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1.
Artículo en Inglés | MEDLINE | ID: mdl-38813746

RESUMEN

ABSTRACT: Gastroesophageal reflux disease (GERD) is one of the most common problems encountered in outpatient general medicine and gastroenterology clinics. GERD may present with classic esophageal symptoms, extraesophageal symptoms, or mixed symptoms. The diagnosis and treatment of GERD are challenging due to the variety of symptoms and multifactorial pathophysiology. Since there is no consensus on the diagnosis and treatment of GERD in Saudi Arabia, the Saudi Gastroenterology Association established an expert group to formulate a consensus on the clinical care pathway for the diagnosis and treatment of GERD to update health-care providers in Saudi Arabia. The expert group reviewed the literature including recently published international guidelines, clinical trials, and expert opinion and conducted virtual and in-person meetings. A total of 22 statements on the definition, diagnosis, and treatment of GERD were formulated, and three algorithms for the clinical care of GERD were developed with a detailed description for each step. The expert group endorsed the new definition of GERD, the practical principles of interpretation of the diagnostic GERD evaluation, and the practical guidance for GERD treatment including medical, surgical, and endoscopic therapy. The expert group recommends further studies to investigate local data on the diagnosis and treatment of GERD.

2.
Arch Razi Inst ; 78(3): 1065-1070, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-38028853

RESUMEN

Chicken production is quickly rising due to the low associated costs and the capability of poultry to convert nutrients into biological protein along with chicken meat accounting for 30% of all animal protein eaten by humans. Despite advances in poultry production, parasitic illnesses in laying hens remain a problem. Farm birds reared in semi-intensive and free-range systems are more prone to parasite infections due to the absorption of polluted water and food from scavenging behaviors and waste droppings. In this study, the effects of Ascaridia galli infection on the immune response and liver function of two laying hen lines are compared, and their infection resistance is determined. In total, 50 laying hens at eight weeks of age were used (25 Lohmann brown-classic and 25 Lohmann lsl-lite), and each line was divided into two groups: an infected group (n=15), which was orally infected with a single dose of 500 A. galli embryonated eggs, and a control group (n=10), which was given normal saline. After four and eight weeks, blood was collected from the wing vein to assess the serum's AST, ALT, total protein, and IgY levels. The results demonstrated that the infected Lohmann brown-classic and Lohmann lsl-lite chickens presented significantly increased (P≤0.05) AST, ALT, and IgY, compared to the respective control group. Moreover, Lohmann brown-classic hens presented a significantly increased (P≤0.05) IgY concentration four weeks after infection, compared to Lohmann lsl-lite hens. From our results, it can be concluded that genetic variation plays a crucial role in the immune response against A. galli, where the Lohmann brown-classic line was found to be more resistant, compared to the Lohmann lsl-lite line.


Asunto(s)
Ascaridia , Ascaridiasis , Humanos , Animales , Femenino , Ascaridia/fisiología , Ascaridiasis/veterinaria , Ascaridiasis/parasitología , Pollos , Inmunidad , Hígado
4.
Curr Med Chem ; 30(28): 3215-3237, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35986535

RESUMEN

Immune checkpoints are vital molecules and pathways of the immune system with defined roles of controlling immune responses from being destructive to the healthy cells in the body. They include inhibitory receptors and ligands, which check the recognition of most cancers by the immune system. This happens when proteins on the surface of T cells called immune checkpoint proteins identify partner proteins on the cancer cells and bind to them, sending brake signals to the T cells to evade immune attack. However, drugs called immune checkpoint inhibitors block checkpoint proteins from binding to their partner proteins, thereby inhibiting the brake signals from being sent to T cells. This eventually allows the T cells to destroy cancer cells and arbitrate robust tumor regression. Many such inhibitors have already been approved and are in various developmental stages. The well-illustrated inhibitory checkpoints include the cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1). Though many molecules blocking these checkpoints have shown promise in treating many malignancies, such treatment options have limited success in terms of the immune response in most patients. Against this backdrop, exploring new pathways and next-generation inhibitors becomes imperative for developing more responsive and effective immune checkpoint therapy. Owing to the complex biology and unexplored ambiguities in the mechanistic aspects of immune checkpoint pathways, analysis of the activity profile of new drugs is the subject of strenuous investigation. We herein report the recent progress in developing new inhibitory pathways and potential therapeutics and delineate the developments based on their merit. Further, the ensuing challenges towards developing efficacious checkpoint therapies and the impending opportunities are also discussed.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/metabolismo , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Linfocitos T
5.
Res Vet Sci ; 141: 42-47, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34662833

RESUMEN

The laminar tissue of bovine laminitis may undergo energy failure. The expression of glucose transport protein-1 (GLUT-1) and 5'-adenosine monophosphate-activated protein kinase (AMPK) affects the energy metabolism of digital laminar tissue. This study aimed to determine the expression of glucose uptake and AMPK in laminar wall corium of Holstein heifer claw by oral administration of oligofructose. A total of twelve clinically healthy Holstein heifers were selected and divided into two groups, including control (CON, n = 6) and experimental (OF, n = 6) groups. The heifers of OF group were given 17 g/kg BW oligofructose dissolved in water (20 mL/kg BW) and the heifers of CON group were given water only (20 mL/kg BW). The laminar tissues were collected after euthanasia. The amount of protein and transcript expression of AMPK and GLUT-1 were determined by western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. Expressions of phosphoenolpyruvate carboxy-kinase (PEPCK), receptor-c coactivator1-α (PGC-1α) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were determined by qRT-PCR. The heifers of OF group showed no significant change in the expression and concentration of AMPK. The phosphor-(Thr172) AMPK and GLUT-1 were significantly decreased, while the gene contents of PPAR-γ and PGC-1α were significantly increased. The activation of AMPK and GLUT-1 in digital laminar tissues of heifers was inhibited, which may contribute to digital laminar tissue damage.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Pezuñas y Garras/enzimología , Oligosacáridos , Proteínas Quinasas Activadas por AMP/genética , Adenosina Monofosfato , Animales , Bovinos , Femenino , Glucosa , Oligosacáridos/farmacología
6.
Cureus ; 13(7): e16777, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34513384

RESUMEN

INTRODUCTION:  Typhoid remains a major healthcare problem in low and middle-income countries. The emergence of extremely drug-resistant (XDR) typhoid strains from the Indian subcontinent has led to very limited therapeutic options. Azithromycin being the only oral option for XDR typhoid faces a threat of rapid resistance due to its overuse after the COVID-19 pandemic. OBJECTIVE:  To evaluate the reliability of azithromycin disc diffusion testing against clinical isolates of typhoidal salmonellae in comparison with E-test minimum inhibitory concentrations (MICs). STUDY DESIGN:  This is a cross-sectional validation study. Place and duration of the study: The Department of Microbiology, Pakistan Navy Ship Shifa hospital, Karachi from June 1 to December 31, 2020. METHODOLOGY:  Antimicrobial susceptibility was performed by Kirby Bauer disc diffusion method for 60 isolates including Salmonella enterica ser. Typhi and Paratyphi A using Clinical Laboratory Standard Institute (CLSI) guidelines. MICs by the E-test method were determined for Azithromycin only. RESULTS:  A significant proportion of the isolates (55%) had high azithromycin MIC in the wild-type distribution range (8-16 µg/ml). Ten (16.6%) isolates showed false resistance, i.e., zone diameter <13 mm by disc diffusion method when compared to E-test MIC results. Isolates with MICs close to breakpoint, i.e., 16 µg/ml were more likely to show discordant results. The sensitivity, specificity, negative predictive value, positive predictive value, and diagnostic accuracy of the disc diffusion method versus E-test were 100%, 83%, 100%, 9%, and 83%, respectively. CONCLUSIONS:  Disc diffusion method as recommended by CLSI is not reliable for azithromycin susceptibility testing particularly for isolates with high MICs in the susceptible range. The E-test method may be a better alternative to disc diffusion provided appropriate training is done prior to its application.

7.
Epidemiol Infect ; 149: e182, 2021 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-34340726

RESUMEN

COVID-19 research has been produced at an unprecedented rate and managing what is currently known is in part being accomplished through synthesis research. Here we evaluated how the need to rapidly produce syntheses has impacted the quality of the synthesis research. Thus, we sought to identify, evaluate and map the synthesis research on COVID-19 published up to 10 July 2020. A COVID-19 literature database was created using pre-specified COVID-19 search algorithms carried out in eight databases. We identified 863 citations considered to be synthesis research for evaluation in this project. Four-hundred and thirty-nine reviews were fully assessed with A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) and rated as very low-quality (n = 145), low-quality (n = 80), medium-quality (n = 208) and high-quality (n = 151). The quality of these reviews fell short of what is expected for synthesis research with key domains being left out of the typical methodology. The increase in risk of bias due to non-adherence to systematic review methodology is unknown and prevents the reader from assessing the validity of the review. The responsibility to assure the quality is held by both producers and publishers of synthesis research and our findings indicate there is a need to equip readers with the expertise to evaluate the review conduct before using it for decision-making purposes.


Asunto(s)
COVID-19 , Investigación/tendencias , Revisiones Sistemáticas como Asunto/normas , Humanos , Metaanálisis como Asunto , Investigación/normas
8.
Patient Prefer Adherence ; 15: 69-76, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33519192

RESUMEN

OBJECTIVE: Access to dental care is a key factor influencing oral health outcomes. Individuals with special healthcare needs are at risk of not having access to dental care services which they need to maintain their oral health. This study assessed the magnitude of this problem and identified barriers responsible for the difficulties in accessing dental care in Qatif, Saudi Arabia, as reported by caregivers of individuals with special healthcare needs. METHODS: This cross-sectional study collected data using a self-administered survey questionnaire from caregivers of individuals with special healthcare needs across 11 centers (eight special needs centers and three schools) in Qatif, Eastern Province of Saudi Arabia, between February and April 2019. RESULTS: A total of 186 caregivers participated in the study, 102 (54.8%) of whom reported difficulties in getting access to dental care. The key barriers included lack of time on the part of caregivers (60.8%), unsuitable clinic environment (53.9%), difficulties with transportation (51.9%), medical/health status of the individual with special healthcare needs (51.0%), and geographically distant dental clinics (51.0%). Caregiver demographics (age, gender, and educational level) had no significant influence on the difficulties reported by caregivers in getting access to dental care for individuals with special healthcare needs (p>0.05). CONCLUSION: A large proportion of caregivers in Qatif, Saudi Arabia, experience difficulties with access to dental care services for individuals with special healthcare needs. The most common barriers are physical accessibility of dental facilities (for individuals with special healthcare needs), affordability, and lack of skills and knowledge of dental care providers.

9.
Anticancer Agents Med Chem ; 21(13): 1671-1679, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33238853

RESUMEN

BACKGROUND: Aromatase, a cytochrome P450 hemoprotein that is responsible for estrogen biosynthesis by conversion of androgens into estrogens, has been an attractive target in the treatment of hormonedependent breast cancer. Design of new steroidal aromatase inhibitors becomes imperative. OBJECTIVE: Synthesis and biological evaluation of two classes of structurally and functionally diverse D-ring pregnenolone pyrazoles as type I aromatase inhibitors and antiproliferative agents. METHODS: Pregnenolone (1) was converted to 3ß-hydroxy-21-hydroxymethylidenepregn-5-en-20-one (2), which upon cyclization with phenylhydrazine generated regioisomeric pairs of pyrazoles 4 and 5. Further, Knoevenagel condensation of pregnenolone (1) with 3-oxo-3-phenylpropanenitrile (6) produced 2-benzoyl-3-(3b-hydroxyandrostan- 5-ene-20-ylidene)-but-2-enenitrile (7), which upon cyclization with hydrazine or phenylhydrazine generated the pyrazoles 8 and 9. All new steroidal derivatives were tested for their aromatase inhibition activity using Dibenzylfluorescein (DBF) based fluorescence assay developed by Stresser et al. Antiproliferative activities were measured using Sulforhodamine B assay. The activities were promising and there was a coherence between aromatase inhibitory and antiproliferative activities. RESULTS: The study reveals the immense potential of pregnenolone pyrazoles as aromatase inhibitors for the treatment of breast cancer. Molecular docking studies proved efficient binding of the new steroidal analogs on human placental aromatase. CONCLUSION: In the overall study, most of the compounds exhibited potential activity for the treatment of hormone dependent breast cancer. Compounds 4c and 4d were found to be the most promising pharmacons. Furthermore, compounds 4c and 4d were applied for their molecular docking study on human placental aromatase to predict their possible binding modes with the enzyme. These studies revealed that such molecules have high scope and potential for further investigation towards the treatment of estrogen dependent breast cancer.


Asunto(s)
Antineoplásicos/farmacología , Inhibidores de la Aromatasa/farmacología , Aromatasa/metabolismo , Pregnenolona/farmacología , Pirazoles/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Inhibidores de la Aromatasa/síntesis química , Inhibidores de la Aromatasa/química , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Modelos Moleculares , Estructura Molecular , Pregnenolona/síntesis química , Pregnenolona/química , Pirazoles/síntesis química , Pirazoles/química , Células Tumorales Cultivadas
10.
SLAS Discov ; 25(10): 1097-1107, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32692266

RESUMEN

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was first reported in Wuhan, China, in December 2019. Since then, the virus has stretched its grip to almost all the countries in the world, affecting millions of people and causing enormous casualties. The World Health Organization (WHO) declared COVID-19 a pandemic on March 11, 2019. As of June 12, 2020, almost 7.30 million people have already been infected globally, with 413,000 reported casualties. In the United States alone, 2.06 million people have been infected and 115,000 have succumbed to this pandemic. A multipronged approach has been launched toward combating this pandemic, with the main focus on exhaustive screening, developing efficacious therapies, and vaccines for long-term immunity. Several pharmaceutical companies in collaboration with various academic institutions and governmental organizations have started investigating new therapeutics and repurposing approved drugs so as to find fast and affordable treatments against this disease. The present communication is aimed at highlighting the efforts that are currently underway to treat or prevent SARS-CoV-2 infection, with details on the science, clinical status, and timeline for selected investigational drugs and vaccines. This article is going to be of immense help to the scientific community and researchers as it brings forth all the necessary clinical information of the most-talked-about therapeutics against SARS-CoV-2. All the details pertaining to the clinical status of each therapeutic candidate have been updated as of June 12, 2020.


Asunto(s)
Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , Vacunas contra la COVID-19/farmacología , Reposicionamiento de Medicamentos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/farmacología , Alanina/análogos & derivados , Alanina/farmacología , Amidas/farmacología , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados/farmacología , COVID-19/prevención & control , Cloroquina/farmacología , Ensayos Clínicos como Asunto , Ciclopropanos , Evaluación Preclínica de Medicamentos , Humanos , Isoindoles , Lactamas/farmacología , Lactamas Macrocíclicas , Ratones Transgénicos , Prolina/análogos & derivados , Pirazinas/farmacología , SARS-CoV-2/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacología , Sulfonamidas/farmacología , Vacunas Sintéticas/farmacología
11.
Gulf J Oncolog ; 1(33): 64-67, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32476652

RESUMEN

BACKGROUND: Alpha-fetoprotein (AFP) is a serum tumor marker used in the past for surveillance and screening of hepatocellular carcinoma (HCC) in patients with cirrhosis. Its prognostic value is still debated in the literature. The aim of this study was to evaluate the prognostic impact of the AFP rate at diagnosis on the overall survival of patients with a small HCC (<3cm) in patients with cirrhosis. PATIENTS AND METHODS: Among the 122 patients diagnosed with HCC during the study period, 49 patients had a small HCC at diagnosis, including 40,8% (N 20) patients with a negative AFP (group I) and 59,18% (N 29) with an AFP >10 ng / ml (group II). Both groups of patients were comparable for age and WHO status (World Health Organization). Patient survival was assessed by the Kaplan-Meier method. The survival at 5 years was 35.7% in group 1 vs 12.3% in group 2. The AFP level was identified as an independent prognostic factor of survival. CONCLUSION: Alpha-fetoprotein serum positivity seems to have prognostic value in patients with single small HCC.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , alfa-Fetoproteínas/metabolismo , Carcinoma Hepatocelular/mortalidad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
12.
Front Nutr ; 7: 596787, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33598473

RESUMEN

Background: Sub-optimal HDL is a prognostic marker of cardiovascular disease. South Asia has a high prevalence of sub-optimal HDL compared to other parts of the world. Intermittent fasting (IF) is a type of energy restriction which may improve serum HDL and other lipids thereby reducing the risk of cardiovascular diseases. Objective: The aim of the study was to evaluate the effect of IF on lipid profile and HDL-cholesterol in a sample of South Asian adults. Methods: A 6-week quasi-experimental (non-randomized) clinical trial was conducted on participants with low HDL (< 40 mg/dl for men and < 50 mg/dl for women). Participants of the control group were recommended not to change their diet. The intervention group was recommended to fast for ~12 h during day time, three times per week for 6 weeks. Pulse rate, blood pressure, body weight, waist circumference, serum lipid profile, and blood glucose levels were measured at baseline and after 6 weeks. Result: A total of 40 participants were enrolled in the study (N = 20 in each group), while 35 (20 control and 15 intervention) completed the trial and were included in data analysis of the study. Body measurements, including body weight, BMI and waist circumference, showed significant interaction effects (p's < 0.001), indicating that there were larger reductions in the IF group than in the control group. Significant interaction effects were also observed for total (p = 0.033), HDL (p = 0.0001), and LDL cholesterol (p = 0.010) with larger improvements in the IF group. Conclusion: This study suggests that intermittent fasting may protect cardiovascular health by improving the lipid profile and raising the sub-optimal HDL. Intermittent fasting may be adopted as a lifestyle intervention for the prevention, management and treatment of cardiovascular disorders. Clinical Trial Registration: NCT03805776, registered on January 16, 2019, https://clinicaltrials.gov/ct2/show/NCT03805776.

13.
Int J Mol Sci ; 20(24)2019 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-31835656

RESUMEN

BACKGROUND: Sudden cardiac arrest is a major global health concern, and survival of patients with ischemia-reperfusion injury is a leading cause of myocardial dysfunction. The mechanism of this phenomenon is not well understood because of the complex pathophysiological nature of the disease. Aim of the study was to investigate the cardioprotective role of fingolimod in an in vivo model of cardiac arrest and resuscitation. METHODS: In this study, an in vivo rat model of cardiac arrest using extracorporeal membrane oxygenation resuscitation monitored by invasive hemodynamic measurement was developed. At the beginning of extracorporeal life support (ECLS), animals were randomly treated with fingolimod (Group A, n = 30) or saline (Group B, n = 30). Half of the animals in each group (Group A1 and B1, n = 15 each) were sacrificed after 1 h, and the remaining animals (Group A2 and B2) after 24 h of reperfusion. Blood and myocardial tissues were collected for analysis of cardiac features, inflammatory biomarkers, and cell signaling pathways. RESULTS: Treatment with fingolimod resulted in activation of survival pathways resulting into reduced inflammation, myocardial oxidative stress and apoptosis of cardiomyocytes. This led to significant improvement in systolic and diastolic functions of the left ventricle and improved contractility index. CONCLUSIONS: Sphingosine1phosphate receptor activation with fingolimod improved cardiac function after cardiac arrest supported with ECLS. Present study findings strongly support a cardioprotective role of fingolimod through sphingosine-1-phosphate receptor activation during reperfusion after circulatory arrest.


Asunto(s)
Reanimación Cardiopulmonar , Clorhidrato de Fingolimod/uso terapéutico , Paro Cardíaco/tratamiento farmacológico , Miocardio/patología , Animales , Apoptosis/efectos de los fármacos , Biomarcadores/metabolismo , Colágeno/metabolismo , Modelos Animales de Enfermedad , Clorhidrato de Fingolimod/farmacología , Paro Cardíaco/sangre , Paro Cardíaco/fisiopatología , Hemodinámica/efectos de los fármacos , Mediadores de Inflamación/sangre , Infiltración Neutrófila/efectos de los fármacos , Estrés Nitrosativo/efectos de los fármacos , Nucleótidos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas Sprague-Dawley , Transducción de Señal , Función Ventricular Izquierda/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo
14.
Gulf J Oncolog ; 1(31): 36-40, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31591989

RESUMEN

BACKGROUND: Although its incidence has decreased over the last 20 years, gastric adenocarcinoma remains frequent (1,033,701 new cases worldwide per year, Globocan 2018). Its prognosis is still poor, with overall survival rates of 10 to 25% despite improvement in surgical and perioperative treatment. In Morocco, we do not have data on survival and predictors of mortality in our population, the present study aims to describe the epidemiological and clinicopathological features of gastric adenocarcinoma and the survival rate. MATERIALS AND METHODS: We retrospectively reviewed data files of 265 patients with histological diagnosis of gastric adenocarcinoma between January 2007 and June 2017. Survival was estimated by the Kaplan Meier method and prognostic factors in multivariate analysis (Cox model). RESULTS: The mean age of our population was 54.48 ±15.53 with a sex ratio M/F of 1.76. Clinical symptomatology dominated by epigastralgia episodes in two-thirds of the cases and deterioration of the general state in most cases (61.7%). Proximal localization accounted for 17.4%. According to histological classification, poorly differentiated adenocarcinoma was the most common histological type (51.7%). Metastatic or locally advanced tumors accounted for 92% of cases. Only 11% of patients received curative resection. The 5-year survival was 6%. Multivariate analysis revealed three prognostic factors: vascular invasion, advanced stage and differentiation. DISCUSSION: The high mortality of gastric adenocarcinoma in our Moroccan series is probably explained by the late stage at diagnosis. Symptoms are nonspecific and endoscopy is usually performed for advanced symptoms such as anemia, bleeding or weight loss. The main identified prognostic factors in gastric adenocarcinoma are tumor subtype (Linitic forms), stage at diagnosis, vascular and lymph nodes invasion and general performance status which correlates to available data in the literature. Besides, the age distribution of GC in our series showed that the proportion of affected young adult is high (30.6%) compared to data from developed countries varying between 6 and 15%. This age distribution can be explained by the Westernization of diet, the increase of obesity in our population and more exposure to alcohol and tobacco. CONCLUSION: Overall cancer survival in our population does not exceed 7%, a rate that remains low compared to studies published in the occidental literature. Recommendations have to be elaborated to make a strategy for screening and early diagnosis of gastric adenocarcinoma to improve the survival rate.


Asunto(s)
Adenocarcinoma/epidemiología , Neoplasias Gástricas/epidemiología , Adenocarcinoma/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Marruecos , Neoplasias Gástricas/mortalidad , Tasa de Supervivencia
15.
Molecules ; 24(19)2019 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-31569697

RESUMEN

Cancer vaccine is a promising immunotherapeutic approach to train the immune system with vaccines to recognize and eliminate tumors. Adjuvants are compounds that are necessary in cancer vaccines to mimic an infection process and amplify immune responses. The Toll-like receptor 2 and 6 (TLR2/TLR6) agonist dipalmitoyl-S-glyceryl cysteine (Pam2Cys) was demonstrated as an ideal candidate for synthetic vaccine adjuvants. However, the synthesis of Pam2Cys requires expensive N-protected cysteine as a key reactant, which greatly limits its application as a synthetic vaccine adjuvant in large-scaled studies. Here, we report the development of N-acetylated Pam2Cys analogs as TLR2/TLR6 agonists. Instead of N-protected cysteine, the synthesis utilizes N-acetylcysteine to bring down the synthetic costs. The N-acetylated Pam2Cys analogs were demonstrated to activate TLR2/TLR6 in vitro. Moreover, molecular docking studies were performed to provide insights into the molecular mechanism of how N-acetylated Pam2Cys analogs bind to TLR2/TLR6. Together, these results suggest N-acetylated Pam2Cys analogs as inexpensive and promising synthetic vaccine adjuvants to accelerate the development of cancer vaccines in the future.


Asunto(s)
Lipopéptidos/química , Lipopéptidos/farmacología , Receptor Toll-Like 2/agonistas , Receptor Toll-Like 2/química , Receptor Toll-Like 6/agonistas , Receptor Toll-Like 6/química , Humanos , Lipopéptidos/síntesis química , Conformación Molecular , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular
16.
Anticancer Agents Med Chem ; 18(13): 1919-1926, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29697032

RESUMEN

BACKGROUND: The potential of steroids for development into lead pharmacological molecules lies in the regulation of a variety of biological processes by these molecules and also because of these being a fundamental class of signaling molecules. Steroid based scaffolds have been extensively used as active pharmaceutical agents for the treatment of various diseases including the deadly disease of cancer which despite the recent advances in the early diagnosis, prevention and therapy, remains a clinical challenge affecting millions of people world over and is one of the leading causes of death. It thus warrants the development of new drugs against this dreadful disease through exploitation of emerging molecularly defined targets. METHODS: The present study explores the effect of novel steroidal pyrazolines as presumed inhibitors of 5α- reductase (5AR) and 17α-hydroxylase-C17,20-lyase as a target for treatment of prostate cancer. A series of 1,5- diaryl pyrazoline pregnenolones were synthesized and screened for 5α-reductase inhibitory activities. Synthesis of the analogs is multistep and proceeds in good overall yields. The key step in the synthesis of 1,5- disubstituted pyrazolinyl pregnenolones is the heterocyclization of bezylidine derivatives (3) in presence of phenylhydrazines (4) through the initial formation of the phenylhydrazones, which undergo concomitant cyclization to generate the stable pyrazoline derivatives. RESULTS: All the synthesised D-ring 1,5-disubstituted pyrazolinyl pregnenolone derivatives (5a-l) were screened for prostate cancer cell inhibitory, 5α-reductase and 17α-hydroxylase-C17,20-lyase inhibitory activity. Amongst all the compounds screened for their 5α-reductase inhibitory activities, compound 5c, 5e, 5g and 5l were found to be the most active. Further, compounds 5g and 5h were found to have moderate 17α-hydroxylase-C17,20-lyase inhibitory activities. CONCLUSION: A series of D-ring 1,5-disubstituted pyrazolinyl pregnenolone derivatives (5a-l) were synthesized and screened for their prostate cancer cell inhibitory, 5a-reductase and 17α-hydroxylase-C17,20-lyase inhibitory activity. Amongst all the compounds screened for their 5α-reductase inhibitory activities, compound 5c, 5e, 5g and 5l were found to be the most active whereas compounds 5g and 5h were found to have moderate 17α- hydroxylase-C17,20-lyase inhibitory activities.


Asunto(s)
Antineoplásicos/farmacología , Inhibidores Enzimáticos/farmacología , Pregnenolona/farmacología , Esteroide 17-alfa-Hidroxilasa/antagonistas & inhibidores , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Conformación Molecular , Pregnenolona/síntesis química , Pregnenolona/química , Esteroide 17-alfa-Hidroxilasa/metabolismo , Relación Estructura-Actividad , Células Tumorales Cultivadas
17.
Tunis Med ; 96(10-11): 606-619, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30746653

RESUMEN

INTRODUCTION: Viral hepatitis represents a serious public health problem in the world especially in the Maghreb where the prevalence of the 5 viruses A, B, C, D, and E remains high and varies from one Maghreb country to another, there is few published studies on these infections in our Maghreb countries. METHOD OF STUDY: Our work is a review of the literature about prevalence, the most common mode of transmission, and the most exposed population for these viruses in the Maghreb countries through published studies between 2011 and 2017. RESULT: It has been found that the Maghreb countries are endemic for the five viruses with variable prevalence from one country to another, with sometimes heterogeneous data in the same country. For hepatitis B, Mauritania is the Maghreb country most affected by this infection unlike the rest of the Maghreb countries which are moderately endemic for this virus, the lowest prevalence of VHB was noted in Morocco, the genotype the most common is the D for the majority of Maghreb countries, and the precore mutant profile is also the most common. For hepatitis C the prevalence of infection does not vary much from one Maghreb country to another, but it remains slightly higher in Mauritania. The population most exposed to the virus C in the five countries is hemodialysis patients. The most common genotype in all Maghreb countries is genotype 1 except for Libya, where genotype 4 remains the most common probably related to its borders with Egypt. For hepatitis D, Mauritania is the only Maghreb country with a high endemicity for the virus. Tunisia has the lowest prevalence for hepatitis A and E compared to the rest of the Maghreb countries, all of which are endemic for these two viruses with fecal-oral transmission. CONCLUSION: The management of these viral hepatitis is costly for the health economy and to reduce their prevalence, prevention measures must be followed like vaccination and improving hygiene conditions.


Asunto(s)
Hepatitis Viral Humana/epidemiología , África del Norte/epidemiología , Argelia/epidemiología , Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepatitis Viral Humana/diagnóstico , Hepatitis Viral Humana/terapia , Hepatitis Viral Humana/virología , Humanos , Libia/epidemiología , Mauritania/epidemiología , Marruecos/epidemiología , Prevalencia , Túnez/epidemiología
18.
J Forensic Leg Med ; 46: 66-71, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28157592

RESUMEN

The present study provides a database of various morphometric dimensions of the foramen magnum region in the Saudi population. The objective of this study was to evaluate various measurements of the foramen magnum region for sex determination in the Saudi population by using computed tomography (CT) images. The various radiological measurements of the foramen magnum region were measured in a total of 200 adult subjects of Saudi origin including 100 males and 100 females. Sexual dimorphism was observed in five parameters related to the foramen magnum, namely length of the right occipital condyle (LROC), length of the left occipital condyle (LLOC), width of the foramen magnum (WFM), area of the foramen magnum (AFM) and length of the foramen magnum (LFM). The accuracy to discriminate sex ranged from 65.5% to 62.5% when LROC, LLOC, WFM, AFM, and LFM were considered as individual parameters. When multiple parameters were combined to discriminate sex, the highest accuracy of 71% was achieved.


Asunto(s)
Foramen Magno/diagnóstico por imagen , Determinación del Sexo por el Esqueleto/métodos , Adulto , Anciano , Análisis Discriminante , Femenino , Foramen Magno/anatomía & histología , Antropología Forense , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Arabia Saudita , Adulto Joven
19.
Enzyme Microb Technol ; 95: 4-12, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27866625

RESUMEN

The biological synthesis of nanoparticles (NPs) by bacteria and biofilms via extracellular redox reactions has received attention because of the minimization of harmful chemicals, low cost, and ease of culturing and downstream processing. Bioreduction mechanisms vary across bacteria and growth conditions, which leads to various sizes and shapes of biosynthesized NPs. NP synthesis in biofilms offers additional advantages, such as higher biomass concentrations and larger surface areas, which can lead to more efficient and scalable biosynthesis. Although biofilms have been used to produce NPs, the mechanistic details of NP formation are not well understood. In this review, we identify three critical areas of research and development needed to advance our understanding of NP production by biofilms: 1) synthesis, 2) mechanism and 3) stabilization. Advancement in these areas could result in the biosynthesis of NPs that are suitable for practical applications, especially in drug delivery and biocatalysis. Specifically, the current status of methods and mechanisms of nanoparticle synthesis and surface stabilization using planktonic bacteria and biofilms is discussed. We conclude that the use of biofilms to synthesize and stabilize NPs is underappreciated and could provide a new direction in biofilm-based NP production.


Asunto(s)
Biopelículas , Nanopartículas , Bacterias/metabolismo , Transporte de Electrón , Tecnología Química Verde , Microscopía Electrónica de Transmisión , Nanopartículas/química , Nanopartículas/metabolismo , Oxidación-Reducción , Difracción de Polvo , Análisis Espectral
20.
Enzyme Microb Technol ; 95: 69-75, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27866628

RESUMEN

The goal of this work was to synthesize gold nanoparticles (AuNPs) using electrode-respiring Geobacter sulfurreducens biofilms. We found that AuNPs are generated in the extracellular matrix of Geobacter biofilms and have an average particle size of 20nm. The formation of AuNPs was verified using TEM, FTIR and EDX. We also found that the extracellular substances extracted from electrode-respiring G. sulfurreducens biofilms reduce Au3+ to AuNPs. From FTIR spectra, it appears that reduced sugars were involved in the bioreduction and synthesis of AuNPs and that amine groups acted as the major biomolecules involved in binding.


Asunto(s)
Geobacter/metabolismo , Oro/química , Nanopartículas del Metal/química , Biopelículas , Biotecnología , Técnicas Electroquímicas , Matriz Extracelular/metabolismo , Tecnología Química Verde , Nanopartículas del Metal/ultraestructura , Microscopía Electrónica de Transmisión , Nanotecnología , Oxidación-Reducción , Tamaño de la Partícula , Espectrometría por Rayos X , Espectroscopía Infrarroja por Transformada de Fourier
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