Uranium induces apoptosis in lung epithelial cells

Uranium is a naturally occurring radioactive material present everywhere in the environment. It is toxic because of its chemical or radioactive properties. Uranium enters environment mainly from mines and industry and cause threat to human health by accumulating in lungs as a result of inhalation. In our previous study, we have shown the effectiveness of antioxidant system response to the oxidative stress induced by uranyl acetate (UA) in rat lung epithelial (LE) cells. As part of our continuing studies; here, we investigated the mechanism underlying when LE cells are exposed to different concentration of UA. Oxidative stress may lead to apoptotic signaling pathways. LE cells treated with 0.25, 0.5 and 1 mM of UA results in dose and time-dependent increase in activity of both caspases-3 and -8. Increase in the concentration of cytochrome-c oxidase in cytosol was seen in LE cells treated with 1 mM UA as a result of mitochondria membrane permeability. The cytochrome-c leakage may trigger the apoptotic pathway. TUNEL assay performed in LE cells treated with 1 mM of UA showed significant incorporation of dNTPs in the nucleus after 24 h. In the presence of the caspase inhibitors, we observed the significant decrease in the activity of caspases-8 and -3 in 0.5 and 1 mM UA-treated LE cells.     

The unequal burden related to the risk of oral cancer in the different regions of the Kingdom of Saudi Arabia

OBJECTIVES: To estimate the burden and risk of oral cancer in Saudi Arabia and highlight differences between regions. METHODS: Using the National Cancer Registry Saudi Arabia, data was collated on numbers of cases of oral cancer (1996-1998) by site, age group, gender and region, plus relative frequencies of all cancer cases. Using Globocan, age-standardised rate (ASR) of oral cancer in Saudi Arabia was compared with five other neighbouring countries in the region. RESULTS: A total of 208 lip, mouth and tongue cancers for men and 209 for women were reported to the registry during this period. ASR of oral cancer was 1.81/100,000 for males and 2.13/100,000 for females. It was ranked 15th most common cancer for males and 11th for females, with a ratio of 1:1 and median age at diagnosis of 62 years. Very wide regional disparities in the incidence of oral cancer were found, with an almost thirty-fold difference in ASR between the regions with the lowest and highest rates. Jizan Region had the highest ASR (6.2/100,000 for males and 9.82/100,000 for females). Here oral cancer was ranked 2nd for males and 1st for females, with a ratio of 0.73:1 and the median age at diagnosis for females was lower. The third highest ASR (4.48/100,000) was found in females in Najran. In these two high incidence regions oral cancer was commonly reported on the gingiva. CONCLUSIONS: Overall the burden and risk of oral cancer in Saudi Arabia are not large. However, cancer of the oral cavity is a significant public health problem for the residents of Jizan and the women of Najran. Saudi females in both these regions have a higher burden of oral cancer.     

An initial assessment of the systemic pharmacokinetics of botulinum toxin

Botulinum toxin is an extraordinarily potent molecule that has an unusually long duration of action. Despite this, there is little information available on natural mechanisms for metabolism or elimination and virtually no information on pharmacologically induced mechanisms for metabolism and elimination. Therefore, a number of experiments were performed on laboratory animals that addressed two major issues: 1) the effect of blood on the structure, function, and biologic half-life of the toxin, and 2) the effect of neutralizing antibodies on half-life and elimination of circulating toxin. In the first series of studies, the metabolic transformation of toxin was assessed by incubating it in blood for varying lengths of time. At each time point, aliquots were examined to determine the amount of toxin, the structure of toxin, the catalytic activity of toxin, and the neuromuscular blocking activity of toxin. This work demonstrated that blood did not alter any characteristic of the toxin molecule. Experiments were also done in which toxin was administered to mice and rats at doses that produced clinical poisoning. The results demonstrated that the elimination half-life for native (nonmetabolized) toxin in blood and serum was 230 to 260 min. During the second series of studies, the rate of elimination of circulating toxin was studied in the presence of antibodies directed against the carboxyl-terminal half of the toxin molecule. This work demonstrated that neutralizing antibodies 1) enhanced clearance of toxin from the circulation and 2) enhanced tissue accumulation of toxin, particularly in liver and spleen.     

Porcine buccal mucosa as in vitro model: Effect of biological and experimental variables

Porcine buccal mucosa has been used as an in vitro model to assess the potential of delivering a molecule via the transbuccal route. However, permeation studies across porcine buccal mucosa show high variability due to various experimental and biological factors. The variability associated with the use of different mucosal regions, tissue storage conditions and tissue processing methods on drug permeation was investigated in this study. The permeability of model diffusants was significantly higher in the region behind the lip when compared to the cheek region because the latter has a thicker epithelium. Porcine buccal mucosa retained its integrity in Kreb's bicarbonate ringer solution at 4°C for 24 h while many other storage conditions resulted in loss of epithelial integrity. Separation of the epithelium from underlying connective tissue either surgically or by heat treatment resulted in an epithelial thickness of approximately 150 µm. Separation of epithelium from the underlying connective tissue by heat treatment did not adversely affect its permeability and integrity characteristics. Investigation of these important biological and experimental variables provides guidance for conducting in vitro transbuccal permeation studies. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1265–1277, 2010     

Haemosuccus pancreaticus: diagnostic and therapeutic challenges

Background:

Haemosuccus pancreaticus (HP) is a rare cause of upper gastrointestinal bleeding. The objective of our study was to highlight the challenges in the diagnosis and management of HP.

Methods:

The records of 31 patients with HP diagnosed between January 1997 and June 2008 were reviewed retrospectively.

Results:

Mean patient age was 34 years (11–55 years). Twelve patients had chronic alcoholic pancreatitis, 16 had tropical pancreatitis, two had acute pancreatitis and one had idiopathic pancreatitis. Selective arterial embolization was attempted in 22 of 26 (84%) patients and was successful in 11 of the 22 (50%). Twenty of 31 (64%) patients required surgery to control bleeding after the failure of arterial embolization in 11 and in an emergent setting in nine patients. Procedures included distal pancreatectomy and splenectomy, central pancreatectomy, intracystic ligation of the blood vessel, and aneurysmal ligation and bypass graft in 11, two, six and one patients, respectively. There were no deaths. Length of follow-up ranged from 6 months to 10 years.

Conclusions:

Upper gastrointestinal bleeding in a patient with a history of chronic pancreatitis could be caused by HP. Diagnosis is based on investigations that should be performed in all patients, preferably during a period of active bleeding. These include upper digestive endoscopy, contrast-enhanced computed tomography (CECT) and selective arteriography of the coeliac trunk and superior mesenteric artery. Contrast-enhanced CT had a high positive yield comparable with that of selective angiography in our series. Therapeutic options consist of selective embolization and surgery. Endovascular treatment can control unstable haemodynamics and can be sufficient in some cases. However, in patients with persistent unstable haemodynamics, recurrent bleeding or failed embolization, surgery is required.     

Pancreaticogastrostomy for pancreatic ascites

BACKGROUND/AIMS: Management of pancreatic ascites is challenging. The aim of the present study was to study the role of pancreaticogastrostomy in management of pancreatic ascites. METHODOLOGY: Retrospective analysis of twelve operated cases with pancreatic ascites following failed conservative and endoscopic treatment was done for its outcome in terms of morbidity and a successful outcome. Patient data, imaging information and surgical procedure were noted. RESULTS: Four of the 12 patients with leak from the dilated main pancreatic duct had longitudinal pancreaticogastrostomy. The gross edematous jejunum and a shortened mesentery due to sub-acute peritonitis necessitated this surgery. None had recurrence of ascites. Steatorrhea was distinctly absent. None had deterioration of endocrine function. CONCLUSIONS: Longitudinal pancreaticogastrostomy is a viable option in patients with pancreatic ascites and dilated main pancreatic duct especially in those with a shortened mesentery and an edematous small bowel.     

Neoadjuvant endocrine therapy in breast cancer

The use of endocrine therapy is well established as a primary treatment for locally advanced breast cancer. However, despite the current popularity of neoadjuvant chemotherapy for operable tumours, there is relatively little published evidence for pre-operative endocrine therapy in operable disease, particularly outside of the elderly population. The wider use of aromatase inhibitors (AIs) has encouraged studies that compare the efficacy of AIs with tamoxifen in the neoadjuvant setting, but there remains a lack of comparison of neoadjuvant with adjuvant endocrine therapies. This review discusses the current evidence regarding primary endocrine therapy, along with the factors involved in choosing appropriate patients for neoadjuvant therapy and the current opinions on length of treatment time and measurement of response prior to surgery.     

Results of concomitant aortic valve replacement and coronary artery bypass grafting in the VA population

BACKGROUND AND AIM OF THE STUDY: Concomitant aortic valve replacement (AVR) and coronary artery bypass grafting (CABG) is an established risk factor for diminished postoperative survival. Results from a VA population were reviewed in order to determine factors influencing early and late survival. METHODS: Between 1993 and 2003, a total of 401 patients underwent AVR at the authors' institution. Of these patients, 249 (62%; mean age 70.6 years) had combined AVR and CABG. Surgical indications were primarily aortic valve pathology (group A: n = 168; 68%), primarily coronary artery disease (CAD) (group B: n = 55; 22%), and both severe aortic and coronary disease (group C: n = 26; 10%). In total, 177 patients (71%) received a bioprosthesis, and 72 (29%) received a mechanical valve. Short- and long-term outcomes were explored using univariate and multivariable hazard analyses. RESULTS: Overall operative mortality was 6.4%; mortality for groups A, B and C was 4.8%, 9.1% and 11.5%, respectively. On multivariable analysis, significant factors associated with early-phase mortality were NYHA class IV, diabetes, bioprosthetic valve and combined severe aortic and coronary disease. Survival at one and five years was 86% and 62%, respectively. Five-year survival for groups A, B and C was 71%, 63% and 54%, respectively. Significant associated factors for late-phase mortality were the presence of preoperative peripheral vascular disease (PVD) and cerebrovascular disease (CVD). Factors such as age, prior cardiac surgery, number of grafted coronary arteries, and/or effective orifice area index (EOAI) had no significant effect on outcome. CONCLUSION: Combined AVR/CABG is a marker for decreased survival. Pre-existing factors such as diabetes, PVD and CVD, as well as poor preoperative NYHA functional status, affected survival. Further investigation is needed to assess the influence of the severity of CAD and EOAI on survival. Thoughtful consideration of all these factors is essential for an accurate prediction of survival, and to determine the appropriate type of aortic prosthesis to be used.