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1.
Dig Liver Dis ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38556409

RESUMO

BACKGROUND: Long-intergenic non-protein coding gene 01140 (LINC01140) a long non-coding RNA is highly expressed in various cancers. However, its biological functions in gastric cancer progression is still unknown. METHOD: To elucidate LINC01140 function, 70 GC tumor samples and 30 normal gastric tissues were collected. LINC01140 expression level were determined by qRT-PCR analysis and correlated with different clinico-pathological parameters. Then we tried to see the impact of LINC01140 on gastric cell line aggressiveness by knocking down the target gene and performing cell viability assay, migration assay and invasive capacity of the cell lines along with immunoblotting to check several protein levels. RESULT: LINC01140 RNA is found to be positively correlated with FGF9 and significantly up regulated in GC tissues. LINC01140 knockdown inhibited the viability, migratory capacity and invasive capacity of AGS cells. LINC01140 targets miR-140-5p, while miR-140-5p targeted FGF9 to form lncRNA-miRNA-mRNA axis. The affect of miR-140-5p inhibition on gastric cancer cell aggressiveness were opposite to those of LINC01140 or FGF9 knockdown. Additionally, inhibition partially reversed the effects of LINC01140 knockdown on FGF9 protein levels, gastric cancer cell phenotypes. CONCLUSION: LINC01140, miR-140-5p and FGF9 form a lncRNA-miRNA-mRNA axis that modulates the gastric cancer phenotypes and in turn affects gastric cancer cell aggressiveness.

2.
South Asian J Cancer ; 12(2): 135-140, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37969677

RESUMO

Manas Kumar BeheraBackground and Aims Gastric cancer is the third most common cause of cancer-related mortality worldwide after lungs and colorectum. Although controversial, Her2neu overexpression by immunohistochemistry is usually associated with poor prognosis in patients with carcinoma stomach. We conducted a prospective study to evaluate the prognostic role of Her2neu and its correlation with clinical, pathologic type, and stage of the disease. Methods A prospective study was performed on paraffin blocks of 111 gastric cancer specimens (88 patients were biopsy specimens and 23 were gastrectomy specimens). The paraffin blocks were processed for Her2neu receptor immunohistochemical staining and fluorescence in situ hybridization, and scoring was done. Results Her2neu overexpression was detected in 30 out of 111 (27%) patients. The mean age was 57.68 ± 12.82 years, with males constituting two-thirds of total patients. Tobacco addiction was found in 44% of the patients and smoking in 33% of the patients. Her2neu expression was similar in Lauren's intestinal and diffuse histologic type; however, proximal gastric tumors overexpressed Her2neu as compared with distal tumors. Her2neu 2+ or 3 + (odds ratio: 2.52, 95% CI: 1.61-3.95, p = 0.001) was the only independent predictor of survival in gastric cancer patients. Kaplan-Meir survival analysis showed that the survival of gastric cancer patients with Her2neu overexpression (Her2neu 2+ or 3 + ) was significantly lower than that of those with Her2neu nonexpression ( p = 0.001). Conclusion Her2neu positivity was a significant predictor of mortality in patients with carcinoma stomach, and Her2neu overexpression was associated with a lower overall survival rate compared with Her2neu nonexpression.

3.
J Clin Transl Res ; 9(1): 26-32, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36687298

RESUMO

Background: Isolated ileo-cecal region (ICR) ulcers may represent underlying Crohn's disease (CD), intestinal tuberculosis (ITB), bacterial infections (including typhoid), amoebiasis, eosinophilic enteritis, drug-induced sequelae, or neoplasm. Overlapping morphological and microscopic characteristics of many of these diseases make it challenging to unequivocally confirm a diagnosis. Aims: The aim of the study was to investigate the etiology and clinical outcomes of isolated ileo-cecal ulcers discovered during an ileocolonoscopy in patients with gastrointestinal symptoms. Methods: Patients with isolated ileo-cecal ulcers and symptoms within the age range of 10 - 80 years were included in the study (N = 100). Patients not giving consent (assent in case of a minor), with a prior diagnosis of tuberculosis or inflammatory bowel disease, with incomplete colonoscopy and associated colonic lesions other than ICR were excluded from the study. Demographics, clinical information, and relevant biochemical and serological tests were recorded. During the colonoscopy, multiple biopsies were taken from the ileo-cecal ulcers for histopathological examination. Repeat ileocolonoscopy was performed as needed in consenting patients. Results: The mean age and mean duration of symptoms were 36.0 ± 15.6 years and 18.8 ± 21.6 months, respectively. The majority of the patients presented with abdominal pain (59%), followed by diarrhea (47%), weight loss (20%), gastrointestinal bleeding (15%), and fever (11%). A history of taking nonsteroidal anti-inflammatory drugs was present in only 5% of the patients. Mean hemoglobin, C-reactive protein, and albumin levels were 11.6 ± 2.8 g/dL, 6.9 ± 9.5 mg/L, and 3.7 ± 0.8 g/dL, respectively. Based on clinical, colonoscopic, and histopathological findings, initial treatment was symptomatic/antibiotics in 55%, anti-tubercular treatment in 21%, 5-aminosalicylic acid/steroids for CD in 13%, oral budesonide in 10% of patients, and one patient was referred for management of malignancy. Final diagnoses after 8 - 24 weeks of follow-up were non-specific ileitis/colitis (45%), CD (20%), ITB (18%), infective (7%), eosinophilic ileitis/colitis (6%), non-steroidal anti-inflammatory drug-induced (2%), and amoebic and malignant in 1% of patients each. Conclusions: The majority of patients with ileo-cecal ulcers have specific etiologies. Non-specific ulcers at the ICR can be managed symptomatically; however, close follow-up is necessary as sometimes the ulcers may harbor an underlying specific disease. Relevance for Patients: Isolated ileo-cecal ulcers are common findings during colonoscopy in both symptomatic and asymptomatic patients. The majority of these ulcers harbor underlying significant diseases that can cause morbidity and mortality if left undiagnosed and untreated. Reaching a specific diagnosis in such cases is not straightforward, and patients are often subjected to repeat examinations.

4.
J Clin Transl Res ; 8(3): 176-180, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35813897

RESUMO

Background: Acute pancreatitis (AP) continues to be one of the common abdominal emergencies encountered in tertiary care hospitals. The majority of AP is caused by gall stones and alcohol. Hypercalcemia though uncommon has been reported to cause AP, recurrent AP, and chronic pancreatitis (CP). Aim: The aim of this study was to describe hypercalcemia-induced AP in different settings. Materials and Methods: In total 100 patients with AP, admitted from January 2021 to December 2021 at our center, etiologies were biliary (36%), alcohol (19%), idiopathic (21%), alcohol plus Biliary (5%), post-endoscopic retrograde cholangiopancreaticography (7%), drug-induced (6%), hypercalcemia (3%), and dengue infection (3%). Overall mortality was 11%. Results: In three patients with hypercalcemia-induced pancreatitis, causes of hypercalcemia were multiple myeloma, parathyroid adenoma leading to hyperparathyroidism, and hypervitaminosis D in association with hyperthyroidism. Conclusion: Hypercalcemia-induced AP is not a rare phenomenon and should be actively investigated to prevent further attacks of AP and progression to CP. Relevance for Patients: Hypercalcemia is a potentially treatable cause of AP and its identification will not only help to treat and prevent further episodes of pancreatitis but also to manage underlying diseases leading to hypercalcemia.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34023500

RESUMO

Gallbladder cancer (GBC) is an aggressive malignancy of gastrointestinal tract. Due to uncontrolled growth, GBC cells rapidly synthesize biomolecules including lipids. The lipids are integral component of cell membrane with a wide range of cellular functions. In this study, we measured the clinicopathological features in 40 cases of histologically confirmed GBC and 16 cases of chronic cholecystitis (CC). The female to male ratio in the GBC and CC groups were 3.44:1 and 2.2:1, respectively. The GBC patients exhibited well to poorly differentiated tumor. In the CC group, all patients showed cholecystitis with no evidence of dysplasia or malignancy. The majority of GBC and CC patients reported pain. Using 1H NMR spectroscopy, we observed 4-folds increase in the level of choline containing phospholipids (CCPLs) in the gallbladder of GBC patients as compared to CC patients. Other lipid metabolites such as cholesterol ester, C18-cholesterol and saturated fatty acids were insignificantly changed between GBC and CC patients. Moreover, the level of CCPLs in the GBC patients with BMI <25 kg/m2 was significantly higher as compared to CC patients. Further, a significant increase in the CCPLs level was observed in GBC female patients in comparison to CC patients. From the computational analyses, we observed that the genes involved in the biosynthesis of phosphatidylcholine (PtdCho) indirectly interact with the RELA, which encodes the NF-κB p65 subunit. The genes involved in the PtdCho biosynthesis were also correlated with the overall and disease-free survival of cholangiocarcinoma patients. The study opens new window for exploring the diagnostic and therapeutic potential of CCPLs in GBC patients.


Assuntos
Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/metabolismo , Núcleo Celular/metabolismo , NF-kappa B/metabolismo , Fosfatidilcolinas/biossíntese , Espectroscopia de Prótons por Ressonância Magnética , Adulto , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Indian J Gastroenterol ; 40(1): 22-29, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33548019

RESUMO

BACKGROUND: Around 10% to 30% patients with acute pancreatitis (AP) do not have a cause after the routine investigations, and are considered as having idiopathic acute pancreatitis (IAP). Establishing the etiology in such patients will prevent recurrences and evolution to chronic pancreatitis. Endoscopic ultrasonography (EUS) and magnetic resonance cholangiopancreatography (MRCP) characteristically are used to diagnose IAP when routine methods fail, but their exact role is not determined. METHODS: This prospective study was undertaken in a tertiary care hospital, in which patients admitted initially with diagnosis of IAP were evaluated. These patients underwent MRCP and EUS at least 4 weeks after an attack of AP. The results of EUS and MRCP were compared and analyzed with various clinical variables using suitable statistical tests. RESULTS: A total of 31 patients with IAP were included. EUS and/or MRCP was able to establish at least one etiology in 17 patients (54.8%). The diagnoses revealed were gallbladder (GB) microlithiasis, GB sludge, choledocholithiasis, pancreatobiliary ductal anomalies, pancreatic adenocarcinoma, and intraductal papillary mucinous neoplasm. Comparing the diagnostic accuracy of both the modalities, EUS (14/31) was able to diagnose more cases than MRCP (8/31). The diagnostic capability of EUS was lower in patients who had a cholecystectomy (12.5% vs. 56.5%; p = 0.03). CONCLUSIONS: EUS and MRCP are useful modalities in the etiological diagnosis of IAP and should be used in conjunction. EUS is better for establishing a possible biliary etiology and MRCP for an anatomical alteration in pancreatobiliary ducts.


Assuntos
Doenças Biliares/diagnóstico por imagem , Colangiopancreatografia por Ressonância Magnética/métodos , Endossonografia/métodos , Pancreatopatias/diagnóstico por imagem , Pancreatite/diagnóstico , Adulto , Doenças Biliares/complicações , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Pâncreas/diagnóstico por imagem , Pancreatopatias/complicações , Pancreatite/etiologia , Estudos Prospectivos , Reprodutibilidade dos Testes
7.
Indian J Gastroenterol ; 38(5): 411-440, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31802441

RESUMO

The Indian Society of Gastroenterology developed this evidence-based practice guideline for management of gastroesophageal reflux disease (GERD) in adults. A modified Delphi process was used to develop this consensus containing 58 statements, which were generated by electronic voting iteration as well as face-to-face meeting and review of the supporting literature primarily from India. These statements include 10 on epidemiology, 8 on clinical presentation, 10 on investigations, 23 on treatment (including medical, endoscopic, and surgical modalities), and 7 on complications of GERD. When the proportion of those who voted either to accept completely or with minor reservation was 80% or higher, the statement was regarded as accepted. The prevalence of GERD in India ranges from 7.6% to 30%, being < 10% in most population studies, and higher in cohort studies. The dietary factors associated with GERD include use of spices and non-vegetarian food. Helicobacter pylori is thought to have a negative relation with GERD; H. pylori negative patients have higher grade of symptoms of GERD and esophagitis. Less than 10% of GERD patients in India have erosive esophagitis. In patients with occasional or mild symptoms, antacids and histamine H2 receptor blockers (H2RAs) may be used, and proton pump inhibitors (PPI) should be used in patients with frequent or severe symptoms. Prokinetics have limited proven role in management of GERD.


Assuntos
Gastroenterologia/normas , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/terapia , Guias de Prática Clínica como Assunto , Adulto , Antiácidos/uso terapêutico , Consenso , Dieta/efeitos adversos , Esofagite/epidemiologia , Esofagite/etiologia , Feminino , Refluxo Gastroesofágico/etiologia , Infecções por Helicobacter/complicações , Helicobacter pylori , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Índia/epidemiologia , Masculino , Prevalência , Inibidores da Bomba de Prótons/uso terapêutico , Sociedades Médicas
8.
Hepatobiliary Pancreat Dis Int ; 18(2): 188-193, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30573300

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) protocol is a multimodal, multidisciplinary and evidence-based approach to reduce surgical stress and enhance recovery in the postoperative period. This study aimed to analyze the outcome of ERAS protocol in patients after pancreaticoduodenectomy (PD). METHODS: A total of 50 consecutive patients with pancreatic/periampullary cancer who underwent PD between January 2016 to August 2017 were included in the study. As per the institute ERAS protocol, nasogastric tube (NGT) was removed on postoperative day (POD) 1 if output was less than 200 mL and oral sips were allowed; oral liquids were allowed on POD2; semisolid diet by POD3; abdominal drain was removed on POD 4 if output was less than 100 mL with no evidence of postoperative pancreatic fistula (POPF); normal diet was allowed on POD5. Discharge criteria on POD6 were afebrile, tolerating oral normal diet, pain free and no surgery related complications (defined as per the ISGPS definitions). RESULTS: NGT was removed on POD1 in 45 (90%) patients, abdominal drain removed by POD4 in 41 (82%) and 43 (86%) patients were discharged on POD6. There was no 30-day postoperative mortality. Three (6%) patients had delayed gastric emptying (DGE). None had postoperative hemorrhage and POPF. Readmission rate was 8%. A significant relation was found between the length of hospital stay (LOS) with age (P < 0.05) and a marginal relation between LOS and postoperative albumin (P = 0.05). CONCLUSIONS: ERAS protocol can be safely followed in the perioperative care of patients who undergo PD. Early removal of NGT and allowing oral diet restore bowel function early. ERAS decreases the LOS and postoperative complications.


Assuntos
Deambulação Precoce/métodos , Tempo de Internação , Fístula Pancreática/prevenção & controle , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Fatores Etários , Idoso , Anastomose Cirúrgica/métodos , Distribuição de Qui-Quadrado , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/reabilitação , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/reabilitação , Nutrição Parenteral/métodos , Alta do Paciente/estatística & dados numéricos , Segurança do Paciente/estatística & dados numéricos , Cuidados Pós-Operatórios/métodos , Prognóstico , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais
9.
J Clin Diagn Res ; 11(5): EC43-EC45, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28658772

RESUMO

INTRODUCTION: After the recent approval of Trastuzumab (anti-HER2 antibody) for the treatment of HER2 overexpressed Gastric Adenocarcinoma (GA), importance of HER2 testing is increasingly recognized. However, there is paucity of studies for HER2 overexpression in the Indian patients of GA. Similarly, study of p53 expression in the Indian patients of GA is infrequent. AIM: To study immunohistochemical expression of HER2 and p53 in GA biopsy samples. MATERIALS AND METHODS: This was a cross-sectional observational study. The expression of HER2 and p53 by immunohistochemistry were analyzed in 50 cases of GA. The HER2 expression was scored as negative (0 and 1+), equivocal (2+), and overexpression (3+). The p53 expression was quantified as negative (0-9% tumour cells) and positive (≥10% tumour cells). The intensity of p53 expression was assessed as strong and weak. RESULTS: Mean age of the patients was 56.8±14.8 years. Male:female ratio was 2:1. Histological types of adenocarcinoma were intestinal (68%), diffuse (28%), and indeterminate (4%). HER2 overexpression and equivocal results were present in 10% cases, each. Overall, a positive expression of p53 was seen in 72% (strong and weak intensities: 66.7% and 33.3% cases, respectively). CONCLUSION: As compared to HER2 overexpression, a higher incidence of p53 expression was seen (10% vs.72%) in GA.

10.
J Gastrointest Surg ; 20(6): 1270-1, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26768007

RESUMO

A 3-year-old girl presented with multiple episodes of vomiting, fever, and hematemesis for the past 2 months. Except for hemoglobin, her rests of the laboratory tests were unremarkable. Her barium X-ray showed absence of the duodenal bulb and the C-loop. Her endoscopy showed deformed stomach with multiple ulcers and diverticuli. The gastric outlet was not visualized. Distal gastrectomy with gastro-duodenal anastomosis was performed. Histopathological findings revealed transmural dense infiltrates of eosinophils, consistent with eosinophilic gastritis.


Assuntos
Enterite/diagnóstico , Eosinofilia/diagnóstico , Obstrução da Saída Gástrica/etiologia , Gastrite/diagnóstico , Pré-Escolar , Enterite/complicações , Eosinofilia/complicações , Feminino , Obstrução da Saída Gástrica/diagnóstico , Gastrite/complicações , Hematemese/etiologia , Humanos
11.
Indian J Gastroenterol ; 34(4): 286-91, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26243587

RESUMO

BACKGROUND AND AIMS: Limited data is available from India on outcome and efficacy of tenofovir and entecavir in hepatitis B virus (HBV)-related cirrhosis when used for prolonged time. We report the long-term efficacy and outcome of these antiviral drugs in patients with chronic HBV infection, with compensated or decompensated cirrhosis. METHODS: We retrospectively analyzed laboratory and clinical data of 400 HBV-related cirrhotic patients without access to liver transplantation, who were treated with tenofovir/entecavir therapy, from January 2007 to January 2014. Two hundred and ten (52.5 %) patients had at least one of the components of decompensation at baseline. Two hundred and twenty (55 %) and 180 (45 %) patients were initiated tenofovir and entecavir, respectively. Follow up period was 45 (12-68) months for tenofovir and 36 (11-60) months for entecavir. RESULTS: At the end of 1 year, levels of HBV DNA <20 IU/mL were achieved in 91.8 % and 88.8 % of patients, and alanine aminotransferase normalized in 54.5 % and 55.5 % of patients who received tenofovir and entecavir, respectively. At the last visit, Child-Turcotte-Pugh scores improved among 29.5 % of patients who received tenofovir, 25 % of those who received entecavir, and remained stable in 61.9 % and 65 % patients, respectively, in both groups. The 5-year cumulative rate of liver decompensation, hepatocellular carcinoma, and cirrhosis-related complications were 3.1 %, 1.9 %, and 2.1 % with an annual incidence of 0.8 %, 0.3 %, and 0.5 % per person-year, respectively. CONCLUSION: Tenofovir and entecavir were effective and potent drugs for prolonged treatment of HBV cirrhosis and improved the overall clinical course.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Tenofovir/uso terapêutico , Adulto , Idoso , Antivirais/administração & dosagem , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/prevenção & controle , Feminino , Seguimentos , Guanina/administração & dosagem , Guanina/uso terapêutico , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tenofovir/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
World J Gastroenterol ; 19(7): 1056-67, 2013 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-23466902

RESUMO

AIM: To characterize oxidase- and urease-producing bacterial isolates, grown aerobically, that originated from antral biopsies of patients suffering from acid peptic diseases. METHODS: A total of 258 antral biopsy specimens were subjected to isolation of bacteria followed by tests for oxidase and urease production, acid tolerance and aerobic growth. The selected isolates were further characterized by molecular techniques viz. amplifications for 16S rRNA using universal eubacterial and HSP60 gene specific primers. The amplicons were subjected to restriction analysis and partial sequencing. A phylogenetic tree was generated using unweighted pair group method with arithmetic mean (UPGMA) from evolutionary distance computed with bootstrap test of phylogeny. Assessment of acidity tolerance of bacteria isolated from antrum was performed using hydrochloric acid from 10(-7) mol/L to 10(-1) mol/L. RESULTS: Of the 258 antral biopsy specimens collected from patients, 179 (69.4%) were positive for urease production by rapid urease test and 31% (80/258) yielded typical Helicobacter pylori (H. pylori) after 5-7 d of incubation under a microaerophilic environment. A total of 240 (93%) antral biopsies yielded homogeneous semi-translucent and small colonies after overnight incubation. The partial 16S rRNA sequences revealed that the isolates had 99% similarity with Pseudomonas species. A phylogenetic tree on the basis of 16S rRNA sequences denoted that JQ927226 and JQ927227 were likely to be related to Pseudomonas fluorescens (P. fluorescens). On the basis of HSP60 sequences applied to the UPGMA phylogenetic tree, it was observed that isolated strains in an aerobic environment were likely to be P. fluorescens, and HSP60 sequences had more discriminatory potential rather than 16S rRNA sequences. Interestingly, this bacterium was acid tolerant for hours at low pH. Further, a total of 250 (96.9%) genomic DNA samples of 258 biopsy specimens and DNA from 240 bacterial isolates were positive for the 613 bp amplicons by targeting P. fluorescens-specific conserved putative outer membrane protein gene sequences. CONCLUSION: This study indicates that bacterial isolates from antral biopsies grown aerobically were P. fluorescens, and thus acid-tolerant bacteria other than H. pylori can also colonize the stomach and may be implicated in pathogenesis/protection.


Assuntos
Pseudomonas fluorescens/isolamento & purificação , Antro Pilórico/microbiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biópsia , Chaperonina 60/genética , Humanos , Concentração de Íons de Hidrogênio , Viabilidade Microbiana , Oxirredutases/metabolismo , Filogenia , Pseudomonas fluorescens/classificação , Pseudomonas fluorescens/genética , Pseudomonas fluorescens/crescimento & desenvolvimento , Pseudomonas fluorescens/metabolismo , RNA Bacteriano/isolamento & purificação , RNA Ribossômico 16S/isolamento & purificação , Ribotipagem , Urease/metabolismo
15.
Integr Cancer Ther ; 12(3): 236-47, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22914874

RESUMO

PURPOSE: The study was designed to screen Sphaeranthus indicus, Ganoderma lucidum, and Urtica dioica for their anticancer activity against human cancer cell lines. Phytochemical screening of active extracts was also planned. METHODS: Petroleum ether, ethanolic, and aqueous extracts of S indicus Linn, G lucidum P Karst, and U dioica Linn were subjected to cytotoxicity studies using 7 different cancer cell lines. Potent cytotoxicity was noted in petroleum ether extract of S indicus (SIP), which inhibited proliferation of various cancer cell lines. Growth inhibition was determined by sulforhodamine B assay. Two biochemical markers, namely ß-sitosterol and 7-hydroxyfrullanolide were isolated and characterized using high-performance thin layer chromatography, melting point, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and mass analysis. Cytotoxicity of isolated ß-sitosterol and 7-hydroxyfrullanolide were also determined. The IC(50) of SIP was calculated in the HL-60 cells and was found to be 53 µg/mL. Furthermore, SIP induced apoptosis in human leukemia HL-60 cells as measured by several biological end points. Cell cycle analysis and change in mitochondrial membrane potential was quantified by flow cytometry. Subsequently, using annexin V/PI assay, proportion of cells actively undergoing apoptosis was determined. Changes in DNA were observed by DNA ladder assay. RESULTS: SIP induced apoptotic bodies formation, induced DNA laddering, enhanced annexin-V-FITC binding of the cells, increased sub-G(0) DNA fraction, and induced loss of mitochondrial membrane potential (ΔΨm) in HL-60 cells. SIP also elevated the caspase 3 and caspase 9 levels in the HL-60 cells, which clearly indicates the involvement of the intrinsic proteins in inducing apoptosis. DISCUSSION: All the above parameters revealed that SIP induced apoptosis through the mitochondrial-dependent pathway in HL-60 cells. The criterion for anticancer activity in cytotoxicity assay was ≥70% growth inhibition at 100 µg/mL against at least 4 cell lines. As G lucidum and U dioica did not exhibit appreciable inhibitory activity against human cancer cell lines (less than 50%), they were not included in the study thereafter. The results established that SIP has apoptosis-inducing effect against HL-60 cells in vitro and is a promising candidate for further anticancer study. ß-Sitosterol and 7-hydroxyfrullanolide can be considered to be potent anticancer compounds isolated from SIP on the basis of present studies.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Asteraceae/química , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Anexina A5/metabolismo , Antineoplásicos Fitogênicos/química , Caspase 3/metabolismo , Caspase 9/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA/metabolismo , Células HL-60 , Humanos , Potencial da Membrana Mitocondrial , Mitocôndrias/metabolismo , Extratos Vegetais/química , Reishi/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sitosteroides/química , Sitosteroides/farmacologia , Urtica dioica/química
16.
Pharm Dev Technol ; 18(3): 645-52, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22380019

RESUMO

Goserelin acetate (Gos) is a luteinizing hormone-releasing hormone agonist, used in treatment of prostate cancer in which desired concentration of Gos in blood is maintained for longer duration. The aim of this study is to improve the efficacy of Gos targeted at the site of action and eliminate the need for frequent administration. Gos-encapsulated nanoparticles were fabricated by double emulsification process. The physicochemical traits of the nanoparticles including morphology, particle size, zeta-potential, entrapment efficiency, and in-vitro release profile were studied. The in-vitro cytotoxicity of the blank nanoparticles and Gos-loaded nanoparticles were also evaluated on LNCaP cell line by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Blank methoxy PEG-poly(ε-caprolactone) (mPEG-PCL) nanoparticles exhibited low cytotoxicity, which increased with increase in concentration of Gos-loaded nanoparticles. Serum Gos and testosterone levels were analyzed after subcutaneous administration in Wistar rats. In-vivo study showed that a sustained serum level of Gos successfully suppressed the plasma testosterone concentration to castration level. So, it can be concluded that mPEG-PCL nanoparticles might prove to be useful for site specific and sustain protein delivery.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Hormônio Liberador de Gonadotropina/análogos & derivados , Gosserrelina/administração & dosagem , Nanopartículas/administração & dosagem , Neoplasias da Próstata , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Gosserrelina/química , Humanos , Masculino , Nanopartículas/química , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Ratos , Ratos Wistar
17.
J Ethnopharmacol ; 138(2): 286-313, 2011 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-21982793

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus amarus Schum. & Thonn. belongs to the family Euphorbiaceae is a small herb well known for its medicinal properties and widely used worldwide. P. amarus is an important plant of Indian Ayurvedic system of medicine which is used in the problems of stomach, genitourinary system, liver, kidney and spleen. It is bitter, astringent, stomachic, diuretic, febrifuge and antiseptic. The whole plant is used in gonorrhea, menorrhagia and other genital affections. It is useful in gastropathy, diarrhoea, dysentery, intermittent fevers, ophthalmopathy, scabies, ulcers and wounds. MATERIALS AND METHODS: The present review covers a literature across from 1980 to 2011. Some information collected from traditional Ayurvedic texts and published literature on ethanomedicinal uses of Phyllanthus amarus in different countries worldwide. RESULTS: Phytochemical studies have shown the presence of many valuable compounds such as lignans, flavonoids, hydrolysable tannins (ellagitannins), polyphenols, triterpenes, sterols and alkaloids. The extracts and the compounds isolated from P. amarus show a wide spectrum of pharmacological activities including antiviral, antibacterial, antiplasmodial, anti-inflammatory, antimalarial, antimicrobial, anticancer, antidiabetic, hypolipidemic, antioxidant, hepatoprotective nephroprotective and diurectic properties. CONCLUSION: The present review summarizes information concerning the morphology, ecology, ethnopharmacology, phytochemistry, biological activities, clinical applications and toxicological reports of P. amarus. This review aims at gathering the research work undertaken till date on this plant in order to provide sufficient baseline information for future works and commercial exploitation.


Assuntos
Ayurveda , Phyllanthus/química , Humanos
18.
Phytother Res ; 25(12): 1839-48, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21503998

RESUMO

The present study reports the attenuating effect of Sphaeranthus indicus extracts (SI) on prostatic hyperplasia induced by testosterone in albino rats. In vitro studies were conducted to assess the 5α-reductase inhibitory potential of the petroleum ether, ethanolic and aqueous extracts of SI. A biochemical marker, ß-sitosterol, was isolated and extracts were characterized utilizing HPTLC. Testosterone (3 mg/kg s.c.) was administered to the rats along with the test extracts and isolated ß-sitosterol for a period of 28 days. The weight of the rats, the urine output, serum testosterone concentrations and prostate-specific antigen (PSA) levels were recorded. The prostate/body weight ratio (P/BW) was calculated and histological studies were performed to observe the changes in the histoarchitecture of the prostate. Finasteride was used as a positive control (1 mg/kg p.o.). Sphaeranthus indicus extracts attenuated the increase in the P/BW ratio induced by testosterone in the treated groups. The petroleum ether extract exhibited the best activity, although the ethanol and aqueous extracts also exhibited significant activity. Urine output was also improved significantly, demonstrating the clinical implications of the study. Histological studies, testosterone levels which were measured weekly and PSA levels measured at the end of the study also support claims for the potential use of Sphaeranthus indicus in the treatment of prostatic hyperplasia.


Assuntos
Asteraceae/química , Extratos Vegetais/farmacologia , Hiperplasia Prostática/tratamento farmacológico , Testosterona/efeitos adversos , Animais , Peso Corporal , Flores/química , Masculino , Tamanho do Órgão , Extratos Vegetais/química , Próstata/patologia , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Testosterona/sangue
19.
Pharm Biol ; 48(11): 1247-54, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20843161

RESUMO

CONTEXT: Anacyclus pyrethrum DC (Compositae) roots, commonly known as Pellitory root and locally as akarkara, are widely recognized in the Indian traditional systems of medicine, Ayurveda, as a 'rasayana', i.e. a plant with immunomodulatory properties. OBJECTIVE: Evaluation of A. pyrethrum extract for its effect on normal and chemically suppressed immune systems in vivo. MATERIALS: Petroleum ether extract (PEE) of roots was tested at 50 and 100 mg/kg dose. The effect of both doses on total and differential leukocyte count, cyclophosphamide-induced immunosuppression, survival rate against Candida albicans infection, delayed type hypersensitivity reaction, percentage neutrophil adhesion, and phagocytic activity were tested. RESULTS: The PEE-treated rats were able to overcome cyclophosphamide-induced myelo-suppression as evidenced by the normalization of blood parameters. Survival rate of albino rats was improved in Candida albicans-infected animals by treatment with the extract (p <0.05). An increase in delayed type hypersensitivity response (DTH), percentage neutrophil adhesion, and in vivo phagocytosis by carbon clearance method was observed after treatment. Extract administration also increased the HA titer value and IgG antibodies. DISCUSSION: Immunostimulant activity increased two-fold upon doubling the dosage of extract administered. While a significant (p <0.05) improvement was observed in the humoral component, a highly significant (p <0.01) effect was observed in the cellular components of the immunity evaluated. The results thus provide a basis for the use of A. pyrethrum as an adaptogen and immunomodulator in the Ayurvedic system of medicine.


Assuntos
Adjuvantes Imunológicos/farmacologia , Asteraceae/química , Fatores Imunológicos/farmacologia , Extratos Vegetais/farmacologia , Alcanos , Animais , Candidíase/tratamento farmacológico , Candidíase/imunologia , Adesão Celular/efeitos dos fármacos , Ciclofosfamida/toxicidade , Eritrócitos/imunologia , Feminino , Hematínicos/farmacologia , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Tardia/imunologia , Imunoglobulina G/sangue , Terapia de Imunossupressão , Masculino , Ayurveda , Neutrófilos/efeitos dos fármacos , Neutrófilos/fisiologia , Fagocitose/efeitos dos fármacos , Raízes de Plantas/química , Ratos , Ratos Wistar , Ovinos
20.
Zhong Xi Yi Jie He Xue Bao ; 8(8): 767-73, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20727332

RESUMO

OBJECTIVE: The roots of Anacyclus pyrethrum DC. (Compositae) are employed in Ayurvedic system of medicine as "Vajikaran Rasayana"--a category of drugs for vitality and virility. They are believed to have aphrodisiac action. The present investigation was undertaken to evaluate their effects on sexual behavior in male rats. METHODS: Thirty-two male Wistar rats were divided into control group, testosterone group, low-dose (50 mg/kg) petroleum ether extract (PEE) group and high-dose (100 mg/kg) PEE group. PEE obtained from the roots of Anacyclus pyrethrum was administered orally to albino rats once daily, and 0.5 mg/kg (body weight) of testosterone was given intramuscularly twice weekly and served as positive control. The course of treatment was 28 days. The effects of PEE and testosterone on changes in body and accessory sexual organ weights, sexual behavior, penile erection and sexual performance were studied before treatment, after 15 and 28 days of treatment and 7 and 15 days after treatment. RESULTS: After 28 days of treatment, PEE and testosterone had a marked influence on body and accessory sexual organ weights as compared with arachis oil. The treated male rats were more receptive and oriented towards female rats and increased precopulatory activities like licking and sniffing of female anogenital were observed. The penile erection index was significantly increased with reduction in mount latency and intromission latency period. There were four-fold increase in mount and three-fold increase in intromission frequency in treated rats reflecting improved sexual performance. The behavioral and sexual parameters were also observed after a lapse of 7 and 15 days of discontinuance of drug treatment. CONCLUSION: Unlike testosterone, the PEE of Anacyclus pyrethrum shows efficacy in rats tested after the lapse of 7 and 15 days of discontinuation of treatment. This suggests that the drug has prolonged effect and capacitate the treated rats for improved sexual potential.


Assuntos
Afrodisíacos/farmacologia , Asteraceae/química , Petróleo , Extratos Vegetais/farmacologia , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Masculino , Ayurveda , Ereção Peniana/efeitos dos fármacos , Raízes de Plantas/química , Ratos , Ratos Wistar
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