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1.
Br J Cancer ; 128(9): 1765-1776, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36810910

RESUMO

BACKGROUND: Ovarian cancers are hallmarked by chromosomal instability. New therapies deliver improved patient outcomes in relevant phenotypes, however therapy resistance and poor long-term survival signal requirements for better patient preselection. An impaired DNA damage response (DDR) is a major chemosensitivity determinant. Comprising five pathways, DDR redundancy is complex and rarely studied alongside chemoresistance influence from mitochondrial dysfunction. We developed functional assays to monitor DDR and mitochondrial states and trialled this suite on patient explants. METHODS: We profiled DDR and mitochondrial signatures in cultures from 16 primary-setting ovarian cancer patients receiving platinum chemotherapy. Explant signature relationships to patient progression-free (PFS) and overall survival (OS) were assessed by multiple statistical and machine-learning methods. RESULTS: DR dysregulation was wide-ranging. Defective HR (HRD) and NHEJ were near-mutually exclusive. HRD patients (44%) had increased SSB abrogation. HR competence was associated with perturbed mitochondria (78% vs 57% HRD) while every relapse patient harboured dysfunctional mitochondria. DDR signatures classified explant platinum cytotoxicity and mitochondrial dysregulation. Importantly, explant signatures classified patient PFS and OS. CONCLUSIONS: Whilst individual pathway scores are mechanistically insufficient to describe resistance, holistic DDR and mitochondrial states accurately predict patient survival. Our assay suite demonstrates promise for translational chemosensitivity prediction.


Assuntos
Neoplasias Ovarianas , Platina , Humanos , Feminino , Platina/uso terapêutico , Dano ao DNA , Recidiva Local de Neoplasia , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Aprendizado de Máquina
2.
J Environ Manage ; 301: 113792, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34607137

RESUMO

Jaggery is a kind of unrefined non-centrifugal sugar (NCS) used mainly in Asia, Africa, Latin America, and the Caribbean. Traditionally, jaggery is produced by concentrating sugarcane juice in open pans with the help of bagasse combustion. However, due to thermal energy loss with flue gases and an unscientific approach in plant construction, jaggery plants have a poor thermal efficiency of less than 25%, poor emission characteristics, and a high bagasse consumption rate. Advanced jaggery-making techniques use solar energy and heat pumps for jaggery production. However, these techniques are in the early stage of development, and the literature indicates that these techniques should be used in conjuction with traditional ones to improve the performance of jaggery making plants. This literature review describes advances in jaggery-making methods, critically analyzed them, and provides a qualitative comparison of these methods. Further, gaps in the existing literature are identified and reported for future research direction. In addition, efforts have been made to quantify and estimate the emissions reduction and bagasse consumption potentials from the traditional jaggery industry to make this rural industry a sustainable and profitable business for rural entrepreneurs. The comparison with the recently developed clean combustion device exhibits that the harmful emissions from the jaggery industry could be reduced drastically viz. 95%-98% of PM2.5; 92%-95% of CO, and 52-60% of CO2, while saving more than 35% of bagasse consumption. Implemented at a national scale, it may reduce nearly 3% of all harmful emissions in the country, which is equally applicable elsewhere.


Assuntos
Extratos Vegetais , Saccharum , Gases , Temperatura Alta
3.
Cryo Letters ; 43(3): 150-157, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36626139

RESUMO

BACKGROUND: The increasing use of nanoparticles (NP) for gender-selected spermatozoa, sperm-enriched semen and novel extenders raises the concern of undesirable effects on fertility and sperm function. OBJECTIVE: To investigate the effects of gold (Au-), silver (Ag-), and titanium dioxide (TiO2-) NPs on the motility and sperm functions in bovine spermatozoa at various stages of cryopreservation. MATERIALS AND METHODS: Frieswal (Sahiwal × Holstein Friesian) bull semen ejaculates (N = 24) were challenged with unconjugated and ligand-free Au-, Ag-, and TiO2-NPs. RESULTS: At post-dilution (fresh) stage, there was no significant difference observed in progressive motility and viability amongst the control and any nanoparticle-treated groups, though plasma membrane integrity was significantly reduced in nanoparticle-treated groups (p < 0.05). The acrosome intactness was also significantly reduced in the groups of Ag-NP and TiO2 -NP (p < 0.05), while there was no effect observed in the Au-NP group. At post-equilibration stage, a significant reduction in motility, viability, and plasma membrane integrity was observed in all three nanoparticle-treated groups (p < 0.05). There was no difference in intact acrosome between the control and Au-NPs groups; which was significantly higher than the Ag-NP and TiO2 -NP groups (p < 0.05). At post-thaw stage, all NP groups resulted in a significant reduction of motility, viability, acrosome intactness and plasma membrane integrity (p < 0.05). Besides, TiO2-NPs appear to be significant more toxic (p < 0.05) among three NP groups, and Au-NPs appear to be lesser toxic. CONCLUSION: Bovine spermatozoa are adversely affected by Au-, Ag- and TiO2 -NPs that may impair sperm motility and other functions. doi.org/10.54680/fr22310110512.


Assuntos
Nanopartículas , Preservação do Sêmen , Masculino , Animais , Bovinos , Criopreservação/veterinária , Criopreservação/métodos , Prata/farmacologia , Sêmen , Ouro/farmacologia , Motilidade dos Espermatozoides , Espermatozoides , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos
4.
Cryo Letters ; 43(6): 322-327, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36629826

RESUMO

BACKGROUND: The bacterial contaminants in the semen are a major concern for most of the semen production laboratories because they adversely affect the semen quality. During sperm cryopreservation, the inclusion of antimicrobials in extenders may help to minimize bacterial growth. However, due to bacterial resistance to commonly used antimicrobials, they cannot fully assure microbiological safety to the frozen semen. OBJECTIVE: To estimate the microbial load and antibiogram of microorganisms isolated from the fresh and frozen bull semen. MATERIALS AND METHODS: The bacterial load was estimated in fresh and frozen semen samples of crossbred Frieswal bulls by the pour plate method. Microorganisms were identified as Gram positive and Gram negative by Gram staining. The representative bacterial colonies were streaked onto different specific media which were further confirmed by biochemical tests. Bacterial isolates were subjected to in vitro antibiotic sensitivity test. RESULTS: The average microbial load of fresh and frozen semen samples was found to be 8397.4 ± 524.3 cfu per mL and 680.9 ± 105.4 cfuper mL, respectively. Microorganisms belonging to Staphylococcus aureus, Staphylococcus epidermidis, Proteus, Klebsiella, Bacillus cereus, Bacillus subtilis, Actinomyces, E. coli, Rhodococcus, Neisseria and Micrococcus were identified in the semen samples. The antibiotic sensitivity testing of the bacterial isolates revealed that benzyl penicillin was found to be the least effective against the isolated organisms while gentamicin and spectinomycin were found to be most effective among the antibiotics used. Lincomycin, tylosin and streptomycin showed moderate efficacy against the bacterial isolates. CONCLUSION: Gentamicin, tylosin, lincomycin, and spectinomycin (GTLS) antibiotic combination is more effective against bacterial isolates and may be added to semen extender to better control bacterial load and semen quality. doi.org/10.54680/fr22610110512.


Assuntos
Preservação do Sêmen , Espectinomicina , Masculino , Animais , Bovinos , Espectinomicina/farmacologia , Tilosina/farmacologia , Análise do Sêmen , Preservação do Sêmen/veterinária , Escherichia coli , Sêmen , Criopreservação/veterinária , Antibacterianos/farmacologia , Lincomicina/farmacologia , Gentamicinas/farmacologia , Testes de Sensibilidade Microbiana , Espermatozoides
5.
Cryo Letters ; 43(5): 276-282, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36626132

RESUMO

BACKGROUND: Cryopreservation process negatively affects spermatozoa functions. Humanin, a small polypeptide encoded in the mitochondrial genome, is well known for its role in cell survival. OBJECTIVE: To quantify the endogenous levels of humanin in seminal plasma of crossbred Frieswal bulls and to study its role in cryoprotection. The presence of humanin in bull spermatozoa was also investigated. MATERIALS AND METHODS: A total of 40 semen samples were separated into two groups based on the initial progressive motility (IPM): Good (IPM >70%) and Poor (IPM <50%) groups; and/or based on the post-thaw motility (PTM): Freezable (PTM>50%) and Non-freezable (PTM < 50%) groups. Humanin concentration in seminal plasma (SP-HN) was quantified using ELISA. RESULTS: SP-HN concentration ranged from undetectable to 67.6 pg/mL with a median level of 35.2 pg/mL. SP-HN level was significantly higher in the good quality semen group than in the poor quality semen group (p<0.001), and also significantly higher in the freezable group than in the non-freezable group (p<0.001). SP-HN level was positively correlated with initial progressive motility, post-thaw semen motility, viability, acrosome intactness and plasma membrane integrity, but negatively correlated the level of reactive oxygen species and malondialdehyde content. Immunochemical localization showed the presence of humanin in the proximal region of the middle piece of spermatozoa. CONCLUSION: Endogenous humanin level had significant correlation with semen quality and might protect sperm cells against freeze-induced oxidative stress. doi.org/10.54680/fr22510110712.


Assuntos
Preservação do Sêmen , Sêmen , Masculino , Animais , Bovinos , Análise do Sêmen , Criopreservação/veterinária , Preservação do Sêmen/veterinária , Espermatozoides/química , Peptídeos e Proteínas de Sinalização Intracelular/análise , Motilidade dos Espermatozoides
6.
Cryobiology ; 98: 187-193, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33476643

RESUMO

Despite many cryopreservation techniques in bovine semen, various stressors' detrimental effects remain a significant issue. The present study targeted to assess the role of semen quality parameters, sperm function tests, lipid peroxidation, reactive oxygen species (ROS), and different antioxidants in the cryopreservation of bovine semen. Further, the kinetics of lipid peroxidation, ROS, and antioxidants on repeated semen collection under short ejaculatory abstinence were studied. We designed a comparative study where bulls were grouped into good and low freezable semen groups (Freeze-groups) based on their post-thaw motility. All the bulls included had similar initial motility and qualified minimum standards for initial semen parameters viz. semen volume and sperm concentration. The present study detected a higher lipid peroxidation and ROS viz. superoxide anions (•O2-) and a lower total antioxidant capacity (TAC) in the low freeze-group compared to the good freeze-group. The ROS and antioxidants showed unique kinetics on repeated semen collection at short intervals, and no significant change was detected in semen volume, sperm motility, and sperm concentration. This study detected higher head abnormalities and poor acrosome integrity in the low freeze-groups. The present study results indicated that the sperm head might be the most vulnerable part of the sperm to cryopreservation stress. The present study finds significantly higher lipid peroxidation and ROS levels and reduced antioxidant capacity as the primary reasons for low cryopreservability. Further, repeated semen collection with a shorter or lack of abstinence does not impose any significant change in the semen volume and sperm concentration; moreover, it could be beneficial for higher antioxidant levels and lower lipid peroxidation levels. As seminal plasma has both inhibitory and stimulatory roles in sperm function and cryopreservation, identifying the critical role players of seminal plasma and identifying sperm related changes in cryopreservation could predict the cryopreservability potential of semen.


Assuntos
Preservação do Sêmen , Sêmen , Animais , Antioxidantes , Bovinos , Criopreservação/métodos , Cinética , Peroxidação de Lipídeos , Masculino , Espécies Reativas de Oxigênio , Análise do Sêmen , Preservação do Sêmen/veterinária , Motilidade dos Espermatozoides , Espermatozoides
7.
Int J Biometeorol ; 65(7): 1025-1032, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33683454

RESUMO

The kinetic patterns of CpG methylation of the cis-regulatory region of heat stress-related genes on exposed to heat stress (at 42 °C) between the Sahiwal and Frieswal cattle was compared in the present study. Using an in vitro whole blood culture model, cells were continuously exposed to heat stress (at 42 °C) for 6 h. Methylation levels of five genes, viz., GPX1, HSP70, HSP90, c-FOS, and JUN were estimated by SyberGreen-based quantitative methylation-specific PCR (qMSP) assay. CpG methylation kinetics at different time points of heat stress (0.5, 1, 2, 4, 6 h) were analyzed using mixed ANOVA. The initial methylation level, estimated at 37 °C, of HSP70 was significantly high in the Sahiwal breed. A significant (p<0.001) time-dependent hypomethylation of an antioxidant gene (GPX1) CpG islands was detected at the acute phase of the stress. Heat shock protein gene (HSP70) showed a similar CpG methylation kinetics where the hypomethylation was prominent from 1 h and persisted up to 4 h. The heat stress responses of both Sahiwal and Frieswal cattle were identical as there was no distinctiveness in the methylation kinetics of CpG islands of studied genes. The acclimatization of Frieswal cattle-a breed developed in India over the years to the tropical climatic conditions, maybe one of the reasons for this similarity. Thus, the present study results could pave a path to understand the molecular mechanism of heat stress and adaptation of indigenous and crossbred cattle populations to the changing scenario in tropical climate conditions.


Assuntos
Proteínas de Choque Térmico HSP70 , Resposta ao Choque Térmico , Animais , Bovinos/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Resposta ao Choque Térmico/genética , Índia , Cinética , Metilação , Sequências Reguladoras de Ácido Nucleico
8.
Mikrochim Acta ; 187(9): 536, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32870369

RESUMO

Amine group-containing isoreticular metal-organic framework (IRMOF-3) particles are utilized for the first time as a trinitrotoluene (TNT) sensing material. IRMOF-3 particles are synthesized using zinc nitrate as a metal precursor and 2-amino-1,4-benzenedicarboxylic acid as a linker. The nitrogen-doped carbon quantum dots (NCQDs) are synthesized from citric acid and ethylenediamine as carbon and nitrogen precursor, respectively. The NCQDs are conjugated with IRMOF-3 particles as IRMOF-3/NCQDs. The TEM micrograph revealed the average size of IRMOF-3 particles to be 363.66 nm. The photoluminescence emission intensity of IRMOF-3 particles at λem 430 nm is highly increased in the presence of NCQDs (λex 330 nm). Both the as-synthesized IRMOF-3 and IRMOF-3/NCQD particles are explored for TNT detection to compare the effect of NCQDs on the IRMOF-3 particle surface. Lower limit of detection (7.5 × 10-8 M) and higher Stern-Volmer constant (4.46 × 106 M-1) are achieved by IRMOF-3/NCQD particles. The association constant also increased from 5.3 × 104 to 2.78 × 106 M-1 after the conjugation of IRMOF-3 particles with NCQDs. Moreover, enhanced selectivity for TNT over trinitrophenol is achieved using the IRMOF-3/NCQD particles. Graphical Abstract.

9.
J Therm Biol ; 87: 102457, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31999598

RESUMO

Impact of global warming on the dairy industry has gained attention due to huge economic losses through low production and fertility caused by heat stress. Exposure to hyperthermia provokes a series of complex responses in mammals which are been related to morphological and physiological alterations including the production of reactive oxygen species (ROS). A quantitative spectrophotometric based nitroblue tetrazolium (NBT) reduction assay was used to estimate the superoxide anion (•O2-) level in heat stressed (at 42 °C) whole blood cultures of native and crossbred bulls (Sahiwal and Frieswal), in vitro. The breed effect in the kinetics of •O2- production at different time periods of continual heat stress was analyzed by repeated measures ANOVA. Comparison between different time periods in reference to 37 °C was analyzed by paired t-test. The •O2- level was significantly different (p < 0.05) between cells at 37 °C and 42 °C at different periods of incubation. Kinetics study showed increment of •O2- production on the acute phase of stress followed by a reduction in both Sahiwal and Frieswal breeds. In Sahiwal breed, the inflated superoxide level continued abated till 4 h and raised again at 6 h, while in Frieswal •O2- level reverted to raise sooner with in 2 h of incubation itself. Contrarily, kinetic of •O2- level in plasma showed a significant reduction (p < 0.001) at 30 min of 42 °C incubation followed by increment of •O2- level. Further, the breed variation was significant (p < 0.05) and a significant high reduction of •O2- level was observed in Sahiwal breed. Our finding indicates that, a better and longer •O2- production homeostasis and higher plasma scavenging ability of native breed may be one of the reasons for the higher thermal tolerance of these breeds in tropical climate.


Assuntos
Doenças dos Bovinos/sangue , Bovinos/fisiologia , Transtornos de Estresse por Calor/veterinária , Superóxidos/sangue , Animais , Análise Química do Sangue/métodos , Análise Química do Sangue/veterinária , Bovinos/sangue , Bovinos/genética , Doenças dos Bovinos/genética , Células Cultivadas , Transtornos de Estresse por Calor/sangue , Transtornos de Estresse por Calor/genética , Hibridização Genética , Indicadores e Reagentes , Nitroazul de Tetrazólio , Espectrofotometria/métodos , Espectrofotometria/veterinária
10.
Reprod Domest Anim ; 53(3): 588-608, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29417653

RESUMO

Male infertility is one of the prime concerns of dairy cattle production. The study was designed to find out differentially expressed proteins in categorized crossbred (Holstein Friesian × Sahiwal) bull semen to serve as potential biomarkers for male infertility. Frozen crossbred bull semen with satisfactory phenotypic records were defined as "good" and "poor" based on their fertility rates. A total of 1,547 proteins were detected in bull spermatozoa using liquid chromatography-mass spectrometer (LC-MS/MS) analysis. Results revealed that 558 (36.1%) and 653 (42.2%) proteins were expressed to good and poor quality bull spermatozoa, respectively. A total of 336 proteins (21.7%) were reported to be unique for both good and poor quality bull semen, and among the common proteins, 224 (66.7%) and 112 (33.3%) were up- and downregulated in good and poor quality categorized bull semen, respectively. Gene Ontology analysis of global proteomes identified different signalling pathways, and most of them were related to cellular motility, immune systems as well as cellular metabolisms. The distinctive presence of some of the proteins may provide an insight into the molecular mechanistic role played by these proteins in crossbred bull infertility.


Assuntos
Bovinos/genética , Infertilidade Masculina/veterinária , Proteômica , Animais , Biomarcadores , Bovinos/metabolismo , Cruzamentos Genéticos , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Masculino , Análise do Sêmen , Transdução de Sinais/genética , Espermatozoides/metabolismo
11.
12.
J Food Sci Technol ; 53(9): 3408-3423, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27777447

RESUMO

Plant-based or non-dairy milk alternative is the fast growing segment in newer food product development category of functional and specialty beverage across the globe. Nowadays, cow milk allergy, lactose intolerance, calorie concern and prevalence of hypercholesterolemia, more preference to vegan diets has influenced consumers towards choosing cow milk alternatives. Plant-based milk alternatives are a rising trend, which can serve as an inexpensive alternate to poor economic group of developing countries and in places, where cow's milk supply is insufficient. Though numerous types of innovative food beverages from plant sources are being exploited for cow milk alternative, many of these faces some/any type of technological issues; either related to processing or preservation. Majority of these milk alternatives lack nutritional balance when compared to bovine milk, however they contain functionally active components with health promoting properties which attracts health conscious consumers. In case of legume based milk alternatives, sensory acceptability is a major limiting factor for its wide popularity. New and advanced non-thermal processing technologies such as ultra high temperature treatment, ultra high pressure homogenization, pulsed electric field processing are being researched for tackling the problems related to increase of shelf life, emulsion stability, nutritional completeness and sensory acceptability of the final product. Concerted research efforts are required in coming years in functional beverages segment to prepare tailor-made newer products which are palatable as well as nutritionally adequate.

13.
J Food Sci Technol ; 53(4): 1834-44, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27413210

RESUMO

Present study was undertaken to optimize the level of food materials viz. groundnut meal, beetroot juice and refined wheat flour for development of nutritious pasta using response surface methodology. Box-benken design of experiments was used to design different experimental combinations considering 10 to 20 g groundnut meal, 6 to 18 mL beetroot juice and 80 to 90 g refined wheat flour. Quality attributes such as protein content, antioxidant activity, colour, cooking quality (solid loss, rehydration ratio and cooking time) and sensory acceptability of pasta samples were the dependent variables for the study. The results revealed that pasta samples with higher levels of groundnut meal and beetroot juice were high in antioxidant activity and overall sensory acceptability. The samples with higher content of groundnut meal indicated higher protein contents in them. On the other hand, the samples with higher beetroot juice content were high in rehydration ratio and lesser cooking time along with low solid loss in cooking water. The different level of studied food materials significantly affected the colour quality of pasta samples. Optimized combination for development of nutritious pasta consisted of 20 g groundnut meal, 18 mL beetroot juice and 83.49 g refined wheat flour with overall desirability as 0.905. This pasta sample required 5.5 min to cook and showed 1.37 % solid loss and rehydration ratio as 6.28. Pasta sample prepared following optimized formulation provided 19.56 % protein content, 23.95 % antioxidant activity and 125.89 mg/100 g total phenols with overall sensory acceptability scores 8.71.

14.
Reprod Domest Anim ; 50(3): 505-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25845404

RESUMO

Mammalian circadian locomotor output cycles kaput (CLOCK) gene encodes a transcription factor that affects both the persistence and the period of circadian rhythms. Earlier reports suggested that CLOCK gene might be associated with male infertility in human. Present investigation, for the first time, reports that CLOCK gene expresses differentially between good and poor quality crossbred bull semen. The relative expression of CLOCK was significantly (p < 0.05) higher among good quality bull semen than motility-impaired ones. Clusterins (CLU) are series of genes associated with a variety of physiological activities including spermatogenesis, apoptosis and degenerative disease conditions. In the present context, we also investigated that the expression of CLU gene was significantly (p < 0.05) higher among motility-impaired crossbred bull semen compared to the good quality one.


Assuntos
Proteínas CLOCK/metabolismo , Bovinos/fisiologia , Clusterina/metabolismo , Regulação da Expressão Gênica/fisiologia , RNA Mensageiro/metabolismo , Espermatozoides/metabolismo , Animais , Proteínas CLOCK/genética , Bovinos/genética , Células Cultivadas , Clusterina/genética , Masculino , RNA Mensageiro/genética , Motilidade dos Espermatozoides
15.
J Assoc Physicians India ; 63(3 Suppl): 30-5, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26529865

RESUMO

BACKGROUND: The incidence of aplastic anaemia (AA) is higher in Asia than in the West. The precise incidence of AA in India is not known due to lack of epidemiological study. 20-40% of pancytopenic patients in referral centres are of aplastic anaemia. PATIENTS AND METHODS: This was an analysis of 1501 patients diagnosed with aplastic anaemia over a period of seven and half years (January 2007- June 2014) attending the Aplastic clinic of department of haematology of All India Institute of Medical Sciences, New Delhi. The details regarding medical history, physical examination, complete blood count, bone marrow aspirate and biopsy, treatment received, were retrieved. Inherited bone marrow failure was screened in patients below 35 years. Treatment response was analysed for various treatment modalities. RESULTS: 1501 patients of AA from 20 different states of India were analysed. The bulk of patients were from Uttar Pradesh (28.7%), Bihar (23.6%), Delhi/NCR (20%) and Haryana (7%).The average number of new aplastic anaemia patients enrolled per year 214 (range: 101 -263). The median age at presentation was 25 years (range 2-83),with M;F - 2.3:1. Severity of AA revealed: severe (SAA): 75%, very severe (VSAA): 15%, non-severe (NSAA): 10%. Inherited bone marrow failure syndromes constituted 5% (75 patients) of all aplastic anaemia patients. The most common clinical presentations were pallor (97%), bleeding manifestations (69.6%) and fever (54%). The haematological parameters showed: median level of haemoglobin level: 5.9 gm/dL, WBC: 2700/mm3, ANC: 380/mm3, platelet: 1 0000/mm3. PNH clone was present in 13.5% of patients. 107 patients (7%) were lost to follow up or expired before any treatment was initiated. Only 69 patients (4.5%) received treatment with HLA-matched sibling stem cell transplantation and another 232 (15.5%) patients received ATG plus cyclosporine as immunosuppressive therapy. Seven hundred thirteenpatients (47.5%) received cyclosporine. The overall response to various treatment modalities was: HLA matched sibling haematopoietic stem cell transplant: 75.3%, Anti-thymocyte globulin plus cyclosporine: 58.7%, cyclosporine plus androgen: 45.6%, cyclosporine alone: 32.2%. CONCLUSION: Management of AA is a real challenge in developing countries.This is one of the largest case series from a single centre from India. It is our endeavour to reduce the detrimental outcome by increasing awareness among patients and referring physicians to reduce the delay between diagnosis and treatment.


Assuntos
Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Terapia de Imunossupressão , Adulto , Anemia Aplástica/sangue , Anemia Aplástica/diagnóstico , Anemia Aplástica/epidemiologia , Anemia Aplástica/fisiopatologia , Anemia Aplástica/terapia , Exame de Medula Óssea/estatística & dados numéricos , Gerenciamento Clínico , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Terapia de Imunossupressão/métodos , Terapia de Imunossupressão/estatística & dados numéricos , Incidência , Índia/epidemiologia , Masculino , Avaliação de Resultados em Cuidados de Saúde , Gravidade do Paciente , Estudos Retrospectivos
16.
Mol Cell Biochem ; 387(1-2): 55-61, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24213682

RESUMO

Although normally folic acid is given during pregnancy, presumably to prevent neural tube defects, the mechanisms of this protection are unknown. More importantly it is unclear whether folic acid has other function during development. It is known that folic acid re-methylates homocysteine (Hcy) to methionine by methylene tetrahydrofolate reductase-dependent pathways. Folic acid also generates high-energy phosphates, behaves as an antioxidant and improves nitric oxide (NO) production by endothelial NO synthase. Interestingly, during epigenetic modification, methylation of DNA/RNA generate homocysteine unequivocally. The enhanced overexpression of methyl transferase lead to increased yield of Hcy. The accumulation of Hcy causes vascular dysfunction, reduces perfusion in the muscles thereby causing musculopathy. Another interesting fact is that children with severe hyperhomocysteinaemia (HHcy) have skeletal deformities, and do not live past teenage. HHcy is also associated with the progeria syndrome. Epilepsy is primarily caused by inhibition of gamma-amino-butyric-acid (GABA) receptor, an inhibitory neurotransmitter in the neuronal synapse. Folate deficiency leads to HHcy which then competes with GABA for binding on the GABA receptors. With so many genetic and clinical manifestations associated with folate deficiency, we propose that folate deficiency induces epigenetic alterations in the genes and thereby results in disease.


Assuntos
Epigênese Genética , Deficiência de Ácido Fólico/genética , Homocisteína/fisiologia , Metionina/fisiologia , Animais , Síndrome de Fadiga Crônica/genética , Ácido Fólico/administração & dosagem , Ácido Fólico/fisiologia , Interação Gene-Ambiente , Humanos , Defeitos do Tubo Neural/genética , Progéria/genética
17.
J Obstet Gynaecol ; 34(1): 104-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24359071

RESUMO

Uterine arteriovenous malformations are rare lesions which have a varied presentation that may range from the patient being asymptomatic to varying degrees of menorrhagia. It can be diagnosed by Doppler sonography but a strong index of suspicion is necessary. Management of this condition depends on presentation and available resources. In asymptomatic patients, we can leave the patients on regular follow-up as many lesions regress spontaneously. In patients with excessive haemorrhage not responding to embolisation or when facilities of embolisation are not available, hysterectomy needs to be done. Uterine artery embolisation should be considered the optimum treatment, as it has a high success rate coupled with few complications and also has fertility-preserving potential. Clinical follow-up usually suffices but sonography may occasionally be required.


Assuntos
Malformações Arteriovenosas/diagnóstico , Útero/irrigação sanguínea , Adulto , Malformações Arteriovenosas/terapia , Feminino , Humanos , Embolização da Artéria Uterina
18.
J Clin Neurosci ; 120: 30-35, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176112

RESUMO

Intraoperative bleeding poses a substantial challenge, particularly in neuro-spine surgeries leading to complications such as hematomas, infections, and hemodynamic instability. Despite their proven efficacy, use of topical hemostatic agents (THAs) lacks comprehensive published literature and guidelines particularly in the Indian setting. The present study provides the first-ever Indian expert panel recommendations for effective adjunct THA use in different intraoperative bleeding sites and situations in neuro-spine surgeries. A comprehensive approach, encompassing a literature review, followed by experience sharing in a meeting using a survey helped integrate expert opinions in the form of practical algorithms to guide THA selection. Our survey results revealed a strong inclination towards specific THAs, flowable gelatin + thrombin being choice of THA for difficult to access and problematic bleeding situations during tumor removal/resection, transsphenoidal hypophysectomy and skull-based procedures. Both oxidized regenerated cellulose (ORC)/Fibrillar and flowable gelatin + thrombin were recommended for continuous oozing. ORC/Fibrillar was preferred for arteriovenous and cavernous malformations. This expert-panel guidance on THA use aims to optimize hemostat use practices and improve surgical outcomes in neuro-spine surgery.


Assuntos
Hemostáticos , Humanos , Hemostáticos/uso terapêutico , Trombina/uso terapêutico , Gelatina , Hemostasia Cirúrgica , Perda Sanguínea Cirúrgica/prevenção & controle
19.
Pharmacology ; 91(5-6): 287-96, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23736684

RESUMO

BACKGROUND: Vasomotor responses conducted from terminal arterioles to proximal vessels may contribute to match tissue demands and blood supply during skeletal muscle contraction. Conduction of vasodilatation (CVD) from distal resistance arterioles to the proximal arterioles and feeding arteries during metabolic demand is mediated by intercellular gap junctions in the vascular endothelium. The role of hyperhomocysteinemia (HHcy) in the musculoskeletal system during CVD is unclear. We hypothesize that during HHcy, there is impaired CVD due to decreased expression of endothelial-associated connexins and thus decreased tissue perfusion to the contracting skeletal muscles. METHODS: CVD studies were performed in a gluteus maximus muscle preparation of wild-type (C57BL6/J) and CBS-/+ (HHcy) mice using intravital microscopy. Expression of connexins and myostatin protein (an antiskeletal muscle statin) was studied by Western blot and immunohistochemistry methods. Tissue perfusion to acetylcholine was assessed by the laser Doppler technique. RESULTS: There was decreased CVD and tissue perfusion in response to acetylcholine in CBS-/+ mice compared to wild-type controls. There was decreased expression of connexins 37, 40 and 43 and increased expression of myostatin in CBS-/+ mice compared to wild-type controls. CONCLUSION: Our findings suggest that CVD in skeletal muscle is decreased during HHcy due to decreased expression of gap junction connexins.


Assuntos
Arteríolas/fisiopatologia , Hiper-Homocisteinemia/fisiopatologia , Músculo Esquelético/irrigação sanguínea , Animais , Colágeno/metabolismo , Conexinas/metabolismo , Hiper-Homocisteinemia/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Músculo Esquelético/metabolismo , Miostatina/metabolismo , Vasodilatação
20.
J Obstet Gynaecol ; 33(8): 810-3, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24219719

RESUMO

The aim of this study was to evaluate scar thickness in cases of pregnancy with previous caesarean section, by trans-vaginal sonography (TVS) and magnetic resonance imaging (MRI), and to correlate precision of radiologically-measured scar thickness with actual measurement of scar thickness. A total of 35 pregnant patients with previous caesarean section planned for elective caesarean section, were evaluated prospectively. Their scar thickness was measured by TVS and MRI on the day of elective repeat caesarean section. These measurements were correlated with each other and with scar thickness measured during elective repeat caesarean section by using a caliper. The correlation coefficients between scar thickness measured by TVS and MRI with peroperative evaluation with a caliper, were +0.72 and +0.59, respectively. The study concluded that as MRI is a costlier modality and TVS has better correlation coefficient with actual scar thickness, TVS can be considered to be the better modality for antenatal scar thickness measurement.


Assuntos
Cesárea/efeitos adversos , Cicatriz/diagnóstico por imagem , Adulto , Cicatriz/etiologia , Cicatriz/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Gravidez , Ultrassonografia , Útero/diagnóstico por imagem , Útero/patologia , Adulto Jovem
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