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1.
Public Health ; 145: 124-131, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28359380

ABSTRACT

OBJECTIVES: Reliable and valid measures of waterpipe smoking are essential to study its health effects. The purpose of this study was to examine the reliability and validity of an Arabic translation of Maziak questionnaire that assesses various aspects of waterpipe smoking in epidemiological studies. STUDY DESIGN: A cross-sectional study. METHODS: This questionnaire was translated, back translated, and culturally adapted to the local Arabic dialect. Construct and convergent validity were assessed in a sample of 119 daily waterpipe smokers (WPS) and 30 occasional WPS, defined as smoking at least one waterpipe per week but less than daily from Beirut and Doha (mean age = 52.4 years, males = 61.7%). Construct validity was assessed by comparing the smoking behavior of daily and occasional WPS. Convergent validity was assessed by correlating daily smoking intensity ('number of waterpipe smoked per day') with 'number of waterpipe smoked yesterday' and by correlating lifetime smoking exposure (waterpipe-year) calculated by multiplying number of waterpipe smoked per day × duration of waterpipe smoking with alternate measures obtained graphically (graphical waterpipe-year) or adjusted (adjusted waterpipe-year). Criterion validity was assessed by correlating daily smoking intensity and lifetime smoking exposure with serum cotinine level. Test-retest reliability was analyzed by re-administering the questionnaire to 30 daily and 30 occasional WPS after 2 weeks. RESULTS: Smoking intensity, patterns of use, and willingness to quit differed significantly between daily and occasional WPS. Daily smoking intensity correlated strongly with the number of waterpipe smoked yesterday (rs = 0.68, P < 0.001), but not in the occasional WPS (rs = 0.13, P = 0.70). Waterpipe-year correlated very strongly with adjusted waterpipe-year and graphical waterpipe-year (rs = 0.98, P < 0.001 and rs = 0.92, P < 0.001, respectively). Waterpipe-year, daily smoking intensity, and number of waterpipe smoked yesterday, correlated weakly but significantly with serum cotinine levels (rs = 0.243, P = 0.01; rs = 0.359, P < 0.01 and rs = 0.387, P < 0.01, respectively). The type and pattern of waterpipe use items showed high test-retest reliability with near perfect agreement (k > 0.9), the sharing and intention to quit waterpipe items had substantial agreement (k > 0.6), and the intent to quit item showed moderate agreement (k > 0.4). CONCLUSION: The questionnaire showed strong reliability, face validity, construct and convergent validity, and a weak but statistically significant criterion validity. Maziak questionnaire is valid and reliable for assessing waterpipe smoking patterns, intensity, and willingness to quit.


Subject(s)
Arabs , Behavior, Addictive/diagnosis , Language , Smoking/adverse effects , Surveys and Questionnaires/standards , Adult , Behavior, Addictive/psychology , Cross-Sectional Studies , Female , Humans , Lebanon , Male , Middle Aged , Psychometrics , Qatar , Reproducibility of Results , Sensitivity and Specificity , Tobacco Use Disorder/diagnosis
2.
Phytother Res ; 30(5): 768-73, 2016 May.
Article in English | MEDLINE | ID: mdl-27145225

ABSTRACT

Luteolin-7-O-glycoside (LG), an abundant component in many edible plants, was found to be one of the major constituents of the aqueous methanol extract of Trifolium alexandrinum L. family Fabaceae, a fodder plant widely cultivated in Egypt. The estrogenic activity of LG concerning the effect on uterotrophy, lipid profile, weight gain and bone enhancement activity was determined in ovariectomized rat model at a dose of 5 mg/kg. Luteolin-7-O-glycoside showed significant estrogenic effect through the preservation of normal uterine weight and plasma estradiol level. It also significantly inhibited the bone turnover markers plasma bone-specific alkaline phosphatase, plasma osteocalsin, type I procollagen N-terminal, and C-telopeptide of type II collagen levels. It induced a significant improvement in plasma lipid profile. The effect of LG was comparable with estradiol with lower effect on uterine weight. Liver and kidney functions revealed a wide safety of LG at this dose level. The present study revealed that LG may be a promising hormone replacement therapy after being examined thoroughly on human. Copyright © 2016 John Wiley & Sons, Ltd.


Subject(s)
Flavones/chemistry , Glucosides/chemistry , Lipids/chemistry , Plant Extracts/chemistry , Trifolium/chemistry , Animals , Estrogens/pharmacology , Female , Humans , Plant Extracts/pharmacology , Rats
4.
Data Brief ; 53: 110170, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38439990

ABSTRACT

These datasets contain measures from multi-modal data sources. They include objective and subjective measures commonly used to determine cognitive states of workload, situational awareness, stress, and fatigue using data collection tools such as NASA-TLX, SART, eye tracking, EEG, Health Monitoring Watch, a survey to assess training, and a think-aloud situational awareness assessment following the SPAM methodology. Also, data from a simulation formaldehyde production plant based on the interaction of the participants in a controlled control room experimental setting is included. The interaction with the plant is based on a human-in-the-loop alarm handling and process control task flow, which includes Monitoring, Alarm Handling, Recovery planning, and intervention (Troubleshooting, Control and Evaluation). Data was collected from 92 participants, split into four groups while they underwent the described task flow. Each participant tested three scenarios lasting 15-18 min with a -10-min survey completion and break period in between using different combinations of decision support tools. The decision support tools tested and varied for each group include alarm prioritisation vs. none, paper-based vs. Digitised screen-based procedures, and an AI recommendation system. This is relevant to compare current practices in the industry and the impact on operators' performance and safety. It is also applicable to validate proposed solutions for the industry. A statistical analysis was performed on the dataset to compare the outcomes of the different groups. Decision-makers can use these datasets for control room design and optimisation, process safety engineers, system engineers, human factors engineers, all in process industries, and researchers in similar or close domains.

5.
Cureus ; 15(10): e47351, 2023 Oct.
Article in English | MEDLINE | ID: mdl-38021980

ABSTRACT

Gabapentin contains a cyclohexyl group and is a form of gamma-aminobutyric acid (GABA). Despite its name, gabapentin does not affect the inhibitory neurotransmitter GABA or its receptors. Instead, it acts as a ligand, binding strongly to the α2δ (Ca) channel subunit and interfering with its regulatory function and the release of excitatory neurotransmitters. Gabapentin is approved by the FDA for treating seizure disorders and neuropathic pain, except for trigeminal neuralgia. However, it is frequently used off-label to treat other pain conditions and psychological disorders, such as anxiety. Unlike other drugs, gabapentin is not metabolized in the liver and is solely excreted by the kidneys. Therefore, it is crucial to adjust the dosage in patients with renal insufficiency to avoid severe adverse effects. In this case report, we present a patient with chronic renal impairment who experienced devastating myoclonic jerky movements shortly after increasing his gabapentin dose.

6.
J Med Case Rep ; 17(1): 203, 2023 May 18.
Article in English | MEDLINE | ID: mdl-37198611

ABSTRACT

BACKGROUND: While breast cancer is the most common cancer in women, cutaneous metastases are rare in breast cancer. Additionally, scalp involvement in breast cancer metastasis is extremely rare. That being said, scalp lesions should always be thoroughly investigated to distinguish metastatic lesions from other neoplasms. CASE PRESENTATION: A 47-year-old female Middle-Eastern patient presented with metastatic breast cancer in the lungs, bone, liver, and brain with no signs of multiple organ failure, in addition to cutaneous metastases, including the scalp. Between 2017 and 2022, she was managed through modified radical mastectomy, radiotherapy, and several lines of chemotherapy. She presented in September of 2022 with enlarging scalp nodules, which started developing 2 months prior to her presentation. Physical examination revealed firm, non-tender, and immobile skin lesions. Magnetic resonance imaging scan of the head showed soft tissue nodules in different sequences. A punch biopsy was taken from the largest scalp lesion and showed metastatic invasive ductal carcinoma. A panel of immunohistochemistry stains was applied, because a single specific marker for differentiating primary cutaneous adnexal tumors or other malignant neoplasms from breast cancer has not yet been identified. The panel showed positive estrogen receptor 95%, progesterone receptor 5%, negative human epidermal growth factor receptor 2, positive GATA binding protein 3, positive cytokeratin-7, negative P63, and negative KIT (CD117). CONCLUSION: Breast cancer metastases to the scalp are extremely uncommon. When a scalp metastasis is present, it might be the only symptomatic sign of disease progression or widespread metastatic lesions. However, such lesions warrant a comprehensive radiologic and pathologic workup to rule out other possibilities of skin pathologies, such as sebaceous skin adenocarcinoma as it effects the management plan.


Subject(s)
Breast Neoplasms , Carcinoma, Ductal, Breast , Skin Neoplasms , Humans , Female , Middle Aged , Breast Neoplasms/pathology , Scalp/pathology , Mastectomy , Skin Neoplasms/pathology , Carcinoma, Ductal, Breast/therapy , Melanoma, Cutaneous Malignant
7.
Cureus ; 15(10): e47856, 2023 Oct.
Article in English | MEDLINE | ID: mdl-38021845

ABSTRACT

INTRODUCTION: Deep vein thrombosis (DVT) is a medical disorder that arises when a coagulation of blood forms in a deep vein, entirely or partially blocking veins, and commonly affects the lower limb. The occurrence is fairly common worldwide and it is said to increase with age, with males being at a higher risk than females. OBJECTIVE: This study aims to determine the prevalence and risk factors of DVT among adult surgical patients in Aseer Central Hospital in the Aseer Region of Saudi Arabia. METHODS: This is a cross-sectional study involving 602 adult surgical patients hospitalized in the Aseer Central Hospital. Self-administered questionnaires were used to collect data from the respondents, and the data collected were analyzed using IBM SPSS Statistics for Windows, Version 24.0 (Released 2016; IBM Corp., Armonk, New York, United States). Statistical tests of association were used among the categorical variables. Association between variables was considered significant when p-value was less than 0.05. Binary logistic regression was performed to eliminate the effect of confounders in determining the risk factors for developing DVT among the respondents. RESULTS: The questionnaire response rate was 100%, with the mean age of the respondents being 44.2 ± 19.7 years. The prevalence of DVT was 7% (n=42). Obesity with adjusted OR (aOR) 17.9 (95%CI =5.39-59.18), hypertension with aOR 0.3 (95%CI =0.08-1.03), ischemic heart disease with aOR4.5 (95%CI =1.18-16.83), and orthopedics aOR 0.1 (95%CI=0.013-.240) were found to be independent risk factors for developing DVT among the respondents (p-value <=0.05). Other variables like diabetes, contraception, and pregnancy were not statistically associated with the development of DVT (p-value> 0.05) in these respondents. CONCLUSION: The findings of this study indicated a significantly low prevalence in comparison to Saudi Arabian research. Key risk factors included obesity (18x higher risk), ischemic heart disease, and hypertension. Surgery location, orthopedic cast, and Doppler ultrasound also influenced risk, while age and sex weren't significant predictors.

8.
Materials (Basel) ; 16(7)2023 Mar 29.
Article in English | MEDLINE | ID: mdl-37049042

ABSTRACT

This study investigated the structural behavior of a beam-slab member fabricated using a steel C-Purlins beam carrying a profile steel sheet slab covered by a dry board sheet filled with recycled aggregate concrete, called a CBPDS member. This concept was developed to reduce the cost and self-weight of the composite beam-slab system; it replaces the hot-rolled steel I-beam with a steel C-Purlins section, which is easier to fabricate and weighs less. For this purpose, six full-scale CBPDS specimens were tested under four-point static bending. This study investigated the effect of using double C-Purlins beams face-to-face as connected or separated sections and the effect of using concrete material that contains different recycled aggregates to replace raw aggregates. Test results confirmed that using double C-Purlins beams with a face-to-face configuration achieved better concrete confinement behavior than a separate configuration did; specifically, a higher bending capacity and ductility index by about +10.7% and +15.7%, respectively. Generally, the overall bending behavior of the tested specimens was not significantly affected when the infill concrete's raw aggregates were replaced with 50% and 100% recycled aggregates; however, their bending capacities were reduced, at -8.0% and -11.6%, respectively, compared to the control specimen (0% recycled aggregates). Furthermore, a new theoretical model developed during this study to predict the nominal bending strength of the suggested CBPDS member showed acceptable mean value (0.970) and standard deviation (3.6%) compared with the corresponding test results.

9.
Retina ; 32(6): 1171-80, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22088983

ABSTRACT

PURPOSE: The purpose of this article is to evaluate the effect of nicotine on anti-vascular endothelial growth factor therapy in the treatment of neovascular age-related macular degeneration. METHODS: One group of mice received nicotine in drinking water and the other group received water only. Choroidal neovascularization (CNV) was induced with a laser. Nicotinic acetylcholine receptor-α7 (nAChRα7) expression was evaluated by immunohistochemistry. Bevacizumab or adiponectin peptide II (APNpII) was injected intravitreally on Day 7 postlaser, and the effects were evaluated on Days 14 and 21. α-Bungarotoxin was injected intraperitoneally on Days 2 to 5, and its effect was evaluated on Day 14. RESULTS: Expression of nAChRα7 was 2 to 7 times higher between Days 3 and 7 postlaser compared with naive mice. In water-fed mice, APNpII, bevacizumab, and α-bungarotoxin significantly reduced CNV size. In nicotine-fed mice, treatment with APNpII or bevacizumab did not significantly reduce CNV size, whereas α-bungarotoxin did have an effect. Comparing water- and nicotine-fed mice, CNV size was 61% to 86% smaller in water-fed mice except for the α-bungarotoxin group, where there was no difference. Platelet-derived growth factor and vascular endothelial growth factor expression was 1.5- to 2.5-fold higher at Day 14 in nicotine-treated mice. CONCLUSION: Nicotine significantly blocks the effect of anti-vascular endothelial growth factor therapy in the treatment of laser-induced neovascular age-related macular degeneration. nAChRα7 is significantly upregulated during the formation of CNV, and treatment with an nAChRα7 antagonist decreases CNV size irrespective of nicotine administration.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Choroidal Neovascularization/drug therapy , Nicotine/pharmacology , Vascular Endothelial Growth Factors/antagonists & inhibitors , Adiponectin/therapeutic use , Analysis of Variance , Animals , Bevacizumab , Bungarotoxins/pharmacology , Choroid/metabolism , Choroidal Neovascularization/metabolism , Choroidal Neovascularization/pathology , Disease Models, Animal , Immunohistochemistry , Intravitreal Injections , Male , Mice , Mice, Inbred C57BL , Receptors, Nicotinic/metabolism , Retinal Pigment Epithelium/metabolism , Vascular Endothelial Growth Factors/metabolism , alpha7 Nicotinic Acetylcholine Receptor
10.
Eur Rev Med Pharmacol Sci ; 15(12): 1429-44, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22288304

ABSTRACT

BACKGROUND AND OBJECTIVES: The present study aimed to evaluate the effect of fish oil and Artichoke (Cynara scolymus I.) against diethylnitrosamine (DEN) induced hepatocellular carcinoma in rats. MATERIALS AND METHODS: Animals were divided into 8 groups. Group 1, control rats. Group 2: rats injected with single dose of DEN (100 mg/kg body weight). Groups 3-8 supplemented with different concentrations of either fish oil or artichoke for 25 days before DEN injection. RESULTS: DEN treatment revealed a significant decrease in tissue xanthine oxidase (XO), glutathione, glutathione-s-transferase (GST), and a marked increase in malondialdehyde (MDA) and nitric oxide (NO) levels. Vascular endothelial growth factor (VEGF), alpha-fetoprotein (AFP), and ferritin levels showed a significant increase. A significant increase in serum aspartate amino transferase (AST), alanine amino transferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and total bilirubin levels were found. A significant decrease in tissue total proteins and serum albumin was observed. The administration of DEN affected the liver cell through occurrence of hepatic cellular degeneration and necrosis. Treatment with fish oil (5%, 10%) or artichoke heads or leaves (0.5, 1 g) for 25 days led to significant amelioration of DEN-induced changes in the biochemical parameters. An almost normal histological architecture of the liver, in treated groups, was showed as compared to the controls. CONCLUSIONS: The results pointed that 10% fish oil and 1 g% leaves of artichoke succeeded to protect from hepatocellular carcinoma to a certain degree. In addition, they may be considered as protective foods against angiogenesis.


Subject(s)
Carcinoma, Hepatocellular/prevention & control , Cynara scolymus/chemistry , Fish Oils/pharmacology , Liver Neoplasms, Experimental/prevention & control , Plant Extracts/pharmacology , Animals , Carcinoma, Hepatocellular/pathology , Diethylnitrosamine/toxicity , Dose-Response Relationship, Drug , Female , Fish Oils/administration & dosage , Liver Neoplasms, Experimental/pathology , Plant Extracts/administration & dosage , Rats , Rats, Sprague-Dawley
11.
Tunis Med ; 89(1): 37-42, 2011 Jan.
Article in French | MEDLINE | ID: mdl-21267826

ABSTRACT

BACKGROUND: The TCI is a mode of administration that provides greater security by allowing more accurate titration of the anesthetic agent. It leads to a better adaptation to the desired effects, and provide a great interest for the realization of anesthetic induction and the prediction of waking for a well- determined population. OBJECTIVE: The aim of our prospective study was to evaluate the feasibility of TCI in patients with morbid obesity undergoing laparoscopic surgery for obesity. METHODS: Thirty patients were included in this study. Age and BMI means were 32 years and 49.31 kg / m2. Our protocol was proposed to associate an hypnotic agent (propofol) to an opioid one (remifentanil) using the technique of the TCI, with respectively Schnider and Minto models. RESULTS: The induction protocol has brought good conditions for laryngoscopy with no hypertensive peak or desaturation episode. The period of unconsciousness was 89 seconds with an average target concentration of propofol of 5.1 mg / ml. We also noted hemodynamic stability in 79% of patients at induction. During both preparation phase and final installation of the patients, a low ERC to 2 hg / ml was consistent with a suitable hemodynami profile. We obtained hemodynamic stability by adapting target concentration of remifentanil at different operating times (Surgical incision: 3.64 hg / ml, insufflation of the peritoneum: 5.37 hg / ml, jejuno-jejunal resection anastomosis: 9 hg / ml, gastric resection and gastrojejunal anastomosis: 14.2 hg / ml). During this period, no episodes of bradycardia or hypotension were noticed. During the recovery phase and while doing the distribution of CEP and CER according to the BMI of patients, we identified two groups: Group 1 (BMI <49 kg / m2): fast time extubation (11 min) and target concentrations of propofol and remifentanil respectively at 1.3 mg / ml and 1.25 hg / ml which is similar to most publications on this subject and Group 2 (BMI> 49 kg / m2): time-delayed extubation (23 min) with very low values of CEP and CER inconsistent with the literature data.


Subject(s)
Analgesics, Opioid/administration & dosage , Anesthetics, Intravenous/administration & dosage , Laparoscopy , Obesity, Morbid/surgery , Adult , Feasibility Studies , Humans , Infusions, Intravenous , Middle Aged , Pain, Postoperative/prevention & control , Piperidines/administration & dosage , Propofol/administration & dosage , Prospective Studies , Remifentanil
12.
Trop Biomed ; 38(1): 8-13, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33797517

ABSTRACT

Coccidiosis is the most important protozoan disease in broilers all over the world. Controlling of broilers coccidiosis via vaccination rather than chemicals is a new trend with promising results. Thus, the present work describes an evaluation of Eimeria tenella Lab-made vaccine of local Egyptian strain and its comparative efficacy with a commercial live vaccine "Fortegra®". Eighty broiler chickens one day old were used; they were divided in to 4 equal groups; 20 chicks each. Group 1 (G1) kept as control negative, G2 administrated orally with lab-made sporulated oocysts vaccine at 5 days old, the birds of G3 vaccinated orally with Fortegra® at day 6 of age, and G4 served as control positive. All birds were challenge by 50,000 sporulated oocysts of E. tenella at day 21. For testing the efficacy and comparison; OPG (oocyst per gram), serum Interleukin4 (IL4) levels, Immunoglobulin A (IgA) levels in both serum and ceca, cecal lesion score, as well as histopathological changes in ceca of tested groups were evaluated. The results demonstrated significantly elevated IL4 level in serum and IgA level in serum and cecum of G2 than G3. IgA in cecum significantly elevated in G2 than G3. OPG significantly decreased in both vaccinated groups (G2 and G3), and have lower lesion score than nonimmunized group. Cecal tissues of vaccinated groups had mild pathological changes. Conclusively, good immunization by the currently tested vaccine, against experimental E. tenella infection was observed.


Subject(s)
Coccidiosis/veterinary , Poultry Diseases/prevention & control , Protozoan Vaccines/immunology , Animals , Cecum/immunology , Chickens , Coccidiosis/prevention & control , Egypt , Eimeria tenella , Immunoglobulin A , Interleukin-4 , Oocysts , Poultry Diseases/parasitology , Vaccines, Attenuated
13.
Pediatrics ; 145(3)2020 03.
Article in English | MEDLINE | ID: mdl-32051219

ABSTRACT

BACKGROUND: Opioid overprescription has the potential to lead to harmful medications remaining in homes and to a rise in accidental or deliberate ingestion by children and adolescents. Although methods for opioid disposal are available, many are costly or require greater than minimal effort for the patient. In this study, we used a mail-back return envelope to retrieve unused opioids after ambulatory pediatric surgery. METHODS: This feasibility study was performed to assess the rate of opioid return by using a mail-back envelope for children ages 0 to 18 prescribed opioids after outpatient surgery. Participants were provided a return envelope as well as instruction on the dangers of opioids in the home. Our primary outcome was to assess the absolute percent return rate through the use of a mail-back envelope. RESULTS: Between November 2017 and October 2018, we identified 355 patients, of whom 331 were included in the analysis. In total, 64 (19.3%) returned opioids. In total, >2000 mL of liquid opioids and >250 tablets or nearly 3000 mg of oral morphine equivalents were removed from the homes of the 64 participants. Of those patients returning unused medications, the median rate of return was 58% (interquartile range = 34.7%-86.1%) of the written prescription. CONCLUSIONS: The findings suggest that providing a free mail-back return envelope is a suitable way to remove unused opioids from the home after pediatric surgery. Additional research is needed to identify barriers to return of unused medications.


Subject(s)
Ambulatory Surgical Procedures , Analgesics, Opioid/therapeutic use , Patient Discharge , Postal Service , Accidents, Home/prevention & control , Adolescent , Child , Feasibility Studies , Female , Hospitals, Pediatric , Humans , Male , Opioid-Related Disorders/prevention & control , Pain, Postoperative/drug therapy , Poisoning/prevention & control , Prescription Drug Diversion/prevention & control , Texas
14.
HSS J ; 15(1): 72-75, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30863236

ABSTRACT

BACKGROUND: The opioid prescribing patterns of orthopedic surgeons have been shown to play a role in exacerbating rates of opioid misuse among post-surgical patients. Demonstrable success has been appreciated by combining policy-level approaches and clinical education-based strategies to inform patients of alternative modalities of post-operative analgesia. QUESTIONS/PURPOSES: The purpose of this review was to address two questions: What are the most substantiated measures orthopedic surgeons can take to limit opioid misuse or addiction among their patients? What advantages are gained in orthopedic surgeons' collaborating with other healthcare professionals with influence over patients' post-operative opioid exposure? METHODS: We searched two databases for articles on multidisciplinary policy-based solutions to mitigating the opioid overdose crisis among musculoskeletal patients. Articles produced from the search were searched for further evidence supporting the use of standardized clinical and administrative protocols in mitigating opioid misuse within this patient population. Successful approaches to mitigating misuse of opioids in this demographic were synthesized from recurring themes in the studies. RESULTS: Multiple articles support orthopedic surgeons being aware of the risk factors for chronic opioid use among their patients, as well as multidisciplinary strategies involving orthopedic surgeons and other healthcare/governmental professionals to address the burden of the opioid crisis on surgical patients. CONCLUSIONS: Addressing the misuse of opioids among orthopedic patients requires appropriate prescribing practices and long-term support of patients. Collaboration between surgeons and policymaking entities is recognized as an effective population-wide approach to preventing opioid dependence, misuse, and addiction.

15.
Oncogene ; 37(1): 39-51, 2018 01 04.
Article in English | MEDLINE | ID: mdl-28846107

ABSTRACT

Malignant tumors, such as colorectal cancer (CRC), are heterogeneous diseases characterized by distinct metabolic phenotypes. These include Warburg- and reverse Warburg phenotypes depending on differential distribution of the lactate carrier proteins monocarboxylate transporter-4 and -1 (MCT4 and MCT1). Here, we elucidated the role of the antioxidant transcription factor nuclear factor E2-related factor-2 (Nrf2) as the key regulator of cellular adaptation to inflammatory/environmental stress in shaping the metabolism toward a reverse Warburg phenotype in malignant and premalignant colonic epithelial cells. Immunohistochemistry of human CRC tissues revealed reciprocal expression of MCT1 and MCT4 in carcinoma and stroma cells, respectively, accompanied by strong epithelial Nrf2 activation. In colorectal tissue from inflammatory bowel disease patients, MCT1 and Nrf2 were coexpressed as well, relating to CD68+inflammatory infiltrates. Indirect coculture of human NCM460 colonocytes with M1- but not M2 macrophages induces MCT1 as well as G6PD, LDHB and TALDO expression, whereas MCT4 expression was decreased. Nrf2 knockdown or reactive oxygen species (ROS) scavenging blocked these coculture effects in NCM460 cells. Likewise, Nrf2 knockdown inhibited similar effects of tBHQ-mediated Nrf2 activation on NCM460 and HCT15 CRC cells. M1 coculture or Nrf2 activation/overexpression greatly altered the lactate uptake but not glucose uptake and mitochondrial activities in these cells, reflecting the reverse Warburg phenotype. Depending on MCT1-mediated lactate uptake, Nrf2 conferred protection from TRAIL-induced apoptosis in NCM460 and HCT15 cells. Moreover, metabolism-dependent clonal growth of HCT15 cells was induced by Nrf2-dependent activation of MCT1-driven lactate exchange. These findings indicate that Nrf2 has an impact on the metabolism already in premalignant colonic epithelial cells exposed to inflammatory M1 macrophages, an effect accompanied by growth and survival alterations. Favoring the reverse Warburg effect, these Nrf2-dependent alterations add to malignant transformation of the colonic epithelium.


Subject(s)
Colorectal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Monocarboxylic Acid Transporters/genetics , Muscle Proteins/genetics , NF-E2-Related Factor 2/metabolism , Symporters/genetics , Apoptosis/genetics , Biopsy , Cell Line, Tumor , Cell Transformation, Neoplastic/genetics , Coculture Techniques , Colon/cytology , Colon/metabolism , Colon/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Fibroblasts , Gene Knockdown Techniques , Humans , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/pathology , Intestinal Mucosa/cytology , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Lactic Acid/metabolism , Macrophages , Monocarboxylic Acid Transporters/metabolism , Muscle Proteins/metabolism , NF-E2-Related Factor 2/genetics , Oxidative Stress , RNA, Small Interfering/metabolism , Reactive Oxygen Species/metabolism , Stromal Cells/metabolism , Stromal Cells/pathology , Symporters/metabolism , Tumor Microenvironment/genetics
16.
Food Funct ; 8(3): 985-996, 2017 Mar 22.
Article in English | MEDLINE | ID: mdl-28197590

ABSTRACT

The complexity of the metabolic changes in obese individuals still presents a challenge for the understanding of obesity-related metabolic disruptions and for obesity management. In this study, a gas chromatography mass spectrometry (GC-MS) based metabolomics approach targeting urine metabolism has been applied to assess the potential roles of functional foods and exercise for obesity management in rats. Male albino rats diagnosed as obese via histopathology and biochemical assays were administered functional foods in common use for obesity management including pomegranate, grapefruit, and red cabbage juice extracts in parallel with swimming exercise. Urine samples were collected from these rats, and likewise from healthy control animals, for metabolite analysis using (GC-MS) coupled to multivariate data analysis. The results revealed a significant elevation in oxalate and phosphate levels in obese rat urine concurrent with lower lactate levels as compared to the control group. Furthermore, and to pinpoint the bioactive agents in the administered functional foods, ultra performance liquid chromatography (UPLC) coupled to high resolution time-of-flight mass spectrometry (TOF-MS) was employed for secondary metabolite profiling. The different phenolic classes found in the examined functional foods, viz. ellagitannins in pomegranate, flavanones in grapefruit and flavonols in red cabbage, are likely to mediate their anti-obesity effects. The results indicate that these functional foods and exercise were quite effective in reverting obesity-related metabolic disruptions back to normal status, as revealed by orthogonal partial least squares-discriminant analysis (OPLS-DA).


Subject(s)
Exercise Therapy , Fruit and Vegetable Juices/analysis , Functional Food/analysis , Obesity/therapy , Urine/chemistry , Animals , Brassica/metabolism , Citrus paradisi/metabolism , Gas Chromatography-Mass Spectrometry , Humans , Lythraceae/metabolism , Male , Metabolomics , Obesity/metabolism , Rats
17.
Nat Prod Res ; 20(1): 57-61, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16286310

ABSTRACT

Two new flavonoids, 8-hydroxyisoscoparin (1) and luteolin 7-O-glucoside 4''-sulfate (2), along with eight known flavonoids, including luteolin 7-O-glucoside 2''-sulfate, were isolated and identified from Washingtonia filifera. All compounds were characterized by (1)H-NMR, (13)C-NMR, CI-MS, FABMS and UV. The antioxidant activities of various W. filifera extracts were determined.


Subject(s)
Antioxidants/pharmacology , Arecaceae/chemistry , Flavonoids/pharmacology , Antioxidants/chemistry , Antioxidants/isolation & purification , Flavonoids/chemistry , Flavonoids/isolation & purification , Magnetic Resonance Spectroscopy , Spectrometry, Mass, Fast Atom Bombardment , Spectrophotometry, Ultraviolet
18.
Rev Neurol (Paris) ; 162(6-7): 729-33, 2006 Jun.
Article in French | MEDLINE | ID: mdl-16840981

ABSTRACT

INTRODUCTION: Tunisia is considered as a low zone of prevalence for multiple sclerosis (MS). Consequently, only very few studies have taken an interest in this disorder in North Africa. The objective of this study was to compare the clinical and paraclinical parameters and the outcome of the disease in patients affected with MS in Tunisia during two periods (1974-1978 and 1996-2000) and to determine the incidence of the disease and the impact of the use of diagnostic criteria, including the MRI. PATIENTS AND METHODS: We report the results of a retrospective study concerning patients classified with MS and followed in the National Institute of Neurology in Tunis between 1974 and 2000, with 1058 records examined. We divided the patients into two groups belonging to two periods: Group I (1974-1978, 125 patients classified according to the McAlpine criteria) and Group II (1996-2000, 247 patients classified according to Poser's criteria. We compared the clinical and paraclinical parameters of the two groups. RESULTS: The incidence of the disease was evaluated at 1.3 per 100,000 individuals, placing Tunisia in the middle zone of prevalence. There was no significant difference in the mean age of onset (32.4+/-10.1 years) between the two groups. A slight male preponderance was observed in Group I (M/F sex ratio=1.25). The clinical outcome factors were age of onset after 40 years, pyramidal signs as the first symptom, and the progressive forms of the disease. Although Group II had an earlier diagnosis of the disease and a more systematic treatment of relapses, the functional outcome was similar between the two groups. CONCLUSION: MS in Tunisia has the same clinical characteristics and disease outcome as in other countries. The use of MRI allowed earlier diagnosis but did not increase the overall proportion of definite MS.


Subject(s)
Brain/pathology , Multiple Sclerosis/epidemiology , Multiple Sclerosis/pathology , Adult , Disability Evaluation , Disease Progression , Female , Humans , Incidence , Magnetic Resonance Imaging , Male , Middle Aged , Prevalence , Prognosis , Retrospective Studies , Severity of Illness Index , Tunisia/epidemiology
19.
Tunis Med ; 84(6): 361-4, 2006 Jun.
Article in French | MEDLINE | ID: mdl-17042210

ABSTRACT

Emery Dreifuss muscular dystrophy (EDMD) is an uncommon hereditary myopathy characterized by 3 symptoms: slow progressive muscular atrophy, muscular contractures and cardiac disease which affect prognosis. We report a 22 year-old patient with EDMD which shows the typical features of the associated dilated cardiomyopathy, ventricular arrhythmia, atrio-ventricular block, atrial standstill then atrial paralysis.


Subject(s)
Heart Diseases/etiology , Muscular Dystrophy, Emery-Dreifuss/complications , Adult , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/etiology , Echocardiography , Electrocardiography , Follow-Up Studies , Heart Block/diagnosis , Heart Block/etiology , Heart Block/therapy , Heart Diseases/diagnosis , Heart Diseases/physiopathology , Heart Diseases/therapy , Humans , Male , Muscular Dystrophy, Emery-Dreifuss/diagnosis , Pacemaker, Artificial , Prognosis , Stroke Volume , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/therapy , Time Factors
20.
Rev Neurol (Paris) ; 161(4): 477-9, 2005 Apr.
Article in French | MEDLINE | ID: mdl-15924087

ABSTRACT

A paradigmatic case of acute combined spinal cord degeneration and delirium due to inappropriate administration of folic acid in the context of chronic cobalamin deficiency is described. Rapid improvement was obtained with immediate cessation of folate administration and parenteral cobalamin supplementation. Folic acid and cobalamin prescription rules are recalled. Pathophysiological hypotheses tentatively explaining the neurotoxicity of folic acid in case of vitamin B12 deficiency are summarized.


Subject(s)
Folic Acid/adverse effects , Neurotoxicity Syndromes/etiology , Vitamin B 12 Deficiency/chemically induced , Vitamin B 12 Deficiency/complications , Acute Disease , Female , Humans , Middle Aged
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