RESUMO
The oncology community has shown growing interest to understand how body composition measures can be utilized to improve cancer treatment and survivorship care for about 20 million individuals diagnosed with cancer annually. Recent observational studies demonstrate that muscle and adipose tissue distribution are risk factors for clinical outcomes such as postoperative complications, and worse overall survival. There is an emergent recognition that body mass index (BMI) is neither adequate to identify patients with adverse health outcomes due to poor muscle health or excess adiposity, nor does BMI accurately classify the distribution of adiposity. Abdominal CT is a most frequently imaging examination for a wide variety of clinical indications, but it is only used to diagnose the immediate problem. Additionally, each CT examination contains very robust data on body composition which generally goes unused in routine clinical practice. The field is eager to identify therapeutic interventions that modify body composition and reduce the incidence of poor clinical outcomes in this population. Large scale population based screening is feasible now by making all of these relevant biometric measures fully automated through the use of artificial intelligence algorithms, which provide rapid and objective assessment.
Assuntos
Composição Corporal , Índice de Massa Corporal , Neoplasias , Humanos , Tomografia Computadorizada por Raios X/métodos , AdiposidadeRESUMO
The topical application of essential oils is considered an effective treatment for skin diseases. Cymbopogon distans (Nees ex Steud.) Wats (Poaceae) is a promising aromatic grass widespread in the Himalayan temperate zone. Therefore, using in-vitro and in-vivo bioassays, we examined the chemical and pharmacological characteristics of essential oil hydro-distilled from C. distans coded as CDA-01, specifically concerning skin inflammation. Characterization using GC-FID and GC-MS provided a chemical fingerprint for CDA-01, enabling the identification of 54 compounds; amongst them, citral (34.3%), geranyl acetate (21.2%), and geraniol (16.4%) were the most abundant. To examine the anti-inflammatory potential, CDA-01 treatment on LPS-stimulated macrophage cells in addition to 12-O-tetradecanoylphorbol-13-acetate (TPA) generated cutaneous inflammatory reaction in the mouse ear was assessed through quantification of the inflammatory markers. Consequently, CDA-01 demonstrated protection against inflammation caused by LPS by lowering the pro-inflammatory cytokines (IL-6 and TNF-α) level in HaCaT cells with negligible cytotoxicity. Consistent with the in-vitro findings, CDA-01 treatment reduced pro-inflammatory mediators (TNF-, IL-6, and NO) and lipid peroxidation in an in-vivo investigation. Subcutaneous inflammation in TPA-treated mice ears was similarly decreased, as evidenced by the histological and morphological studies. As a result of our findings, it is possible that CDA-01 could be an effective treatment for skin inflammation disorders.
Assuntos
Cymbopogon , Dermatite , Óleos Voláteis , Animais , Camundongos , Monoterpenos/farmacologia , Interleucina-6 , Lipopolissacarídeos , Inflamação/tratamento farmacológico , Óleos Voláteis/farmacologiaRESUMO
The needle powder of Taxus wallichiana is in use for the management of diabetes and inflammation-related complications in the Indian and Chinese Systems of Traditional Medicine but the lack of proper pharmacological intervention has prompted us to investigate the pharmacological mechanism against inflammation-induced insulin resistance in high-fat diet-fed C57BL/6 mice. Hexane (Tw-H), chloroform (Tw-C), and ethyl acetate (Tw-EA) extracts were prepared from a needle of T. wallichiana and its effect on glucose uptake against TNF-α-induced insulin resistance in skeletal muscle cells was studied. Among all, Tw-EA extract has shown promising glucose uptake potential. Tw-EA treatment is also able to decrease the lipid accumulation in adipocytes. Chemical signature of Tw-EA using HPLC showed the presence of taxoids. Efficacy of taxoids-rich extract from T. wallichiana (Tw-EA) was further validated in in vivo system against high-fat diet (HFD)-induced insulin resistance in C57BL/6 mice. Oral treatment of Tw-EA showed significant reduction in blood glucose, pro-inflammatory cytokine production and body weight gain when compared with vehicle-treated HFD-induced insulin resistance in C57BL/6 mice. Histopathology and immunohistochemistry study in skeletal muscle and adipose tissue revealed that oral treatment of Tw-EA is able to reduce the infiltration of inflammatory cells in skeletal muscles, ameliorate the hypertrophy in adipose tissue and upregulate the GLUT4 protein expression. Treatment with Tw-EA significantly up-regulated mRNA expression of insulin signaling pathway (IRS-1, PI3K, AKT, GLUT 4). This study suggested the beneficial effect of taxoids-rich extract from Taxus wallichiana against the inflammation-associated insulin resistance condition.
Assuntos
Resistência à Insulina , Taxus , Camundongos , Animais , Resistência à Insulina/fisiologia , Dieta Hiperlipídica , Taxus/metabolismo , Taxoides/uso terapêutico , Camundongos Endogâmicos C57BL , Inflamação/tratamento farmacológico , Insulina/metabolismo , Glicemia/metabolismoRESUMO
Rutin (3, 3', 4' 5 and 7-pentahydroxyflavone-3-rhamnoglucoside) is a flavonoid glycoside, found in many edible plants such as buckwheat and berries. Severe malaria is an inflammatory response triggered by oxidative stress that results in multi-organ pathologies and a high mortality rate in children and pregnant women worldwide. Rutin is recommended as a food supplement for the treatment of various diseases due to its anti-oxidative and anti-inflammatory properties, which prompted us to investigate its ameliorative effects in severe malaria pathogenesis against oxidative stress and inflammatory response using in vitro and in vivo bioassays. Rutin was examined in this work for its anti-plasmodial activity against chloroquine-sensitive and resistant Plasmodium falciparum strains, as well as its anti-oxidative and anti-inflammatory activity against LPS-stimulated macrophage cells. The in vitro data were subsequently verified in mice fed orally with rutin alone or in combination with chloroquine in Plasmodium berghei-induced malaria pathogenesis. The anti-plasmodial and anti-inflammatory properties of rutin were demonstrated in in vitro results. Apart from its anti-inflammatory and anti-oxidant effects in malaria pathogenesis, in vivo efficacy studies indicated that oral treatment with rutin reduced parasitaemia, increased mean survival time, and restored haemoglobin and glucose levels in mice at lower dose. Interestingly, both rutin and chloroquine demonstrated synergy in in vitro and in vivo experiments. The findings of the present study thus highlighted the suitability of rutin for further study in the management of drug resistant malaria in combination with standard anti-malarial drugs.
Assuntos
Antimaláricos , Malária , Animais , Antimaláricos/farmacologia , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Feminino , Humanos , Malária/tratamento farmacológico , Camundongos , Plasmodium berghei , Gravidez , Rutina/farmacologiaRESUMO
Cymbopogon martini variety sofia, commonly known as ginger-grass, is an important aromatic crop used by the perfumery, medicinal and cosmetic industries worldwide. This study explores the chemical and possible pharmacological profile of hydro-distilled essential oil of C. martini variety sofia against skin inflammation. The essential oil extracted by the hydrodistillation process was analyzed by gas chromatography (GC), gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) to identify its constituents, and was coded as CMA-01 for further in vitro and in vivo pharmacological study related to skin inflammation. The chemical fingerprint revealed that CMA-01 oil has (E)-p-mentha-2,8-dien-1-ol (21.0%), (E)-p-mentha-1(7),8-dien-2-ol (18.1%), (Z)-p-mentha-1(7),8-dien-2-ol (17.4%), (Z)-p-mentha-2,8-dien-1-ol (9.0%), limonene (7.7%), and (E)-carveol (5.7%) as major components. The pre-treatment of CMA-01 showed significant inhibition of pro-inflammatory markers in activated HaCat cells without cytotoxic effect. The in vivo study revealed the ameliorative impact of CMA-01 against skin inflammation induced by TPA in mouse ears as evidenced by a reduction of ear edema, pro-inflammatory mediators (IL-6, TNF-α), oxidative stress markers (malondialdehyde and nitric-oxide) and histological changes in ear tissues without any skin irritation response on rabbit skin. These findings suggest the suitability of CMA-01 as a valuable therapeutic candidate for the treatment of skin inflammation.
Assuntos
Cymbopogon , Dermatite , Óleos Voláteis , Animais , Cymbopogon/química , Cromatografia Gasosa-Espectrometria de Massas , Inflamação/tratamento farmacológico , Camundongos , Óleos Voláteis/farmacologia , CoelhosRESUMO
Plumbagin, a vitamin K3 analogue is the major active constituent in several plants including root of Plumbago indica Linn. This compound has been shown to exhibit a wide spectrum of pharmacological activities. The present investigation was to evaluate the ameliorative effects of plumbagin (PL) against severe malaria pathogenesis due to involvement of oxidative stress and inflammatory response in Plasmodium berghei infected malaria in mice. Malaria pathogenesis was induced by intra-peritoneal injection of P. berghei infected red blood cells into the Swiss albino mice. PL was administered orally at doses of 3, 10 and 30 mg/kg/day following Peter's 4 day suppression test. Oral administration of PL showed significant reduction of parasitaemia and increase in mean survival time. PL treatment is also attributed to significant increase in the blood glucose and haemoglobin level when compared with vehicle-treated infected mice. Significant inhibition in level of oxidative stress and pro-inflammation related markers were observed in PL treated group. The trend of inhibition in oxidative stress markers level after oral treatment of PL was MPO > LPO > ROS in organ injury in P. berghei infected mice. This study showed that plumbagin is able to ameliorate malaria pathogenesis by augmenting anti-oxidative and anti-inflammatory mechanism apart from its effect on reducing parasitaemia and increasing mean survival time of malaria-induced mice.
Assuntos
Antimaláricos/administração & dosagem , Malária/tratamento farmacológico , Naftoquinonas/administração & dosagem , Plasmodium berghei/efeitos dos fármacos , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antimaláricos/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inflamação/tratamento farmacológico , Inflamação/parasitologia , Malária/parasitologia , Masculino , Camundongos , Naftoquinonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Plasmodium berghei/isolamento & purificação , Plumbaginaceae/químicaRESUMO
BACKGROUND: Curcuma longa L. is an important industrial crop used by medicinal and cosmetic industries in the world. Its leaves are a waste material after harvesting rhizomes. The aim of the study was to evaluate the chemical and pharmacological profile of essential oil from waste leaves of Curcuma longa (EOCl) against skin inflammation. METHODS: EOCl was subjected to gas chromatography (GC) analysis for identification of essential oil constituents and its anti-inflammatory evaluation through in vitro and in vivo models. RESULTS: Chemical fingerprinting using GC and GC-MS analysis of EOCl revealed the presence of 11 compounds, representing 90.29% of the oil, in which terpinolene (52.88%) and α-phellandrene (21.13%) are the major components. In the in vitro testing EOCl inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) in lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in the human keratinocyte cell line (HaCaT). Topical application of EOCl produced anti-inflammatory effects by reducing ear thickness, ear weight and ameliorating the level of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) at protein and mRNA levels as well as regulating the overproduction of oxidative markers and restoring the histopathological damage in a TPA-induced mouse model of inflammation. CONCLUSION: These findings of topical anti-inflammatory properties of EOCl provide a scientific basis for medicinal use of this plant material against inflammatory disorders.
Assuntos
Curcuma/química , Dermatite/tratamento farmacológico , Óleos Voláteis/uso terapêutico , Folhas de Planta/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Camundongos , Óleos Voláteis/farmacologia , Coelhos , Acetato de TetradecanoilforbolRESUMO
Hitherto unreported hybrid nanofillers (CNC:MgO) reinforced chitosan (CTS) based composite (CNC:MgO)/CTS films were synthesized using a solution-casting blend technique and synergistic effect of hybrid nanofiller in terms of properties enhancement were investigated. Optical microscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD) technique, fourier-transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (FESEM) were used to characterize the films. The hybrid nanofiller considerably changed the transparency and color of the CTS films. The tensile strengths of (3 wt%) CNC/CTS, (3 wt%) MgO/CTS, (1:1)(CNC:MgO)/CTS, (1:2)(CNC:MgO)/CTS and (2:1)(CNC:MgO)/CTS films were 27.49 %, 35.60 %, 91.62 %, 38.22 %, and 29.32 % higher than pristine CTS films respectively, while the water vapor permeation were 28.21 %, 30.77 %, 34.62 %, 38.46 %, and 37.44 % lower than pristine CTS film, respectively. Moreover, the CTS composite films exhibited an improvement in overall water barrier properties after incorporating hybrid nanofillers. Our observations suggest that chitosan-based hybrid nanofiller composite films are a good replacement for plastic-based packaging materials within the food industry.
Assuntos
Quitosana , Nanopartículas , Celulose/química , Quitosana/química , Óxido de Magnésio , Nanopartículas/química , Embalagem de Alimentos/métodosRESUMO
We have investigated effect of Moringa oleifera leaf and fruit extracts on markers of oxidative stress, its toxicity evaluation, and correlation with antioxidant properties using in vitro and in vitro assays. The aqueous extract of leaf was able to increase the GSH and reduce MDA level in a concentration-dependent manner. The ethanolic extract of fruit showed highest phenolic content, strong reducing power and free radical scavenging capacity. The antioxidant capacity of ethanolic extract of both fruit and leaf was higher in the in vitro assay compared to aqueous extract which showed higher potential in vivo. Safety evaluation studies showed no toxicity of the extracts up to a dose of 100 mg/kg body weight. Our results support the potent antioxidant activity of aqueous and ethanolic extract of Moringa oleifera which adds one more positive attribute to its known pharmacological importance.
RESUMO
Ellagic acid (EA), a fruit- and vegetable-derived flavonoid, has been reported for multiple pharmacological activities, which encouraged us to examine its useful effect in severe malaria pathogenesis, especially malaria-induced cytokine storms and oxidative stress linked to damage in major organs. Malaria was induced by injecting Plasmodium berghei-infected RBCs intraperitoneally into the mice. EA was given orally (5, 10, and 20 mg/kg) following Peter's 4-day suppression test. EA exhibited the suppression of parasitemia, production of inflammatory cytokine storms and oxidative stress marker level quantified from vital organs significantly and an increase in hemoglobin, blood glucose, and mean survival time compared to the vehicle-treated infected group. EA administration also restored the blood-brain barrier integrity evidenced through Evans blue staining. Furthermore, we demonstrated the protecting effect of EA in LPS-induced inflammatory cytokine storms and oxidative stress in glial cells. The present study conclude that ellagic acid is able to alleviate severe malaria pathogenesis by reducing cytokine storms and oxidative stress-induced by malarial parasites. It also attributed promising antimalarial activity and afforded to improve the blood glucose and hemoglobin levels in treated mice. These research findings suggested the suitability of ellagic acid as a useful bioflavonoid for further study for the management of severe malaria pathogenesis.
RESUMO
Eugenol is a phytochemical present in aromatic plants has generated considerable interest in the pharmaceutical industries mainly in cosmetics. A series of eugenol esters (ST1-ST7) and chloro eugenol (ST8) have been synthesized. The structures of newly synthesized compounds were confirmed by 1H and 13C NMR and mass spectrometry. In an effort to evaluate the pharmacological activity of eugenol derivatives, we explored its anti-inflammatory potential against skin inflammation using in-vitro and in-vivo bioassay. Synthesized derivatives significantly inhibited the production of pro-inflammatory cytokines against LPS-induced inflammation in macrophages. Among all derivatives, ST8 [Chloroeugenol (6-chloro, 2-methoxy-4-(prop-2-en-1-yl)-phenol)] exhibited most potent anti-inflammatory activity without any cytotoxic effect. We have further evaluated the efficacy and safety in in-vivo condition. ST8 exhibited significant anti-inflammatory activity against TPA-induced skin inflammation without any skin irritation effect on experimental animals. These findings suggested that ST8 may be a useful therapeutic candidate for the treatment of skin inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Dermatite/tratamento farmacológico , Eugenol/síntese química , Animais , Anti-Inflamatórios/síntese química , Citocinas/antagonistas & inibidores , Eugenol/análogos & derivados , Eugenol/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Compostos Fitoquímicos/farmacologiaRESUMO
CONTEXT: Due to limited resources and/or affordability by majority of the patients, many centers in low- and middle-income countries are still not able to adapt three-dimensional image-based brachytherapy planning in their routine practice. AIM: The aim of the study was to see the feasibility of using computed tomography (CT)-based plan of the first fraction to treat successive fractions of intracavitary brachytherapy based on the estimation of the physical dosimetric differences between successive applications. MATERIALS AND METHODS: CT image-based brachytherapy plans of 38 patients who received three insertions of intracavitary application with high-dose-rate brachytherapy have been analyzed. Revised plans for the second and third insertions were generated by adapting dwell time and dwell position of the first insertion plan. The dose to point "A" and maximum doses to 2, 1, and 0.1 cc volumes of the rectum and bladder have been used for dosimetric comparison. RESULTS: The statistical differences of mean point "A" doses were observed insignificant except between original and revised plans for the second insertions. The dosimetric differences between consecutive original and revised plans for the bladder and rectum have not shown any significance except minimum dose to 0.1 cc volume of the rectum for the third insertions. CONCLUSIONS: Dosimetric deviation for tumor and organs at risk is within acceptable limit while using CT image-based brachytherapy plan of the first fraction for treating successive fractions.
Assuntos
Braquiterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia Guiada por Imagem , Tomografia Computadorizada por Raios X , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/radioterapia , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Fracionamento da Dose de Radiação , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Órgãos em Risco , Radiometria , Reto/efeitos da radiação , Bexiga Urinária/efeitos da radiaçãoRESUMO
Rutin, a polyphenolic plant flavonoid, is found in citrus fruits, mulberry, cranberries and buckwheat with reported anti-diabetic, anti-fungal, anti-inflammatory and anti-bacterial activity. We appraise the effect of rutin on hydrogen peroxide (H2O2) mediated deregulation of antioxidant enzyme activity, non-enzymatic biomarkers, reactive oxygen species production (in vitro and in vivo) and on echinocyte formation (ex-vivo). In addition to it the interaction studies (in silico) against targeted enzymes and membrane proteins were also performed. A pre-treatment with rutin (16.3⯵M) significantly attenuate the altered level of glutathione, sulfhydryl, malondialdehyde and carbonyl content. The activity and expression of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase were also decreased significantly (pâ¯<â¯0.01) in presence of H2O2, while pre-treatment of rutin ameliorates the effect of H2O2. Furthermore, rutin at higher tested concentration protects the morphology of erythrocytes by decreasing the reactive oxygen species level (pâ¯<â¯0.01) as compared to H2O2 treatment. In silico analysis with selected membrane proteins and enzymes revealed that the rutin did not modulate the structure and function of the preferred proteins. In addition, rutin down regulates the inducible nitric oxide synthase expression and up-regulate the nuclear factor (erythroid-related factor 2) expression. Moreover, the lower mean erythrocyte fragility values of rutin (0.53⯱â¯0.024-0.61⯱â¯0.014) alone or with H2O2 (0.65⯱â¯0.021) indicate the protection and non-toxic behaviour. These finding suggests that rutin; a nutritional compound can reduce oxidative stress induced by H2O2 by increasing the expression of Nrf2 and endogenous antioxidant enzymes.
Assuntos
Simulação por Computador , Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Rutina/farmacologia , Regulação para Cima/efeitos dos fármacos , Animais , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Oxirredução/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Citrus fruit peels are traditionally used in folk medicine for the treatment of skin disorders but it lacks proper pharmacological intervention. Citrus limetta Risso (Rutaceae) is an important commercial fruit crops used by juice processing industries in all continents. Ethnopharmacological validation of an essential oil isolated from its peels may play a key role in converting the fruit waste materials into therapeutic value added products. AIM OF THE STUDY: To evaluate the chemical and pharmacological (in-vitro and in-vivo) profile of essential oil isolated from Citrus limetta peels (Clp-EO) against skin inflammation for its ethnopharmacological validation. MATERIALS AND METHODS: Hydro-distilled essential oil extracted from Citrus limetta peels (Clp-EO) was subjected to gas chromatography (GC) analysis for identification of essential oil constituents and its anti-inflammatory evaluation through in vitro and in vivo models. RESULTS: Chemical fingerprint of Clp-EO revealed the presence of monoterpene hydrocarbon and limonene is the major component. Pre-treatment of Clp-EO to the macrophages was able to inhibit the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) in LPS-induced inflammation as well as the production of reactive oxygen species (ROS) in H2O2-induced oxidative stress. In in-vivo study, topical application of Clp-EO was also able to reduce the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear thickness, ear weight, lipid peroxidation, pro-inflammatory cytokines production and ameliorate the histological damage in the ear tissue. In-vitro and in-vivo toxicity study indicate that it is safe for topical application on skin. CONCLUSION: These findings suggested the preventive potential of Clp-EO for the treatment of inflammation linked skin diseases.
Assuntos
Citrus/química , Inflamação/tratamento farmacológico , Ceratolíticos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Animais , Feminino , Humanos , Ceratolíticos/química , Peroxidação de Lipídeos , Camundongos , Óleos Voláteis/química , Fitoterapia , Óleos de Plantas/química , Coelhos , Testes de Irritação da PeleRESUMO
Malaria the parasitic disease of tropical countries is seeking newer therapeutic strategies owing to the drug resistance to existing drugs. The pathogenesis after infection renders the host to oxidative stress resulting in an altered immune status. Natural products rich in phenols are a source of bio-actives that could have a role in alleviating such condition. The present study reports the phenol rich ethyl acetate extract from the petals of Rosa damascena (RdEa) to be active against Plasmodium falciparum in-vitro and Plasmodium berghei in-vivo. It restores the haemoglobin level while increasing the mean survival time and chemo-suppression in P. berghei infected mice. The HPLC characterised RdEa was found to be rich in Gallic acid and Rutin besides other phenols. RdEa was capable of scavenging the free radicals and modulating the pro-inflammatory mediators (IL6, TNF, IFN and NO) favourably and also restored the architecture of hepatocytes as evidenced through histopathology. The extract was able to arrest the lipopolysaccharide (LPS) induced damage of J774A.1 cells (murine macrophages) and was found to be safe in mice upto 2000 mg/kg body weight.
Assuntos
Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Extratos Vegetais/uso terapêutico , Plasmodium falciparum/efeitos dos fármacos , Rosa/química , Animais , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Malária Falciparum/patologia , Camundongos , Extratos Vegetais/farmacologia , Testes de Toxicidade AgudaRESUMO
In an effort to evaluate novel pharmacological activity of 1-chloro-2-formyl indene and tetralene analogues possessing potential antitubercular and antistaphylococcal agents, we explored its anti-inflammatory potential against lipopolysaccharide(LPS)-induced inflammation using in-vitro and in-vivo bioassay. Synthesized analogues significantly inhibited the production and expression of pro-inflammatory cytokines against LPS-induced inflammation in macrophages isolated from mice. Among all the analogues, TAF-5 (1-Chloro-2-formyl-1-tetralene) exhibited most potent anti-inflammatory activity without any cytotoxic effect. We have further evaluated the therapeutic efficacy and safety of TAF-5 in in-vivo system using LPS-induced sepsis, a systemic inflammation model and acute oral toxicity respectively in mice. Oral administration of TAF-5 inhibited the pro-inflammatory cytokines in serum, attenuated the organs injuries and improved host survival in dose dependent manner. Acute oral toxicity study showed TAF-5 is non-toxic at higher dose in mice. These results suggest the suitability of indene and tetralene analogues as new chemical entities for further investigation towards the management of inflammation related diseases.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Citocinas/imunologia , Indenos/química , Indenos/uso terapêutico , Inflamação/tratamento farmacológico , Sepse/tratamento farmacológico , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Citocinas/sangue , Citocinas/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Indenos/administração & dosagem , Inflamação/sangue , Inflamação/genética , Inflamação/imunologia , Lipopolissacarídeos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Simulação de Acoplamento Molecular , Sepse/sangue , Sepse/genética , Sepse/imunologiaRESUMO
BACKGROUND: Measurement of accurate attenuation of photon flux in tissue is important to obtain reconstructed images using single-photon emission computed tomography (SPECT). Computed tomography (CT) scanner provides attenuation correction data for SPECT as well as anatomic information for diagnostic purposes. Segmentation is a process of dividing an image into regions having similar properties such as gray level, color, texture, brightness, and contrast. Image segmentation is an important tool for evaluation of medical images. X-ray beam used in CT scan is poly-energetic; therefore, we have used a copper filter to remove the low energy X-rays for obtaining correct attenuation factor. Images obtained with and without filters were quantitatively evaluated by segmentation method to avoid human error. MATERIALS AND METHODS: Axial images of AAPM CT phantom were acquired with 3 mm copper filter (low intensity) and without copper filter (high intensity) using low-dose CT (140 kvp and 2.5 mA) of SPECT/CT system (Hawkeye, GE Healthcare). For segmentation Simulated Annealing Based Fuzzy c-means, algorithm is applied. Quantitative measurement of quality is done based on universal image quality index. Further, for the validation of attenuation correction map of filtered CT images, Jaszczak SPECT phantom was filled with 500 MBq of (99m)Tc and SPECT study was acquired. Low dose CT images were acquired for attenuation correction to be used for reconstruction of SPECT images. Another set of CT images were acquired after applying additional 3 mm copper filter. Two sets of axial SPECT images were reconstructed using attenuation map from both the CT images obtained without and with a filter. RESULTS AND CONCLUSIONS: When we applied Simulated Annealing Based Fuzzy c-means segmentation on both the CT images, the CT images with filter shows remarkable improvement and all the six section of the spheres in the Jaszczak SPECT phantom were clearly visualized.
RESUMO
INTRODUCTION: Positron emission tomography has been established as an important imaging modality in the management of patients, especially in oncology. The higher gamma radiation energy of positron-emitting isotopes poses an additional radiation safety problem. Those working with this modality may likely to receive higher whole body doses than those working only in conventional nuclear medicine. The radiation exposure to the personnel occurs in dispensing the dose, administration of activity, patient positioning, and while removing the intravenous (i.v.) cannula. The estimation of radiation dose to Nuclear Medicine Physician (NMP) involved during administration of activity to the patient and technical staff assisting in these procedures in a positron emission tomography/computed tomography (PET/CT) facility was carried out. MATERIALS AND METHODS: An i.v access was secured for the patient by putting the cannula and blood sugar was monitored. The activity was then dispensed and measured in the dose calibrator and administered to the patient by NMP. Personnel doses received by NMP and technical staff were measured using electronic pocket dosimeter. The radiation exposure levels at various working locations were assessed with the help of gamma survey meter. RESULTS AND DISCUSSION: The radiation level at working distance while administering the radioactivity was found to be 106-170 µSv/h with a mean value of 126.5 ± 14.88 µSv/h which was reduced to 4.2-14.2 µSv/h with a mean value of 7.16 ± 2.29 µSv/h with introduction of L-bench for administration of radioactivity. This shows a mean exposure level reduction of 94.45 ± 1.03%. The radiation level at working distance, while removing the i.v. cannula postscanning was found to be 25-70 µSv/h with a mean value of 37.4 ± 13.16 µSv/h which was reduced to 1.0-5.0 µSv/h with a mean value of 2.77 ± 1.3 µSv/h with introduction of L-bench for removal of i.v cannula. This shows a mean exposure level reduction of 92.85 ± 1.78%. CONCLUSION: This study shows that good radiation practices are very helpful in reducing the personnel radiation doses. Use of radiation protection devices such as L-bench reduces exposure significantly. PET/CT staff members must use their personnel monitors diligently and should do so in a consistent manner so that comparisons of their doses are meaningful from one monitoring period to the next.
RESUMO
BACKGROUND: Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases risk of having a range of gastrointestinal problems. Therefore, new anti-inflammatory, analgesic, antipyretic drugs having lesser side effects are being searched all overthe world as alternatives to NSAIDs. AIMS: To evaluate the anti-inflammatory, analgesic and antipyretic profile of Ocimum sanctum root extracts. MATERIALS AND METHODS: Anti-inflammatory profile of hexane (STH), chloroform (STC), ethyl acetate (STE), butanol (STB) and water (STW) extracts of OS was carried out by using carrageenan induced paw edema. STE a most active extract was further validated in dose dependent manner for anti-inflammatory, analgesic and antipyretic activity as well as oral toxicity profile in small laboratory animals. Identification of bioactives flux and chemical signature of most active fraction STE was developed by using the high-performance liquid chromatography fingerprinting. RESULTS: An ethyl acetate fraction (STE) exhibit most potent anti-inflammatory activity followed by STB, STW, STC and STH. Dose response study of STE showed anti-inflammatory, analgesic and anti-pyretic potential in dose-dependent manner without any toxic effect at dose 2000 mg/kg. Chemical fingerprint revealed the presence of flavanoids. CONCLUSIONS: The present research revealed that STE possess anti-inflammatory, analgesic and anti-pyretic properties. However, future research is advocated to evaluate the pharmacological properties of isolated bioactive compounds.
RESUMO
Liquid-liquid partitioning of Ricinus communis root methanol extract resulted in enrichment of compounds. Purification of the n-hexane fraction led to the isolation and characterisation of two triterpenes: one known compound lupeol (1) and a new diketone pentacyclic triterpene named as erandone (urs-6-ene-3,16-dione) (2), from the plant. Their structures were determined by various spectroscopic techniques. Crude methanolic, enriched n-hexane fraction and isolates at doses 100 mg/kg p.o. exhibited significant (P < 0.001) anti-inflammatory activity in carrageenan-induced hind paw oedema model.