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1.
J Postgrad Med ; 68(2): 93-97, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34747876

RESUMO

INTRODUCTION: Despite the impressive responses achieved with tyrosine kinase inhibitor (TKI) therapy, treatment resistance develops in 16-33% of patients of chronic myelogenous leukemia (CML). Of the BCR-ABL1 dependent mechanisms, mutations in the tyrosine kinase domain (TKD) are the commonest cause of resistance. MATERIAL AND METHODS: Allele specific oligonucleotide - polymerase chain reaction (ASO-PCR) was done for testing the six common TKD mutations, T315I, G250E, E255K, M244V, M351T, and Y253F. RESULTS AND CONCLUSION: TKD mutation study was done on 83 patients. Of these 44 (53%) were positive for one or more mutations. On analyzing specific mutations, E255K was the commonest mutation seen in 24 (29%) cases, followed by T315I in 23(28%) cases. Y253F mutation was not seen in the present study sample. In the present cohort of 83 patients, 29 (35%) cases were positive for single mutation, 12 (14%) had two mutations and 3 (4%) had three mutations.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Antineoplásicos/uso terapêutico , Estudos de Coortes , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/uso terapêutico , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Mutação
2.
Contemp Clin Dent ; 15(1): 27-34, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707668

RESUMO

Background: Four different designs of mini-implant-assisted rapid palatal expansion (MARPE) and protraction in nasomaxillary complex and mid-palatal sutures in late adolescent skeletal Class III malocclusion were compared using a three-dimensional finite element analysis. Methods: A finite element model of skull and related sutures was constructed using the computed tomography scan of a 16-year-old female patient with skeletal Class III and ANB of -2°. Four appliance designs: Type I: MARPE with palatal force, Type II: MARPE with buccal force, Type III: Hybrid hyrax with palatal force, and Type IV: Hybrid hyrax with buccal force. Protraction vectors were and analyzed using Ansys software (ANSYS 2021 R2). The displacement pattern of the nasomaxillary structures and the stress distribution in the sutures were examined in all four appliance designs. Results: All the appliance designs resulted in a forward movement of the maxilla, while Type I and III, which used palatal protraction force, caused the greatest forward displacement. In Type I, II, and III, along with forward movement, a clockwise rotation of maxilla was observed, while in Type IV, an anticlockwise rotation of maxilla was observed. Type I, II, and III resulted in higher stress distribution around the superior structures, while Type IV resulted in less stress distribution around the superior structures of maxilla. Conclusion: The forward displacement was enhanced when palatal plates were used to protract the maxilla. The effective appliance design for skeletal class III with open bite case was Type I, II, and III and Type IV for deep bite cases.

3.
Acta Crystallogr Sect E Struct Rep Online ; 69(Pt 6): o840, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23795028

RESUMO

In the title compound, C28H24F6N2O3, the mean plane of the central pyrazoline ring forms dihedral angles of 2.08 (9) and 69.02 (16)° with the 2-benz-yloxy-6-hy-droxy-4-methyl-phenyl and 3,5-bis-(tri-fluoro-meth-yl)phenyl rings, respectively. The dihedral angle between the mean planes of the pyrazoline and 3,5-bis-(tri-fluoro-meth-yl)phenyl rings is 68.97 (9)°. An intra-molecular O-H⋯N hydrogen bond is observed, which forms an S(6) graph-set motif. In the crystal, pairs of weak C-H⋯F halogen inter-actions link the mol-ecules into inversion dimers while molecular chains along [100] are formed by C-H⋯O contacts.

4.
Contemp Clin Dent ; 14(1): 25-31, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37249992

RESUMO

Background: Temporary anchorage devices or mini-implants have gained great attraction due to its capability to provide absolute anchorage, low cost, versatility, and can be loaded immediately after placement. Aims and Objectives: The aim of this study is to use FEA analysis to assess the strain and insertion torque of mini-implants on a bone model at two distinct angulations of 45° and 90°. Materials and Methods: A computer-aided three-dimensional (3-D) model representing alveolar bone and mini-implants were developed using ANSYS software. Computed tomography scan images of the implant and the alveolar bone were taken and exported in DICOM format for 3-D image processing. The thickness of the bone model is 1 mm. Ti6Al4V orthodontic single and double threaded mini-implants (L = 7 mm, D = 1.5 mm) were inclined at 45° and 90° on to the bone surface to measure the insertion torque and strain produced. Results: Maximum insertion torque (MIT) for single-threaded mini implant at 45° and 90° angulations are 20.001 Nmm and 19.977 Nmm, respectively. MIT for double-threaded mini-implants obtained is 19.977 Nmm at 90° and 19.991 Nmm at 45° angulation. The strain of the bone at 90° angulation for single-threaded mini-implant is 0.00893 mm and for single-threaded mini implant at 45° angulation is 0.01257 mm. The strain in double-threaded mini-implant at 90° angulation is 0.0125 mm and that of 45° angulation is 0.01773 mm. Conclusion: For maximum stability single-threaded mini-implant with perpendicular insertion, angle is preferred.

5.
Indian J Occup Environ Med ; 27(1): 21-25, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37303999

RESUMO

Context: Excessive daytime sleepiness (EDS) due to obstructive sleep apnoea (OSA) is reported to be a major contributor to many road traffic accidents. Lack of awareness and diagnosis of OSA among public transport workers remains a threat to the society. Aims: The primary aim of this study was to assess the risk of OSA among transport drivers of south Kerala using modified Berlin questionnaire. The secondary objective included craniofacial assessment of the high-risk patients identified through the questionnaire using lateral cephalogram. Settings and Design: A cross-sectional study was conducted among 180 transport drivers of south Kerala. Methods and Material: Modified Berlin questionnaire and limited physical examination [body mass index (kg/m2), neck circumference (cm), waist circumference (cm), hip circumference and waist to hip ratio, blood pressure (mm Hg)] were recorded. The screened subjects were categorized as high-risk snorers and low-risk snorers based on modified Berlin questionnaire. Craniofacial morphological variations of high-risk group were assessed by lateral cephalograms. Statistical Analysis Used: The descriptive statistics were represented as mean and standard deviation and percentage. Inter-group comparison was performed with independent sample t test. Results: The study demonstrated 64.4% of subjects were non-snorers and 35.6% were snorers. Furthermore, among the snorers, 46.9% were identified as high-risk snorers, whereas the remaining 53.1% represented low-risk snorers. Conclusions: The study revealed the concealed risk of OSA among transport drivers could be screened through the questionnaires and demographics assessment. The application of the proposed screening protocol would triage and enhance safety of OSA affected transport drivers.

6.
Diabet Med ; 29(9): e255-62, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22248392

RESUMO

AIM: To test the hypothesis that fluconazole plus standard care is superior to the standard care for diabetic foot wounds infected with deep-seated fungal infections. METHODS: We carried out a randomized, controlled, open-label, parallel-arm study in 75 patients with both fungal and bacterial infections in deep tissues of diabetic foot wounds. Thirty-seven patients (control group) were given standard care (surgical debridement + culture-specific antibiotics + offloading + glycaemic control) and 38 patients (treatment group) were given fluconazole 150 mg daily plus standard care. Wound surface area was measured every 2 weeks until the endpoints (complete epithelialization or skin grafting) were met. RESULTS: By week 4, the mean wound surface area reduced to 27.3 from 111.5 cm(2) in the treatment group, as opposed to 67.1 from 87.3 cm(2) in the control group. Subsequently, the mean wound surface areas were remarkably smaller in the treatment group compared with the control group, and statistically significant differences (P ≤ 0.05) in mean wound surface area were observed between the treatment group and the control group at week 6. However, no statistically significant (P ≤ 0.47) difference in complete healing was observed between the treatment group and the control group, 20 vs. 24. The mean wound healing time for the treatment group was 7.3 weeks, whereas for the control group it was 11.3 weeks (P ≤ 0.022). Similarly, the probability of wound healing in the treatment group was 50 vs. 20% in the control group at week 10. CONCLUSIONS: Fluconazole plus standard care was superior to standard care alone in accelerating wound reduction among patients with diabetes with deep-seated fungal infections in diabetic foot wounds. Those in the treatment group who did heal, healed more quickly (P ≤ 0.022), but overall healing was not different.


Assuntos
Antifúngicos/farmacologia , Diabetes Mellitus Tipo 2/complicações , Pé Diabético/microbiologia , Pé Diabético/terapia , Micoses/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Idoso , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Glicemia/metabolismo , Estudos de Casos e Controles , Comorbidade , Desbridamento , Pé Diabético/epidemiologia , Feminino , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/epidemiologia , Resultado do Tratamento , Cicatrização/fisiologia
7.
J Conserv Dent ; 25(3): 269-273, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35836559

RESUMO

Introduction and Aim: Postoperative inflammation and endodontic failure occur due to apical extrusion of debris. The purpose of this in vitro study was to assess the amount of apically extruded debris during the root canal preparation using rotary and reciprocating nickel-titanium instrumentation systems. Materials and Methods: The mesiobuccal canals of seventy five mature, human mandibular molars were randomly divided into three groups (n = 25 teeth/group). Each group was instrumented using one of the three different instrumentation systems: Hyflex EDM (HEDM) rotary file, Flexicon X7 rotary, and Flexicon X1 reciprocating files. The canals were irrigated using distilled water. The debris extruded apically was collected in preweighed Eppendorf tubes and assessed with an electronic balance and compared. Statistical Analysis: Data were statistically analyzed by one-way analysis of variance and the intergroup comparison with single factor ANOVA. Results: The Flexicon X1 reciprocating system showed the maximum amount of apical extrusion of debris among all the groups. The least amount of debris was observed in Flexicon X7 rotary instrument (P > 0.05). Conclusion: Flexicon X7 rotary extruded significantly lesser amount of debris than Flexicon X1 reciprocating and HEDM rotary file systems.

9.
Indian J Dent Res ; 31(5): 784-790, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33433520

RESUMO

CONTEXT: Obstructive sleep apnea (OSA) is a condition affecting the upper airway among a vast number of people around the world. AIMS: To determine the prevalent risk factors of OSA and its association with craniofacial skeletal pattern. SETTINGS AND DESIGN: Cross-sectional, community-based study. MATERIALS AND METHODS: In the first stage, questionnaire and physical examination were done for 1000 subjects between 20 and 70 years of age. Subjects were categorized as snorers and non-snorers. Snorers were further grouped as high-risk and low-risk snorers. In the second stage, polysomnography (PSG) was done for randomly selected high-risk subjects. Craniofacial skeletal pattern of OSA-diagnosed subjects were compared with non-OSA subjects using lateral cephalograms. STATISTICAL ANALYSIS: Analysis was performed using IBM SPSS 20. Independent sample t-test was used. A P value < 0.05 was considered as statistically significant. RESULTS: The study population represented the following: high-risk snorers: 22.4%, low-risk snorers: 13.9%, and non-snorers: 63.7%. Excessive daytime sleepiness was present in 7.7%. Among high-risk, 80 underwent PSG, and 75 were diagnosed as OSA (94%) and 5 non-OSA subjects. Increased body mass index and neck circumference were statistically significant. Cephalometric evaluation showed difference in maxillomandibular relationship, narrowing of airway space, and inferiorly displaced hyoid. CONCLUSION: OSA is a major public health problem. Obesity is a strong predictor for OSA. Thus, high-risk subjects for sleep apnea could be identified using routine clinical examination, investigations, and anthropometric parameters.


Assuntos
Apneia Obstrutiva do Sono , Adulto , Idoso , Índice de Massa Corporal , Cefalometria , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Polissonografia , Fatores de Risco , Apneia Obstrutiva do Sono/epidemiologia , Adulto Jovem
10.
Mol Cell Biochem ; 319(1-2): 133-9, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18642056

RESUMO

We investigated the possible mechanisms of All-trans retinoic acid (ATRA)-promoted apoptosis induced by alpha-tocopherol succinate (alpha-TS) in freshly isolated leukemic cells obtained from chronic myeloid leukemic patients. alpha-TS at 50 microM concentration significantly decreased superoxide dismutase (SOD) activity and reduced glutathione (GSH) by 29% and 25%, respectively, and increased lipid peroxidation level by 33%. Though 10 microM ATRA did not affect these parameters, it further significantly enhanced alpha-TS-induced changes. Bax expression in the leukemic cells was increased by treatment with ATRA, alpha-TS, and their combination to 40%, 240%, and 320%, respectively, without any change in Bcl2 and p53 expression. C-myc was down regulated by treatment with ATRA, alpha-TS and their combination to 22%, 48.5%, and 52%, respectively. In conclusion, the data reveal that enhancement of alpha-TS-induced apoptosis by ATRA in leukemic cells was through up regulation of Bax and lipid peroxidation, and down regulation of c-myc and GSH.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Proteínas Proto-Oncogênicas c-myc/biossíntese , Tretinoína/farmacologia , alfa-Tocoferol/farmacologia , Proteína X Associada a bcl-2/biossíntese , Adulto , Antineoplásicos/agonistas , Sinergismo Farmacológico , Feminino , Glutationa/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Superóxido Dismutase/metabolismo , Tretinoína/agonistas , Células Tumorais Cultivadas , alfa-Tocoferol/agonistas
11.
Biotech Histochem ; 93(8): 581-588, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30253670

RESUMO

Methyl green (MG) is an inexpensive, nonproprietary, traditional histological stain for cell nuclei. When bound to DNA and upon excitation with orange-red light, it fluoresces brightly in the far red region. We compared MG with ethidium bromide (EtBr), the conventional stain for DNA in gels, and Serva DNA stain G™ (SDsG), a proprietary stain marketed as a safer alternative to EtBr for staining of electrophoresed DNA bands in agarose and polyacrylamide gels. DNA-MG fluorescence was recorded and 2.4 µg/ml MG produced crisp images of electrophoresed DNA after incubation for 10 min. Stain solutions were stable and detection limits for faint bands as well as relative densitometric quantitation were equivalent to EtBr. MG, EtBr and SDsG cost 0.0192, 0.024 and 157.5 US cents/test, respectively. MG is an effective stain for visualizing DNA in agarose and polyacrylamide gels. Its major advantages including low cost, comparable quality of staining, storage at room temperature, photo-resistance and low mutagenic profile outweigh its disadvantages such as staining of tracking dye and requirement for a gel documentation system with a red filter.


Assuntos
DNA/química , Verde de Metila , Resinas Acrílicas , Eletroforese em Gel de Poliacrilamida , Humanos , Limite de Detecção , Verde de Metila/química , Coloração e Rotulagem
13.
Contemp Clin Dent ; 8(1): 71-80, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28566855

RESUMO

OBJECTIVE: The objective of this study was to compare the surface morphology and dimensional stability of the bracket slot at the onset of treatment and after 12 months of intraoral exposure. The study also compared the amount of calcium at the bracket base which indicates enamel loss among the three orthodontic brackets following debonding after 12 months of intraoral exposure. MATERIALS AND METHODS: The sample consisted of 60 (0.022" MBT) canine brackets. They were divided into three groups: self-ligating, ceramic bracket with metal slot, and stainless steel (SS) brackets. The slot dimensions, micromorphologic characteristics of as-received and retrieved brackets were measured with a stereomicroscope and scanning electron microscope (SEM), respectively. The amount of calcium at the bracket base which indicates enamel damage was quantified using energy-dispersive X-ray spectrometry (EDX). RESULTS: The results showed statistically significant alterations (P < 0.05) in the right vertical dimension, internal tie wing width (cervical), right and left depth of the slot (Kruskal-Wallis test). Multiple comparison using Mann-Whitney test showed that ceramic brackets underwent (P < 0.05) minimal alterations in the right vertical dimension, internal tie wing width (cervical), right and left depth of the slot (0.01 mm, -0.003 mm, 0.006 mm, -0.002 mm, respectively) when compared with the changes seen in SS and self-ligating brackets. SEM analysis revealed an increase in the surface roughness of ceramic with metal slot brackets and self-ligating bracket showed the least irregularity. The presence of calcium was noted on all evaluated brackets under EDX, but ceramic with metal slot brackets showed a significantly greater amount of enamel loss (P = 0.001). CONCLUSION: Ceramic brackets were found to be dimensionally stable when compared to SS and self-ligating. Self-ligating bracket showed minimal surface irregularity. Ceramic with metal slot brackets showed a greater amount of enamel loss following debonding.

14.
J Otolaryngol Head Neck Surg ; 46(1): 16, 2017 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-28241867

RESUMO

BACKGROUND: The residency match is an important event in an aspiring physician's career. Otolaryngology - Head and Neck Surgery (OTL-HNS) is a surgical specialty that has enjoyed high numbers of applicants to its residency programs. However, recent trends in Canada show a decline in first-choice applicants to several surgical fields. Factors thought to influence a medical student's choice include role models, career opportunities and work-life balance. The notion of perceived competitiveness is a factor that has not yet been explored. This study sought to compare competitiveness of OTL-HNS, as perceived by Canadian medical students to residency match statistics published yearly by CaRMS (Canadian Residency Matching Service), with the hope of informing future decisions of surgical residency programs. METHODS: An electronic survey was created and distributed to all medical students enrolled in the 17 Canadian medical schools. After gathering demographic information, students were asked to rank what they perceived to be the five most competitive disciplines offered by CaRMS. They were also asked to rank surgical specialties from most to least competitive. Publically available data from CaRMS was then collected and analyzed to determine actual competitiveness of admissions to Canadian OTL-HNS residency programs. RESULTS: 1194 students, from first to fourth year of medical school, completed the survey. CaRMS statistics over the period from 2008 to 2014 demonstrated that the five most competitive specialties were Plastic Surgery, Dermatology, Ophthalmology, Emergency Medicine and OTL-HNS. Among surgical disciplines, OTL-HNS was third most competitive, where on average 72% of students match to their first-choice discipline. When students were questioned, 35% ranked OTL-HNS amongst the top five most competitive. On the other hand 72%, 74% and 80% recognized Opthalmology, Dermatology and Plastic Surgery as being among the five most competitive, respectively. We found that fourth-year medical students were significantly more knowledgeable about the competitiveness of both OTL-HNS and Plastic Surgery compared to first-year students (p < 0.01). CONCLUSION: Overall, Canadian medical students may underestimate the competitiveness of OTL-HNS. Furthermore, competitiveness would appear to be a concept that resonates with medical students during the match process.


Assuntos
Internato e Residência , Otolaringologia/educação , Percepção , Estudantes de Medicina , Adulto , Canadá , Escolha da Profissão , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e Questionários
15.
Int J Lab Hematol ; 38(5): 543-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27339905

RESUMO

INTRODUCTION: A good bone marrow (BM) sample is essential in evaluating many hematologic disorders. An unsuccessful BM aspiration (BMA) procedure precludes a successful flow cytometric immunophenotyping (FCI) in most hematologic malignancies. Apart from FCI, most ancillary diagnostic techniques in hematology are less informative. We describe the feasibility of FCI in vortex-dislodged cell preparation obtained from unfixed trephine biopsy (TB) specimens. METHODS: In pancytopenic patients and dry tap cases, routine diagnostic BMA and TB samples were complemented by additional trephine biopsies. These supplementary cores were immediately transferred into sterile tubes filled with phosphate-buffered saline, vortexed, and centrifuged. The cell pellet obtained was used for flow cytometric immunophenotyping. RESULTS: Of 7955 BMAs performed in 42 months, 34 dry tap cases were eligible for the study. Vortexing rendered a cell pellet in 94% of the cases (32 of 34), and FCI rendered a rapid diagnosis in 100% of the cases (32 of 32) where cell pellets were available. CONCLUSION: We describe an efficient procedure which could be effectively utilized in resource-limited centers and reduce the frequency of repeat BMA procedures.


Assuntos
Células da Medula Óssea , Medula Óssea , Citometria de Fluxo/métodos , Neoplasias Hematológicas , Imunofenotipagem/métodos , Adolescente , Adulto , Idoso , Biópsia , Medula Óssea/metabolismo , Medula Óssea/patologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Criança , Pré-Escolar , Feminino , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
J Neurosci ; 21(24): RC188, 2001 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-11734603

RESUMO

Endocannabinoids are key intercellular signaling molecules in the brain, but the physiological regulation of the endocannabinoid system is not understood. We used the retrograde signal process called depolarization-induced suppression of inhibition (DSI) to study the regulation of this system. DSI is produced when an endocannabinoid released from pyramidal cells suppresses IPSCs by activating CB1R cannabinoid receptors located on inhibitory interneurons. We now report that activation of group I metabotropic glutamate receptors (mGluRs) enhances DSI and that this effect is blocked by antagonists of both mGluRs and of CB1R. We also found that DSI is absent in CB1R knock-out (CB1R(-/-)) mice, and, strikingly, that mGluR agonists have no effect on IPSCs in these mice. We conclude that group I mGluR-induced enhancement of DSI, and suppression of IPSCs, is actually mediated by endocannabinoids. This surprising result opens up new approaches to the investigation of cannabinoid actions in the brain.


Assuntos
Canabinoides/metabolismo , Hipocampo/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Animais , Moduladores de Receptores de Canabinoides , Canabinoides/antagonistas & inibidores , Relação Dose-Resposta a Droga , Endocanabinoides , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hipocampo/citologia , Técnicas In Vitro , Interneurônios/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Camundongos , Camundongos Knockout , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Técnicas de Patch-Clamp , Piperidinas/farmacologia , Células Piramidais/metabolismo , Pirazóis/farmacologia , Ratos , Receptor de Glutamato Metabotrópico 5 , Receptores de Canabinoides , Receptores de Droga/antagonistas & inibidores , Receptores de Droga/deficiência , Receptores de Droga/metabolismo , Receptores de Glutamato Metabotrópico/agonistas , Receptores de Glutamato Metabotrópico/antagonistas & inibidores
17.
Circulation ; 101(18): 2185-92, 2000 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-10801760

RESUMO

BACKGROUND: Increased diastolic chamber stiffness (increased DCS) during angina (demand ischemia) has been postulated to be generated by increased diastolic myocyte calcium concentration. METHODS AND RESULTS: We reproduced demand ischemia in isolated isovolumically contracting red-cell-perfused rabbit hearts by imposing pacing tachycardia during global low coronary blood flow (32% of baseline). This increased lactate production without increasing oxygen consumption and resulted in increased DCS (isovolumic left ventricular end-diastolic pressure [LVEDP] increased 10 mm Hg, P<0. 001, n=38). To determine the mechanism of increased DCS, we assessed responses to a quick-stretch-release maneuver (QSR), in which the intraventricular balloon was rapidly inflated and deflated to achieve a 3% circumferential muscle fiber length change. QSR was first validated as an effective method of discriminating between calcium-driven and rigor-mediated increased DCS. QSR imposed during demand ischemia when DCS had increased (LVEDP pretachycardia versus posttachycardia, 15+/-1 versus 27+/-2 mm Hg, P<0.001, n=6) reduced DCS to pretachycardia values (LVEDP post-QSR, 15+/-1 mm Hg, P<0.001), ie, elicited a response characteristic of rigor, without any component of calcium-generated tension. CONCLUSIONS: A rigor force, possibly resulting from high-energy phosphate depletion and/or an increase in ADP, appears to be the primary mechanism underlying increased DCS in this model of global LV demand ischemia.


Assuntos
Cálcio/fisiologia , Isquemia Miocárdica/fisiopatologia , Animais , Diástole , Modelos Animais de Doenças , Eletrocardiografia , Isquemia Miocárdica/metabolismo , Consumo de Oxigênio , Coelhos
18.
Circulation ; 102(21): 2643-9, 2000 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-11085969

RESUMO

BACKGROUND: Ischemia is characterized by an increase in intracellular calcium and occurrence of diastolic dysfunction. We investigated whether the myocyte calcium level is an important direct determinant of ischemic diastolic dysfunction. METHODS AND RESULTS: We exposed isolated, perfused isovolumic (balloon in left ventricle) rat and rabbit hearts to low-flow ischemia and increased extracellular calcium (from 1.5 to 16 mmol/L) for brief periods. Intracellular calcium was measured by aequorin. Low-flow ischemia resulted in a 270% increase (P:<0.05) in diastolic intracellular calcium, a 50% (P:<0.05) calcium transient amplitude decrease, and a 52% (P:<0.05) slowing of calcium transient decline. Diastolic pressure increased by 6+/-2 mm Hg (P:<0.05), and rate of systolic pressure decay decreased by 65% (P:<0.05). Experimentally increasing extracellular calcium doubled both intracellular diastolic calcium and calcium transient amplitude, concomitant with a developed pressure increase; however, there was no increase in ischemic diastolic pressure, slowing of the calcium transient decay, or further slowing of systolic pressure decay. Similarly, after 45 minutes of low-flow ischemia, after diastolic pressure had increased from 8.5+/-0.6 to 19.7+/-3.5 mm Hg (P:<0.001), intracoronary high-molar calcium chloride infusion increased systolic pressure from 36+/-4 to 63+/-11 mm Hg (P:<0.001), indicating an increase in intracellular calcium, but it decreased diastolic pressure from 19. 7+/-3.5 to 17.5+/-3.7 mm Hg (P:<0.01). Conversely, EGTA infusion decreased systolic pressure, indicating a decrease in intracellular calcium, but did not decrease diastolic pressure. CONCLUSIONS: When calcium availability was experimentally altered during ischemia, there was no alteration in left ventricular diastolic pressure, suggesting that ischemic diastolic dysfunction is not directly mediated by a calcium activated tension.


Assuntos
Cálcio/metabolismo , Diástole , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Cálcio/farmacologia , Quelantes/farmacologia , Diástole/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ácido Egtázico/farmacologia , Espaço Extracelular/metabolismo , Técnicas In Vitro , Masculino , Isquemia Miocárdica/fisiopatologia , Coelhos , Ratos , Ratos Wistar , Sístole
19.
J Am Coll Cardiol ; 37(8): 2144-53, 2001 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-11419901

RESUMO

OBJECTIVES: The goal of this study was to determine the subcellular mechanism(s) underlying increased left ventricular (LV) diastolic chamber stiffness (DCS) during angina (demand ischemia). BACKGROUND: Increased DCS may result from increased diastolic myocyte calcium concentration and/or rigor. Therefore, we assessed the effects of direct alterations of both calcium-activated tension and high-energy phosphates on increased DCS. METHODS: Demand ischemia was reproduced in isolated, isovolumic, red-cell perfused rabbit hearts by imposing low-flow ischemia and pacing tachycardia. This resulted in increased DCS. Interventions were performed after LV end-diastolic pressure had increased approximately 7 mm Hg. Initially, to determine the effects of altered calcium concentration or myofilament calcium responsiveness, hearts received either: 1) 5 or 14 mmol/L calcium chloride; 2) 8 mmol/L egtazic acid; 3) 5 mmol/L butane-dione-monoxime (BDM); or 4) 50 mmol/L ammonium chloride (NH4Cl). Then, to assess the contribution of decreased high-energy phosphate supply, hearts received 5) glucose (25 mmol/L) and insulin (400 microU/ml). RESULTS: 1) Calcium chloride, 5 and 14 mmol/L, increased LV systolic pressure by 42% and 70%, respectively (p < 0.001), indicating increased calcium-activated tension, but did not further increase DCS, implying intact diastolic calcium resequestration. 2) Egtazic acid reduced LV systolic pressure by 30% (p < 0.001), indicating reduced intracellular calcium, but failed to reduce increased DCS. 3) Butane-dione-monoxime and NH4Cl chloride affected contractile function (i.e., a calcium-driven force) but did not alter increased DCS. 4) Glucose and insulin, which increase high-energy phosphates during ischemia, reduced increased DCS by 50% (p < 0.001). CONCLUSIONS: Increased DCS during demand ischemia was insensitive to maneuvers altering intracellular calcium concentration or myofilament calcium-responsiveness, that is, evidence against an etiology of calcium-activated tension. In contrast, increased glycolytic substrate ameliorated increased DCS, supporting a primary mechanism of rigor-bond formation.


Assuntos
Angina Pectoris/fisiopatologia , Cálcio/fisiologia , Glicólise/fisiologia , Disfunção Ventricular Esquerda/fisiopatologia , Animais , Modelos Animais de Doenças , Hemodinâmica , Técnicas In Vitro , Coelhos
20.
J Clin Pathol ; 58(3): 320-1, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15735169

RESUMO

The incidence of myelodysplastic syndrome (MDS) with erythroid hypoplasia/aplasia is probably underestimated because in most patients it is mistaken for acquired pure red blood cell aplasia. This report describes three children who fulfilled the criteria for MDS with erythroid hypoplasia/aplasia. All these patients had transfusion dependent anaemia, reticulocytopenia, erythroid hypoplasia/aplasia, severe dysgranulopoiesis, and dysmegakaryopoiesis.


Assuntos
Síndromes Mielodisplásicas/diagnóstico , Aplasia Pura de Série Vermelha/diagnóstico , Transfusão de Sangue , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Masculino , Síndromes Mielodisplásicas/terapia , Aplasia Pura de Série Vermelha/terapia
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