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1.
Clin Exp Immunol ; 199(1): 24-38, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31777058

RESUMEN

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease that results from a dysregulated immune response against specific environmental triggers in a genetically predisposed individual. Increasing evidence has indicated a causal role for changes in gut microbiota (dysbiosis) contributing to this immune-mediated intestinal inflammation. These mechanisms involve dysregulation of multiple facets of the host immune pathways that are potentially reversible. Faecal microbiota transplantation (FMT) is the transfer of processed stool from a healthy donor into an individual with an illness. FMT has shown promising results in both animal model experiments and clinical studies in IBD in the resolution of intestinal inflammation. The underlying mechanisms, however, are unclear. Insights from these studies have shown interactions between modulation of dysbiosis via changes in abundances of specific members of the gut microbial community and changes in host immunological pathways. Unravelling these causal relationships has promising potential for a translational therapy role to develop targeted microbial therapies and understand the mechanisms that underpin IBD aetiopathogenesis. In this review, we discuss current evidence for the contribution of gut microbiota in the disruption of intestinal immune homeostasis and immunoregulatory mechanisms that are associated with the resolution of inflammation through FMT in IBD.


Asunto(s)
Disbiosis , Trasplante de Microbiota Fecal , Enfermedades Inflamatorias del Intestino , Animales , Modelos Animales de Enfermedad , Disbiosis/inmunología , Disbiosis/microbiología , Disbiosis/terapia , Humanos , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/terapia
2.
Nature ; 496(7446): 528-32, 2013 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-23575629

RESUMEN

In 2010 there were more than 200 million cases of malaria, and at least 655,000 deaths. The World Health Organization has recommended artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria caused by the parasite Plasmodium falciparum. Artemisinin is a sesquiterpene endoperoxide with potent antimalarial properties, produced by the plant Artemisia annua. However, the supply of plant-derived artemisinin is unstable, resulting in shortages and price fluctuations, complicating production planning by ACT manufacturers. A stable source of affordable artemisinin is required. Here we use synthetic biology to develop strains of Saccharomyces cerevisiae (baker's yeast) for high-yielding biological production of artemisinic acid, a precursor of artemisinin. Previous attempts to produce commercially relevant concentrations of artemisinic acid were unsuccessful, allowing production of only 1.6 grams per litre of artemisinic acid. Here we demonstrate the complete biosynthetic pathway, including the discovery of a plant dehydrogenase and a second cytochrome that provide an efficient biosynthetic route to artemisinic acid, with fermentation titres of 25 grams per litre of artemisinic acid. Furthermore, we have developed a practical, efficient and scalable chemical process for the conversion of artemisinic acid to artemisinin using a chemical source of singlet oxygen, thus avoiding the need for specialized photochemical equipment. The strains and processes described here form the basis of a viable industrial process for the production of semi-synthetic artemisinin to stabilize the supply of artemisinin for derivatization into active pharmaceutical ingredients (for example, artesunate) for incorporation into ACTs. Because all intellectual property rights have been provided free of charge, this technology has the potential to increase provision of first-line antimalarial treatments to the developing world at a reduced average annual price.


Asunto(s)
Artemisininas/metabolismo , Artemisininas/provisión & distribución , Vías Biosintéticas , Saccharomyces cerevisiae/metabolismo , Antimaláricos/economía , Antimaláricos/aislamiento & purificación , Antimaláricos/metabolismo , Antimaláricos/provisión & distribución , Artemisininas/química , Artemisininas/economía , Artemisininas/aislamiento & purificación , Biotecnología , Fermentación , Ingeniería Genética , Malaria Falciparum/tratamiento farmacológico , Datos de Secuencia Molecular , Saccharomyces cerevisiae/clasificación , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Oxígeno Singlete/metabolismo
3.
Br Med Bull ; 124(1): 181-190, 2017 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-29140453

RESUMEN

BACKGROUND: Faecal microbiota transplantation (FMT) as a potential treatment for inflammatory bowel disease (IBD) is an area of active current research, having been stimulated by the remarkable efficacy of FMT in treatment of Clostridium difficile-associated colitis. SOURCES OF DATA: This review is based on data from numerous case series on FMT in IBD since 1989 and results of four RCTs in ulcerative colitis (UC); three fully published. AREAS OF AGREEMENT: Early signals of short to medium-term efficacy of FMT for UC are promising. AREAS OF CONTROVERSY: Methodology, underlying mechanisms and questions regarding safety of FMT remain controversial. GROWING POINTS: Many trials of FMT in adults and children are currently recruiting. AREAS TIMELY FOR DEVELOPING RESEARCH: Future trials of FMT will likely revisit Crohn's disease and patients undergoing pouch surgery. Advances in microbial culture complementing genetic sequencing and investigations into the virome and mycobiome in IBD will be of great future interest.


Asunto(s)
Trasplante de Microbiota Fecal , Enfermedades Inflamatorias del Intestino/terapia , Medicina Basada en la Evidencia , Trasplante de Microbiota Fecal/métodos , Trasplante de Microbiota Fecal/tendencias , Microbioma Gastrointestinal/inmunología , Microbioma Gastrointestinal/fisiología , Humanos , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/microbiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Inducción de Remisión , Resultado del Tratamiento
4.
J Biol Regul Homeost Agents ; 31(4): 1023-1027, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29254309

RESUMEN

B-Cell Lymphoma protein-2 (BCL-2) is one of the most studied proteins with substantial regulatory potential for both apoptosis and autophagy. BCL-2 confer chemoresistance through influencing cancer pathophysiology. Serum level of lactate dehydrogenase (LDH) predicts increased anaerobic glycolysis and is associated with metabolic modulation in cancer cells. In the present research, the interplay of BCL-2, total oxidative status (TOS) and LDH was investigated in patients with acute lymphoblastic leukemia (ALL). The studied parameters, BCL-2 protein (p less than 0.001), TOS (p less than 0.001) and LDH (p less than 0.001) were significantly elevated in the ALL group compared to the normal group (N-group). However, the total antioxidant status (TAS) was reduced significantly (p less than 0.01) in ALL patients. In the ALL group, the TOS had significant negative correlation with TAS (p less than 0.01). Furthermore, non-significant positive correlations were found between BCL-2 and LDH, BCL-2 and TAS and LDH and TAS (each with; p>0.05). However, a negative non-significant correlation was observed between BCL-2 and TOS and LDH and TOS (each with; p>0.05).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Regulación Leucémica de la Expresión Génica , L-Lactato Deshidrogenasa/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , L-Lactato Deshidrogenasa/sangre , Masculino , Oxidación-Reducción , Estrés Oxidativo , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Proteínas Proto-Oncogénicas c-bcl-2/sangre , Transducción de Señal
5.
Int J Immunopathol Pharmacol ; 29(1): 17-22, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26519524

RESUMEN

The effect of acetaminophen on sulfamethazine N-acetylation by human N-acetyltrasferase-2 (NAT2) was studied in 19 (n=19) healthy male volunteers in two different phases. In the first phase of the study the volunteers were given an oral dose of sulfamethazine 500 mg alone and blood and urine samples were collected. After the 10-day washout period the same selected volunteers were again administered sulfamethazine 500 mg along with 1000 mg acetaminophen. The acetylation of sulfamethazine by human NAT2 in both phases with and without acetaminophen was determined by HPLC to establish their respective phenotypes. In conclusion obtained statistics of present study revealed that acetaminophen significantly (P<0.0001) decreased sulfamethazine acetylation in plasma of both slow and fast acetylator male volunteers. A highly significant (P<0.0001) decrease in plasma-free and total sulfamethazine concentration was also observed when acetaminophen was co-administered. Urine acetylation status in both phases of the study was found not to be in complete concordance with that of plasma. Acetaminophen significantly (P<0.0001) increased the acetyl, free and total sulfamethazine concentration in urine of both slow and fast acetylators. Urine acetylation analysis has not been found to be a suitable approach for phenotypic studies.


Asunto(s)
Acetaminofén/farmacología , Sulfametazina/metabolismo , Acetilación , Adulto , Arilamina N-Acetiltransferasa/antagonistas & inhibidores , Humanos , Masculino
6.
Colorectal Dis ; 16(10): 794-800, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24916374

RESUMEN

AIM: The study aimed to analyse the feasibility and efficacy of administration of a single intravenous iron infusion (IVI) in the preoperative optimization of colorectal cancer patients with anaemia. METHOD: Twenty patients were recruited at least 14 days before the planned date of surgery. A single 1000 mg dose of ferric carboxymaltose (Ferinject) was administered as an outpatient procedure. Blood samples were taken at recruitment prior to drug administration (REC), on the day of surgery prior to any intervention (DOS) and on the first postoperative day. Allogeneic red blood cell transfusions (ARBT) and outcomes were recorded from recruitment throughout the study period. RESULTS: There was a significant median rise in haemoglobin levels (Hb) from REC to DOS of 1.8 g/dl [interquartile range (IQR) 0.75-2.45, P < 0.001] for the entire cohort. Two patients received ARBT preoperatively, and for those not transfused preoperatively (n = 18), this incremental Hb rise remained significant (P < 0.001, median 1.65 g/dl, IQR 0.5-2.3). Of these patients, those who responded to IVI had higher erythropoietin (EPO) levels at recruitment (P < 0.01) and lower recruitment Hb values, transferrin-saturation (TSAT) and C-reactive protein (CRP) levels (P < 0.05). REC Hb (Rs = -0.62, P < 0.01), REC TSAT levels (Rs = -0.67, P < 0.01) and REC EPO (Rs = 0.69, P < 0.01) correlated with the magnitude of treatment change in Hb levels. Five patients received ARBT until the fourth postoperative day, which was significantly fewer than predicted (P < 0.05). CONCLUSION: IVI can be administered preoperatively in the outpatient clinic to colorectal cancer patients with anaemia, with associated reduction in ARBT use and increase in Hb levels.


Asunto(s)
Adenocarcinoma/cirugía , Anemia/tratamiento farmacológico , Neoplasias Colorrectales/cirugía , Compuestos Férricos/administración & dosificación , Maltosa/análogos & derivados , Adenocarcinoma/complicaciones , Anciano , Anciano de 80 o más Años , Anemia/sangre , Anemia/complicaciones , Proteína C-Reactiva/metabolismo , Neoplasias Colorrectales/complicaciones , Transfusión de Eritrocitos , Eritropoyetina/sangre , Estudios de Factibilidad , Femenino , Hemoglobinas/metabolismo , Humanos , Infusiones Intravenosas , Tiempo de Internación , Masculino , Maltosa/administración & dosificación , Persona de Mediana Edad , Proyectos Piloto , Complicaciones Posoperatorias , Cuidados Preoperatorios , Transferrinas/sangre
7.
Ann Burns Fire Disasters ; 37(1): 28-34, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38680832

RESUMEN

The scarcity of data on burn-related injuries in Pakistan prompted this study. The study is specifically aimed at assessing the burn patients who were admitted to a national burn care center (BCC) in Pakistan. This single-center retrospective analysis was conducted for 12 months from January to December 2021. During this time period, 14,069 patients visited BCC with burn injuries of diverse natures while 613 of them were admitted. The patients' information was abstracted from the hospital database. This information included age, sex, diagnosis, burn depth/degree, time of arrival, circumstances of burn injury, TBSA (total burn surface area), complications, outcome, and management plan. This information was shifted to Microsoft Office Excel Worksheet 2015 and then coded into the IBM Statistical Package for the Social Sciences (SPSS) version 24.0. Armonk, NY: IBM Corp. Of 14,069 patients, 613 were admitted to the burn care center, indicating an admission rate of 4.35%. Among these 613 patients, there was a high proportion of males (58.89%) and a mean age of 20.2±12.5 years. Most patients (40.4%) visited within the first hour after being burnt and flame burns were the most common (41.10%). Most patients were burnt due to accidents (97.7%). The mean length of hospital stay was 15.5 days. Flames were the main cause of burns among our cohort of patients. Most patients had a TBSA of >10% and generally had a second-degree burn, mostly in the pediatric population. An urgent appraisal of burn policies and related legislation is needed to halt the burn burden in the country.


Cette étude a été décidée en raison de la pauvreté des données épidémiologiques concernant les brûlures au Pakistan. Il s'agit d'une étude monocentrique rétrospective sur dossier conduite dans le CTB national d'Islamabad sur l'année 2021. Sur les 14 069 patients brûlés qui s'y sont présentés, 613 (4,35%) ont été hospitalisés. Nous avons recueilli l'âge, le sexe, la SCB, la profondeur, la cause, le délai de présentation, la stratégie thérapeutique, les complications et le devenir des patients. Les données ont été implantée dans Excel et analysées avec SSPS 24.0. Parmi les patients hospitalisés, 58,89% étaient des hommes âgés de 20,2±12,5 ans. Le délai de présentation était de moins de 1h dans 40,4% des cas et l'atteinte était quasiment toujours accidentelle (97,7%), majoritairement par flamme (41%). La DMS était de 15,5 j. L'atteinte était le plus souvent > 10% SCT, habituellement au 2ème degré en particulier en population pédiatrique. Une évaluation de la législation préventive est urgente, afin de mettre fin au fardeau que représentent les brûlures dans notre pays.

8.
Ann Burns Fire Disasters ; 37(2): 134-139, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38974791

RESUMEN

Burns are a major public health issue. Psychiatric issues require special attention. According to research, lowering stigma and anxiety and raising self-esteem are efficient ways to encourage the social reintegration of burn patients. The current study was aimed at investigating the association between burn patients' anxiety, depression, low self-esteem levels and the total body surface area (TBSA) affected by burn injuries. This single-center, cross-sectional study was conducted from January to June 2022. A sample size of 200 burn patients was calculated. Any patient with a prior psychiatric diagnosis was disqualified from the trial except for nicotine dependency. The patients were evaluated for anxiety, depression and self-esteem using specific scales. The data were tabulated and statistically analyzed using SPSS 25.0. There was male predominance as 55% (n=110) of participants were males. The age range was 18-70 years, and the average age of participants was 36.4±8.6 years. About 68.50% of participants were married, 29.50% were unmarried and 2% were divorced/widowed. Men tended to experience anxiety symptoms more frequently. More than half (58.0%) suffered from burns involving 20-39% of total body surface area (TBSA). No significant relationship was found between TBSA and anxiety, depression or self-esteem. Psychiatric issues are highly prevalent in burn victims. More research is necessary to determine the extent and determinants of psychological issues in burn patients.


Les brûlures sont un problème de santé publique majeur et leurs conséquences psychiatriques ne doivent pas être négligées. La prise en compte de la baisse thymique, de l'anxiété et de la perte de confiance en soi promeuvent la réintégration sociale de ces patients. Cette étude a cherché une corrélation entre la surface brûlée et les conséquences psychologiques et/ou psychiatriques. Cette étude monocentrique cas- témoin a été conduite entre janvier et juin 2022, permettant de recruter l'effectif calculé de 200 brûlés, exempts de pathologie psychiatrique préalable (hors addiction au tabac). Anxiété, dépression et estime de soi ont été mesurées au moyen d'échelles spécifiques puis analysées avec SSPS 25.0. Cent dix (55%) des patients étaient de sexe masculin. L'âge moyen était de 36,4 +/- 8,6 ans (18-70). Environ 68,5% des patients étaient mariés, 29,5% célibataires et 2% séparés ou veufs. Les hommes tendaient à présenter plus souvent des symptômes anxieux. Plus de la moitié (58%) avaient une atteinte sur 20 à 39% de SCT, cependant il n'a pas été trouvé de corrélation entre la SCT et les variables étudiées. Les séquelles psychiatriques étant très fréquentes après une brûlure, il est nécessaire d'en déterminer la gravité et les facteurs déclenchants.

9.
Ann Burns Fire Disasters ; 37(3): 226-232, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39350893

RESUMEN

The management of burn wounds is a major challenge throughout the globe. Superficial and partial-thickness burns generally do not need any surgical intervention, however, severe cases of burn injury require dressings (antimicrobial) and surgery in the worst-case scenario. The present study was conducted to assess the efficacy of bacterial nanocellulose dressing versus hydrocolloid dressing. All patients presenting with partial-thickness second-degree burns from June 2021 to May 2022 were screened for this randomized control trial; 65 burn patients were included in each group of this trial. The control group of patients was treated with hydrocolloid dressing and the experimental group with bacterial nanocellulose dressing sheets. Every third day, the wound was assessed. Other data collected included age, sex, %TBSA burned, signs of infection, time for epithelialization, and length of hospital stay. Statistical analyses were performed to see the significance of differences between the treatment groups by adjusting for size and depth of burn, and the patient's age. There were 130 patients (65 in each group). The median age for the whole group was 17.4 years, and 51.53% (n=67) were males. The average TBSA was 22.4%, with a minimum of 10% and a maximum of 31%. Eleven of the patients had their burns excised, and four were given skin grafts in the control group. In the case of the experimental group, four excisions were performed, and one skin graft. Wound-related pain scores were low (mean of 2.6) for the bacterial nanocellulose group and higher for the hydrocolloid group. Hydrocolloid dressing is more cost effective than bacterial nanocellulose dressing. However, the pain scores were high, and healing time was less in the bacterial nanocellulose group. Moreover, the hydrocolloid group is more prone to infection due to frequent dressing changes.


La prise en charge des brûlés est un problème mondial de santé publique. Si les brûlures superficielles et intermédiaires guérissent habituellement spontanément, les plus sévères nécessitent une prise en charge chirurgicale, après pansements antibactériens. Cette étude a pour but de comparer l'efficacité des pansements à l'hydrocellulose bactérien et l'hydrocolloïde. Tous les patients souffrant de brûlures intermédiaires vus entre juin 2021 et mai 2022 ont été tirés au sort pour former 2 groupes de 65, de 17,4 ans d'âge médian avec une légère prédominance masculine (67 soit 51,53%), brûlés sur 22,4% de SCT en moyenne (10-31). Le groupe contrôle avait des pansements à l'hydrocolloïde (HC), le groupe à l'étude au nanocellulose bactérien (NB), la plaie étant évaluée tous les 3 jours. Les variables à l'étude étaient l'âge, le sexe, la surface brûlée, les signes d'infection, le délai d'épithélialisation et la durée de séjour. Les comparaisons ont été ajustées sur la surface, la profondeur et l'âge. Dans le groupe HC, 11 patients ont été excisés et 4 greffés contre 4 et 1 dans le groupe NB. La douleur des NB était à 2,6 ; elle était plus élevée dans le groupe HC. Le NB est plus cher que le HC. Il faut toutefois rapporter ce coût à une douleur moindre et à une cicatrisation plus rapide. Qui plus est, les patients sous HC sont plus à risque d'infection en raison de changements de pansements plus fréquents.

10.
J Hosp Infect ; 148: 189-219, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38609760

RESUMEN

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.


Asunto(s)
Infecciones por Clostridium , Trasplante de Microbiota Fecal , Trasplante de Microbiota Fecal/métodos , Humanos , Infecciones por Clostridium/terapia , Reino Unido , Clostridioides difficile , COVID-19/terapia , Recurrencia , Gastroenterología/normas , Gastroenterología/métodos , SARS-CoV-2 , Sociedades Médicas
11.
J Mol Cell Cardiol ; 59: 67-75, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23402927

RESUMEN

Heart rates during ischaemia and reperfusion are possible determinants of reperfusion arrhythmias. We used ivabradine, a selective If current inhibitor, to assess the effects of heart rate reduction (HRR) during ischaemia-reperfusion on reperfusion ventricular arrhythmias and assessed potential anti-arrhythmic mechanisms by optical mapping. Five groups of rat hearts were subjected to regional ischaemia by left anterior descending artery occlusion for 8min followed by 10min of reperfusion: (1) Control n=10; (2) 1µM of ivabradine perfusion n=10; (3) 1µM of ivabradine+5Hz atrial pacing throughout ischaemia-reperfusion n=5; (4) 1µM of ivabradine+5Hz pacing only at reperfusion; (5) 100µM of ivabradine was used as a 1ml bolus upon reperfusion. For optical mapping, 10 hearts (ivabradine n=5; 5Hz pacing n=5) were subjected to global ischaemia whilst transmembrane voltage transients were recorded. Epicardial activation was mapped, and the rate of development of ischaemia-induced electrophysiological changes was assessed. HRR observed in the ivabradine group during both ischaemia (195±11bpm vs. control 272±14bpm, p<0.05) and at reperfusion (168±13bpm vs. 276±14bpm, p<0.05) was associated with reduced reperfusion ventricular fibrillation (VF) incidence (20% vs. 90%, p<0.05). Pacing throughout ischaemia-reperfusion abolished the protective effects of ivabradine (100% VF), whereas pacing at reperfusion only partially attenuated this effect (40% VF). Ivabradine, given as a bolus at reperfusion, did not significantly affect VF incidence (80% VF). Optical mapping experiments showed a delay to ischaemia-induced conduction slowing (time to 50% conduction slowing: 10.2±1.3min vs. 5.1±0.7min, p<0.05) and to loss of electrical excitability in ivabradine-perfused hearts (27.7±4.3min vs. 14.5±0.6min, p<0.05). Ivabradine administered throughout ischaemia and reperfusion reduced reperfusion VF incidence through HRR. Heart rate during ischaemia is a major determinant of reperfusion arrhythmias. Heart rate at reperfusion alone was not a determinant of reperfusion VF, as neither a bolus of ivabradine nor pacing immediately prior to reperfusion significantly altered reperfusion VF incidence. This anti-arrhythmic effect of heart rate reduction during ischaemia may reflect slower development of ischaemia-induced electrophysiological changes.


Asunto(s)
Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/tratamiento farmacológico , Benzazepinas/uso terapéutico , Frecuencia Cardíaca/efectos de los fármacos , Isquemia Miocárdica/complicaciones , Daño por Reperfusión Miocárdica/complicaciones , Fibrilación Ventricular/tratamiento farmacológico , Animales , Arritmias Cardíacas/etiología , Ivabradina , Masculino , Ratas , Ratas Sprague-Dawley
12.
Mol Cell Biochem ; 380(1-2): 83-96, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23620341

RESUMEN

Although, several novel forms of intervention aiming at newly identified therapeutic targets are currently being developed for diabetes mellitus (DM), it is well established that physical exercise continues to be one of the most valuable forms of non-pharmacological therapy. The aim of the study was to investigate the effects of exercise training on excitation-contraction coupling and related gene expression in the Goto-Kakizaki (GK) type 2 diabetic rat heart and whether exercise is able to reverse diabetes-induced changes in excitation-contraction coupling and gene expression. Experiments were performed in GK and control rats aged 10-11 months following 2-3 months of treadmill exercise training. Shortening, [Ca(2+)]i and L-type Ca(2+) current were measured in ventricular myocytes with video edge detection, fluorescence photometry and whole cell patch clamp techniques, respectively. Expression of mRNA was assessed in ventricular muscle with real-time RT-PCR. Amplitude of shortening, Ca(2+) transients and L-type Ca(2+) current were not significantly altered in ventricular myocytes from GK sedentary compared to control sedentary rats or by exercise training. Expression of mRNA encoding Tpm2, Gja4, Atp1b1, Cacna1g, Cacnb2, Hcn2, Kcna3 and Kcne1 were up-regulated and Gja1, Kcnj2 and Kcnk3 were down-regulated in hearts of sedentary GK rats compared to sedentary controls. Gja1, Cav3 and Kcnk3 were up-regulated and Hcn2 was down-regulated in hearts of exercise trained GK compared to sedentary GK controls. Ventricular myocyte shortening and Ca(2+) transport were generally well preserved despite alterations in the profile of expression of mRNA encoding a variety of cardiac muscle proteins in the adult exercise trained GK diabetic rat heart.


Asunto(s)
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatología , Expresión Génica , Contracción Miocárdica/fisiología , Miocardio/metabolismo , Condicionamiento Físico Animal/fisiología , Animales , Calcio/metabolismo , Canales de Calcio Tipo L/metabolismo , Canales de Calcio Tipo L/fisiología , Caveolina 3/genética , Forma de la Célula , Células Cultivadas , Conexina 43/genética , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/genética , Espacio Intracelular , Masculino , Potenciales de la Membrana , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/fisiología , Proteínas del Tejido Nervioso/genética , Técnicas de Placa-Clamp , Canales de Potasio de Dominio Poro en Tándem/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
13.
Colorectal Dis ; 15(7): 836-41, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23691950

RESUMEN

AIM: The diagnosis and treatment of ulcerative colitis (UC) is traditionally the realm of gastroenterologists. However, the symptoms of UC overlap with those of bowel cancer and patients may be initially referred to colorectal surgery clinics. The aims of this study were to define which specialty most frequently diagnoses UC and to determine if there were differences in management between the two specialities. METHOD: The demographics, presenting symptoms and clinical management of patients with newly diagnosed UC were determined and compared by speciality clinic of initial referral. Histopathology reports and clinic letters were reviewed to identify patients newly diagnosed with UC at a large university teaching hospital from January 2007 to January 2012. RESULTS: Patients were more commonly referred to colorectal surgeons (74 vs 41 patients) than gastroenterologists. Patients referred to gastroenterology were younger (36.0 vs 59.6 years, P < 0.01) but there were no significant differences in gender, presenting symptoms or disease extent. Rigid sigmoidoscopy ± biopsy was more commonly performed in colorectal clinic (93.2 vs 31.7%, P < 0.01). There was a significantly shorter delay in starting disease-specific treatment for those patients referred initially to colorectal surgery (13.8 vs 33.6 days, P = 0.01). Performing rigid sigmoidoscopy in clinic was associated with starting disease-specific treatment at this visit. CONCLUSION: Patients with first presentation UC are more commonly seen in colorectal surgery clinics where rigid sigmoidoscopy is more frequently undertaken, allowing earlier commencement of UC treatment.


Asunto(s)
Colitis Ulcerosa/terapia , Colonoscopía/estadística & datos numéricos , Cirugía Colorrectal/estadística & datos numéricos , Gastroenterología/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Tiempo de Tratamiento/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria , Colitis Ulcerosa/diagnóstico , Diagnóstico Tardío , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
14.
Ann Burns Fire Disasters ; 36(4): 286-292, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38680245

RESUMEN

Burns are a public health concern burdening the healthcare delivery system across the globe. Mortality rates are significant outcome parameters after a burn injury. The objective of the current study was to analyze the characteristics of the patients admitted to our burn care center and identify the factors related to mortality in the burn patients. This was a cross-sectional single-center study involving a retrospective analysis of mortality rates in burn patients over a period of 15 years from July 2007 to December 2021. During the study period, 7,866 burn patients were admitted to the ICU of the burn care center. Patients who died [Group 1] were compared to the group of survivors (control cases [Group 2]) to ascertain the contributing factors that might forecast a high risk for mortality. The mortality rate was calculated as 23.16% (1,822/7,866). The majority of the patients (both groups) had a total body surface area (TBSA) of >50% (p 0.001). The average duration of stay at the burn care center was 15.5 days for the survivors' group (Group 2) while it was 11.4 days for the patients who died (Group 1) during the course of their treatment. About 23.16% of all admitted patients died mostly from flame burns, and sepsis was the commonest cause of death. Patients with risk factors should be classified as high risk for mortality at the time of ICU admission. It is necessary to initiate educational and awareness programs for sensitization related to the prevention of burn injuries.


Les brûlures représentent une pathologie impactant les systèmes de santé du monde entier. Le taux de mortalité sont des marqueurs significatifs de l'évolution des brûlés. Cette étude rétrospective monocentrique cas- témoins analyse les caractéristiques des patients admis dans notre CTB pour brûlure pendant 15 ans (juillet 2007- Décembre 2021) et recherche les paramètres liés à la mortalité. Les 7 866 patients ont été répartis entre morts (1 822 ; 23,16%) et vivants. La majorité des patients, quel que soit le groupe, étaient brûlés sur au moins 50% de SCT. La DMS était plus longue chez les survivants (15,5 jours) que chez les morts (11,4 jours). La majorité des patients décédés étaient brûlés par flamme et le sepsis était la cause la plus fréquente de l'exitus. Ces patients devraient être classés comme à risque majeur de décès dès l'entrée. Il est nécessaire de mettre en œuvre des programmes d'éducation et de sensibilisation pour diminuer l'incidence des brûlures.

15.
Ann Burns Fire Disasters ; 36(3): 261-265, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38680442

RESUMEN

The transfusion of blood and blood components is a life-saving medical procedure, however, it is linked with adverse reactions to transfusions. Information about different types of adverse transfusion reactions (ATRs) will assist in their early identification and subsequent management, as well as in devising strategies to minimize the occurrence of adverse reactions related to blood component transfusion. The current study was therefore executed to analyze the pattern of ATRs in patients with burn injuries at a national burn center. This was a cross-sectional, prospective study involving an analysis of immediate ATRs from January 2020 to June 2021 (18 months). ATRs observed during the study period were documented and analyzed. During the study period, 2,220 units of blood and blood components were transfused to 1,075 burn patients (2.06 transfusions per patient). A total of 27 ATRs were recorded (1.21%). Allergic reactions were the commonest (55.55%) followed by febrile non-haemolytic transfusion reaction (37.03%). The mean volume of blood unit transfused, when the reactions were noted, was approximately 75 ml (range: 15-230 ml). The mean time at which transfusion reactions were noted was 17 min (range: 5-220 minutes). The ATRs were more common in patients with multiple transfusions compared to those receiving a single transfusion. The common adverse reactions were allergic and febrile non-haemolytic transfusion reactions. It is vital to report all transfusion reactions to the attached blood center and hospital transfusion committee (HTC) on standardized reporting forms. Continuous medical education through seminars and sensitization workshops will support consolidating haemovigilance systems.


La transfusion de sang et de ses dérivés peut être salvatrice mais aussi être responsables d 'effets indésirables (EI). Les données concernant ces EI permettent de les diagnostiquer et les traiter précocement ainsi que de développer des protocoles destinés à en diminuer la prévalence. Cette étude rétrospective a analysé les EI transfusionnels survenus dans un CTB pakistanais sur une période de 18 mois (janvier 2020- juin 2021). Deux mille deux cent vingt unités ont été transfusées à 1 075 brûlés (2,06/patient). Vingt- sept (1,21%) EI ont été enregistrés. Les plus courantes étaient allergiques (55,55%), suivies des réactions fébriles non hémolytiques (37,03%). Cette réaction survenait à la 17ème minute (5- 220) lorsque 75 mL (15 à 230) avaient été passés. Ils étaient plus fréquents chez les multitransfusés que lors de la première perfusion. Il est crucial de rapporter tout EI au CTS et à l'hémovigilance locaux, sous un format standardisé et d'éduquer prescripteurs et utilisateurs.

16.
Case Rep Dermatol Med ; 2022: 2542404, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36338291

RESUMEN

A rare form of dermatofibroma (DF) is described in the literature as giant dermatofibroma. Due to the rarity and distinct presentation that can be confused with more sinister skin tumours, these can cause diagnostic uncertainty and require clinicopathologic correlation. Familiarity with this rare presentation of an otherwise common entity is required to prevent unnecessary clinical doubt and excessive interventions. We report a case of giant dermatofibroma on the leg of a 29-year-old healthy male that presented with a 7 cm, nonulcerated pink, brown plaque, adding to the limited literature of less than 30 known cases.

17.
Braz J Biol ; 82: e250865, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34378681

RESUMEN

Cadmium (Cd) is one of the major toxicants, which affects human health through occupational and environmental exposure. In the current study, we evaluated the protective effects of morel mushrooms against Cd-induced reproductive damages in rats. For this purpose, 30 male rats were divided into 6 groups (n=5/group), the first group served as the control group, second group was treated with an intraperitoneal (i.p) injection of 1 mg/kg/day of Cd. Third and fourth groups were co-treated with 1 mg/kg/day of Cd (i.p) and 10 and 20 mg/kg/day of morel mushroom extract (orally) respectively. The final 2 groups received oral gavage of 10 and 20 mg/kg/day of morel mushroom extract alone. After treatment for 17 days, the animals were euthanized, and testes and epididymis were dissected out. One testis and epididymis of each animal were processed for histology, while the other testis and epididymis were used for daily sperm production (DSP) and comet assay. Our results showed that Cd and morel mushrooms have no effect on animal weight, but Cd significantly decreases the DSP count and damages the heritable DNA which is reversed in co-treatment groups. Similarly, the histopathological results of testes and epididymis show that morel mushrooms control the damage to these tissues. Whereas the morel mushroom extract alone could enhance the production of testosterone. These results conclude that morel mushrooms not only control the damage done by Cd, but it could also be used as a protection mechanism for heritable DNA damage.


Asunto(s)
Agaricales , Cadmio , Animales , Ascomicetos , Cadmio/toxicidad , Masculino , Ratas , Espermatozoides , Testículo
18.
Braz J Biol ; 84: e249664, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34787236

RESUMEN

The impact of antibiotics on growth, cocoon production was assessed in addition to isolation and characterization of bacteria associated with silkworm gut of infected larvae. Larval rearing was maintained at recommended conditions of temperature and humidity. Silkworm larvae showing abnormal symptoms were collected from the control group and dissected for gut collection. Bacteria were isolated from the gut content by spreading on agar plates and incubated at 37 °C for 48 hrs. Bacterial identification and phylogenetic analysis were carried out by 16S rRNA gene sequencing. The isolated bacteria were subjected to antimicrobial susceptibility test (disc diffusion methods) by using Penicillin (10 µg/mL), Tetracycline (30 µg/mL), Amoxicillin (25 µg/mL), Ampicillin (10 µg/mL), and Erythromycin (15 µg/mL). All isolated strains showed positive results for the catalase test. We isolated and identified bacterial strains (n = 06) from the gut of healthy and diseased silkworm larvae. Based on the 16S rRNA gene sequence, isolated bacteria showed close relation with Serratia, Bacillus, and Pseudomonas spp. Notably, 83.3% of strains were resistant to Penicillin, Tetracycline, Amoxicillin, Ampicillin, and Erythromycin but 16.6% showed antibiotic susceptibility to the above-mentioned commonly used antibiotics. Silkworm larvae fed on penicillin-treated leaves showed significant improvement in larval weight, larval length, and cocoon production. Significantly higher larval weight (6.88g), larval length (5.84cm), and cocoon weight (1.33g) were recorded for larvae fed on leaves treated with penicillin as compared to other antibiotics. Isolated bacterial strains showed close relation with Serratia spp., Bacillus spp. and Pseudomonas spp.


Asunto(s)
Antibacterianos , Bombyx , Animales , Antibacterianos/farmacología , Bacterias/genética , Larva , Pruebas de Sensibilidad Microbiana , Filogenia , ARN Ribosómico 16S/genética
19.
Plant Biol (Stuttg) ; 23(3): 464-472, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33215799

RESUMEN

In the maize-soybean intercropping system, shade is the major chronic restraint that affects normal growth of soybean. Different spatial patterns of this system affect the microclimate of soybean through shading from maize plants. However, the negative impacts of shading stress can be mitigated by providing optimal ratios of different fertilizers. Therefore, to test this hypothesis, soybean plants were grown under different light conditions (normal light or shade) to evaluate the response to varying NH4 + /NO3 - ratios. Seeds of soybean (Glycine max L. cv. Nan-99-6) were grown in nutrient solution with a total concentration of 5 mM N using different NH4 + /NO3 - ratios (T0  = 0:0, T1  = 0:100, T2  = 25:75, T3  = 50:50 and T4  = 75:25) for 40 days in a greenhouse at PPFD 320.95 µmol m-2  s-1 (low light) or 967.53 µmol m-2  s-1 (normal light). Under low light, growth and photosynthesis of soybean seedlings significantly decreased as compared to normal light conditions. However, the optimal ratios of NH4 + / NO3 - improved growth and photosynthesis of soybean seedlings under both light conditions. Our results indicated that soybean seedlings supplied with optimal NH4 + /NO3 - ratios (25:75 and 50:50) have maximum biomass yield, chlorophyll pigments, leaf gas exchange, photochemical activity and root growth as compared to low and high NH4 + /NO3 - ratios (T1 and T4 ). High ratios of NH4 + /NO3 - (T4 ) resulted in reduced plant growth due to nutrient accumulation in plant tissues; therefore, we suggest that optimal ratios of NH4 + /NO3 - (T2 and T3 ) can enhance the shade tolerance of soybean seedlings.


Asunto(s)
Fabaceae , Plantones , Clorofila , Nitratos , Fotosíntesis , Hojas de la Planta , Glycine max
20.
East Mediterr Health J ; 16 Suppl: S5-14, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21495583

RESUMEN

Pakistan, with Nigeria, India and Afghanistan, is one of the four remaining polio endemic countries in the world. Since the start of polio eradication initiative in 1994, the country has succeeded in reducing the number of polio cases from an estimated 20,000 annually to 89 in 2009. Furthermore, persistent transmission is largely localized to three transmission zones in which ten of the fifteen highest risk areas are situated. Insecurity, operational issues, governance lapses, low routineimmunization coverage, inadequate trickle-down of the political commitment existing at the national level to sub-national level and extensive population movement are the main barriers to the process. A robust strategic plan was developed for 2010-2012 encompassing district-specific plans and focused strategy on securitycompromised areas, performance-based payment, independent monitoring, attention to migratory populations, social mobilization, and strategic cooperation with Afghanistan. This will provide Pakistan a strong and imminent opportunity to interrupt polio virus circulation.


Asunto(s)
Enfermedades Endémicas/prevención & control , Programas de Inmunización/organización & administración , Poliomielitis/prevención & control , Vacunas contra Poliovirus , Poliovirus , Vigilancia de la Población/métodos , Preescolar , Femenino , Humanos , Lactante , Masculino , Pakistán/epidemiología , Poliomielitis/epidemiología , Poliomielitis/transmisión
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