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1.
Indian J Otolaryngol Head Neck Surg ; 71(Suppl 1): 679-683, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31742041

ABSTRACT

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.

2.
Indian J Otolaryngol Head Neck Surg ; 71(Suppl 2): 1320-1326, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31750172

ABSTRACT

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.

3.
Neurogastroenterol Motil ; 30(9): e13371, 2018 09.
Article in English | MEDLINE | ID: mdl-29781137

ABSTRACT

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.


Subject(s)
Actins/genetics , Genetic Predisposition to Disease/genetics , Intestinal Pseudo-Obstruction/genetics , Adolescent , Adult , Australasia , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Mutation, Missense , Young Adult
4.
Oncogene ; 35(9): 1111-21, 2016 Mar 03.
Article in English | MEDLINE | ID: mdl-25982283

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor/biosynthesis , RNA-Binding Proteins/biosynthesis , Transcription Factors/biosynthesis , Triple Negative Breast Neoplasms/genetics , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Humans , Neoplastic Stem Cells , Prognosis , RNA, Messenger/biosynthesis , RNA-Binding Proteins/genetics , SOXB1 Transcription Factors/genetics , Snail Family Transcription Factors , Transcription Factors/genetics , Triple Negative Breast Neoplasms/pathology
5.
Indian J Exp Biol ; 53(4): 216-21, 2015 Apr.
Article in English | MEDLINE | ID: mdl-26011982

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Cucurbita , Diet , Apoptosis/drug effects , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans
6.
J Laryngol Otol ; 127(11): 1071-7, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24169084

ABSTRACT

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.


Subject(s)
Otitis Externa/therapy , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Combined Modality Therapy/methods , Debridement , Diabetes Complications/complications , Earache/etiology , Early Diagnosis , Female , Humans , Length of Stay , Male , Middle Aged , Otitis Externa/diagnosis , Pseudomonas Infections/diagnosis , Pseudomonas Infections/therapy , Pseudomonas aeruginosa , Retrospective Studies , Treatment Outcome
7.
J Indian Soc Pedod Prev Dent ; 29(6 Suppl 2): S61-5, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22169840

ABSTRACT

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.


Subject(s)
Gingival Neoplasms/pathology , Leiomyoma/pathology , Adolescent , Female , Gingival Neoplasms/surgery , Humans , Leiomyoma/surgery , Mandible
8.
Br J Cancer ; 104(4): 629-34, 2011 Feb 15.
Article in English | MEDLINE | ID: mdl-21285984

ABSTRACT

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.


Subject(s)
Adenocarcinoma/prevention & control , Antineoplastic Agents/therapeutic use , Cell Proliferation/drug effects , Guanidines/therapeutic use , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Lactams, Macrocyclic/therapeutic use , Prostatic Neoplasms/prevention & control , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Animals , Antineoplastic Agents/pharmacology , Cells, Cultured , Disease Models, Animal , Disease Progression , Drug Evaluation, Preclinical , Female , Genetic Predisposition to Disease , Guanidines/pharmacology , HSP90 Heat-Shock Proteins/metabolism , Lactams, Macrocyclic/pharmacology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mitochondria/drug effects , Mitochondria/metabolism , Molecular Targeted Therapy/methods , Neoplasm Metastasis , Prostatic Intraepithelial Neoplasia/genetics , Prostatic Intraepithelial Neoplasia/pathology , Prostatic Intraepithelial Neoplasia/prevention & control , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology
9.
Andrologia ; 43(1): 75-7, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21219388

ABSTRACT

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.


Subject(s)
Abortion, Spontaneous/genetics , Infertility, Male/genetics , Translocation, Genetic/genetics , Abortion, Spontaneous/epidemiology , Chromosome Aberrations , Chromosomes, Human, Pair 13/genetics , Chromosomes, Human, Pair 8/genetics , Female , Humans , Male , Middle Aged , Pedigree , Recurrence
10.
Pharm Dev Technol ; 16(1): 57-64, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20028210

ABSTRACT

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.


Subject(s)
Models, Chemical , Powders/chemistry , Tablets/chemistry , Adsorption , Chemistry, Pharmaceutical , Chitosan/chemistry , Compressive Strength , Domperidone/administration & dosage , Domperidone/chemistry , Drug Stability , Excipients/chemistry , Glycine/chemistry , Metoclopramide/administration & dosage , Metoclopramide/chemistry , Ondansetron/administration & dosage , Ondansetron/chemistry , Solubility , Time Factors , Water
11.
BJOG ; 115(5): 633-8, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18333945

ABSTRACT

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.


Subject(s)
Interleukin 1 Receptor Antagonist Protein/genetics , Interleukin-1/genetics , Interleukin-1beta/genetics , Polymorphism, Genetic/genetics , Uterine Cervical Neoplasms/genetics , Case-Control Studies , DNA/genetics , Female , Genetic Predisposition to Disease , Genotype , Haplotypes , Humans , Middle Aged , Risk Factors
12.
Diabetologia ; 50(5): 1058-69, 2007 May.
Article in English | MEDLINE | ID: mdl-17333113

ABSTRACT

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.


Subject(s)
Focal Adhesion Protein-Tyrosine Kinases/physiology , Insulin Resistance/physiology , Muscle, Skeletal/physiology , Animals , Cell Line , Focal Adhesion Protein-Tyrosine Kinases/genetics , Kinetics , Mice , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , RNA, Small Interfering/genetics , Transfection
13.
Mol Cell Biochem ; 295(1-2): 93-103, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17029008

ABSTRACT

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.


Subject(s)
Gamma Rays , Immunosuppression Therapy , Podophyllum/metabolism , Radiation Protection , Animals , Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Bone Marrow Cells/radiation effects , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/radiation effects , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/radiation effects , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Cell Survival/drug effects , Cell Survival/radiation effects , Cells, Cultured , Chromatography, High Pressure Liquid , Colony-Forming Units Assay , Immunoglobulin Isotypes/immunology , Interleukins/blood , Macrophages, Peritoneal/cytology , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/radiation effects , Male , Mice , Mice, Inbred BALB C , Nitric Oxide/biosynthesis , Plant Extracts/analysis , Plant Extracts/pharmacology , Spleen/cytology , Spleen/drug effects , Spleen/radiation effects , Titrimetry
14.
Oncogene ; 26(19): 2678-84, 2007 Apr 26.
Article in English | MEDLINE | ID: mdl-17072337

ABSTRACT

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.


Subject(s)
Gene Expression Regulation, Neoplastic , Insulin-Like Growth Factor I/pharmacology , Microtubule-Associated Proteins/genetics , Neoplasm Proteins/genetics , Prostatic Neoplasms/metabolism , Protein Kinases/metabolism , Signal Transduction , Animals , Apoptosis , Cell Cycle , Cell Proliferation , Down-Regulation , HeLa Cells , Humans , Inhibitor of Apoptosis Proteins , Male , Mice , Mice, Knockout , Microtubule-Associated Proteins/antagonists & inhibitors , Microtubule-Associated Proteins/metabolism , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/metabolism , Promoter Regions, Genetic , Prostatic Neoplasms/genetics , Protein Kinases/genetics , RNA Stability , RNA, Small Interfering/pharmacology , Receptor, IGF Type 1/genetics , Receptor, IGF Type 1/physiology , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Sirolimus , Survivin , TOR Serine-Threonine Kinases , Transcription, Genetic , Tumor Cells, Cultured/drug effects
15.
Andrologia ; 38(6): 199-207, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17081171

ABSTRACT

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.


Subject(s)
Gamma Rays/adverse effects , Hippophae , Plant Preparations/pharmacology , Radiation-Protective Agents/therapeutic use , Spermatogenesis/drug effects , Spermatogenesis/radiation effects , Animals , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Cell Survival/drug effects , Cell Survival/radiation effects , Dose-Response Relationship, Radiation , Male , Mice , Phenols/pharmacology , Phytotherapy/methods , Plant Preparations/therapeutic use , Radiation-Protective Agents/pharmacology , Sperm Count , Stem Cells/drug effects , Stem Cells/pathology , Stem Cells/radiation effects , Tannins/pharmacology , Testis/drug effects , Testis/pathology , Testis/radiation effects
16.
J Med Food ; 9(2): 154-60, 2006.
Article in English | MEDLINE | ID: mdl-16822199

ABSTRACT

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.


Subject(s)
Radiation-Protective Agents/administration & dosage , Rhodiola/chemistry , Whole-Body Irradiation/adverse effects , Animals , Ethanol , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/radiation effects , Male , Maximum Tolerated Dose , Mice , Spleen/cytology , Spleen/radiation effects , Stem Cells , Time Factors , Water
17.
J Pharm Pharmacol ; 57(8): 1065-72, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16102264

ABSTRACT

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.


Subject(s)
Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/physiology , Macrophages, Peritoneal/drug effects , Plant Extracts/pharmacology , Radiation-Protective Agents/pharmacology , Spleen/drug effects , Animals , CD4 Antigens/analysis , CD8 Antigens/analysis , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Cell Survival/drug effects , Cell Survival/radiation effects , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Gamma Rays , Hippophae , Macrophages, Peritoneal/metabolism , Macrophages, Peritoneal/radiation effects , Male , Mice , Mice, Inbred BALB C , Nitrites/metabolism , Plant Extracts/administration & dosage , Proteins/metabolism , Radiation-Protective Agents/administration & dosage , Spleen/cytology , Spleen/metabolism , Spleen/radiation effects , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/radiation effects
18.
Nat Prod Res ; 18(3): 219-23, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15143831

ABSTRACT

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.


Subject(s)
Acorus/chemistry , Anisoles/chemistry , Carcinogens/chemistry , Phenylpropionates/isolation & purification , Piper/chemistry , Allylbenzene Derivatives , Anisoles/toxicity , Carcinogens/toxicity , Oxidation-Reduction , Phenylpropionates/toxicity , Ultrasonics
19.
Biomed Pharmacother ; 58(2): 129-35, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14992795

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Podophyllum , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Free Radicals/metabolism , HSP70 Heat-Shock Proteins/biosynthesis , Humans , Membrane Potentials , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondria/physiology , Plant Extracts/pharmacology , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Rhizome
20.
Mol Cell Biochem ; 267(1-2): 167-76, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15663198

ABSTRACT

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.


Subject(s)
Plant Extracts/pharmacology , Podophyllum , Radiation-Protective Agents/pharmacology , Spermatogenesis/radiation effects , Whole-Body Irradiation , Animals , Comet Assay , Gamma Rays , Glutathione Peroxidase/radiation effects , Glutathione Reductase/radiation effects , Glutathione Transferase/radiation effects , Lipid Peroxidation/radiation effects , Male , Mice , Mice, Inbred A , Phytotherapy , Plant Extracts/therapeutic use , Plants, Medicinal , Proteins/analysis , Proteins/radiation effects , Sulfhydryl Compounds/radiation effects , Time Factors
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