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1.
Hum Mol Genet ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832639

RESUMO

Spinocerebellar ataxia type 10 (SCA10) is a rare autosomal dominant ataxia caused by a large expansion of the (ATTCT)n repeat in ATXN10. SCA10 was described in Native American and Asian individuals which prompted a search for an expanded haplotype to confirm a common ancestral origin for the expansion event. All patients with SCA10 expansions in our cohort share a single haplotype defined at the 5'-end by the minor allele of rs41524547, located ~35 kb upstream of the SCA10 expansion. Intriguingly, rs41524547 is located within the miRNA gene, MIR4762, within its DROSHA cleavage site and just outside the seed sequence for mir4792-5p. The world-wide frequency of rs41524547-G is less than 5% and found almost exclusively in the Americas and East Asia-a geographic distribution that mirrors reported SCA10 cases. We identified rs41524547-G(+) DNA from the 1000 Genomes/International Genome Sample Resource and our own general population samples and identified SCA10 repeat expansions in up to 25% of these samples. The reduced penetrance of these SCA10 expansions may be explained by a young (pre-onset) age at sample collection, a small repeat size, purity of repeat units, or the disruption of miR4762-5p function. We conclude that rs41524547-G is the most robust at-risk SNP allele for SCA10, is useful for screening of SCA10 expansions in population genetics studies and provides the most compelling evidence to date for a single, prehistoric origin of SCA10 expansions sometime prior to or during the migration of individuals across the Bering Land Bridge into the Americas.

2.
Immunology ; 169(2): 132-140, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36465031

RESUMO

Breast cancer liver metastases (BCLM) are usually unresectable and difficult to treat with systemic chemotherapy. A major reason for chemotherapy failure is that BCLM are typically small, avascular nodules, with poor transport and fast washout of therapeutics from surrounding capillaries. We have previously shown that nanoalbumin-bound paclitaxel (nab-PTX) encapsulated in porous silicon multistage nanovectors (MSV) is preferentially taken up by tumour-associated macrophages (TAM) in the BCLM microenvironment. The TAM alter therapeutic transport characteristics and retain it in the tumour vicinity, increasing cytotoxicity. Computational modeling has shown that therapeutic regimens could be designed to eliminate single lesions. To evaluate clinically-relevant scenarios, this study develops a modeling framework to evaluate MSV-nab-PTX therapy targeting multiple BCLM. An experimental model of BCLM, splenic injection of breast cancer 4 T1 cells was established in BALB/C mice. Livers were analyzed histologically to determine size and density of BCLM. The data were used to calibrate a 3D continuum mixture model solved via distributed computing to enable simulation of multiple BCLM. Overall tumour burden was analyzed as a function of metastases number and potential therapeutic regimens. The computational model enables realistic 3D representation of metastatic tumour burden in the liver, with the capability to evaluate BCLM growth and therapy response for hundreds of lesions. With the given parameter set, the model projects that repeated MSV-nab-PTX treatment in intervals <7 days would control the tumour burden. We conclude that nanotherapy targeting TAM associated with BCLM may be evaluated and fine-tuned via 3D computational modeling that realistically simulates multiple metastases.


Assuntos
Neoplasias Hepáticas , Animais , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Hepáticas/tratamento farmacológico , Macrófagos , Paclitaxel/uso terapêutico , Microambiente Tumoral , Melanoma Maligno Cutâneo
3.
Chromosoma ; 129(3-4): 215-226, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32651609

RESUMO

Heterochromatin protein 1ß (HP1ß), encoded by the Cbx1 gene, has been functionally linked to chromatin condensation, transcriptional regulation, and DNA damage repair. Here we report that testis-specific Cbx1 conditional knockout (Cbx1 cKO) impairs male germ cell development in mice. Depletion of HP1ß negatively affected sperm maturation and increased seminiferous tubule degeneration in Cbx1 cKO mice. In addition, the spermatogonia have elevated γ-H2AX foci levels as do Cbx1 deficient mouse embryonic fibroblasts (MEFs) as compared to wild-type (WT) control MEFs. The increase in γ-H2AX foci in proliferating Cbx1 cKO cells indicates defective replication-dependent DNA damage repair. Depletion or loss of HP1ß from human cells and MEFs increased DNA replication fork stalling and firing of new origins of replication, indicating defective DNA synthesis. Taken together, these results suggest that loss of HP1ß in proliferating cells leads to DNA replication defects with associated DNA damage that impact spermatogenesis.


Assuntos
Proteínas Cromossômicas não Histona/genética , Replicação do DNA , Regulação da Expressão Gênica no Desenvolvimento , Espermatogênese/genética , Alelos , Animais , Apoptose/genética , Linhagem Celular , Homólogo 5 da Proteína Cromobox , Proteínas Cromossômicas não Histona/metabolismo , Replicação do DNA/efeitos dos fármacos , Imunofluorescência , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Marcação de Genes , Loci Gênicos , Histonas/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Knockout , Fenótipo , Maturação do Esperma/genética , Espermatogênese/efeitos dos fármacos , Espermatogônias/citologia , Espermatogônias/metabolismo
4.
J Biol Chem ; 294(37): 13619-13628, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31320473

RESUMO

Prion diseases are a group of incurable neurodegenerative disorders that affect humans and animals via infection with proteinaceous particles called prions. Prions are composed of PrPSc, a misfolded version of the cellular prion protein (PrPC). During disease progression, PrPSc replicates by interacting with PrPC and inducing its conversion to PrPSc As PrPSc accumulates, cellular stress mechanisms are activated to maintain cellular proteostasis, including increased protein chaperone levels. However, the exact roles of several of these chaperones remain unclear. Here, using various methodologies to monitor prion replication (i.e. protein misfolding cyclic amplification and cellular and animal infectivity bioassays), we studied the potential role of the molecular chaperone heat shock protein 70 (HSP70) in prion replication in vitro and in vivo Our results indicated that pharmacological induction of the heat shock response in cells chronically infected with prions significantly decreased PrPSc accumulation. We also found that HSP70 alters prion replication in vitro More importantly, prion infection of mice lacking the genes encoding stress-induced HSP70 exhibited accelerated prion disease progression compared with WT mice. In parallel with HSP70 being known to respond to endogenous and exogenous stressors such as heat, infection, toxicants, and ischemia, our results indicate that HSP70 may also play an important role in suppressing or delaying prion disease progression, opening opportunities for therapeutic intervention.


Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Doenças Priônicas/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Progressão da Doença , Retículo Endoplasmático/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Feminino , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Priônicas/metabolismo , Príons/metabolismo , Dobramento de Proteína
5.
Cerebellum ; 18(1): 99-108, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29987489

RESUMO

Cerebellar Purkinje cells (PCs) show conspicuous damages in many ataxic disorders. Targeted delivery of short nucleic acids, such as antisense oligonucleotides, to PCs may be a potential treatment for ataxic disorders, especially spinocerebellar ataxias (SCAs), which are mostly caused by a gain of toxic function of the mutant RNA or protein. However, oligonucleotides do not cross the blood-brain barrier (BBB), necessitating direct delivery into the central nervous system (CNS) through intra-thecal, intra-cisternal, intra-cerebral ventricular, or stereotactic parenchymal administration. We have developed a novel liposome (100 to 200 nm in diameter) formulation, DCL64, composed of dipalmitoyl-phosphatidylcholine, cholesterol, and poloxamer L64, which incorporates oligonucleotides efficiently (≥ 70%). Confocal microscopy showed that DCL64 was selectively taken up by brain microvascular endothelial cells by interacting with low-density lipoprotein receptor (LDLr) family members on cell surface, but not with other types of lipid receptors such as caveolin or scavenger receptor class B type 1. LDLr family members are implicated in brain microvascular endothelial cell endocytosis/transcytosis, and are abundantly localized on cerebellar PCs. Intravenous administration of DCL64 in normal mice showed distribution of oligonucleotides to the brain, preferentially in PCs. Mice that received DCL64 showed no adverse effect on hematological, hepatic, and renal functions in blood tests, and no histopathological abnormalities in major organs. These studies suggest that DCL64 delivers oligonucleotides to PCs across the BBB via intravenous injection with no detectable adverse effects. This property potentially makes DCL64 particularly attractive as a delivery vehicle in treatments of SCAs.


Assuntos
Lipossomos , Oligonucleotídeos/administração & dosagem , Células de Purkinje/efeitos dos fármacos , Administração Intravenosa , Animais , Linhagem Celular , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Fibroblastos/metabolismo , Humanos , Camundongos Endogâmicos ICR , Microvasos/citologia , Microvasos/metabolismo , Oligonucleotídeos/farmacocinética , Células de Purkinje/citologia , Células de Purkinje/metabolismo , Receptores de LDL/metabolismo , Ataxias Espinocerebelares/tratamento farmacológico
6.
bioRxiv ; 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37292856

RESUMO

Traumatic Brain Injury (TBI) can have long-lasting physical, emotional, and cognitive consequences due to the neurodegeneration caused by its robust inflammatory response. Despite advances in rehabilitation care, effective neuroprotective treatments for TBI patients are lacking. Furthermore, current drug delivery methods for TBI treatment are inefficient in targeting inflamed brain areas. To address this issue, we have developed a liposomal nanocarrier (Lipo) encapsulating dexamethasone (Dex), an agonist for the glucocorticoid receptor utilized to alleviate inflammation and swelling in various conditions. In vitro studies show that Lipo-Dex were well tolerated in human and murine neural cells. Lipo-Dex showed significant suppression of inflammatory cytokines, IL-6 and TNF-α, release after induction of neural inflammation with lipopolysaccharide. Further, the Lipo-Dex were administered to young adult male and female C57BL/6 mice immediately after a controlled cortical impact injury. Our findings demonstrate that Lipo-Dex can selectively target the injured brain, thereby reducing lesion volume, cell death, astrogliosis, the release of proinflammatory cytokines, and microglial activation compared to Lipo-treated mice in a sex-dependent manner, showing a major impact only in male mice. This highlights the importance of considering sex as a crucial variable in developing and evaluating new nano-therapies for brain injury. These results suggest that Lipo-Dex administration may effectively treat acute TBI.

7.
Neurotherapeutics ; 18(3): 1710-1728, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34160773

RESUMO

CAG repeat expansion is the genetic cause of nine incurable polyglutamine (polyQ) diseases with neurodegenerative features. Silencing repeat RNA holds great therapeutic value. Here, we developed a repeat-based RNA-cleaving DNAzyme that catalyzes the destruction of expanded CAG repeat RNA of six polyQ diseases with high potency. DNAzyme preferentially cleaved the expanded allele in spinocerebellar ataxia type 1 (SCA1) cells. While cleavage was non-allele-specific for spinocerebellar ataxia type 3 (SCA3) cells, treatment of DNAzyme leads to improved cell viability without affecting mitochondrial metabolism or p62-dependent aggresome formation. DNAzyme appears to be stable in mouse brain for at least 1 month, and an intermediate dosage of DNAzyme in a SCA3 mouse model leads to a significant reduction of high molecular weight ATXN3 proteins. Our data suggest that DNAzyme is an effective RNA silencing molecule for potential treatment of multiple polyQ diseases.


Assuntos
DNA Catalítico/administração & dosagem , DNA Catalítico/genética , Doença de Machado-Joseph/genética , Peptídeos/genética , RNA/genética , Expansão das Repetições de Trinucleotídeos/genética , Animais , Ataxina-3/genética , Linhagem Celular Tumoral , Inativação Gênica/fisiologia , Células HEK293 , Humanos , Doença de Machado-Joseph/terapia , Camundongos , Peptídeos/metabolismo , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/terapia , Técnicas Estereotáxicas
8.
Indian J Community Med ; 45(2): 159-163, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32905269

RESUMO

BACKGROUND: Maternal health is severely affected by home deliveries because it contributes to maternal mortality, especially if home births are not made safer. OBJECTIVES: The present study aimed to assess the determinants of home delivery among mothers in urban and rural Vadodara district, Gujarat. MATERIALS AND METHODS: This community-based, cross-sectional study was carried out during April 2017-July 2017. The mothers who delivered at home and hospital in urban and rural Vadodara district between April 15 and March 16 were included in the study. A semi-structured questionnaire was used for interviewing all the mothers. Information regarding sociodemographic and obstetrics characteristics of mothers was recorded. The study finding was presented in the form of frequencies and percentages, and the association was found with Chi-square test.P ≤0.05 was considered statistically significant. RESULTS: The present study was carried out among 138 mothers, of them, 71.7% were in the age group of 20-25 years. The mean age of mothers was 24.5 ± 4.4 years. The analysis of sociodemographic and obstetric factors revealed that mothers age more than 25 years, mothers from nuclear family, illiterate mothers, late antenatal care registration by mothers, mothers not registered in Janani Suraksha Yojna/Chiranjeevi Yojana scheme, and prior experience of home delivery by mothers were significantly associated with home delivery (P < 0.05 each). CONCLUSIONS: This study highlighted that several sociodemographic and obstetrics determinants related to mother were associated with home delivery in the study setting. Taking these findings into consideration, it is recommended that appropriate maternity services should be designed with a special focus on poor, uneducated, and multiparous women as well as it should ensure early registration of pregnancy for every pregnant woman. Institutional delivery should be encouraged and advocated among mothers having all previous deliveries at home.

9.
PLoS One ; 15(3): e0228789, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160188

RESUMO

Large expansions of microsatellite DNA cause several neurological diseases. In Spinocerebellar ataxia type 10 (SCA10), the repeat interruptions change disease phenotype; an (ATTCC)n or a (ATCCT)n/(ATCCC)n interruption within the (ATTCT)n repeat is associated with the robust phenotype of ataxia and epilepsy while mostly pure (ATTCT)n may have reduced penetrance. Large repeat expansions of SCA10, and many other microsatellite expansions, can exceed 10,000 base pairs (bp) in size. Conventional next generation sequencing (NGS) technologies are ineffective in determining internal sequence contents or size of these expanded repeats. Using repeat primed PCR (RP-PCR) in conjunction with a high-sensitivity pulsed-field capillary electrophoresis fragment analyzer (FEMTO-Pulse, Agilent, Santa Clara, CA) (RP-FEMTO hereafter), we successfully determined sequence content of large expansion repeats in genomic DNA of SCA10 patients and transformed yeast artificial chromosomes containing SCA10 repeats. This RP-FEMTO is a simple and economical methodology which could complement emerging NGS for very long sequence reads such as Single Molecule, Real-Time (SMRT) and nanopore sequencing technologies.


Assuntos
Ataxina-10/genética , Eletroforese Capilar/métodos , Repetições de Microssatélites/genética , Ataxias Espinocerebelares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Expansão das Repetições de DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
11.
Environ Monit Assess ; 155(1-4): 467-75, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18629441

RESUMO

A study was conducted to test the effects of soil amendments on the bioavailability of heavy metals in a zinc mine tailings containing soil to plants, using the Indian mustard plant (Brassica juncea) as a test organism. Zinc mine tailing containing soil was amended with humus soil (HS) and phosphatic clay (PC). The zinc mine tailing containing soil (ZMTS) was characterized for heavy metals. It was mixed with PC and HS, and four mixtures were prepared. The first mixture contained ZMTS, and served as a control. The second mixture contained ZMTS and PC in the ratio of 1:1 (w/w). The third mixture contained ZMTS and HS in the ratio of 1:1(w/w). The fourth mixture containing ZMTS, PC and HS in the ratio of (2:1:1) (w/w). A slight increase in the bioavailability of Pb, Cu, Zn and Mn was noticed with increase in the incubation time from 14 to 42 days. The bioavailability of Pb, Cu, Zn and Mn from ZMTS alone in Brassica plant was in the range of 94-99% up to 42 days. Addition of PC and HS to the ZMTS soil reduced the bioavailabilities of Pb by (15%), of Cu by (20%), of Zn by (20%) and of Mn by (25%) in the mustard plant. The data showed that PC in the presence of HS had a high affinity for the heavy metals in the order of Pb, Cu, Zn and Mn.


Assuntos
Mineração , Mostardeira/metabolismo , Poluentes do Solo/farmacocinética , Solo/análise , Zinco/farmacocinética , Disponibilidade Biológica , Monitoramento Ambiental , Índia , Poluentes do Solo/metabolismo , Zinco/metabolismo
12.
Anim Reprod Sci ; 101(1-2): 179-85, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17196345

RESUMO

Early embryonic development and implantation were studied in tropical short-nosed fruit bat Cyanopterus sphinx. We report preimplantation development and embryo implantation. Different stages of cleavage were observed in embryo by direct microscopic examination of fresh embryos after retrieving them either from the oviduct or the uterus at different days, up to the day of implantation. Generally, the embryos enter the uterus at the 8-cell stage. Embryonic development continued without any delay and blastocyst were formed showing attachment to the uterine epithelium at the mesometrial side of the uterus. A distinct blue band was formed in the uterus. The site of blastocyst attachment was visualized as a blue band following intravenous injection of pontamine blue. Implantation occurred 9+/-0.7 days after mating. This study reports that bat embryonic development can be studied like other laboratory animals and that this bat shows blue dye reaction, indicating the site and exact time of implantation. This blue dye reaction can be used to accurately find post-implantational delay. We prove conclusively that this species of tropical bat does not have any type of embryonic diapause.


Assuntos
Permeabilidade Capilar/fisiologia , Quirópteros/fisiologia , Implantação do Embrião/fisiologia , Endométrio/irrigação sanguínea , Prenhez , Animais , Embrião de Mamíferos/citologia , Desenvolvimento Embrionário/fisiologia , Feminino , Gravidez , Coloração e Rotulagem , Fatores de Tempo , Azul Tripano/farmacologia
13.
Stem Cell Reports ; 9(5): 1660-1674, 2017 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-29103969

RESUMO

The nitric oxide (NO)-cyclic GMP pathway contributes to human stem cell differentiation, but NO free radical production can also damage DNA, necessitating a robust DNA damage response (DDR) to ensure cell survival. How the DDR is affected by differentiation is unclear. Differentiation of stem cells, either inducible pluripotent or embryonic derived, increased residual DNA damage as determined by γ-H2AX and 53BP1 foci, with increased S-phase-specific chromosomal aberration after exposure to DNA-damaging agents, suggesting reduced homologous recombination (HR) repair as supported by the observation of decreased HR-related repair factor foci formation (RAD51 and BRCA1). Differentiated cells also had relatively increased fork stalling and R-loop formation after DNA replication stress. Treatment with NO donor (NOC-18), which causes stem cell differentiation has no effect on double-strand break (DSB) repair by non-homologous end-joining but reduced DSB repair by HR. Present studies suggest that DNA repair by HR is impaired in differentiated cells.


Assuntos
Diferenciação Celular , Células-Tronco Embrionárias/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Reparo de DNA por Recombinação , Células Cultivadas , Dano ao DNA , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Compostos Nitrosos/toxicidade
14.
Life Sci ; 79(23): 2217-20, 2006 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-16934298

RESUMO

The ovulation induction property of ICI 182,780 a pure antiestrogen and enclomiphene citrate (ENC) was carried out in Scotophilus heathi, an Indian tropical vespertillionid bat, during December to February i.e., preovulatory period. This bat ovulates two ova naturally and shows ovulatory asynchrony. The study showed that 100 ìg of ENC followed by 10 IU hCG resulted in significantly lower number of ovulation. Whereas, the pure antiestrogen ICI 182,780 at a dose of 100 ìg followed by 10 IU hCG resulted in ovulation induction (4.2 +/- 0.4), which is significantly different in comparison to other groups. This is possibly the first report of ovulation induction using this pure antiestrogen i.e., ICI 182,780 in any bat as well as in any animal model that exhibits temporary anovulation similar to polycystic ovary disease (PCOD). This antiestrogen may be useful to induce ovulation in PCOD patients.


Assuntos
Antineoplásicos Hormonais/farmacologia , Quirópteros/metabolismo , Clomifeno/farmacologia , Enclomifeno , Estradiol/análogos & derivados , Ovulação/efeitos dos fármacos , Animais , Anovulação/tratamento farmacológico , Anovulação/patologia , Estradiol/farmacologia , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Fulvestranto , Humanos , Índia , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/patologia
15.
Artigo | IMSEAR | ID: sea-200983

RESUMO

Background: Poor outcomes of cataract surgery are a major problem in developing countries, including India which affects the demand and uptake of cataract surgical services. The present study was aimed to assess the visual outcomes after cataract surgery and identify factors associated with it, among persons aged 50 year and above in urban slums of Raipur.Methods: A community-based, cross-sectional study was conducted in15 randomly selected clusters (urban slums) of Raipur from June 2012 to March 2013. Interviews, Visual Acuity measurements and ocular examinations were performed on all persons aged 50 year and above through house to house visits. Details about surgical intervention i.e. date, setting, type of cataract surgery were obtained from cataract operated persons, for each eye that had cataract surgery. Collected data were analyzed by using both descriptive and inferential statistics. The chi- square test was used to determine the associations of different cataract related parameters with visual outcomes in cataract operated eyes.Results: Of the 870 participants, 203 persons (329 eyes) had undergone cataract surgery. Among all operated eyes, visual outcome was good (VA ?6/18) in 84.5%, borderline (VA <6/18 and ?6/60) in 12.5%, and poor (VA <6/60) in 3% of eyes with available correction. Visual outcome of cataract surgery was significantly associated with age at time of surgery, literacy, type of surgery, place of surgery and time since surgery.Conclusions: The visual outcomes of cataract surgery were excellent in study area; it can be further improved by appropriate refractive correction, provision of glasses and adequate follow up after cataract surgery.

16.
Artigo | IMSEAR | ID: sea-198644

RESUMO

Background: The DCT is lined with simple cuboidal cells that are shorter than those of the proximal convolutedtubule (PCT). The lumen appears larger in DCT, the histological changes DCT in kidney after death have beenstudied in various land animals and sea marine animals but yet very few studies with same view which mayprovide keen and fruitful results for human distal convoluted tubule in kidney have been done. It will be helpfulfor estimation of time after death.Aim: To determine the time since death by histological changes in Distal convoluted tubule.Materials and Methods: 50 Human kidneys samples at different time intervals between 4hrs to 52.30 hr,temperature between17.3/22.3-31.3/450C, humidity between 11/36 to 75/95, were of different age and sex obtainedas and when available from cadavers with a known time of death where death had resulted from natural death,suffocation and trauma, dead individual health and not suffering from disease affecting kidney.Result: Increase the rate of postmortem histological changes in DCT was found to be increased with rise in thetemperature and duration. In Distal convoluted tubules lumens were found swelling of epithelial cells. Retractionof epithelium from the basement membrane and its disruption with individualization of cells, nuclear pyknosis,karyolysis and loss of tubular architecture with debris in the lumen were observed.Conclusion: In this current research, sequence of postmortem histological changes in DCT was studied. Thesecriteria’s presented in this study could be used to determine the time after death

17.
Artigo | IMSEAR | ID: sea-201896

RESUMO

Background: Acquired immunodeficiency syndrome (AIDS) is one of the deadliest diseases that modern medicine has ever had to tackle. Understanding the knowledge about HIV/AIDS in general populations will help in formulating strategy for prevention and treatment. With this background, this study was conducted to assess the knowledge and awareness about HIV/AIDS among general population.Methods: A cross sectional study was conducted at C.C.M. Medical College and Hospital, Durg during December 2018 to January 2019. The data was collected from 450 patients attending the medicine outpatient department. Study subjects were selected using convenient sampling technique. Patients giving consent and willing to participate were included in the study. The data was collected in predesigned and pretested questionnaire.Results: 77.11% study participants were aware that unprotected sex can lead to transmission of HIV, 73.78% knew that shaking hands will not transmit the disease. 79.8% knew that use of condom can prevent transmission of HIV/AIDS. Overall males had better knowledge than females. 76.85% said they would behave friendly with people having HIV/AIDS and 69.78% were willing to take care of relatives with HIV.Conclusions: This study indicates that majority participants have good knowledge about difference between HIV and AIDS, modes of transmission and prevention though they were not completely aware of it. The proportion of those with lack of correct knowledge though comparatively less, needs to be taken as a challenge and addressed through well planned health educational activities at various platforms including teaching hospital premises.

18.
J Clin Invest ; 124(9): 3767-80, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25083987

RESUMO

Metaplasia can result when injury reactivates latent developmental signaling pathways that determine cell phenotype. Barrett's esophagus is a squamous-to-columnar epithelial metaplasia caused by reflux esophagitis. Hedgehog (Hh) signaling is active in columnar-lined, embryonic esophagus and inactive in squamous-lined, adult esophagus. We showed previously that Hh signaling is reactivated in Barrett's metaplasia and overexpression of Sonic hedgehog (SHH) in mouse esophageal squamous epithelium leads to a columnar phenotype. Here, our objective was to identify Hh target genes involved in Barrett's pathogenesis. By microarray analysis, we found that the transcription factor Foxa2 is more highly expressed in murine embryonic esophagus compared with postnatal esophagus. Conditional activation of Shh in mouse esophageal epithelium induced FOXA2, while FOXA2 expression was reduced in Shh knockout embryos, establishing Foxa2 as an esophageal Hh target gene. Evaluation of patient samples revealed FOXA2 expression in Barrett's metaplasia, dysplasia, and adenocarcinoma but not in esophageal squamous epithelium or squamous cell carcinoma. In esophageal squamous cell lines, Hh signaling upregulated FOXA2, which induced expression of MUC2, an intestinal mucin found in Barrett's esophagus, and the MUC2-processing protein AGR2. Together, these data indicate that Hh signaling induces expression of genes that determine an intestinal phenotype in esophageal squamous epithelial cells and may contribute to the development of Barrett's metaplasia.


Assuntos
Esôfago de Barrett/etiologia , Esôfago/embriologia , Proteínas Hedgehog/fisiologia , Fator 3-beta Nuclear de Hepatócito/fisiologia , Transdução de Sinais/fisiologia , Animais , Esôfago de Barrett/metabolismo , Feminino , Fator 3-beta Nuclear de Hepatócito/análise , Fator 3-beta Nuclear de Hepatócito/genética , Fatores de Transcrição Kruppel-Like , Camundongos , Camundongos Endogâmicos C57BL , Mucina-2/genética , Mucoproteínas/genética , Proteínas Oncogênicas , Fatores de Transcrição SOX9/fisiologia , Proteína GLI1 em Dedos de Zinco
19.
Endocrinology ; 153(12): 6054-64, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23087172

RESUMO

Cervical ripening is associated with loss of structural integrity and tensile strength, thus enabling the cervix to dilate at term. It is characterized by changes in glycosaminoglycan composition, increased water content, and a progressive reorganization of the collagen network. The peptide hormone relaxin via interaction with its receptor, relaxin family peptide receptor 1 (RXFP1), promotes tissue hydration and increases cervical hyaluronan (HA) concentrations, but the mechanisms that regulate these effects are not known. This study in relaxin mutant (Rln(-/-)) mice tested the hypothesis that relaxin regulates HA synthase and aquaporin (AQP) expression in the cervix. We also assessed expression of the RXFP1 protein by immunohistochemistry. Pregnant Rln(-/-) mice had lower Has2 and Aqp3 expression on d 18.5 of pregnancy and decreased cervical HA compared with wild-type Rln(+/+) mice. Chronic infusion of relaxin for 4 or 6 d in pregnant Rln(-/-) mice reversed these phenotypes and increased Has2 and Aqp3 compared with placebo controls. Relaxin-treated mice also had lower Has1 and Aqp5. Changes in gene expression were paralleled by increases in cervical HA and variations in AQP3 and AQP5 protein localization in epithelial cells of Rln(-/-) cervices. Our findings demonstrate that relaxin alters AQP expression in the cervix and initiates changes in glycosaminoglycan composition through increased HA synthesis. These effects are likely mediated through RXFP1 localized to subepithelial stromal cells and epithelial cells. We suggest these actions of relaxin collectively promote water recruitment into the extracellular matrix to loosen the dense collagen fiber network.


Assuntos
Aquaporinas/metabolismo , Colo do Útero/metabolismo , Regulação da Expressão Gênica , Ácido Hialurônico/biossíntese , Relaxina/fisiologia , Animais , Maturidade Cervical/metabolismo , Feminino , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fenótipo , Gravidez , Prenhez , Fatores de Tempo
20.
Artigo em Inglês | IMSEAR | ID: sea-165767

RESUMO

Lifestyle diseases characterized by those diseases whose occurrence is primarily based on the daily habits of people and are a result of an inappropriate relationship of people with their environment. The main factors contributing to lifestyle diseases include bad food habits, physical inactivity, wrong body posture, and disturbed biological clock. Lifestyle diseases are the most common causes of disability, morbidity and premature mortality. They account for 52% of deaths, 43% Disability Adjusted Life Years (DALYs) and 62% of total disease burden in India. Life style disease can be prevented through focused and comprehensive public health intervention by establishment of Healthy Life Style Centre (HLSC). HLSC will be a comprehensive approach which will provide health services for Non-Communicable diseases under the one roof. The HLSC will offer consultation, learning, counselling and testing facilities regarding Diabetes and other Non-Communicable diseases (NCD). Life style diseases can be prevented through public health intervention by special task force and policy document related to life style disorders.

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