Search

Background: Racial and ethnic disparities have been observed in the multidisciplinary management of pancreatic ductal adenocarcinoma. Intraductal papillary mucinous neoplasm is the most common identifiable precursor to pancreatic ductal adenocarcinoma, where early surgical intervention before the development of an invasive intraductal papillary mucinous neoplasm improves survival. The association of race/ethnicity with the risk of identifying invasive intraductal papillary mucinous neoplasms during resection has not been previously defined., Methods: The American College of Surgeons National Quality Improvement Program targeted pancreatectomy database (2014-2021) was queried for patients with race/ethnicity data who underwent resection of an intraductal papillary mucinous neoplasm. Backward Wald logistic regression modeling (P ≤ 0.05 for entry; P > .10 for removal) was used to identify independent predictors of invasion., Results: A total of 4,505 cases of resected intraductal papillary mucinous neoplasms were identified, with 923 (20.5%) demonstrating invasive intraductal papillary mucinous neoplasms. The cohort of individuals other than non-Hispanic Whites were significantly more likely to have invasive intraductal papillary mucinous neoplasms (White, 19.9%; Black, 24.2%; Asian, 23.7%; Hispanic, 22.6%; P = .026). Such disparity could not be explained by greater comorbidity, as non-White patients were significantly younger (age <65 years: 41.7% vs 33.2%, P < .001) and had better physical status (American Society of Anesthesiologists score ≤2: 28.8% vs 25.2%, P = .053). After controlling for clinicodemographic variables, being an individual of race/ethnicity other than White was independently associated with higher odds of invasive intraductal papillary mucinous neoplasms (odds ratio, 1.280; 95% confidence interval, 1.046-1.566; P = .017). No differences in postoperative morbidity were observed., Conclusion: In a national cohort of patients with resected intraductal papillary mucinous neoplasms, individuals who identified as being of race/ethnicity other than White were significantly more likely to have invasive intraductal papillary mucinous neoplasms during surgical resection., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Bowel obstruction is one of the most common surgical emergencies. The management of SBO is variable and influenced by numerous confounding factors. Recent studies have identified mental health as a health disparity that affects surgical outcomes. We aim to assess whether mental illness is a health disparity and its association with postoperative complications and secondary outcomes for bowel obstruction in Emergency General Surgery (EGS)., Methods: This was a retrospective study utilizing the National Inpatient Sample. Individuals aged 18-64 who underwent emergency adehesiolysis or bowel resection from 2015 to 2017 were identified. Postoperative complications, in-hospital mortality, length of stay, and total cost for surgical patients with and without mental illness were recorded. Univariate and multivariate analyses were used to evaluate the association between mental health and bowel obstruction., Results: 20,574 patients who underwent surgery for bowel obstruction were identified. 3756 of these patients had mental illness and 16,998 patients did not. Patients with mental illness did not have significantly worse outcomes compared to patients without mental illness. Among 3576 patients with mental illness, sex, race, patient location, insurance, location/teaching status of hospital, hospital control and procedure type were significant predictors of prolonged length of stay, higher cost, and increased postoperative complications., Conclusions: Mental health does not appear to be a health disparity in outcomes for bowel obstruction procedures. However, the intersection of mental health with race and insurance status predicts worse outcomes. This essential area should be further explored to determine how marginalized populations are affected in emergency surgical care., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: A laparoscopic approach to bariatric surgeries confers a favorable side-effect profile as compared to an open approach. However, literature regarding the independent association of race with access to and postoperative outcomes in laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (GS) is scarce., Materials and Methods: All RYGB and GS cases recorded in American College of Surgeons National Quality Improvement Program data from 2012 to 2020 were subjected to propensity score matching to assess the independent association between Black self-identified race on access to a laparoscopic approach and postoperative complications. Finally, a series of logistic regressions enabled evaluation of the mediating effect of operative approach on racial disparities in postoperative complications., Results: 55,846 cases of RYGB and 94,209 cases of GS were identified. Following propensity score matching, logistic regression identified Black race as an independent predictor of open approach to RYGB (P < 0.001) and GS (P = 0.019). Black patients had increased incidence of any, minor and severe postoperative complications and unplanned readmissions in both RYGB (P < 0.001, P < 0.001, P = 0.0412, and P < 0.001, respectively) and GS (P < 0.001, P < 0.001, P = 0.0037, and P < 0.001, respectively). Open approach to RYGB was identified as a partial mediator of the independent association between Black race and any complication, minor complications, and unplanned readmission., Conclusions: This methodology identified racial disparities in complications following RYGB and GS. Interestingly, reduced access to a laparoscopic approach mediated racial disparities in complications following RYGB but not GS. Further research might elucidate upstream determinants of health that catalyze these disparities., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: With the increasing popularity of electric scooters (ES) and the introduction of ES sharing systems in 2017, hospitals are seeing more ES-related injuries. The effects of sharing systems on traumatic injuries are lacking in the literature. We, therefore, sought to describe trends in ES injuries., Methods: The Nationwide Inpatient Sample was queried for patients hospitalized with ES-related injuries in the United States from 2015 to 2019. Admissions due to ES were divided into two cohorts: before (≤2017) and after (>2018) the introduction of sharing systems. Patients were stratified by injuries sustained, age, gender, and race. Inpatient hospital charges and length of stay were compared. Exclusion criteria included patients older than 65 and patients with neurological disorders. Traumatic injuries were compared after adjusting for age, gender, and race in a multivariate logistic regression analysis., Results: During the study period, there were 686 admissions, of which 220 remained due to exclusion criteria. There was a consistent increase in ES-related injuries over the years (r = 0.91, p = 0.017). Patients who were injured after the introduction of sharing systems were more likely to sustain facial fractures (OR, 2.63; 95%CI, 1.30-5.32; p = 0.007) after controlling for age, gender, and race. The incidence of lumbar and pelvic fractures was higher following the introduction of such systems (7.1% vs. 0%; p<0.05)., Conclusions: The introduction of ES sharing systems resulted in increased incidence of facial, pelvic, and lumbar fractures. Federal and state regulations need to be implemented to mitigate the detrimental effects of ES sharing systems., Competing Interests: Declaration of Competing Interest The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Pancreatic cancer is diagnosed histologically through percutaneous biopsy (PB), endoscopic biopsy (EB), or surgical biopsy (SB). Factors and outcomes associated with method type are not clearly understood. We aimed to evaluate the relationship between insurance status, length of hospital stay (LOS), complications, and different pancreatic biopsy modalities., Study: The 2001-2013 database from the National (Nationwide) Inpatient Sample (NIS) was queried for those with pancreatic cancer who underwent biopsies using International Classification of Diseases, Ninth Revision (ICD-9) codes. Data regarding insurance status, hospital stay, demographics, and complications were analyzed using chi-square and multivariate analysis with α < 0.001., Results: A total of 824,162 patients with pancreatic cancer were identified. Uninsured and Medicaid patients were more likely to get PB compared to SB. Patients were more likely to have acute renal failure (ARF) with an EB compared to SB. Patients were more likely to have a urinary tract infection (UTI) with EB or PB compared to SB. All biopsy types were less likely to have pneumonia; pancreatitis was more prevalent in EB compared to PB and SB., Conclusions: Uninsured and Medicaid patients were most likely to have a PB compared to EB despite unclear indications which may represent an underlying discrepancy in healthcare utilization. EB patients had the shortest LOS while SB patients stayed three more days; those who underwent a combination of biopsies had the greatest LOS. Patients with EB were more likely to develop ARF, UTI, and pancreatitis than SB, possibly attributed to the advanced nature of endoscopic ultrasound. It is important to establish appropriate algorithm contributors to guide decision-making., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Mittal et al.)

Background: Esophageal cancer and gastric cancer are two important causes of upper GI malignancies. Literature has shown that minimally invasive esophagectomies (MIE) and gastrectomies (MIG), have shorter length of stay and fewer complications. However, limited literature exists about the association between race and access to MIE and MIG. This study aims to identify the racial disparities in the different approaches to esophagectomy and gastrectomy. We further evaluate the relationship between the race and postoperative complications., Methods: This IRB-approved retrospective study utilized data from the American College of Surgeons National Quality Improvement Program. All recorded cases of MIE, MIG, open gastrectomy, and esophagectomy between 2012 and 2019 were isolated. Propensity score matching and univariate analysis was performed to assess the independent effect of black self-identified race on access and outcomes. p < 0.05 was required to achieve statistical significance., Results: 7891 cases of esophagectomy and 5,132 cases of gastrectomy cases were identified. Using Propensity and logistic regression, we identified that black self-reported race is an independent predictor of open approach to gastrectomy (OR 1.6871943, 95% CI 1.431464-1.989829, p < 0.001). Black self-reported race was not predictive of operative approach among esophagectomy patients (OR 0.7942576, 95% CI 0.5698645-1.124228, p = 0.183). In contrast, black self-reported is an independent predictor of postoperative complications among esophagectomy patients only. Esophagectomy patients of black self-reported race were more likely to experience any complication (OR 1.4373437, 95% CI 1.1129239-1.8557096, p = 0.00537), severe complications (OR 1.3818966, 95% CI 1.0653087-1.7888454, p = 0.0144), and death (OR 2.00779762, 95% CI 1.08034921-3.56117535, p = 0.0211) within 30 days of their surgeries., Conclusion: Our analysis revealed a significant racial disparity in access to MIG and a higher incidence of post-operative complications amongst esophagectomy patients. Minimally invasive techniques are underutilized in racial minorities. The findings herein warrant further investigation to eliminate barriers and disparities., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The number of regular smartphone users has increased dramatically worldwide. Headaches, followed by sleep difficulties, forgetfulness, dizziness, and other ailments, are among the most prevalent complaints among smartphone users during or after use. In addition, migraine is a debilitating disease and is the world's second leading cause of disability. Hence, we performed this study to determine how smartphone overuse influenced migraine patients' level of disability, pain intensity, sleep quality, and overall quality of life., Methods: In this observational study, the patients were divided into two groups high mobile phone use group (HMPUG) and the low mobile phone user group (LMPUG) using the Mobile Phone Problematic Use Scale. We assessed, for each group, patients' level of disability, pain intensity, sleep quality, daytime sleepiness, and quality of life through the Migraine Disability Assessment Scale, Visual Analogue Scale, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and 24-h Migraine Quality of Life Questionnaire, respectively., Results: Our study showed that the respondents' average age was  27.59 (9.79) years. The average number of family members was 5.98 (2.3251). A total of 65.8% (n = 263) of the 400 participants were female, while 34.3 % (n = 137) were male. Greater pain intensity, poor sleep quality, and reduced medication effectivity were found in HMPUG compared to LMPUG (p < .05). However, increased duration of migraine and medication intake was reported in the LMPUG (p < .05)., Conclusion: We observed that smartphone overuse could worsen pain, sleep, and reduce treatment efficacy in individuals with migraine. Therefore, controlled smartphone use is recommended to avoid worsening symptoms., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Laparoscopy has become the standard of care for the majority of cases for inguinal hernia repair, cholecystectomy, appendectomy, and colectomy due to the shortened patient recovery time compared to open surgery. This study sought to determine if there exists racial disparity in access to a laparoscopic approach to these common surgeries., Methods: This was an IRB-approved retrospective study utilizing data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Individuals who underwent inguinal hernia repair, cholecystectomy, appendectomy, and colectomy in 2016 were identified. Information on self-reported race and ethnicity and other demographic and pre-operative clinical covariates were recorded. Propensity matching was conducted to evaluate the association between race and a laparoscopic approach to surgery., Results: There were 44,522, 60,444, 50,523, and 58,012 cases of inguinal hernia repair, cholecystectomy, appendectomy, and colectomy identified, respectively. Of these patients, 8.38, 8.76, 6.69, and 9.02% self-identified as black, respectively. Confounding effects of variables other than race were balanced by propensity matching. After propensity matching, there were 7460, 10,574, 10,470, and 6758 cases of hernia repair, cholecystectomy, colectomy, and appendectomy, respectively. On univariate (Chi square) analysis with laparoscopic surgery as the primary outcome, black race was significantly associated with lower likelihood of undergoing a minimally-invasive surgical approach in all four surgical procedures under investigation (33.86% of white patients and 21.69% of black patients, p < 0.0001 for hernia repair; 97.98% of white patients and 94.29%, p < 0.0001 of black patients for cholecystectomy; 70.93% of white patients and 48.60% of black patients, p < 0.0001 for colectomy; and 98.85% of white patients and 92.81% of black patients, p < 0.0001 for appendectomy)., Conclusions: There appears to be a significant racial disparity in the application of a laparoscopic approach to routine intra-abdominal surgery. This warrants further investigation into the barriers preventing access to laparoscopic general surgical procedures that certain populations face.

Background: Increasing efforts have been made to reduce the incidence and severity of concussion in high-contact sports. Despite these efforts, a relative lack of knowledge is available regarding modulating factors affecting concussion injury., Purpose: To analyze the potential influence of game characteristics and outcomes on concussion incidence and severity in professional football., Study Design: Descriptive epidemiology study., Methods: PBS Frontline Concussion Watch was used to collect concussion injury data from regular-season games of 32 National Football League (NFL) teams from 2012 to 2015. Game characteristic variables such as rushing and passing attempts, turnovers, and margin of victory were collected from ESPN. Analysis included descriptive statistics, analysis of variance, t tests, and correlation tests., Results: Away teams demonstrated a significantly greater concussion incidence per game than home teams. Losing teams had a significantly greater concussion incidence per game than winning teams. Being both the away team and the losing team appeared to have an additive effect. The home-versus-away and win-versus-loss effects were significant for offensive but not defensive positions. Within individual positions, significantly greater concussion incidence was associated with tight ends, running backs, wide receivers, and cornerbacks. When running versus passing positions were compared, passing positions (wide receiver, tight end, cornerback, safety) had significantly greater concussion incidence. A total of 626 games were missed as a result of reported concussions. Away teams had significantly more games missed due to concussion when they lost. Play time did not significantly differ before or after concussion injury. Other game characteristic variables did not significantly affect concussion frequency or intensity., Conclusion: Position, game location, and game outcome affect concussion incidence for professional football players. In a subset of analyses, the number of games missed aligned with concussion incidence, but this appeared to be an imperfect measure. These findings highlight new factors that may modulate concussion incidence and merit further study on how they may influence concussion evaluation., Competing Interests: The authors declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

The incidence of blast-induced traumatic brain injury (bTBI) has increased substantially in recent military conflicts. However, the consequences of bTBI on the blood-brain barrier (BBB), a specialized cerebrovascular structure essential for brain homeostasis, remain unknown. In this study, we utilized a shock tube driven by compressed gas to generate operationally relevant, ideal pressure profiles consistent with improvised explosive devices (IEDs). By multiple measures, the barrier function of an in vitro BBB model was disrupted following exposure to a range of controlled blast loading conditions. Trans-endothelial electrical resistance (TEER) decreased acutely in a dose-dependent manner that was most strongly correlated with impulse, as opposed to peak overpressure or duration. Significantly increased hydraulic conductivity and solute permeability post-injury further confirmed acute alterations in barrier function. Compromised ZO-1 immunostaining identified a structural basis for BBB breakdown. After blast exposure, TEER remained significantly depressed 2 days post-injury, followed by spontaneous recovery to pre-injury control levels at day 3. This study is the first to report immediate disruption of an in vitro BBB model following primary blast exposure, which may be important for the development of novel helmet designs to help mitigate the effects of blast on the BBB.

AML-M6 has a peak incidence in the seventh decade with slight male preponderance, and can also present at a younger age. The usual features are anaemia, thrombocytopenia, malaise, fatigue, easy bruising, epistaxis and petechiae. Splenomegaly may occur in 20-40 % of the cases but massive splenomegaly is rare presentation and have been only reported once in humans and once in animals. A 22 year Asian female, presented with fatigue, pallor, mild jaundice, exertional dyspnoea, epigastric pain, tender right hypochondrium and massive splenomegaly. Investigations revealed anaemia and thrombocytopenia, tear drop cells, basophilic stippling, piokilocytosis and anisochromia; increased uric acid and LDH. Abdominal ultrasound showed enlarged liver (22cm) and spleen (20cm). Bone marrow aspiration revealed 51% erythroid and 24% non-erythroid precursors, depressed leukopoeisis and megakarypoeisis. Erythroblasts were PAS and CD71 positive and also reacted to Antihaemoglobin-Antibody. This report highlights characteristic features and diagnostic criteria of erythroleukaemia, differential diagnosis of massive splenomegaly and their rare association.

Objective: To evaluate the difference between pre- and post-menopausal breast cancer regarding menstrual and reproductive risk factors, Methods: The case-control study was conducted in Mayo Hospital, Lahore, between October 2008 and April 2009. Cases were breast cancer patients admitted in the surgical and oncology floors of the hospital. Controls were hospital patients without breast cancer. The study enrolled 150 cases and 300 controls. Menstrual and reproductive history was taken from both the cases and the controls. For every risk factor age-adjusted odds ratio (OR) and 95% confidence interval (CI) was calculated by logistic regression analysis, separate for pre- and post-menopausal women., Results: Among the breast cancer patients, 42.7% were pre-menopausal and 57.3% were post-menopausal. Age at menarche had no association with breast cancer for both pre- and post-menopausal women. Nulliparity was a risk factor for both pre-menopausal (OR 4.1, 95% CI 1.4-12.6) and post-menopausal breast cancer (OR 8.2, 95% CI 1.7-40.4). Among parous women only post-menopausal females having < 3 children were at increased risk for breast cancer (OR 4.5, 95% CI 1.8-11.5) compared with females having > or = 3 children. Younger age at first live birth decreased breast cancer risk in both pre- and post-menopausal women. Breastfeeding was not associated with both pre- and post-menopausal breast cancer., Conclusions: Majority of risk factors for pre-menopausal breast cancer are also associated with postmenopausal breast cancer except less parity, which increased the risk for post-menopausal breast cancer only.

Objective: To study the prevalence of anxiety and depression symptoms in patients with dengue and to examine their correlation with symptom severity., Methods: In this cross sectional study, 531 consecutive patients who met the World Health Organization criteria for dengue fever admitted to Mayo Hospital, Lahore between September and November 2011 were administered the Hospital Anxiety and Depression Scale (HADS). In addition to the HADS, the severity of their symptoms, like headache, myalgias/arthralgias, fever, and retro/periorbital pain, was assessed on a 3-point scale (mild, moderate, and severe)., Results: About 60% of the patients in our study met the criteria for anxiety and 62.2% of the patients met criteria for depression. Severity of fever, headache, myalgias and arthralgias, and retro/periorbital pain was positively correlated with both anxiety (Correlation coefficients: 0.148, 0.247, 0.184, 0.184 respectively and P < 0.01 for all) and depression scores (Correlation coefficients: 0.098, 0.154, 0.131, 0.125 respectively and P value < 0.01 for all). The strongest correlation was found between severity of headache and scores for both anxiety and depression. Both mean anxiety and depression scores were significantly higher in patients with platelet count below median (30,000/mm3) than in patients with platelet count above median (9.1 +/- 4.7 vs 8.2 +/- 4.7, P < 0.03, and 9.5 +/- 4.5 vs 8.5 +/- 4.5, P < 0.01, respectively)., Conclusion: A majority of patients with dengue have anxiety and depression symptoms. Psychiatric evaluation should be done in all Dengue patients so timely treatment can be initiated.

Objective: To determine the accuracy of pallor of conjunctiva, nailbed, and palm in detecting mild and severe anaemia., Methods: Three hundred and five consecutive patients admitted in the medical and surgical wards of Mayo Hospital, Lahore were enrolled in the study. Conjunctiva, nailbed, and palm of patients were assessed. Mild anaemia was defined as Hb < 11.5 g/dl for females and Hb <13 g/dl for males. Severe anaemia was defined as Hb <7 g/dl. Likelihood ratios (LR) and their 95% confidence intervals (CI) for both presence and absence of pallor at each site were calculated. To compare the accuracy of different pallor sites in diagnosing severe anaemia, their areas under receiver operating characteristics curves (AUC) were compared., Results: Mild anaemia was present in 64.3% patients while severe anaemia was present in 7% patients. Presence of nailbed pallor had moderate accuracy for diagnosing mild anaemia (LR 5.6, 95% CI 4.7-6.7) while absence of pallor at nailbed, conjunctiva, and palm (LR 0.6 for all) did not rule out mild anaemia. All sites had modest accuracy for detecting severe anaemia (LR 2.5-3.0). Absence of pallor at conjunctiva (LR 0.1, 95% CI 0.03-0.5) and palm (LR 0.1, 95% CI 0.03-0.5) convincingly ruled out severe anaemia. Comparison of the AUC for different pallor sites showed that all sites were equally useful for detecting severe anaemia., Conclusion: Pallor is not an accurate sign for mild anaemia. Pallor of conjunctiva, palm, and nailbed has modest accuracy in detecting severe anaemia. Absence of pallor at conjunctiva and palm convincingly rules out severe anaemia.

Background: Anomalous expression of activation-induced cytidine deaminase (AID) in Helicobacter pylori-infected gastric epithelial cells has been postulated as one of the key mechanisms in the development of gastric cancer. AID is overexpressed in the cells through nuclear factor (NF)-kappaB activation by H. pylori and hence, inhibition of NF-kappaB pathway can downregulate the expression of AID. Curcumin, a spice-derived polyphenol, is known for its anti-inflammatory activity via NF-kappaB inhibition. Therefore, it was hypothesized that curcumin might suppress AID overexpression via NF-kappaB inhibitory activity in H. pylori-infected gastric epithelial cells., Materials and Methods: MKN-28 or MKN-45 cells and H. pylori strain 193C isolated from gastric cancer patient were used for co-culture experiments. Cells were pretreated with or without nonbactericidal concentrations of curcumin. Apoptosis was determined by DNA fragmentation assay. Enzyme-linked immunosorbent assay was performed to evaluate the anti-adhesion activity of curcumin. Real-time polymerase chain reaction was employed to evaluate the expression of AID mRNA. Immunoblot assay was performed for the analysis of AID, NF-kappaB, inhibitors of NF-kappaB (IkappaB), and IkappaB kinase (IKK) complex regulation with or without curcumin., Results: The adhesion of H. pylori to gastric epithelial cells was not inhibited by curcumin pretreatment at nonbactericidal concentrations (< or =10 micromol/L). Pretreatment with nonbactericidal concentration of curcumin downregulated the expression of AID induced by H. pylori. Similarly, NF-kappaB activation inhibitor (SN-50) and proteasome inhibitor (MG-132) also downregulated the mRNA expression of AID. Moreover, curcumin (< or =10 micromol/L) has suppressed H. pylori-induced NF-kappaB activation via inhibition of IKK activation and IkappaB degradation., Conclusion: Nonbactericidal concentrations of curcumin downregulated H. pylori-induced AID expression in gastric epithelial cells, probably via the inhibition of NF-kappaB pathway. Hence, curcumin can be considered as a potential chemopreventive candidate against H. pylori-related gastric carcinogenesis.

Inflammatory cytokine interleukin-8 (IL-8) and reactive oxygen species (ROS) overexpressed in the gastric mucosa when exposed to Helicobacter pylori, defined as a class I carcinogen. Moreover, infection with H. pylori leads to morphological changes in co-cultured cells known as hummingbird phenomenon along with increased motility. Resveratrol, a highly abundant polyphenol in red grapes, has shown anti-inflammatory, anti-cancer, cardioprotective and neuroprotective activities. However, the effect of resveratrol in H. pylori-infected cells has not been investigated. The present study was, therefore, aimed to evaluate the effect of resveratrol on the induction of IL-8, ROS and hummingbird morphology in H. pylori-infected gastric epithelial cells. The non-toxic concentration of resveratrol for both H. pylori and epithelial cells was determined by brucella broth dilution method and DNA fragmentation assay. The non-toxic resveratrol (< or =100 microM) treatment did not demonstrate any inhibitory effect against H. pylori adhesion to gastric epithelial cells. However, preincubation of the cells with 75 and 100 muM of resveratrol significantly (p<0.05 and p<0.01 respectively) inhibited the secretion of IL-8 from H. pylori-infected cells. In addition, resveratrol pretreatment at 1-100 muM suppressed H. pylori-induced ROS generation in a concentration dependent manner. Moreover, H. pylori-initiated morphological changes were markedly blocked by resveratrol. Hence, resveratrol can be considered as a potential candidate against various H. pylori related gastric pathogenic processes.

In the quest for potent anti-Helicobacter pylori agents, we found 70% EtOH extract of Mallotus philippinensis (LAM.) MUELL. (MPM) with strong bactericidal activity at the concentration of 15.6-31.2 mg/l against eight H. pylori strains. Further fractionation and purification of 70% EtOH extract of MPM led to the isolation of 5 compounds, namely 5,7-dihydroxy-8-methyl-6-prenylflavanone (1), 3'-prenylrubranine (2), red compound (3), isorottlerin (4), and rottlerin (5) which were elucidated on the basis of nuclear magnetic resonance and mass spectroscopy. Among the isolated compounds, rottlerin exhibited most potent bactericidal activity with minimum bactericidal concentration (MBC) value of 3.12-6.25 mg/l against several clinical H. pylori isolates including Japanese and Pakistani strains, nine clarithromycin resistant (CR), and seven metronidazole resistant (MR) strains. Minimum inhibitory concentration (MIC) values of CR (8->256 mg/l) and MR (>256 mg/l) strains were analyzed by E test. Moreover, the clarithromycin resistant strains were evaluated for A2143G and A2144G point mutations of 23s rRNA gene to correlate the MBC values with mutation type. Our results revealed the potent in vitro anti-H. pylori activity of MPM and rottlerin, specially against CR and MR strains, which could be gainfully utilized for the development of novel antimicrobials to prevent H. pylori related disorders.

The apoptosis-inducing ability of hybrid compounds composed of macrosphelide and thiazole-containing side chain of epothilones was investigated. Among the tested series of hybrid compounds the one containing thiazole side chain at C15 (MSt-2) showed the maximum potency to induce apoptosis, while another containing thiazole side chain at C3 (MSt-6) was less potent. MSt-2 was found to induce apoptosis in human lymphoma (U937) cells in a dose- and time-dependent manner as confirmed by DNA fragmentation analysis. MSt-2 treated cells showed rapid reactive oxygen species (ROS) formation and c-Jun N-terminal kinase (JNK) activation. Furthermore, significant activation of extrinsic pathway as evident by Fas expression and caspase-8 activation was also observed. MSt-2-mediated decreased expression of Bid is an important event for cross talk between intrinsic and extrinsic signaling. N-acetyl-l-cysteine pre-treatment rescued cells from MSt-2-induced ROS formation, mitochondrial membrane potential (Delta psi(m)) loss, Fas expression, caspase-8 and -3 activation and DNA fragmentation. Moreover, antioxidant enzymes catalase and/or superoxide dismutase conjugated with polyethylene glycol also inhibit MSt-2-induced ROS formation, apoptosis and Delta psi(m) loss suggesting thereby pro-oxidant effects of MSt-2. Furthermore, JNK and pan-caspase inhibitors also protect cells from MSt-2-induced apoptosis. In addition to this, MSt-2 was found to be more potent in human colon carcinoma (HCT116) and human gastric cancer (AGS) cells while it has no effect on human normal dermal fibroblast. The important structure-activity relationship observed in the current study which makes MSt-2 more potent than MSt-6 is the position of thiazole side chain and stereochemistry of position 3 in chemical structure. In short the results of our study demonstrate that MSt-2-induced rapid ROS generation and mitochondrial dysfunction in cells trigger events responsible for mitochondria-dependent apoptosis pathway.

Aim of the Study: Helicobacter pylori infection plays a crucial role in the pathogenesis of peptic ulcer, and gastric cancer. The current PPI-based triple regimens for the eradication of Helicobacter pylori faces uprising resistance problem demanding for the search of novel candidates. Medicinal plants have always been a source of lead compounds for drug discovery. In the present study, we evaluated the anti-Helicobacter pylori activity of 50 commonly used Unani (traditional) medicine plants from Pakistan that are extensively utilized for the cure of gastrointestinal disorders to explore the natural source for pilot compounds against Helicobacter pylori., Materials and Methods: Total seven clinical isolates and one standard strain were employed to examine the bactericidal effects of medicinal plants. Helicobacter pylori was isolated from the antral biopsy specimens and confirmed through the standard microbiology procedures. Minimum bactericidal concentration (MBC) of the active plants was determined at the concentration range from 7.8 to 500 microg/ml., Results: Among the herbs evaluated, more than 50% inhibited the growth of eight strains at the concentration of 500 microg/ml. The 70% aqueous-ethanol extracts of Curcuma amada Roxb., Mallotus phillipinesis (Lam) Muell., Myrisctica fragrans Houtt., and Psoralea corylifolia L. demonstrated strong anti-Helicobacter pylori activity with MBC value ranged from 15.6 to 62.5 microg/ml. The most potent bactericidal activity was exhibited by Mallotus phillipinesis (Lam) Muell. which completely killed the bacteria at the concentration of 15.6-31.2 microg/ml., Conclusion: The results revealed significant anti-Helicobacter pylori activity of medicinal plants which could be the potential source of new bactericidal agents.

The effects of acacetin (1) and 4,5-O-dicaffeoylquinic acid methyl ester (2), compounds contained in the flowers of Chrysanthemum sinense SABINE, on the serum uric acid level were investigated using the rats pretreated with the uricase inhibitor potassium oxonate as an animal model for hyperuricemia. When administered per orally at doses of 20 and 50 mg/kg, 1 reduced the serum uric acid level by 49.9 and 63.9%, respectively and 2 reduced the level by 31.2 and 44.4%, respectively. On the other hand, when the same doses were given intraperitoneally, both of compounds also exhibited a dose-dependent and more marked reduction of the serum uric acid level (% reduction at 20 and 50 mg/kg were 63.0 and 95.1% in 1, respectively and 66.9 and 86.5% in 2, respectively). Furthermore, the compounds 1 and 2 inhibited the rat liver xanthine oxidase activity with IC(50) values of 2.22 muM and 5.27 muM, respectively. These results demonstrated the hypouricemic action of 1 and 2, which may be attributable to their xanthine oxidase inhibitory activity.