Cereals of baking quality with absent or reduced toxicity are actively sought as alternative therapy to a gluten-free diet (GFD) for patients with coeliac disease (CD). Triticum monococcum, an ancient wheat, is a potential candidate having no toxicity in in-vitro and exvivo studies. The aim of our study was to investigate on the safety of administration of a single dose of gluten of Tm in patients with CD on GFD.
Antioxidant-mediated up-regulation of OGG1 via NRF2 induction is associated ...Enrique Moreno Gonzalez
Estrogen metabolism-mediated oxidative stress is suggested to play an important role in estrogen-induced breast carcinogenesis. We have earlier demonstrated that antioxidants,
vitamin C (Vit C) and butylated hydroxyanisole (BHA) inhibit 17β-estradiol (E2)-mediated oxidative stress and oxidative DNA damage, and breast carcinogenesis in female August
Copenhagen Irish (ACI) rats. The objective of the present study was to characterize the mechanism by which above antioxidants prevent DNA damage during breast carcinogenesis.
ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grad...Enrique Moreno Gonzalez
High-grade (WHO grade III and IV) astrocytomas are aggressive malignant brain tumors affecting humans with a high risk of recurrence in both children and adults. To date, limited information is available on the genetic and molecular alterations important in the onset and progression of pediatric high-grade astrocytomas and, even less, on the prognostic factors that influence long-term outcome in children with recurrence. A-to-I RNA editing is an essential post-transcriptional mechanism that can alter the nucleotide sequence of several RNAs and is
mediated by the ADAR enzymes. ADAR2 editing activity is particularly important in mammalian brain and is impaired in both adult and pediatric high-grade astrocytomas.
Moreover, we have recently shown that the recovered ADAR2 activity in high-grade astrocytomas inhibits in vivo tumor growth. The aim of the present study is to investigate whether changes may occur in ADAR2-mediated RNA editing profiles of relapsed highgrade astrocytomas compared to their respective specimens collected at diagnosis, in four pediatric patients.
OSU-03012 sensitizes breast cancers to lapatinib-induced cell killing: a role...Enrique Moreno Gonzalez
Lapatinib is characterized as an ErbB1/ErbB2 dual inhibitor and has recently been approved for the treatment of metastatic breast cancer. In this study, we examined mechanisms
associated with enhancing the activity of lapatinib via combination with other therapies.
Variant G6PD levels promote tumor cell proliferation or apoptosis via the STA...Enrique Moreno Gonzalez
Glucose-6-phosphate dehydrogenase (G6PD), elevated in tumor cells, catalyzes the first reaction in the pentose-phosphate pathway. The regulation mechanism of G6PD and pathological change in human melanoma growth remains unknown.
A new assay for measuring chromosome instability (CIN) and identification of...Enrique Moreno Gonzalez
Aneuploidy is a feature of most cancer cells that is often accompanied by an elevated rate of chromosome mis-segregation termed chromosome instability (CIN). While CIN can act as a driver of cancer genome evolution and tumor progression, recent findings point to the existence of a threshold level beyond which CIN becomes a barrier to tumor growth and therefore can be exploited therapeutically. Drugs known to increase CIN beyond the therapeutic threshold are currently few in number, and the clinical promise of targeting the
CIN phenotype warrants new screening efforts. However, none of the existing methods, including the in vitro micronuclei (MNi) assay, developed to quantify CIN, is entirely satisfactory.
Abnormal expression of Pygopus 2 correlates with a malignant phenotype in hum...Enrique Moreno Gonzalez
Pygopus 2 (Pygo2) is a Pygo family member and an important component of the Wnt signaling transcriptional complex. Despite this data, no clinical studies investigating Pygo2 expression in lung cancer have yet been reported.
CXCR7 is induced by hypoxia and mediates glioma cell migration towards SDF-1a...Enrique Moreno Gonzalez
Glioblastomas, the most common and malignant brain tumors of the central nervous system, exhibit high invasive capacity, which hinders effective therapy. Therefore, intense efforts aimed at improved therapeutics are ongoing to delineate the molecular mechanisms governing glioma cell migration and invasion.
Antioxidant-mediated up-regulation of OGG1 via NRF2 induction is associated ...Enrique Moreno Gonzalez
Estrogen metabolism-mediated oxidative stress is suggested to play an important role in estrogen-induced breast carcinogenesis. We have earlier demonstrated that antioxidants,
vitamin C (Vit C) and butylated hydroxyanisole (BHA) inhibit 17β-estradiol (E2)-mediated oxidative stress and oxidative DNA damage, and breast carcinogenesis in female August
Copenhagen Irish (ACI) rats. The objective of the present study was to characterize the mechanism by which above antioxidants prevent DNA damage during breast carcinogenesis.
ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grad...Enrique Moreno Gonzalez
High-grade (WHO grade III and IV) astrocytomas are aggressive malignant brain tumors affecting humans with a high risk of recurrence in both children and adults. To date, limited information is available on the genetic and molecular alterations important in the onset and progression of pediatric high-grade astrocytomas and, even less, on the prognostic factors that influence long-term outcome in children with recurrence. A-to-I RNA editing is an essential post-transcriptional mechanism that can alter the nucleotide sequence of several RNAs and is
mediated by the ADAR enzymes. ADAR2 editing activity is particularly important in mammalian brain and is impaired in both adult and pediatric high-grade astrocytomas.
Moreover, we have recently shown that the recovered ADAR2 activity in high-grade astrocytomas inhibits in vivo tumor growth. The aim of the present study is to investigate whether changes may occur in ADAR2-mediated RNA editing profiles of relapsed highgrade astrocytomas compared to their respective specimens collected at diagnosis, in four pediatric patients.
OSU-03012 sensitizes breast cancers to lapatinib-induced cell killing: a role...Enrique Moreno Gonzalez
Lapatinib is characterized as an ErbB1/ErbB2 dual inhibitor and has recently been approved for the treatment of metastatic breast cancer. In this study, we examined mechanisms
associated with enhancing the activity of lapatinib via combination with other therapies.
Variant G6PD levels promote tumor cell proliferation or apoptosis via the STA...Enrique Moreno Gonzalez
Glucose-6-phosphate dehydrogenase (G6PD), elevated in tumor cells, catalyzes the first reaction in the pentose-phosphate pathway. The regulation mechanism of G6PD and pathological change in human melanoma growth remains unknown.
A new assay for measuring chromosome instability (CIN) and identification of...Enrique Moreno Gonzalez
Aneuploidy is a feature of most cancer cells that is often accompanied by an elevated rate of chromosome mis-segregation termed chromosome instability (CIN). While CIN can act as a driver of cancer genome evolution and tumor progression, recent findings point to the existence of a threshold level beyond which CIN becomes a barrier to tumor growth and therefore can be exploited therapeutically. Drugs known to increase CIN beyond the therapeutic threshold are currently few in number, and the clinical promise of targeting the
CIN phenotype warrants new screening efforts. However, none of the existing methods, including the in vitro micronuclei (MNi) assay, developed to quantify CIN, is entirely satisfactory.
Abnormal expression of Pygopus 2 correlates with a malignant phenotype in hum...Enrique Moreno Gonzalez
Pygopus 2 (Pygo2) is a Pygo family member and an important component of the Wnt signaling transcriptional complex. Despite this data, no clinical studies investigating Pygo2 expression in lung cancer have yet been reported.
CXCR7 is induced by hypoxia and mediates glioma cell migration towards SDF-1a...Enrique Moreno Gonzalez
Glioblastomas, the most common and malignant brain tumors of the central nervous system, exhibit high invasive capacity, which hinders effective therapy. Therefore, intense efforts aimed at improved therapeutics are ongoing to delineate the molecular mechanisms governing glioma cell migration and invasion.
Polymorphism in Glutatione S-Transferase P1 and ManganeseSuperoxide Dismmutas...iosrjce
Susceptibility to preeclampsia is believed to have a genetic component. Several studies have reported
associations between polymorphisms of oxidative stress- related genes and preeclampsia. The aim of the present
study was to study the polymorphisms in anti-oxidant genes glutathione S-transferase P1 (GSTP1) and Mnsuperoxide
dismutase (Mn-SOD) in patients with of preeclampsia. Seventy four preeclampsia patients and fifty
age-matched healthy pregnant female controls were genotyped for GSTP1 and Mn-SOD. DNA was extracted
from peripheral blood of all patients and control women. DNA analysis was carried out by polymerase chain
reaction (PCR), and then digestion of the PCR products by restriction enzymes (RFLP) for both genes was
performed. As regards GSTP1, the carriers of Val (G) allele were significantly more frequent among
preeclampsia patients when compared to the control group (45.95% Vs. 19%, X
2=10.40, OR=2.418, 95%CI
(1.3698 - 4.269); p=0.0023). Preeclampsia patients had a lower frequency of GSTP1 Ile/Ile (AA) genotype
(31.1% Vs. 68% in control; X
2=13.09, OR=0.457, 95%CI (0.241 - 0.866); p =0.0164). The frequency of
GSTP1 Ile/Val (AG) and Val/Val (GG) genotypes was higher in preeclampsia patients than control (68.9%Vs.
32%; X
2= 12.83, OR=2.154, 95%CI (1.106 - 4.194); p =0.0241). However, non significant frequencies
differences as regards Mn-SOD genotypes or alleles were found between preeclampsia patients and control. It
could be concluded that, pregnant Egyptian women carrying the Val (G) allele of GSTP1 GSTP1 -105 Ile →Val
(-313 A to G) polymorphism may be more susceptible to preeclampsia either in homozygous or heterozygous state
Efficiency of cape gooseberry in attenuating some biochemical disorders and o...Professor-Dr Hanaa Hassan
In conclusion, the present data indicated the efficacy of CG juice supplementation as an
anti-hepatocellular carcinoma in addition to its ability as a chemosensitizer for ADR treatment. This is
mediated by intracellular pathways, involving improvement the alterations in liver functions as well as
other aspects of HCC, the suppression of oxidative stress and modulation of antioxidant defense
mechanism. Thus, supplementation with edible CG may help in safe application of cancer technology
in medicine as well as in many other aspects of nowadays life. Fractionation guided evaluation could
help in the development of ideal anticancer in the near future.
These are the abstracts indexed with my name in the Proceedings of the National Symposium on Evolving Paradigm to Improve Productivity from Dynamic Management and Value Addition for Plant Genetic Resources.
A phase I/II trial to evaluate the safety, feasibility and activity of salvag...Enrique Moreno Gonzalez
The current standard treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma (DLBCL) primarily consists of intensified salvage therapy and, if the disease is chemo-sensitive, high dose therapy followed with autologous stem cell transplantation. In the rituximab era however, this treatment approach has shown only limited benefit. In particular, patients relapsing after rituximab-containing primary treatment have an adverse prognosis, especially if this occurs within the first year after therapy or if the disease is primarily refractory. Therefore there is an ultimate need for improved salvage treatment approaches.
Fatty liver index correlates with non-alcoholic fatty liver disease, but not ...Enrique Moreno Gonzalez
Fatty liver index (FLI) was recently established to predict non-alcoholic fatty liver disease (NAFLD) in general population, which is known to be associated with coronary artery atherosclerotic disease (CAD).
This study aims to investigate whether FLI correlates with NAFLD and with newly diagnosed CAD in a special Chinese population who underwent coronary angiography.
Assessment of preoperative exercise capacity in hepatocellular carcinoma pati...Enrique Moreno Gonzalez
Cardiopulmonary exercise testing measures oxygen uptake at increasing levels of work and predicts cardiopulmonary performance under conditions of stress, such as after abdominal surgery. Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative prognosis. This study examined the relationship between preoperative exercise capacity and event-free survival in hepatocellular carcinoma (HCC) patients with chronic liver injury who underwent hepatectomy.
Polymorphism in Glutatione S-Transferase P1 and ManganeseSuperoxide Dismmutas...iosrjce
Susceptibility to preeclampsia is believed to have a genetic component. Several studies have reported
associations between polymorphisms of oxidative stress- related genes and preeclampsia. The aim of the present
study was to study the polymorphisms in anti-oxidant genes glutathione S-transferase P1 (GSTP1) and Mnsuperoxide
dismutase (Mn-SOD) in patients with of preeclampsia. Seventy four preeclampsia patients and fifty
age-matched healthy pregnant female controls were genotyped for GSTP1 and Mn-SOD. DNA was extracted
from peripheral blood of all patients and control women. DNA analysis was carried out by polymerase chain
reaction (PCR), and then digestion of the PCR products by restriction enzymes (RFLP) for both genes was
performed. As regards GSTP1, the carriers of Val (G) allele were significantly more frequent among
preeclampsia patients when compared to the control group (45.95% Vs. 19%, X
2=10.40, OR=2.418, 95%CI
(1.3698 - 4.269); p=0.0023). Preeclampsia patients had a lower frequency of GSTP1 Ile/Ile (AA) genotype
(31.1% Vs. 68% in control; X
2=13.09, OR=0.457, 95%CI (0.241 - 0.866); p =0.0164). The frequency of
GSTP1 Ile/Val (AG) and Val/Val (GG) genotypes was higher in preeclampsia patients than control (68.9%Vs.
32%; X
2= 12.83, OR=2.154, 95%CI (1.106 - 4.194); p =0.0241). However, non significant frequencies
differences as regards Mn-SOD genotypes or alleles were found between preeclampsia patients and control. It
could be concluded that, pregnant Egyptian women carrying the Val (G) allele of GSTP1 GSTP1 -105 Ile →Val
(-313 A to G) polymorphism may be more susceptible to preeclampsia either in homozygous or heterozygous state
Efficiency of cape gooseberry in attenuating some biochemical disorders and o...Professor-Dr Hanaa Hassan
In conclusion, the present data indicated the efficacy of CG juice supplementation as an
anti-hepatocellular carcinoma in addition to its ability as a chemosensitizer for ADR treatment. This is
mediated by intracellular pathways, involving improvement the alterations in liver functions as well as
other aspects of HCC, the suppression of oxidative stress and modulation of antioxidant defense
mechanism. Thus, supplementation with edible CG may help in safe application of cancer technology
in medicine as well as in many other aspects of nowadays life. Fractionation guided evaluation could
help in the development of ideal anticancer in the near future.
These are the abstracts indexed with my name in the Proceedings of the National Symposium on Evolving Paradigm to Improve Productivity from Dynamic Management and Value Addition for Plant Genetic Resources.
A phase I/II trial to evaluate the safety, feasibility and activity of salvag...Enrique Moreno Gonzalez
The current standard treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma (DLBCL) primarily consists of intensified salvage therapy and, if the disease is chemo-sensitive, high dose therapy followed with autologous stem cell transplantation. In the rituximab era however, this treatment approach has shown only limited benefit. In particular, patients relapsing after rituximab-containing primary treatment have an adverse prognosis, especially if this occurs within the first year after therapy or if the disease is primarily refractory. Therefore there is an ultimate need for improved salvage treatment approaches.
Fatty liver index correlates with non-alcoholic fatty liver disease, but not ...Enrique Moreno Gonzalez
Fatty liver index (FLI) was recently established to predict non-alcoholic fatty liver disease (NAFLD) in general population, which is known to be associated with coronary artery atherosclerotic disease (CAD).
This study aims to investigate whether FLI correlates with NAFLD and with newly diagnosed CAD in a special Chinese population who underwent coronary angiography.
Assessment of preoperative exercise capacity in hepatocellular carcinoma pati...Enrique Moreno Gonzalez
Cardiopulmonary exercise testing measures oxygen uptake at increasing levels of work and predicts cardiopulmonary performance under conditions of stress, such as after abdominal surgery. Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative prognosis. This study examined the relationship between preoperative exercise capacity and event-free survival in hepatocellular carcinoma (HCC) patients with chronic liver injury who underwent hepatectomy.
The dyslipidemia-associated SNP on the APOA1/C3/A5 gene cluster predicts post...Enrique Moreno Gonzalez
Post-surgery therapies are given to early-stage breast cancer patients due to the possibility of residual micrometastasis, and optimized by clincopathological parameters such as tumor stage, and hormone receptor/lymph node status. However, current efficacy of post-surgery therapies is unsatisfactory, and may be varied according to unidentified patient genetic factors. Increases of breast cancer occurrence and recurrence have been associated with dyslipidemia, which can attribute to other known risk factors of breast cancer including obesity, diabetes and metabolic syndrome. Thus we reasoned that dyslipidemia-associated nucleotide polymorphisms (SNPs) on the APOA1/C3/A5 gene cluster may predict breast cancer risk and tumor progression.
Antibiotic exposure and the development of coeliac disease: a nationwide case...Enrique Moreno Gonzalez
The intestinal microbiota has been proposed to play a pathogenic role in coeliac disease (CD). Although antibiotics are common environmental factors with a profound impact on intestinal microbiota, data on antibiotic use as a risk factor for subsequent CD development are scarce.
Recently, a phase II clinical trial in hepatocellular carcinoma (HCC) has suggested that the combination of sorafenib and 5-fluorouracil (5-FU) is feasible and side effects are manageable. However, preclinical experimental data explaining the interaction mechanism(s) are lacking. Our objective is to investigate the anticancer efficacy and mechanism of combined sorafenib and 5-FU therapy in vitro in HCC cell lines MHCC97H and SMMC-7721.
Perceived benefits and barriers to exercise for recently treated patients wit...Enrique Moreno Gonzalez
Understanding the physical activity experiences of patients with multiple myeloma (MM) is essential to inform the development of evidence-based interventions and to quantify the benefits of physical activity. The aim of this study was to gain an in-depth understanding of the physical activity experiences and perceived benefits and barriers to physical activity for patients with MM.
Cost profiles of colorectal cancer patients in Italy based on individual patt...Enrique Moreno Gonzalez
Due to changes in cancer-related risk factors, improvements in diagnostic procedures and treatments, and the aging of the population, in most developed countries cancer accounts for an increasing proportion of health care expenditures. The analysis of cancer-related costs is a topic of several economic and epidemiological studies and represents a research area of great interest to public health planners and policy makers. In Italy studies are limited either to some specific types of expenditures or to specific groups of cancer patients. Aim of the paper is to estimate the distribution of cancer survivors and associated health care expenditures according to a disease pathway which identifies three clinically relevant phases: initial (one year following diagnosis), continuing (between initial and final) and final (one year before death).
Overexpression of peptide deformylase in breast, colon, and lung cancersEnrique Moreno Gonzalez
Human mitochondrial peptide deformylase (PDF) has been proposed as a novel cancer therapeutic target. However, very little is known about its expression and regulation in human tissues. The purpose of this study was to characterize the expression pattern of PDF in cancerous tissues and to identify mechanisms that regulate its expression.
Association between variations in the fat mass and obesity-associated gene an...Enrique Moreno Gonzalez
It is clear that genetic variations in the fat mass and obesity-associated (FTO) gene affect body mass index and the risk of obesity. Given the mounting evidence showing a positive association between obesity and pancreatic cancer, this study aimed to investigate the relation between variants in the FTO gene, obesity and pancreatic cancer risk.
Nitroglycerin 0.4% ointment vs placebo in the treatment of pain resulting fro...Enrique Moreno Gonzalez
Complications of chronic anal fissure (CAF) treatments are prompting interest in lower-risk therapies. This study was conducted to compare nitroglycerin (NTG) 0.4% ointment with placebo for pain associated with CAF.
Inorganic phosphate and the risk of cancer in the Swedish AMORIS studyEnrique Moreno Gonzalez
Both dietary and serum levels of inorganic phosphate (Pi) have been linked to development of cancer in experimental studies. This is the first population-based study investigating the relation between serum Pi and risk of cancer in humans.
Implication from thyroid function decreasing during chemotherapy in breast ca...Enrique Moreno Gonzalez
Thyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy.
The influence of variants at the 9p21 locus on melanoma risk has been reported through investigation of CDKN2A variants through candidate gene approach as well as by genome wide association studies (GWAS).
Defect in recruiting effector memory CD8+ T-cells in malignant pleural effusi...Enrique Moreno Gonzalez
Malignant pleural effusions (MPE) are a common and fatal complication in cancers including lung or breast cancers, or malignant pleural mesothelioma (MPM). MPE animal models and immunotherapy trials in MPM patients previously suggested defects of the cellular immunity in MPE. However only few observational studies of the immune response were done in MPM patients, using questionable control groups (transudate…).
Optimal schedule of Bacillus Calmette-Guerin for non-muscle-invasive bladder ...Enrique Moreno Gonzalez
To explore the necessity of maintenance, efficacy of low-dose and superiority of various combination therapies of Bacillus Calmette-Guérin (BCG) in treatment of superficial bladder cancer (BCa).
Functional p53 is required for rapid restoration of daunorubicin-induced lesi...Enrique Moreno Gonzalez
The tumour suppressor and transcription factor p53 is a major determinant of the therapeutic response to anthracyclines. In healthy tissue, p53 is also considered pivotal for side effects of anthracycline treatment such as lesions in haematopoietic tissues like the spleen. We used a Trp53null mouse to explore the significance of p53 in anthracycline (daunorubicin) induced lesions in the spleen.
Impaired mitochondrial beta-oxidation in patients with chronic hepatitis C: r...Enrique Moreno Gonzalez
Hepatic steatosis is often seen in patients with chronic hepatitis C (CH-C). It is still unclear whether these patients have an impaired mitochondrial β-oxidation. In this study we assessed mitochondrial β-oxidation in CH-C patients by investigating ketogenesis during fasting.
Arterial bleeding during EUS-guided pseudocyst drainage stopped by placement...Enrique Moreno Gonzalez
Hemorrhagic complications during EUS-guided pseudocyst drainage can occur, because the vessels on the internal wall of the pseudocyst might be compressed by the fluid and thus not visible on color Doppler or even power Doppler EUS.
Arterial bleeding during EUS-guided pseudocyst drainage stopped by placement...
Similar to Search for atoxic cereals: a single blind, cross-over study on the safety of a single dose of Triticum monococcum, in patients with celiac disease
Transglucosidase improves the gut microbiota profile of type 2 diabetes melli...Enrique Moreno Gonzalez
Recently, the relationship between gut microbiota and obesity has been highlighted. The
present randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy of
transglucosidase (TGD) in modulating blood glucose levels and body weight gain in patients
with type 2 diabetes mellitus (T2DM) and to clarify the underlying mechanism by analyzing
the gut microbiota of T2DM patients.
Role of Serum Zinc and Copper in Children with Gastroenteritisiosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
It appears that you have provided information about the "Indo-American Journal of Agricultural and Veterinary Sciences" . This journal seems to be an international online publication in English, published quarterly. It emphasizes fast publication while maintaining a rigorous peer-review process of the published journals.
Comparative Evaluation of the Effect of Doxycycline As An Adjunct to Non-Surg...QUESTJOURNAL
Background: The association between diabetes and periodontal disease has long been discussed with conflicting conclusions. Earlier studies demonstrating the relationship between diabetes and severity of periodontal disease has been equivocal. However, recent studies have clearly proven that diabetes increases the risk of periodontal disease progression. Less clear is the impact of periodontal disease on diabetes. It has been hypothesised that periodontal therapy may improve the metabolic control of diabetes. Aim: To determine the effect of doxycycline as an adjunct to non-surgical periodontal therapy in improving the metabolic control of poorly controlled type 2 diabetic subjects with chronic generalized periodontitis. Method: 30 poorly controlled type 2 diabetic subjects with chronic generalized periodontitis and receiving antidiabetic therapy were selected for the study. The subjects were randomly allotted to either of two treatment groups containing 15 subjects each: Group 1 (scaling and root planing(SRP)+ 15 days Doxycycline) or Group 2 (scaling and root planing(SRP). The Glycated haemoglobin (HbA1c) values, Gingival Index(GI), and Probing pocket depth of both the groups were assessed at baseline and after 3 months. Results: Both the treatment groups exhibited reductions in HbA1c, G I and Probing pocket depth compared to baseline over time. The amount of reduction in the glycated haemoglobin and gingival parameters was higher in Group I compared to group 2 after 3 months. Conclusion: Both treatments improved glycemic control in patients with type 2 diabetes; however, the reduction in HbA1c values reached statistical significance only in the group receiving doxycycline as an adjunct to scaling and root planing.
Similar to Search for atoxic cereals: a single blind, cross-over study on the safety of a single dose of Triticum monococcum, in patients with celiac disease (20)
Incidence of pneumonia and risk factors among patients with head and neck can...Enrique Moreno Gonzalez
This study investigated the incidence and patient- and treatment-related risk factors related to pneumonia acquired during radiotherapy (PNRT) in head and neck cancer (HNC) patients.
Gene expression analysis of a Helicobacter pyloriinfected and high-salt diet-...Enrique Moreno Gonzalez
Helicobacter pylori (H. pylori) infection and excessive salt intake are known as important risk factors for stomach cancer in humans. However, interactions of these two factors with gene expression profiles during gastric carcinogenesis remain unclear. In the present study, we investigated the global gene expression associated with stomach carcinogenesis and prognosis of human gastric cancer using a mouse model.
Acute myeloid leukemia (AML) is a hematopoietic malignancy with a dismal outcome in the majority of cases. A detailed understanding of the genetic alterations and gene expression changes that contribute to its pathogenesis is important to improve prognostication, disease monitoring, and therapy. In this context, leukemia-associated misexpression of microRNAs (miRNAs) has been studied, but no coherent picture has emerged yet, thus warranting further investigations.
Differences in microRNA expression during tumor development in the transition...Enrique Moreno Gonzalez
The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate.
Multicentric and multifocal versus unifocal breast cancer: differences in the...Enrique Moreno Gonzalez
The aim of this study was to evaluate the expression of the cell adhesion-related glycoproteins MUC-1, β-catenin and E-cadherin in multicentric/multifocal breast cancer in comparison to unifocal disease in order to identify potential differences in the biology of these tumor types.
The life in sight application study (LISA): design of a randomized controlled...Enrique Moreno Gonzalez
It is widely recognized that spiritual care plays an important role in physical and psychosocial well-being of cancer patients, but there is little evidence based research on the effects of spiritual care. We will conduct a randomized controlled trial on spiritual care using a brief structured interview scheme supported by an e-application. The aim is to examine whether an assisted reflection on life events and ultimate life goals can improve quality of life of cancer patients.
Clinical and experimental studies regarding the expression and diagnostic val...Enrique Moreno Gonzalez
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in nonsmall-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC.
Overexpression of YAP 1 contributes to progressive features and poor prognosi...Enrique Moreno Gonzalez
Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear.
Differentiation of irradiation and cetuximab induced skin reactions in patien...Enrique Moreno Gonzalez
In order to improve the clinical outcome of patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) not being capable to receive platinum-based chemoradiation, radiotherapy can be intensified by addition of cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR). The radioimmunotherapy with cetuximab is a feasible treatment option showing a favourable toxicity profile. The most frequent side effect of radiotherapy is radiation dermatitis, the most common side effect of treatment with cetuximab is acneiform rash. Incidence and severity of these frequent, often overlapping and sometimes limiting skin reactions, however, are not well explored. A clinical and molecular differentiation between radiogenic skin reactions and skin reactions caused by cetuximab which may correlate with outcome, have never been described before.
Cholestasis induces reversible accumulation of periplakin in mouse liverEnrique Moreno Gonzalez
Periplakin (PPL) is a rod-shaped cytolinker protein thought to connect cellular adhesion junctional complexes to cytoskeletal filaments. PPL serves as a structural component of the cornified envelope in the skin and interacts with various types of proteins in cultured cells; its level decreases dramatically during tumorigenic progression in human epithelial tissues. Despite these intriguing observations, the physiological roles of PPL, especially in noncutaneous tissues, are still largely unknown. Because we observed a marked fluctuation of PPL expression in mouse liver in association with the bile acid receptor farnesoid X receptor (FXR) and cholestasis, we sought to characterize the role of PPL in the liver and determine its contributions to the etiology and pathogenesis of cholestasis.
Post-diagnosis hemoglobin change associates with overall survival of multiple...Enrique Moreno Gonzalez
Anemia refers to low hemoglobin (Hb) level and is a risk factor of cancer patient survival. The National Comprehensive Cancer Network recently suggested that post-diagnosis Hb change, regardless of baseline Hb level, indicates the potential presence of anemia. However, there is no epidemiological study evaluating whether Hb change has direct prognostic values for cancer patients at the population level.
Cost-effectiveness of MRI for breast cancer screening in BRCA1/2 mutation car...Enrique Moreno Gonzalez
Women with mutations in BRCA1 or BRCA2 are at high risk of developing breast cancer and, in British Columbia, Canada, are offered screening with both magnetic resonance imaging (MRI) and mammography to facilitate early detection. MRI is more sensitive than mammography but is more costly and produces more false positive results. The purpose of this study was to calculate the cost-effectiveness of MRI screening for breast cancer in BRCA1/2 mutation carriers in a Canadian setting.
Intraepithelial lymphocyte distribution differs between the bulb and the seco...Enrique Moreno Gonzalez
Evaluation of intraepithelial duodenal lymphocytosis (IDL) is important in celiac disease (CD). There is no established cut-off value for increased number of IELs in the bulb. We therefore investigated the relation between IEL counts in the bulb and duodenal specimens in non-celiac subjects.
Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on...Enrique Moreno Gonzalez
Melanoma represents one of the most aggressive and therapeutically challenging malignancies as it often gives rise to metastases and develops resistance to classical chemotherapeutic agents. Although diverse therapies have been generated, no major improvement of the patient prognosis has been noticed. One promising alternative to the conventional therapeutic approaches currently available is the inactivation of proteins essential for survival and/or progression of melanomas by means of RNA interference. Survivin and cyclin B1, both involved in cell survival and proliferation and frequently deregulated in human cancers, are good candidate target genes for siRNA mediated therapeutics.
The cysteinyl leukotriene 2 receptor contributes to all-trans retinoic acid-i...Enrique Moreno Gonzalez
Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory mediators that are increased in samples from patients with inflammatory bowel diseases (IBDs). Individuals with IBDs have enhanced susceptibility to colon carcinogenesis. In colorectal cancer, the balance between the pro-mitogenic cysteinyl leukotriene 1 receptor (CysLT1R) and the differentiation-promoting cysteinyl leukotriene 2 receptor (CysLT2R) is lost. Further, our previous data indicate that patients with high CysLT1R and low CysLT2R expression have a poor prognosis. In this study, we examined whether the balance between CysLT1R and CysLT2R could be restored by treatment with the cancer chemopreventive agent all-trans retinoic acid (ATRA).
Clinical features and outcome of cryptogenic hepatocellular carcinoma compare...Enrique Moreno Gonzalez
Cryptogenic hepatocellular carcinoma (HCC) is thought to arise due to non-alcoholic fatty liver disease (NAFLD). This study investigated the prevalence, clinical features, and outcomes of cryptogenic HCC and compared them with those of HCC related to hepatitis B virus infection (HBV-HCC), hepatitis C virus infection (HCV-HCC), and alcohol (ALCHCC) in Korea.
Environment inside even a small tumor is characterized by total (anoxia) or partial oxygen deprivation, hypoxia. It has been shown that radiotherapy and some conventional chemotherapies may be less effective in hypoxia, and therefore it is important to investigate how different drugs act in different microenvironments. In this study we perform a large screening of the effects of 19 clinically used or experimental chemotherapeutic drugs on four different cell lines in conditions of normoxia, hypoxia and anoxia.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
2. Search for atoxic cereals: a single blind, cross-over
study on the safety of a single dose of Triticum
monococcum, in patients with celiac disease
Barbara Zanini1
Email: b_zanini@tin.it
Beatrice Petroboni1
Email: beatricepetroboni@hotmail.it
Tarcisio Not2
Email: not@burlo.trieste.it
Nicola Di Toro2
Email: n.ditoro@inwind.it
Vincenzo Villanacci3
Email: villanacci@spedalicivili.brescia.it
Francesco Lanzarotto1
Email: francesco.lanzarotto@spedalicivili.brescia.it
Norberto Pogna4
Email: norberto.pogna@entecra.it
Chiara Ricci1
Email: riccic@med.unibs.it
Alberto Lanzini1*
*
Corresponding author
Email: lanzini@med.unibs.it
1
Gastroenterology Unit, University and Spedali Civili of Brescia, Brescia, Italy
2
Paediatric Gastroenterology, Burlo-Garofolo Hospital and University of Trieste,
Trieste, Italy
3
Histopathology Unit, University and Spedali Civili of Brescia, Brescia, Italy
4
Research Unit for Cereals Development, CRA, Rome, Italy
3. Abstract
Background
Cereals of baking quality with absent or reduced toxicity are actively sought as alternative
therapy to a gluten-free diet (GFD) for patients with coeliac disease (CD). Triticum
monococcum, an ancient wheat, is a potential candidate having no toxicity in in-vitro and ex-
vivo studies. The aim of our study was to investigate on the safety of administration of a
single dose of gluten of Tm in patients with CD on GFD.
Methods
We performed a single blind, cross-over study involving 12 CD patients who had been on a
GFD for at least 12 months, challenged on day 0, 14 and 28 with a single fixed dose of 2.5
grams of the following (random order): Tm, rice (as reference atoxic protein) and Amygluten
(as reference toxic protein) dispersed in a gluten-free pudding. The primary end-point of the
study was the change in intestinal permeability, as assessed by changes in the urinary
lactulose/rhamnose ratio (L/R ratio) measured by High Pressure Liquid Chromatography. We
also assessed the occurrence of adverse gastrointestinal events, graded for intensity and
duration according to the WHO scale. Variables were expressed as mean ± SD; paired t-test
and χ2
test were used as appropriate.
Results
The urinary L/R ratio did not change significantly upon challenge with the 3 cereals, and was
0.055 ± 0.026 for Tm Vs 0.058 ± 0.035 for rice (p = 0.6736) and Vs 0.063 ± 0.054 with
Amygluten (p = 0.6071). Adverse gastrointestinal events were 8 for Tm, Vs 11 for rice (p =
0.6321) and Vs 31 for Amygluten p = 0.0016), and, in all cases events were graded as “mild”
or “moderate” with TM and rice, and as “severe” or “disabling” in 4 cases during Amygluten.
Conclusions
No definite conclusion can be drawn on the safety of Tm, based on no change in urinary L/R
because even Amygluten, a toxic wheat protein, did not cause a significant change in urinary
L/R indicating low sensitivity of this methodology in studies on acute toxicity. Tm was,
however, well tolerated by all patients providing the rationale for further investigation on the
safety of this cereal for CD patients.
Trial registration
EudraCT-AIFA n2008-000697-20
www.clinicaltrialsregister.eu/ctr-search/trial/2008-000697-20/IT
Keywords
Triticum monococcum, Intestinal permeability, Toxicity, Celiac disease
4. Background
Lifelong adherence to a strict gluten free diet (GFD) is at present the only treatment for
patients with celiac disease (CD) [1] to reduce morbidity and mortality. Compliance to GFD
is however difficult and affects the quality of life of patients because, besides economic and
social factors [2,3], it involves the consumption of poorly palatable unleavened bakery
products. This is the reason why alternative strategies are actively sought [4], which include
the search for baking quality wheat that does not contain toxic gluten. This strategy takes
advantages of the notion that there is natural variation in grain toxicity [5,6], and the old
diploid grass-like species of Triticum genus are potential candidates as grains with reduced or
absent toxicity. In particular Triticum monococcum (TM) has been shown to contain a low
number of stimulatory epitopes of Tcell lines obtained from small intestinal biopsies on CD
patients [6], and to lack the genes encoding the immunodominant 33 mer fragment [5].
Furthermore, the presence of a “protective” peptide similar to the 10-mer peptide
(QQPQDAVQPF) of Durum wheat [7] has been detected in Tm [8].
Preliminary in-vitro and ex-vivo studies have provided encouraging results. Absent in vitro
toxicity has been reported from in vitro studies, where Tm was unable to agglutinate K562(S)
cells [9] and had no effect on NO and TGII expression in Caco-2/TC7 cells [10]. Absent
toxicity of Tm has been reported by Pizzuti et al. [11] in a study ex vivo showing no
morphological changes in duodenal biopsies cultured with peptic-tryptic digest of Tm gliadin.
Taken together, the studies reported above suggest a favourable safety profile of Tm for CD
patients and provide the rationale for testing Tm administration for toxicity in CD patients. It
is however noteworthy that, in contrast with previous studies, in vitro toxicity of Tm has been
recently reported by Gianfrani et al. [12]; such information was not available when we
planned our study.
The aim of our study was to assess the safety of Tm administration by challenging CD
patients complying with a GFD with a single 2.5 g protein extract of Tm by comparison, in
random order, with that of an atoxic protein extract of rice, and with that of a toxic gluten,
Amygluten. We measured changes in urinary recovery of lactulose and rhamnose (L/R) as an
experimental biomarker of intestinal permeability [13].
Methods
We selected 12 consecutive CD patients on GFD for at least one year, at follow-up in our
Celiac Clinic, and meeting the following selection criteria: strict compliance with the GFD,
absence of symptoms, reconstitution of villous structure and negative tissue transglutaminase
(t-TG) and/or antiendomysial (AMA) antibodies during GFD. Compliance with the GFD was
assessed as previously described [14] using a 4 point Likert scale that includes no dietary
indiscretions (score 1), 1 serving with gluten per month (score 2), < 4 servings per month
(score 3) or = > 4 servings per month (score 4). We also selected 7 CD patients freshly
diagnosed with villous atrophy and positive CD related serology and on a gluten containing
diet. Twelve asymptomatic healthy subjects selected among the health care professionals in
our Institution volunteered in the study as normal controls.
CD patients on GFD entered a single blind cross over study involving challenge with 3
proteins (random order): rice (MyProtein, Cent Ltd, Northwick, UK) as atoxic control, pure
gluten (Amygluten, Tereos Syral, Marckolsheim, France) as toxic control, and Tm (Triticum
5. monococcum ssp monococcum, cultivar “Monlis”, CRA, Rome, Italy) as investigational
protein. Challenge with different proteins was carried out on 3 separate occasions on day 0,
14 and 28. The primary endpoints were the effect of challenge on the urinary recovery L/R
ratio as a measure of intestinal permeability, and the effect on symptoms. Patients were
instructed to report any symptom experienced during the challenge, which was graded for
severity according to the WHO toxicity grading scale as mild (grade 1), moderate (grade 2),
severe (grade 3) and life threatening (grade 4) [15]. We used a 2.5 g protein dose for the
challenge, corresponding approximately to one slice of bread and to the dose used by others
[16-18] for “proof of the concept” challenge studies.
The timetable in the study was as follows: fasted patients were admitted to a day-case Unit,
asked to empty the urinary bladder and immediately after they were asked:
t 0 to eat a gluten free pudding (BiAglut VAN, Heinz, Italy) with dispersed 2.5 g cereal
protein
t 2 h to drink a solution of 5 g lactulose + 1 g rhamnose in 60 ml water
t 2-7 h to collect urine and to record symptoms
At t 7 h urine volume was measured, a sample was retained, frozen and stored until analysis.
Urinary samples were analyzed by using HPLC [19] for L and R concentration and for
calculation of the L/R ratio in one batch for each patient. The normal urinary L/R, for our
laboratory, calculated in 40 healthy controls is 0.045. All analyses were carried out at the
Burlo-Garofolo Paediatric Hospital in Trieste (Italy) under the supervision of one of the
authors (T.N.).
The same protocol used for CD patients on GFD challenged with cereal proteins was also
adopted, with the exclusion of protein challenge, to measure intestinal permeability in 7 CD
patients on gluten containing diet and in 12 healthy controls. Five CD patients on GFD and 5
healthy controls were also studied with the same protocol on 2 occasions, one day apart, to
test for reproducibility of results.
Results were expressed as mean ± SD. Paired or unpaired t-test and χ2
test were used as
appropriate to compare continuous and categorical variables. The statistical analysis was
carried out using GraphPad Prism 5 statistical package (GraphPad Software, San Diego, Ca,
USA). The study was approved by the Ethics Committee of Spedali Civili of Brescia on
February 5th, 2008 and was given the number n 2008-000697-20 in our national registry of
clinical trials (EudraCT-AIFA). Patients and controls signed a written informed consent to
the study.
Results
Anthropometric and clinical characteristics of the subjects enrolled are reported in Table 1.
All 12 CD patients had normal duodenal mucosa, and serology was negative during GFD in
all but 1 patient who was t-TG negative and weakly positive at EMA testing. All seven CD
patients on gluten containing diet had similar characteristics to patients on GFD, and all had
duodenal atrophy and tested positive at serology. Mean age was lower and M/F was similar in
the 12 healthy subjects as in CD patients.
6. Table 1 Characteristics of celiac patients on gluten free diet (GFD) (panel A), on gluten
containing diet (panel B), and of healthy controls (panel C)
Marsh t-TG
Age Sex BMI Baseline GFD Baseline GFD GFD
(years) (U/mL) (years)
A 53 M 23.8 3B 2 5/5 6/16 5
46 F 19.5 3C 2 8/7 1/7 18
50 M 26.5 3C 2 3/8 1/7 4
48 M 25.4 3A 2 15/8 4/9 4
35 F 22.7 3A 2 23/7 7/9 2
42 M 21.6 3C 2 9/7 2/16 2
35 f 18.4 3B 2 99/5 8/9 4
62 F 21.5 3C 2 22/7 7/16 2
31 F 26.6 3A 2 19/16 3/16 1
59 F 24.7 3B 0 12/9 5/16 2
32 F 18.4 3C 2 12/9 2/4 6
41 F 25.03 3C 2 107/9 13/16 2
X 44.5 22.8
SD 10.3 3.0
B 52 M 26.0 3C 159/16 - -
37 F 20.7 3C - 96/16 - -
42 F 21.5 3A - 29/16 - -
16 F 18.0 3A - 22/16 - -
42 M 27.4 3B - 153/16 - -
41 F 25.4 3C - 100/9 - -
36 F 24.2 3B - 157/16 - -
X 40.9 23.3
SD 14.3 3.4
C 36 F 21.7
25 M 23.1 - - - - -
63 M 26.4 - - - - -
42 M 23.4 - - - - -
26 F 18.9 - - - - -
25 F 21.1 - - - - -
28 F 24.5 - - - - -
36 F 19.9 - - - - -
26 M 20.8 - - - - -
26 F 20.3 - - - - -
25 M 21.7 - - - - -
39 M 30.7 - - - - -
X* 33.1 22.7
SD 11.3 3.3
* : p = 0.0168 by comparison with panel A.
7. Validation study
Urinary L/R was higher in CD patients on gluten containing diet (0.078 ± 0.022) than in
controls (0.052 ± 0.031, p = 0.0345) and in patients on GFD (0.058 ± 0.034, p = 0.1852).
Five control subjects and 5 CD patients entered the reproducibility study. Mean value of L/R
was 0.046 ± 0.024 Vs 0.048 ± 0.021 (p = 0.5746) and was 0.033 ± 0.016 Vs 0.031 ± 0.018 (p
= 0.6228) on day1 Vs day 2 in CD patients and control subjects, respectively, and coefficient
of variation of measurements was 5.4% and 5.3% (Figure 1).
Figure 1 Reproducibility on 2 successive days of urinary lactulose/rhamnose ratio (L/R)
as an index of intestinal permeability in (A) healthy controls and (B) celiac patients.
Urinary recovery of R ranged between 92% and 98% in urinary samples of the 31 subjects
cumulatively entering the study.
Cereal challenge
Results of urinary L/R in the 12 CD patients on GFD challenged with 3 cereals are shown in
Figure 2. There was no consistent trend for L/R ratio to change during acute challenge with
Tm, Amygluten or rice, and mean values were 0.055 ± 0.03 for Tm Vs 0.058 ± 0.035 for rice
(p = 0.6736) and Vs 0.063 ± 0.02 for Amygluten (p = 0.6071).
Figure 2 Effect of acute challenge with 2.5 g of rice protein, Triticum monococcum
protein and Amygluten on changes of intestinal permeability as measured by urinary
lactulose/rhamnose ratio (L/R) ratio in celiac patients on gluten free diet.
The effect of cereal challenge on symptoms is shown in Table 2. Eleven and 8 adverse
gastrointestinal events were reported during challenge with rice and with Tm (p = 0.6321),
respectively, and 31 events were reported during Amygluten, a significantly (p = 0.0016)
higher value than for the other 2 cereals. Severity of adverse events was graded as mild or
moderate with rice and Tm, and as “severe” or “disabling” in 4 cases during Amygluten.
Table 2 Number of adverse events reported during challenge with the 3 cereals studied
Rice Triticum monococcum Amygluten
Symptoms n n n
Abdominal pain 1 2 7
Bloating 2 1 11
Constipation - - -
Diarrhoea 2 - -
Flatus - - -
Disgeneusia 1 - 2
Nausea 5 5 9
Vomiting - - 2
Heartburn - - -
Total n 11 8 31
8. Discussion
The main objective of our study was to assess the effect of challenge with Tm in CD patients
on GDF using urinary L/R ratio as a method to measure changes in intestinal permeability in
order to test in vivo safety and toxicity of a single low dose of Tm. Our results show that
urinary L/R ratio was unchanged during Tm challenge in comparison with the results
obtained with rice, an atoxic cereal for CD patients. This potentially interesting observation is
however of limited interest because, as in Tm, even challenge with the toxic reference protein
Amygluten caused no significant change in the urinary L/R ratio in relation to that measured
during rice challenge. The reason for this lack of effect of Amygluten in uncertain. Our
preliminary validation studies indicating high reproducibility of results for urinary L/R
recovery both in celiacs and in healthy controls, and the ability of the test to discriminate
healthy controls from CD patients on gluten containing diet, support the validity of
methodology used for measurements. On the other hand, the lack of effect observed during
challenge with toxic Amygluten indicates inadequacy of the experimental conditions for
testing the working hypothesis. The most likely explanation is that the protein dose used for
challenge, 2.5 g as a single dose, may be too low to cause the alteration of intestinal
permeability that was reported by Greco et al. [13] which occured using 50 g protein
challenge. Alternatively, the timing of urinary collection may be inadequate for detecting
changes in the L/R ratio. Whatever the case, the methodology we used was clearly not
sensitive enough to achieve the aims of our study.
Though results on urinary L/R ratio were disappointing, results on symptoms reported by
patients during the challenge provided a clear-cut response, indicating that a single low dose
of Tm is well tolerated by CD patients. Symptom incidence with Tm was similar to that
observed during challenge with rice, the atoxic cereal, and symptoms were in all cases mild.
In contrast, incidence of symptoms was 3 times higher during Amygluten than during Tm and
rice challenge, indicating that the dose used for challenge was large enough to cause
symptoms in case of toxicity. This clinical finding is in keeping with previous in vitro and ex-
vivo observations suggesting no toxicity of Tm for CD patients, although we are well aware
that our finding on symptoms cannot be taken as evidence of lack of toxicity of Tm.
Conclusions
In conclusion our study indicates that a protocol involving short-term challenge with a single
low dose of cereal protein using urinary L/R recovery is not sensitive enough to discriminate
the effect of toxic and atoxic cereals on intestinal permeability to sugars. As a consequence,
no conclusion can be drawn on the safety of acute administration of Tm on CD patients.
However, the lack of side effects reported by patients during challenge with Tm encourages
to further explore the characteristic of this cereal as a potentially harmless wheat for CD
patients, or as a cereal that may be tolerable for patients who are not celiacs but do not
tolerate wheat based products because of gluten sensitivity.
Abbreviations
CD, Celiac disease; GFD, Gluten free diet; R, Rhamnose; L, Lactulose; Tm, Triticum
monococcum; HPLC, High Pressure Liquid Chromatography
9. Competing interest
A.L. financial support to the study from “Fondazione Antica Terra”.
All other authors declare that they have no competing interest.
Authors’ contributions
BZ: participated in conception and design of the study, coordinated the challenge procedure
and carried out the analysis and interpretation of data. BP: coordinated the challenge
procedure, participated in analysis and interpretation of data. TN: carried out the analysis of
urinary rhamnose and lactulose. NDT: carried out the analysis of urinary rhamnose and
lactulose. VV: revised biopsies of patients involved. FL: performed endoscopic biopsies,
participated in analysis and interpretation of data. NP: provided relevant background
information and participated in analysis and interpretation of data. CR: participated in
analysis and interpretation of data. AL conceived and designed the study, participated in
analysis and interpretation of data, wrote and finalized the manuscript. All authors read and
approved the final manuscript.
Acknowledgments
The study was supported with a grant from “Antica Terra Foundation”, Cigole, Brescia, Italy.
Triticum monococcum protein extract was kindly provided by Centre for Agricoltural
Research, Rome, Italy
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