RESUMEN
PURPOSE OF THE REVIEW: Acid suppression with proton pump inhibitors (PPIs) represents the standard of care in the treatment of acid-related diseases. However, despite their effectiveness, PPIs display some intrinsic limitations, which underlie the unmet clinical needs that have been identified over the past decades. The aims of this review are to summarize the current status and future development of the new class of antisecretory drugs (potassium-competitive acid blockers, P-CABs) that have recently been introduced into medical practice. RECENT FINDINGS: Over the past decades, clinical needs unmet by the current acid suppressants have been recognized, especially in the management of patients with GERD, Helicobacter pylori infection and NSAID-related peptic ulcer. The failure to address these needs is mainly due to their inability to achieve a consistent acid suppression in all patients and, particularly, to control nighttime acidity. It was then realized that an extended duration of acid suppression would exert additional benefits. The available data with P-CABs show that they are able to address these unmet clinical needs. Four different P-CABs (vonoprazan, tegoprazan, fexuprazan and keverprazan) are currently available. However, only two of them are approved outside Asia. Vonoprazan is available in North, Central and South America while tegoprazan is marketed only in Latin American countries. Two other compounds (namely linazapran glurate and zestaprazan) are presently under clinical development. While clinical trials on GERD have been performed with all P-CABs, only vonoprazan and tegoprazan have been investigated as components of Helicobacter pylori eradication regimens. The available data show that-in the above two clinical indications-P-CABs provide similar or better efficacy in comparison with PPIs. Their safety in the short-term overlaps that of PPIs, but data from long-term treatment are needed.
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BACKGROUND: Helicobacter pylori (H. pylori) was discovered 40 years ago and has set a milestone in human medicine. The discovery led to rejection of the dogma of the acidic stomach as a sterile organ and requested to rewrite the chapters on gastric pathophysiology and gastroduodenal diseases. SUMMARY: Over a period of 40 years following the discovery, more than 50,000 articles can be retrieved in PubMed as of today and illustrate the amount and the intensity of research around the role of this bacterium. H. pylori emerged as cause of chronic gastritis and principal cause of peptic ulcer disease (PUD). Eradication of H. pylori became standard of care in management in PUD. The importance of this was highlighted in 2005 with the Nobel Prize in Medicine awarded to Barry Marshall and Robin Warren. H. pylori became eventually recognized for its oncogenic potential in the stomach and as the main risk factor for gastric cancer development. KEY MESSAGES: H. pylori gastritis is defined as infectious disease and requires therapy in all infected individuals. Strategies of gastric cancer prevention and development of therapies to overcome the increasing antibiotic resistance are main targets in clinical research of today.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/complicaciones , Úlcera Péptica/microbiología , Úlcera Péptica/terapia , Úlcera Péptica/tratamiento farmacológico , Historia del Siglo XX , Gastritis/microbiología , Gastritis/terapia , Antibacterianos/uso terapéutico , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/terapia , Historia del Siglo XXIRESUMEN
Helicobacter pyloriInfection is formally recognised as an infectious disease, an entity that is now included in the International Classification of Diseases 11th Revision. This in principle leads to the recommendation that all infected patients should receive treatment. In the context of the wide clinical spectrum associated with Helicobacter pylori gastritis, specific issues persist and require regular updates for optimised management.The identification of distinct clinical scenarios, proper testing and adoption of effective strategies for prevention of gastric cancer and other complications are addressed. H. pylori treatment is challenged by the continuously rising antibiotic resistance and demands for susceptibility testing with consideration of novel molecular technologies and careful selection of first line and rescue therapies. The role of H. pylori and antibiotic therapies and their impact on the gut microbiota are also considered.Progress made in the management of H. pylori infection is covered in the present sixth edition of the Maastricht/Florence 2021 Consensus Report, key aspects related to the clinical role of H. pylori infection were re-evaluated and updated. Forty-one experts from 29 countries representing a global community, examined the new data related to H. pylori infection in five working groups: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) H. pylori and the gut microbiota. The results of the individual working groups were presented for a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in various clinical fields.
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BACKGROUND: COVID-19 was initially considered a respiratory disease but the SARS-CoV-2 virus can lead to serious systemic consequences affecting major organs including the digestive system. SUMMARY: This review brings new clinically important information for the gastroenterologist. This includes: the mechanisms of tissue damage seen with the SARS-CoV-2 virus; the consequences of immunosuppression in patients with inflammatory bowel disease (IBD) and chronic liver disease with the additional risks of decompensation in patients with cirrhosis; the impact of COVID-19 on gastrointestinal emergencies, on gastrointestinal endoscopy, diagnosis and treatments. These highlight the need to understand the clinical pharmacology, toxicology and therapeutic implications of drugs commonly used by gastroenterologists and their links with COVID-19. Key Messages: Any part of the digestive system may be affected by the SARS-CoV-2 virus, and those with pre-existing disease are at greatest risk of adverse outcomes. The risk for drug-drug interactions is considerable in patients seriously ill with COVID-19 who often require mechanical ventilation and life support. Some repurposed drugs used against SARS-CoV-2 can cause or aggravate some of the COVID-19-related gastrointestinal symptoms and can also induce liver injury. Ongoing clinical studies will hopefully identify effective drugs with a more favourable risk-benefit ratio than many initially tried treatments.
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COVID-19/complicaciones , Gastroenterólogos , Enfermedades Gastrointestinales/virología , COVID-19/epidemiología , COVID-19/virología , Enfermedades Gastrointestinales/tratamiento farmacológico , Humanos , Enfermedades Inflamatorias del Intestino/virología , SARS-CoV-2/fisiología , Internalización del VirusRESUMEN
BACKGROUND: The SEMOS gold mine in Sadiola, southwestern Mali, has been implementing a malaria vector control programme for 15 y using indoor residual house spraying and sporadic larval control. Periodic screening of the vector populations have been carried out over the years to provide information to the control programme, mainly on vector species present and their insecticide resistance status. The data from five entomological surveys, carried out in 2006, 2011, 2014, 2016 and 2018, are presented. METHODS: Adult mosquitoes were collected resting on walls inside houses and on verandas. Insecticide susceptibility assays were carried out and mosquitoes subsequently identified by species using molecular assays. RESULTS: The major malaria vector mosquitoes, Anopheles gambiae and Anopheles arabiensis were abundant at each sampling period with Anopheles coluzzii and Anopheles funestus being rare or absent. Anopheles rivulorum was identified in 2006 and Anopheles leesoni in 2016. The presence of Anopheles rivulorum-like, identified for the first time in 2018, was not screened for in previous surveys. Insecticide susceptibility bioassays showed resistance in both A. gambiae and A. arabiensis to pyrethroids, carbamates and dichlorodiphenyltrichloroethane over the 12 y. CONCLUSIONS: This is the first record of A. rivulorum-like west of Côte d'Ivoire. Resistance levels to the three classes of insecticides were variable but appeared to decrease after pyrethroids were discontinued for house spraying.
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Anopheles , Insecticidas , Malaria , Piretrinas , Adulto , Animales , Côte d'Ivoire , Humanos , Resistencia a los Insecticidas , Insecticidas/farmacología , Malaria/prevención & control , Malí , Mosquitos Vectores , Piretrinas/farmacologíaRESUMEN
The introduction of acid inhibition in clinical practice has revolutionized the management of acid-related diseases, leading to the virtual abolition of elective surgery for ulcer disease and relegating antireflux surgery to patients with gastroesophageal reflux disease (GERD) not adequately managed by medical therapy. Proton pump inhibitors (PPIs) are the antisecretory drugs of choice for the treatment of reflux disease. However, these drugs still leave some unmet clinical needs in GERD. PPI-refractoriness is common, and persistent symptoms are observed in up to 40-55% of daily PPI users. Potassium-competitive acid blockers (P-CABs) clearly overcome many of the drawbacks and limitations of PPIs, achieving rapid, potent, and prolonged acid suppression, offering the opportunity to address many of the unmet needs. In recent years, it has been increasingly recognized that impaired mucosal integrity is involved in the pathogenesis of GERD. As a consequence, esophageal mucosal protection has emerged as a new, promising therapeutic avenue. When P-CABS are used as add-on medications to standard treatment, a growing body of evidence suggests a significant additional benefit, especially in the relief of symptoms not responding to PPI therapy. On the contrary, reflux inhibitors are considered a promise unfulfilled, and prokinetic agents should only be used on a case-by-case basis.
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Mucosa Esofágica/patología , Reflujo Gastroesofágico/tratamiento farmacológico , Inhibidores de la Bomba de Protones/uso terapéutico , Cimetidina/uso terapéutico , Esomeprazol/uso terapéutico , Reflujo Gastroesofágico/diagnóstico , Humanos , Lansoprazol/uso terapéutico , Omeprazol/uso terapéutico , Pirroles/uso terapéutico , Sulfonamidas/uso terapéuticoRESUMEN
Gastroesophageal reflux disease (GERD) is primarily a motor disorder, and its pathogenesis is multifactorial. As a consequence, treatment should be able to address the underlying pathophysiology. Proton pump inhibitors (PPIs) are the mainstay of medical therapy for GERD, but these drugs only provide the control of symptoms and lesions without curing the disease. However, continuous acid suppression with PPIs is recommended for patients with Barrett's esophagus because of their potential chemopreventive effects. In addition to the antisecretory activity, these compounds display several pharmacological properties, often overlooked in clinical practice. PPIs can indeed affect gastric motility, exert a mucosal protective effect, and an antioxidant, anti-inflammatory, and antineoplastic activity, also protecting cancer cells from developing chemo- or radiotherapeutic resistance. Even in the third millennium, current pharmacologic approaches to address GERD are limited. Reflux inhibitors represent a promise unfulfilled, effective and safe prokinetics are lacking, and antidepressants, despite being effective in selected patients, give rise to adverse events in a large proportion of them. While waiting for new drug classes (like potassium-competitive acid blockers), reassessing old drugs (namely alginate-containing formulations), and paving the new avenue of esophageal mucosal protection are, at the present time, the only reliable alternatives to acid suppression.
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Esófago de Barrett/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Esofágicas/tratamiento farmacológico , Reflujo Gastroesofágico/tratamiento farmacológico , Motilidad Gastrointestinal/efectos de los fármacos , Inhibidores de la Bomba de Protones , Esófago de Barrett/metabolismo , Mucosa Esofágica/metabolismo , Mucosa Esofágica/patología , Neoplasias Esofágicas/metabolismo , Reflujo Gastroesofágico/metabolismo , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
PURPOSE OF REVIEW: Gastroesophageal reflux disease (GERD) is primarily a motor disorder, but its pathogenesis is multifactorial. Although gastric acid secretion is usually normal in GERD patients, treatment with proton pump inhibitors (PPIs) has become the standard of care, despite increasing awareness of their shortcomings. In this article, a new class of antisecretory drugs (namely potassium-competitive acid blockers, P-CABs), developed to overcome these limitations, is discussed. RECENT FINDINGS: P-CABs block the K exchange channel of the proton pump, resulting in rapid, competitive, reversible inhibition of acid secretion. These drugs offer a more rapid elevation of intragastric pH than PPIs, while maintaining similar antisecretory effect, the duration of which is dependent on half-life and can be prolonged with extended release formulations. Thus, P-CABs offer advances in the treatment of GERD including rapid heartburn relief, faster and more reliable healing of severe grades of erosive esophagitis, as a consequence of better control of nighttime acid secretion than PPIs. SUMMARY: P-CABs overcome many of the drawbacks of PPIs. The unique antisecretory effects of vonoprazan might be especially useful in the long-term treatment of patients with Barrett's esophagus.
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Reflujo Gastroesofágico , Preparaciones Farmacéuticas , Reflujo Gastroesofágico/tratamiento farmacológico , Pirosis , Humanos , Potasio , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
PURPOSE OF THE REVIEW: Acid suppression treatment has revolutionized the management of the acid-related disorders since the introduction of the H2-receptor antagonists (H2-RAs) and the proton pump inhibitors (PPIs). However, there has been increasing identification of needs for improvement in antisecretory therapy, especially in gastroesophageal reflux disease (GERD), the eradication of Helicobacter pylori (H. pylori), protection from aspirin (ASA) and non-steroidal inflammatory drug (NSAID) injury and the management of upper gastrointestinal (UGI) bleeding. There have also been increasing publications addressing safety concerns of antisecretory drugs. RECENT FINDINGS: The needs have been identified as shortcomings of the pharmacology of the delayed release-PPIs (DR-PPIs), which have short plasma half-lives, required to be given before a meal and show poor control of nocturnal acid secretion. New-generation PPIs have been developed, including dexlansoprazole modified release (MR), instant release omeprazole (IR-omeprazole), while metered release preparations such as Durasec™ or novel molecules such as tenatoprazole have also been developed and achieve superior control of intragastric pH especially at night. The major advance has been the development of the potassium channel acid blocking drugs, which block the K+,H+-ATPase K+ channel, are food independent, reversible, have a rapid onset of action, and maintain a prolonged and consistent elevation of intragastric pH. Vonoprazan, the first P-CAB, has so far been introduced only into a small number of Asian countries. Safety issues have been extensively addressed in numerous publications. This review sets the needs, individual new drug classes and key individual new treatments into clinical context. Acid suppression treatment is reviewed including the pharmacology, the unmet clinical needs across the acid-related disorders, the place of new drug treatments, and where superiority exists. The safety of antisecretory drugs is broadly summarized with reference to several recent comprehensive reviews and set within the clinical context of patient management, particularly those on long-term treatment who are the greatest risk of some adverse events.
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Barrett's esophagus (BE) is the only known precursor of esophageal adenocarcinoma, one of the few cancers with increasing incidence in developed countries. The pathogenesis of BE is unclear with regard to either the cellular origin of this metaplastic epithelium or the manner in which malignant transformation occurs, although recent data indicate a possible junctional origin of stem cells for BE. Treatment of BE may be achieved using endoscopic eradication therapy; however, there is a lack of discriminatory tools to identify individuals at sufficient risk for cancer development in whom intervention is warranted. Reduction in gastroesophageal reflux of gastric contents including acid is mandatory to achieve remission from BE after endoscopic ablation, and can be achieved using medical or nonmedical interventions. Research topics of greatest interest include the mechanism of BE development and transformation to cancer, risk stratification methods to identify individuals who may benefit from ablation of BE, optimization of eradication therapy, and surveillance methods to ensure that remission is maintained after eradication is achieved.
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Adenocarcinoma , Esófago de Barrett , Neoplasias Esofágicas , Reflujo Gastroesofágico , Células Madre Neoplásicas , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/terapia , Esófago de Barrett/metabolismo , Esófago de Barrett/patología , Esófago de Barrett/terapia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Reflujo Gastroesofágico/metabolismo , Reflujo Gastroesofágico/patología , Reflujo Gastroesofágico/terapia , Humanos , Metaplasia , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patologíaRESUMEN
Gastrointestinal (GI) disorders present with signs that are objective and symptoms that are subjective, evaluable only if an individual can recognize, characterize, describe, and communicate them to a healthcare professional (HCP). The aim of this study was to quantify the extent to which healthcare seekers perceive difficulties in communicating their GI symptoms to HCPs. Interviews were conducted in two settings where individuals were expected to acknowledge experiencing GI symptoms: a tertiary-care, ambulatory GI clinic and the digestive health medication area of a large retail pharmacy. A 13-item questionnaire was designed to identify subjects' perceptions of the component stages of a symptom communication process. Surveys were completed by 100 participants, 50 from the clinic and 50 from the pharmacy. Most participants reported that it was difficult to know if their symptom descriptions had been understood (clinic: 68%; pharmacy: 86%), that difficulty in describing symptoms hampered access to healthcare (clinic: 82%; pharmacy: 76%), and that use of different descriptors (e.g., icons) would facilitate symptom reporting (clinic: 90%; pharmacy: 98%). Apart from difficulties in selecting a standard term and in providing a specific description for their symptoms, perceived barriers to communicating symptoms did not differ between the clinic and pharmacy settings. Most individuals with GI symptoms perceive difficulty in communicating their symptoms to healthcare professionals. Improved access and improved GI healthcare require new, patient-centered tools for symptom communication. These may be pictogram- or icon-based tools rather than traditional verbal descriptors.
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Barreras de Comunicación , Comunicación , Enfermedades Gastrointestinales , Medición de Resultados Informados por el Paciente , Percepción , Relaciones Profesional-Paciente , Adulto , Actitud del Personal de Salud , Femenino , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/patología , Personal de Salud/normas , Humanos , Entrevistas como Asunto , Masculino , Satisfacción del Paciente/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
Non-variceal upper gastrointestinal bleeding (NVUGIB) is bleeding that develops in the oesophagus, stomach or proximal duodenum. Peptic ulcers, caused by Helicobacter pylori infection or use of NSAIDs and low-dose aspirin (LDA), are the most common cause. Although the incidence and mortality associated with NVUGIB have been decreasing owing to considerable advances in the prevention and management of NVUGIB over the past 20 years, it remains a common clinical problem with an annual incidence of â¼67 per 100,000 individuals in the United States in 2012. NVUGIB is a medical emergency, and mortality is in the range â¼1-5%. After resuscitation and initial assessment, early (within 24 hours) diagnostic and therapeutic endoscopy together with intragastric pH control with proton pump inhibitors (PPIs) form the basis of treatment. With a growing ageing population treated with antiplatelet and/or anticoagulant medications, the clinical management of NVUGIB is complex as the risk between gastrointestinal bleeding events and adverse cardiovascular events needs to be balanced. The best clinical approach includes identification of risk factors and prevention of bleeding; available strategies include continuous treatment with PPIs or H. pylori eradication in those at increased risk of developing NVUGIB. Treatment with PPIs and/or use of cyclooxygenase-2-selective NSAIDs should be implemented in those patients at risk of NVUGIB who need NSAIDs and/or LDA.
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Hemorragia Gastrointestinal/diagnóstico , Infecciones por Helicobacter/complicaciones , Tracto Gastrointestinal Superior/irrigación sanguínea , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/farmacocinética , Anticoagulantes/uso terapéutico , Aspirina/efectos adversos , Aspirina/uso terapéutico , Duodeno/irrigación sanguínea , Duodeno/lesiones , Endoscopía/métodos , Esófago/irrigación sanguínea , Esófago/lesiones , Hemorragia Gastrointestinal/epidemiología , Hemorragia Gastrointestinal/fisiopatología , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/fisiopatología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/patogenicidad , Humanos , Pronóstico , Estómago/irrigación sanguínea , Estómago/lesiones , Tracto Gastrointestinal Superior/lesiones , Vitamina K/uso terapéuticoRESUMEN
BACKGROUND: It is anticipated that malaria elimination efforts in Africa will be hampered by increasing resistance to the limited arsenal of insecticides approved for use in public health. However, insecticide susceptibility status of vector populations evaluated under standard insectary test conditions can give a false picture of the threat, as the thermal environment in which the insect and insecticide interact plays a significant role in insecticide toxicity. METHODS: The effect of temperature on the expression of the standard WHO insecticide resistance phenotype was examined using Anopheles arabiensis and Anopheles funestus strains: a susceptible strain and the derived resistant strain, selected in the laboratory for resistance to DDT or pyrethroids. The susceptibility of mosquitoes to the pyrethroid deltamethrin or the carbamate bendiocarb was assessed at 18, 25 or 30 °C. The ability of the pyrethroid synergist piperonyl-butoxide (PBO) to restore pyrethroid susceptibility was also assessed at these temperatures. RESULTS: Temperature impacted the toxicity of deltamethrin and bendiocarb. Although the resistant An. funestus strain was uniformly resistant to deltamethrin across temperatures, increasing temperature increased the resistance of the susceptible An. arabiensis strain. Against susceptible An. funestus and resistant An. arabiensis females, deltamethrin exposure at temperatures both lower and higher than standard insectary conditions increased mortality. PBO exposure completely restored deltamethrin susceptibility at all temperatures. Bendiocarb displayed a consistently positive temperature coefficient against both susceptible and resistant An. funestus strains, with survival increasing as temperature increased. CONCLUSIONS: Environmental temperature has a marked effect on the efficacy of insecticides used in public health against important African malaria vectors. Caution must be exercised when drawing conclusions about a chemical's efficacy from laboratory assays performed at only one temperature, as phenotypic resistance can vary significantly even over a temperature range that could be experienced by mosquitoes in the field during a single day. Similarly, it might be inappropriate to assume equal efficacy of a control tool over a geographic area where local conditions vary drastically. Additional studies into the effects of temperature on the efficacy of insecticide-based interventions under field conditions are warranted.
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Anopheles/efectos de los fármacos , Resistencia a los Insecticidas , Insecticidas/farmacología , Malaria/prevención & control , Mosquitos Vectores/efectos de los fármacos , Temperatura , Animales , Bioensayo/métodos , Ambiente , Femenino , Malaria/transmisión , Control de Mosquitos , Nitrilos/farmacología , Piretrinas/farmacología , Pruebas de Toxicidad/métodosRESUMEN
BACKGROUND: Anopheles funestus has been recognized as a major malaria vector in Africa for over 100 years, but knowledge on many aspects of the biology of this species is still lacking. Anopheles funestus, as with most other anophelines, mate through swarming. A key event that is crucial for the An. funestus male to mate is genitalia rotation. This involves the 135° to 180° rotation of claspers, which are tipped with claws. This physical change then enables the male to grasp the female during copulation. The aim of this investigation was to molecularly characterize wild An. funestus swarms from Zambia and examine the degree of genitalia rotation within the swarm. METHODS: Anopheles funestus swarms were collected from Nchelenge, northern Zambia, during dusk periods in May 2016. All the adults from the swarm were analysed morphologically and identified to species level using a multiplex PCR assay. Anopheles funestus s.s. specimens were molecularly characterized by restriction fragment length polymorphism type and Clade type assays. The different stages of genitalia rotation were examined in the adult males. RESULTS: A total of six swarms were observed during the study period and between 6 and 26 mosquitoes were caught from each swarm. Species analysis revealed that 90% of the males from the swarms were An. funestus s.s. MW-type, with 84% belonging to clade I compared to 14% clade II and 2% failed to amplify. Very few specimens (3.4%) were identified as Anopheles gambiae s.s. Eighty percent of the males from the swarm had complete genitalia rotation. CONCLUSIONS: This is the first time that An. funestus swarms have been molecularly identified to species level. Anopheles funestus swarms appear to be species-specific with no evidence of clade-type differentiation within these swarms. The An. funestus swarms consist mainly of males with fully rotated genitalia, which strongly suggests that swarming behaviour is triggered primarily when males have matured.
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Anopheles/genética , Anopheles/fisiología , Conducta Animal/fisiología , Inseminación/fisiología , Animales , ADN/genética , Femenino , Genitales Femeninos/fisiología , Genitales Masculinos/fisiología , Masculino , Polimorfismo de Longitud del Fragmento de Restricción , ZambiaRESUMEN
There is much evidence that a combination of ibuprofen (IBU) and Aspirin (ASA) can antagonize the irreversible inhibition of platelet function. This study was designed to investigate the degree of gastric damage, bleeding time (BT) and fluctuations in the serum levels of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) after oral administration of ASA (200 mg/kg) and IBU (50 mg/kg) either alone or in combination in rats in vivo. The stomach was assessed for any damage either after 6 h, 18 h or 6 days and carboxymethylcellulose (1% CMC) served as a vehicle and control. ELISA was used to measure TXA2 and PGE2 in serum. Bleeding time was assessed using tail blood. The results show that ASA and IBU either alone or in combination can cause gastric ulceration in 25-100% of the rats at 6 and 18 h. In contrast, gastric ulceration was seen in 50% of rats with a combination of ASA given before IBU only after 6 days of oral administration. BT was unaffected either by ASA or IBU when administered alone except after 18 h for IBU. In contrast, BT was significantly reduced when IBU was administered before ASA after 18 h and 6 days (P < 0.001). Serum PGE2 levels decreased significantly after ASA administered either alone or in combination with IBU for 6 h, 18 h and 6 days (P < 0.05). Serum TXA2 levels were significantly reduced after 6 h, 18 h and 6 days following ASA and IBU administration except for IBU alone which caused a significant increase in serum TXA2 6 days after its administration (P < 0.01). It can be concluded that ASA and IBU administered either alone or in combination can cause gastric ulcers in the rat stomach after 6 h and 18 h, but less severe after 6 days. IBU either alone or in combination with ASA reduced BT only after 18 h and 6 days of administration. Together, the results show that gastric ulceration correlated well with the inhibition of serum PGE2 and TXA2 levels.
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Aspirina , Dinoprostona/sangre , Mucosa Gástrica/metabolismo , Ibuprofeno , Úlcera Gástrica , Tromboxano A2/sangre , Anestesia , Animales , Aspirina/efectos adversos , Aspirina/farmacocinética , Tiempo de Sangría , Femenino , Mucosa Gástrica/patología , Ibuprofeno/efectos adversos , Ibuprofeno/farmacología , Masculino , Ratas , Ratas Wistar , Úlcera Gástrica/sangre , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patologíaRESUMEN
BACKGROUND: The Democratic Republic of the Congo (DRC) is characterized as a holoendemic malaria area with the main vectors being Anopheles funestus and members of the Anopheles gambiae complex. Due to political instability and socio-economic challenges in the region, knowledge of insecticide resistance status and resistance mechanisms in these vectors is limited. Mosquitoes were collected from a mining site in the north-eastern part of the country and, following identification, were subjected to extensive testing for the target-site and biochemical basis of resistance. Quantitative real-time PCR was used to assess a suite of 10 genes frequently involved in pyrethroid and dichlorodiphenyltrichloroethane (DDT) resistance in An. gambiae females and males. In An. funestus, gene expression microarray analysis was carried out on female mosquitoes. RESULTS: In both species, deltamethrin resistance was recorded along with high resistance and suspected resistance to DDT in An. gambiae and An. funestus, respectively. A total of 85% of An. gambiae carried the kdr mutations as either homozygous resistant (RR) (L1014S, L1014F or both) or heterozygous (RS), however only 3% carried the rdl mutant allele (RS) and no ace-1 mutations were recorded. Synergist assays indicated a strong role for P450s in deltamethrin resistance in both species. In An. gambiae, analysis of transcription levels showed that the glutathione-S-transferase, GSTS1-2, produced the highest fold change in expression (7.6-fold in females and 31-fold in males) followed by GSTE2, thioredoxin peroxidase (TPX2), and cytochrome oxidases (CYP6M2 and CYP6P1). All other genes tested produced fold change values below 2. Microarray analysis revealed significant over-transcription of cuticular proteins as well as CYP6M7, CYP6P9a and CYP6P9b in insecticide resistant An. funestus. CONCLUSIONS: These data show that high levels of deltamethrin resistance in the main malaria vector species, conferred by enzymatic detoxification, are present in the DRC.
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Anopheles/genética , Resistencia a los Insecticidas , Insecticidas , Mosquitos Vectores/genética , Animales , DDT , República Democrática del Congo , Femenino , Expresión Génica , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Resistencia a los Insecticidas/genética , Malaria/transmisión , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Piretrinas , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
This article describes the clinical progression of symptoms over a period of 5 days of a bite inflicted by a Philodromus sp. spider. Commonly known as 'running spiders', these are not considered to be harmful to humans. This report, however, is the first description of an actual bite by a member of this group of spiders showing cytotoxic envenomation. Management of the bites should be as recommended for other cytotoxic spider bites.