RESUMO
ABSTRACTThis study compares semantic and phonological interference vulnerability across the full range of learning processes. Method: 43 controls aged 61-88 underwent a neuropsychological examination, French adaptation of the LASSI-L, and an experimental phonological test, the TIP-A. Paired sample t-tests, factorial ANOVA and hierarchical regressions were conducted, psychometric properties were calculated. Results: TIP-A efficiently generated phonological interference between concurrent word lists and was associated with short-term memory, unlike LASSI-L. On LASSI-L, proactive interference was higher than retroactive interference; the opposite pattern was found on TIP-A. Memory performance was better explained by age in the semantic than in the phonological task. Age was not associated with interference vulnerability. Intrusions and false recognition were associated with cognitive functioning regardless of age, particularly in the semantic context. Conclusion: To our knowledge, this is the first study to assess phonological and semantic interference using homologous concurrent word list tasks, and not a working memory build-up or DRM paradigm. The pattern obtained illustrates the weak initial memory trace in a phonological context and results are discussed according to depth-of-processing and dual-process theories. Similar paradigms could be studied among various pathologies for a better understanding of generalised interference vulnerability vs. specific semantic or phonological impairment.
Assuntos
Envelhecimento , Semântica , Humanos , Aprendizagem , Memória de Curto Prazo , CogniçãoRESUMO
Relying on procedural memory is a promising approach for interventions that address the cognitive difficulties found in semantic dementia. The aim of this study was to determine if procedural memory could be used to optimise learning of relevant smartphone functions in MH, a 55-year-old man with semantic dementia. The impact of learning to use specific smartphone applications, which display concepts and their semantic characteristics, on relearning useful significant concepts, was also explored in MH. This patient, who showed no deficits in procedural learning on a serial reaction time paradigm, was able to learn manipulations related to 15 smartphone functions although, because of his deficit in word comprehension, he generally needed verbal cues to clarify which functions he was asked to perform. Six months after the end of the intervention, he was still using 8 of the 15 functions regularly. However, repeated exposure to concepts through the use of two applications did not improve naming or retrieval of semantic attributes. This study showed the potential of relying on procedural memory to optimise learning of new technologies in the ecological rehabilitation of semantic dementia.
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Atividades Cotidianas , Demência Frontotemporal/reabilitação , Memória de Longo Prazo , Aplicativos Móveis/estatística & dados numéricos , Smartphone/estatística & dados numéricos , Encéfalo/patologia , Sinais (Psicologia) , Demência Frontotemporal/patologia , Demência Frontotemporal/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Destreza Motora , Testes Neuropsicológicos , Prática Psicológica , Tempo de ReaçãoRESUMO
This prospective clinical audit of the utilization of red cell concentrates assesses 55 consecutive transfusion episodes in chronically anaemic adult patients. It examines the appropriateness and outcome of the transfusion episodes; over-transfusion and wastage rates, assessment of anaemia, the informed consent process, and if teaching influenced these parameters when compared to an earlier retrospective audit. The audit revealed several strengths and weaknesses relating to our institution's transfusion practices. Training sessions led to clinically and economically important improvements in transfusion decisions, the investigation of anaemia and the obtainment of informed consent prior to transfusions.
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Preservação de Sangue/métodos , Transfusão de Eritrócitos/métodos , Eritrócitos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , África do Sul , Adulto JovemRESUMO
Melanoma diagnosis in dogs can be challenging due to the variety of histological appearances of canine melanocytic neoplasms. Markers of malignancy are needed. Receptor for activated C-kinase 1 (RACK1) was found to characterize melanomas in other mammals. We investigated the value of RACK1 detection in the classification of 19 cutaneous and 5 mucosal melanocytic neoplasms in dogs. These tumors were categorized as melanocytomas or benign and melanomas or malignant after evaluation of their morphology, mitotic index, and Ki-67 growth fraction. Using immunofluorescence, we confirmed microphthalmia-associated transcription factor (MITF) as a marker of normal and transformed melanocytic cells in dog tissues. All control (n = 10) and tumoral (n = 24) samples stained positively for MITF (34/34, 100%). Whereas RACK1 was not detected in healthy skin melanocytes, melanocytic lesions were all positive for RACK1 signal (24/24, 100%). RACK1 cytoplasmic staining appeared with 2 distinct distribution patterns: strong, diffuse, and homogeneous or granular and heterogeneous. All melanoma samples (13/13, 100%) stained homogeneously for RACK1. All melanocytomas (11/11, 100%) stained heterogeneously for RACK1. Immunohistochemistry was less consistent than immunofluorescence for all labelings in melanocytic lesions, which were often very pigmented. Thus, the fluorescent RACK1-MITF labeling pattern helped to distinguish melanomas from melanocytomas. Furthermore, RACK1 labeling correlated with 2 of 11 morphological features linked to malignancy: cell and nuclear size. These results suggest that RACK1 may be used as a marker in dog melanomas.
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Biomarcadores Tumorais/metabolismo , Doenças do Cão/diagnóstico , Melanoma/veterinária , Receptores de Superfície Celular/metabolismo , Neoplasias Cutâneas/veterinária , Animais , Diagnóstico Diferencial , Doenças do Cão/metabolismo , Cães , Feminino , Imuno-Histoquímica/veterinária , Antígeno Ki-67/metabolismo , Masculino , Melanócitos/metabolismo , Melanócitos/patologia , Melanoma/diagnóstico , Melanoma/metabolismo , Receptores de Quinase C Ativada , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/metabolismoRESUMO
Resistance to endocrine therapy is a major complication of luminal breast cancer and studies of the biological features of hormonal resistance are limited by the lack of adequate preclinical models. The aim of this study is to establish and characterize a panel of primary human luminal breast carcinoma xenografts, and to evaluate their response to endocrine therapies. Four hundred and twenty-three tumor fragments obtained directly from patients have been grafted in the interscapular fatpad of Swiss nude mice. After stable engraftment with estradiol supplementation, xenografted tumors have been validated by conventional pathology and immunohistochemistry examination, and additional molecular studies. In vivo tumor growth and response to different endocrine treatments were evaluated. We have engrafted 423 tumors including 314 ER+ tumors, and 8 new luminal breast cancer xenografts have been obtained (2.5%). Tumor take was much lower for luminal tumors than for non-luminal tumors (2.5 vs. 24.7%, P < 0.0001), and was associated with two independent criteria, i.e., ER status (P < 0.0001) and a high grade tumor (P = 0.05). Histological and immunohistochemical analyses performed on patient's tumors and xenografts showed striking similarities in the tumor morphology as well as in the expression level of ER, PR, and HER2. Response to hormone therapy, evaluated in 6 luminal models, showed different sensitivities, thus exhibiting heterogeneity similar to what is observed in the clinic. We have established a panel of primary human luminal breast cancer xenografts, recapitulating the biological and clinical behaviors of patient tumors, and therefore suitable for further preclinical experiments.
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Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias da Mama/genética , Hibridização Genômica Comparativa , Feminino , Humanos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Resultado do Tratamento , Carga Tumoral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Metaplastic breast cancer (MBC) is a rare form of breast cancer characterized by an aggressive clinical presentation, with a poor response to standard chemotherapy. MBCs are typically triple-negative breast cancers (TNBCs), frequently with alterations to genes of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways. The objective of this study was to determine the response to PI3K and MAPK pathway inhibitors in patient-derived xenografts (PDXs) of MBCs with targetable alterations. METHODS: We compared survival between triple-negative MBCs and other histological subtypes, in a clinical cohort of 323 TNBC patients. PDX models were established from primary breast tumors classified as MBC. PI3K-AKT-mTOR and RTK-MAPK pathway alterations were detected by targeted next-generation sequencing (NGS) and analyses of copy number alterations. Activation of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways was analyzed with reverse-phase protein arrays (RPPA). PDXs carrying an activating mutation of PIK3CA and genomic changes to the RTK-MAPK signaling pathways were treated with a combination consisting of a PI3K inhibitor and a MEK inhibitor. RESULTS: In our clinical cohort, the patients with MBC had a worse prognosis than those with other histological subtypes. We established nine metaplastic TNBC PDXs. Three had a pathogenic mutation of PIK3CA and additional alterations to genes associated with RTK-MAPK signaling. The MBC PDXs expressed typical EMT and stem cell genes and were of the mesenchymal or mesenchymal stem-like TNBC subtypes. On histological analysis, MBC PDXs presented squamous or chondroid differentiation. RPPA analysis showed activation of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways. In vivo, the combination of PI3K and MAPK inhibitors displayed marked antitumor activity in PDXs carrying genomic alterations of PIK3CA, AKT1, BRAF, and FGFR4. CONCLUSION: The treatment of metaplastic breast cancer PDXs by activation of the PI3K-AKT-mTOR and RTK-MAPK pathways at the genomic and protein levels with a combination of PI3K and MEK inhibitors resulted in tumor regression in mutated models and may therefore be of interest for therapeutic purposes.
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Antineoplásicos/uso terapêutico , Classe I de Fosfatidilinositol 3-Quinases/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Humanos , Camundongos Nus , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Mutação/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
INTRODUCTION: Pure progressive amnesia, a form of progressive focal cortical atrophy is thought to represent the early stages of a rare form of Alzheimer's disease (AD). This syndrome is characterized by the insidious and slowly progressive breakdown of memory, in the absence of a significant impairment in other cognitive domains or in the realm of behavior. The aims of the present study were to contribute to the characterization of this poorly documented type of amnesia, to compare it with other forms of amnestic syndromes resulting from lesions to the medial temporal lobes and to discuss its potential pathophysiological basis. PATIENTS AND METHOD: We carried out three single case studies in patients presenting with pure progressive amnesia. They all underwent a neuropsychological evaluation that included an extensive assessment of spatial and recognition memory, along with brain magnetic resonance imaging and a cerebral blood flow study. RESULTS: All three patients had a severe deficit in the storage of context-free information, along with a severe visual recognition memory impairment, as previously reported in a case study on a patient with pure progressive amnesia (Cognitive Neuropsychology 23 (2006) 1230-1247). Yet, spatial memory remained well preserved, and patients maintained totally independent in everyday life. In addition, a significant atrophy of the medial temporal structures was found. DISCUSSION: This specific pattern of impairment differs from other types of amnestic syndromes after medial temporal damage and raises the question of lesional topography, as well as possible compensatory phenomena. We suggest that pure progressive amnesia results from selective damage to the ventral subhippocampal route into the hippocampal formation leading to impaired context-free memory. Spatial memory may remain intact because the dorsal parahippocampal route into the hippocampus remains functional. Pure progressive amnesia may contribute to a better understanding of the neural systems involved in declarative memory and provide a better understanding into the nature of the memory impairment that characterizes the initial stages of AD.
Assuntos
Atividades Cotidianas , Amnésia/psicologia , Idoso , Idoso de 80 Anos ou mais , Amnésia/patologia , Encéfalo/patologia , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Desempenho Psicomotor/fisiologiaRESUMO
INTRODUCTION: The Verbal Fluency Test (VF) is commonly used in neuropsychology. Some studies have demonstrated a marked impairment of semantic VF compared to phonemic VF in Alzheimer's disease (AD). Since amnestic Mild Cognitive Impairment (aMCI) is associated with increased risk of conversion to incident AD, it is relevant to examine whether a similar impairment is observed in this population. The objective of the present empirical study is to compare VF performance of aMCI patients to those of AD and elderly controls matched one-to-one for age and education. METHOD: Ninety-six participants divided into three equal groups (N = 32: AD, aMCI and Controls) were included in this study. Participants in each group were, on average, 76 years of age and had 13 years of education. A repeated measures ANOVA with the Group (AD, aMCI, NC) as between-subject factor and the Fluency condition ("P" and "animals") as within-subject factor was performed. T-tests and simple ANOVAs were also conducted to examine the interaction. RESULTS: There was a significant interaction between the groups and the verbal fluency condition. In AD, significantly fewer words were produced in both conditions. In contrast, participants with aMCI demonstrated a pattern similar to controls in the phonemic condition, but generated significantly fewer words in the semantic condition. CONCLUSION: These results indicate a semantic memory impairment in aMCI revealed by a simple, commonly-used neuropsychological test. Future studies are needed to investigate if semantic fluency deficits can help predict future conversion to AD.
Assuntos
Doença de Alzheimer/psicologia , Amnésia/psicologia , Disfunção Cognitiva/psicologia , Comportamento Verbal , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Amnésia/complicações , Estudos de Casos e Controles , Disfunção Cognitiva/complicações , Feminino , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , SemânticaRESUMO
Chronic and subchronic toxicity resulting from exposure to microcystins (MCs) receives increasing attention due to the risk of bioaccumulation of these toxins by aquatic animals, including fish. The mechanisms of action of MCs that target the liver, involve modifications of protein phosphorylation resulting from phosphatases 1 and 2A inhibition. Therefore, studying phosphoprotein modifications by using a specific phosphoprotein stain Pro-Q Diamond in fish liver contaminated with MC-leucine-arginine (MC-LR), the most toxic MC, should help dissecting disturbed signaling and metabolic networks. We have recently used this technology to identify several proteins that are modulated either in expression or phosphorylation in the liver of medaka following short-term exposure to MC-LR by balneation. In the present study, we have decided to use an alternative way of introducing the toxin into fish; that is by gavage (force-feeding). This was first achieved using tritiated MC-LR and allowed us to quantify the quantity of toxin incorporated into fish and to demonstrate that the toxin is mainly accumulated in liver. Afterwards a proteomics study limited to liver cytosolic proteins of contaminated animals showed that several proteins were up or down regulated either in quantity or in phosphorylation or both. Some of them had been previously detected as modified in balneation experiments but new molecules were identified as involved in signal transduction pathways activated by the toxin. In addition, in the conditions used (5 microg toxin/g body weight) anatomopathological studies supported a process of apoptonecrosis established after 24h, which was suggested to proceed by the evolution of some of the proteins after 2h contamination.
Assuntos
Proteínas de Peixes/metabolismo , Microcistinas/toxicidade , Oryzias/metabolismo , Fosfoproteínas/metabolismo , Proteômica , Animais , Caspase 3/análise , Caspase 3/metabolismo , Citosol/metabolismo , Eletroforese em Gel Bidimensional , Nutrição Enteral , Regulação da Expressão Gênica , Marcação In Situ das Extremidades Cortadas , Fígado/citologia , Fígado/metabolismo , Toxinas Marinhas , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Espectrometria de Massas por Ionização por Electrospray , Estatísticas não Paramétricas , TrítioRESUMO
While the semantic variant of primary progressive aphasia (svPPA) is characterized by a predominant semantic memory impairment, episodic memory impairments are the clinical hallmark of Alzheimer's disease (AD). However, AD patients also present with semantic deficits, which are more severe for semantically unique entities (e.g. a famous person) than for common concepts (e.g. a beaver). Previous studies in these patient populations have largely focused on famous-person naming. Therefore, we aimed to evaluate if these impairments also extend to other semantically unique entities such as famous places and famous logos. In this study, 13 AD patients, 9 svPPA patients, and 12 cognitively unimpaired elderly subjects (CTRL) were tested with a picture-naming test of non-unique entities (Boston Naming Test) and three experimental tests of semantically unique entities assessing naming of famous persons, places, and logos. Both clinical groups were overall more impaired at naming semantically unique entities than non-unique entities. Naming impairments in AD and svPPA extended to the other types of semantically unique entities, since a CTRL>AD>svPPA pattern was found on the performance of all naming tests. Naming famous places and famous persons appeared to be most impaired in svPPA, and both specific and general semantic knowledge for these entities were affected in these patients. Although AD patients were most significantly impaired on famous-person naming, only their specific semantic knowledge was impaired, while general knowledge was preserved. Post-hoc neuroimaging analyses also showed that famous-person naming impairments in AD correlated with atrophy in the temporo-parietal junction, a region functionally associated with lexical access. In line with previous studies, svPPA patients' impairment in both naming and semantic knowledge suggest a more profound semantic impairment, while naming impairments in AD may arise to a greater extent from impaired lexical access, even though semantic impairment for specific knowledge is also present. These results highlight the critical importance of developing and using a variety of semantically-unique-entity naming tests in neuropsychological assessments of patients with neurodegenerative diseases, which may unveil different patterns of lexical-semantic deficits.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/psicologia , Afasia Primária Progressiva/diagnóstico por imagem , Afasia Primária Progressiva/psicologia , Encéfalo/diagnóstico por imagem , Semântica , Idoso , Atrofia , Feminino , Humanos , Testes de Linguagem , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Tamanho do Órgão , Reconhecimento Visual de Modelos , Reconhecimento PsicológicoRESUMO
BACKGROUND: Inconsistencies regarding the risk of developing Alzheimer disease after traumatic brain injury (TBI) remain in the literature. Indeed, why AD develops in certain TBI patients while others are unaffected is still unclear. OBJECTIVE: The aim of this study was to performed a systematic review to investigate whether certain variables related to TBI, such as TBI severity, loss of consciousness (LOC) and post-traumatic amnesia (PTA), are predictors of risk of AD in adults. METHODS: From 841 citations retrieved from MEDLINE via PubMed, EMBASE, PSYINFO and Cochrane Library databases, 18 studies were eligible for the review. RESULTS: The review revealed that about 55.5% of TBI patients may show deteriorated condition, from acute post-TBI cognitive deficits to then meeting diagnostic criteria for AD, but whether TBI is a risk factor for AD remains elusive. CONCLUSIONS: Failure to establish such a link may be related to methodological problems in the studies. To shed light on this dilemma, future studies should use a prospective design, define the types and severities of TBI and use standardized AD and TBI diagnostic criteria. Ultimately, an AD prediction model, based on several variables, would be useful for clinicians detecting TBI patients at risk of AD.
Assuntos
Doença de Alzheimer/etiologia , Lesões Encefálicas Traumáticas/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Amnésia/etiologia , Transtornos Cognitivos/etiologia , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Cytoplasmic estrogen receptors were detected in 12 of 13 male breast cancer tumors. There was no significant correlation of receptor levels with the age of the patient, size and histological grading of the tumor, and stage and nodal involvement of the disease. Nuclear estrogen receptors were found in eight of 10 tumors and six of nine patients had tumors positive for cytoplasmic progesterone receptors, two of which were also found to contain nuclear progesterone receptors. The presence of cytoplasmic progesterone receptors, in addition to cytoplasmic and nuclear estrogen receptors, may be indicative of truly hormone-dependent tumors in male breast cancer. Treatment offered to patients included surgery, X-ray therapy, chemotherapy, and orchiectomy, but as yet, no general conclusions of the efficacy of the therapeutic regime can be drawn.
Assuntos
Neoplasias da Mama/metabolismo , Núcleo Celular/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Neoplasias da Mama/terapia , Castração , Citoplasma/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
No differences in steroid hormone receptor status were detected in premenopausal breast cancer patients of different races. In postmenopausal women, 65% of Whites were found to have tumors positive for cytoplasmic estrogen receptors (CER) compared with 58, 52, and 41% in women of mixed race, Blacks, and Asians, respectively. The proportions of tumors which contained a full complement of receptors (CER, nuclear estrogen receptors, and cytoplasmic progesterone receptors) were similar in Blacks, Whites, and Asians in each menopausal group. In postmenopausal patients, significantly fewer White women had tumors devoid of all receptors, while having a higher incidence of tumors with an abnormal or defective receptor distribution. Neither the stage of the disease nor the degree of nodal involvement appeared to affect receptor status in any population group, but very large tumors had fewer receptors. White patients with large neoplasms had a significantly higher incidence of CER than Blacks or Asians. Similar observations were made for White patients presenting with Stage III disease, whose tumors were greater of histological Grade I tumors were positive for CER, compared with Grade III neoplasms. Indications are that receptor status is inherent to the natural history of the disease and is not influenced by clinical features.
Assuntos
Neoplasias da Mama/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Adulto , Idoso , Povo Asiático , População Negra , Núcleo Celular/análise , Citoplasma/análise , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Estadiamento de Neoplasias , População BrancaRESUMO
The insulin response to a 100-g oral glucose load was studied in 40 obese (percent desirable weight greater than or equal to 120%) and 40 nonobese (less than 120%) age- and sex-matched Indian patients with non-insulin-dependent diabetes in the young. There were no significant differences between the obese and nonobese patients with respect to their insulin and glucose responses. Thus, it appears that obesity does not exert a significant modulating effect on insulin secretion in patients with fasting hyperglycemia.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus/metabolismo , Hiperglicemia/sangue , Insulina/metabolismo , Obesidade , Adolescente , Adulto , Glicemia/análise , Feminino , Teste de Tolerância a Glucose , Humanos , Índia/etnologia , Insulina/sangue , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , África do SulRESUMO
In 85 patients diagnosed as having non-insulin-dependent diabetes in the young (NIDDY), 6 were found to have nephropathy. The duration of diabetes ranged from 2 to 17 yr; 5 of the 6 patients had retinopathy as evidenced by fluoroscein angiography (3 with proliferative changes). All 6 patients had a 24-h urinary protein excretion greater than 0.5 g and a glomerular filtration rate less than 80 ml/min. Serum beta 2-microglobulin levels were increased in all 6 patients, while only 3 had increased serum creatinine levels.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Adulto , Diabetes Mellitus Tipo 2/genética , Retinopatia Diabética/etiologia , Feminino , Humanos , Índia , Testes de Função Renal , Masculino , Proteinúria/etiologia , RiscoRESUMO
Acute insulin release in response to maximal intravenous doses of glucose (0.5 g/kg), tolbutamide (1 g), and glucagon (1 mg) was studied in 10 subjects with non-insulin-dependent diabetes of the young (NIDDY) and 10 age-, sex-, and weight-matched controls. Diabetic subjects had attenuated insulinemic responses to all three stimuli, in comparison with control subjects. However, insulin responses to glucagon and tolbutamide were higher than those obtained with intravenous glucose. This study demonstrates that the pancreatic beta-cell is more responsive to nonglucose secretagogues than to glucose stimuli in individuals with NIDDY.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Glucagon/farmacologia , Glucose/farmacologia , Insulina/metabolismo , Tolbutamida/farmacologia , Diabetes Mellitus Tipo 2/genética , Humanos , Secreção de Insulina , Taxa Secretória/efeitos dos fármacosRESUMO
In this study seven normal weight Indian patients with polycystic ovarian disease (PCOD) with no evidence of acanthosis nigricans and 7 age- and weight-matched normal Indian women were studied to determine whether PCOD patients were insulin-resistant. While all 14 women had normal glucose tolerance, the PCOD women had significantly higher mean plasma glucose levels at 30 and 60 min and higher mean incremental glucose areas [incremental areas: PCOD, 9.0 +/- 2.2 (+/- SEM); normal women, 4.0 +/- 0.8 mmol/L; P less than 0.05]. Insulin responses were significantly higher in the PCOD compared to normal women (incremental areas: PCOD, 623.8 +/- 78.3; normal women, 226.2 +/- 30.3 microU/mL; P less than 0.001). Both serum testosterone and androstenedione levels correlated with the insulin areas (r = 0.82; P less than 0.001 and r = 0.86; P less than 0.001, respectively). [125I] Insulin binding to erythrocytes revealed decreased maximum specific binding in the PCOD women (6.9 +/- 0.6%) compared to that in normal women (9.2 +/- 0.7%; P less than 0.02). While Scatchard analysis revealed similar receptor numbers, ID50 values demonstrated decreased receptor affinity in the women with PCOD. In conclusion, in the absence of acanthosis nigricans, nonobese patients with PCOD are insulin resistant, and this insulin resistance correlates with the hyperandrogenism.
Assuntos
Resistência à Insulina , Síndrome do Ovário Policístico/complicações , Adulto , Androstenodiona/sangue , Glicemia/metabolismo , Desidroepiandrosterona/análogos & derivados , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona , Eritrócitos/metabolismo , Feminino , Hormônio Foliculoestimulante/sangue , Teste de Tolerância a Glucose , Humanos , Índia/etnologia , Insulina/sangue , Hormônio Luteinizante/sangue , Síndrome do Ovário Policístico/sangue , Receptor de Insulina/metabolismo , África do Sul , Testosterona/sangueRESUMO
We studied the cause of the low serum progesterone, 17 beta-estradiol, and 17-hydroxyprogesterone levels that occur in women with an ectopic pregnancy. Only women who had been amenorrheic for less than 8 weeks were studied in order to assess corpus luteum rather than placental biosynthesis of these steroids; each woman with an ectopic pregnancy was matched to a woman with a normal intrauterine pregnancy on the basis of serum intact hCG levels within 10% of one another to obviate the influence of different levels of this luteotropic hormone. Every woman with an ectopic pregnancy had lower serum progesterone, estradiol, and 17-hydroxyprogesterone levels than her matched normal pregnant pairmate (median values: progesterone, 27.9 vs. 83.5 mmol/L; estradiol, 0.36 vs. 1.79 nmol/L; 17-hydroxyprogesterone, 4.95 vs. 22.1 nmol/L, respectively; all P less than 0.002). The ratios of intact hCG, measured by immunoradiometric assay, to hCG, measured by a hCG beta-specific RIA, were similar in the two groups. Serum hCG bioactivity was assayed by measuring the ability of serum to stimulate testosterone secretion from mouse Leydig cells. The mean biological to intact immunological hCG ratios were 2.06 +/- 1.39 (+/- SD) for ectopic pregnancy and 1.91 +/- 0.81 for normal pregnancy (P greater than 0.05). The biological hCG to immunoreactive hCG beta ratios were 1.98 +/- 0.75 and 2.02 +/- 0.82, respectively. Serum hCG from both groups of women stimulated cAMP generation by testicular cells similarly. We conclude that the lower serum steroid levels in women with ectopic pregnancy cannot be explained by altered hCG bioactivity. The lower steroid levels may thus reflect a primary defect of the corpus luteum, absence of another stimulator of ovarian steroid biosynthesis, or more subtle alterations in hCG glycosylation which are important in vivo but not assessed by the in vitro bioassay.
Assuntos
Gonadotropina Coriônica/sangue , Corpo Lúteo/fisiopatologia , Gravidez Ectópica/fisiopatologia , Animais , Bioensaio , AMP Cíclico/biossíntese , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Concentração Osmolar , Gravidez , Gravidez Ectópica/sangueRESUMO
Mobilization of arachidonic acid from glycerophospholipids and prostaglandin (PG) release from fetal membranes were studied in women with dysfunctional labor in the absence of cephalopelvic disproportion or fetal malposition. Using superfusion of intact amnion and chorion, we found a slight decrease in PGE and a more significant decrease in PGF release by the amniotic side of the fetal membrane obtained from women with dysfunctional labor compared to that in women with normal labor (PGE: normal labor, 2992 pg/cm2.h; dysfunctional labor, 1846 pg/cm2.h; P less than 0.05; PGF: normal labor, 662 pg/cm2.h; dysfunctional labor, 204 pg/cm2.h; P less than 0.02). Release of both prostanoids was significantly greater from the amniotic side in tissues obtained after labor compared to that in prelabor tissue. Analysis of arachidonic acid (by gas liquid chromatography) and phospholipid content (by two-dimensional thin layer chromatography) confirmed metabolic disposal of arachidonic acid from the amnion after the onset of labor. However, no difference in either phospholipid or phospholipase A2-releasable arachidonic acid of individual phospholipid classes was found in amnion tissue from women with normal and dysfunctional labor, suggesting similar activities of phospholipase A2 in these two groups. The finding of decreased free and phospholipase A2-releasable arachidonic acid of the total lipid extract of the amnion of women with dysfunctional labor could suggest further metabolic exhaustion of the substrate or failure of liberation of this fatty acid from glycerophospholipids by enzymes other than phospholipase A2, such as phospholipase C or diacyl and monoacylglycerolipases.
Assuntos
Âmnio/metabolismo , Complicações do Trabalho de Parto/metabolismo , Prostaglandinas F/biossíntese , Adulto , Âmnio/análise , Líquido Amniótico/metabolismo , Ácido Araquidônico , Ácidos Araquidônicos/análise , Ácidos Araquidônicos/metabolismo , Dinoprosta , Feminino , Humanos , Lipídeos/análise , Concentração Osmolar , Fosfolipídeos/análise , Gravidez , Prostaglandinas/metabolismoRESUMO
Oestrogen and progesterone receptors were studied in the non-pregnant state, in early pregnancy and at term using monoclonal antibody enzyme immunoassays. Receptors for both steroids were found in tissues from non-pregnant patients and patients in early pregnancy. At term oestrogen receptors were undetectable in all tissues studied. Progesterone receptors were undetectable in chorion, amnion and placenta at term, while present in extremely low concentrations in decidua and myometrium.