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1.
J Postgrad Med ; 70(2): 105-108, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38629272

RESUMO

ABSTRACT: Arsenic compounds are colorless and odorless and toxicity can occur either acutely following ingestion of arsenicals with gastrointestinal disturbances or due to chronic exposure usually presenting with dermatologic lesions and peripheral neuropathy. We report a young couple who presented with signs and symptoms of painful sensorimotor peripheral neuropathy in a typical "stocking and glove" pattern. They had raised urinary arsenic levels with normal blood levels and thus, a diagnosis of chronic arsenic poisoning due to contaminated water intake was made after detecting elevated arsenic levels in their home water supply. Both patients underwent chelation therapy with dimercaprol for 14 days and reported subjective and objective improvement in symptoms with the reduction in urinary arsenic levels at the end of therapy.


Assuntos
Intoxicação por Arsênico , Doenças do Sistema Nervoso Periférico , Humanos , Arsênio/urina , Intoxicação por Arsênico/complicações , Quelantes/uso terapêutico , Terapia por Quelação , Doença Crônica , Dimercaprol/uso terapêutico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Resultado do Tratamento
2.
Transcult Psychiatry ; 60(3): 602-609, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37491885

RESUMO

The field of Global Mental Health (GMH) aims to address the global burden of mental illness by focusing on closing the "treatment gap" faced by many low- and middle-income countries (LMICs). To increase access to services, GMH prioritizes "scaling up" mental health services, primarily advocating for the export of Western centred and developed biomedical and psychosocial "evidence-based" approaches to the Global South. While this emphasis on scalability has resulted in the increased availability of mental health services in some LMICs, there have been few critical discussions of this strategy. This commentary critically appraises the scalability of GMH by questioning the validity and sustainability of its approach. We argue that the current approach emphasizes the development of mental health services and interventions in "silos," focusing on the treatment of mental illnesses at the exclusion of a holistic and contextualized approach to people's needs. We also question the opportunities that the current approach to GMH offers for the growth of mental health programmes of local NGOs and investigate the potential pitfalls that scalability may have on NGOs' impact and ability to innovate. This commentary argues that any "scaling up" of mental health services must place sustainability at the core of its mission by favouring the growth and development of local solutions and wider forms of support that prioritize social inclusion and long-lasting mental health recovery.


Assuntos
Transtornos Mentais , Serviços de Saúde Mental , Humanos , Saúde Mental , Transtornos Mentais/terapia , Saúde Global , Acessibilidade aos Serviços de Saúde
3.
J Appl Microbiol ; 125(1): 111-120, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29573314

RESUMO

AIM: To explore the potential of Rosellinia sanctae-cruciana an endophytic fungus associated with Albizia lebbeck for pharmaceutically important cytotoxic compounds. METHODS AND RESULTS: One novel cytochalasin, named jammosporin A (1) and four known analogues (2-5) were isolated from the culture of the endophytic fungus R. sanctae-cruciana, harboured from the leaves of the medicinal plant A. lebbeck. Their structures were elucidated by extensive spectroscopic analyses including one-dimensional and two-dimensional nuclear magnetic resonance data along with MS data and by comparison with literature reports. In preliminary screening the ethyl acetate extract of the fungal culture was tested for cytotoxic activity against a panel of four cancer cell lines (MOLT-4, A549, MIA PaCa-2 and MDA-MB-231), and found to be active against MOLT-4 with an IC50 value of 10 µg ml-1 . Owing to the remarkable cytotoxic activity of the extract the isolated compounds (1-5) were evaluated for their cytototoxicity against the MOLT-4 cell line by MTT assay. Interestingly, compounds 1-2, 4 and 5 showed considerable cytotoxic potential against the human leukaemia cancer cell line (MOLT-4) with IC50 values of 20·0, 10·0, 8·0 and 6·0 µmol l-1 , respectively, while compound 3 showed an IC50 value of 25 µmol l-1 . This is the first report of the existence of this class of secondary metabolites in R. sanctae-cruciana fungus. CONCLUSION: This study discovered a novel compound, named jammosporin A, isolated for the first time from R. sanctae-cruciana, an endophytic fungus of A. lebbeck with anticancer activity against the MOLT-4 cell line. SIGNIFICANCE AND IMPACT OF THE STUDY: Rosellinia sanctae-cruciana represents an interesting source of a new compound with bioactive potential as a therapeutic agent against a human leukaemia cancer cell line (MOLT-4).


Assuntos
Albizzia/microbiologia , Ascomicetos/química , Sobrevivência Celular/efeitos dos fármacos , Citocalasinas/isolamento & purificação , Citocalasinas/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Citocalasinas/química , Citocalasinas/toxicidade , Humanos , Concentração Inibidora 50 , Folhas de Planta/microbiologia , Plantas Medicinais/microbiologia
4.
Andrologia ; 48(8): 880-93, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27681645

RESUMO

Male sexual dysfunction is a common disorder that appears to be a consequence of a wide range of physical and psychological conditions. Due to mental stress, insufficient physical exercise and various aetiological factors, human being's life is becoming less pleasant, which leads to incapability to have sexual pleasure. The allopathic drugs used for sexual dysfunction are believed to produce a variety of side effects and affect other physiological processes and, ultimately, general health. Therefore, the search for natural supplement from medicinal plants is being intensified probably because of less side effects availability and affordability. Ethnobotanical surveys have indicated a large number of plants traditionally used as aphrodisiacs but only few of them are scientifically validated for the management and treatment of male sexual dysfunction. This article has summarised the medicinal plants traditionally recommended and scientifically validated for the management and treatment of male sexual dysfunction.


Assuntos
Afrodisíacos/uso terapêutico , Fitoterapia , Preparações de Plantas/uso terapêutico , Plantas Medicinais , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Disfunção Erétil/tratamento farmacológico , Humanos , Libido , Masculino , Ejaculação Precoce/tratamento farmacológico
5.
Spinal Cord ; 54(12): 1076-1087, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27163452

RESUMO

STUDY DESIGN: Experimental study. OBJECTIVES: To investigate the role of hypothalamus in abnormal feeding behaviour after spinal cord injury (SCI) and the effect of exposure to extremely low frequency magnetic field (ELF-MF) on it. SETTING: India. METHODS: Male Wistar rats (n=44) were divided into Sham (laminectomy), SCI (complete transection of T13 spinal cord), SCI+MF (ELF-MF exposure to SCI rats), VMHL (lesion of ventromedial hypothalamus; VMH), SCI+VMHL (VMHL after SCI) and SCI+VMHL+MF (ELF-MF exposure to SCI+VMHL rats) groups. Food intake (FI), water intake (WI), calorie intake (CI), body weight (BWT), taste preference and sucrose-induced biphasic (SIB) response to noxious stimulus were studied pre and post surgery. Neuronal activity at VMH was assessed by c-Fos immunohistochemistry. The extent of neuronal degeneration and regeneration in spinal cord was assessed microscopically. RESULTS: Data revealed post-SCI decrease in FI, WI, CI and BWT, preference for sodium chloride and citric acid, prolonged analgesic phase of SIB and increased c-Fos immunoreactivity in VMH of SCI rats vs Sham rats. VMH lesion increased FI, WI, CI, BW, preference for sweet tastants and abolished SIB, whereas in SCI+VMHL rats it abolished the effects of SCI on these parameters indicating probable involvement of VMH in SCI-induced alteration in feeding behaviour. Exposure to MF improved the study parameters in SCI rats and reduced the c-Fos immunoreactivity in VMH besides reduction in lesion volume, greater myelination and neuronal regeneration at SCI site. CONCLUSION: SCI influences VMH, leading to alteration in feeding behaviour, which is improved by exposure to ELF-MF.


Assuntos
Comportamento Alimentar/fisiologia , Hipotálamo/metabolismo , Magnetoterapia/métodos , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia , Animais , Peso Corporal , Modelos Animais de Doenças , Ingestão de Alimentos/fisiologia , Hipotálamo/patologia , Imuno-Histoquímica , Masculino , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Regeneração Nervosa/fisiologia , Dor Nociceptiva/patologia , Dor Nociceptiva/fisiopatologia , Dor Nociceptiva/terapia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Wistar , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/patologia , Percepção Gustatória/fisiologia
6.
J Food Sci Technol ; 51(10): 2499-507, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25328189

RESUMO

The use of plant extracts could be a useful alternative to synthetic fungicides in the post harvest handling of fruits and vegetables. The aim of this study was to access the efficacy of extracts obtained from four plants (neem, Pongamia, custard apple leaf and marigold flowers) on the extension of shelf life of mango fruits cv. Dashehri under two storage conditions (Cool store and ambient condition). The fruits were treated with 2 concentrations of each plant extracts (10 % and 20 %) were placed in perforated linear low density poly ethylene bags and stored in storage conditions viz., cool storage and ambient condition, respectively. The treatment of neem leaf extract in combination with cool storage gave encouraging results. Up to the end of the storage study the treatment combination of 20 % neem leaf extract and cool store completely inhibited the pathogens, and no spoilage was observed. There was minimum physiological loss in weight (6.24 %), minimum girth reduction (0.62 %), maximum ascorbic acid content (29.96 mg/ 100 g of pulp), maximum acidity (0.19 %), minimum pH (5.28), maximum total soluble solids (20.96 %), maximum total sugars (12.50 %), reducing sugars (4.12 %) and non- reducing sugars (7.96 %) and best organoleptic score (7.93/10) in this interaction. The inhibitory effect of neem leaf extract was ascribed to the presence of active principle azadirachtin.

7.
Eur J Clin Nutr ; 68(10): 1148-53, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24961547

RESUMO

BACKGROUND/OBJECTIVES: Vitamin D, L-cysteine (LC) and glutathione (GSH) levels are lower in the blood of diabetic patients. This study examined the hypothesis that the levels of vitamin D and LC correlate with those of GSH in the blood of type 2 diabetic patients (T2D), and that vitamin D and LC upregulate glutamate-cysteine ligase (GCLC), which catalyzes GSH biosynthesis, in cultured monocytes. SUBJECTS/METHODS: Fasting blood was obtained after written informed consent from T2D (n=79) and healthy controls (n=22). U937 monocytes were pretreated with 1,25 (OH)2 vitamin D (0-25 nM) or LC (0-500 µM) for 24 h and then exposed to control or high glucose (25 mM) for 4 h. RESULTS: Plasma levels of vitamin D, LC, GSH and GCLC protein were significantly lower in T2D versus those in age-matched healthy controls. Multiple linear regression analyses and adjustment for body weight showed a significant positive correlation between plasma levels of vitamin D (r=0.26, P=0.05) and LC (r=0.81, P=0.001) and that of GSH, and between LC and vitamin D (r=0.27, P=0.045) levels. Plasma levels of GSH (r=-0.34, P=0.01) and LC (r=-0.33, r=0.01) showed a negative correlation with triglyceride levels. Vitamin D correlated inversely with HbA1C (-0.30, P=0.01) and homeostatic model assessment insulin resistance (r=-0.31, P=0.03), which showed a significant positive correlation with triglycerides (r=0.44, P=0.001) in T2D. Cell culture studies demonstrate that supplementation with vitamin D and LC significantly increased GCLC expression and GSH formation in control and high-glucose-treated monocytes. CONCLUSIONS: This study suggests a positive relationship between the concentrations of the micronutrients vitamin D and LC and that of GSH. Some of the beneficial effects of vitamin D and LC supplementation may be mediated by an increase in the levels of GSH and a decrease in triglyceride levels in T2D patients.


Assuntos
Cisteína/sangue , Diabetes Mellitus Tipo 2/sangue , Glutationa/sangue , Resistência à Insulina , Vitamina D/sangue , Linhagem Celular , Cisteína/farmacologia , Suplementos Nutricionais , Feminino , Glutamato-Cisteína Ligase/farmacologia , Glutationa/biossíntese , Humanos , Insulina/sangue , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Triglicerídeos/sangue , Vitamina D/farmacologia
8.
Clin Vaccine Immunol ; 21(6): 886-97, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24789797

RESUMO

A Plasmodium falciparum chimeric protein, PfMSP-Fu24, was constructed by genetically coupling immunodominant, conserved regions of two merozoite surface proteins, the 19-kDa region C-terminal region of merozoite surface protein 1 (PfMSP-119) and an 11-kDa conserved region of merozoite surface protein 3 (PfMSP-311), to augment the immunogenicity potential of these blood-stage malaria vaccine candidates. Here we describe an improved, efficient, and scalable process to produce high-quality PfMSP-Fu24. The chimeric protein was produced in Escherichia coli SHuffle T7 Express lysY cells that express disulfide isomerase DsbC. A two-step purification process comprising metal affinity followed by cation exchange chromatography was developed, and we were able to obtain PfMSP-Fu24 with purity above 99% and with a considerable yield of 23 mg/liter. Immunogenicity of PfMSP-Fu24 formulated with several adjuvants, including Adjuplex, Alhydrogel, Adjuphos, Alhydrogel plus glucopyranosyl lipid adjuvant, aqueous (GLA-AF), Adjuphos+GLA-AF, glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE), and Freund's adjuvant, was evaluated. PfMSP-Fu24 formulated with GLA-SE and Freund's adjuvant in mice and with Alhydrogel and Freund's adjuvant in rabbits produced high titers of PfMSP-119 and PfMSP-311-specific functional antibodies. Some of the adjuvant formulations induced inhibitory antibody responses and inhibited in vitro growth of P. falciparum parasites in the presence as well as in the absence of human monocytes. These results suggest that PfMSP-Fu24 can form a constituent of a multistage malaria vaccine.


Assuntos
Antígenos de Protozoários/imunologia , Vacinas Antimaláricas/imunologia , Proteína 1 de Superfície de Merozoito/imunologia , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Proteínas Recombinantes de Fusão/imunologia , Adjuvantes Imunológicos , Animais , Anticorpos Antiprotozoários/imunologia , Formação de Anticorpos/imunologia , Antígenos de Protozoários/genética , Avaliação Pré-Clínica de Medicamentos , Escherichia coli/genética , Feminino , Humanos , Vacinas Antimaláricas/genética , Malária Falciparum/prevenção & controle , Proteína 1 de Superfície de Merozoito/genética , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Protozoários/genética , Coelhos , Proteínas Recombinantes de Fusão/genética , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
9.
J Biol Regul Homeost Agents ; 28(1): 53-63, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24750791

RESUMO

The aim of this study was to assess whether the concomitant supplementation of certified fermented papaya preparation (FPP, ORI, Gifu, Japan) together with iron supplementation could beneficially affect lipid peroxidation either systemically and at a intraluminal gut level in women with low iron stores. Treatment compliance and iron absorption was assessed as well. Fifty-two non-pregnant, fertile, non-smokers, healthy women with iron deficiency were recruited. The women were given iron supplements (100 mg Fe/d as ferrous sulfate) to be taken daily for 12 weeks (group A). Group B patients were also supplemented with 6g/day of a FPP. A detailed life style questionnaire was administered to all subjects. Iron, ferritin, transferrin receptors (Tf R) and malondialdehyde (MDA) in plasma were measured. The RBCs lysate was used for the estimation of superoxide dismutase (SOD) and glutathione peroxidase (GPx). The total and free iron concentration as well as analysis of oxidative stress in the feces was measured. FPP-supplemented subjects showed a significantly lower degree of gastrointestinal discomfort (p less than 0.05) and abolished the iron supplementation-induced increase of MDA (p less than 0.001) and the depletion of SOD and GPx (p less than 0.01). Moreover, the nutraceutical co-administration brought about a significant reduction of gut oxidative damage and lower fecal content of either total and free iron (p less than 0.05 vs group A). Overall, group B showed a better TfR/ferritin ratio response (p less than 0.05 vs group A). While iron supplementation maintains its clinical relevance considering the prevalence of iron deficiency among females, a careful clinical evaluation and a protective nutraceutical co-administration, as our data suggest with FPP, should be considered.


Assuntos
Suplementos Nutricionais , Trato Gastrointestinal/metabolismo , Ferro/administração & dosagem , Adulto , Feminino , Fermentação , Humanos , Deficiências de Ferro , Malondialdeído/sangue , Oxirredução , Estresse Oxidativo , Receptores da Transferrina/sangue
10.
Indian J Cancer ; 51(4): 477-80, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26842169

RESUMO

BACKGROUND: Hospitalization for fever in cancer patients is associated with considerable morbidity, mortality, and cost. AIM: The aim of this study was to study the bacterial spectrum and susceptibility patterns of pathogens in culture positive patients from the oncology unit of our hospital. METHODS: We retrospectively reviewed the medical records of patients admitted in our cancer center (medical, radiation, and surgical oncology) from January to December 2013. Blood and respiratory secretions from the indoor patients were evaluated. RESULTS: Of the total 693 samples, 76.4% were Gram-negative and 23.6% were Gram-positive. The most common bacterial isolates among Gram-negative organisms in blood were Escherichia coli, Salmonella and among the Gram-positive organism were Staphylococcus aureus and Enterococcus. Among the blood isolates extended spectrum of beta-lactamase, multidrug-resistant (carbapenem-resistant) and pan resistant bugs were seen in 47%, 15%, and 5% of the blood isolates. Among the Gram-positive organisms, 25% respiratory isolates were vancomycin-resistant Enterococci. CONCLUSION: We observed a high incidence of Gram-negative isolates with clinically significant resistance to first-line antibiotics such as cephalosporin's, piperacillin tazobactum, and fluoroquinolones.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/microbiologia , Farmacorresistência Bacteriana , Bactérias Aeróbias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Neoplasias/complicações , Infecções Bacterianas/tratamento farmacológico , Institutos de Câncer , Bactérias Aeróbias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Índia , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Centros de Atenção Terciária
12.
Indian J Med Res ; 137(5): 916-21, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23760377

RESUMO

BACKGROUND & OBJECTIVES: Regular practice of slow breathing has been shown to improve cardiovascular and respiratory functions and to decrease the effects of stress. This pilot study was planned to evaluate the short term effects of pranayama on cardiovascular functions, pulmonary functions and galvanic skin resistance (GSR) which mirrors sympathetic tone, and to evaluate the changes that appear within a short span of one week following slow breathing techniques. METHODS: Eleven normal healthy volunteers were randomized into Pranayama group (n=6) and a non-Pranayama control group (n=5); the pranayama volunteers were trained in pranayama, the technique being Anuloma-Viloma pranayama with Kumbhak. All the 11 volunteers were made to sit in similar environment for two sessions of 20 min each for seven days, while the pranayama volunteers performed slow breathing under supervision, the control group relaxed without conscious control on breathing. Pulse, GSR, blood pressure (BP) and pulmonary function tests (PFT) were measured before and after the 7-day programme in all the volunteers. RESULTS: While no significant changes were observed in BP and PFT, an overall reduction in pulse rate was observed in all the eleven volunteers; this reduction might have resulted from the relaxation and the environment. Statistically significant changes were observed in the Pranayama group volunteers in the GSR values during standing phases indicating that regular practice of Pranayama causes a reduction in the sympathetic tone within a period as short as 7 days. INTERPRETATION & CONCLUSIONS: Beneficial effects of pranayama started appearing within a week of regular practice, and the first change appeared to be a reduction in sympathetic tone.


Assuntos
Exercícios Respiratórios , Fenômenos Fisiológicos Cardiovasculares , Resposta Galvânica da Pele/fisiologia , Ventilação Pulmonar , Adolescente , Adulto , Pressão Sanguínea , Feminino , Voluntários Saudáveis , Frequência Cardíaca/fisiologia , Humanos , Pulmão/fisiologia , Projetos Piloto , Estresse Psicológico/reabilitação , Yoga
13.
Bioprocess Biosyst Eng ; 36(3): 301-15, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22833226

RESUMO

The marine strain Pseudomonas otitidis was isolated to hydrolyze the cooked sunflower oil (CSO) followed by the production of lipase. The optimum culture conditions for the maximum lipase production were determined using Plackett-Burman design and response surface methodology. The maximum lipase production, 1,980 U/ml was achieved at the optimum culture conditions. After purification, an 8.4-fold purity of lipase with specific activity of 5,647 U/mg protein and molecular mass of 39 kDa was obtained. The purified lipase was stable at pH 5.0-9.0 and temperature 30-80 °C. Ca(2+) and Triton X-100 showed stimulatory effect on the lipase activity. The purified lipase was highly stable in the non-polar solvents. The functional groups of the lipase were determined by Fourier transform-infrared (FT-IR) spectroscopy. The purified lipase showed higher hydrolytic activity towards CSO over the other cooked oil wastes. About 92.3 % of the CSO hydrolysis was observed by the lipase at the optimum time 3 h, pH 7.5 and temperature 35 °C. The hydrolysis of CSO obeyed pseudo first order rate kinetic model. The thermodynamic properties of the lipase hydrolysis were studied using the classical Van't Hoff equation. The hydrolysis of CSO was confirmed by FT-IR studies.


Assuntos
Biotecnologia/métodos , Lipase/biossíntese , Óleos de Plantas/metabolismo , Detergentes , Concentração de Íons de Hidrogênio , Hidrólise , Lipólise , Peso Molecular , Octoxinol , Filogenia , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Óleo de Girassol , Propriedades de Superfície , Temperatura , Termodinâmica
14.
J Biol Regul Homeost Agents ; 26(3): 327-35, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23034252

RESUMO

The aim of this study is to test the activity of a marine bioactive compound containing high-purity caviar-derived DNA, collagen elastin and protein extracts from sturgeon (LD-1227, Caviarlieri, Laboratoires Dom, Switzerland) to exert neuroprotective properties in an experimental setting while also being potential triggers of neurogenesis in a separate in vitro study. Supplementation with high-DHA mixture of LD-1227 was applied for 30 days to stress model rats. Both supplementations significantly mitigated the histological brain damage when analyzing hippocampal subregions and corticosterone level. However, LD-1227 was most significantly efficient in preventing SOD, Catalase and ascorbic acid decrease in brain tissue. Both supplementations stimulated neurogenesis in vitro and neuron markers in particular but og olygodendrocyte markers and glia increased only in LD-1227-enriched medium. Taken together, these data suggest that LD-1227 is able to significantly protect the brain structure redox system to higher degree than DHA. Moreover, from in vitro study it appears that marine bioactive compound, through it wide array of small unsaturated fatty acids, phospholipids and neurotransmitter precursors, is likely to influence neuronal and glial lineage to act differently from a DHA-rich mixture.


Assuntos
Misturas Complexas/farmacologia , Proteínas de Peixes/farmacologia , Peixes , Hipocampo/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Neurogênese/efeitos dos fármacos , Animais , Antígenos de Diferenciação/metabolismo , Células Cultivadas , Misturas Complexas/química , Proteínas de Peixes/química , Hipocampo/patologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Ratos , Ratos Sprague-Dawley
15.
J Biol Regul Homeost Agents ; 26(2): 285-94, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22824755

RESUMO

The role of oxidants in viral diseases is fairly complex because it includes metabolic regulation both of host metabolism and viral replication. However, a role for reactive oxygen species (ROS) and reactive nitrogen species (RNS) as mediators of virus-induced lung damage is supported by studies and antioxidants can thus be expected to act at many different levels. The aim of the present pilot study was to test an antioxidant nutraceutical approach on some relevant immunological parameters known to be affected in common seasonal respiratory tract infection. The study population consisted of 90 sedentary healthy patients, previously selected as being GSTM1-positive, divided into three groups: A) 20-40 years; B) 41-65 years; B) over 65 years. Each patients was administered a life style and dietary questionnaire. Subjects were supplemented for 6 weeks with either 9g/day (4.5g twice a day sublingually) of a fermented papaya preparation (Osato Research Institute, Gifu, Japan) or placebo. After a further month period of wash out, subjects were treated again in a crossover manner. Parameters checked were as follows: routine blood tests with WBC formula, saliva flow rate and secretary IgA and lysozyme production and redox gene expression of Phase II enzyme and SOD from upper airways cells (from nasal lavage). Salivary secretion rate showed an age-related decline and was significantly increased by FPP supplementation only in the youngest age-group (p less than 0.05). Subjects treated with FPP showed a significantly higher lever of IgA and lisozyme production., irrespective of age group while their baseline production was significantly lower in the oldest age-group as compared to the youngest one (C vs A, p less than 0.05). FPP treatment brought about a significant upregulation of all phase II enzyme and SOD gene expression tested in nasal lavage cells. In conclusion, FPP supplementation during 1 month resulted in higher salivary IgA and increase in phase II and SOD enzyme expression, i.e the most important antioxidant in the respiratory tract. The biological significance of these effects i.e., whether it will help reducing the whole respiratory oxidative stress in the human airway and, hopefully, the incidence and/or severity of URTI remains to be demonstrated in longer clinical trials.


Assuntos
Antioxidantes/uso terapêutico , Carica , Infecções Respiratórias/tratamento farmacológico , Doença Aguda , Adulto , Fatores Etários , Idoso , Estudos Cross-Over , Suplementos Nutricionais , Epigenômica , Fermentação , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Humanos , Pessoa de Meia-Idade , Salivação/efeitos dos fármacos , Superóxido Dismutase/genética
16.
Mini Rev Med Chem ; 12(7): 632-49, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22512551

RESUMO

Chromone alkaloids and flavoalkaloids are an important group of natural products possessing promising medicinal properties. A chromone alkaloid rohitukine is a major bioactive chemical constituent of plant Dysoxylum binectariferum (Meliaceae) Hook. which is phylogenetically related to the Ayurvedic plant, D. malabaricum Bedd. used for treatment of rheumatoid arthritis. This chromone alkaloid led to discovery of two synthetic flavoalkaloids: flavopiridol (Sanofi) and P-276-00 (Piramal) which have reached to advanced stages of clinical development for cancer treatment. Flavopiridol (Alvocidib; L868275; HMR-1275; NSC 649890 of Sanofi-Aventis + NCI) is approved as an orphan drug for treatment of chronic lymphocytic leukemia and is currently undergoing phase II studies as monotherapy and also as in combination regimes with traditional chemotherapy agents. P-276-00 (12) is currently in phase II clinical studies for advanced refractory neoplasms and multiple myeloma. Extensive amount of medicinal chemistry efforts have been reported on these flavoalkaloids. Flavopiridol demonstrated potent and specific in vitro inhibition of variety of cyclindependent kinases with clear block in cell cycle progression at the G1/S and G2/M phases. Preclinical studies demonstrated the capacity of flavopiridol to induce programmed cell death, promote differentiation, inhibit angiogenic processes and modulate transcriptional events. The co-crystallised structure of deschloro-flavopiridol with CDK-2 is available and key interactions in the ATP binding site have been reported. Flavopiridol has also been studied for the treatment of arthritis and atherosclerotic plaque formation. The present review comprises discovery, medicinal chemistry, pharmacology and preclinical/clinical development of flavoalkaloids as CDK inhibitors.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Quinases Ciclina-Dependentes/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Alcaloides/síntese química , Animais , Ciclo Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Quinases Ciclina-Dependentes/química , Avaliação Pré-Clínica de Medicamentos , Humanos , Inibidores de Proteínas Quinases/síntese química , Relação Estrutura-Atividade
17.
Hum Exp Toxicol ; 31(7): 686-97, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22262262

RESUMO

Dementia is a syndrome of progressive nature, affects wide range of cognitive abilities like memory, language, calculation and so on, neuropsychiatric and social deficits to impair the routine social functions. The present study was designed to assess the effect of curcumin against colchicine-induced cognitive dysfunction and oxidative stress in rats and compare it with rivastigmine. Colchicine (15 µg/5µl) was administered to male Wistar rats intracerebroventricularly (i.c.v.) by stereotaxic apparatus to induce cognitive dysfunction. Administration of colchicine caused poor retention of memory in elevated plus maze, passive avoidance apparatus and Morris water maze paradigms. Chronic treatment with curcumin (100, 200 and 400 mg/kg, p.o.) twice daily and rivastigmine (2.5 mg/kg, p.o.) daily for a period of 28 days beginning 7 days prior to colchicine injection significantly improved colchicine-induced cognitive impairment. Biochemical assessment revealed that i.c.v. colchicine injection significantly increased lipid peroxidation, depleted reduced glutathione levels and decreased acetyl cholinesterase (AChE) activity in rat brains. Chronic administration of curcumin significantly reduced the elevated lipid peroxidation, restored the reduced glutathione levels and AChE activity; however, rivastigmine failed to prevent oxidative stress. The results of the current study indicate that curcumin (100, 200 and 400 mg/kg, p.o.) twice daily has a protective role against colchicine-induced cognitive impairment and associated oxidative stress.


Assuntos
Antioxidantes/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Curcumina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Catalase/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/fisiopatologia , Colchicina , Curcumina/farmacologia , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Memória/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fenilcarbamatos/farmacologia , Fenilcarbamatos/uso terapêutico , Ratos , Ratos Wistar , Rivastigmina
18.
PLoS One ; 7(12): e51714, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23300557

RESUMO

BACKGROUND: Nyctanthes arbor-tristis (Harshringar, Night Jasmine) has been traditionally used in Ayurveda, Unani and other systems of medicine in India. The juice of its leaves has been used by various tribal populations of India in treatment of fevers resembling malaria. AIM OF THE STUDY: This work reports the antiplasmodial activity guided fractionation of Harshringar leaves extract. METHODOLOGY: Crude ethanolic Harshringar leaves extract and its RPHPLC purified fractions were studied for antiplasmodial potency against 3D7 (CQ sensitive) and Dd2 (CQ resistant) strains of P.falciparum and subsequently subjected to bioassay guided fractionation using reverse phase chromatography to pursue the isolation of active fractions. PRINCIPAL FINDINGS: Harshringar crude leaves extract and some of its RPHPLC purified fractions exhibited promising antiplasmodial potency against 3D7 and Dd2 strains of P.falciparum. CONCLUSIONS: The present study has provided scientific validity to the traditional use of leaves extract of Harshringar against malaria leading to the conclusion that this plant holds promise with respect to antimalarial phytotherapy. This is the first scientific report of antiplasmodial activity of RPHPLC fractions of Harshringar leaves extract against P.falciparum strains.


Assuntos
Antimaláricos/farmacologia , Eritrócitos/efeitos dos fármacos , Malária Falciparum/tratamento farmacológico , Fitoterapia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Plasmodium falciparum/efeitos dos fármacos , Células Cultivadas , Fracionamento Químico , Eritrócitos/parasitologia , Humanos , Índia , Malária Falciparum/parasitologia , Espectrofotometria Ultravioleta
19.
J Perinatol ; 32(2): 129-31, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21818063

RESUMO

OBJECTIVE: To determine whether transcutaneous bilirubin (TcB) from covered skin (TcB-C) during and after discontinuing phototherapy (PHT) is reliable in treating neonatal jaundice. STUDY DESIGN: In this prospective observational study, before starting PHT, part of the forehead was covered. TcB-C and TcB from exposed skin (TcB-E) to PHT were measured before starting PHT, on a 12-hourly basis while receiving PHT and 6 h after stopping PHT. We used ANOVA (analysis of variance) and Bonferroni's t-tests. RESULT: A total of 39 infants were enrolled (mean gestation 39 weeks, 51% males and 80% Hispanic). The mean TSB over all time periods was 10.9±2.4, TcB-C 10.9±2.4 and TcB-E 7.2±3.4. Before PHT, there were no significant differences in bilirubin by all three techniques. TcB-C was not significantly different from TSB at any time point. However, TcB-E was significantly lower during PHT and after stopping PHT. CONCLUSION: TcB-C is a reliable method in the management of neonatal jaundice.


Assuntos
Bilirrubina/análise , Icterícia Neonatal/diagnóstico , Icterícia Neonatal/terapia , Fototerapia/métodos , Pele/química , Bilirrubina/sangue , Biomarcadores/análise , Estudos de Coortes , Feminino , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Masculino , Monitorização Fisiológica/métodos , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Resultado do Tratamento
20.
J Perinatol ; 32(9): 716-21, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22094493

RESUMO

OBJECTIVE: To evaluate efficacy of predischarge transcutaneous bilirubin (TcB) measurement and clinical risk assessment in predicting hyperbilirubinemia needing treatment. STUDY DESIGN: A diagnostic test was performed in a prospective cohort study conducted at a teaching hospital in North India. Subjects included healthy neonates with a gestation period of ≥35 weeks or birth weight ≥2000 g. Maternal, neonatal and delivery risk factors for hyperbilirubinemia were prospectively collected. TcB was measured in all enrolled neonates at 24±6, 72 to 96 and 96 to 144 h of postnatal age and when indicated clinically. Neonates were followed up during hospital stay and after discharge till completion of the 7th postnatal day. The key outcome was significant hyperbilirubinemia defined as need of phototherapy on the basis of modified American Academy of Pediatrics guidelines. In neonates born at ≥38 weeks of gestation and in neonates born at ≤37 completed weeks of gestation, middle line and lower line of phototherapy thresholds were used to initiate phototherapy, respectively. Variables observed to be significantly associated with significant hyperbilirubinemia on multivariate analysis were used for construction of a clinical risk assessment tool. Predictive ability of the risk assessment tool was assessed by calculating sensitivity, specificity, positive predictive value and negative predictive value, by plotting receiver-operating characteristics curve and calculating c-statistic. RESULT: A total of 997 neonates (birth weight: 2627±536 g, gestation: 37.8±1.5 weeks) were enrolled in the study, of which 931 completed follow-up. Among enrolled neonates, 344 (34.5%) were low birth weight. Overall, a total of 199 (20%) neonates developed significant hyperbilirubinemia. On stepwise logistic regression analysis, predischarge TcB percentile and gestation were significantly found to be associated with significant hyperbilirubinemia. A risk assessment graph was constructed to predict subsequent development of significant hyperbilirubinemia. Area under curve for this risk assessment strategy was 0.75. CONCLUSION: A risk assessment graphical tool consisting of TcB and gestation accurately predicted subsequent need of phototherapy. Further studies are needed to validate performance of this risk assessment tool.


Assuntos
Bilirrubina/sangue , Hiperbilirrubinemia Neonatal/diagnóstico , Doenças do Prematuro/diagnóstico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Alta do Paciente , Valor Preditivo dos Testes , Medição de Risco , Sensibilidade e Especificidade
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