic evaluation of patients with epilepsy (GE), however, there is scarcity of information on the yield and potential clinical variables that are associated with EEG abnormalities in people with GE. OBJECTIVE: The study aimed to evaluate the yield and pattern of EEG abnormalities in patients with GE with the view to determining factors that are independently associated with abnormal EEG in them. METHODS: We characterized EEG features and evaluated associated factors in a sample of people with GE in a Saudi population. Standard definition of interictal epileptiform discharges was used. RESULTS: A total of 1105 (77%) out of 1436 GE patients had EEG. Five hundred and ninety-five (53.85%) patients had abnormal EEG. Factors associated with EEG abnormalities before adjustment for confounders were age, gender, duration of epilepsy, and seizure frequency. However, only frequency of seizure (P = 0.0018), gender (P < 0.0001), and age (P < 0.0001) were independently associated with EEG abnormalities. CONCLUSION: The study showed a modest yield (54%) of abnormal EEG in the cohort of patients with GE. Frequency of seizure, age, and gender, independently predicted the presence of EEG abnormality in people living with GE.

Penile autotransplantation in rats: An animal model.

CONTEXT: Penile allotransplantation might be a viable option for patients who need penile reconstruction. AIMS: A successful autotransplantation rat model is the first step toward proceeding for allotransplantation. We herein evaluate autotransplantation following transaction of the rat penis just distal to the urethral bulb. SETTINGS AND DESIGN: Experimental animal study. MATERIALS AND METHODS: Five Sprague-Dawely rats weighing 520 g (SD 19) were used. Utilizing a magnification of 6-40, transection and immediate anastomosis of the tunica albuginea, urethra, dorsal vein and nerves were carried out. Vesicostomy was made to divert urine. The glandular skin was sutured to the perineum and the abdominal wall was closed in layers. STATISTICAL ANALYSIS USED: Descriptive statistics. RESULTS: Average surgery time was 8 h. The first two rats had no vesicostomy and died in the first postoperative day from retention. Three rats tolerated well the procedure and survived to the end point. One rat was sacrificed at day 10 and histopathology showed 30-50% necrosis of the implanted penis. Another rat was sacrificed at day 20 and showed normal cavernous tissue. The fifth rat was sacrificed 3 months postoperatively and showed evidence of moderate corporal fibrosis. Urethral fistula and necrosis of corpus spongiosum, dorsal nerve necrosis and dorsal vein occurred in all animals. CONCLUSIONS: Penile autotransplantation in rats is feasible and provides the basis for evaluation of the corpora cavernosa in an allotransplantation model. Long-term urethral continuity and dorsal neurovascular bundle survival in this model is difficult to establish.

Role of Nigella sativa and a number of its antioxidant constituents towards azoxymethane-induced genotoxic effects and colon cancer in rats.

This study examined the chemopreventive effect of Nigella sativa and some of its antioxidant constituents on a number of colon cancer biomarkers in rats induced with azoxymethane (AOM). Sixty male Sprague-Dawley rats were randomly assigned into ten subgroups: vehicle (1-5) and experimental (6-10). The rats in each group were fed one of the following diets: basal diet, (200 mg/kg) Nigella sativa, (0.2 mg/kg) selenium, (1.2 mg/kg) all-trans-retinol plus (100 mg/kg) DL-alpha-tocopherol and (10 mg/kg) thymoquinone, respectively. Only rats in subgroups 6-10 were injected with AOM (15 mg/kg) once per week for 2 weeks. Both groups were fed their respective diets for 5 weeks. Then they were killed and examined for colonic aberrant crypt foci (ACF). Our result showed that only vitamin supplementation was effective on ACF. Nigella sativa revealed inhibitory effects only on DNA damage (day 34) in the AOM-treated rat group. Alternatively, selenium, thymoquinone and vitamins inhibited the MDA content in the liver. Although the exact mechanisms involved in the protective role of Nigella sativa against the initiation of colon carcinogenesis are not clearly understood, the results suggest that its inhibitory effects might depend on the combined competitive inhibition of various antioxidant constituents of this plant.

Bortezomib (Velcade) induces p27Kip1 expression through S-phase kinase protein 2 degradation in colorectal cancer.

S-phase kinase protein 2 (SKP2), an F-box protein, targets cell cycle regulators including cycle-dependent kinase inhibitor p27Kip1 via ubiquitin-mediated degradation. SKP2 is frequently overexpressed in a variety of cancers. We investigated the role of SKP2 and its ubiquitin-proteasome pathway in colorectal carcinoma using a panel of cell lines, clinical samples, and the NUDE mouse model. Using immunohistochemical analysis on a large tissue microarray of 448 samples, an inverse association of SKP2 expression with p27Kip1 protein levels was seen. A colorectal cancer (CRC) subset with high level of SKP2 and low level of p27Kip1 showed a decreased overall survival (P = 0.0057). Treatment of CRC cell lines with bortezomib or expression of small interfering RNA of SKP2 causes down-regulation of SKP2 and accumulation of p27Kip1. Furthermore, treatment of CRC cells with bortezomib causes apoptosis by involving the mitochondrial pathway and activation of caspases. In addition, treatment of CRC cells with bortezomib down-regulated the expression of XIAP, cIAP1, and survivin. Finally, treatment of CRC cell line xenografts with bortezomib resulted in growth inhibition of tumors in NUDE mice via down-regulation of SKP2 and accumulation of p27Kip1. Altogether, our results suggest that SKP2 and the ubiquitin-proteasome pathway may be potential targets for therapeutic intervention for treatment of CRC.

Crural tunica albuginea autograft for corporoplasty: an experimental animal study of hemodynamic, histopathological, and molecular effects in the long term.

INTRODUCTION: Correction of penile deformity caused by Peyronie's disease by a variety of grafts varies in success. A long-term follow-up shows a significant number of graft scarring and erectile dysfunction. The clinical success of autologous crural tunica albuginea graft (TAG) has not resulted in wide application. AIM: To identify in healthy baboons the limitations and merits of autologous crural TAG over 1 year in a way difficult to pursue in humans. METHODS: Under general anesthesia, eight sexually active adult baboons underwent pharmacological cavernosometry (CM) and cavernosography. TAG from crus was implanted in the distal penile shaft. After 6 months, six animals were reevaluated and two were sacrificed, and the penises were excised. After 1 year, the remaining six animals were evaluated and sacrificed. The TAG and underlying corpus cavernosum (CC) were examined histologically and by Western blot analysis for nitric oxide synthase (NOS), neuronal (nNOS), endothelial (eNOS) and inducible (iNOS) isoforms, and transforming growth factor-beta1 (TGF-beta1). MAIN OUTCOME MEASURES: Sexual activity, CM, cavernosography, histopathology, and Western blot analysis. RESULTS: All animals resumed normal sexual activity 1 month postsurgery. Cavernous pressure was comparable before, at 6 months, and 1 year after surgery. A cavernovenous insufficiency developed in four animals at 6 months, and ceased in two at 1 year. Penile angulation (<20 degrees) was seen in three animals at 6 months, and an additional two at 1 year. Histologically, TAG was indistinguishable from the adjacent tunica with no fibrosis. In CC, iNOS and nNOS decreased at 1 year, whereas there was no change in TGF-beta1 levels. In TAG, there was no significant change in TGF-beta1 and eNOS levels, but there was a significant decrease in iNOS at 1 year. CONCLUSION: Autologous free TAG is associated with normal sexual activity, minimal hemodynamic changes, excellent histological outcome, and no rise in iNOS or TGF-beta1. However, cavernovenous insufficiency, mild penile angulation, and decreased nNOS persisted at 1 year.

Glucocorticoids do not protect against the lethal effects of experimental heatstroke in baboons.

The mortality and neurological morbidity in heatstroke have been attributed to the host's inflammatory responses to heat stress, suggesting that anti-inflammatory therapy may improve outcome. We tested the hypothesis that a high dose of dexamethasone protects baboons against the lethal effects of heatstroke. Ten anesthetized baboons (Papio hamadryas) were assigned randomly to dexamethasone (n = 5) or control group (n = 5). Dexamethasone (2 mg/kg i.v.) was administered in four divided doses every 6 h starting immediately before heat stress and continuing during cooling. All animals were heat-stressed in a prewarmed neonatal incubator at 44 degrees C to 47 degrees C until systolic blood pressure fell less than 90 mmHg and then cooled passively at the ambient temperature. Mortality and neurological morbidity were noted, and biochemical markers of tissue injury/organ dysfunction were determined. Circulating interleukin (IL) 6 and complement components (C3 and C4) were measured sequentially. All heat-stressed animals had systemic inflammation indicated by increased plasma IL-6 and decreased C3 and C4 levels. Dexamethasone attenuated the complement system activation and maintained a higher plasma concentration of IL-6, with a significant augmentation of arterial blood pressure. Dexamethasone did not prevent the occurrence of severe heatstroke but unexpectedly aggravated significantly the tissue injury and multiorgan system dysfunction. Two animals (40%) in the control group and one in the steroid group survived (P > 0.05). Dexamethasone failed to protect the baboons from the lethal effects of heatstroke. These results do not support clinical testing of corticosteroids as beneficial in preventive or therapeutic strategies for the treatment of heatstroke in humans.

Experimental heatstroke in baboon: analysis of the systemic inflammatory response.

The objective of this study was to analyze the pattern of the inflammatory response to heatstroke in an experimental baboon model with a view to identifying potential target for therapeutic interventions. Blinded analysis of plasma collected from 12 juvenile baboons (Papio hamadryas) in heatstroke was used. Eight anesthetized animals were heat-stressed in an incubator at 44 degrees C to 47 degrees C until rectal temperature was 42.5 degrees C (moderate heatstroke; n = 4) or systolic arterial pressure fell to <90 mmHg (severe heatstroke; n = 4) and were allowed to recover at room temperature. Four sham-heated animals served as a control group. We performed sequential measurement of cytokines. The rectal temperature on completion of heat stress was 42.5 degrees C +/- 0.0 degrees C and 43.3 degrees C +/- 0.1 degrees C in moderate and severe heatstroke, respectively. Heat stress elicited early, simultaneous release of anti-inflammatory cytokines and chemokines (IL-10, IL-1ra, sTNFr I and II, and IL-8). Circulating levels of IL-12p40 were significantly decreased, whereas TNFalpha, IL-1beta, and IL-4 were below the detection limit in all animals. No baboon survived severe heatstroke; there was neurological morbidity without mortality in moderate heatstroke. Nonsurvivors displayed significantly greater activity/alterations in inflammation markers than survivors. Sham-heated animals had no evidence of inflammation activation. These results show that heatstroke activates complex systemic inflammatory and regulatory responses associated with outcome. Further definition of this ambivalent response is needed before identification of target of successful modulation may become possible.

A pressure overload model to track the molecular biology of heart failure.

OBJECTIVES: Pressure overload plays an important role in left ventricular remodelling and the development of heart failure. The underlying molecular mechanisms behind these processes are poorly understood at the myocyte level. To investigate this, we developed an ovine model of pressure overload-induced heart failure, in which serial left ventricular biopsies were obtained. METHODS: Adult male sheep were chronically banded with a novel variable aortic constriction device. This was progressively inflated via a subcutaneous port to increase left ventricular afterload. The animals were monitored clinically and echocardiographically. Serial left ventricular endomyocardial biopsies were obtained via the right external carotid artery under fluoroscopic guidance. They were used to measure mRNA expression of the genetic regulators of apoptosis by reverse transcription polymerase chain reaction. In a subset of the animals, once left ventricular failure had been established, the constriction device was deflated to produce unloading of the left ventricle. RESULTS: Ten of the 17 sheep banded developed left ventricular failure. Over the first 3-4 weeks, left ventricular mass index increased acutely (88+/-18 vs. 44+/-10 g/m(2), P<0.01) followed by gradual left ventricular dilatation (diastolic left ventricular internal diameter 4.1+/-0.7 vs. 3.2+/-0.3 cm, P<0.01). Ventricular function remained stable until 7-8 weeks postoperatively, when there was significant deterioration (fractional shortening 17+/-8 vs. 40+/-8%, P<0.01) associated with clinical heart failure. Expression of the pro-apoptotic genes (bax and Fas) increased significantly following inflation of the constriction device and persisted through the transition to left ventricular failure. Following deflation of the constriction device, myocardial contractility gradually improved over a 3 week period (fractional shortening 32+/-1 vs. 17+/-8%). CONCLUSIONS: Progressively increasing the afterload on the left ventricle produces a clinical and echocardiographical picture of chronic heart failure. Obtaining myocardial tissue during this transition will allow the molecular correlates of pressure overload-induced heart failure and potential myocardial recovery to be investigated.