Comparative evaluation of quality of life in oral cancer patients undergoing 3-dimensional conformal radiation therapy with or without concomitant chemotherapy - A longitudinal study.

OBJECTIVES: To assess and compare the quality of life (QOL) in Oral Cancer patients undergoing 3-DCRT with or without concomitant Chemotherapy at three different time intervals. MATERIALS AND METHODS: This unicentric longitudinal study included 50 patients of oral cancer undergoing 3-DCRT with or without concomitant chemotherapy. QOL was recorded using the EORTC H and N 35 Questionnaire at baseline, end of treatment (EOT), and 3 months after treatment. RESULTS: Maximum deterioration of most QOL domains were noted at End of treatment (EOT) in all the patients. A highly statistically significant difference was noted between different time intervals with the highest scores noted at the EOT (P < 0.01). There was a statistically significant difference in patients undergoing 3DCRT with chemotherapy when compared to those with 3DCRT without chemotherapy (P < 0.05). CONCLUSION: There is substantial deterioration in QOL at the EOT after head-neck irradiation by 3-DCRT with or without concomitant Chemotherapy although it gradually improves over time. However, 3DCRT results in clinically meaningful and statistically better QOL scores at 3 months after treatment compared to baseline and EOT.

Postpartum Depression at a Tertiary Care Hospital in Saudi Arabia: Prevalence and Associated Factors.

Objectives Postpartum depression (PPD) is a significant health concern associated with several risk factors. This study aims to assess the prevalence of PPD and its related factors in a tertiary care hospital in Riyadh, Saudi Arabia, specifically King Khalid University Hospital (KKUH). Methods A cross-sectional study was conducted of 187 females aged 18 to 50 years old who gave birth at KKUH. Data were collected from the same participants at two stages using the same questionnaire, which consisted of the Edinburgh Postnatal Depression Scale (EPDS) and demographic questions. In the first stage, the participants were selected randomly. The second stage included participants who scored less than 9 on the EPDS in the first stage and were asked to retake the questionnaire four weeks later. Results The prevalence of PPD found in this study was 50.3%, which is higher than in other studies that have been conducted in the country. Furthermore, factors such as sleep disturbances (p = 0.005), loss of interest in daily activities (p = 0.031), mood swings (p = 0.021), frequent bouts of sadness (p < 0.0001), and frustration or worry (p < 0.0001) were all found to significantly increase the risk of PPD. Conclusion This study demonstrates a high prevalence of PPD in women who delivered at KKUH. More studies with a more rigorous methodology are warranted.

Comparative evaluation of oral mucositis in oral cancer patients undergoing 3-dimensional conformal radiation therapy and intensity modulated radiation therapy with or without chemotherapy.

Context: Oral cancer is a significant cause of death across the world. A combined multimodal approach integrating surgery and radiation therapy (RT) with or without chemotherapy (CT) is commonly employed in advanced oral cancer to prevent recurrences and locoregional spread. Oral mucositis is a common acute toxicity reported in patients undergoing RT and CT. The delivery of optimal cancer therapy protocols is compromised due to morbidity caused by oral mucositis. Aims: To compare the severity of oral mucositis in oral cancer patients undergoing 3-Dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) with or without concomitant CT. Settings and Design: This was a prospective, unicentric and longitudinal study conducted in a cancer centre. Methods and Material: One hundred four patients with locally advanced oral cancer were enrolled in this study. Fifty-two patients were treated with IMRT and 52 patients with 3DCRT to a dose of >60 Gy, along with concurrent cisplatin weekly CT. Mucositis was recorded before the start, in the end, 1 month, and 3 months post-chemoradiotherapy treatment. Statistical Analysis Used: Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software (v. 21.0, Chicago. 2012). Descriptive and frequency statistics were performed for different parameters assessed in 3DCRT and IMRT group. Results: Grade 3 mucositis was the most predominant grade observed in both groups at the end of treatment. Thirty-six patients (69.3%) versus 24 patients (46.1%) developed grade 3 mucositis in 3DCRT and IMRT group, respectively (P = 0.013). Healing was better with IMRT group when compared to 3DCRT group 1 month and 3 months post-RT. Mucositis was severe in patients undergoing concomitant CT. Conclusions: IMRT reduced the incidence of severe mucositis and also improved the treatment-compliance compared to 3DCRT in locally advanced head neck cancer patients treated by chemoradiotherapy.

Squamous papilloma of the proximal oesophagus associated with an inlet patch: a potential aetiological relationship.

Squamous papillomas are rare benign lesions that can be found in the oesophagus. It has been theorised that irritation of the esophageal mucosa leads to squamous papilloma formation. There is evidence to suggest that squamous papillomas of the distal oesophagus are related to irritation due to reflux of gastric acid. In this case report, we describe for the first time a squamous papilloma of the upper oesophagus located just distal to an inlet patch. Inlet patches consist of gastric mucosa located in the proximal oesophagus. They are capable of producing acid. This case raises the possibility that just as squamous papillomas of the distal oesophagus may be related to acid exposure from the reflux of gastric acid, squamous papillomas of the proximal oesophagus may be related to acid exposure from the locally-produced acid of inlet patches.

Real world management of esophageal ulcers: analysis of their presentation, etiology, and outcomes.

BACKGROUND AND STUDY AIMS: Esophageal ulcers are a rare cause of upper gastrointestinal morbidity and may be due to different etiologies. We sought to systematically evaluate patients with esophageal ulcers and describe their presentations, endoscopic findings, etiologies, treatments, and outcomes. PATIENTS AND METHODS: Patients diagnosed with esophageal ulcers over an 11-year period were retrospectively identified from our institution's electronic medical records. RESULTS: We identified 100 patients with esophageal ulcers (0.49% of patients undergoing upper endoscopy). Half of them presented due to gastrointestinal bleeding and three-quarters were admitted to the hospital. The majority were in the lower esophagus. Twenty-two unique etiologies, including multiple iatrogenic causes, were diagnosed in 91 of the cases. The most common etiology was gastroesophageal reflux disease (57%), followed by non-steroidal anti-inflammatory drug use (7%), malignancies (3%), vomiting (3%), caustic ingestion (2%), pill esophagitis (2%) and radiation (2%). Many etiologies showed a predilection for specific segments of the esophagus. Nine ulcers required endoscopic intervention and all were treated successfully. Repeat endoscopies were performed 5 times for diagnostic or "second look" reasons, none of which changed the patients' diagnosis or treatment. No patients required surgery or stricture dilation. One patient's ulcer was complicated by perforation and he subsequently died. Four other patients died from non-ulcer related causes. CONCLUSIONS: While the majority of ulcers were due to gastroesophageal reflux disease, 22 different etiologies were identified. Many were due to medication or iatrogenic causes. Repeat endoscopy did not appear to be helpful. While the incidence was low, they were frequently associated with significant morbidity.

Counseling interactions between patients living with persistent pain and pharmacists in Australia: are we on the same page?

BACKGROUND: People living with persistent pain in Australia often cannot access adequate care to manage their pain. Therefore, as the most accessible healthcare professionals, community pharmacists have an important role to play in helping to improve patient outcomes. Hence, it is important to investigate patient needs and expectations in terms of counseling interactions with pharmacists, along with pharmacists' approach to counseling interactions with these patients. METHOD: The nature of patient-pharmacist counseling interactions was explored with seven patients (one focus group), and 10 practicing pharmacists (two focus groups, three semi-structured interviews). The themes identified informed the development of an online survey that was advertised online to patients and pharmacists across Australia. RESULTS: A total of 95 patients and 208 pharmacists completed the survey. Overall, more than half of patients (77/95) were satisfied with the care provided by their pharmacist, but only a third (71/205) of pharmacists were satisfied with the care they provided to patients. The majority of patients (67/94) reported that pharmacists provided good information about medications. This aligned with pharmacists' responses, as most reported focusing on medication side effects (118/188) and instructions for taking pain medication (93/183) during patient interactions. However, when asked about empathy and rapport from pharmacists, only half to two-thirds (48-61/95) of patients expressed positive views. Overall, half of the patients (39/75) wanted a caring, empathetic, respectful, and private conversation with the pharmacist, and nearly half (40/89) perceived the pharmacist's role as providing (new) information on alternative pharmacological and non-pharmacological therapies, including general advice on pain management. CONCLUSION: There was a disparity in the nature of the interaction and information that patients wanted from pharmacists, compared to what was provided by pharmacists. Training and education may help pharmacists to better engage in patient-centered care when interacting with people living with persistent pain, thereby improving health outcomes for these patients.

Safety, tolerability and efficacy of a novel self-use biodegradable device for management of obesity.

OBJECTIVE: Obesity is a major public health issue with significant impact on quality of life, morbidity and mortality rates. It is estimated that if the current trends continue, 18% of men and 21% of women worldwide will be obese by 2025. All the current therapies are not optimal due to limited efficacy or safety; thus, there is a need for additional devices for the treatment of obesity. This study aimed to examine the safety, tolerability, and efficacy of a biodegradable encapsulated Epitomee device for weight loss. The technology is based on absorbent pharmaceuticals polymers and bonding materials that self-expand in the stomach to create a pH-sensitive super absorbent gel structure for weight loss. METHODS: A prospective, 12-week twice daily use of the encapsulated device in patients with body mass index of 27-40 kg m-2. Efficacy endpoints were the percent total body weight loss (%TBWL), proportion of participants with 5% TBWL and changes in cardio-metabolic markers. Safety analysis included evaluation of adverse events, laboratory and endoscopic findings. RESULTS: Overall, 52 patients completed the study. TBWL per intension-to-treat analysis was 3.68 ± 3.07% (3.23 ± 2.69 kg) and 4.52 ± 2.97% (3.95 ± 2.57 kg) per protocol. No device serious adverse effects reported. The most common adverse events were headache (18.1%), viral infection (11.5%), abdominal discomfort (10.1%), bloating (7.9%), nausea and constipation (5% each) and flatulence (4.3%). Endoscopy in 26 patients revealed mild, asymptomatic gastric/duodenal erythema without erosions in five patients. CONCLUSIONS: Twelve weeks of Epitomee capsules treatment combined with lifestyle counselling resulted in 3.68-4.52% of TBWL. With continued research, the Epitomee capsules have considerable potential to become a non-invasive, safe and effective treatment option for weight loss.

Why Abortion is Illegal? Comparison of Legal and Illegal Abortion: A Critical Review.

Abortion is the termination of pregnancy that occurs spontaneously or purposely. In the most developed world, abortion is legally allowed for women seeking safe termination of pregnancies. Particularly, when access to legal abortion is restricted, abortion is the resort to unsafe methods. The aim of this review is to necessitate safe abortion and to accentuate the consequences of illegal abortion in case of legal prohibition. We used Pubmed, MedLine and Scopus databases to review previous literatures of safe, unsafe, legal and illegal abortions. Research work and reports from organizations such as World Health Organization (WHO), World Bank (WB) and United Nations (UN) were included. Snowball sampling was used to obtain relevant journals. Abortion is conventional whether it is safe, unsafe, legal or illegal. The intention of the antiabortion policy was to reduce the number of abortions globally. However, instead of decreasing rates, evidences show significant increase in abortions. When abortion is legal, the preconditions to be ensured are availability, accessibility, affordability and acceptability for the safe abortion facilities. When abortion is illegal, risk reduction strategies are needed to decrease maternal morbidity and mortality. We can reduce abortion related morbidity and mortality, whether it is legal or illegal if we can ensure the appropriate access to health care, including abortion services, education on sexuality, access to contraceptives, post abortion care, and suitable interventions and liberalization of laws. The paper reviewed the Mexico City Policy and the US foreign aid strategies and highlighted the evidence based analysis for policy reform. The liberalized abortion law can save pregnant women from abortion related complications and death.

Introduction of new formulas and evaluation of the previous red blood cell indices and formulas in the differentiation between beta thalassemia trait and iron deficiency anemia in the Makkah region.

BACKGROUND: Many formulas from red blood cell (RCB) indices are instructed to differentiate between iron deficiency anemia (IDA) and beta thalassemia trait. None had 100% Youden index. AIM OF THE WORK: To introduce two new formulas and evaluate them in the differentiation between IDA and beta thalassemia trait in adults Saudi (male and female; male; female) in the Makkah region. Furthermore, to evaluate the previous formulas in our population. METHODS: A total of 249 participants, 91 with IDA, 123 with beta thalassemia trait, and 35 healthy persons. All subjected to complete blood count, measurement of iron profile, hemoglobin electrophoresis and hemoglobin A2 by column chromatography. The first new formula equal hemoglobin (Hb) + hematocrit (Hct) + RBC and second equals Hb + Hct + RBC-red cell distribution (RDW). The previous formula used is England and Fraser, Mentzer, Strivastava, Ehsani, Green and King, red cell distribution index, Ricerca, and Shine and Lal Results: In both men and women, the England and Fraser was the best with a Youden's index of 70.4%, followed by Green and King 67.4%. In men, the England and Fraser and our new formula 1 had the highest Youden' index 84.7% and 84.1%, respectively. In women, the England and Fraser and RDW index had the highest Youden' index 74% and 69.2%, respectively. CONCLUSION: The England and Fraser and our new formula 1 are the best formulas in men. The England and Fraser and RDW index are the best formulas in women.

Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn's disease with low rate of side effects: results of double blind Phase II clinical trial.

Therapy for Crohn's disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn's Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62(+) expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects.

Soluble endothelial protein C receptor and high sensitivity C reactive protein levels as markers of endothelial dysfunction in patients with type 1 and type 2 diabetes mellitus: their role in the prediction of vascular complications.

BACKGROUND AND OBJECTIVE: Endothelial dysfunction in diabetes mellitus (DM) is an important factor in the pathogenesis of micro and macrovascular complications. We aimed to measure soluble endothelial protein C receptor (sEPCR) and high sensitivity C reactive protein (hsCRP) levels as markers of endothelial damage in both types of diabetes mellitus and to determine if they can be used as predictors of vascular complications. METHODS: Fifty patients with DM, 20 with type 1 and 30 with type 2 as well as 30 healthy subjects were included. All were subjected to measurement of sEPCR and hsCRP by enzyme linked immunosorbent assay. RESULTS: sEPCR and hsCRP were significantly increased when compared to the control group in both types of DM. sEPCR was a significant predictor of macrovascular complications and thrombosis in type 1 p=0.02, and p=0.015, respectively. hsCRP was a significant predictor of macrovascular complications in type 2 p=0.04. CONCLUSION: Patients with type 1 and type 2 DM exhibit higher sEPCR and hsCRP levels compared to healthy controls which suggesting endothelial damage. sEPCR could be used as a predictor of macrovascular complications and thrombosis in type 1 DM, whereas, hsCRP might be used as a predictor of macrovascular complications in type 2 DM.

Reduced GLP-1R expression in gastric glands of patients with type 2 diabetes mellitus.

BACKGROUND: The incretin effect is reduced in type 2 diabetes mellitus (T2DM) patients. Whether the impaired function of the enteropancreatic axis in these patients is due to defective GLP-1 receptor (GLP-1R) expression in extrapancreatic target organs is not known. AIMS AND METHODS: To compare the GLP-1R expression and distribution in gastric mucosa biopsies of patients with (n =22) and without (n =22) T2DM referred for routine esophagogastroduodenoscopies. GLP-1R mRNA levels were estimated by real-time PCR. The intensity of GLP-1R immunostaining, frequency, and types of glandular cells bearing GLP-1R and their glandular distribution in different stomach mucosa regions were evaluated by immunohistochemical morphological semiquantitative and quantitative analysis. RESULTS: Mean mRNA GLP-1R levels were significantly reduced in patients with T2DM compared with nondiabetic patients (P < .02). Immunohistochemical analysis revealed that the reduced GLP-1R expression in T2DM patients was due to a decreased intensity of immunostaining (P < .01). The number of glandular GLP-1R-bearing cells in both body and antrum mucosa was decreased in T2DM patients. Most notably, the frequency of GLP-1R immunoreactive acid-secreting parietal cells was reduced in the neck area of the gastric principal glands of T2DM patients (P < .01). No correlation was found between the reduced GLP-1R expression and clinical parameters including body mass index, age, glycosylated hemoglobin, and disease duration. CONCLUSION: This is the first evidence of reduced GLP-1R expression in gastric glands of T2DM patients. These data demonstrate that the defective function of the incretin axis in T2DM may also result from decreased GLP-1R expression in its extrapancreatic target organs.

Levels of muscle enzymes in the serum after esophageal pneumatic dilation in patients with achalasia.

The success rate of pneumatic dilation of the esophagus in patients with achalasia is variable. We aim to assess whether levels of muscle enzymes in the serum are useful for predicting the efficacy of this procedure. Consecutive adults with symptomatic achalasia treated with pneumatic dilation were included. Blood samples were taken immediately before the procedure and after 12, 24 and 32 h. Clinical efficacy of the pneumatic dilation was evaluated on the basis of a symptom score defined prior to, and 2 months after the procedure. Eleven patients underwent 13 pneumatic dilations. In nine patients this was the first dilation attempt. Ten dilations were clinically effective. The study was discontinued after enzyme levels did not show a trend of increase in any of our patients. Moreover, a statistically significant unexpected decrease in creatine phosphokinase values was found 12 h after the procedure, among the 10 successful dilations. We believe that levels of muscle enzymes in the serum cannot predict the efficacy of pneumatic dilation in patients with achalasia.

Hepatic haemangiomas: possible association with female sex hormones.

BACKGROUND AND AIMS: The association of hepatic haemangiomas with female sex hormones is not entirely clear. We prospectively evaluated the impact of female sex hormones on the natural history of liver haemangiomas. METHODS: We followed 94 women with 181 haemangiomas diagnosed by ultrasound for a period of1-17 years (mean 7.3 (5.5) years). The location, number, size, and ultrasonographic pattern of the lesions were evaluated. Patients were also evaluated by questionnaire for gynaecological and reproductive history. We compared the change in number and size of haemangiomas in patients who received or did not receive exogenous hormonal treatment. RESULTS: Age at first period was inversely associated with the size of haemangiomas (r = 0.181, p = 0.015) while age at menopause was positively correlated with the number of haemangiomas detected at first ultrasound (r = 0.542, p<0.0001). During follow up, no change in the ultrasonographic pattern or number of haemangiomas was observed. An increase in the size of the lesions was demonstrated in 5/22 (22.7%) hormone therapy exposed patients compared with 7/72 (9.7%) controls. Three variables (ultrasonographic pattern, number of haemangiomas, and hormone therapy) predicted whether or not a given haemangioma would increase in size. A hypoechoic pattern increased the risk of progression while a hyperechoic pattern decreases that risk (p = 0.003). The number of haemangiomas was inversely associated with the likelihood of progression (p = 0.006) and hormone therapy increased the risk of haemangioma enlargement (p = 0.05). CONCLUSIONS: Hepatic haemangiomas seem to be influenced by both endogenous and exogenous female sex hormones although significant enlargement occurs only in a minority of patients. Consequently, routine liver ultrasound follow up in women with hepatic haemangiomas receiving hormone therapy appears appropriate.

Masking of 13C urea breath test by proton pump inhibitors is dependent on type of medication: comparison between omeprazole, pantoprazole, lansoprazole and esomeprazole.

BACKGROUND: The need to withhold acid suppression therapy while awaiting urea breath test results is a common clinical problem in symptomatic patients. It is unclear at present if the dose or type of proton pump inhibitor or the type of test meal govern the apparent masking effect of proton pump inhibitors on the urea breath test. AIM: To prospectively evaluate Helicobacter pylori detection rates during treatment with four different proton pump inhibitors, utilizing a high-dose citric acid-based 13C urea breath test. METHODS: Patients positive for Helicobacter pylori by urea breath test were randomized to receive either omeprazole 20 mg/day, pantoprazole 40 mg/day, lansoprazole 30 mg/day or esomeprazole 40 mg/day for 14 days. A repeat breath test was performed on day 14 of treatment. RESULTS: One hundred and seventy-nine patients, mean age 45.8 +/- 16.8, completed the study. Treatment with omeprazole or pantoprazole prior to urea breath test (UBT) was associated with low false negative results, while lansoprazole and esomeprazole caused clinically unacceptable high false negative rates (pantoprazole 2.2% vs. lansoprazole 16.6%, P = 0.02, vs. esomeprazole 13.6%, P = 0.05; omeprazole 4.1% vs. lansoprazole 16.6%, P = 0.05). CONCLUSIONS: Proton pump inhibitor-induced false negative results on high-dose citric acid based urea breath test vary with the type of proton pump inhibitor used. Selection of the appropriate test meal and proton pump inhibitor may allow symptomatic individuals to continue their proton pump inhibitors prior to performing a urea breath test.

Prevalence of Helicobacter pylori infection in health-care personnel of primary care and gastroenterology clinics.

BACKGROUND & AIMS: Helicobacter pylori (Hp) infection clusters within families, is usually acquired early in life, and is strongly associated with lower socioeconomic status during childhood. Transmission in adulthood is relatively rare, and reports on the prevalence of Hp infection among health personnel, especially endoscopists, are controversial. The present prospective study evaluated the prevalence of Hp infection in health-care workers in primary-care clinics and in gastroenterology units. METHODS: Health care personnel from gastrointestinal units (n = 191) and primary care-clinics (n = 98) of the Clalit Health Services (CHS) in Israel underwent the carbon 13 breath test (13C-UBT) and completed a 21-item demographic and socioeconomic questionnaire. The control group consisted of 4633 symptomatic patients with no evidence of previous Hp infection. RESULTS: The 13C-UBT was positive in 108 gastrointestinal unit personnel (73%) and 70 primary-care workers (71%); both rates were statistically higher significantly than the 53% positivity in the controls. Comparison of the 13C-UBT Hp-positive and Hp-negative health-care personnel yielded a significantly higher index of crowded living conditions in the Hp-positive group. In the gastrointestinal unit workers, Hp positivity was also associated with several years in practice, and in the primary-care workers, with Sephardic (Asian and African origin) versus Ashkenazi (Europe and American) origin. Profession (physician, nurse, technician, secretary, or maintenance worker), history of duodenal ulcer, smoking, marital status, and blood group did not have predictive value for Hp colonization. CONCLUSIONS: The prevalence of Hp infection in Israel is higher in health-care staff of primary-care clinics and gastrointestinal units than in the general population. This may be related to socioeconomic facts and professional hazard. Further studies are needed to clarify this issue.

Cox-2 is needed but not sufficient for apoptosis induced by Cox-2 selective inhibitors in colon cancer cells.

The role of Cox-2 in NSAID-induced apoptosis is debated. We studied the role of Cox-2 inhibition in apoptosis induced by a selective Cox-2 inhibitor, SC236 (a structural analogue of celecoxib) in two colon cancer cell lines, HT29 (expressing Cox-2 protein) and HCT116 (not expressing Cox-2 protein). Apoptosis was quantified by flow cytometry. SC236 0-75 microM decreased cell numbers and induced apoptosis to identical levels in HT29 and HCT116 cells. However, SC236, concentrations >75 microM reduced Cox-2 protein expression in HT29 cells and induced greater levels of apoptosis in HT29 than in HCT116 cells. In contrast, sulindac sulfide (SSD) (which inhibits Cox-1 and Cox-2) 0-200 microM or sulindac sulfone (SSN) 0-500 microM (without significant activity against Cox-1 or Cox-2) caused identical decreases in cell number and increases in apoptosis in HT29 and HCT116 cells. Neither SSD nor SSN altered the expression of Cox-2 in HT29 cells. To determine that the higher levels of apoptosis in HT29 cells with SC236 >75 microM were related to decreased Cox-2 protein levels, we decreased Cox-2 protein expression in HT29 cells with curcumin (diferuloylmethane) and studied its effect on SC236-induced apoptosis. Curcumin augmented apoptosis induced by SC236 in HT29 cells but not in Cox-2 lacking HCT116 cells. In conclusion, selective Cox-2 inhibitors can induce apoptosis independent of Cox-2 expression. However they may selectively target cells that express Cox-2 by decreasing their Cox-2 protein expression.

Effects of H. pylori infection of gastric epithelial cells on cell cycle control.

Chronic infection of the gastric mucosa by the bacterium H. pylori results in an intense inflammatory response which can last for decades. An associated host response is a chronic hyperproliferative state, in which there is increased cell turnover and also increased apoptosis of the gastric epithelial cells. Recent studies have also demonstrated abnormalities in the expression of cell cycle control proteins. This review describes these events, emphasizing recent studies on the effects of H. pylori infection on cell cycle progression and the expression of cell cycle regulatory proteins. The systems that have been studied include in vivo studies in humans and in experimental animals, and in vitro studies in which gastric epithelial cells were co-cultivated with H. pylori. The earliest event following H. pylori's interaction with epithelial cells appears to be growth inhibition and apoptosis. The hyperproliferative response observed in the gastric mucosa is secondary to this initial insult and is associated with increased expression of cyclin D1, the cyclin dependent kinase inhibitor p16ink4a and of p53 and decreased expression of the cyclin dependent kinase inhibitor p27kip1. Dysregulation of the hyperproliferative response may, ultimately, be responsible for the ability of H. pylori to enhance the development of gastric cancer.

Prevention of hepatic cirrhosis in rats by hydroxyl radical scavengers.

BACKGROUND/AIMS: Reactive oxygen species and oxidative stress were implicated in hepatic stellate cell activation and liver fibrosis. The aim of the present study was to examine whether the administration of free radical scavengers in vivo would prevent experimentally-induced hepatic cirrhosis in rats. METHODS: Cirrhosis was induced by administration of thioacetamide (TAA; 200 mg/kg, i.p.) twice/week, for 12 weeks. Rats were treated concurrently with either dimethylsulfoxide (DMSO; 4 g/kg, s.c. or p.o.) or dimethylthiourea (DMTU; 200 mg/kg i.p.) three times a week. RESULTS: Liver fibrosis (histopathological score, spleen weight, and hepatic hydroxyproline) was abolished in rats treated with TAA and either DMSO or DMTU (P < 0.001). Accordingly, the hepatic expression of alpha smooth muscle actin, tissue inhibitor of metalloproteinase 2 and collagen alpha1 (I) gene were inhibited. The hepatic level of methane-sulfinic acid (produced by the interaction of DMSO with hydroxyl radicals) was increased in rats treated with TAA + DMSO (P = 0.0005) and decreased after pretreatment of these rats with DMTU (P = 0.008). However, the hepatic levels of malondialdehyde, lipid peroxides and protein carbonyls were not lower in the DMSO- and DMTU-treated groups. CONCLUSIONS: The administration of free radical scavengers prevented the development of TAA-induced liver cirrhosis probably associated with decreased oxidative stress.