RESUMO
Intestinal absorption in human is routinely predicted in drug discovery using in vitro assays such as permeability in the Madin-Darby canine kidney cell line. In silico models trained on these data are used in drug discovery efforts to prioritize novel chemical targets for synthesis; however, their proprietary nature and the limited validation available, which is usually restricted to predicting in vitro permeability, are barriers to widespread adoption. Because of the categorical nature of the in vitro permeability assay, intrinsic assay variability, and the challenges often encountered when translating in vitro data to an in vivo drug property, validation based solely on in vitro data might not be a good characterization of the usefulness of the in silico tool. In this work, we analyze the performance of three different in silico models in predicting the in vitro and in vivo permeability of 300 marketed drugs and 86 discovery compounds. The models differ in their approach (mechanistic vs quantitative structure-activity relationship) and the degree of complexity; one of them is a linear equation based on seven simple physicochemical descriptors and is presented for the first time in this work. Results show that in silico models can be successfully used to complement the discovery toolbox for characterizing in vivo intestinal permeability, defined using fraction of dose absorbed in human (Fa) and human jejunal permeability (Peff). While the in vitro permeability models outperformed the in silico approach at predicting each of the in vivo end points explored, the gap in predictivity between the in vitro and the in vivo data was generally comparable to the gap between in silico and in vitro data. The in vitro and in silico approaches shared many of the same outliers, which can often be explained by the route of drug absorption (paracellular vs transcellular, active vs passive). Data suggest that the discovery process can greatly benefit from an early adoption of in silico models for predicting permeability as well as from a careful analysis of the in silico to in vivo disconnects.
Assuntos
Modelos Teóricos , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Animais , Permeabilidade da Membrana Celular , Simulação por Computador , Cães , Humanos , Células Madin Darby de Rim Canino , Relação Quantitativa Estrutura-AtividadeRESUMO
The 129 mouse strain is commonly used for the generation of genetically engineered mice. Genetic drift or accidental contamination during outcrossing has resulted in several 129 substrains. Comprehensive data on spontaneous age-related pathology exist for the 129S4/SvJae substrain, whereas only limited information is available for other 129 substrains. This longitudinal aging study describes the life span and spontaneous lesions of 44 male and 18 female mice of the 129S6/SvEvTac substrain. Median survival time was 778 and 770 days for males and females, respectively. Tumors of lung and Harderian gland were the most common neoplasms in both sexes. Hepatocellular tumors occurred mainly in males. Hematopoietic tumors were observed at low frequency. Suppurative and ulcerative blepharoconjunctivitis was the most common nonneoplastic condition in both sexes. Corynebacteria (primarily Corynebacterium urealyticum and C. pseudodiphtheriticum) were isolated from animals with blepharoconjunctivitis and in some cases from unaffected mice, although a clear causal association between corynebacterial infections and blepharoconjunctivitis could not be inferred. Polyarteritis occurred only in males and was identified as the most common nonneoplastic contributory cause of death. Eosinophilic crystalline pneumonia occurred in both sexes and was a relevant cause of death or comorbidity. Epithelial hyalinosis at extrapulmonary sites was noted at higher frequency in females. This study contributes important data on the spontaneous age-related pathology of the 129S6/SvEvTac mouse substrain and is a valuable reference for evaluation of the phenotype in genetically engineered mice obtained with this 129 substrain.
Assuntos
Envelhecimento/patologia , Neoplasias/patologia , Animais , Feminino , Longevidade , Estudos Longitudinais , Masculino , Camundongos , Camundongos Endogâmicos , Modelos Animais , Morbidade , Mortalidade , Neoplasias/mortalidade , FenótipoRESUMO
Ringtail is a pathologic condition of laboratory rodents characterized by annular constrictions of the tail. Traditionally, it is classified as an environmental disorder caused by low relative humidity, but other factors (temperature, dietary deficiencies, genetic susceptibility, and caging type) have also been proposed. Twenty litters of mice with ringtail lesions occurred from September 2010 to August 2013 in a facility located in the northern Italy. Mice were maintained under controlled environmental conditions and fed a standard diet. Retrospective analysis of environmental data (relative humidity, temperature) was carried out. Gross, histopathologic, scanning, and transmission electron microscopy examination of tails and limbs was performed. The incidence of ringtail was 0.075% (20/26 800) of all weaned litters over the 3-year period of examination. Temperature and relative humidity remained within accepted limits in all cases except one. We observed annular constrictions in tail, digits of pes, crus, and antebrachium in 116 (100.0%), 47 (40.5%), 11 (9.5%), and 2 (1.7%) of 116 affected mice, respectively. Histologic and ultrastructural examination revealed abnormal keratin desquamation and presence of a keratin ring encircling the tail, causing progressive strangulation of the growing tail with subsequent compression and ulceration of underlying soft tissues, resulting in circulatory changes (edema, hyperemia, thrombosis, hemorrhages), ischemic necrosis, and eventually auto-amputation distal to the constriction. On the basis of our findings, we suggest a disorder of cornification as the primary lesion of ringtail in mice. The cause of these cases, however, remained undetermined, even though traditional etiologic factors (relative humidity, temperature, diet, caging type) were reasonably excluded.
Assuntos
Constrição Patológica/veterinária , Doenças dos Roedores/patologia , Animais , Animais de Laboratório , Constrição Patológica/patologia , Meio Ambiente , Feminino , Umidade , Incidência , Masculino , Camundongos , Estudos Retrospectivos , TemperaturaRESUMO
This report describes the clinicopathological features of a case of diffuse scaling dermatitis that occurred in a 16-week-old female athymic nude (CrTac:NCr-Foxn1(nu)) mouse. Gross presentation was suggestive of Corynebacterium bovis infection (scaly skin disease). However, C. bovis was not isolated from the skin of the affected animal or from the skin of unaffected CrTac:NCr-Foxn1(nu) mice housed in the same cage or room. Staphylococcus xylosus was instead isolated in high numbers from the skin lesion, whereas only a few colonies were recovered from the skin of unaffected mice. Microscopically, the affected skin was characterized by chronic hyperplastic and hyperkeratotic dermatitis with focal ulcerations, extensive serocellular crusts, and intralesional clusters of Gram-positive coccoid bacteria. Although gross presentation of the reported case was suggestive of C. bovis infection, epidemiological, histopathological, and bacteriological findings definitively ruled out an outbreak of scaly skin disease. A diagnostic hypothesis of hyperplastic and hyperkeratotic dermatitis associated with opportunistic S. xylosus infection was formulated based on increased bacterial burden and presence of intralesional Gram-positive coccoid bacteria.
Assuntos
Dermatite/veterinária , Camundongos Nus , Infecções Oportunistas/veterinária , Doenças dos Roedores/microbiologia , Infecções Estafilocócicas/microbiologia , Animais , Dermatite/microbiologia , Dermatite/patologia , Diagnóstico Diferencial , Feminino , Camundongos , Infecções Oportunistas/microbiologia , Infecções Oportunistas/patologia , Doenças dos Roedores/patologia , Pele/microbiologia , Pele/patologia , Infecções Estafilocócicas/patologia , Staphylococcus/classificação , Staphylococcus/isolamento & purificaçãoRESUMO
The direct interaction between large-scale interplanetary disturbances emitted from the Sun and the Earth's magnetosphere can lead to geomagnetic storms representing the most severe space weather events. In general, the geomagnetic activity is measured by the Dst index. Consequently, its accurate prediction represents one of the main subjects in space weather studies. In this scenario, we try to predict the Dst index during quiet and disturbed geomagnetic conditions using the interplanetary magnetic field and the solar wind parameters. To accomplish this task, we analyzed the response of a newly developed neural network using interplanetary parameters as inputs. We strongly demonstrated that the training procedure strictly changes the capability of giving correct forecasting of stormy and disturbed geomagnetic periods. Indeed, the strategy proposed for creating datasets for training and validation plays a fundamental role in guaranteeing good performances of the proposed neural network architecture.
Assuntos
Atividade Solar , Tempo (Meteorologia) , Humanos , Campos Magnéticos , Redes Neurais de Computação , VentoRESUMO
Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive agent that may act as a cofactor in the progression of AIDS. Here, we describe the first small animal model of HHV-6 infection. HHV-6 subgroup A, strain GS, efficiently infected the human thymic tissue implanted in SCID-hu Thy/Liv mice, leading to the destruction of the graft. Viral DNA was detected in Thy/Liv implants by quantitative polymerase chain reaction (PCR) as early as 4 d after inoculation and peaked at day 14. The productive nature of the infection was confirmed by electron microscopy and immunohistochemical staining. Atypical thymocytes with prominent nuclear inclusions were detected by histopathology. HHV-6 replication was associated with severe, progressive thymocyte depletion involving all major cellular subsets. However, intrathymic T progenitor cells (ITTPs) appeared to be more severely depleted than the other subpopulations, and a preferred tropism of HHV-6 for ITTPs was demonstrated by quantitative PCR on purified thymocyte subsets. These findings suggest that thymocyte depletion by HHV-6 may be due to infection and destruction of these immature T cell precursors. Similar results were obtained with strain PL-1, a primary isolate belonging to subgroup B. The severity of the lesions observed in this animal model underscores the possibility that HHV-6 may indeed be immunosuppressive in humans.
Assuntos
Herpesvirus Humano 6/imunologia , Timo/imunologia , Animais , Células Cultivadas , DNA Viral/análise , Modelos Animais de Doenças , Herpesvirus Humano 6/metabolismo , Humanos , Imuno-Histoquímica , Imunossupressores/imunologia , Camundongos , Camundongos SCID , Microscopia Eletrônica , Subpopulações de Linfócitos T/imunologia , Timo/patologia , Timo/virologia , Transplante de Tecidos , Tropismo/imunologia , Replicação Viral/genéticaRESUMO
Circulating endothelial cells (CECs) were evaluated by flow cytometry in immunodeficient mice bearing human lymphoma. A trend toward higher CEC values was observed on days 7 and 14 after transplant, and differences versus controls were highly significant on day 21 (P = 0.0061). A strong correlation was found between CEC and tumor volume (r, 0.942; P = 0.004) and between CEC and tumor-generated VEGF (r, 0.669; P = 0.02). In mice given cyclophosphamide, most of the circulating apoptotic cells were hematopoietic and not endothelial. Conversely, in mice given endostatin, all of the increase in apoptotic cells was in the endothelial cell compartment. CEC evaluation is promising as a noninvasive, surrogate angiogenesis marker.
Assuntos
Linfoma de Burkitt/sangue , Linfoma de Burkitt/patologia , Endotélio Vascular/patologia , Neovascularização Patológica/sangue , Neovascularização Patológica/patologia , Inibidores da Angiogênese/farmacologia , Animais , Ciclo Celular , Sobrevivência Celular , Colágeno/farmacologia , Ciclofosfamida/farmacologia , Modelos Animais de Doenças , Endostatinas , Citometria de Fluxo , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neovascularização Patológica/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Recent studies have suggested that non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice transplanted with human hematological malignancies show higher levels of engraftment compared with other strains. We used this model to compare xenotransplantability of human leukemia and lymphoma cell lines and to investigate angiogenesis in hematopoietic malignancies. Ten of 12 evaluated cell lines were able to engraft NOD/SCID mice within 120 days. A strong correlation was observed between the amount of vascular endothelial growth factor (VEGF) produced in vitro by cultured cells and the efficiency of tumor engraftment (r = 0.808; P = 0.001), and an inverse correlation was found between VEGF production and the time of tumor engraftment (r = -0.792; P = 0.006) and between VEGF production and the frequency of apoptotic/dead cells in solid tumors (r = -0.892; P = 0.007). Moreover, VEGF production correlated with the frequency of endothelial (CD31+/CD34+) cells in solid tumors (r = 0.897; P = 0.001). Taken together with in vitro data presented here and indicating that the VEGF antagonist Flt-1/Fc chimera inhibits leukemia and lymphoma cell proliferation, our findings support a role for tumor-derived VEGF in leukemia and lymphoma progression. Furthermore, the present study confirms previous observations indicating that VEGF expression may play a crucial role in xenotransplantability of human solid malignancies in SCID mice. The NOD/SCID model is promising for future evaluations of antiangiogenic drugs, alone or in combination with established chemo- or immunotherapy regimens.
Assuntos
Apoptose , Fatores de Crescimento Endotelial/biossíntese , Leucemia Mieloide/patologia , Linfocinas/biossíntese , Doença Aguda , Idoso , Animais , Medula Óssea/irrigação sanguínea , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fatores de Crescimento Endotelial/antagonistas & inibidores , Feminino , Fator 2 de Crescimento de Fibroblastos/biossíntese , Citometria de Fluxo , Humanos , Células Jurkat , Leucemia Mieloide/metabolismo , Linfocinas/antagonistas & inibidores , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/patologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade , Transplante de Neoplasias , Neovascularização Patológica/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
OBJECTIVES: The study aims to analyse the physiological characteristics of top level off-road motocross, enduro, and desert rally motorcyclists to facilitate the design of a specific training program. METHODS: Twenty seven off-road top level riders participated in this study which measured anthropometric data, maximum aerobic power with incremental tests of both arms and legs, isokinetic dynamometry of the knee and elbow, handgrip strength, heart rate, and blood lactate concentrations during competition. RESULTS: The physical demands of the various races appear to influence the development of distinct musculoskeletal characteristics, as well as aerobic and anaerobic metabolism. Motocross riders have more muscle mass, higher isokinetic handgrip strength, and greater aerobic power than enduro and desert rally riders. However, there are no significant anthropometric and physiological differences between desert rally and enduro riders. Desert rally riders tend to be overweight with maximum aerobic power similar to that of healthy individuals. The mechanical characteristics of the motorcycle and the technical and tactical skills of the riders seem to be more important for race success than the metabolic capabilities of the rider. CONCLUSIONS: Desert rally and enduro riders present similar anthropometric and physiological characteristics. Both have a maximum aerobic power similar to that of healthy normal individuals, although desert rally riders tend to be overweight. Motocross riders on the other hand, have more muscle mass, more strength, and greater aerobic power. The differences observed suggest the need for a specific training program to address the requirements of different riders to reduce the possibility of injury.
Assuntos
Traumatismos em Atletas/prevenção & controle , Veículos Off-Road , Aptidão Física/fisiologia , Esportes/fisiologia , Adulto , Antropometria , Composição Corporal/fisiologia , Estatura/fisiologia , Peso Corporal/fisiologia , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Educação Física e Treinamento/métodosRESUMO
This review describes the current knowledge about cell subsets involved in vasculogenesis (i.e., differentiation of endothelial cells from mesodermal precursors) and angiogenesis (i.e., blood vessel generation from pre-existing vessels), together with recent findings about angiogenesis and antiangiogenic therapies in hematopoietic malignancies such as leukemia, lymphoma, myeloma, and myelodysplastic syndromes.
Assuntos
Neoplasias Hematológicas/fisiopatologia , Neovascularização Patológica/fisiopatologia , Animais , Antineoplásicos/farmacologia , Hematopoese/fisiologia , Humanos , Neovascularização Fisiológica/fisiologia , Células-Tronco/imunologia , Células-Tronco/fisiologiaRESUMO
This study describes a new human acute lymphoblastic leukemia (ALL) cell line (ALL-PO) with the t(4;11) translocation established in SCID mice. The ALL-PO line can be maintained by serial transplant in SCID mice with stable immunophenotypic, molecular and karyotypic features. After intravenous (i.v.) injection ALL-PO spread systemically involving the hematopoietic organs and the central nervous system (CNS) of all mice. The homing and the progression of the disease are evaluated by histological analysis and reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of the t(4;11) translocation in the bone marrow, spleen and CNS of SCID mice at different times after engraftment. Occult leukemia was detectable by PCR in the bone marrow of SCID mice as early as three days after the i.v. injection of leukemic cells whereas the first signs of involvement of the spleen and CNS appeared after 14 days; after 24 days all the mice were euthanized because they were moribund and the bone marrow, spleen and CNS showed ample infiltration by leukemic cells. The sensitivity to conventional chemotherapy was tested in this model. ALL-PO in SCID mice did not respond to treatment with vincristine or idarubicin but cyclophosphamide (150 mg kg(-1) i.v., single injection) significantly increased the survival of the mice. The efficacy of such a treatment was more evident when cyclophosphamide was given in the early stages of the disease (detectable only by molecular analysis) but much less effective when the drug was administered when the disease could be detected by conventional histological analysis. The biological behavior and molecular characteristics of ALL-PO make it a good model for studying novel therapeutic strategies for a better control of minimal residual disease.
Assuntos
Cromossomos Humanos Par 11 , Cromossomos Humanos Par 4 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Animais , Antineoplásicos Alquilantes/farmacologia , Ciclo Celular/fisiologia , Sistema Nervoso Central/patologia , Ciclofosfamida/farmacologia , Modelos Animais de Doenças , Humanos , Lactente , Infiltração Leucêmica , Camundongos , Camundongos SCID , Transplante de Neoplasias , Neoplasia Residual , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Transcrição Gênica , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
Four different combinations of 9644Ru and 9640Zr nuclei, both as projectile and target, were investigated at the same bombarding energy of 400A MeV using a 4pi detector. The degree of isospin mixing between projectile and target nucleons is mapped across a large portion of the phase space using two different isospin-tracer observables, the number of measured protons and the tritium to 3He yield ratio. The experimental results show that the global equilibrium is not reached even in the most central collisions. Quantitative measures of stopping and mixing are extracted from the data. They are found to exhibit a quite strong sensitivity to the in-medium ( n,n) cross section used in microscopic transport calculations.
RESUMO
Most agrochemical and pharmaceutical companies have set up high-throughput screening programs which require large numbers of compounds to screen. Combinatorial libraries provide an attractive way to deliver these compounds. A single combinatorial library with four variable positions can yield more than 10(12) potential compounds, if one assumes that about 1000 reagents are available for each position. This is far more than any high-throughput screening facility can afford to screen. We have proposed a method for iterative compound selection from large databases, which identifies the most active compounds by examining only a small fraction of the database. In this article, we describe the extension of this method to the problem of selecting compounds from large combinatorial libraries. Copyright 1998 John Wiley & Sons, Inc.
RESUMO
Ringtail is a pathologic condition of the tail of rats and other rodents that is traditionally attributed to low environmental humidity, although dietary deficiencies, genetic susceptibility, environmental temperature, and degree of hydration of the animal also have been suggested as possible causes. To the authors' knowledge, a detailed histopathologic study that may serve to shed light on the etiopathogenesis of this disease has not yet been published. We describe the histologic findings of ringtail observed in 12 suckling Munich Wistar Fromter (MWF) rats from two litters. Epidermal hyperplasia characterized by orthokeratotic and parakeratotic hyperkeratosis and acanthosis was observed in all affected rats. Numerous often dilated vessels were present in the dermis of tails that appeared of red/brown color at gross examination. In severe cases, the dilated vascular structures were thrombotic and accompanied by dermal hemorrhages and focal coagulative necrosis of the overlying epidermis. These findings suggest that epidermal acanthosis and hyperkeratosis are the main and primary events in the development of ringtail. To clarify the cause of this disease, future studies should be focused on the numerous factors that can induce such epidermal changes.
Assuntos
Proteínas Alimentares/administração & dosagem , Ratos Wistar/fisiologia , Doenças dos Roedores/patologia , Dermatopatias/veterinária , Cauda/patologia , Animais , Animais Lactentes , Feminino , Histocitoquímica/veterinária , Masculino , Ratos , Doenças dos Roedores/etiologia , Dermatopatias/etiologia , Dermatopatias/patologiaRESUMO
Hyperkeratotic dermatitis of athymic nude mice is an infectious disease caused by a coryneform bacterium. During the spring of 1995, outbreaks of hyperkeratotic dermatitis were observed in several nude mice facilities in northern Italy. In this report we describe the clinical, histopathological and microbiological features of the disease in two different animal facilities. Affected animals showed a typical 'scaly' appearance with small white flakes of material adherent to the skin. In one of the outbreaks (facility 2) the lesions were less severe and involved only limited areas of the body. The infection spread very quickly and the morbidity reached more than 80% in a few days, while the mortality was about 1%. The lesions resolved spontaneously within 7-10 days. Histological examination of affected skin revealed orthokeratotic hyperkeratosis, acanthosis and dermal inflammatory infiltration which were more severe in mice from facility 1. In Gram-stained sections groups of rods consistent with coryneform bacteria were detectable in the keratin layers covering the epidermal surface. A coryneform bacterium, biochemically typed as Corynebacterium bovis, was isolated from 11 out of 11 mice from facility 1 and from 8 out of 11 mice from facility 2.
Assuntos
Infecções por Corynebacterium/veterinária , Surtos de Doenças/veterinária , Camundongos Nus , Doenças dos Roedores/epidemiologia , Dermatopatias Bacterianas/epidemiologia , Pele/patologia , Animais , Corynebacterium/isolamento & purificação , Infecções por Corynebacterium/epidemiologia , Infecções por Corynebacterium/patologia , Feminino , Itália/epidemiologia , Masculino , Camundongos , Morbidade , Doenças dos Roedores/microbiologia , Doenças dos Roedores/patologia , Pele/microbiologia , Dermatopatias Bacterianas/microbiologia , Dermatopatias Bacterianas/patologiaRESUMO
Hyperkeratosis-associated coryneform (HAC) is a coryneform bacterium, with a biochemical profile similar to Corynebacterium bovis, that causes hyperkeratotic dermatitis in athymic nude mice. In the present study 28 severe combined immunodeficient (SCID) mice coming from six different animal facilities were submitted for bacteriological and pathological examination. HAC was isolated from 10 SCID mice belonging to two of these facilities. Two of the HAC-infected mice showed macroscopical lesions consisting in large alopecic areas, with small white flakes, involving the dorsum, flanks, neck and cheeks. Histologically, the skin of these animals was characterized by diffuse acanthosis and hyperkeratosis. In the other eight HAC-infected SCID mice no macroscopical lesions were observed but focal areas of minimal to mild acanthosis were histologically detected in five cases. These results suggest that HAC can infect SCID mice inducing skin lesions similar, although generally less severe, to those observed in nude mice with hyperkeratotic dermatitis. Our results pointed out that SCID mice may play an important role in the epidemiology of hyperkeratotic dermatitis of athymic nude mice.
Assuntos
Infecções por Corynebacterium/patologia , Ceratose/microbiologia , Dermatopatias Bacterianas/patologia , Animais , Corynebacterium , Feminino , Ceratose/patologia , Masculino , Camundongos , Camundongos SCID , Pele/patologiaRESUMO
A case of acute lead poisoning caused by drinking wine that had been kept in a decorative amphora is reported. Chomico-physical analysis of the internal surface of the recipient evidenced a layer of lead paint very soluble in wine. It is hoped that this report will draw the attention of the practising physician and Preventive Medicine Departments to this unusual cause of saturnism. The craft production of earthenware recipients that have been inadequately glazed and their improper use as containers of drings of foods could be commoner than might be thought on the basis of the sporadic reporting of such cases of lead poisoning.
Assuntos
Intoxicação por Chumbo/etiologia , Vinho/intoxicação , Adulto , Utensílios de Alimentação e Culinária , Humanos , Chumbo/análise , Masculino , Vinho/análiseRESUMO
The figures obtained in simultaneous radioimmunological assays of serum folate and vitamin B12 concentrations and erythrocyte folate concentration in 74 patients are presented. All these patients had a regular daily intake of over 80 g ethyl alcohol and presented an increase in mean blood cell volume. Most of the patients were males hospitalised with liver disease and/or anaemia. All were given bone narrow needle aspirations and liver biopsies. 46% of the patients presented a reduction in erythrocyte folates but vitamin B12 deficiency was rarely encountered. Megaloblastic transformation of the bone narrow was present in 56% of the alcoholics with reduced erythrocyte folates and in 10% of those with normal folate concentration. No correlation was found between serum and erythrocyte folate concentration and degree of liver damage. Serum vitamin B12 levels were higher in patients with cirrhosis. Inadequate diet was frequently found in the alcoholics with reduced folate concentrations. Due to variations in patient selection it is difficult to compare these data with those of other series but they do seem to confirm the hypothesis that the macrocytosis in most "healthy" alcoholics reflects a direct toxic action of the alcohol on erythropoiesis. In contrast folate deficiency is found among "derelict" chronic alcoholics in whom the vitamin deficiency has often not yet produced megaloblastosis of the bone marrow.
Assuntos
Alcoolismo/sangue , Anemia Macrocítica/sangue , Anemia Megaloblástica/sangue , Eritrócitos/análise , Ácido Fólico/sangue , Vitamina B 12/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Alcoolismo/patologia , Eritrócitos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
T-cell chronic lymphocytic leukemia: clinical aspects and laboratory findings of five patients. This study illustrates the main clinical aspects and laboratory findings for five patients suffering from T-cell chronic lymphocytic leukemia. They make up 5% of our observations in the Department of Oncology-Hematology at the Busto Arsizio Hospital. Three patients with phenotype CD3+/CD4+ showed a fast course with skin involvement and poor response to chemotherapy (mean survival: 12 months). The course of a patient with unusual phenotype CD3-/CD4+ associated with autoimmune hemolytic anemia and end-stage prolymphocytic transformation was better (survival: 58 months). For 12 years we have been observing a woman suffering from the recently defined CD3+/CD8+/HNK1+ large granular lymphocytes chronic lymphocytosis with associated neutropenia. The disease has good prognosis, with poor symptomatology even without therapy. This study supports the immunological classification of the chronic lymphoproliferative diseases of leukemia and lymphoma with different clinical aspects and prognoses. This method of classification may be important in the consideration of some therapeutical approaches.