RESUMO
Generation 4 of polyamidoamine dendrimer (G4-PAMAM) has several biological effects due to its tridimensional globular structure, repetitive branched amides, tertiary amines, and amino-terminal subunit groups liked to a common core. G4-PAMAM is cytotoxic due to its positive charges. However, its cytotoxicity could increase in cancer cells due to the excessive intracellular negative charges in these cells. Furthermore, this work reports G4-PAMAM chemical structural characterization using UHPLC-QTOF-MS/MS (LC-MS) by electrospray ionization to measure its population according to its positive charges. Additionally, the antiproliferative effects and intracellular localization were explored in the HMC-1 and K-562 cell lines by confocal microscopy. The LC-MS results show that G4-PAMAM generated multivalent mass spectrum values, and its protonated terminal amino groups produced numerous positive charges, which allowed us to determine its exact mass despite having a high molecular weight. Additionally, G4-PAMAM showed antiproliferative activity in the HMC-1 tumor cell line after 24 h (IC50 = 16.97 µM), 48 h (IC50 = 7.02 µM) and 72 h (IC50 = 5.98 µM) and in the K-562 cell line after 24 h (IC50 = 15.14 µM), 48 h (IC50 = 14.18 µM) and 72 h (IC50 = 9.91 µM). Finally, our results showed that the G4-PAMAM dendrimers were located in the cytoplasm and nucleus in both tumor cell lines studied.
Assuntos
Dendrímeros/farmacologia , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Nylons/farmacologia , Antineoplásicos/análise , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cromatografia Líquida , Dendrímeros/análise , Dendrímeros/farmacocinética , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Concentração Inibidora 50 , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Células K562 , Leucemia/patologia , Nylons/análise , Nylons/farmacocinética , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Distribuição TecidualRESUMO
AIM: To evaluate the effects of progressive apical enlargement on the amount of unprepared root canal surface area and remaining dentine thickness. METHODOLOGY: The root canals of 30 extracted mandibular incisors with Vertucci's type I configuration were instrumented with rotary HyFlex CM instruments (Coltene-Whaledent, Altstätten, Switzerland) up to 4 instruments larger than the first one that bound at the working length (WL). Teeth were scanned in a micro-computed tomography (micro-CT) device before canal preparation and after instrumentation with the 2nd, 3rd and 4th larger instruments. The amount of unprepared surface area in the full canal or in the apical 4 mm as well as the remaining dentine thickness at 10 mm from the WL were calculated and compared. The general linear model for repeated measures adjusted by Bonferroni's post hoc test was used for statistic analysis. RESULTS: There was a significant reduction in the amount of unprepared areas after each increase in preparation size (P < 0.01). This was observed for both the full canal length and the 4-mm apical segment. The amount of remaining dentine was also significantly reduced after each file size (P < 0.01). However, dentine thickness always remained greater than 1 mm, even after using the largest instrument. CONCLUSION: Apical preparations up to 4 instruments larger than the first one to bind at the WL caused a significant progressive reduction in the unprepared canal area.
Assuntos
Cavidade Pulpar/diagnóstico por imagem , Preparo de Canal Radicular/instrumentação , Ápice Dentário/diagnóstico por imagem , Raiz Dentária/diagnóstico por imagem , Microtomografia por Raio-X , Humanos , Técnicas In Vitro , IncisivoRESUMO
AIM: To microscopically examine the cleanliness of root canal walls that remained unprepared as revealed by micro-CT. METHODOLOGY: The root canals of 10 freshly extracted mandibular premolars with necrotic pulps and apical periodontitis along with the mesiobuccal canals of 11 mandibular molars with vital pulps were prepared using Reciproc instruments R40 and R25, respectively, and 2.5% sodium hypochlorite irrigation. Specimens were scanned in micro-CT before and after preparation, and the unprepared areas were identified. The outer root surface corresponding to the untouched areas was marked on each root third to guide further analysis using histological (for teeth with vital pulps) and scanning electron microscopic (SEM; for necrotic teeth) examination. In the teeth with vital pulps, the root canal area occupied by tissue remnants was calculated. In SEM analysis of teeth with necrotic pulps, scores were attributed for the amount of debris on the untouched areas. RESULTS: The proportion of unprepared areas in the mesiobuccal molar canals was 18.1% and 9.6% over the full canal length and apical canal, respectively. In premolars, corresponding figures were 34.6% and 17.6%, respectively. Histological analysis of canals with vital pulps revealed tissue remnants over the untouched walls almost exclusively in the apical canal. SEM analysis of the canals with necrotic pulps revealed debris along the untouched walls in all root canal thirds. CONCLUSION: The areas that remain untouched by Reciproc instruments used with 2.5% NaOCl irrigation as revealed by micro-CT analysis were usually covered with debris, in the form of pulp tissue remnants, bacteria and dentine chips, especially in the apical root canal.
Assuntos
Cavidade Pulpar/patologia , Cavidade Pulpar/diagnóstico por imagem , Cavidade Pulpar/ultraestrutura , Necrose da Polpa Dentária/patologia , Humanos , Microscopia Eletrônica de Varredura , Periodontite Periapical/patologia , Preparo de Canal Radicular , Microtomografia por Raio-XRESUMO
We studied the features of parallel immunoneuroendocrine responses in patients with different degrees of chronic Chagas myocarditis (indeterminate, mild/moderate or severe). A systemic inflammatory scenario was evident in patients with severe myocarditis compared to healthy subjects. This was paralleled by a disrupted activation of the hypothalamus-pituitary-adrenal axis, characterized by decreased concentrations of dehydroepiandrosterone-sulfate (DHEA-s) and an unbalanced cortisol/DHEA-s ratio, reinforcing the view that severe Chagas disease is devoid of an adequate anti-inflammatory milieu, likely involved in pathology. Our study constitutes the first demonstration of neuroendocrine disturbances, in parallel to a systemic inflammatory profile, during progressive human Chagas disease.
Assuntos
Doença de Chagas/imunologia , Doença de Chagas/patologia , Progressão da Doença , Mediadores da Inflamação/fisiologia , Adulto , Doença de Chagas/metabolismo , Doença Crônica , Feminino , Hormônio do Crescimento Humano/fisiologia , Humanos , Interleucina-17/fisiologia , Interleucina-6/fisiologia , Masculino , Pessoa de Meia-Idade , Células Neuroendócrinas/imunologia , Células Neuroendócrinas/metabolismo , Células Neuroendócrinas/patologia , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
Kidney transplantation has been performed in Cuba since 1970. In 1979, compatible living-related donors were introduced into our renal transplantation program. There are 43 hospitals distributed around the country with a multidisciplinary group that attends cadaveric donors with encephalic death. The donor rate in Cuba oscillates between 15 and 18 per million; 90% of them are from cadaveric donors. This program includes 47 dialysis centers throughout the country with 2300 patients as supported by a National Coordinating Center at The Nephrology Institute. Cuba is one of the first countries in our region with this experience.
Assuntos
Transplante de Rim/estatística & dados numéricos , Cadáver , Causas de Morte , Cuba/epidemiologia , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/cirurgia , Doadores de TecidosRESUMO
Tumour necrosis factor (TNF)-alpha is crucial for resistance to Trypanosoma cruzi acute infection, but there is scant information on its role during the chronic phase. To address this issue, we analysed whether a short treatment with a TNF-alpha blocker affected the course and characteristics of chronic disease in a rat experimental model of T. cruzi infection. An anti-TNF-alpha agent (infliximab) was administered during the chronic phase for a period of 4 weeks (3 mg/kg/week), while control infected rats were inoculated with saline physiological solution. Search for parasites yielded non-successful results in all infected groups, irrespective of treatment. Nevertheless, the presence of T. cruzi kDNA in heart tissue was detected in infected and infected plus treated animals. Because infliximab might induce changes in the anti-parasite cytokine response, circulating levels of interleukin (IL)-10, interferon-gamma and nitric oxide were evaluated. An increase in IL-10 levels was observed only in the infected group treated with the anti-TNF-alpha blocker compared to the remaining groups (P < 0.05). A clear attenuation of histological damage associated with a diminution of cardiac TNF-alpha mRNA expression was observed in the infected and treated animals compared to the infected and non-treated group. Blocking of TNF-alpha during a relatively short period in chronically infected rats did not lead to evident parasite reactivation but reduced myocarditis severity significantly, indicating a role of this cytokine in the pathogenesis of chronic myocardial damage.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Cardiomiopatia Chagásica/tratamento farmacológico , Imunossupressores/uso terapêutico , Trypanosoma cruzi , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Antiprotozoários/imunologia , DNA de Protozoário/análise , Coração/parasitologia , Imuno-Histoquímica , Imunossupressores/farmacologia , Infliximab , Masculino , Modelos Animais , Parasitemia/diagnóstico , RNA Mensageiro/análise , Distribuição Aleatória , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Trypanosoma cruzi/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The well-established model of Chagas' disease in "l" rats was used to evaluate the effects of three injections of heat-killed Gordonia bronchialis, Rhodococcus coprophilus or saline on Trypanosoma cruzi parasitaemia and acute and chronic myocarditis, sequelae of the infection. Two vaccinating injections were given prior to challenge with T. cruzi, and the third, immunotherapeutic, injection was given 7 days after challenge. Treatment with either actinomycete significantly reduced acute parasitaemia (p<0.04), modified cellular infiltration during acute myocarditis and limited chronic myocarditis (p<0.03) in comparison with the saline-treated control animals. Immunological investigations showed that both bacterial preparations achieved their results through different mechanisms. The relevance of our findings to human Chagas' disease is discussed.
Assuntos
Actinomycetales/imunologia , Doença de Chagas/imunologia , Imunização , Animais , Anticorpos Antiprotozoários/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Cardiomiopatia Chagásica/imunologia , Microbiologia Ambiental , Imunoglobulina G/sangue , Masculino , Parasitemia/prevenção & controle , Ratos , SuspensõesRESUMO
Earlier work in Trypanosoma cruzi-infected C57BL/6 and BALB/c mice revealed an acute disease, of lethal outcome in the former group and lesser severity in BALB/c mice. Fatal course was not accompanied by an increased parasite load, but by a substantial imbalance between pro- and anti-inflammatory cytokine serum levels. To better characterise the mechanisms allowing the host to restrain the infection, we have now studied the specific IgG production and in vitro behaviour of peritoneal macrophages (PMs) when exposed to T. cruzi. BALC/c mice displayed higher serum levels of specific immunoglobulins in the first weeks of acute infection. In vitro infected PMs showed no between-group differences in the number of intracellular parasites, although TNFalpha levels were significantly higher in culture supernatants from C57BL/6 mice. Because an LPS-based pretreatment (desensitisation protocol followed by a sublethal LPS dose) reduced disease severity of C57BL/6 mice, we next explored the features of the in vitro infection in PMs from mice subjected to such protocol. PMs from LPS-pretreated mice had a decreased production of TNFalpha and IL-1beta, becoming more permissive to parasite replication. It is concluded that deficient control of T. cruzi infection in C57BL/6 mice may also involve a less satisfactory specific IgG response and increased TNFalpha production by PMs. Improved disease outcome in LPS-pretreated mice may be associated with the reduced inflammatory cytokine production by PMs, but the impaired ability of these cells to control parasite growth suggests that compensatory mechanisms are operating in the in vivo situation.
Assuntos
Doença de Chagas/imunologia , Citocinas/metabolismo , Imunoglobulina G/imunologia , Macrófagos Peritoneais/metabolismo , Trypanosoma cruzi/imunologia , Animais , Citocinas/imunologia , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Técnica Indireta de Fluorescência para Anticorpo , Interleucina-1/imunologia , Interleucina-1/metabolismo , Lipopolissacarídeos , Macrófagos Peritoneais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não Paramétricas , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The prevalence of H. pylori infection in AIDS patients has been controversial. A. controlled prospective and descriptive study was conducted in a group of 64 HIV-infested patients. H. pylori detection was carried out by endoscopic study during which two biopsy samples of gastric antrum and body were taken for the histologic study and other 2 samples of gastric antrum and body for urease testing. H.pylori infection prevalence was 56.3%. The comparison group was composed by 110 serologically HIV-negative patients, with an infection prevalence rate of 77.2%. In the HIV-AIDS group, the frequency of gastric ulcer was 1,5% and no duodenal ulcer was found whereas the comparison group showed a frequency of gastric and duodenal ulcers of 1.8 and 15.5% respectively. HIV+/AIDS patients in category I exhibited an H. pylori infection prevalence of 68.7%, category II, 39.2% and category III, 21,0%. A reversed association was observed between the level of immune deterioration and the prevalence of H. pylori infection.
Assuntos
Infecções por HIV/complicações , Infecções por Helicobacter/etiologia , Helicobacter pylori , Síndrome da Imunodeficiência Adquirida/complicações , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The barotrauma cases related to childbirth are an uncommon event, especially the neumopericardium. This entity must be suspected in a patient with subcutaneuos emphysema and confirmed by chest X-ray. The management is based on closed observation, support measures and antibiotic to prevent infection. The radiological follow up is important to evaluate the resolution of this problem. The patient must be followed with caution if the neumopericardium increases because this could lead to a cardiac tamponade with fatal consequences. The description of a case diagnosed and managed in our hospital is done herein which evolution was satisfactory towards resolution of the pneumopericardium without the need of further intervention.
Assuntos
Pneumopericárdio/etiologia , Enfisema Subcutâneo/etiologia , Adulto , Feminino , Humanos , Recém-Nascido , Pneumopericárdio/diagnóstico por imagem , Período Pós-Parto , Gravidez , Radiografia , Enfisema Subcutâneo/diagnóstico por imagemRESUMO
Stomas and pregnancy is an uncommon event and the literature in this regard is scarce, this poses significant concern on its management. Among the etiology we found the ulcerative colitis, trauma, and rectovaginal fistula, etc. The management should include a perinatologist and a specialist in colon and rectum. We should be familiarized with the potential complication as the intestinal obstruction, stoma prolapse, narrowing of the stoma and bleeding. The route delivery should be vaginal and the c-section is reserved for obstetric indications. The patient must receive education regarding stoma complications, and how to copy to live with a stoma.
Assuntos
Colostomia , Resultado da Gravidez , Adulto , Feminino , Humanos , GravidezRESUMO
There is a broad epidemiologic evidence related with the increase of the incidence and prevalence of diabetes mellitus type 2 throughout the world, especially in Western populations, at rates considered epidemic. Cerebrovascular disease and myocardial infarction are two of the most important complications of this disease and they have very high social and economic consequences. Treatment of this disease is directed good metabolic control, diminishing toward obtain co-morbidity, and reducing acute and chronic diabetic complications. Diet, hypoglycemic drugs or insulin, and programs of physical activity are used for this purpose. This document presents some thoughts on the difficulties related with the prescription of physical exercise in the diabetic patient and a brief proposal to solve those problems in the clinical practice.
Assuntos
Diabetes Mellitus Tipo 2/terapia , Exercício Físico , Fatores Etários , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Angiopatias Diabéticas/prevenção & controle , Exercício Físico/fisiologia , Guias como Assunto , Humanos , Fatores Sexuais , Fatores de TempoRESUMO
The Ogilvie's Syndrome is a major surgical complication. It is defined as a severe dilatation of the colon, the cecum, ascendant and transverse, without the presence air at the distal colon following abdominal surgery. The causes are unknown. We described a clinical case of patient delivered by C-S who developed this syndrome and a review of the literature. We emphasized on the importance of the early diagnosis by the use of the traditional abdomen X-Rays and we described a relatively new approach for this patients through the decompression by colonoscopy using a Levin's catheter successfully. This is an alternative minimum-invasive treatment which could be of a great benefit for the patients with this disease.
Assuntos
Pseudo-Obstrução do Colo/terapia , Colonoscopia , Adulto , Feminino , Humanos , RetoRESUMO
UNLABELLED: We performed a prospective, controlled, randomized trial to compare de safety and efficacy between the vaginal assisted delivery with vacum extractor forceps. We included a control group of primigravidae. We use the ACOG application criteria for operative obstetrics. We measured the differences in regard to indication for operative delivery, obstetric trauma and the general characteristics of the patients. A total of 210 patients were included which were distributed in three groups. In the first group we included the patients of vacum extractor, the second group of forceps and the third the control group. In our results we found no statistically significant differences among three groups in regard to the general characteristics and obstetric trauma. In the vacum extractor group we found six cefalohematomas (8.5%), two newborns with skin laceration (2.8%) and four newborns with cerebral edema (5.7%). In the forceps group we had two newborns diagnosed with cefalohematomas (2.8%), seven newborns with cerebral edema (10%) and scalp laceration on four newborns (6%). In the control group we found one cefalohematoma (1.4%) and cerebral edema in four newborns (5.7%). We did not find statistically significant differences when we compared the group of the vacum and the forceps. CONCLUSION: With this information we concluded that both instruments are equal in regard to efficacy and safety when they are use by experimented hands and following the application criteria. Nevertheless, there is a high incidence of vaginal injuries and obstetric trauma in the newborn in the operative delivery compared with the control group without an important increase in the perinatal mortality.
Assuntos
Forceps Obstétrico , Vácuo-Extração , Adulto , Desenho de Equipamento , Feminino , Humanos , Gravidez , Estudos Prospectivos , VaginaRESUMO
The pregnancy increases the risk of cardiovascular ischemic events, The longitudinal sinus thrombosis is very rare, but the incidence increases during pregnancy and puerperium. The mortality rates range from 25% to 50%. This report consists of a case which was studied and managed at the Military Central Hospital. It occurred on the 12th day post C-S. The diagnostic was confirmed by MRI. The treatment consisted of rest and heparin with a successful development. Our findings agreed with the studies reported at the literature that suggested a beneficial effect with the heparin's use, lowering drastically the mortality rates. Some still oppose to its use because of the risk of an intracranial hemorrhage.
Assuntos
Transtornos Puerperais , Trombose dos Seios Intracranianos , Adulto , Anticoagulantes/uso terapêutico , Cesárea , Feminino , Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Transtornos Puerperais/diagnóstico , Transtornos Puerperais/tratamento farmacológico , Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/tratamento farmacológico , Varfarina/uso terapêuticoRESUMO
The coarctation of the aorta is an uncommon pathology which has a high mortality rate during pregnancy; a very thorough antenatal control must be performed due to the serious complications that may cause death. It is important to eliminate any congenital malformations related to this pathology, such as aneurysms of the Willis polygon, Ductus Persistent or ventricular intercommunication; arterial pressure must be strictly controlled using antihypertensive drugs when needed with beta-blockers. The delivery route may be vaginal, C-section must be reserved only for obstetric reasons. We present a case studied in the Military Hospital, treated with antihypertensives, the fetus had intrauterine growth retardation and was delivered by C-section successfully.
Assuntos
Coartação Aórtica/cirurgia , Retardo do Crescimento Fetal/etiologia , Complicações Cardiovasculares na Gravidez/cirurgia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Anti-Hipertensivos/uso terapêutico , Coartação Aórtica/complicações , Coartação Aórtica/diagnóstico por imagem , Cesárea , Ecocardiografia , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Monitorização Fetal , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Resultado da Gravidez , Ultrassonografia Pré-NatalRESUMO
Peripatum cardiomyopathy is a rare disease, which appears as cardiac failure, at the end of pregnancy and puerperium without an apparent cause. The diagnosis is done clinically based in accepted criteria by Demakis, and it is confirmed by auxiliary tests. Treatment includes rest, digitalic and diuretic medications. Prognosis is bad when there is not symptomatic regression, with a high mortality soon after. The experience at Hospital Central Militar from 1967 to 1995, is presented. There were nine cases, two of which had died; and the presentation of the last case, is done herein.
Assuntos
Cardiomiopatias/diagnóstico , Complicações Cardiovasculares na Gravidez/diagnóstico , Adulto , Cardiomegalia/diagnóstico , Cardiomegalia/terapia , Cardiomiopatias/terapia , Cesárea , Digoxina/uso terapêutico , Procedimentos Cirúrgicos Eletivos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Hospitais Militares , Humanos , México , Gravidez , Complicações Cardiovasculares na Gravidez/terapia , Edema Pulmonar/diagnóstico , Edema Pulmonar/terapia , Ultrassonografia Pré-NatalRESUMO
El Eritema Discrómico Perstans (EDP) y el Vitiligo son dos dermatosis pigmentarias cutáneas de etiología desconocida. En el presente estudio los infiltrados leucocitarios de EDP (n=10) y de Vitiligo (n=5) fueron estudiados, usando la técnica de la inmunoperoxidasa de avidinabiotina (ABC) y anticuerpos monoclonales que reconocen las siguientes subpoblaciones celulares: T-Supresor-Citotóxico (CD8=Leu-2), T-cooperadores (CD4=OKT4), T-Supresores (Leu-15), Pan T (Leu-4), Macrófagos (Leu-M3) y células de Langerhans (CD1=Leu-6); y marcadores celulares para antígeno la, Gamma Interferón, Interleucina-2 y receptor para Interleucina-2. El análisis inmunocitoquímico mostró una acumulación selectiva de células T-Citotóxicas Leu-4+, Leu-2+, Leu-15-en la epidermis tanto de EDP como de lesiones recientes de Vitiligo. Además, un aumento en el número de células de Langerhans epidérmicas Leu-6 se observó en algunos de los casos de EDP y de Vitiligo. La relación CD4/CD8 en las lesiones y en la piel no envuelta para ambos desórdenes no mostró diferencias significativas, no obstante valores menores que uno se apreciaron sólo en los infiltrados de piel lesionada. Los macrófagos en los infiltrados dérmicos de EDP se encontraban generalmente yuxtapuestos al pigmento melánico. Los linfocitos que expresaban en su superficie antígenos tipo TAC, IL-2 y Gamma Interferón, fueron muy pocas en los infiltrados dérmicos. Algunas células NK se encontraban también presentes en la epidermis enferma. Estas observaciones morfológicas sugieren una importante participación de la inmunidad celular en la discromia de diversos desórdenes pigmentarios cutáneos