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Inherited iron metabolism defects are possibly missed or underdiagnosed in iron-deficient endemic settings because of a lack of awareness or a methodical screening approach. Hence, we systematically evaluated anemia cases (2019 to 2021) based on clinical phenotype, normal screening tests (high-performance liquid chromatography, α gene sequencing, erythrocyte sedimentation rate, C-reactive protein, and tissue transglutaminase), and abnormal iron profile by targeted next-generation sequencing (26-gene panel) supplemented with whole-exome sequencing, multiplex ligation probe amplification/mitochondrial DNA sequencing, and chromosomal microarray. Novel variants in ALAS2, STEAP3, and HSPA9 genes were functionally validated. A total of 290 anemia cases were screened, and 41 (14%) enrolled for genomic testing as per inclusion criteria. Comprehensive genomic testing revealed pathogenic variants in 23 of 41 cases (56%). Congenital sideroblastic anemia was the most common diagnosis (14/23; 61%), with pathogenic variations in ALAS2 (n = 6), SLC25A38 (n = 3), HSPA9 (n = 2) and HSCB, SLC19A2, and mitochondrial DNA deletion (n = 1 each). Nonsideroblastic iron defects included STEAP3-related microcytic anemia (2/23; 8.7%) and hypotransferrenemia (1/23; 4.3%). A total of 6 of 22 cases (27%) revealed a non-iron metabolism gene defect on whole-exome sequencing. Eleven novel variants (including variants of uncertain significance) were noted in 13 cases. Genotype-phenotype correlation revealed a significant association of frameshift/nonsense/splice variants with lower presentation age (0.8 months versus 9 years; P < 0.01) compared with missense variants. The systematic evaluation helped uncover an inherited iron defect in 41% (17/41) of cases, suggesting the need for active screening and awareness for these rare diseases in an iron-deficient endemic population.
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Anemia Sideroblástica , Hierro , Humanos , Lactante , Hierro/metabolismo , Mutación , Anemia Sideroblástica/epidemiología , Anemia Sideroblástica/genética , Anemia Sideroblástica/diagnóstico , Genómica , ADN Mitocondrial , Proteínas de Transporte de Membrana/genética , 5-Aminolevulinato Sintetasa/genética , 5-Aminolevulinato Sintetasa/metabolismoRESUMEN
Introduction: Phenolic phytochemicals are known for antioxidant-mediated pharmacological effects in various diseases (diabetes, cancer, CVDs, obesity, inflammatory and neurodegenerative disorders). However, individual compounds may not exert the same biological potency as in combination with other phytochemicals. Cyamopsis tetragonoloba (Guar), an underutilized semi-arid legume which has been used as a traditional food in Rajasthan (India), is also a source of the important industrial product guar gum. However, studies on its biological activity, like antioxidant, are limited. Methods: We tested the effect of C. tetragonoloba seed extract to enhance the antioxidant activity of well-known dietary flavonoids (quercetin, kaempferol, luteolin, myricetin, and catechin) and non-flavonoid phenolics (caffeic acid, ellagic acid, taxifolin, epigallocatechin gallate (EGCG), and chlorogenic acid) using DPPH radical scavenging assay. The most synergistic combination was further validated for its cytoprotective and anti-lipid peroxidative effects in in vitro cell culture system, at different concentrations of the extract. LC-MS analysis of purified guar extract was also performed. Results and discussion: In most cases, we observed synergy at lower concentrations of the seed extract (0.5-1 mg/ml). The extract concentration of 0.5 mg/ml enhanced the antioxidant activity of Epigallocatechin gallate (20 µg/ml) by 2.07-folds, implicating its potential to act as an antioxidant activity enhancer. This synergistic seed extract-EGCG combination diminished the oxidative stress nearly by double-fold when compared with individual phytochemical treatments in in vitro cell culture. LC-MS analysis of the purified guar extract revealed some previously unreported metabolites, including catechin hydrate, myricetin-3-galactoside, gossypetin-8-glucoside, and puerarin (daidzein-8-C-glucoside) which possibly explains its antioxidant enhancer effect. The outcomes of this study could be used for development of effective nutraceutical/dietary supplements.
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Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.
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Tronco Encefálico/patología , Accidente Cerebrovascular Isquémico/patología , Corteza Sensoriomotora/patología , Tálamo/patología , Anciano , Anciano de 80 o más Años , Teorema de Bayes , Mapeo Encefálico , Tronco Encefálico/irrigación sanguínea , Tronco Encefálico/diagnóstico por imagen , Revascularización Cerebral/métodos , Estudios de Cohortes , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/terapia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Factores de Riesgo , Corteza Sensoriomotora/irrigación sanguínea , Corteza Sensoriomotora/diagnóstico por imagen , Índice de Severidad de la Enfermedad , Factores Sexuales , Tálamo/irrigación sanguínea , Tálamo/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Essential oils (EOs) are regarded as alternative therapeutic agents for many diseases. In phytotherapy research areas, it is now well reported that conifers are the rich source of EOs. This review aims to update information on the biological sources and the best extraction processes of the significant constituents along with the traditional and therapeutic properties of the EOs from selected conifers of Himachal Pradesh, Northwestern Himalaya. In the present review, ten conifer species of high values have been selected. Results from several studies suggest that the conifers contain monoterpenes, sesquiterpenes, diterpenes, ketones, alcohols, and esters, which are used in medicines, food products, and cosmetics as well as other commercial and industrial products. Traditionally, the EOs from the conifers have been reported to be used against fever, cough, bronchitis, skin diseases, gastrointestinal disorders, and asthma. The pharmacological studies suggest that these EOs can be used as antirheumatic, antiseptic, antispasmodic, anticancer, anti-inflammatory, antitoxic, aphrodisiac, and astringent agents. It is, therefore, concluded that the EOs from the conifers might be one of the promising tools for the treatment of various diseases. Extensive research is required to ascertain the efficacy of the EOs from unstudied conifers.
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Aceites Volátiles/uso terapéutico , Tracheophyta/química , Humanos , Aceites Volátiles/farmacologíaRESUMEN
PURPOSE: To compare and evaluate pain and healing following orthodontic tooth extraction using Low Level Laser Therapy [LLLT] and Cryotherapy. MATERIALS AND METHODS: 62 patients referred for orthodontic extraction of bilateral bicuspids were included. Subjects were alternatively divided into two groups with 31 patients each. One of the bilateral extraction sites was subjected to either intervention, LLLT or Cryotherapy, while the other site was kept as control. Pain was assessed for 7 consecutive days by Visual Analogue Scale and Wound healing on 4th, 7th and 14th days using a modified wound healing scale. RESULTS: Pain scores were generally better for Group I [LLLT] when compared to Group II [Cryotherapy] on all days. The highest mean score for pain observed on the 1st post-extraction day was 4.00 ± 0.93 and 4.16 ± 0.93 for Group I and Group II respectively [p = 0.42]. It was also observed that LLLT helped in better wound healing as compared to cryotherapy with a significant difference in wound healing on 7th [mean score for Group I and Group II- 1.16 ± 0.52 and 1.6 ± 0.62 respectively: p = 0.01] and 14th [mean score Group I and Group II- 0.23 ± 0.43 and 1.0 ± 0.58 respectively: p = 0.00] post-extraction days. CONCLUSION: LLLT has better analgesic and wound healing properties as compared to Cryotherapy, suggesting that LLLT should be preferred over cryotherapy whenever possible.
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Terapia por Luz de Baja Intensidad , Crioterapia , Humanos , Dolor , Manejo del Dolor , Extracción Dental , Cicatrización de HeridasRESUMEN
PURPOSE: The purpose of this prospective, randomized, comparative clinical study was to compare treatment outcome of removal of foci and incision and drainage, with or without oral antibiotic therapy, in the management of single primary maxillofacial space infection with a known focus. MATERIALS AND METHODS: A total of 40 patients with single primary maxillofacial space infection with a known infectious focus were divided into two groups, one treated with incision and drainage only, and the other with incision and drainage along with oral antibiotics. The focus of infection was addressed in both groups. Parameters evaluated included pain score, maximum mouth opening, swelling, purulent discharge and return to normal life, which were assessed on days 1, 2, 3, 5 and 7. The patients were followed up until they reported return to normal life as assessed by a questionnaire. RESULTS: All of the patients rapidly responded to treatment as observed by a reduction in pain, swelling, discharge, and improvement in mouth opening. Pus discharge stopped within first 3 days in 75% of patients. The patients who underwent immediate extraction showed a faster resolution of infection (mean return to normal life = 9 days) than others (mean = 11.2 days). There was no statistically significant difference between the two groups for the five study parameters (p < 0.05). Of the total pus specimens, 75% had no significant bacterial growth, or grew 'oral flora'/contaminants, while only 25% grew specific bacteria. CONCLUSION: This study questions the conventional practice by dental practitioners and surgeons of prescribing antibiotics to all patients with odontogenic infection. Microbial culture and antibiotic sensitivity is of little therapeutic value in selected patient groups.
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Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Enfermedades de la Boca/tratamiento farmacológico , Enfermedades de la Boca/microbiología , Adolescente , Adulto , Bacterias/aislamiento & purificación , Infecciones Bacterianas/microbiología , Niño , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
Parkinson's disease is characterized by the presence of insoluble and neurotoxic aggregates (amyloid fibrils) of an intrinsically disordered protein α-synuclein. In this study we have examined the effects of four naturally occurring polyphenols in combination with ß-cyclodextrin (ß-CD) on the aggregation of α-synuclein in the presence of macromolecular crowding agents. Our results reveal that even at sub-stoichiometric concentrations of the individual components, the polyphenol-ß-CD combination(s) not only inhibited the aggregation of the proteins but was also effective in disaggregating preformed fibrils. Curcumin was found to be the most efficient, followed by baicalein with (-)-epigallocatechin gallate and resveratrol coming in next, the latter two exhibiting very similar effects. Our results suggest that the efficiency of curcumin results from a balanced composition of the phenolic OH groups, benzene rings and flexibility. The latter ensures proper positioning of the functional groups to maximize the underlying interactions with both the monomeric form of α-synuclein and its aggregates. The uniqueness of ß-CD was reinforced by the observation that none of the other cyclodextrin variants [α-CD and HP-ß-CD] used was as effective, in spite of these possessing better water solubility. Moreover, the fact that the combinations remained effective under conditions of macromolecular crowding suggests that these have the potential to be developed into viable drug compositions in the near future. MTT assays on cell viability independently confirmed this hypothesis wherein these combinations (and the polyphenols alone too) appreciably impeded the toxicity of the prefibrillar α-synuclein aggregates on the mouse neuroblastoma cell lines (N2a cells).
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Proteínas Amiloidogénicas/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Polifenoles/administración & dosificación , alfa-Sinucleína/metabolismo , beta-Ciclodextrinas/administración & dosificación , Amiloide/química , Amiloide/efectos de los fármacos , Amiloide/metabolismo , Proteínas Amiloidogénicas/química , Animales , Catequina/análogos & derivados , Catequina/química , Línea Celular , Supervivencia Celular , Dicroismo Circular , Curcumina/administración & dosificación , Curcumina/química , Humanos , Ratones , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Polifenoles/química , Agregación Patológica de Proteínas/tratamiento farmacológico , Agregación Patológica de Proteínas/patología , alfa-Sinucleína/química , beta-Ciclodextrinas/químicaRESUMEN
Abstract Sweet or bell pepper is a member of the Solanaceae family and is regarded as one of the most popular and nutritious vegetable. Blight, in the form of leaf and fruit blight, has been observed to infect bell pepper crops cultivated at the horticulture farm in Rajasthan College of Agriculture, Udaipur, India. Based on disease severity, we attempted to curb this newly emerged problem using different fungicides, plant extracts, bio-control agents, and commercial botanicals against the fungus in laboratory and pot experiments. Bio-control agent Trichoderma viride and plant growth promoting Rhizobacteria (PGPR) isolate Neist-2 were found to be quite effective against bell pepper blight. All evaluated fungicides, botanicals, commercial botanicals, and bio-control agents in vitro were further studied as seed dressers and two foliar sprays at ten days interval in pot experiments. The combinations of Vitavax, PGPR isolate Neist-2, and Mehandi extract were found to be very effective against bell pepper blight followed by Vitavax, T. viride, and Mehandi extract used individually. All treatments in the pot experiments were found to significantly reduce seedling mortality and enhance plant biomass of bell pepper. Thus, these experimental findings suggest that a better integrated management of bell pepper blight could be achieved by conducting field trials in major bell pepper- and chilli-cultivated areas of the state. Besides fungicides, different botanicals and commercial botanicals also seem to be promising treatment options. Therefore, the outcome of the present study provides an alternate option of fungicide use in minimizing loss caused by Drechslera bicolor.
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Enfermedades de las Plantas/microbiología , Ascomicetos , Capsicum/microbiología , Ascomicetos/efectos de los fármacos , Capsicum/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Pruebas de Sensibilidad Microbiana , Plantones/efectos de los fármacos , Antifúngicos/farmacología , Antifúngicos/químicaRESUMEN
Sweet or bell pepper is a member of the Solanaceae family and is regarded as one of the most popular and nutritious vegetable. Blight, in the form of leaf and fruit blight, has been observed to infect bell pepper crops cultivated at the horticulture farm in Rajasthan College of Agriculture, Udaipur, India. Based on disease severity, we attempted to curb this newly emerged problem using different fungicides, plant extracts, bio-control agents, and commercial botanicals against the fungus in laboratory and pot experiments. Bio-control agent Trichoderma viride and plant growth promoting Rhizobacteria (PGPR) isolate Neist-2 were found to be quite effective against bell pepper blight. All evaluated fungicides, botanicals, commercial botanicals, and bio-control agents in vitro were further studied as seed dressers and two foliar sprays at ten days interval in pot experiments. The combinations of Vitavax, PGPR isolate Neist-2, and Mehandi extract were found to be very effective against bell pepper blight followed by Vitavax, T. viride, and Mehandi extract used individually. All treatments in the pot experiments were found to significantly reduce seedling mortality and enhance plant biomass of bell pepper. Thus, these experimental findings suggest that a better integrated management of bell pepper blight could be achieved by conducting field trials in major bell pepper- and chilli-cultivated areas of the state. Besides fungicides, different botanicals and commercial botanicals also seem to be promising treatment options. Therefore, the outcome of the present study provides an alternate option of fungicide use in minimizing loss caused by Drechslera bicolor.
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Ascomicetos , Capsicum/microbiología , Enfermedades de las Plantas/microbiología , Antifúngicos/química , Antifúngicos/farmacología , Ascomicetos/efectos de los fármacos , Capsicum/química , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/química , Extractos Vegetales/farmacología , Plantones/efectos de los fármacosRESUMEN
The chemical investigation of ethanolic extract from rhizomes of Cautleya spicata (Sm.) Baker (Zingiberaceae) has resulted in the isolation of eight compounds which were characterised as ß-sitosterol (1), ß-sitosterol ß-D-glucoside (2), bergapten (3), zerumin A (4), (E)-labda-8(17),12-diene-15,16-dial (5), kaempferol (6), quercetin (7) and astragalin (8). All compounds were identified by spectroscopic and chemical methods. This paper describes the first phytochemical work on C. spicata.
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Fitoquímicos/química , Extractos Vegetales/química , Rizoma/química , Zingiberaceae/química , Glucósidos , Quempferoles , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Quercetina , SitoesterolesRESUMEN
The composition of essential oil isolated from Senecio nudicaulis Wall. ex DC. growing wild in Himachal Pradesh, India, was analysed, for the first time, by capillary gas chromatography (GC) and GC-mass spectrometry. A total of 30 components representing 95.3% of the total oil were identified. The essential oil was characterised by a high content of oxygenated sesquiterpenes (54.97%) with caryophyllene oxide (24.99%) as the major component. Other significant constituents were humulene epoxide-II (21.25%), α-humulene (18.75%), ß-caryophyllene (9.67%), epi-α-cadinol (2.90%), epi-α-muurolol (2.03%), ß-cedrene (1.76%), longiborneol (1.76%), 1-tridecene (1.16%) and citronellol (1.13%). The oil was screened for antioxidant activity using DPPH, ABTS and nitric oxide-scavenging assay. The oil was found to exhibit significant antioxidant activity by scavenging DPPH, ABTS and nitric oxide radicals with IC50 values of 10.61 ± 0.14 µg mL(- 1), 11.85 ± 0.28 µg mL(- 1) and 11.29 ± 0.42 µg mL(- 1), respectively.
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Antioxidantes/química , Aceites Volátiles/química , Aceites de Plantas/química , Senecio/química , Monoterpenos Acíclicos , Alquenos/química , Alquenos/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Cromatografía de Gases y Espectrometría de Masas , India , Sesquiterpenos Monocíclicos , Monoterpenos/química , Monoterpenos/aislamiento & purificación , Plantas Medicinales/química , Sesquiterpenos Policíclicos , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Terpenos/química , Terpenos/aislamiento & purificaciónRESUMEN
The ready-to-drink (RTD) tea beverages are becoming increasingly popular owing to the health benefits associated with tea polyphenols, but instability due to development of haze and formation of tea cream is a common problem encountered in the product. Membrane technology provides a scope to produce natural, additive-free RTD teas while overcoming the major disadvantages associated with the conventional decreaming methods. Approaches employing membranes for the clarification of extracts from black and green tea have been discussed together with their relative advantages and limitations. The article also outlines the concerns to be addressed in the future attempts employing membrane technology.
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Tecnología de Alimentos/métodos , Membranas Artificiales , Té/química , Antioxidantes , Camellia sinensis , Hidrolasas de Éster Carboxílico , Catequina , Estabilidad de Medicamentos , Filtración , Manipulación de Alimentos/métodos , Promoción de la Salud , Humanos , Extractos Vegetales/química , PolifenolesRESUMEN
Plants synthesize volatile alcohol esters on environmental insult or as metabolic induction during flower/fruit development. However, essential oil plants constitutively produce them as the oil constituents. Their synthesis is catalyzed by BAHD family enzymes called alcohol acyltransferases (AATs). However, no AAT has been characterized from plant foliage synthesizing acyclic monoterpenoids containing essential oils. Therefore, we have purified and biochemically characterized a geraniol: acetyl coenzyme A acetyltransferase (GAAT) from Palmarosa aroma grass (Cymbopogon martinii) leaf. MALDI-assisted proteomic study of the 43kDa monomeric enzyme revealed its sequence motif novelties e.g. relaxed conservation at Phe and Trp in DFGWG'. This suggests permissiveness of variations in the conserved motif without loss of catalytic ability. Also, some new conserved/semi-conserved motifs of AATs were recognized. The GAAT k(cat)/K(m) values (300-700M(-1)s(-1)) were low (a generic characteristic for secondary metabolism enzyme) but higher than those of some floral AATs. Wide substrate acceptability for catalyzing acetylation of diverse primary alcohols (chain of ≥C(6)) implied its catalytic description as a 'primary aliphatic alcohol acetyltransferase'. It signifies metabolic ability to deliver diverse aroma esters, should the acceptor alcohols be available in planta. To our knowledge, this is the first report of detailed kinetics of a vegetal monoterpenol acyltransferase.
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Acetiltransferasas/aislamiento & purificación , Cymbopogon/enzimología , Aceites Volátiles/metabolismo , Hojas de la Planta/enzimología , Aceites de Plantas/metabolismo , Terpenos/metabolismo , Acetiltransferasas/química , Acetiltransferasas/metabolismo , Monoterpenos Acíclicos , Cymbopogon/química , Ésteres , Concentración de Iones de Hidrógeno , Cinética , Monoterpenos/metabolismo , Especificidad de Órganos , Hojas de la Planta/química , Proteínas de Plantas/química , Proteínas de Plantas/aislamiento & purificación , Proteínas de Plantas/metabolismo , Proteómica , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Especificidad por Sustrato , TemperaturaRESUMEN
Traditional uses of floristic diversity are the most important component of indigenous knowledge system, which is widely prcatised by human populations all across the world. Keeping this in mind, the present study has been conducted during 2010-2012, to study the ethnobotanical and ethnomedicinal uses of floristic diversity in Murari Devi and surrounding areas of Mandi Disrtict in Himachal Pradesh, India. Total 384 species (71 trees, 97 shrubs, 209 herbs and 07 ferns) belonging to 106 families and 285 genera were recorded and used by the inhabitants of the area. Different parts of these species, such as whole plants, leaves, flowers, fruits, roots, seeds, stems, barks, etc. were used by the inhabitants for curing various ailments. Various anthropogenic activities, over exploitation and habitat degradation have led rapid population depletion of these species. Therefore, study on habitat ecology, development of conventional and in-vitro propagation protocols, development of agro techniques/plantation techniques and introduction in the akin habitats, education and awareness programs for the inhabitants are suggested. So that adequate planning for the conservation of these species could be done.
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Etnobotánica , Medicina Tradicional , Preparaciones de Plantas/uso terapéutico , Conservación de los Recursos Naturales , Características Culturales , Ecosistema , Conocimientos, Actitudes y Práctica en Salud/etnología , Humanos , India , Fitoterapia , Preparaciones de Plantas/clasificación , Plantas MedicinalesRESUMEN
The aim of this study is to document the traditional knowledge on the utilization of Biofencing plants of Himachal Pradesh, Northwest Himalaya. The study was imperative because of dearth in the data pertaining to Biofencing plants in the study areas. The whole study area was stratified into three zones and a widespread field survey and random sampling method was adopted to assess the live fencing diversity of the region. The region occupies total 61 species. 10 (trees), 45 (shrubs), 4 (herbs) and 2 were climbers. These belong to the 25 families. Rosaceae, Fabaceae, Berberidaceae, Elaeagnaceae and Euphorbiaceae are dominant families. Among genera, Berberis and Rosa are dominant. Of the total, 55 species are medicinally important and among these 20% are used for stomach disorders; 17% (skin complaints), 14% (asthma), 11% (fever and joint pains), 3% (aphrodisiac and snake bite), 1% (anticancerous and nerve disorders). Ethnobotanical assessment showed that 33 of the recorded species are used as fuel, 20 (edible), 8 (fodder) and 4 (fiber and ornamental). This traditional knowledge of Biofencing plants contributes to the conservation of biodiversity and provides resource of economic and ecological interest and also decreasing the pressure on forests. So there is need to encourage the practice of using plant species for fencing in this region.
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Agricultura/métodos , Productos Agrícolas/clasificación , Etnobotánica , Adulto , Anciano , Biodiversidad , Productos Agrícolas/crecimiento & desarrollo , Abastecimiento de Alimentos , Humanos , India , Conocimiento , Persona de Mediana Edad , Fitoterapia , Plantas Medicinales/clasificación , Plantas Medicinales/crecimiento & desarrolloRESUMEN
BACKGROUND: The MTHFR 677CâT polymorphism has been associated with raised homocysteine concentration and increased risk of stroke. A previous overview showed that the effects were greatest in regions with low dietary folate consumption, but differentiation between the effect of folate and small-study bias was difficult. A meta-analysis of randomised trials of homocysteine-lowering interventions showed no reduction in coronary heart disease events or stroke, but the trials were generally set in populations with high folate consumption. We aimed to reduce the effect of small-study bias and investigate whether folate status modifies the association between MTHFR 677CâT and stroke in a genetic analysis and meta-analysis of randomised controlled trials. METHODS: We established a collaboration of genetic studies consisting of 237 datasets including 59,995 individuals with data for homocysteine and 20,885 stroke events. We compared the genetic findings with a meta-analysis of 13 randomised trials of homocysteine-lowering treatments and stroke risk (45,549 individuals, 2314 stroke events, 269 transient ischaemic attacks). FINDINGS: The effect of the MTHFR 677CâT variant on homocysteine concentration was larger in low folate regions (Asia; difference between individuals with TT versus CC genotype, 3·12 µmol/L, 95% CI 2·23 to 4·01) than in areas with folate fortification (America, Australia, and New Zealand, high; 0·13 µmol/L, -0·85 to 1·11). The odds ratio (OR) for stroke was also higher in Asia (1·68, 95% CI 1·44 to 1·97) than in America, Australia, and New Zealand, high (1·03, 0·84 to 1·25). Most randomised trials took place in regions with high or increasing population folate concentrations. The summary relative risk (RR) of stroke in trials of homocysteine-lowering interventions (0·94, 95% CI 0·85 to 1·04) was similar to that predicted for the same extent of homocysteine reduction in large genetic studies in populations with similar folate status (predicted RR 1·00, 95% CI 0·90 to 1·11). Although the predicted effect of homocysteine reduction from large genetic studies in low folate regions (Asia) was larger (RR 0·78, 95% CI 0·68 to 0·90), no trial has evaluated the effect of lowering of homocysteine on stroke risk exclusively in a low folate region. INTERPRETATION: In regions with increasing levels or established policies of population folate supplementation, evidence from genetic studies and randomised trials is concordant in suggesting an absence of benefit from lowering of homocysteine for prevention of stroke. Further large-scale genetic studies of the association between MTHFR 677CâT and stroke in low folate settings are needed to distinguish effect modification by folate from small-study bias. If future randomised trials of homocysteine-lowering interventions for stroke prevention are undertaken, they should take place in regions with low folate consumption. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).
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Suplementos Dietéticos , Ácido Fólico/administración & dosificación , Homocisteína/sangre , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético , Accidente Cerebrovascular/prevención & control , Complejo Vitamínico B/administración & dosificación , Homocisteína/genética , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/genéticaRESUMEN
Tendon disorders are debilitating, and difficult to manage. Current management strategies offer symptomatic relief, but do not result in definitive disease resolution. Despite remodeling, the biochemical and mechanical properties of healed tendon tissue may never match those of intact tendons. This article presents a detailed up-to-date review of possible strategies for optimizing tendon healing and repair, such as growth factor therapy, gene therapy, and tissue engineering.
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Tendinopatía/terapia , Traumatismos de los Tendones/terapia , Animales , Ablación por Catéter , Terapia Genética , Humanos , Inmovilización , Péptidos y Proteínas de Señalización Intercelular/uso terapéutico , Terapia por Láser , Magnetoterapia , Trasplante de Células Madre Mesenquimatosas , Estrés Mecánico , Ingeniería de Tejidos , Andamios del Tejido , Terapia por Ultrasonido , Cicatrización de HeridasRESUMEN
PURPOSE: To compare the results of small incision trabeculectomy avoiding Tenon's capsule (SIT) vis-à-vis intraoperative use of Mitomycin-C (MMC) in primary chronic angle closure glaucoma. METHODS: A controlled prospective study was conducted on 60 consecutive primary chronic angle closure glaucoma patients requiring glaucoma filtration surgery. Patients were divided into two groups, Group I (n = 30): those undergoing SIT and Group II (n = 30): those undergoing trabeculectomy with MMC. Patients were followed up serially for 24 months and their intraocular pressure (IOP) was monitored. Success was defined as IOP < or = 22 mm Hg with no additional anti-glaucoma medication or laser/surgical intervention. Success was also defined as a 30% reduction from the initial IOP at which optic disc cupping and/or visual field changes occurred. RESULTS: The final mean IOP with SIT was 16.80 +/- 4.20 mm Hg as against 17.84 +/- 3.80 mm Hg with trabeculectomy with MMC. Final success rate of 93.3% was obtained with SIT versus 90% with trabeculectomy with MMC. No major complications were seen with either procedure. CONCLUSION: Small incision trabeculectomy safely and effectively reduces the IOP in over 90% cases. The advantages of this procedure over trabeculectomy with MMC are its low cost, use of a small (2.5 mm) limbal incision which obviates the dissection of Tenon's capsule and absence of any major complication.
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Antibióticos Antineoplásicos/administración & dosificación , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Glaucoma de Ángulo Abierto/cirugía , Mitomicina/administración & dosificación , Trabeculectomía/métodos , Adulto , Anciano , Terapia Combinada , Femenino , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Estudios Prospectivos , Resultado del Tratamiento , Agudeza VisualRESUMEN
BACKGROUND AND OBJECTIVE: The purpose of this study was to compare the results of small incision trabeculectomy (SIT) avoiding Tenon's capsule vis-à-vis conventional trabeculectomy, and find a safe, effective alternative to conventional trabeculectomy with or without pharmacological wound modulation. PATIENTS AND METHODS: A controlled prospective study was conducted on 80 consecutive open-angle glaucoma patients requiring glaucoma filtration surgery. They were divided into two groups: Group I (n = 40): patients undergoing conventional trabeculectomy; and Group II (n = 40): patients undergoing limbal approach SIT. Patients were followed up serially for a minimum of 12 months and their intraocular pressure was monitored. Success of the procedure was defined as an intraocular pressure (IOP) <22 mm Hg with no additional antiglaucoma medication or surgery, and achieving at least a 30% reduction from the initial IOP at which optic disc cupping and/or visual field changes occurred. RESULTS: A significant fall (P <0.0001) in the final mean IOP was present in both groups at all time intervals in comparison to their preoperative values. The final mean intraocular pressure achieved with conventional trabeculectomy was 18.90 +/- 4.86 mm Hg versus 16.60 +/- 5.93 mm Hg with SIT. The final success rate of 90% was obtained with SIT vs 80% with conventional trabeculectomy. No major complications were encountered with either procedure although complications such as shallow anterior chamber and progression of cataractogenesis were seen more often in patients undergoing conventional trabeculectomy. CONCLUSION: Small incision trabeculectomy avoiding Tenon's capsule is a low-cost and safe alternative to conventional trabeculectomy that effectively reduces IOP in 90% of cases. The use of a small 2.5 mm limbal incision, which obviates the dissection of Tenon's capsule and absence of any major complication, suggests that this procedure be used more often in glaucomatous eyes needing filtering surgery.