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1.
J Endocr Soc ; 8(3): bvad173, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38249432

RESUMO

Context: Diabetic ketoacidosis (DKA) is a preventable, deadly, and costly complication of type 1 diabetes mellitus (T1DM). Some individuals with T1DM have recurrent DKA admissions. Objective: We sought to characterize social factors that differ between patients with single vs multiple DKA admissions at an urban, safety-net hospital. Methods: We queried the electronic health records for T1DM patients admitted for DKA from 2019 to 2021. Admission laboratory values, demographic information, and detailed social histories were collected and analyzed statistically, including logistical regression. Results: A total of 243 patients were admitted for DKA, 64 of whom had multiple DKA admissions. There was no significant difference between the groups in their admission laboratory values, hospital length of stay, health-care payer status, history of homelessness, current employment, living alone, independence of activities of daily living, and barriers to discharge. T1DM patients with multiple DKA admissions had greater rates of substance use disorder (33.0% vs 60.9%; P < .001), especially with cannabis (6.7% vs 25.0%; P < .001), tobacco (26.3% vs 46.3%; P = .002), and psychoactive substance use (1.1% vs 6.3%; P = .043). Regression models of substance use showed increased risk with any substance use (odds ratio [CI] 3.17 [1.78-5.73]; P < .001) and cannabis (3.70 [1.55-8.83]; P = .003). Conclusion: We identified substance use as a possible predictor of T1DM patients at risk for multiple DKA admissions. Our findings identify a group of T1DM patients for whom interventions may help to decrease recurrence of DKA episodes within similar community hospital populations.

2.
Work ; 76(4): 1311-1316, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37393483

RESUMO

BACKGROUND: Childcare center providers in Miami-Dade County, Florida a COVID-19 hotspot, are made up almost entirely of ethnic minority women. This is a critical frontline staff that is now encountering the triple threat of respiratory illnesses from respiratory syncytial virus (RSV), influenza viruses (or the seasonal flu), and COVID-19. OBJECTIVE: To examine sociodemographic characteristics, anthropometrics, and health behaviors that were collected from a sample of CCC teachers in Miami Dade County, a COVID-19 hotspot. METHODS: Cross-sectional data were used from Healthy Caregivers, Healthy Children (HC2), a randomized controlled intervention trial (#NCT02697565) for healthy weight maintenance among children 2-to-5 years old, conducted in 24 subsidized childcare centers in MDC in 2015-2018. Prevalence was determined by frequency or mean/standard deviation of each variable. Chi-squared analyses were performed to test for differences in BMI categories. RESULTS: In this sample of childcare center providers (n = 255), the majority (61%) had an elevated body mass index. Positive health behaviors such as regular exercise and eating fruits and vegetables were only reported in about a third of the sample. CONCLUSION: It is vital that we encourage the uptake of regular vaccination schedules as a means to protect our community, especially the critical frontline workers that have been caring for our young children.


Assuntos
COVID-19 , Cuidado da Criança , Pré-Escolar , Feminino , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Etnicidade , Nível de Saúde , Grupos Minoritários , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
J Clin Med ; 12(9)2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37176641

RESUMO

Older adults who face systemic health issues and lack adequate social support are at risk for oral health deterioration. How rapidly such changes take place depends on the severity of their medical condition and their ability to access oral health services in a timely manner. The management of dental caries and periodontal disease in this cohort is made complex by the interaction of local and host factors such as the presence of dry mouth, involvement of root surfaces, and altered wound healing. in addition to enhanced maintenance needs to avoid recurrence or progression. Tooth replacement can be beneficial in restoring oral function, allowing patients to enjoy a healthy and nutritious diet but requires careful consideration to avoid further damage to remaining dental units. Establishing a dental home for the older adult can facilitate routine surveillance, disease prevention, and patient/caregiver education to achieve oral health goals commensurate with overall health. This narrative review details oral health factors that are related to rapid oral health deterioration among older adults.

4.
Spec Care Dentist ; 43(3): 359-369, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36782274

RESUMO

From the widespread use of smartphones and tablets to the multitude of applications available, older adults are showing an interest in utilizing technology to maintain their independence and to improve their quality of life. As technology continues to advance and be incorporated into many day-to-day activities, the baby boom generation will see these changes affecting the way they access and utilize dental services. Innovative toothbrushes and chemotherapeutics are continuing to be developed and utilized by many older adults. Within the dental office, older adults are seeing greater application of technology in every day dental procedures. These include the use of teledentistry, artificial intelligence (AI), innovative restorative materials, digitization of fixed and removable prosthodontics, cone beam computed tomography (CBCT) scans to guide dental implant placement and endodontic procedures. There is also new technology to aid in cancer detection and shielding during cancer treatment. Improved communication between the medical and dental fields has become increasingly necessary to facilitate effective patient care and a few innovative healthcare systems have begun to consolidate these services. Overall, the baby boom generation will continue to see dental innovations that will change the way they experience everyday life and dental services.


Assuntos
Inteligência Artificial , Qualidade de Vida , Humanos , Idoso , Tomografia Computadorizada de Feixe Cônico/métodos , Saúde Bucal , Atenção à Saúde
5.
Cureus ; 14(4): e24218, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35602836

RESUMO

Introduction With the advent of fixed- and variable-loop suspensory fixation devices for arthroscopic anterior cruciate ligament (ACL) reconstruction, a maximum number of grafts can be placed within the femoral tunnel. Although several biomechanical studies have been conducted comparing these two devices, only a few comparative clinical studies are available. This study was conducted to compare the functional outcomes of arthroscopic ACL reconstruction using fixed-loop devices with those of variable-loop devices by determining their effect on graft laxity clinical assessment and patient-reported outcome scores. Methodology Out of 32 patients (27 males and five females) who underwent primary ACL reconstruction using tripled hamstring autograft, fixed- and variable-loop devices were used for 13 and 19 patients, respectively. Thirteen patients in each group were evaluated over a period of one year using the Lysholm knee score. Six patients in the variable-loop group had only six months of follow-up. Anterior drawer and Lachman tests were performed at six-month and one-year follow-ups, respectively. Results The mean ages of patients in the fixed- and variable-loop groups were 34.5[Formula: see text]11 and 34.1[Formula: see text]9.1 years, respectively. The Lysholm knee score at six weeks was fair in 7.7% of the patients in the fixed-loop group when compared to 52.6% of those in the variable-loop group (p<0.05). All the other parameters were comparable between the two groups. One patient in each group had ligament laxity at six-month and one-year follow-up, respectively. Conclusion This study showed no statistically significant difference in graft laxity or functional outcomes of arthroscopic ACL reconstruction with fixed- and variable-loop devices, except for a better patient-reported outcome score in the variable-loop group at six weeks of follow-up. Hence, there is a need for more comparative studies in this direction.

6.
Phys Rev Lett ; 126(19): 196601, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34047606

RESUMO

Little is known about the spin-flip diffusion length l_{sf}, one of the most important material parameters in the field of spintronics. We use a density-functional-theory based scattering approach to determine values of l_{sf} that result from electron-phonon scattering as a function of temperature for all 5d transition metal elements. l_{sf} does not decrease monotonically with the atomic number Z but is found to be inversely proportional to the density of states at the Fermi level. By using the same local current methodology to calculate the spin Hall angle Θ_{sH} that characterizes the efficiency of the spin Hall effect, we show that the products ρ(T)l_{sf}(T) and Θ_{sH}(T)l_{sf}(T) are constant.

7.
J Int Soc Prev Community Dent ; 10(5): 591-596, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282768

RESUMO

AIM: The aim of this study was to assess the changes in maxillary and mandibular third molar inclinations in individuals with class II div 1 malocclusion, before and after orthodontic treatment with extraction of all four first premolars. MATERIALS AND METHODS: This retrospective study consisted of the pretreatment and posttreatment records of 30 patients that were obtained from the archives of the department of orthodontics and dentofacial orthopedics in A B Shetty Memorial Institute of Dental Sciences. The maxillary third molar's relation to the palatal plane and the mandibular third molar's relation to the mandibular plane were measured. The paired t test was used to calculate pre- and posttreatment changes. A value of P < 0.05 was considered to be statistically significant. RESULTS: The maxillary third molars showed a mean correction of 6.15° (P < 0.001) and the mandibular third molars showed a mean correction of 5.10° (P < 0.001). CONCLUSION: Maxillary third molars showed more uprighting when compared to the mandibular third molars and that both maxillary and mandibular third molars showed an improvement in their angulations to their respective planes after extraction of the first premolars. However, the results of the study cannot be analyzed to state if the third molars do become fully functional.

8.
J Dent Educ ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32905621

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic presented formidable challenges in our ability to impart in-person extra-mural clinical training, including the Geriatric and Special Needs Program, to a group of 20 fourth-year dental students. A new course delivery format was developed wherein students used a validated Rapid Oral Health Deterioration (ROHD) risk assessment tool to critically appraise clinical case information relating to a young adult with special needs. In the alternative virtual educational approach that was created, students applied an interprofessional practice concept leading to patient treatment planning outcomes. Providing adequate information, additional reading resources, a response template, clear instructions and a process-oriented assessment policy all ensured a good level of participation from students in the alternative learning format. An association was noted between students' staging of risk for ROHD and their subsequent recommendations for treatment.

9.
Indian J Dent Res ; 30(2): 314-317, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31169169

RESUMO

Taurodontism is a dental anomaly caused due to the failure of Hertwig's epithelial sheath to invaginate at the proper horizontal level. A huge pulp chamber, displacement of the pulpal floor apically, and no constriction at the level of the cementoenamel junction are the key features representing a taurodontic tooth. This condition is most commonly associated with permanent molars. This clinical entity occurs in the form of an isolated, singular trait in majority of the cases. However, seldom, it may be associated with syndromes or ectodermal anomalies. The large and deep pulp chamber makes instrumentation of canals difficult, thereby challenging an endodontist. This case report describes the endodontic challenge faced in cases of taurodontism as well as the clinical steps involved in its successful endodontic management. Furthermore, it shows the typical presence of bilateral hypertaurodontism with respect to the maxillary first molar.


Assuntos
Cavidade Pulpar , Anormalidades Dentárias , Cavidade Pulpar/anormalidades , Humanos , Maxila , Dente Molar
10.
Open Access Maced J Med Sci ; 7(6): 1042-1046, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30976358

RESUMO

BACKGROUND: The molar incisor hypomineralization (MIH) is defined as a qualitative defect of the enamel characterised by the progressive and simultaneous hypomineralization of the enamel structure of the first permanent molars which is of systemic origin, which may be associated frequently with incisors. Although the reported prevalence of MIH ranges from 2.4% to 40.2% worldwide, very little data is available from India. AIM: To determine the prevalence of molar incisor hypomineralization among school children aged 9 to 12 years in virajpet, Karnataka. METHODS: This cross-sectional descriptive study consisted of 1600 school children aged 9-12 years selected by stratified cluster sampling procedure. The European Academy of Pediatric Dentistry criteria were followed for MIH diagnosis. Chi-square test was used to analyse the categorical data. P ≤ 0.05 was considered for statistical significance. RESULTS: The prevalence of MIH is 13.12% with no gender predilection. Ten-year-old children showed the highest prevalence (15%) among all the age group. Majority of children with MIH (70.2%) have lesions in both molars and incisors with demarcated opacities and atypical restorations being the most frequent defect type. CONCLUSION: Prevalence of MIH was 13.12% in the 9-12-year child population in Virajpet. There is a need for a proper planned preventive and restorative program about the increasing prevalence of MIH.

11.
Indian J Dent Res ; 30(6): 975-977, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31939382

RESUMO

It is mandatory for every clinician to have a thorough knowledge about the normal internal anatomy of teeth; equally important is the awareness about variations in internal anatomy that could be seen with different teeth. The outcome of a root canal therapy depends significantly on the clinician's awareness about root canal anatomy, followed by their clinical skills. Literature states that the permanent maxillary first molar shows a wide variation in the number of canals particularly with respect to the mesiobuccal root. This case report describes the endodontic management of a permanent maxillary first molar with three distinct mesiobuccal canals.


Assuntos
Cavidade Pulpar , Dente Molar , Maxila , Tratamento do Canal Radicular , Raiz Dentária
12.
J Conserv Dent ; 21(4): 354-358, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30122812

RESUMO

INTRODUCTION: The aim of this study is to compare the effectiveness of reciprocating and continuous rotary nickel-titanium instruments during retreatment performed through two different access outlines. METHODOLOGY: A total of 48 freshly extracted mandibular first and second premolars with single root and canal were selected. Initial root canal treatment was completed through a contracted endodontic cavity (CEC) design. Canals were instrumented with F2 ProTaper instrument, obturated with warm lateral condensation of gutta-percha with AH Plus sealer, and allowed to set for 30 days at 37°C and 100% humidity. For retreatment, specimens were divided into two groups (n = 24) on the basis of access outline, CEC or traditional endodontic cavity. Retreatment was initiated using ProTaper Retreatment instruments (D1-D3). Specimens were further divided (n = 12) and reinstrumented up to Neoniti 25/0.08 or WaveOne 25/0.08. Irrigation was performed using 3% sodium hypochlorite and 17% ethylene diamine tetraacetic acid. Retreatment time was recorded. Teeth were sectioned and photographed, and the percentage of remaining obturation material was measured. RESULTS: Data were collected, and statistical analysis was performed using one-way analysis of variance and Tukey honestly significant difference multiple post hoc procedures (P < 0.05). CONCLUSION: None of the systems completely removed the root filling material from root canals. However, ProTaper/Neoniti instruments removed more GP when compared to Protaper/WaveOne instruments with both the access outlines. Both the instruments with traditional access outline required less time for removal of obturating material when compared to CEC.

13.
Lasers Med Sci ; 33(8): 1747-1755, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29802587

RESUMO

Light-based treatment modalities such as photothermal therapy (PTT) or photochemical internalization (PCI) have been well documented both experimentally and clinically to enhance the efficacy of chemotherapy. The main purpose of this study was to examine the cytotoxic effects of silica-gold nanoshell (AuNS)-loaded macrophage-mediated (MaNS) PTT and bleomycin BLM-PCI on monolayers of squamous cell carcinoma cells. The two modalities were applied separately and in simultaneous combination. Two different wavelengths of light were employed simultaneously, one to activate a highly efficient PCI photosensitizer, AlPcS2a (670 nm) and the other for the MaNS-mediated PTT (810 nm), to evaluate the combined effects of these modalities. The results clearly demonstrated that macrophages could ingest sufficient numbers of silica-gold nanoshells for efficient near infrared (NIR) activated PTT. A significant synergistic effect of simultaneously applied combined PTT and PCI, compared to each modality applied separately, was achieved. Light-driven therapies have the advantage of site specificity, non-invasive and non-toxic application, require inexpensive equipment and can be given as repetitive treatment protocols.


Assuntos
Hipertermia Induzida , Macrófagos/metabolismo , Fototerapia , Animais , Bleomicina , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Linhagem Celular Tumoral , Endocitose , Ouro/química , Humanos , Nanoconchas/química , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Ratos
14.
J Contemp Dent Pract ; 19(4): 415-419, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29728546

RESUMO

Aim: The present study was conducted with an aim to assess the antimicrobial activity of Ocimum sanctum (tulsi) extract on Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis.Materials and methods: Tulsi extract with ethanol was prepared using cold extraction method in the present in vitro study. Various concentrations (2, 4, 6, and 8%) were then obtained by dilution with dimethylformamide. A 0.2% chlorhexidine served as the positive control, whereas the negative control was dimeth-ylformamide. Zones of inhibition were measured, each for A. actinomycetemcomitans and P. gingivalis. For comparison within the group and between the study groups, one-way analysis of variance (ANOVA) and Tukey's post hoc tests were used. A statistical significance level of p < 0.05 was established. Results: The 8% concentration of the tulsi extract showed maximum zone of inhibition against A. actinomycetemcomitans and P. gingivalis (40.10 ± 0.90, 33.79 ± 1.82 mm), followed by the 6, 4, and 2% concentrations. The 0.2% chlorhexidine, which was the positive control, had 39.80 ± 1.24 and 32.28 ± 1.28 mm zones of inhibition; dimethylformamide showed 13.55 ± 1.92 and 10.21 ± 2.16 mm zones of inhibition against both the microorganisms. The ANOVA showed highly statistically significant (p < 0.0001) results between and within the groups. The antimicrobial activity of tulsi extract at 6 and 8% concentrations, and 0.2% chlorhexidine against A. actinomycetemcomitans showed statistically significant differences between the groups. The concentration of tulsi extract at 8 and 0.2% chlorhexidine on P. gingivalis showed statistically significant differences between the groups. Conclusion: It was concluded that 8% concentration of O. sanctum (tulsi) extract showed the maximum antimicrobial activity against A. actinomycetemcomitans and P. gingivalis. It is thus recommended that this may be useful as an adjunc-tive to mechanical therapy in the prevention and treatment of periodontal diseases. Clinical significance:O. sanctum (tulsi) is a herb that is abundantly available, easily accessible, economically feasible, and culturally acceptable. Therefore, it is very useful in the management of oral diseases and also for overcoming many barriers that exist for the utilization of dental services, such as affordability, accessibility, availability, and acceptability. Keywords:Aggregatibacter actinomycetemcomitans, Antimicrobial, Ocimum sanctum, Porphyromonas gingivalis.


Assuntos
Aggregatibacter actinomycetemcomitans/efeitos dos fármacos , Antibacterianos/farmacologia , Ocimum/química , Extratos Vegetais/farmacologia , Porphyromonas gingivalis/efeitos dos fármacos , Clorexidina/farmacologia , Relação Dose-Resposta a Droga , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Folhas de Planta
15.
J Clin Orthop Trauma ; 9(Suppl 1): S76-S79, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29628704

RESUMO

OBJECTIVE: To determine the awareness and application of the injury prevention strategies by professional Indian football players through Standard Questionnaire Based Survey. DESIGN: Descriptive Epidemiological Study. SETTING: Professional football clubs in India. PARTICIPANTS: Among 150 professional footballers playing in India, 109 football players participated.. PROCEDURE: The online questionnaire was made in the Google drive application. An online URL (www.tinyurl.com/futbolscptrc) was made in Google accounts by Google drive. 150 professional footballers playing in India were identified and invited to participate in this descriptive epidemiological online survey. All duly filled questionnaire responses were automatically reached in the Google drive inbox. Descriptive analysis was used for the data analysis. RESULTS: Questionnaires were distributed to 150 professional players at nine Indian League clubs. 109 players responded, which represents a response rate of 73%. The player age and number of years as a professional footballers were 25 (4) years (range 18-38 years) and 6 (4) years (range 1-16 years) respectively. The players were from one Premier (9), two Division One (6 and 16), and two Division Two (9 and 15) teams. CONCLUSIONS: Most of the professional Indian football players are aware about the injury prevention strategies. However, the application of these strategies is consistently followed by Premier division players.

16.
Can J Physiol Pharmacol ; 96(2): 173-181, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28800400

RESUMO

Although mitochondrial transcription factor A (TFAM) is a protective component of mitochondrial DNA and a regulator of calcium and reactive oxygen species (ROS) production, the mechanism remains unclear. In heart failure, TFAM is significantly decreased and cardiomyocyte instability ensues. TFAM inhibits nuclear factor of activated T cells (NFAT), which reduces ROS production; additionally, TFAM transcriptionally activates SERCA2a to decrease free calcium. Therefore, decreasing TFAM vastly increases protease expression and hypertrophic factors, leading to cardiomyocyte functional decline. To examine this hypothesis, treatments of 1.0 µg of a TFAM vector and 1.0 µg of a CRISPR-Cas9 TFAM plasmid were administered to HL-1 cardiomyocytes via lipofectamine transfection. Western blotting and confocal microscopy analysis show that CRISPR-Cas9 knockdown of TFAM significantly increased proteases Calpain1, MMP9, and regulators Serca2a, and NFAT4 protein expression. CRISPR knockdown of TFAM in HL-1 cardiomyocytes upregulates degradation factors, leading to cardiomyocyte instability. Hydrogen peroxide oxidative stress decreased TFAM expression and increased Calpain1, MMP9, and NFAT4 protein expression. TFAM overexpression normalizes pathological hypertrophic factor NFAT4 in the presence of oxidative stress.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/metabolismo , Fatores de Transcrição/metabolismo , Animais , Sistemas CRISPR-Cas/genética , Calpaína/metabolismo , Linhagem Celular , Peróxido de Hidrogênio/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Miócitos Cardíacos/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Peptídeo Hidrolases/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático
17.
Photodiagnosis Photodyn Ther ; 21: 156-162, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29221858

RESUMO

BACKGROUND: Macrophage (Ma) vectorization of chemotherapeutic drugs has the advantage for cancer therapy in that it can actively target and maintain an elevated concentration of drugs at the tumor site, preventing their spread into healthy tissue. A potential drawback is the inability to deliver a sufficient number of drug-loaded Ma into the tumor, thus limiting the amount of active drug delivered. This study examined the ability of photochemical internalization (PCI) to enhance the efficacy of released drug by Ma transport. METHODS: Tumor spheroids consisting of either F98 rat glioma cells or F98 cells combined with a subpopulation of empty or doxorubicin (DOX)-loaded mouse Ma (RAW264.7) were used as in vitro tumor models. PCI was performed with the photosensitizer AlPcS2a and laser irradiation at 670 nm. RESULTS: RAW264.7 Ma pulsed with DOX released the majority of the incorporated DOX within two hours of incubation. PCI significantly increased the toxicity of DOX either as pure drug or derived from monolayers of DOX-loaded Ma. Significant growth inhibition of hybrid spheroids was also observed with PCI even at subpopulations of DOX-loaded Ma as low as 11% of the total initial hybrid spheroid cell number. CONCLUSION: Results show that RAW264.7 Ma, pulsed with DOX, could effectively incorporate and release DOX. PCI significantly increased the ability of both free and Ma-released DOX to inhibit the growth of tumor spheroids in vitro. The growth of F98 + DOX loaded Ma hybrid spheroids were synergistically reduced by PCI, compared to either photodynamic therapy or released DOX acting alone.


Assuntos
Doxorrubicina/farmacologia , Portadores de Fármacos/metabolismo , Indóis/farmacologia , Macrófagos/metabolismo , Compostos Organometálicos/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Animais , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Endocitose/fisiologia , Glioma , Indóis/administração & dosagem , Camundongos , Compostos Organometálicos/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Ratos
18.
Photodiagnosis Photodyn Ther ; 18: 140-148, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28257943

RESUMO

INTRODUCTION: Gene-directed enzyme prodrug therapy (GDEPT) employing the cytosine deaminase (CD) gene, which encodes an enzyme that converts the nontoxic agent 5-fluorocytosine (5-FC) into the chemotherapeutic drug 5-fluorouracil (5-FU), has shown promise both in experimental animals and in clinical trials. Nevertheless, with the transfection systems available presently the percentage of tumor cells incorporating the desired gene is usually too low for successful therapy. We have examined the ability of photodynamic therapy (PDT) to enhance the efficacy of the metabolites, converted from 5-FC by CD gene transfected rat glioma cells. METHODS: Hybrid tumor cell spheroids consisting of CD poitive and CD negative F98 glioma cells in varying ratios were used as in vitro tumor models. PDT was performed with the photosensitizer AlPcS2a and λ=670nm laser irradiance, both before and after confrontation with 5-FC. RESULTS: PDT increased the toxicity of 5-FU either as pure drug or derived from monolayers of CD positive cells chalanged with 5-FC. PDT in combination with 5-FC resulted in a significantly enhanced inhibition of hybrid spheroid growth compared to non light treated controls. This was the case even at tumor to producer cell ratios as high as 40:1. CONCLUSION: The results of the present study show that GDEPT and PDT interact in a synergistic manner over a range of prodrug concentration and tumor to transfected cell ratios. The degree of synergy was significant regardless if PDT treatment was given before or after 5-FC administration. The highest degree of interaction was observed though, when PDT was delivered prior to prodrug exposure.


Assuntos
Terapia Enzimática/métodos , Flucitosina/administração & dosagem , Terapia Genética/métodos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/genética , Fotoquimioterapia/métodos , Pró-Fármacos/uso terapêutico , Linhagem Celular Tumoral , Terapia Combinada/métodos , Citosina Desaminase/genética , Sinergismo Farmacológico , Humanos , Neoplasias Experimentais/patologia , Fármacos Fotossensibilizantes/administração & dosagem , Resultado do Tratamento
19.
J Biomed Opt ; 21(7): 78002, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27448101

RESUMO

Activation of sonosensitizers via focused ultrasound (FUS), i.e., sonodynamic therapy has been proposed as an extension to light-activated photodynamic therapy for the treatment of brain as well as other tumors. The use of FUS, as opposed to light, allows treatment to tumor sites buried deep within tissues as well as through the intact skull. We have examined ultrasonic activation of sonosensitizers together with the anticancer agent bleomycin (BLM), i.e., sonochemical internalization (SCI). SCI is a technique that utilizes FUS for the enhanced delivery of endo-lysosomal trapped macromolecules into the cell cytoplasm in a similar manner to light-based photochemical internalization. The released agent can, therefore, exert its full biological activity, in contrast to being degraded by lysosomal hydrolases. Our results indicate that, compared to drug or FUS treatment alone, FUS activation of the sonosensitizer AlPcS2a together with BLM significantly inhibits the ability of treated glioma cells to grow as three-dimensional tumor spheroids in vitro.


Assuntos
Bleomicina/administração & dosagem , Glioma/terapia , Fotoquimioterapia/métodos , Ultrassom , Animais , Bleomicina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ratos
20.
Biomed Opt Express ; 7(4): 1240-50, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27446650

RESUMO

Combination therapies of photochemical internalization (PCI) and moderate hyperthermia (MHT) were investigated in an in vitro system consisting of human and rat glioma spheroids. PCI using the amphiphilic photosensitizer, AlPcS2a and two anti cancer agents BLM or 5-FU were used. Spheroids were irradiated with λ = 670 nm laser light in an incubator at temperatures ranging from 37 to 44°C. For each temperature investigated, spheroids were divided into 4 groups: control, drug-only, photodynamic therapy (PDT), and PCI. PDT and PCI spheroids were exposed to radiant exposures ranging from 0.3 to 2.5 J cm(-2) using an irradiance of 5 mW cm(-2). Toxicity was evaluated from spheroid growth kinetics. The combination of PCI and MHT resulted in significant increases in BLM efficacy at 44°C for both cell line derived spheroids compared to controls at 37°C over the range of radiant exposures examined. 5-FU PCI was ineffective for the human cell line at both 37 and 44°C.

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