Search

Background: Acetaminophen (APAP) hepatotoxicity is characterised by an extensive oxidative stress due to depletion of glutathione (GSH), which results in massive lipid peroxidation and subsequent liver injury. The current paradigm suggests that mitochondria are the main source of reactive oxygen species (ROS), which impair mitochondrial function and are responsible for cell signalling resulting in cell death. This study was designed to compare the potential impact of thymoquinone (THQ), and/or curcumin (CURC) on liver injury induced by APAP toxicity in rats.Materials and Methods: Serum levels of alanine transaminase, aspartate transaminase, total bilirubin, and total protein were measured. In addition, liver nitric oxide (NO), malondialdehyde, reduced glutathione (GSH), and superoxide dismutase (SOD) were estimated. Moreover, these biochemical parameters were confirmed by histopathological and immunohistochemical investigations for the expression of thioredoxin, iNOS and caspase 3.Results: Acetaminophen toxicity elevated most of the above-mentioned parameters but decreased GSH, SOD, and total protein levels. Histologically, liver sections demonstrated liver injury characterised by hepatocellular necrosis with nuclear pyknosis, karyorrhexis and karyolysis. Immunohistochemical study revealed increased expression of iNOS and caspase 3 proteins, while the thioredoxin protein expression was decreased.Conclusions: Treatment with the THQ and CURC regulated the biochemical and histopathological alterations induced by APAP toxicity. It was concluded that the combination strategy of THQ and CURC might be considered as a potential antidote in combating liver injury induced by APAP with minimal side effects. [ABSTRACT FROM AUTHOR]

Acetyl salicylic acid and glutamic acid complex prepared by freeze-drying technique was proposed as a novel oral drug delivery system. The complex was analyzed by using differential scanning calorimetry (DSC), electron microscope, ¹H nuclear magnetic resonance (¹H NMR), mass spectrometry and fourier transform infrared (FTIR). The results revealed a formation of an ionic type complex between acetyl salicylic acid and glutamic acid in a molar ratio of 1:1. In-vitro dissolution testing of the formed complex was performed at pHs of 1.2 and 6.8. The results showed a complete dissolution of the complex within ten minutes. The effect of complex on the gastric mucosal tissues showed that the mucosal epithelium appeared normal (intact) without any change. The present results confirmed that acetyl salicylic acid glutamic acid complex is a promising and safe delivery system that can be utilized for oral administration. [ABSTRACT FROM AUTHOR]

Objective: To use intensive regimen of pulse steroid in the severe forms of Alopecia areata., Methods: This prospective randomized study was conducted at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between 2003 to 2009. Patients with Alopecia universalis, Alopecia totalis, or Alopecia ophiasis were assigned to one of the 3 treatment groups: Group A received oral mega pulse methylprednisolone (MP) for 3 consecutive days once every 2 weeks for 24 weeks; Group B received 2 consecutive daily pulses every 3 weeks; and Group C received 3 consecutive daily pulses every 3 weeks. Patients who showed regrowth of 75% or more at 24 or 36 weeks continued their treatment, while intervals were increased gradually., Results: Forty-two patients were included in this study, and 52.4% of them had atopic diathesis, while 35.7% had autoimmune thyroiditis. At 36 weeks, 12 (28.6%) patients had adequate response, 9 (21.4%) had inadequate response, and 21 (50%) patients had poor response. The response rate shows no statistically significant difference between treatment groups. There were statistically significant differences in age of onset, duration of the disease, and presence of subclinical hypothyroidism between different response groups. At follow-up: 13 (38.2%) patients relapsed; 5 (14.7%) patients developed moderate hair fall; 3 (8.8%) patients developed mild hair fall; 7 (20.1%) patients maintained their hair regrowth; and 6 (17.6%) patients were lost follow up. It was relatively well-tolerated among groups B and C., Conclusion: Oral mega pulse MP use in severe forms of Alopecia areata has relative efficacy and tolerance but with high relapse rate.

Objective: To report our experience of varied presentations and diverse histopathological spectrum of parotid gland malignancies., Methods: This retrospective analysis incorporated patients with histological evidence of malignant parotid tumors at King Khalid University Hospital, Riyadh, Saudi Arabia over a 20-year period from 1984 through 2004. The medical records of these patients were analyzed for their demographic characteristics, clinical features, operations performed, and pathological diversity., Results: Thirty-two patients comprised this study group. There is a male preponderance over females with a ratio of 2.2:1 (22 men and 10 women) and mean age of 51.8 (range 28-81 years). A painless lump was the most frequent clinical manifestation observed in 23 (71.8%) patients followed by facial nerve dysfunction in 14 (43.7%) patients. Parotidectomy was performed in 22 (68.7%) patients: 16 superficial and 6 total. A partial facial nerve sacrifice was undertaken in 14 (43.7%), and total nerve sacrifice in 9 (28.1%) patients. Four (12.5%) patients presented with cervical lymph node metastases necessitating radical neck dissection. Nine (28.1%) patients had mucoepidermoid carcinoma, 8 (25%) adenoid cystic carcinoma, 6 (18.7%) adenocarcinoma, not otherwise specified, and 2 (6.2%) were reported to have carcinoma in pleomorphic adenoma. Twenty (62.5%) specimens revealed high-grade aggressive lesions, and out of these, 19 (59.3%) patients presented with stage III/IV disease., Conclusion: Malignant parotid tumors are exceedingly rare, occurring at a relatively earlier age group with male preponderance, and invariably declare at a late clinical stage in our community. Histopathological features hallmark a locally advanced disease with an aggressive behavior.

Objective: To investigate the impact of tetrahydrobiopterin (BH4) supplementation on the markers of inflammation, and on the histological picture of the kidney in chronic renal failure C-reactive protein (CRF) induced in rats by subtotal nephrectomy (SNx)., Methods: This study was performed at the Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia during the period from December 2005 to January 2007. Chronic renal failure was induced by 5/6 SNx in 20 male Wister rats, and another 10 rats were sham operated by flank incision and served as controls. Ten SNx rats received 10mg kg-1 BH4 intraperitoneally daily for 4 weeks. Plasma C-reactive protein (CRP), interlukin-6 (IL-6), malondialdehyde (MDA), and kidney functions were measured in all rats. Histopathological examination of the kidney tissues was also performed., Results: Untreated CRF rats showed significant elevation of plasma CRP, IL-6, and MDA levels, and significant decrease in plasma albumin and total protein levels, tubuloglomerular fibrosis and, interstitial tubular infiltration with inflammatory cells in comparison with the sham-operated rats. Tetrahydrobiopterin treatment decreased CRP, IL-6, and MDA levels, and decreased tubuloglomerular fibrosis and interstitial inflammation in treated CRF rats., Conclusion: Supplementation with exogenous BH4 decreased markers of inflammation and protected the kidney against post-renal mass reduction histologic damage. Restoration of intracellular BH4 balance could normalize nitrous oxide production. Therefore, BH4 might be a promising strategy in attenuating inflammation in CRF. This may decrease endothelial dysfunction and limit the associated cardiovascular morbidity and mortality of this disease.