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1.
J Nucl Med ; 64(9): 1487-1494, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37321825

RESUMO

Calcific aortic valve disease (CAVD) is a prevailing disease with increasing occurrence and no known medical therapy. Dcbld2-/- mice have a high prevalence of bicuspid aortic valve (BAV), spontaneous aortic valve calcification, and aortic stenosis (AS). 18F-NaF PET/CT can detect the aortic valve calcification process in humans. However, its feasibility in preclinical models of CAVD remains to be determined. Here, we sought to validate 18F-NaF PET/CT for tracking murine aortic valve calcification and leveraged it to examine the development of calcification with aging and its interdependence with BAV and AS in Dcbld2-/- mice. Methods: Dcbld2-/- mice at 3-4 mo, 10-16 mo, and 18-24 mo underwent echocardiography, 18F-NaF PET/CT (n = 34, or autoradiography (n = 45)), and tissue analysis. A subset of mice underwent both PET/CT and autoradiography (n = 12). The aortic valve signal was quantified as SUVmax on PET/CT and as percentage injected dose per square centimeter on autoradiography. The valve tissue sections were analyzed by microscopy to identify tricuspid and bicuspid aortic valves. Results: The aortic valve 18F-NaF signal on PET/CT was significantly higher at 18-24 mo (P < 0.0001) and 10-16 mo (P < 0.05) than at 3-4 mo. Additionally, at 18-24 mo BAV had a higher 18F-NaF signal than tricuspid aortic valves (P < 0.05). These findings were confirmed by autoradiography, with BAV having significantly higher 18F-NaF uptake in each age group. A significant correlation between PET and autoradiography data (Pearson r = 0.79, P < 0.01) established the accuracy of PET quantification. The rate of calcification with aging was significantly faster for BAV (P < 0.05). Transaortic valve flow velocity was significantly higher in animals with BAV at all ages. Finally, there was a significant correlation between transaortic valve flow velocity and aortic valve calcification by both PET/CT (r = 0.55, P < 0.001) and autoradiography (r = 0.45, P < 0.01). Conclusion: 18F-NaF PET/CT links valvular calcification to BAV and aging in Dcbld2-/- mice and suggests that AS may promote calcification. In addition to addressing the pathobiology of valvular calcification, 18F-NaF PET/CT may be a valuable tool for evaluation of emerging therapeutic interventions in CAVD.


Assuntos
Estenose da Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Humanos , Camundongos , Animais , Valva Aórtica/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Modelos Animais de Doenças , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/epidemiologia
2.
Heliyon ; 8(6): e09442, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35677420

RESUMO

The effect of layering structures on mechanical and thermal hybrid bacterial cellulose (BC) sheet/Kevlar reinforced epoxy composites was investigated. The BC sheet was extracted from Nata de Coco and used as green reinforcement material hybrid with Kevlar reinforced epoxy composites. The BC/Kevlar reinforced epoxy composite was fabricated by using hand lay-up technique equipped with vacuum bagging system and the BC sheets and Kevlar layers were laminated into different layered structures. The performance of the hybrid BC/Kevlar reinforced epoxy composites was characterized through tensile test and low velocity impact according to ASTM D3039 and ASTM D7136, respectively. The thermal performance of the hybrid composites was characterized by using dynamic mechanical analysis (DMA) test. Tensile test on BC sheet composites with Kevlar and epoxy demonstrated that the addition of BC sheet in BC/Kevlar could not withstand the tensor stress by reducing the tensile stress and Young's modulus. The one layer of Kevlar which was replaced with three to six BC sheets had increased the ability to absorb impact force. The storage modulus (E') and Tan δ were significantly dependent on the number of BC sheets and its layering structure. The highest value of E' was observed when BC sheets were arranged alternately with the Kevlar layers. Different damage mechanisms associated with the number of BC sheets and its layered-structure suggested that the BC sheet was functioning as an impact energy absorber as well as strengthening fibers. This study will upsurge interest in BC reinforced composites and the development of new ideas in automotive, marine and bullet applications.

3.
JACC Basic Transl Sci ; 7(4): 333-345, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35540096

RESUMO

Expression of a neuropilin-like protein, DCBLD2, is reduced in human calcific aortic valve disease (CAVD). DCBLD2-deficient mice develop bicuspid aortic valve (BAV) and CAVD, which is more severe in BAV mice compared with tricuspid littermates. In vivo and in vitro studies link this observation to up-regulated bone morphogenic protein (BMP)2 expression in the presence of DCBLD2 down-regulation, and enhanced BMP2 signaling in BAV, indicating that a combination of genetics and BAV promotes aortic valve calcification and stenosis. This pathway may be a therapeutic target to prevent CAVD progression in BAV.

4.
Front Physiol ; 13: 1056657, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36620209

RESUMO

Transient receptor potential canonical 1 (TRPC1) channels are Ca2+-permeable ion channels expressed in cardiomyocytes. An involvement of TRPC1 channels in cardiac diseases is widely established. However, the physiological role of TRPC1 channels and the mechanisms through which they contribute to disease development are still under investigation. Our prior work suggested that TRPC1 forms Ca2+ leak channels located in the sarcoplasmic reticulum (SR) membrane. Prior studies suggested that TRPC1 channels in the cell membrane are mechanosensitive, but this was not yet investigated in cardiomyocytes or for SR localized TRPC1 channels. We applied adenoviral transfection to overexpress or suppress TRPC1 expression in neonatal rat ventricular myocytes (NRVMs). Transfections were evaluated with RT-qPCR, western blot, and fluorescent imaging. Single-molecule localization microscopy revealed high colocalization of exogenously expressed TRPC1 and the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2). To test our hypothesis that TRPC1 channels contribute to mechanosensitive Ca2+ SR leak, we directly measured SR Ca2+ concentration ([Ca2+]SR) using adenoviral transfection with a novel ratiometric genetically encoded SR-targeting Ca2+ sensor. We performed fluorescence imaging to quantitatively assess [Ca2+]SR and leak through TRPC1 channels of NRVMs cultured on stretchable silicone membranes. [Ca2+]SR was increased in cells with suppressed TRPC1 expression vs. control and Transient receptor potential canonical 1-overexpressing cells. We also detected a significant reduction in [Ca2+]SR in cells with Transient receptor potential canonical 1 overexpression when 10% uniaxial stretch was applied. These findings indicate that TRPC1 channels underlie the mechanosensitive modulation of [Ca2+]SR. Our findings are critical for understanding the physiological role of TRPC1 channels and support the development of pharmacological therapies for cardiac diseases.

5.
Malays Orthop J ; 15(3): 143-146, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34966511

RESUMO

The management of a patient with traumatic hemipelvectomy is complex. We report the acute management and rehabilitation of a 21-year-old patient as well as her prosthesis modification. She was able to return to society as a K3 level ambulator.

6.
Saudi Pharm J ; 29(10): 1112-1119, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34703364

RESUMO

BACKGROUND: Healthcare-associated infections (HAI) are considered one of the most common adverse events in health care service provision. In order to prevent the occurrence of HAIs, it is important to implement several prevention strategies. OBJECTIVES: This study aims to determine the incidence of healthcare-associated infections in a military hospital in Alkharj and the adherence to the HAIs' prevention strategies. METHODS: This study included exporting data for all infected cases confirmed by the infection disease specialists in 2019. The data were collected from the reports that were written by infection control unit and infectious disease department. RESULTS: The rate of healthcare associated infections (HAIs) in 2019 was 0.43% of total patient admissions. The rate of central line associated bloodstream infections in 2019 was 1.15 per 1000 central line days. The rate of catheter associated urinary tract infections in 2019 was 1.00 per 1000 catheter days. The rate of ventilator associated pneumonia in 2019 was 2.11 per 1000 ventilator days and the rate of surgical site infections in 2019 was 0.41 %. CONCLUSION: The rate of overall healthcare-associated infections (HAI) was low. The compliance rate of health care workers to preventive measures that control HAIs was generally high but there was a need for more awareness particularly regarding personal protective equipment and hand hygiene. So it is important to attend more awareness activities and workshops particularly regarding personal protective equipment and hand hygiene. Furthermore, infection control unit and infectious disease department in the hospital should support the robust HAI prevention programs.

7.
Med J Malaysia ; 76(5): 744-746, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34508387

RESUMO

Ventriculoperitoneal shunt (VPS) is a common procedure in neurosurgery for Cerebrospinal Fluid (CSF) diversion. It is associated with various complication. One of the rarer complications is migration of the shunt catheter. The incidence is higher in the paediatric population, up to 71.2% compared to adults 28.8%. We present a case of a 1 year 4 months old boy post TB meningitis with intrathoracic shunt migration 2 months after implantation of VPS. The child presented with upward gaze palsy, on and off productive cough and fever. He had a ventriculoperitoneal shunt inserted 2 months before, when he was diagnosed and treated for TB meningitis. Radiological imaging revealed the distal catheter tip was at the right lung with pneumothorax. The shunt was removed and after confirming that there is no active infection, a new ventriculoperitoneal shunt was reinserted.


Assuntos
Tuberculose Meníngea , Derivação Ventriculoperitoneal , Catéteres , Criança , Febre , Humanos , Lactente , Masculino , Próteses e Implantes , Derivação Ventriculoperitoneal/efeitos adversos
9.
Int J Clin Pract ; 74(8): e13527, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32386077

RESUMO

INTRODUCTION: In patients with diabetes, better health communication is associated with better health outcomes including medication adherence and glycaemic control. The conventional patient information leaflet does not consider the cultural and behavioral perspectives of diverse patient populations. Consumer medicine information (CMI) is a written information about the prescription drugs developed by organisations or individuals other than a drug manufacturer that is intended for distribution to consumers at the time of medication dispensing. OBJECTIVE: This study aimed to evaluate the impact of CMI on medication adherence and glycaemic control among patients with type 2 diabetes in Qatar. METHODS: We developed and customised CMI for all the anti-diabetic medications used in Qatar. A randomised controlled trial in which the intervention group patients (n = 66) received the customised CMI with usual care, while the control group patients (n = 74) received usual care only, was conducted. Self-reported medication adherence and haemoglobin A1c (HbA1c ) were the primary outcome measures. Glycaemic control and medication adherence parameters were measured at baseline, 3 months, and 6 months in both groups. Medication adherence was measured using the 8-item Morisky Medication Adherence Scale (MMAS-8). RESULTS: Although the addition of CMI resulted in better glycaemic control, this did not reach statistical significance, possibly because of the short-term follow-up. The median MMAS-8 score improved from baseline (6.6 [IQR = 1.5]) to 6-month follow-up (7.0 [IQR = 1.00]) in the intervention group. In addition, there was a statistically significant difference between the intervention and the control groups in terms of MMAS-8 score at the third visit (7.0 [IQR = 1.0]) vs 6.5 (IQR = 1.25; P-value = .010). CONCLUSION: CMI for anti-diabetic medications when added to usual care has the potential to improve medication adherence and glycaemic control among patients with type 2 diabetes. Therefore, providing better health communication and CMI to patients with diabetes is recommended.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Disseminação de Informação/métodos , Adesão à Medicação/estatística & dados numéricos , Educação de Pacientes como Assunto/métodos , Adulto , Informação de Saúde ao Consumidor/métodos , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobinas Glicadas/análise , Humanos , Comportamento de Busca de Informação , Masculino , Pessoa de Meia-Idade , Catar , Projetos de Pesquisa , Autorrelato
10.
Front Physiol ; 11: 44, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32116757

RESUMO

Transient receptor potential canonical 6 (TRPC6) channels are non-selective cation channels that are thought to underlie mechano-modulation of calcium signaling in cardiomyocytes. TRPC6 channels are involved in development of cardiac hypertrophy and related calcineurin-nuclear factor of activated T cells (NFAT) signaling. However, the exact location and roles of TRPC6 channels remain ill-defined in cardiomyocytes. We used an expression system based on neonatal rat ventricular myocytes (NRVMs) to investigate the location of TRPC6 channels and their role in calcium signaling. NRVMs isolated from 1- to 2-day-old animals were cultured and infected with an adenoviral vector to express enhanced-green fluorescent protein (eGFP) or TRPC6-eGFP. After 3 days, NRVMs were fixed, immunolabeled, and imaged with confocal and super-resolution microscopy to determine TRPC6 localization. Cytosolic calcium transients at 0.5 and 1 Hz pacing rates were recorded in NRVMs using indo-1, a ratio-metric calcium dye. Confocal and super-resolution microscopy suggested that TRPC6-eGFP localized to the sarcolemma. NRVMs infected with TRPC6-eGFP exhibited higher diastolic and systolic cytosolic calcium concentration as well as increased sarcoplasmic reticulum (SR) calcium load compared to eGFP infected cells. We applied a computer model comprising sarcolemmal TRPC6 current to explain our experimental findings. Altogether, our studies indicate that TRPC6 channels play a role in sarcolemmal and intracellular calcium signaling in cardiomyocytes. Our findings support the hypothesis that upregulation or activation of TRPC6 channels, e.g., in disease, leads to sustained elevation of the cytosolic calcium concentration, which is thought to activate calcineurin-NFAT signaling and cardiac hypertrophic remodeling. Also, our findings support the hypothesis that mechanosensitivity of TRPC6 channels modulates cytosolic calcium transients and SR calcium load.

11.
J Mol Cell Cardiol ; 139: 113-123, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31982426

RESUMO

Transient receptor potential canonical 1 (TRPC1) protein is abundantly expressed in cardiomyocytes. While TRPC1 is supposed to be critically involved in cardiac hypertrophy, its physiological role in cardiomyocytes is poorly understood. We investigated the subcellular location of TRPC1 and its contribution to Ca2+ signaling in mammalian ventricular myocytes. Immunolabeling, three-dimensional scanning confocal microscopy and quantitative colocalization analysis revealed an abundant intracellular location of TRPC1 in neonatal rat ventricular myocytes (NRVMs) and adult rabbit ventricular myocytes. TRPC1 was colocalized with intracellular proteins including sarco/endoplasmic reticulum Ca2+ ATPase 2 in the sarcoplasmic reticulum (SR). Colocalization with wheat germ agglutinin, which labels the glycocalyx and thus marks the sarcolemma including the transverse tubular system, was low. Super-resolution and immunoelectron microscopy supported the intracellular location of TRPC1. We investigated Ca2+ signaling in NRVMs after adenoviral TRPC1 overexpression or silencing. In NRVMs bathed in Na+ and Ca2+ free solution, TRPC1 overexpression and silencing was associated with a decreased and increased SR Ca2+ content, respectively. In isolated rabbit cardiomyocytes bathed in Na+ and Ca2+ free solution, we found an increased decay of the cytosolic Ca2+ concentration [Ca2+]i and increased SR Ca2+ content in the presence of the TRPC channel blocker SKF-96365. In a computational model of rabbit ventricular myocytes at physiological pacing rates, Ca2+ leak through SR TRPC channels increased the systolic and diastolic [Ca2+]i with only minor effects on the action potential and SR Ca2+ content. Our studies suggest that TRPC1 channels are localized in the SR, and not present in the sarcolemma of ventricular myocytes. The studies provide evidence for a role of TRPC1 as a contributor to SR Ca2+ leak in cardiomyocytes, which was previously explained by ryanodine receptors only. We propose that the findings will guide us to an understanding of TRPC1 channels as modulators of [Ca2+]i and contractility in cardiomyocytes.


Assuntos
Ventrículos do Coração/citologia , Miócitos Cardíacos/metabolismo , Canais de Cátion TRPC/metabolismo , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Proteínas do Citoesqueleto/metabolismo , Modelos Biológicos , Miócitos Cardíacos/ultraestrutura , Coelhos , Ratos , Sarcolema/metabolismo , Retículo Sarcoplasmático/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Canais de Cátion TRPC/ultraestrutura
12.
New Microbes New Infect ; 30: 100560, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31193267

RESUMO

Consumer demand for natural pathogen-control agents for substitution of synthetic food preservatives and traditional antibiotics is increasing. This study aimed to reveal the distribution of lactic acid bacteria (LAB) in raw camel milk and to characterize their antimicrobial traits. The genetic identification by 16S rRNA sequencing of 58 LAB isolates showed the predominance of Enterococcus (24.2%), Lactococcus (22.4%) and Pediococcus (20.7%) genera in raw camel milk. These genera exhibited inhibitory activity against a broad spectrum of Gram-positive and Gram-negative bacteria including multidrug-resistant Salmonella. Among these LAB, two isolates-identified as Pediococcus pentosaceus CM16 and Lactobacillus brevis CM22-were selected for their strong bacteriocinogenic anti-listerial activity estimated at 1600 and 800 AU/mL, respectively. The bacteriocins produced were partially purified by ammonium sulphate precipitation and gel filtration and then biochemically characterized. The proteinaceous nature of bacteriocins was confirmed by the susceptibility to enzymes. These bacteriocins showed significant technological characteristics such as heat-resistance, and stability over a wide range of pH (2.0-10.0). In conclusion, these results indicated that Pediococcus pentosaceus CM16 and Lactobacillus brevis CM22 could be useful as potential probiotics. Moreover, their partially purified bacteriocins may play an important role as food preservatives and feed additives. To our knowledge, this is the first report describing the distribution of LAB population in raw camel milk and the characterization of their bacteriocins from the Arabian Peninsula of western Asia.

14.
Med J Malaysia ; 72(3): 197-198, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28733571

RESUMO

This case report discusses the rare association of cerebral abscess related to conjunctivitis in an otherwise healthy child. A 6 year old boy presented with conjunctivitis was treated with topical antibiotics and resolved after a week. Conjunctival swab cultures grew MRSA. A month later he developed status epileptics and CT scans revealed a large cerebral abscess. He was treated with intravenous antibiotics which covered for MRSA, along with an incision and drainage for the cerebral abscess. Pus cultures grew MRSA. The patient recovered well with no disturbance in visual acuity or visual field. On post-operative follow ups, he had no other neurological deficit apart from a slight limp.


Assuntos
Abscesso Encefálico/etiologia , Conjuntivite Bacteriana/complicações , Infecções Estafilocócicas/microbiologia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Abscesso Encefálico/diagnóstico por imagem , Abscesso Encefálico/tratamento farmacológico , Abscesso Encefálico/microbiologia , Criança , Conjuntivite Bacteriana/tratamento farmacológico , Conjuntivite Bacteriana/microbiologia , Drenagem , Humanos , Infusões Intravenosas , Linezolida/administração & dosagem , Linezolida/uso terapêutico , Masculino , Staphylococcus aureus Resistente à Meticilina , Neuroimagem , Infecções Estafilocócicas/tratamento farmacológico , Tomografia Computadorizada por Raios X
15.
Prog Biophys Mol Biol ; 130(Pt B): 254-263, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28629808

RESUMO

Transient receptor potential canonical (TRPC) channels constitute a family of seven Ca2+ permeable ion channels, named TRPC1 to 7. These channels are abundantly expressed in the mammalian heart, yet mechanisms underlying activation of TRPC channels and their precise role in cardiac physiology remain poorly understood. In this review, we perused original literature regarding TRPC channels in cardiomyocytes. We first reviewed studies on TRPC channel assembly and sub-cellular localization across multiple species and cell types. Our review indicates that TRPC localization in cardiac cells is still a topic of controversy. We then examined common molecular biology tools used to infer on location and physiological roles of TRPC channels in the heart. We subsequently reviewed pharmacological tools used to modulate TRPC activity in both cardiac and non-cardiac cells. Suggested physiological roles in the heart include modulation of heart rate and sensing of mechanical strain. We examined studies on the contribution of TRPC to cardiac pathophysiology, mainly hypertrophic signaling. Several TRPC channels, particularly TRPC1, 3 and 6 were proposed to play a crucial role in hypertrophic signaling. Finally, we discussed gaps in our understanding of the location and physiological role of TRPC channels in cardiomyocytes. Closing these gaps will be crucial to gain a full understanding of the role of TRPC channels in cardiac pathophysiology and to further explore these channels as targets for treatments for cardiac diseases, in particular, hypertrophy.


Assuntos
Miócitos Cardíacos/metabolismo , Canais de Cátion TRPC/metabolismo , Animais , Doença
16.
Vitam Horm ; 104: 263-311, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28215298

RESUMO

Age-related neurodegenerative diseases, such as Alzheimer's disease, will represent one of the largest future burdens on worldwide healthcare systems due to the increasing proportion of elderly in our society. As deficiencies in neurotrophins are implicated in the pathogenesis of many age-related neurodegenerative disorders, it is reasonable to consider that global neurotrophin resistance may also become a major healthcare threat. Central nervous system networks are effectively maintained through aging by neuroprotective and neuroplasticity signaling mechanisms which are predominantly controlled by neurotrophin receptor signaling. Neurotrophin receptors are single pass receptor tyrosine kinases that form dimeric structures upon ligand binding to initiate cellular signaling events that control many protective and plasticity-related pathways. Declining functionality of the neurotrophin ligand-receptor system is considered one of the hallmarks of neuropathological aging. Therefore, it is imperative to develop effective therapeutic strategies to contend with this significant issue. While the therapeutic applications of cognate ligands for neurotrophin receptors are limited, the development of nonpeptidergic, small-molecule ligands can overcome these limitations, and productively regulate this important receptor system with beneficial effects. Using our advanced knowledge of the high-dimensionality complexity of receptor systems, the future generation of precision medicines targeting these systems will be an attainable goal.


Assuntos
Desenho de Fármacos , Drogas em Investigação/uso terapêutico , Fatores de Crescimento Neural/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Precursores de Proteínas/uso terapêutico , Receptores de Fator de Crescimento Neural/agonistas , Animais , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/crescimento & desenvolvimento , Sistema Nervoso Central/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/prevenção & controle , Dimerização , Drogas em Investigação/química , Humanos , Ligantes , Terapia de Alvo Molecular , Fatores de Crescimento Neural/química , Fatores de Crescimento Neural/metabolismo , Doenças Neurodegenerativas/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Nootrópicos/química , Nootrópicos/metabolismo , Nootrópicos/uso terapêutico , Precursores de Proteínas/química , Precursores de Proteínas/metabolismo , Receptores de Fator de Crescimento Neural/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Semin Cancer Biol ; 35 Suppl: S244-S275, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25865774

RESUMO

Cancer is a key health issue across the world, causing substantial patient morbidity and mortality. Patient prognosis is tightly linked with metastatic dissemination of the disease to distant sites, with metastatic diseases accounting for a vast percentage of cancer patient mortality. While advances in this area have been made, the process of cancer metastasis and the factors governing cancer spread and establishment at secondary locations is still poorly understood. The current article summarizes recent progress in this area of research, both in the understanding of the underlying biological processes and in the therapeutic strategies for the management of metastasis. This review lists the disruption of E-cadherin and tight junctions, key signaling pathways, including urokinase type plasminogen activator (uPA), phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase (FAK), ß-catenin/zinc finger E-box binding homeobox 1 (ZEB-1) and transforming growth factor beta (TGF-ß), together with inactivation of activator protein-1 (AP-1) and suppression of matrix metalloproteinase-9 (MMP-9) activity as key targets and the use of phytochemicals, or natural products, such as those from Agaricus blazei, Albatrellus confluens, Cordyceps militaris, Ganoderma lucidum, Poria cocos and Silybum marianum, together with diet derived fatty acids gamma linolenic acid (GLA) and eicosapentanoic acid (EPA) and inhibitory compounds as useful approaches to target tissue invasion and metastasis as well as other hallmark areas of cancer. Together, these strategies could represent new, inexpensive, low toxicity strategies to aid in the management of cancer metastasis as well as having holistic effects against other cancer hallmarks.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/genética , Caderinas/genética , Humanos , Invasividade Neoplásica/genética , Metástase Neoplásica , Neoplasias/patologia , Transdução de Sinais/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/genética
18.
Ir J Med Sci ; 184(2): 305-11, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24652265

RESUMO

BACKGROUND: Active surveillance (AS) is a recognised treatment option for low-risk prostate cancer (PCa). AIMS: To review AS criteria in terms of patient selection, follow-up and indications for intervention. METHODS: A total of 2,959 potential participants were identified and invited via email to complete an online survey. Only urologists practising in an EU country were eligible to participate. Statistical analyses were carried out using SPSS version 18.0. The χ (2) test was used to compare responses between those who do and do not follow an AS protocol. RESULTS: Response rate was 8% (n = 226). Ninety-seven per cent urologists offer AS; 25% (n = 53/215) within a clinical trial and a further 28% (n = 60/215) using an official AS protocol. Gleason score ≤ 3 + 3 = 6 (87 %, n = 173/200) and prostate-specific antigen (PSA) ≤ 10 ng/ml (86%, n = 170/198) are the commonest selection criteria. There was a statistically significant association between having an AS protocol and using PSA as an eligibility criterion (p = 0.03). For urologists not following a protocol, 11% do not consider PSA as an eligibility criterion and 81% consider PSA ≤ 10 ng/ml to decide on AS, compared to 2 and 90%, respectively, who adhere to a protocol. Twenty-four per cent of urologists without a protocol do not re-biopsy in comparison to 11% with a protocol (p = 0.026). Gleason score progression trigger the most intervention (n = 168/192, 87%). CONCLUSIONS: Urologists not adhering to an AS protocol or participating in a clinical trial appear to apply less rigorous criteria for both eligibility and monitoring in AS.


Assuntos
Padrões de Prática Médica , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Urologia , Conduta Expectante , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biópsia , Protocolos Clínicos , Exame Retal Digital , Progressão da Doença , Europa (Continente) , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/patologia , Neoplasias da Próstata/sangue , Fatores de Risco , Urologia/normas
19.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-626457

RESUMO

Aims: Bakanae disease on rice has been widely distributed in all countries where rice is grown commercially, especially in Asian countries including Malaysia. As an alternative measure in controlling Fusarium fujikuroi, two approaches have to be adapted i.e. by using resistant varieties and biocontrol agents as reported in the present study. Methodology and results: A total of 31 Malaysian rice varieties were used in screening and results showed that variety MR211 was the most susceptible and MR220 was slightly susceptible. Out of 60 isolates of Trichoderma harzianum isolated from soils in Malaysia and tested against the pathogen under in vitro condition, 13 isolates showed high percentage of inhibition (PIRG > 60%). All isolates of T. harzianum showed that the PIRGs were significantly different at p≤0.05 with those of control plates. Conclusion, significance and impact of study: Biocontrol agent and resistant variety are better alternative for controlling plant diseases. We found a variety MR220 was slightly susceptible, but none of tested varieties is resistant towards pathogen of bakanae disease. T. harzianum has the ability to inhibit the growth of F. fujikuroi (T3068P) under in vitro condition. The findings of the Malaysian susceptible/resistant variety and potential T. harzianum isolate as a biocontrol agent of bakanae are important for future tests in the plant house and field trials.


Assuntos
Agentes de Controle Biológico , Oryza
20.
Health Expect ; 17(1): 116-28, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22050457

RESUMO

BACKGROUND: An assessment of the process and outcomes of a health promotion programme is necessary for the continuous improvement of a programme. OBJECTIVE: To explore the participants' perceptions of the quality and effectiveness of the 'Love Your Heart Programme'. DESIGN: A qualitative study using semi-structured interviews with a purposive sample of participants of the 'Love Your Heart' programme. Interviews were based on an interview guide that grouped questions into four main subgroups: structure, process, immediate outcomes and impact. The interviews were audio-recorded, transcribed verbatim and analysed using the principles of grounded theory. RESULTS: A total of 17 interviews were conducted. The participants were satisfied with the structural aspects of the programme. Different opinions arose regarding the ideal frequency and duration of the programme. The content of the seminars was thought to be too general. There was also a lack of interest in the 'Road to a Healthy Heart' booklet. All of the respondents had positive opinions about the communication skills and attitude of the health educator. The potential advantages and disadvantages of participating in the programme were discussed. Finally, the respondents expressed their satisfaction with the programme and the impact it had on them. DISCUSSION AND CONCLUSIONS: In general, the participants who were interviewed held the programme, and the health educator conducted the programme in high regard. The suggestions that were received can be used to further improve the acceptability and feasibility of the programme.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Promoção da Saúde/organização & administração , Local de Trabalho , Adulto , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Estilo de Vida , Malásia , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Pesquisa Qualitativa , Fatores de Risco , Fatores Socioeconômicos
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