RESUMO
BACKGROUND: Advances in treatment of peritoneal surface malignancies including cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS±HIPEC) have led to long-term survivorship, yet the subsequent quality of life (QOL) and values of these patients are unknown. PATIENTS AND METHODS: Survivors were offered surveys via online support groups. Novel items assessed how patients prioritized experience, costs, longevity, and wellbeing. RESULTS: Of the 453 gastrointestinal/hepatobiliary (GI/HPB) surgical patients that responded, 74 underwent CRS±HIPEC and were 54±12 years old, 87% female, and 93% white. Respondents averaged 29 months from diagnosis, with a maximum survival of 20 years. With a moderate level of agreement (W = 39%), rankings of value metrics among respondents were predictable (p < 0.001). Longevity and functional independence were ranked highest; treatment experience and cost of treatment were ranked lowest (p < 0.001). Those who underwent CRS±HIPEC or other GI/HPB surgeries reported the same rank order. QOL in CRS±HIPEC survivors, both mental (M-QOL) (44±13) and physical (P-QOL) (41±11) were lower than in the general population (50±10); p < 0.001. Impairments persisted throughout survivorship, but M-QOL improved over time (p < 0.05). When comparing CRS±HIPEC with other GI/HPB cancer surgery survivors, M-QOL (43±13 versus 43±14, p = 0.85) and P-QOL (40±11 versus 42±12, p = 0.41) were similar. CONCLUSIONS: Although CRS±HIPEC survivors experience long-term mental and physical health impairments, they were similar to those experienced by survivors of other GI/HPB cancer surgeries, and their QOL improved significantly throughout survivorship. As CRS±HIPEC survivors prioritize longevity above all other metrics, survival benefit may outweigh a temporary reduction in QOL.
Assuntos
Sobreviventes de Câncer , Hipertermia Induzida , Neoplasias , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Qualidade de Vida , Procedimentos Cirúrgicos de Citorredução , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Taxa de Sobrevida , Estudos RetrospectivosRESUMO
Objective: The aim of this narrative review was to review literature relevant to manual therapists about cognitive impairment, together with screening, potential treatment, and prevention modalities. Methods: A literature search of AMED (Allied and Complementary Medicine Database), CINAHL (Cumulative Index of Nursing and Allied Health Literature), PubMed, and MEDLINE was conducted with the search terms "cognitive decline," "cognitive impairment," "screening," and "prevention." We reviewed current screening practices, including functional exams, imaging, and laboratory testing. We reviewed current potential preventive measures and treatments being implemented in practice. Results: We selected 49 resources for this narrative summary. The Montreal Cognitive Assessment and Mini-Mental State Exam are recommended screening tools. Imaging and laboratory testing are not recommended in screening for cognitive decline. Promotion of healthy, active living through physical and mental activities may assist with prevention of cognitive decline. Conclusion: Cognitive decline affects a large proportion of the US population. Recognizing signs and symptoms of this condition starts with individuals, caretakers, family members, and health care providers. Health care providers should utilize the most appropriate screening tools to assess the presence of cognitive conditions.
RESUMO
Objective: The purpose of this case report was to describe the treatment of an older veteran with chronic low back pain, utilizing flexion-distraction as a primary intervention for management. Clinical Features: A 67-year-old man with chronic low back pain for several decades presented to the chiropractic clinic for evaluation. He reported low back pain that extended into the right lower extremity intermittently. The patient's imaging demonstrated significant degenerative changes in the lumber spinal anatomy. He had never experienced chiropractic interventions or management for his condition. Intervention and Outcome: A trial of conservative care with flexion-distraction was applied as a primary intervention for the management of chronic low back pain. Instrument-assisted soft-tissue mobilization and moist heat were also applied for interventions. Despite having no changes in outcome assessments, the patient reported an improvement in his condition, reduced use of pain medication, and increased mobility after 4 sessions over a 4-week period. Conclusion: Flexion-distraction was a beneficial chiropractic approach to the management of an older veteran with chronic low back pain and intermittent lower extremity pain for several decades.
RESUMO
With the successful development and increased use of targeted radionuclide therapy for treating cancer comes the increased risk of radiation injury to bone marrow-both direct suppression and stochastic effects, leading to neoplasia. Herein, we report a novel radioprotector drug, a liposomal formulation of γ-tocotrienol (GT3), or GT3-Nano for short, to mitigate bone marrow radiation damage during targeted radionuclide therapy. Methods: GT3 was loaded into liposomes using passive loading. 64Cu-GT3-Nano and 3H-GT3-Nano were synthesized to study the in vivo biodistribution profile of the liposome and GT3 individually. The radioprotection efficacy of GT3-Nano was assessed after acute 137Cs whole-body irradiation at a sublethal (4 Gy), a lethal (9 Gy), or a single high-dose administration of 153Sm-ethylenediamine-N,N,N',N'-tetrakis(methylene phosphonic acid) (EDTMP). Flow cytometry and fluorescence microscopy were used to analyze hematopoietic cell population dynamics and the cellular site of GT3-Nano localization in the spleen and bone marrow, respectively. Results: Bone marrow uptake and retention (percentage injected dose per gram of tissue) at 24 h was 6.98 ± 2.34 for 64Cu-GT3-Nano and 7.44 ± 2.52 for 3H-GT3-Nano. GT3-Nano administered 24 h before or after 4 Gy of total-body irradiation (TBI) promoted rapid and complete hematopoietic recovery, whereas recovery of controls stalled at 60%. GT3-Nano demonstrated dose-dependent radioprotection, achieving 90% survival at 50 mg/kg against lethal 9-Gy TBI. Flow cytometry of the bone marrow indicated that progenitor bone marrow cells MPP2 and CMP were upregulated in GT3-Nano-treated mice. Immunohistochemistry showed that GT3-Nano accumulates in CD105-positive sinusoid epithelial cells. Conclusion: GT3-Nano is highly effective in mitigating the marrow-suppressive effects of sublethal and lethal TBI in mice. GT3-Nano can facilitate rapid recovery of hematopoietic components in mice treated with the endoradiotherapeutic agent 153Sm-EDTMP.
Assuntos
Cromanos/administração & dosagem , Cromanos/farmacologia , Hematopoese/efeitos dos fármacos , Hematopoese/efeitos da radiação , Protetores contra Radiação/administração & dosagem , Protetores contra Radiação/farmacologia , Radioterapia/efeitos adversos , Vitamina E/análogos & derivados , Animais , Cromanos/farmacocinética , Lipossomos , Camundongos , Protetores contra Radiação/farmacocinética , Distribuição Tecidual , Vitamina E/administração & dosagem , Vitamina E/farmacocinética , Vitamina E/farmacologiaRESUMO
The purpose of this study was to evaluate preference for and reinforcing efficacy of a therapy dog to increase verbal statements across different contingencies. Five children with autism spectrum disorder ages 3-8 years participated. Alternating treatments and reversal designs were used to compare conditions in which (a) a therapy dog was not present, (b) access to a therapy dog was noncontingent, (c) access to a therapy dog was contingent on interacting with a therapist, and (d) access to another preferred item was contingent on interacting with a therapist. Results varied across participants. Noncontingent access to the therapy dog slightly increased verbal statements for 1 participant. Contingent access to the therapy dog increased social interactions for 2 participants; however, this was the most effective intervention for only 1 participant. Practitioners should be aware that some clients may be better suited for interventions including therapy dogs than others.
Assuntos
Transtorno do Espectro Autista/psicologia , Transtorno do Espectro Autista/terapia , Animais de Terapia , Comportamento Verbal , Animais , Criança , Pré-Escolar , Cães , Feminino , Humanos , MasculinoRESUMO
In 2014 the International Endohernia Society (IEHS) published the first international "Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias". Guidelines reflect the currently best available evidence in diagnostics and therapy and give recommendations to help surgeons to standardize their techniques and to improve their results. However, science is a dynamic field which is continuously developing. Therefore, guidelines require regular updates to keep pace with the evolving literature. METHODS: For the development of the original guidelines all relevant literature published up to year 2012 was analyzed using the ranking of the Oxford Centre for Evidence-Based-Medicine. For the present update all of the previous authors were asked to evaluate the literature published during the recent years from 2012 to 2017 and revise their statements and recommendations given in the initial guidelines accordingly. In two Consensus Conferences (October 2017 Beijing, March 2018 Cologne) the updates were presented, discussed, and confirmed. To avoid redundancy, only new statements or recommendations are included in this paper. Therefore, for full understanding both of the guidelines, the original and the current, must be read. In addition, the new developments in repair of abdominal wall hernias like surgical techniques within the abdominal wall, release operations (transversus muscle release, component separation), Botox application, and robot-assisted repair methods were included. RESULTS: Due to an increase of the number of patients and further development of surgical techniques, repair of primary and secondary abdominal wall hernias attracts increasing interests of many surgeons. Whereas up to three decades ago hernia-related publications did not exceed 20 per year, currently this number is about 10-fold higher. Recent years are characterized by the advent of new techniques-minimal invasive techniques using robotics and laparoscopy, totally extraperitoneal repairs, novel myofascial release techniques for optimal closure of large defects, and Botox for relaxing the abdominal wall. Furthermore, a concomitant rectus diastasis was recognized as a significant risk factor for recurrence. Despite still insufficient evidence with respect to these new techniques it seemed to us necessary to include them in the update to stimulate surgeons to do research in these fields. CONCLUSION: Guidelines are recommendations based on best available evidence intended to help the surgeon to improve the quality of his daily work. However, science is a continuously evolving process, and as such guidelines should be updated about every 3 years. For a comprehensive reference, however, it is suggested to read both the initially guidelines published in 2014 together with the update. Moreover, the presented update includes also techniques which were not known 3 years before.
Assuntos
Parede Abdominal/cirurgia , Hérnia Ventral/cirurgia , Herniorrafia/normas , Laparoscopia/normas , Medicina Baseada em Evidências , Herniorrafia/métodos , Humanos , Laparoscopia/métodos , Sociedades MédicasRESUMO
INTRODUCTION: Multisystem functional gains have been reported in males with spinal cord injury (SCI) after undergoing activity-based training (ABT), including increases in scoring of sexual function and reports of improved erectile function. AIM: This study aims to examine the effect of daily 60-minute locomotor training and exercise in general on sexual function in a rat SCI contusion model. METHODS: Male Wistar rats received a T9 contusion SCI. Animals were randomized into 4 groups: a quadrupedal stepping group (SCI + QT), a forelimb-only exercise group (SCI + FT), a non-trained harnessed group (SCI + NT), and a home cage non-trained group (SCI + HC). The 2 non-trained groups were combined (SCI) post hoc. Daily training sessions were 60 minutes in duration for 8 weeks. Urine samples were collected during bi-weekly 24-hour metabolic cage behavioral testing. Latency, numbers of penile dorsiflexion, and glans cupping were recorded during bi-weekly penile dorsiflexion reflex (PDFR) testing. Terminal electromyography (EMG) recordings of the bulbospongiosus muscle (BSM) were recorded in response to stimulation of the dorsal nerve of the penis (DNP). OUTCOMES: ABT after SCI had a significant effect on PDFR, as well as BSM EMG latency and burst duration. RESULTS: SCI causes a significant decrease in the latency to onset of PDFR. After 8 weeks of ABT, SCI + QT animals had a significantly increased latency relative to the post-SCI baseline. BSM EMG response to DNP stimulation had a significantly decreased latency and increase in average and maximum amplitude in SCI + QT animals. SCI animals had a significantly longer burst duration than trained animals. Time between PDFR events, penile dorsiflexion, glans cupping, and urine testosterone were not affected by ABT. CLINICAL IMPLICATIONS: ABT has a positive influence on sexual function and provides a potential therapy to enhance the efficacy of current sexual dysfunction therapies in the male SCI population. STRENGTHS AND LIMITATIONS: Several significant small improvements in sexual function were found in a clinically relevant rat model of SCI using a readily available rehabilitative therapy. The limited findings could reflect insensitivity of the PDFR as a measure of erectile function. CONCLUSIONS: These results indicate that task-specific stepping and/or loading provide sensory input to the spinal cord impacting the neural circuitry responsible for sexual function. Steadman CJ, Hoey RF, Montgomery LR, et al. Activity-Based Training Alters Penile Reflex Responses in a Rat Model of Spinal Cord Injury. J Sex Med 2019; 16:1143-1154.
Assuntos
Ereção Peniana/fisiologia , Pênis/fisiologia , Condicionamento Físico Animal , Traumatismos da Medula Espinal/fisiopatologia , Animais , Eletromiografia , Masculino , Músculo Esquelético/fisiologia , Pênis/fisiopatologia , Nervo Pudendo/fisiologia , Ratos , Ratos Wistar , Recuperação de Função Fisiológica , Reflexo/fisiologia , Disfunções Sexuais Fisiológicas/etiologiaRESUMO
The mechanistic target of rapamycin (mTOR) is a central regulator of cellular metabolic processes. Dysregulation of this kinase complex can result in a variety of human diseases. Rapamycin and its analogs target mTORC1 directly; however, chronic treatment in certain cell types and in vivo results in the inhibition of both mTORC1 and mTORC2. We have developed a high-throughput cell-based screen for the detection of phosphorylated forms of the mTORC1 (4E-BP1, S6K1) and mTORC2 (Akt) substrates and have identified and characterized a chemical scaffold that demonstrates a profile consistent with the selective inhibition of mTORC1. Stable isotope labeling of amino acids in cell culture-based proteomic target identification revealed that class I glucose transporters were the primary target for these compounds yielding potent inhibition of glucose uptake and, as a result, selective inhibition of mTORC1. The link between the glucose uptake and selective mTORC1 inhibition are discussed in the context of a yet-to-be discovered glucose sensor.
Assuntos
Proteínas Facilitadoras de Transporte de Glucose/efeitos dos fármacos , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Sirolimo/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Glucose/metabolismo , Ensaios de Triagem em Larga Escala/métodos , Humanos , Alvo Mecanístico do Complexo 2 de Rapamicina/efeitos dos fármacos , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Complexos Multiproteicos/metabolismo , Fosforilação , Proteômica/métodos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirolimo/análogos & derivados , Sirolimo/metabolismo , Fatores de Transcrição/metabolismoRESUMO
In 2014, the International Endohernia Society (IEHS) published the first international "Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias." Guidelines reflect the currently best available evidence in diagnostics and therapy and give recommendations to help surgeons to standardize their techniques and to improve their results. However, science is a dynamic field which is continuously developing. Therefore, guidelines require regular updates to keep pace with the evolving literature. METHODS: For the development of the original guidelines, all relevant literature published up to year 2012 was analyzed using the ranking of the Oxford Centre for Evidence-Based Medicine. For the present update, all of the previous authors were asked to evaluate the literature published during the recent years from 2012 to 2017 and revise their statements and recommendations given in the initial guidelines accordingly. In two Consensus Conferences (October 2017 Beijing, March 2018 Cologne), the updates were presented, discussed, and confirmed. To avoid redundancy, only new statements or recommendations are included in this paper. Therefore, for full understanding both of the guidelines, the original and the current, must be read. In addition, the new developments in repair of abdominal wall hernias like surgical techniques within the abdominal wall, release operations (transversus muscle release, component separation), Botox application, and robot-assisted repair methods were included. RESULTS: Due to an increase of the number of patients and further development of surgical techniques, repair of primary and secondary abdominal wall hernias attracts increasing interests of many surgeons. Whereas up to three decades ago hernia-related publications did not exceed 20 per year, currently this number is about 10-fold higher. Recent years are characterized by the advent of new techniques-minimal invasive techniques using robotics and laparoscopy, totally extraperitoneal repairs, novel myofascial release techniques for optimal closure of large defects, and Botox for relaxing the abdominal wall. Furthermore, a concomitant rectus diastasis was recognized as a significant risk factor for recurrence. Despite insufficient evidence with respect to these new techniques, it seemed to us necessary to include them in the update to stimulate surgeons to do research in these fields. CONCLUSION: Guidelines are recommendations based on best available evidence intended to help the surgeon to improve the quality of his daily work. However, science is a continuously evolving process, and as such guidelines should be updated about every 3 years. For a comprehensive reference, however, it is suggested to read both the initial guidelines published in 2014 together with the update. Moreover, the presented update includes also techniques which were not known 3 years before.
Assuntos
Hérnia Abdominal/cirurgia , Hérnia Ventral/cirurgia , Hérnia Incisional/cirurgia , Laparoscopia , Hérnia Abdominal/diagnóstico por imagem , Hérnia Ventral/diagnóstico por imagem , Herniorrafia/métodos , Herniorrafia/normas , Humanos , Hérnia Incisional/diagnóstico por imagem , Complicações Intraoperatórias , Imageamento por Ressonância Magnética , Obesidade/complicações , Posicionamento do Paciente , Complicações Pós-Operatórias , Recidiva , Procedimentos Cirúrgicos Robóticos , Telas Cirúrgicas , Tomografia Computadorizada por Raios XRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Pastoralist Maasai populations of east Africa use several different wild plants as dietary and medicinal additives in beverages (soups and teas), yet little is known about how the plants used and the rationales for use compare and contrast across different Maasai beverages, including how gender specific dietary and health concerns structure patterns of intake. AIM OF THE STUDY: We investigated three Maasai beverages: almajani (tea or herbal infusion); motorí (traditional soup); and okiti (psychoactive herbal tea). In order to build knowledge about the cultural functions of these Maasai food-medicines and their incidence of use we also investigated use rationales and self-reported frequencies of use. We conclude by examining gender differences and the possible pharmacological antimicrobial activity of the most frequently used plants. MATERIALS AND METHODS: Research was conducted in 2015, with a population of semi-nomadic agropastoralist Maasai residing in northern Tanzania. Data were collected using key informant interviews, plant collections, n = 32 structured surveys, and n = 40 freelist interviews followed by a literature review to determine the known antimicrobial activity of the most used plants. RESULTS: We identified 20 plants that Maasai add to soup, 11 in tea, and 11 in the psychoactive tea, for a total of 24 herbal additives. Seven plant species were used in all three Maasai beverages, and these clustered with 10 common ailments. Based on self-reports, women use the beverages less frequently and in smaller amounts than men. There were also several gender differences in the plants that Maasai add to motorí and their associated use rationales. CONCLUSIONS: There are several intersections concerning the plant species used and their associated rationales for use in almajani, motori, and okiti. Moving outward, Maasai beverages and their additives increasingly involve gender specific concerns. Female use of food-medicines, relative to men, is structured by concerns over pregnancy, birth, and lactation. The frequent consumption of herbal additives, many of which contain antimicrobial compounds, potentially helps modulate infections, but could have other unintentional effects as well.
Assuntos
Anti-Infecciosos/administração & dosagem , Bebidas , População Negra , Alimentos , Medicinas Tradicionais Africanas , Extratos Vegetais/administração & dosagem , Plantas Medicinais/química , Psicotrópicos/administração & dosagem , Migrantes , Administração Oral , Adulto , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/isolamento & purificação , População Negra/psicologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Fitoterapia , Extratos Vegetais/efeitos adversos , Extratos Vegetais/isolamento & purificação , Plantas Medicinais/efeitos adversos , Plantas Medicinais/classificação , Psicotrópicos/efeitos adversos , Psicotrópicos/isolamento & purificação , Fatores de Risco , Fatores Sexuais , Tanzânia , Migrantes/psicologiaRESUMO
The objective of this study was to determine if astaxanthin (ASTX), a xanthophyll carotenoid, can prevent obesity-associated metabolic abnormalities, inflammation and fibrosis in diet-induced obesity (DIO) and nonalcoholic steatohepatitis (NASH) mouse models. Male C57BL/6J mice were fed a low-fat (6% fat, w/w), a high-fat/high-sucrose control (HF/HS; 35% fat, 35% sucrose, w/w), or a HF/HS containing ASTX (AHF/HS; 0.03% ASTX, w/w) for 30 weeks. To induce NASH, another set of mice was fed a HF/HS diet containing 2% cholesterol (HF/HS/HC) a HF/HS/HC with 0.015% ASTX (AHF/HS/HC) for 18 weeks. Compared to LF, HF/HS significantly increased plasma total cholesterol, triglyceride and glucose, which were lowered by ASTX. ASTX decreased hepatic mRNA levels of markers of macrophages and fibrosis in both models. The effect of ASTX was more prominent in NASH than DIO mice. In epididymal fat, ASTX also decreased macrophage infiltration and M1 macrophage marker expression, and inhibited hypoxia-inducible factor 1-α and its downstream fibrogenic genes in both mouse models. ASTX significantly decreased tumor necrosis factor α mRNA in the splenocytes from DIO mice upon lipopolysaccharides stimulation compared with those from control mice fed an HF/HS diet. Additionally, ASTX significantly elevated the levels of genes that regulate fatty acid ß-oxidation and mitochondrial biogenesis in the skeletal muscle compared with control obese mice, whereas no differences were noted in adipose lipogenic genes. Our results indicate that ASTX inhibits inflammation and fibrosis in the liver and adipose tissue and enhances the skeletal muscle's capacity for mitochondrial fatty acid oxidation in obese mice.
Assuntos
Tecido Adiposo/patologia , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Obesidade/complicações , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Modelos Animais de Doenças , Fibrose/prevenção & controle , Regulação da Expressão Gênica/efeitos dos fármacos , Lipídeos/sangue , Lipídeos/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/etiologia , Obesidade/prevenção & controle , Paniculite/metabolismo , Paniculite/patologia , Paniculite/prevenção & controle , Xantofilas/farmacologiaRESUMO
While biofeedback is often said to increase self-control of physiological states by increasing awareness of their subjective correlates, relatively few studies have analyzed the relationship between control (standard biofeedback) and awareness (a discrimination paradigm). We hypothesized that the two skills would generalize and facilitate each other for 8-12Hz EEG amplitude (alpha). Participants were given 7 sessions of training to either control or discriminate Pz alpha followed by 3 sessions of the other paradigm. Another group was given 7 sessions with time divided equally between the two types of training. The control-training first group showed significant generalization of skills to the discrimination task. However, the reverse was not true, and the combined task group did no better in either task than the other two groups. These results provide ambivalent support for the role of awareness in biofeedback, and suggest possible improvements in the discrimination paradigm.
Assuntos
Ritmo alfa/fisiologia , Biorretroalimentação Psicológica/métodos , Condicionamento Operante/fisiologia , Eletroencefalografia , Generalização Psicológica/fisiologia , Adolescente , Adulto , Idoso , Conscientização , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autocontrole , Adulto JovemRESUMO
Several Gram-positive pathogens scavenge host-derived heme to satisfy their nutritional iron requirement. However, heme is a toxic molecule capable of damaging the bacterial cell. Gram-positive pathogens within the phylum Firmicutes overcome heme toxicity by sensing heme through HssRS, a two-component system that regulates the heme detoxification transporter HrtAB. Here we show that heme sensing by HssRS and heme detoxification by HrtAB occur in the insect pathogen Bacillus thuringiensis We find that in B. thuringiensis, HssRS directly regulates an operon, hrmXY, encoding hypothetical membrane proteins that are not found in other Firmicutes with characterized HssRS and HrtAB systems. This novel HssRS-regulated operon or its orthologs BMB171_c3178 and BMB171_c3330 are required for maximal heme resistance. Furthermore, the activity of HrmXY is not dependent on expression of HrtAB. These results suggest that B. thuringiensis senses heme through HssRS and induces expression of separate membrane-localized systems capable of overcoming different aspects of heme toxicity.
Assuntos
Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Regulação Bacteriana da Expressão Gênica , Heme/metabolismo , Bacillus thuringiensis/patogenicidade , Bacillus thuringiensis/fisiologia , Proteínas de Bactérias/genética , Transporte Biológico , Ferro/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mutação , Óperon , Regiões Promotoras GenéticasRESUMO
BACKGROUND/OBJECTIVES: Evidence indicates that berry anthocyanins are anti-atherogenic, antioxidant, and anti-inflammatory. However, berries differ vastly in their anthocyanin composition and thus potentially in their biological and metabolic effects. The present study compared hypolipidemic, antioxidant, and anti-inflammatory properties of blueberry (BB), blackberry (BK), and blackcurrant (BC) in a diet-induced obesity (DIO) mouse model. MATERIALS/METHODS: Male C57BL/6J mice were fed a high fat (HF; 35% fat, w/w) control diet or a HF diet supplemented with freeze-dried 5% BB, 6.3% BK or 5.7% BC for 12 weeks (10 mice/group) to achieve the same total anthocyanin content in each diet. Plasma lipids, antioxidant status and pro-inflammatory cytokines were measured. The expression of genes involved in antioxidant defense, inflammation, and lipid metabolism was determined in the liver, epididymal adipose tissue, proximal intestine, and skeletal muscle. Histological analysis was performed to identify crown-like structure (CLS) in epididymal fat pads to determine macrophage infiltration. RESULTS: No differences were noted between the control and any berry-fed groups in plasma levels of liver enzymes, insulin, glucose, ferric reducing antioxidant power, superoxide dismutase, and tumor necrosis factor α. However, BK significantly lowered plasma triglyceride compared with the HF control and other berries, whereas BC significantly reduced F4/80 mRNA and the number of CLS in the epididymal fat pad, indicative of less macrophage infiltration. CONCLUSIONS: The present study provides evidence that BB, BK and BC with varying anthocyanin composition differentially affect plasma lipids and adipose macrophage infiltration in DIO mice, but with no differences in their antioxidant capacity and anti-inflammatory potential.
Assuntos
Animais , Humanos , Masculino , Camundongos , Tecido Adiposo , Antocianinas , Mirtilos Azuis (Planta) , Citocinas , Dieta , Frutas , Glucose , Inflamação , Insulina , Intestinos , Metabolismo dos Lipídeos , Fígado , Macrófagos , Músculo Esquelético , Obesidade , Plasma , RNA Mensageiro , Rubus , Superóxido Dismutase , Triglicerídeos , Fator de Necrose Tumoral alfaRESUMO
Hyperlipidemia and inflammation contribute to the development of atherosclerotic lesions. Our objective was to determine antiatherogenic effect of edible blue-green algae (BGA) species, that is, Nostoc commune var. sphaeroides Kützing (NO) and Spirulina platensis (SP), in apolipoprotein E knockout (ApoE(-/-)) mice, a well-established mouse model of atherosclerosis. Male ApoE(-/-) mice were fed a high-fat/high-cholesterol (HF/HC, 15% fat and 0.2% cholesterol by wt) control diet or a HF/HC diet supplemented with 5% (w/w) of NO or SP powder for 12 weeks. Plasma total cholesterol (TC) and triglycerides (TG) were measured, and livers were analyzed for histology and gene expression. Morphometric analysis for lesions and immunohistochemical analysis for CD68 were conducted in the aorta and the aortic root. NO supplementation significantly decreased plasma TC and TG, and liver TC, compared to control and SP groups. In the livers of NO-fed mice, less lipid droplets were present with a concomitant decrease in fatty acid synthase protein levels than the other groups. There was a significant increase in hepatic low-density lipoprotein receptor protein levels in SP-supplemented mice than in control and NO groups. Quantification of aortic lesions by en face analysis demonstrated that both NO and SP decreased aortic lesion development to a similar degree compared with control. While lesions in the aortic root were not significantly different between groups, the CD68-stained area in the aortic root was significantly lowered in BGA-fed mice than controls. In conclusion, both NO and SP supplementation decreased the development of atherosclerotic lesions, suggesting that they may be used as a natural product for atheroprotection.
Assuntos
Aterosclerose/prevenção & controle , Suplementos Nutricionais , Lipídeos/sangue , Fígado , Nostoc , Spirulina , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Aorta , Apolipoproteínas E/genética , Aterosclerose/etiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Dieta Hiperlipídica , Gorduras na Dieta/efeitos adversos , Fígado/metabolismo , Masculino , Camundongos Knockout , Receptores de LDL/metabolismoRESUMO
Non-alcoholic fatty liver disease (NAFLD) is significantly associated with hyperlipidaemia and oxidative stress. We have previously reported that astaxanthin (ASTX), a xanthophyll carotenoid, lowers plasma total cholesterol and TAG concentrations in apoE knockout mice. To investigate whether ASTX supplementation can prevent the development of NAFLD in obesity, male C57BL/6J mice (n 8 per group) were fed a high-fat diet (35%, w/w) supplemented with 0, 0.003, 0.01 or 0.03% of ASTX (w/w) for 12 weeks. The 0.03% ASTX-supplemented group, but not the other groups, exhibited a significant decrease in plasma TAG concentrations, suggesting that ASTX at a 0.03% supplementation dosage exerts a hypotriacylglycerolaemic effect. Although there was an increase in the mRNA expression of fatty acid synthase and diglyceride acyltransferase 2, the mRNA levels of acyl-CoA oxidase 1, a critical enzyme in peroxisomal fatty acid ß-oxidation, exhibited an increase in the 0.03% ASTX-supplemented group. There was a decrease in plasma alanine transaminase (ALT) and aspartate transaminase (AST) concentrations in the 0.03% ASTX-supplemented group. There was a significant increase in the hepatic mRNA expression of nuclear factor erythroid 2-related factor 2 and its downstream genes, which are critical for endogenous antioxidant mechanism, in the 0.03% ASTX-supplemented group. Furthermore, there was a significant decrease in the mRNA abundance of IL-6 in the primary splenocytes isolated from the 0.03% ASTX-supplemented group upon lipopolysaccharide (LPS) stimulation when compared with that in the splenocytes isolated from the control group. In conclusion, ASTX supplementation lowered the plasma concentrations of TAG, ALT and AST, increased the hepatic expression of endogenous antioxidant genes, and rendered splenocytes less sensitive to LPS stimulation. Therefore, ASTX may prevent obesity-associated metabolic disturbances and inflammation.
Assuntos
Fígado/efeitos dos fármacos , Obesidade/sangue , Obesidade/tratamento farmacológico , Triglicerídeos/sangue , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Alanina Transaminase/sangue , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/sangue , Dieta Hiperlipídica , Suplementos Nutricionais , Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Obesidade/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Baço/efeitos dos fármacos , Baço/metabolismo , Xantofilas/administração & dosagem , Xantofilas/farmacologiaRESUMO
Obesity is closely associated with chronic, low-grade inflammation. We investigated if polyphenol-rich blackcurrant extract (BCE) can prevent inflammation in vivo. Male C57BL/6J mice were fed a modified AIN-93M control diet containing high fat/high cholesterol (16% fat, 0.25% cholesterol by weight) or the control diet supplemented with 0.1% BCE (wt/wt) for 12 weeks. In BCE-fed mice, the percentage of body weight and adipocyte size of the epididymal fat were significantly lower than those of control mice. There were fewer crown-like structures (CLS) with concomitant decreases in F4/80, cluster of differentiation 68 and inhibitor of nuclear factor κB kinase ε (IKKε) mRNA in the epididymal adipose of BCE-fed mice. F4/80 and IKKε mRNA levels were positively correlated with CLS number. In the skeletal muscle of mice fed with BCE, mRNA expression of genes involved in energy expenditure and mitochondrial biogenesis, including PPARα, PPARδ, UCP-2, UCP-3 and mitochondrial transcription factor A, were significantly increased. When splenocytes from BCE-fed mice were stimulated by lipopolysaccharides, tumor necrosis factor α and interleukin-1ß mRNA were significantly lower than control splenocytes. Together, the results suggest that BCE supplementation decreases obesity-induced inflammation in adipose tissue and splenocytes, at least in part, by modulating energy metabolism in skeletal muscle.
Assuntos
Inflamação/prevenção & controle , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Ribes/química , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Antocianinas/análise , Antocianinas/farmacologia , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Peso Corporal , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dieta Hiperlipídica/efeitos adversos , Repressão Epigenética , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Inflamação/tratamento farmacológico , Inflamação/etiologia , Interleucina-1beta/metabolismo , Canais Iônicos/genética , Canais Iônicos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Renovação Mitocondrial , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Obesidade/complicações , Obesidade/tratamento farmacológico , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Extratos Vegetais/análise , Polifenóis/análise , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Baço/citologia , Baço/efeitos dos fármacos , Baço/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína Desacopladora 2 , Proteína Desacopladora 3RESUMO
OBJECTIVE: The maintenance of youthful skin appearance is strongly desired by a large proportion of the world's population. The aim of the present study was therefore to evaluate the effect on skin wrinkling, of a combination of ingredients reported to influence key factors involved in skin ageing, namely inflammation, collagen synthesis and oxidative/UV stress. A supplemented drink was developed containing soy isoflavones, lycopene, vitamin C and vitamin E and given to post-menopausal women with a capsule containing fish oil. METHOD: We have performed a double-blind randomized controlled human clinical study to assess whether this cocktail of dietary ingredients can significantly improve the appearance of facial wrinkles. RESULTS: We have shown that this unique combination of micronutrients can significantly reduce the depth of facial wrinkles and that this improvement is associated with increased deposition of new collagen fibres in the dermis. CONCLUSION: This study demonstrates that consumption of a mixture of soy isoflavones, lycopene, vitamin C, vitamin E and fish oil is able to induce a clinically measureable improvement in the depth of facial wrinkles following long-term use. We have also shown, for the first time with an oral product, that the improvement is associated with increased deposition of new collagen fibres in the dermis.