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1.
Indian J Otolaryngol Head Neck Surg ; 71(Suppl 2): 1320-1326, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31750172

RESUMEN

Tympanoplasty which is the repair of the tympanic membrane using temporalis fascia, has been done worldwide and has stood the test of time. However in cases of reperforation or large/subtotal perforations, we are often left in need of some sturdy material for grafting. To compare the graft uptake and hearing improvement in patients undergoing type I tympanoplasty using temporalis fascia alone and temporalis fascia along with conchal cartilage. The current research is a prospective study of 60 patients with chronic suppurative otitis media (Tubo tympanic type), undergoing type I tympanoplasty, using temporalis fascia alone and temporalis fascia along with conchal cartilage. The graft uptake and hearing improvement was much better using temporalis fascia along with conchal cartilage graft as compared to cartilage alone. The use of temporalis fascia along with conchal cartilage graft is beneficial for patients with chronic suppurative otitis media (tubotympanic type) undergoing type I tympanoplasty than using temporalis fascia alone.

2.
Indian J Otolaryngol Head Neck Surg ; 71(Suppl 1): 679-683, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31742041

RESUMEN

Teachers are heavy voice users, and they suffer from voice problems more frequently than other occupational voice users. Various studies have demonstrated that teachers speak longer than other professionals and that school teachers in particular, are at risk for voice problems such as vocal fatigue and vocal nodules. The present study is undertaken to study the prevalence of voice disorders in the teachers in different schools at any time and accesses the relationship of different working conditions like class room size, background noise, number of hours taught every day and role of chalk allergy in development of these voice disorders. The study was carried out on 133 school teachers with self reporting of voice problems through detailed questionnaire. A significant number of teachers, more so females had voice problems attributed to various factors. Voice amplification and reduction of background noise along with measures to control allergy are suggested.

3.
Neurogastroenterol Motil ; 30(9): e13371, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29781137

RESUMEN

BACKGROUND: Primary chronic intestinal pseudo-obstruction (CIPO) is a rare, potentially life-threatening disorder characterized by severely impaired gastrointestinal motility. The objective of this study was to examine the contribution of ACTG2, LMOD1, MYH11, and MYLK mutations in an Australasian cohort of patients with a diagnosis of primary CIPO associated with visceral myopathy. METHODS: Pediatric and adult patients with primary CIPO and suspected visceral myopathy were recruited from across Australia and New Zealand. Sanger sequencing of the genes encoding enteric gamma-actin (ACTG2) and smooth muscle leiomodin (LMOD1) was performed on DNA from patients, and their relatives, where available. MYH11 and MYLK were screened by next-generation sequencing. KEY RESULTS: We identified heterozygous missense variants in ACTG2 in 7 of 17 families (~41%) diagnosed with CIPO and its associated conditions. We also identified a previously unpublished missense mutation (c.443C>T, p.Arg148Leu) in one family. One case presented with megacystis-microcolon-intestinal hypoperistalsis syndrome in utero with subsequent termination of pregnancy at 28 weeks' gestation. All of the substitutions identified occurred at arginine residues. No likely pathogenic variants in LMOD1, MYH11, or MYLK were identified within our cohort. CONCLUSIONS AND INFERENCES: ACTG2 mutations represent a significant underlying cause of primary CIPO with visceral myopathy and associated phenotypes in Australasian patients. Thus, ACTG2 sequencing should be considered in cases presenting with hypoperistalsis phenotypes with suspected visceral myopathy. It is likely that variants in other genes encoding enteric smooth muscle contractile proteins will contribute further to the genetic heterogeneity of hypoperistalsis phenotypes.


Asunto(s)
Actinas/genética , Predisposición Genética a la Enfermedad/genética , Seudoobstrucción Intestinal/genética , Adolescente , Adulto , Australasia , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mutación Missense , Adulto Joven
4.
Oncogene ; 35(9): 1111-21, 2016 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-25982283

RESUMEN

IMP3 (insulin-like growth factor-2 mRNA binding protein 3) is an oncofetal protein whose expression is prognostic for poor outcome in several cancers. Although IMP3 is expressed preferentially in triple-negative breast cancer (TNBC), its function is poorly understood. We observed that IMP3 expression is significantly higher in tumor initiating than in non-tumor initiating breast cancer cells and we demonstrate that IMP3 contributes to self-renewal and tumor initiation, properties associated with cancer stem cells (CSCs). The mechanism by which IMP3 contributes to this phenotype involves its ability to induce the stem cell factor SOX2. IMP3 does not interact with SOX2 mRNA significantly or regulate SOX2 expression directly. We discovered that IMP3 binds avidly to SNAI2 (SLUG) mRNA and regulates its expression by binding to the 5' UTR. This finding is significant because SLUG has been implicated in breast CSCs and TNBC. Moreover, we show that SOX2 is a transcriptional target of SLUG. These data establish a novel mechanism of breast tumor initiation involving IMP3 and they provide a rationale for its association with aggressive disease and poor outcome.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Proteínas de Unión al ARN/biosíntesis , Factores de Transcripción/biosíntesis , Neoplasias de la Mama Triple Negativas/genética , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Células Madre Neoplásicas , Pronóstico , ARN Mensajero/biosíntesis , Proteínas de Unión al ARN/genética , Factores de Transcripción SOXB1/genética , Factores de Transcripción de la Familia Snail , Factores de Transcripción/genética , Neoplasias de la Mama Triple Negativas/patología
5.
Indian J Exp Biol ; 53(4): 216-21, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26011982

RESUMEN

In this study, we investigated few dietary cucurbits for anticancer activity by monitoring cytotoxic (MTT and LDH assays), apoptotic (caspase-3 and annexin-V assays), and also their anti-inflammatory effects by IL-8 cytokine assay. Aqua-alcoholic (50:50) whole extracts of cucurbits [Lagenaria siceraria (Ls), Luffa cylindrica (Lc) and Cucurbita pepo (Cp)] were evaluated in colon cancer cells (HT-29 and HCT-15) and were compared with isolated biomolecule, cucurbitacin-B (Cbit-B). MTT and LDH assays revealed that the cucurbit extracts and Cbit-B, in a concentration dependent manner, decreased the viability of HT-29 and HCT-15 cells substantially. The viability of lymphocytes was, however, only marginally decreased, yielding a potential advantage over the tumor cells. Caspase-3 assay revealed maximum apoptosis with Ls while annexin V assay demonstrated maximum efficacy of Lc in this context. These cucurbits have also shown decreased secretion of IL-8, thereby revealing their anti-inflammatory capability. The results have demonstrated the therapeutic potential of dietary cucurbits in inhibiting cancer and inflammatory cytokine.


Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos Fitogénicos/farmacología , Cucurbita , Dieta , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos
6.
J Laryngol Otol ; 127(11): 1071-7, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24169084

RESUMEN

BACKGROUND: Necrotising otitis externa, which is typically seen in elderly diabetics, is a severe infective disorder caused by Pseudomonas aeruginosa. There is lack of standard management policy for necrotising otitis externa, hence this study attempted to frame a protocol for management based on clinical parameters. METHOD: A retrospective study of 27 patients with necrotising otitis externa was conducted over 6 years in a tertiary care hospital. Data were analysed with regards to demographic characteristics, clinical features, investigations, staging and treatment modalities. RESULTS: Out of 27 patients, 26 were diabetics. The commonest organism isolated was P aeruginosa, which was sensitive to third generation cephalosporins and fluoroquinolones. Nine patients had cranial nerve involvement. Twelve of 15 patients treated with medical therapy recovered, as did 11 of 12 patients that underwent surgery. CONCLUSION: A high index of suspicion, early diagnosis and prompt intervention are key factors to decrease morbidity and mortality. Fluoroquinolones, third generation cephalosporins and surgical debridement are the mainstay of treatment.


Asunto(s)
Otitis Externa/terapia , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Terapia Combinada/métodos , Desbridamiento , Complicaciones de la Diabetes/complicaciones , Dolor de Oído/etiología , Diagnóstico Precoz , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Otitis Externa/diagnóstico , Infecciones por Pseudomonas/diagnóstico , Infecciones por Pseudomonas/terapia , Pseudomonas aeruginosa , Estudios Retrospectivos , Resultado del Tratamiento
7.
J Indian Soc Pedod Prev Dent ; 29(6 Suppl 2): S61-5, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22169840

RESUMEN

Leiomyoma is a benign smooth muscle tumor that rarely affects children and occurs most frequently in the uterine myometrium and gastrointestinal tract. Its occurrence in the oral cavity is considered rare probably because of the scarcity of smooth muscle tissue in the oral cavity. The most common intraoral sites for leiomyoma are lips, palate and tongue. The purpose of this case report is to present the clinical features, diagnosis and treatment of a rare case of oral leiomyoma in a 13-year-old girl with a 4-month history of a swelling in her left mandibular area extending from first molar to retromolar region.


Asunto(s)
Neoplasias Gingivales/patología , Leiomioma/patología , Adolescente , Femenino , Neoplasias Gingivales/cirugía , Humanos , Leiomioma/cirugía , Mandíbula
8.
Br J Cancer ; 104(4): 629-34, 2011 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-21285984

RESUMEN

BACKGROUND: The molecular chaperone heat shock protein-90 (Hsp90) is a promising cancer drug target, but current Hsp90-based therapy has so far shown limited activity in the clinic. METHODS: We tested the efficacy of a novel mitochondrial-targeted, small-molecule Hsp90 inhibitor, Gamitrinib (GA mitochondrial matrix inhibitor), in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. The TRAMP mice receiving 3-week or 5-week systemic treatment with Gamitrinib were evaluated for localised or metastatic prostate cancer, prostatic intraepithelial neoplasia (PIN) or localised inflammation using magnetic resonance imaging, histology and immunohistochemistry. Treatment safety was assessed histologically in organs collected at the end of treatment. The effect of Gamitrinib on mitochondrial dysfunction was studied in RM1 cells isolated from TRAMP tumours. RESULTS: Systemic administration of Gamitrinib to TRAMP mice inhibited the formation of localised prostate tumours of neuroendocrine or adenocarcinoma origin, as well as metastatic prostate cancer to abdominal lymph nodes and liver. The Gamitrinib treatment had no effect on PIN or prostatic inflammation, and caused no significant animal weight loss or organ toxicity. Mechanistically, Gamitrinib triggered acute mitochondrial dysfunction in RM1 cells, with loss of organelle inner membrane potential and release of cytochrome-c in the cytosol. CONCLUSIONS: The Gamitrinib has pre-clinical activity and favourable tolerability in a genetic model of localised and metastatic prostate cancer in immunocompetent mice. Selective targeting of mitochondrial Hsp90 could provide novel molecular therapy for patients with advanced prostate cancer.


Asunto(s)
Adenocarcinoma/prevención & control , Antineoplásicos/uso terapéutico , Proliferación Celular/efectos de los fármacos , Guanidinas/uso terapéutico , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Lactamas Macrocíclicas/uso terapéutico , Neoplasias de la Próstata/prevención & control , Adenocarcinoma/genética , Adenocarcinoma/patología , Animales , Antineoplásicos/farmacología , Células Cultivadas , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Predisposición Genética a la Enfermedad , Guanidinas/farmacología , Proteínas HSP90 de Choque Térmico/metabolismo , Lactamas Macrocíclicas/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Terapia Molecular Dirigida/métodos , Metástasis de la Neoplasia , Neoplasia Intraepitelial Prostática/genética , Neoplasia Intraepitelial Prostática/patología , Neoplasia Intraepitelial Prostática/prevención & control , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología
9.
Andrologia ; 43(1): 75-7, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21219388

RESUMEN

In this case report we present a family with infertile, azoospermic but otherwise apparently healthy males with history of recurrent spontaneous abortions (RSA) in females. Karyotype of the infertile man revealed a reciprocal balanced translocation t(8; 13) with breakpoints at 8q22 and 13p11.2. The reported reciprocal balanced translocation is associated with azoospermia. The same translocation is probably the cause of RSA in females of the family.


Asunto(s)
Aborto Espontáneo/genética , Infertilidad Masculina/genética , Translocación Genética/genética , Aborto Espontáneo/epidemiología , Aberraciones Cromosómicas , Cromosomas Humanos Par 13/genética , Cromosomas Humanos Par 8/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje , Recurrencia
10.
Pharm Dev Technol ; 16(1): 57-64, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20028210

RESUMEN

The objective of the study was to develop a mathematical model for predicting the disintegration time of fast disintegrating tablets (FDTs) by estimating the powder characteristics of powder blend prior to compression. A combination of chitosan-alginate complex and glycine in the ratio of 50:50 was used for preparing FDTs. The developed mathematical model allowed water sorption time (WST), effective pore radius (R(eff.p)) and swelling Index (SI) of powder mixture as well as tablet crushing strength to be successfully correlated with disintegration time (DT) of FDTs. The predicted model showed that disintegration time of FDTs to be directly correlated with powder characteristics and inversely correlated with tablet crushing strength. Furthermore, a correlation of 0.97 was obtained when DT of FDTs was compared with SI/(WST * R(eff.p)). This correlation was not affected by inclusion of water soluble (ondansetron hydrochloride or metaclopramide hydrochloride) or water insoluble (domperidone) drugs in the powder blend or FDTs. These observations indicated the versatility of the mathematical model in predicting the disintegration time of FDTs by evaluating the selected characteristics of the powder blends without actually preparing the FDTs.


Asunto(s)
Modelos Químicos , Polvos/química , Comprimidos/química , Adsorción , Química Farmacéutica , Quitosano/química , Fuerza Compresiva , Domperidona/administración & dosificación , Domperidona/química , Estabilidad de Medicamentos , Excipientes/química , Glicina/química , Metoclopramida/administración & dosificación , Metoclopramida/química , Ondansetrón/administración & dosificación , Ondansetrón/química , Solubilidad , Factores de Tiempo , Agua
11.
BJOG ; 115(5): 633-8, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18333945

RESUMEN

OBJECTIVES: Inflammation plays a major role in pathogenesis of cervical cancer. We planned to study whether polymorphisms in inflammation-related genes, IL-1RN (VNTR) and IL-1beta (-511C/T), are associated with risk of cervical cancer. DESIGN: Case-control study. SETTING: Uttar Pradesh state in India. SAMPLE: One hundred and fifty, histopathologically confirmed cases with cervical cancer and 162 age-, ethnicity-matched, cervical cytology negative, healthy controls were recruited to this study. METHODS: Genotyping of IL-1RN (VNTR) and IL-1beta (-511C/T) polymorphisms was performed using polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism. Power of study was 80% with type 1 error of 0.05. Haplotypes frequencies were obtained by computer package 'Arlequin'. MAIN OUTCOME MEASURES: Haplotype IL-1RN*2/IL-1beta*T is associated with higher risk and of cervical cancer. RESULTS: IL-1RN genotypes 1/2 and 2/2 were associated with significantly elevated risk of cervical cancer (OR = 3.3; P= 4.9 x 10(-6) and OR = 2.9, P= 0.02). Similarly, TT genotype of IL-1betapolymorphism was significantly higher in cases compared with controls (57.7 versus 38.3%; OR = 2.8; P = 0.012). 2/2 genotype of IL-1RN (OR = 4.8, P = 0.0006) and TT genotype of IL-1beta(OR = 5.2; P = 0.02) were associated with the higher stages (III) of cervical cancer. Haplotypes 1T (IL-1RN*1/IL-1beta*T) and 2T (IL-1RN*2/IL-1beta*T) were also significantly associated with higher susceptibility to cervical cancer and its progression. Logistic regression analysis suggests IL-1RN allele 2 and IL-1beta-511T were independently associated with increased risk for cervical cancer. CONCLUSION: IL-1RN*2 and IL-1beta -511*T in various combinations of genotypes and haplotypes are associated with higher susceptibility for cervical cancer.


Asunto(s)
Proteína Antagonista del Receptor de Interleucina 1/genética , Interleucina-1/genética , Interleucina-1beta/genética , Polimorfismo Genético/genética , Neoplasias del Cuello Uterino/genética , Estudios de Casos y Controles , ADN/genética , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Persona de Mediana Edad , Factores de Riesgo
12.
Diabetologia ; 50(5): 1058-69, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17333113

RESUMEN

AIMS/HYPOTHESIS: On the basis of our previous studies, we investigated the possible role of focal adhesion kinase (FAK) in the development of insulin resistance in skeletal muscle, a major organ responsible for insulin-stimulated glucose uptake. MATERIALS AND METHODS: Insulin-resistant C2C12 skeletal muscle cells were transfected with FAK wild-type or FAK mutant plasmids, knocked down using small interfering RNA (siRNA), and their effects on the levels and activities of insulin-signalling molecules and on glucose uptake were determined. RESULTS: A significant decrease in tyrosine phosphorylation of FAK in insulin-resistant C2C12 cells was observed. A similar decrease was observed in skeletal muscle obtained from insulin-resistant Sprague-Dawley rats fed a high-fat diet. Increased levels of FAK in insulin-resistant C2C12 skeletal muscle cells increased insulin sensitivity and glucose uptake. These effects were reversed by an increase in the level of kinase activity mutant FAK or suppression of endogenous FAK by siRNA. FAK was also found to interact downstream with insulin receptor substrate-1, phosphatidylinositol 3-kinase and protein kinase C and glycogen synthase kinase 3beta, leading to translocation of glucose transporter 4 and resulting in the regulation of glucose uptake. CONCLUSIONS/INTERPRETATION: The present study provides strong evidence that the modulation of FAK level regulates the insulin sensitivity of skeletal muscle cells. The results demonstrate a direct role of FAK in insulin-resistant skeletal muscle cells for the first time.


Asunto(s)
Proteína-Tirosina Quinasas de Adhesión Focal/fisiología , Resistencia a la Insulina/fisiología , Músculo Esquelético/fisiología , Animales , Línea Celular , Proteína-Tirosina Quinasas de Adhesión Focal/genética , Cinética , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , ARN Interferente Pequeño/genética , Transfección
13.
Oncogene ; 26(19): 2678-84, 2007 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-17072337

RESUMEN

Survivin is a dual regulator of cell proliferation and cell viability overexpressed in most human tumors. Although strategies to lower survivin levels have been pursued for rational cancer therapy, the molecular circuitries controlling survivin expression in tumors have not been completely elucidated. Here, we show that stimulation with insulin-like growth factor-1 (IGF-1) results in increased survivin expression in prostate cancer cells. This response is independent of de novo gene transcription, changes in mRNA expression or modifications of survivin protein stability. Instead, IGF-1 induced persistence and translation of a pool of survivin mRNA, in a reaction abolished by the mTOR (mammalian target of rapamycin) inhibitor, rapamycin. Forced expression of the mTOR target p70S6K1 reproduced the increase in survivin expression in prostate cancer cells, whereas acute ablation of endogenous p70S6K1 by small interfering RNA downregulated survivin levels. Rapamycin, alone or in combination with suboptimal concentrations of taxol reduced survivin protein levels, and decreased viability of prostate cancer cells. Therefore, IGF-1/mTOR signaling elevates survivin in prostate cancer cells via rapid changes in mRNA translation. Antagonists of this pathway may be beneficial to lower an antiapoptotic threshold maintained by survivin in prostate cancer.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Factor I del Crecimiento Similar a la Insulina/farmacología , Proteínas Asociadas a Microtúbulos/genética , Proteínas de Neoplasias/genética , Neoplasias de la Próstata/metabolismo , Proteínas Quinasas/metabolismo , Transducción de Señal , Animales , Apoptosis , Ciclo Celular , Proliferación Celular , Regulación hacia Abajo , Células HeLa , Humanos , Proteínas Inhibidoras de la Apoptosis , Masculino , Ratones , Ratones Noqueados , Proteínas Asociadas a Microtúbulos/antagonistas & inhibidores , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Regiones Promotoras Genéticas , Neoplasias de la Próstata/genética , Proteínas Quinasas/genética , Estabilidad del ARN , ARN Interferente Pequeño/farmacología , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/fisiología , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Sirolimus , Survivin , Serina-Treonina Quinasas TOR , Transcripción Genética , Células Tumorales Cultivadas/efectos de los fármacos
14.
Mol Cell Biochem ; 295(1-2): 93-103, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17029008

RESUMEN

Aqueous extract of Podophyllum hexandrum (RP-1), which has been reported to render more than 82% survival against whole body lethal (10 Gy) gamma-irradiation in mice, was further investigated for its immunomodulatory potential. In this study, no significant change could be scored in peritoneal macrophages survival up to 8th day after whole body irradiation. RP-1 treatment (200 mg/kg body weight, i.p.) alone or 2 h before whole body irradiation enhanced macrophage survival significantly (p<0.05) as compared to irradiated control mice. In irradiated animals, there was significant (p<0.01) reduction in splenocyte survival and proliferation as revealed by 3H-TdR method. RP-1 treatment (200 mg/kg) alone or 2 h before irradiation countered the decrease in survival of splenocytes and proliferation significantly (p<0.05) as compared to irradiated control group. Whole body irradiation also significantly (p<0.05) reduced the population of CD4+ and CD8+ T cells and bone marrow GM-CFU at 24 h and 72 h post-irradiation intervals, respectively, as compared to unirradiated control. RP-1 treatment 2 h before whole body irradiation countered the decrease in CD4+ and CD8+ T cells populations and CGM-CFU. Nitric oxide free radicals generation was enhanced significantly (p<0.05) in the supernatant of peritoneal macrophage cultures exposed to 2 Gy gamma radiation ex vivo in comparison to unirradiated control, which was reduced by pre-irradiation (-2 h) administration of RP-1. Whole body irradiation (10 Gy) also reduced the serum titres of IL-3, IL-1 and various IgG isotypes observed at different post-irradiation time interval. RP-1 treatment alone or before whole body irradiation countered radiation induced decrease in the titre of IL-1, IL-3 and IgG's in the serum of mice. These findings indicate immunostimulatory potential of RP-1.


Asunto(s)
Rayos gamma , Terapia de Inmunosupresión , Podophyllum/metabolismo , Protección Radiológica , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/efectos de la radiación , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/efectos de la radiación , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/efectos de la radiación , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Células Cultivadas , Cromatografía Líquida de Alta Presión , Ensayo de Unidades Formadoras de Colonias , Isotipos de Inmunoglobulinas/inmunología , Interleucinas/sangre , Macrófagos Peritoneales/citología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/efectos de la radiación , Masculino , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico/biosíntesis , Extractos Vegetales/análisis , Extractos Vegetales/farmacología , Bazo/citología , Bazo/efectos de los fármacos , Bazo/efectos de la radiación , Volumetría
15.
Andrologia ; 38(6): 199-207, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17081171

RESUMEN

The radioprotective action of a preparation from Hippophae rhamnoides berries RH-3, already reported to render >80% survival against whole body 10 Gy gamma irradiation, was further investigated with respect to the testicular system. RH-3 was administered to mice 30 min before gamma irradiation (5 and 10 Gy) and histological parameters such as testis weight, sperm count, frequency of abnormal sperm, repopulation index, stem cell survival index and seminiferous tubular diameter were assessed on the 35th day. RH-3 administration partially countered radiation induced reduction in testis weight, sperm count, repopulation index and stem cell survival index (p < 0.01). The increase in the frequency of abnormal sperm (15.17 +/- 1.046%) caused by irradiation (5 Gy) was counteracted by pre-irradiation treatment with RH-3, which significantly decreased the level of abnormal spermatozoa to 7.99 +/- 0.918% (p < 0.001), i.e. 52% abnormalities in comparison with 5 Gy irradiated group. RH-3 treatment alone did not elicit any toxic or adverse effect on the process of spermatogenesis. The present study suggests that RH-3 treatment protected spermatogenesis by enhancing the spermatogonial proliferation, enhancing the stem cell survival and reducing sperm abnormalities. The presence of polyphenolic flavonoids and tannins in the extract and the radical scavenging activity might be responsible for the radioprotective action of RH-3.


Asunto(s)
Rayos gamma/efectos adversos , Hippophae , Preparaciones de Plantas/farmacología , Protectores contra Radiación/uso terapéutico , Espermatogénesis/efectos de los fármacos , Espermatogénesis/efectos de la radiación , Animales , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Masculino , Ratones , Fenoles/farmacología , Fitoterapia/métodos , Preparaciones de Plantas/uso terapéutico , Protectores contra Radiación/farmacología , Recuento de Espermatozoides , Células Madre/efectos de los fármacos , Células Madre/patología , Células Madre/efectos de la radiación , Taninos/farmacología , Testículo/efectos de los fármacos , Testículo/patología , Testículo/efectos de la radiación
16.
J Med Food ; 9(2): 154-60, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16822199

RESUMEN

Rhodiola imbricata, an Indian medicinal plant, was investigated for protection against whole-body lethal gamma irradiation (10 Gy)-induced mortality in Swiss albino strain "A" mice. The maximum tolerance dose values for aqueous (RD-I) and aqua-alcoholic (RD-II) extracts were 1,100 and 1,300 mg/kg of body weight, respectively. Pre-irradiation administration of RD-I produced >90% survival, while RD-II produced >83% survival beyond the 30-day observation period. The optimal radioprotective dose for RD-I as well as RD-II was 350 mg/kg of body weight; the aqua-alcoholic extract, however, had an advantage over the aqueous extract at lower as well as at higher doses. The optimal time interval between administration of extract and irradiation was 30 minutes for both RD-I and RD-II. The number of colony-forming units per spleen in irradiated mice was 1.91 +/- 0.15, while in mice given RD-I or RD-II, 30 minutes before irradiation (10 Gy), it increased to 17.3 +/- 0.67 and 15.6 +/- 0.61, respectively. These findings have important implications in the development of a suitable radioprotector of herbal origin.


Asunto(s)
Protectores contra Radiación/administración & dosificación , Rhodiola/química , Irradiación Corporal Total/efectos adversos , Animales , Etanol , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de la radiación , Masculino , Dosis Máxima Tolerada , Ratones , Bazo/citología , Bazo/efectos de la radiación , Células Madre , Factores de Tiempo , Agua
17.
J Pharm Pharmacol ; 57(8): 1065-72, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16102264

RESUMEN

Alcoholic extract of Hippophae rhamnoides, RH-3, reported to render >80% survival against lethal whole body Co-60-gamma irradiation (10 Gy) in mice, was investigated for its immunostimulatory effects. In comparison with un-irradiated control, whole body irradiation did not reduce peritoneal macrophage counts at 24 h post-irradiation. RH-3 treatment (30 mg kg(-1) body weight) alone or 30 min before whole-body irradiation enhanced viable counts of macrophages significantly (P< or =0.05) compared with both un-irradiated control and irradiated groups. Whole-body irradiation reduced the number of viable splenocytes significantly (P<0.05) compared with un-irradiated control at 24 h post-irradiation. RH-3 treatment alone or before whole-body irradiation appreciably countered radiation-induced decrease in splenocyte count. 3H-thymidine uptake method revealed that whole-body irradiation reduced splenocyte proliferation significantly (159 +/- 45 counts min(-1)/10(6) cells; P< or =0.05) in comparison with control (607 +/- 142 counts min(-1)) at 24 h after irradiation but RH3 treatment before irradiation reduced the steep decrease and maintained it as 444+/-153 counts min(-1). After whole-body irradiation, the ratio of spleen weight/mouse weight decreased to 1.5 +/- 04 compared with 2.9 +/- 0.32 in un-irradiated control at 24 h post-irradiation. Similarly, total protein content in splenocytes also decreased to 48 +/- 6 microg/10(6) cells in comparison with 368 +/- 16 microg/10(6) cells of un-irradiated control. RH-3 treatment before irradiation countered radiation-induced decrease in both spleen weight/mouse weight ratio (4.0 +/- 0.35) and total protein content (360 +/- 13 mug/10(6) splenocytes). In the supernatant of peritoneal macrophage cultures exposed to 2 Gy Co-60-gamma radiation ex-vivo, the total nitrite content was enhanced significantly (P<0.05) to 5.72 +/- 0.09 microM in comparison with un-irradiated control (1.64 +/- 0.09 microM). RH-3 treatment (30 microg mL(-1)) before irradiation reduced total nitrite significantly (0.93 +/- 0.3; P< or =0.05) in comparison with irradiated control group. At 24 h after whole body irradiation, the CD4+/CD8+ ratio reduced to 1.5 in comparison with un-irradiated control (1.9) but RH-3 treatment before irradiation restored the ratio to 2.1. These findings explicitly reveal the immunostimulatory activity of RH-3, which may play an important role in the manifestation of its radioprotective efficacy.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/fisiología , Macrófagos Peritoneales/efectos de los fármacos , Extractos Vegetales/farmacología , Protectores contra Radiación/farmacología , Bazo/efectos de los fármacos , Animales , Antígenos CD4/análisis , Antígenos CD8/análisis , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Rayos gamma , Hippophae , Macrófagos Peritoneales/metabolismo , Macrófagos Peritoneales/efectos de la radiación , Masculino , Ratones , Ratones Endogámicos BALB C , Nitritos/metabolismo , Extractos Vegetales/administración & dosificación , Proteínas/metabolismo , Protectores contra Radiación/administración & dosificación , Bazo/citología , Bazo/metabolismo , Bazo/efectos de la radiación , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/efectos de la radiación
18.
Nat Prod Res ; 18(3): 219-23, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15143831

RESUMEN

Ultrasound-assisted synthesis of bioactive isoacoramone (1), a metabolite of Piper marginatum and Acorus tararinowii, has been achieved by oxidation of toxic beta-asarone (2) with potassium permanganate/copper sulphate/alumina into asaronaldehyde (3) followed by treatment with ethylmagnesium iodide to provide 1-(2,4,5-trimethoxy)phenyl-1-propanol (4) which upon further oxidation with potassium permanganate/copper sulphate afforded 1 in 64% yield (overall 32%). Toxicological evaluation of 1 reveals it to be nontoxic up to 60 mg/kg b.w.


Asunto(s)
Acorus/química , Anisoles/química , Carcinógenos/química , Fenilpropionatos/aislamiento & purificación , Piper/química , Derivados de Alilbenceno , Anisoles/toxicidad , Carcinógenos/toxicidad , Oxidación-Reducción , Fenilpropionatos/toxicidad , Ultrasonido
19.
Biomed Pharmacother ; 58(2): 129-35, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14992795

RESUMEN

The aqueous extract of RP-1, which rendered significant protection to whole body irradiated mice, was found to be tumoricidal. The mode of cytotoxic action of RP-1 attributing to its antitumor action was investigated in U 87 cells with special reference to mitochondrial contribution. RP-1 doses above 0.5 microg/ml reduced colonogenic survival (maximum reduction of 62% at 10 microg/ml) and increased the free radical generation, G2/M fraction and apoptotic frequency. Prolonged exposure to RP-1 rendered significant increase in mitochondrial mass. It also reduced mitochondrial membrane potential in a dose and time dependent manner that was restored by verapamil, a Ca+2 channel blocker. Mitochondrial anti-apoptotic proteins Bcl-2 and Hsp-70 levels were also reduced by RP-1 treatment in a dose and time dependent manner. The ability of RP-1 to disrupt mitochondrial structure and function could be responsible for its cytotoxic action.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Podophyllum , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Radicales Libres/metabolismo , Proteínas HSP70 de Choque Térmico/biosíntesis , Humanos , Potenciales de la Membrana , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/fisiología , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Rizoma
20.
Mol Cell Biochem ; 267(1-2): 167-76, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15663198

RESUMEN

RP-1, a herbal preparation of Podophyllum hexandrum has already been reported to provide protection against whole body lethal gamma irradiation (10 Gy). It has also been reported to render radioprotection to germ cells during spermatogenesis. Present study was undertaken to unravel the cellular and molecular mechanism of action of RP-1 on testicular system in strain 'A' mice. Various antioxidant parameters such as thiol content, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) enzyme activity, lipid peroxidation (LPO) and total protein levels were investigated. Thiol content was seen to increase significantly (p < 0.05) in both RP-1 alone and RP-1 pretreated irradiated groups over the irradiated groups at 8, 16 and 24 h. Irradiation (10 Gy) significantly decreased GPx, GST and GR activity in comparison to untreated control but RP-1 treatment before irradiation significantly (p < 0.05) countered radiation-induced decrease in the activity of these enzymes. Radiation-induced LPO was also found to be reduced at all time intervals by RP-1 treatment before irradiation. As compared to irradiated group the protein content in testicular tissue was increased in RP-1 pretreated irradiated group at 4 and 16 h significantly (p < 0.05). Comets revealed by single-cell gel electrophoresis were significantly longer (p < 0.001) in irradiated mice than in unirradiated control. RP-1 treatment before irradiation, however, rendered significant increase (p < 0.05) in comet length over the corresponding control and irradiated group initially at 4 h but at later time points, this was reduced significantly (p < 0.01) as compared to the irradiated group. RP-1 treatment alone rendered shorter comets at 8, 16 and 24 h than irradiated groups (p < 0.001). This study implies that RP-1 offers radioprotection at biochemical and cytogenetic level by protecting antioxidant enzymes, reducing LPO and increasing thiol content.


Asunto(s)
Extractos Vegetales/farmacología , Podophyllum , Protectores contra Radiación/farmacología , Espermatogénesis/efectos de la radiación , Irradiación Corporal Total , Animales , Ensayo Cometa , Rayos gamma , Glutatión Peroxidasa/efectos de la radiación , Glutatión Reductasa/efectos de la radiación , Glutatión Transferasa/efectos de la radiación , Peroxidación de Lípido/efectos de la radiación , Masculino , Ratones , Ratones Endogámicos A , Fitoterapia , Extractos Vegetales/uso terapéutico , Plantas Medicinales , Proteínas/análisis , Proteínas/efectos de la radiación , Compuestos de Sulfhidrilo/efectos de la radiación , Factores de Tiempo
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