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1.
Microbiol Resour Announc ; : e0009124, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39083690

RESUMEN

We present the draft genome sequences of 23 Brucella melitensis isolates derived from human and animal sources across India with genome size predominantly at 3.207 M and uniform GC content (57.24%) across isolates. The accession numbers and detailed sequencing data enhance the utility of this resource for further genomic studies.

2.
Natl J Maxillofac Surg ; 15(1): 59-66, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38690254

RESUMEN

Background and Aim: As oral submucous fibrosis (OSMF) is a chronic progressive disorder, the treatment is based on the severity of the disease. Surgical treatment is the only choice for grade III and grade IV OSMF cases because the patient can neither clean his/her mouth nor properly chew. The resulting soft tissue defect requires resurfacing with various well-vascularized tissues such as extraoral flaps, intraoral flaps, microvascular flaps, and allografts that have been used. Reconstruction of the resultant defects proved to be challenging. Till date, none of the flaps has been proven to be effective and is universally accepted for the treatment of OSMF because of various drawbacks of the available techniques. This study was conducted to know whether an endoscopic-assisted platysma flap is associated with better outcomes in terms of ease of operation and postoperative function than the conventional approach. Materials and Methods: This study included 40 patients of grade III and grade IV OSMF reporting to the outpatient department of oral and maxillofacial surgery in a tertiary center of North India. These patients were divided randomly into two groups. Group I and Group II had 20 patients each, undergoing endoscopic-assisted platysma flap and non-endoscopic-assisted platysma flap for reconstruction after resection of OSMF bands, respectively. Data were analyzed for the mouth opening, operating time, flap viability, congestion of neck and oral cavity, signs of inflammation, neurologic assessment, and measurement of the drain. Results: The results showed significant increase in mouth opening from the preoperative value to the values immediately after surgery and at 24 h, 1 week, 15 days, 1 month, 3 months, and 6 months after surgery in both the study groups. Reduced bleeding incidence was found in group I compared to group II, with better postoperative outcomes noted during follow-up. But the mean intraoperative time of the subjects in group I was 130.80 ± 5.5.908 min and in group II was 105.74 ± 2. 491 min. Increased time taken in group I may be due to the long learning curve. Conclusion: The present study concluded that the Endoscope-assisted technique has a key role during supra and subplatysmal dissection to allow for better accessibility, handling, and visibility of the flap and its orientation in relation to the underlying structures to avoid postoperative complications and to overcome the drawback of platysma myocutaneous flap in reconstruction of OSMF defects.

3.
Cureus ; 16(4): e59197, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38807816

RESUMEN

BACKGROUND: The most common cause of visual impairment globally is refractive error. The prevalence of refractive error has been on the rise since the coronavirus disease 2019 (COVID-19) pandemic, possibly due to increased indoor activities and excessive use of electronic devices. Impaired vision during childhood can affect the overall development of a child adversely, and it often remains unreported due to the inability of children to complain about impaired vision. AIM: The main aim of this study was to assess the prevalence of refractive errors among school-going children in urban and rural areas. METHODS: This was a cross-sectional study that included 2024 children going to schools situated in urban and rural areas. All study subjects were tested for visual acuity for distance using Snellen's chart with and without glasses after taking a brief history regarding visual complaints. All children who had visual acuity less than 6/6 on Snellen's chart underwent refraction check-ups. Retinoscopy was performed in all study subjects. Analysis of the collected data was done using SPSS for Windows, Version 16.0 (Released 2007; SPSS Inc., Chicago, United States). The analysis of numerical data was done by an unpaired t-test, and the analysis of categorical data was done by a chi-square test. A P-value of less than 0.05 was considered statistically significant. RESULTS: The mean age of the children was 10.92 ± 2.73 years, with 10.93 ± 2.73 years in urban and 10.91 ± 2.73 years in rural groups. Females (n=1031; 50.93%) were more in number than males (n=993; 49.06%). The overall prevalence of refractive error was 17.43%. The prevalence was higher in urban areas (22.14%) than in rural areas (12.71%). The age group below 10 years comprised 886 (43.77%) study subjects, and 218 (62.1%) children with refractive error had no ocular complaints. The most common refractive error found in this study was simple myopia in both groups, and the least common was astigmatism. The prevalence of uncorrected refractive error was higher in urban school-going children as compared to rural children. CONCLUSION: The prevalence of refractive error was 17.43% in our study. The prevalence was high in urban areas (22.67%) as compared to rural areas (13.12%). Regular screening of school-going children for refractive errors should be done. Also, awareness regarding the use of electronic gadgets must be raised, especially among urban children.

4.
J Clin Invest ; 134(1)2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-37917202

RESUMEN

Virophagy, the selective autophagosomal engulfment and lysosomal degradation of viral components, is crucial for neuronal cell survival and antiviral immunity. However, the mechanisms leading to viral antigen recognition and capture by autophagic machinery remain poorly understood. Here, we identified cyclin-dependent kinase-like 5 (CDKL5), known to function in neurodevelopment, as an essential regulator of virophagy. Loss-of-function mutations in CDKL5 are associated with a severe neurodevelopmental encephalopathy. We found that deletion of CDKL5 or expression of a clinically relevant pathogenic mutant of CDKL5 reduced virophagy of Sindbis virus (SINV), a neurotropic RNA virus, and increased intracellular accumulation of SINV capsid protein aggregates and cellular cytotoxicity. Cdkl5-knockout mice displayed increased viral antigen accumulation and neuronal cell death after SINV infection and enhanced lethality after infection with several neurotropic viruses. Mechanistic studies demonstrated that CDKL5 directly binds the canonical selective autophagy receptor p62 and phosphorylates p62 at T269/S272 to promote its interaction with viral capsid aggregates. We found that CDKL5-mediated phosphorylation of p62 facilitated the formation of large p62 inclusion bodies that captured viral capsids to initiate capsid targeting to autophagic machinery. Overall, these findings identify a cell-autonomous innate immune mechanism for autophagy activation to clear intracellular toxic viral protein aggregates during infection.


Asunto(s)
Agregado de Proteínas , Virus , Ratones , Animales , Autofagia/genética , Fosforilación , Ratones Noqueados , Proteínas de la Cápside , Antígenos Virales , Proteínas Serina-Treonina Quinasas/genética
5.
Am J Transl Res ; 15(7): 4763-4769, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37560209

RESUMEN

OBJECTIVES: Genetic variations contribute significantly to inter-individual responses to drugs and side effects. Pharmacogenomics has the potential to be utilized as a tool in disorders like schizophrenia with a high degree of genetic inheritance, although data on pharmacogenomics of schizophrenia are limited. Olanzapine and risperidone are the frequently used anti-psychotic drugs used in clinics. Studies have observed the variability in the response of both drugs in schizophrenic individuals. Considering the pharmacogenomics importance of both drugs, we aim to examine the cytochrome P 4501A1 (CYP1A1) and regulator of G-protein signaling 4 (RGS4) variants and their metabolizing status in 94 schizophrenic individuals of Indian descent. METHODS: The present study is retrospective observational study. The metabolizing status of schizophrenic individuals was examined using Axiom Precision Medicine Diversity Array (PMDA) and the data were analyzed with the help of SNP Axiom Analysis Suite v5.1 (Affymetrix). The pharmacogenomics annotation was performed using PharmGKB. RESULTS: Genotype and allele frequencies were observed. The results reveal the high frequency of poor metabolizers of olanzapine and risperidone in the studied cohort. In lieu of the high distribution of poor metabolizers, we compare observed allele frequencies with global populations' data to understand the variability of the genetic pool attained by Indian schizophrenic individuals. CONCLUSIONS: Interestingly, the Indian schizophrenic cohort forms a different cluster compared to global populations, suggesting that pharmacogenomics testing might play an important role in clinical decision making for schizophrenia drug management.

6.
Indian J Ophthalmol ; 71(6): 2379-2384, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37322647

RESUMEN

Cataract is the leading cause of blindness worldwide. There is an increased incidence of cataract formation in the diabetic population due to several factors. Diabetes mellitus accelerates the development of cataract. Oxidative stress results in most of the diabetic complications including diabetic cataract. Oxidative stress leading to the expression of various enzymes has also been proven as crucial for cataractous changes in the lens in old age. A narrative review was undertaken to investigate the expression of different biochemical parameters as well as enzymes in diabetic and senile cataracts. Identification of these parameters is crucial for the prevention and treatment of blindness. Combinations of MeSH terms and key words were used to do literature search in PubMed. The search resulted 35 articles and among them, 13 were relevant to the topic and were included in synthesis of results. Seventeen different types of enzymes were identified in the senile and diabetic cataracts. Seven biochemical parameters were also identified. Alteration in biochemical parameters and expression of enzymes were comparable. Majority of the parameters were raised or altered in diabetic cataract compared to senile cataract.


Asunto(s)
Catarata , Complicaciones de la Diabetes , Diabetes Mellitus , Cristalino , Humanos , Catarata/etiología , Complicaciones de la Diabetes/complicaciones , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus/epidemiología , Ceguera
7.
Natl J Maxillofac Surg ; 14(1): 109-118, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37273433

RESUMEN

Background: The use of dental implants has become a very predictive method of rehabilitation for patients with partial or complete edentulism. It is more challenging to treat the posterior quadrants of the maxillary ridges using dental implants due to their anatomical and physiological characteristics. So to overcome the limitations of other techniques, short implants were introduced recently as a new approach to simplify implant placement in compromised alveolar bone and to prevent possible damage to vital structures. Purpose: This study aims to compare the clinical outcomes of dental implants placed using the osteotomized sinus floor elevation (OSFE) technique side engaging the bony floor of the maxillary sinus (bicortical anchorage) on one side and the conventional technique by split mouth on the other side. Materials and Method: This study included 15 patients. Study participants had dental implants placed on both sides of the mouth at the same time, so one side was implanted according to the test method, while the other side used the control method. Randomization determined which side would be implanted. Conclusion: The OSFE technique provides greater stability to the implant via bicortical anchorage than conventional techniques, which only provide unicortical anchorage.

8.
J Maxillofac Oral Surg ; 21(3): 870-880, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36274892

RESUMEN

Introduction: Clinicians are baffling for reconstruction of small- to medium-sized defects of the oral cavity since time immemorial, each and every flap has its own limitations, ideal flap should be pliable, easily transferrable that can result in a better restoration of form and function of oral mucosa, we have platysma for the same purpose. Aims: We aim to provide surgical technique of the superiorly-based platysma myocutaneous flap with a single neck incision in this study, as well as the flap design, results, and complications associated with age, gender, the recipient site, and the size of the defect. Materials and methods: Study included 20 patients with oral potentially malignant disorders operated under local anaesthesia with wide local excision and reconstruction with platysma myocutaneous flap at a single tertiary care centre. Statistical Analysis: The association between the variables was calculated using Chi-square tests and paired t tests. P < .05 was considered significant. Results: Five cases of dehiscence were found at varied sites and flap viability was significantly influenced by location of skin paddle. In between anterior jugular vein and posterior external jugular vein it was 100% viable while on and posterior to the vein, had skin paddle loss. Significant improvement in mouth opening was also seen in Oral Sub-mucous Fibrosis patients. Conclusion: The platysma flap is a technique sensitive, and its results are promising for the reconstruction of oral defects.

9.
Natl J Maxillofac Surg ; 13(2): 248-253, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36051797

RESUMEN

Purpose: The behavior of trigeminocardiac reflex (TCR) is limited to few case reports only in maxillofacial surgery, especially for temporomandibular joint (TMJ) ankylosis cases. The present study aims to find out the incidence of bradycardia due to TCR during intraoperative forceful mouth opening in TMJ ankylosis patients. Materials and Methods: A prospective, unicentric observational study was conducted selecting those patients who were planned for osteoarthrectomy with interpositional gap arthroplasty under general anesthesia. Sixty cases of TMJ ankylosis were randomly selected from December 2018 to-03-2020. Predictor variables were patient age, gender, and type of ankylosis, and outcome variables were pulse rate, mean arterial blood pressure (MABP), and oxygen saturation level (SPO2). Data were recorded at baseline and during intraoperative mouth opening via heister jaw stretcher. A Chi-square test was used for testing the association between variables. P values were considered statistically significant at <0.05. Results: The sample size of 60 subjects has been divided into two age groups (10-19) years and (20-40) years. The mean standard deviation age of the patients was 18.32 ± 6.81 years. About 63.3% were male. Out of 60 cases, 14 patients developed bradycardia. The frequency of bradycardia was found 23.3%. According to logistic regression analysis, age and type of ankylosis were the significant predictors of bradycardia. Conclusion: We conclude that bradycardia due to TCR in TMJ ankylosis patients is not an uncommon entity. Incidences are more prevalent in the age group of 10-19 years and type IV bony ankylosis. Male had a high incidence of bradycardia though P value was nonsignificant.

10.
Indian J Ophthalmol ; 70(7): 2225-2230, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35791100

RESUMEN

The prevalence of rare diseases has been estimated to be around 6%-8%, most of which are genetic in origin. Rare eye diseases constitute a critical public health concern. The major concerns for people suffering from these conditions are diagnosis, treatment, rehabilitation, limited resources, and health infrastructure. Also, as the number of people suffering from these disorders is less, it becomes difficult to study the epidemiological distribution and natural course of the disease. Thus, there is a need to establish registries for such rare disorders. This will help in creating a database of those suffering from rare eye diseases and will prove advantageous for both the patients and the researchers. For patients, it will be helpful as it will provide them will access to families suffering from similar problems, provide rehabilitation services, and provide access to clinical trials working on the development of new treatments for these rare disorders. From the researchers' point of view, it will be beneficial for them as they will then have access to a pool of data that can be used as a starting point of research on these rare disorders. At present, very few registries exist around the world and none in India. A systematic review of registries for rare eye diseases on Google and PubMed was done for existing registries, their methodology, services provided, applications, and advantages.


Asunto(s)
Oftalmopatías , Enfermedades Raras , Oftalmopatías/epidemiología , Humanos , India/epidemiología , Salud Pública , Enfermedades Raras/diagnóstico , Enfermedades Raras/epidemiología , Enfermedades Raras/genética , Sistema de Registros
11.
Mol Oncol ; 16(13): 2537-2557, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35064619

RESUMEN

Metastases account for the majority of prostate cancer (PCa) deaths, and targeting them is a major goal of systemic therapy. We identified a novel interaction between two kinases: tousled-like kinase 1 (TLK1) and MAP kinase-activated protein kinase 5 (MK5) that promotes PCa spread. In PCa progression, TLK1-MK5 signalling appears to increase following antiandrogen treatment and in metastatic castration-resistant prostate cancer (mCRPC) patients. Determinations of motility rates (2D and 3D) of different TLK1- and MK5-perturbed cells, including knockout (KO) and knockdown (KD), as well as the use of specific inhibitors, showed the importance of these two proteins for in vitro dissemination. We established that TLK1 phosphorylates MK5 on three residues (S160, S354 and S386), resulting in MK5 activation, and additionally, mobility shifts of MK5 also supported its phosphorylation by TLK1 in transfected HEK 293 cells. Expression of MK5-S354A or kinase-dead MK5 in MK5-depleted mouse embryonic fibroblast (MEF) cells failed to restore their motility compared with that of wild-type (WT) MK5-rescued MK5-/- MEF cells. A pMK5-S354 antiserum was used to establish this site as an authentic TLK1 target in androgen-sensitive human prostate adenocarcinoma (LNCaP) cells, and was used in immunohistochemistry (IHC) studies of age-related PCa sections from TRAMP (transgenic adenocarcinoma of the mouse prostate) mice and to probe a human tissue microarray (TMA), which revealed pMK5-S354 level is correlated with disease progression (Gleason score and nodal metastases). In addition, The Cancer Genome Atlas (TCGA) analyses of PCa expression and genome-wide association study (GWAS) relations identify TLK1 and MK5 as potential drivers of advanced PCa and as markers of mCRPC. Our work suggests that TLK1-MK5 signalling is functionally involved in driving PCa cell motility and clinical features of aggressiveness; hence, disruption of this axis may inhibit the metastatic spread of PCa.


Asunto(s)
Adenocarcinoma , Péptidos y Proteínas de Señalización Intracelular , Neoplasias de la Próstata Resistentes a la Castración , Proteínas Serina-Treonina Quinasas , Adenocarcinoma/patología , Animales , Movimiento Celular , Fibroblastos/metabolismo , Estudio de Asociación del Genoma Completo , Células HEK293 , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Ratones , Fosforilación , Neoplasias de la Próstata Resistentes a la Castración/patología , Proteínas Serina-Treonina Quinasas/metabolismo
12.
Cancers (Basel) ; 12(12)2020 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-33297404

RESUMEN

Most prostate cancer (PCa) deaths result from progressive failure in standard androgen deprivation therapy (ADT), leading to metastatic castration-resistant PCa (mCRPC); however, the mechanism and key players leading to this are not fully understood. While studying the role of tousled-like kinase 1 (TLK1) and never in mitosis gene A (NIMA)-related kinase 1 (NEK1) in a DNA damage response (DDR)-mediated cell cycle arrest in LNCaP cells treated with bicalutamide, we uncovered that overexpression of wt-NEK1 resulted in a rapid conversion to androgen-independent (AI) growth, analogous to what has been observed when YAP1 is overexpressed. We now report that overexpression of wt-NEK1 results in accumulation of YAP1, suggesting the existence of a TLK1>NEK1>YAP1 axis that leads to adaptation to AI growth. Further, YAP1 is co-immunoprecipitated with NEK1. Importantly, NEK1 was able to phosphorylate YAP1 on six residues in vitro, which we believe are important for stabilization of the protein, possibly by increasing its interaction with transcriptional partners. In fact, knockout (KO) of NEK1 in NT1 PCa cells resulted in a parallel decrease of YAP1 level and reduced expression of typical YAP-regulated target genes. In terms of cancer potential implications, the expression of NEK1 and YAP1 proteins was found to be increased and correlated in several cancers. These include PCa stages according to Gleason score, head and neck squamous cell carcinoma, and glioblastoma, suggesting that this co-regulation is imparted by increased YAP1 stability when NEK1 is overexpressed or activated by TLK1, and not through transcriptional co-expression. We propose that the TLK1>NEK1>YAP1 axis is a key determinant for cancer progression, particularly during the process of androgen-sensitive to -independent conversion during progression to mCRPC.

13.
iScience ; 23(9): 101474, 2020 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-32905878

RESUMEN

Through in vitro kinase assays and docking studies, we report the synthesis and biological evaluation of a phenothiazine analog J54 with potent TLK1 inhibitory activity for prostate cancer (PCa) therapy. Most PCa deaths result from progressive failure in standard androgen deprivation therapy (ADT), leading to metastatic castration-resistant PCa. Treatments that can suppress the conversion to mCRPC have high potential to be rapidly implemented in the clinics. ADT results in increased expression of TLK1B, a key kinase upstream of NEK1 and ATR and mediating the DNA damage response that typically results in temporary cell-cycle arrest of androgen-responsive PCa cells, whereas its abrogation leads to apoptosis. We studied J54 as a potent inhibitor of this axis and as a mediator of apoptosis in vitro and in LNCaP xenografts, which has potential for clinical investigation in combination with ADT. J54 has low affinity for the dopamine receptor in modeling and competition studies and weak detrimental behavioral effects in mice and C. elegans.

14.
Cancer Metastasis Rev ; 39(2): 505-517, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32474691

RESUMEN

Caveolae are bulb-like invaginations made up of two essential structural proteins, caveolin-1 and cavins, which are abundantly present at the plasma membrane of vertebrate cells. Since their discovery more than 60 years ago, the function of caveolae has been mired in controversy. The last decade has seen the characterization of new caveolae components and regulators together with the discovery of additional cellular functions that have shed new light on these enigmatic structures. Early on, caveolae and/or caveolin-1 have been involved in the regulation of several parameters associated with cancer progression such as cell migration, metastasis, angiogenesis, or cell growth. These studies have revealed that caveolin-1 and more recently cavin-1 have a dual role with either a negative or a positive effect on most of these parameters. The recent discovery that caveolae can act as mechanosensors has sparked an array of new studies that have addressed the mechanobiology of caveolae in various cellular functions. This review summarizes the current knowledge on caveolae and their role in cancer development through their activity in membrane tension buffering. We propose that the role of caveolae in cancer has to be revisited through their response to the mechanical forces encountered by cancer cells during tumor mass development.


Asunto(s)
Caveolas/patología , Neoplasias/patología , Animales , Caveolas/metabolismo , Caveolina 1/metabolismo , Membrana Celular/metabolismo , Membrana Celular/patología , Humanos , Mecanotransducción Celular , Neoplasias/metabolismo
15.
Cell Cycle ; 19(3): 363-375, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31914854

RESUMEN

The TLK1/Nek1 axis contributes to cell cycle arrest and implementation of the DDR to mediate survival upon DNA damage. However, when the damage is too severe, the cells typically are forced into apoptosis, and the contribution of TLKs in this process has not been investigated. In contrast, it is known that Nek1 may play a role by phosphorylating VDAC1 maintaining proper opening and closure of the channel and thus mitochondrial integrity. We now show that the activating phosphorylation of Nek1-T141 by TLK1 contributes to the phosphorylation and stability of VDAC1 and thereby to mitochondrial permeability and integrity. Treatment of three different cell lines model that overexpress Nek1-T141A mutant with doxorubicin showed exquisite sensitivity to the drug, with implementation of rapid accumulation of cells with subG1 DNA content (apoptotic) and other alterations in the cell cycle. In addition, these cells displayed reduced oxygen consumption under normal conditions and less reliance on mitochondria and more dependence on glycolysis for energy production. Consistent with greater apoptosis, upon treatment with low doses of doxorubicin, cells overexpressing Nek1-T141A displayed leakage of Cyt-C into the cytoplasmic fraction. This suggests that inhibiting the TLK1/Nek1/VDAC1 nexus could sensitize cancer cells to apoptotic killing in combination with an appropriate DNA damaging agent. We in fact have previously reported that Nek1 expression is elevated in advanced Prostate Cancer (PCa) and we now report that VDAC1 expression is elevated and correlated with disease stage, thereby making the TLK1/Nek1/VDAC1 nexus a very attractive target for PCa.


Asunto(s)
Apoptosis/genética , Puntos de Control del Ciclo Celular/genética , Proliferación Celular/genética , Mitocondrias/metabolismo , Quinasa 1 Relacionada con NIMA/metabolismo , Neoplasias de la Próstata/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Canal Aniónico 1 Dependiente del Voltaje/metabolismo , Antibióticos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Citocromos c/metabolismo , Daño del ADN , Doxorrubicina/farmacología , Regulación Neoplásica de la Expresión Génica/genética , Células HEK293 , Humanos , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Quinasa 1 Relacionada con NIMA/genética , Fosforilación , Neoplasias de la Próstata/genética , Proteínas Serina-Treonina Quinasas/genética , Canal Aniónico 1 Dependiente del Voltaje/genética
16.
Natl J Maxillofac Surg ; 11(2): 159-168, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33897175

RESUMEN

Oral mucositis is one of the most common complications of cancer therapy. It is a nonhematologic complication of cytotoxic chemotherapy and radiotherapy and reduces the quality of life. It is estimated that 40% the cases on standard chemotherapy may develop oral mucositis. Patients receiving radiation, especially in the cases of head and neck cancer, have 30%-60% chances of developing mucositis. Chemotherapy and radiotherapy interfere with the normal turnover of epithelial cells, leading to mucosal injuries. These injuries can also occur due to indirect invasion of Gram negative bacteria and fungi as most of the chemo-therapeutic agents will cause neutropenia and will give a favorable environment for the development of mucositis. The patient-related factors are also responsible for developing mucositis in chemo-induced and radiation-induced mucositis. Poor oral hygiene may also be responsible for bacterial super infection followed by chemotherapy. Mucositis is of two kinds: direct and indirect mucositis. Direct mucositis - The epithelial cells of the oral mucosa undergo rapid turnover in usually 7-14 days due to which these cells are more susceptible to the effect of the cytotoxic therapy which results in oral mucositis. Indirect mucositis - it can develop due to the infection caused by Gram-negative bacteria and fungal infection. There will be a greater risk for oral infection due to neutropenia. The onset of mucositis secondary to mylo-suppression varies depending upon the timing of the neutrophil count associated with chemotherapy agents but they typically develop around 10-21 days after chemotherapy administration.

17.
Cancer Lett ; 453: 131-141, 2019 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-30928383

RESUMEN

We recently uncovered the critical TLK1>NEK1>ATR > Chk1 axis in mediating the DDR and cell cycle checkpoint while transiting from Androgen Sensitive to Insensitive growth for LNCaP and TRAMP-C2 cells. However, we did not know the generality of this pathway in PCa progression since there are few cell lines where the transition has been studied. Furthermore, the identification of Nek1, and more importantly the TLK-mediated phosphorylation of T141, has never been studied in PCa biopsies. We now report the first study of a PCa TMA of p-Nek1-T141 and correlation to the Gleason score. In addition we found that TRAMP mice treated with the TLK inhibitor, thioridazine (THD), following castration did not recover cancerous growth of their prostates. Moreover, we recapitulated the process of translational increase in TLK1B expression in a naïve PDX model that was established from an AR + adenocarcinoma. Therefore, we believe that this TLK1-Nek1 mediated DDR axis is likely to be a common adaptive response during the transition of PCa cells toward androgen-insensitive growth, and hence CRPC progression, which has the potential to be targeted with THD and other TLK or Nek1 inhibitors.


Asunto(s)
Quinasa 1 Relacionada con NIMA/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proteínas Serina-Treonina Quinasas/metabolismo , Animales , Línea Celular Tumoral , Daño del ADN , Progresión de la Enfermedad , Humanos , Masculino , Ratones , Ratones SCID , Estadificación de Neoplasias , Orquiectomía , Neoplasias de la Próstata/genética , Transducción de Señal
18.
Indian J Clin Biochem ; 34(1): 45-51, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30728672

RESUMEN

GEMIN4 is a member of the GEMIN gene family which is involved in multiple pathologies including cancer. It is located on Chr17p13.3, the most notorious chromosome and a hotspot for various carcinomas. We therefore intend to find genetic variants of GEMIN4 gene associated with renal cell carcinoma risk (RCC). This study comprised 100 patients and 225 controls. Genotyping of GEMIN4 gene variants was done using Taqman® assay. The association of GEMIN4 variants and risk prediction of RCC was done by statistical analysis. Haplotype analysis was done to see the combined effect of variants on RCC. Patients carrying variant genotype, CC of GEMIN4 T/C rs7813 showed significant association whereas in case of GEMIN4 G/C rs910925 variant genotype, CC significant risk was found. GEMIN4 rs7813 T/C variant genotype, CC showed risk with smoking (p = 0.034). Our study gives a substantive support for the association between the GEMIN4 gene variants and RCC risk.

19.
J Maxillofac Oral Surg ; 18(1): 73-79, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30728696

RESUMEN

Oral cancer is a major health problem in India, and in certain parts, it represents more than 50% of all cancers. Since almost all of these patients receive chemo-radiotherapy with or without surgery for treatment, a vast majority of them also develop oral mucositis, a debilitating adverse effect of chemo-radiation. There have been various reports in the literature regarding the beneficial role of honey in the management of oral mucositis. The objective of this study was to investigate whether the application of honey in mucositis confers any significant improvement in lesions of mucositis and more specifically whether application of honey brings about any improvement in the quality of life of patients suffering from chemo-radiation-induced oral mucositis. If found to be beneficial, honey could provide a simple, elegant and cost-effective solution to a troublesome health problem, thus benefiting a large number of patients.

20.
J Oral Maxillofac Surg ; 77(5): 1040.e1-1040.e9, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30738061

RESUMEN

PURPOSE: The optimal treatment for adult mandibular condylar fractures (MCFs) has largely shifted in favor of open reduction and rigid internal fixation. However, a sizeable portion of these injuries are still being treated in a closed manner based on old literature, convenience, results deemed acceptable, and lesser associated morbidity. Most MCFs with multiple associated facial traumas are appropriately treated under general anesthesia (GA). However, some selected isolated MCFs or those with minimal associated mandibular or low midfacial fractures can be treated optimally with patients under local anesthesia following a protocol presented in this article, thus expediting and simplifying their management. The purpose of this study was to develop a safe, sound, effective protocol for routine surgical management of mandibular subcondylar fractures under local anesthesia. PATIENTS AND METHODS: We carried out a prospective clinical study to assess the feasibility of operating on MCFs with patients under local anesthesia. Seven patients with MCFs and other associated facial fractures underwent surgery after careful case selection following our proposed protocol. The outcome variables were 1) duration of the procedure, 2) intraoperative pain assessed by a visual analog scale, 3) fracture reduction assessed by measuring the preoperative and postoperative average fracture gap, 4) presence of malocclusion preoperatively and postoperatively, 5) deviation on mouth opening, and 6) maximal mouth opening. RESULTS: The mean duration of the procedure was 35.14 minutes, and the mean rating of intraoperative pain or discomfort was 0.57 as reported on the visual analog scale by the patients. Mean mouth opening improved from 17.1 to 40.5 mm, whereas deviation on opening improved from 4.4 to 0.28 mm. The average fracture gap was reduced from 6.32 to 0.97 mm. CONCLUSIONS: The presented protocol is a straightforward, efficient, safe, cost-effective tool for operating on MCFs, avoiding GA with its attendant risks and complications, that can be used routinely, as well as in patients for whom GA is deemed unsuitable.


Asunto(s)
Anestesia Local , Fracturas Mandibulares , Fijación Interna de Fracturas , Humanos , Cóndilo Mandibular , Fracturas Mandibulares/cirugía , Estudios Prospectivos , Resultado del Tratamiento
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