RESUMO
Bread forms an integral part of the daily diet in many cultures worldwide. At the same time, a significant number of people try to avoid wheat-based products for either health reasons or due to personal preferences. The absence of a protein network in gluten free bread affects its structure, taste, texture and shelf-life. This paper suggests a technological solution to this issue that uses a pre-foamed mass of gluten free raw materials which is mixed with the bread's ingredients, then kneaded and baked to form a high quality gluten free bread. To survive the high shear stresses during kneading and temperature increase during baking, the foam requires exceptional stability. This stability was achieved through particle stabilisation of the bubble interfaces. Both of the tested foams (with and without particles) exhibited thermal stability up to 80 °C. However, resistance to shear stresses was higher in the particle stabilised foams. Of all the tested particles, linseed press cake and banana powder led to the best results. In conclusion, particle stabilised foams seem very well suited to applications in gluten free baked goods. Further application potential is seen for vegan foamed desserts.
RESUMO
Cloninger's Unified Biosocial Theory of Personality postulates a relationship between the relative functional activity of central serotonergic, dopaminergic, and noradrenergic neurotransmitter systems, and the strength of three elemental dimensions of personality. These dimensions are Harm Avoidance, Novelty Seeking, and Reward Dependence, respectively. Accordingly, we predicted that neuroendocrine responses to serotonergic challenge would correlate with Harm Avoidance scores, but not with Novelty Seeking or Reward Dependence scores. We examined the relationship between the prolactin and cortisol responses to a 12.5-mg intravenous clomipramine challenge and these personality dimensions as measured by Cloninger's Tridimensional Personality Questionnaire in 32 healthy subjects. The cortisol response correlated only with Harm Avoidance scores, as predicted; however, prolactin response did not correlate with Harm Avoidance scores. Instead, it demonstrated an inverse relationship with Novelty Seeking scores. There was a positive relationship of baseline prolactin with Harm Avoidance in a post hoc analysis. Cortisol response to serotonergic challenge may be a better indicator for responsivity of serotonergic systems as they relate to the personality dimension of Harm Avoidance than is prolactin. Prolactin responses may be overly affected by dopaminergic influences; however, baseline prolactin may still be a valid indicator of serotonergic tone.
Assuntos
Antidepressivos Tricíclicos/farmacologia , Clomipramina/farmacologia , Testes de Personalidade , Adolescente , Adulto , Área Sob a Curva , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Prolactina/sangue , Valores de Referência , Inquéritos e QuestionáriosRESUMO
The effect of an initial challenge with the serotonin (5-HT) uptake inhibitor clomipramine (CMI) on subsequent rechallenge was studied in healthy men who served as volunteers. Carefully screened volunteers were assigned to one of three conditions: (1) CMI challenge followed 2 weeks later by CMI rechallenge; (2) placebo challenge followed 2 weeks later by CMI challenge; and (3) CMI challenge followed 4 weeks later by CMI rechallenge. We found significant blunting of the prolactin response to CMI rechallenge 2 weeks (Signed Rank = -12, p = 0.05), but not 4 weeks after an initial challenge. Placebo challenge did not effect CMI challenge 2 weeks later. These findings suggest that a single exposure to IV CMI may cause 5-HT receptor changes that are present 2, but not 4 weeks later. The ramifications of this finding with regard to the use of 5-HT challenge paradigms in a test-retest design are discussed.
Assuntos
Clomipramina/farmacologia , Prolactina/sangue , Adolescente , Adulto , Esquema de Medicação , Humanos , Masculino , Receptores de Serotonina/efeitos dos fármacos , Receptores de Serotonina/fisiologiaRESUMO
OBJECTIVE: Neuroendocrine challenge paradigms have been used to asses serotonergic systems in depression, but limitations in the specificity of many of these tests have been noted. In this study, the neuroendocrine responses to acute intravenous administration of the serotonin (5-HT) reuptake inhibitor clomipramine were assessed in depressed patients and matched control subjects. METHODS: Thirty hospitalized patients who met DSM-III-R criteria for major depression, and 30 healthy control subjects who were matched for age, sex, and season of year for the time of study, received 12.5 mg of intravenously administered clomipramine. RESULTS: The depressed patients demonstrated significant blunting of prolactin responses to clomipramine, as well as trends toward blunted ACTH and cortisol responses. There was no difference between the patient and control groups in growth hormone responses, plasma clomipramine levels, or self-reports of side effects. CONCLUSIONS: These data support the hypothesis that depressed patients have abnormal neuroendocrine responses to the intravenous administration of the 5-HT reuptake inhibitor clomipramine. Further study is required to delineate the mechanisms responsible for the abnormal response to intravenously administered clomipramine in depression.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Clomipramina , Transtorno Depressivo/diagnóstico , Hidrocortisona/sangue , Prolactina/sangue , Adolescente , Adulto , Clomipramina/administração & dosagem , Clomipramina/sangue , Transtorno Depressivo/sangue , Feminino , Hospitalização , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Receptores de Serotonina/efeitos dos fármacosRESUMO
The syntheses of the ring and four side-chain dihydroretinoic acids and/or their esters, 3-7, are described. The syntheses of several other retinoids containing a substituted aromatic ring are also included. The biological activity of the compounds was evaluated in vivo in a chemically induced mouse skin papilloma test and in vitro in two vitamin A deficient assays. The activity observed for 1a, 1c, and 2a in the former test was partially retained in the dihydro derivatives 4b, 4c, and 6b. Similar results were found in the in vitro assays.
Assuntos
Tretinoína/análogos & derivados , Vitamina A/análogos & derivados , Animais , Células Cultivadas , Cricetinae , Feminino , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Técnicas de Cultura de Órgãos , Papiloma/tratamento farmacológico , RNA/metabolismo , Pele/citologia , Pele/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Tretinoína/síntese química , Tretinoína/farmacologia , Tretinoína/uso terapêutico , Deficiência de Vitamina A/tratamento farmacológicoRESUMO
Transient pure red cell aplasia (PRCA) in three consecutive patients receiving ATG for management of kidney graft rejection prompted a systematic study of the effects on erythropoiesis of the ATG preparation used at our institution. We found that 90% of patients treated with rabbit anti-T lymphoblast globulin developed reticulocytopenia (less than 17,000 reticulocytes/mm3), with complete disappearance of reticulocytes in 65% of patients and increased requirement for red cell transfusion. PRCA, with selective aplasia of erythroblasts was confirmed by bone marrow aspiration in 4 patients volunteering for aspiration, and by the kinetic of the disappearance of blood reticulocytes in relation to the beginning of ATG treatment. The nadir of thrombocytes and lymphocytes, blood cells directly destroyed by ATG in circulation, followed the start of ATG treatment within 1 to 4 days. In contrast the nadir of reticulocyte counts occurred later, between day 7 and 13 after ATG was begun, reflecting the fact that toxicity was directed against red cell precursors rather than mature circulating cells. In agreement with these clinical findings ALG was found to be cytotoxic in vitro for erythroid precursors. Analogously to autoimmune PRCA caused by autoantibodies to erythroblasts, this type of PRCA could be viewed as "heteroimmune disease."
Assuntos
Soro Antilinfocitário/efeitos adversos , Transplante de Rim , Aplasia Pura de Série Vermelha/etiologia , Adolescente , Adulto , Idoso , Azatioprina/efeitos adversos , Contagem de Células Sanguíneas , Cadáver , Eritropoese/efeitos dos fármacos , Humanos , Pessoa de Meia-IdadeRESUMO
The use of neutrophil left-shift parameters in the diagnosis of inflammatory and infective disease (ID) was evaluated. The level of C-reactive protein (CRP), currently the best quantitative parameter of inflammation, was used as the gold standard. Of 292 patients, 230 (79%) had a level of CRP of 1.0 mg/dL or greater and were classified as having inflammation, whereas 62 (21%) had normal levels. The neutrophil band count in each patient was determined by microscopic examination of 200 WBCs. The diagnostic value of the band count as an indicator for ID was evaluated in comparison to the WBC count, the neutrophil count, and the left-shift indicators of two automated hematologic analyzers, H*1 Technicon (Bayer Technicon Instruments, Tarrytown, NY) and Coulter MAX M (Coulter Electronics, Hialeah, Fla). When receiver operating characteristics were used, the band count was superior to the immature to total neutrophil count (I/T) ratio, the total WBC count, and the neutrophil count. The sensitivity and specificity in identifying ID at designated cutoff points were as follows: band count of 20% or greater of total WBC count (53% and 79%, respectively), I/T ratio of 0.25 or greater (59% and 63%), total WBC count of 9.6 x 10(6)/mL or greater (68% and 56%), and neutrophil count of 8.0 x 10(6)/mL or greater (60% and 58%). The performance of the H*1 Technicon left-shift flag was similar but slightly inferior to the band count (sensitivity, 44%; specificity, 79%), whereas the Coulter MAX M flags had a clearly higher sensitivity (79%) and lower specificity (53%). In addition, microscopic evaluation to determine the presence of reactive morphologic changes in neutrophils, such as toxic granules, Döhle bodies, and cytoplasmic vacuoles, had a high sensitivity (80%) but a low specificity (58%) in predicting ID. The diagnostic value of both microscopic and automated neutrophil left-shift parameters as indicators for ID is limited. Morphologic changes in neutrophils, however, either have a high specificity (band count) or a high sensitivity (toxic signs) in predicting ID and therefore may be a clinically useful tool.
Assuntos
Doenças Transmissíveis/diagnóstico , Inflamação/diagnóstico , Contagem de Leucócitos/métodos , Neutrófilos/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Automação , Proteína C-Reativa/análise , Feminino , Humanos , Leucocitose , Masculino , Pessoa de Meia-Idade , Neutrófilos/classificação , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e EspecificidadeRESUMO
We report the occurrence of the syndrome of persistent polyclonal B-cell lymphocytosis in a brother and a sister. Both showed the morphological and immunophenotypic features of this rare disorder. In addition both had mild splenomegaly, increase of serum IgM and serological evidence of previous EBV infection. Of interest, two additional brothers had no evidence of PPBL but were indistinguishable in terms of HLA haplotype (HLA-DR7), smoking habits or evidence of EBV infection. These observations provide additional support for a genetic basis of the syndrome but suggest that pathogenic factors other than those known so far may be required for its full expression.
Assuntos
Linfócitos B/patologia , Proteínas do Capsídeo , Saúde da Família , Linfocitose/etiologia , Antígenos Virais/sangue , Suscetibilidade a Doenças/etiologia , Antígenos Nucleares do Vírus Epstein-Barr/sangue , Feminino , Antígenos HLA-DR , Humanos , Imunoglobulina M/sangue , Linfocitose/diagnóstico , Linfocitose/genética , Masculino , Pessoa de Meia-Idade , Núcleo Familiar , Fatores de Risco , FumarRESUMO
1. Several factors, including age, gender, and season of the year, have been reported to affect physiologic indices of central serotonergic function, although some of these findings have not been consistent across groups of subjects and types of serotonergic measures. 2. The authors investigated the role that each of these variables might play in the neuroendocrine response to acute intravenous challenge with the serotonin reuptake inhibitor clomipramine (CMI) in healthy volunteers. 3. Thirty seven healthy subjects (17 women and 20 men), with an age range of 19 to 50 years, received 12.5 mg of CMI intravenously under standardized conditions. 4. The maximum change from baseline in plasma prolactin concentrations ("delta-max") was significantly related to age, after controlling for gender and season. 5. In contrast, neither gender nor season was significantly related to prolactin delta-max, after controlling for the other two variables. 6. Although the age range and sample size are relatively limited, the results from this study suggest that age, but not gender or season, may influence serotonergic function, as measured by the prolactin response to CMI challenge.
Assuntos
Envelhecimento/fisiologia , Serotonina/fisiologia , Adulto , Proteínas Sanguíneas/metabolismo , Clomipramina , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Prolactina/sangue , Valores de Referência , Estações do Ano , Inibidores Seletivos de Recaptação de Serotonina , Caracteres SexuaisRESUMO
Depression in the aged is common and associated with substantial medical and social morbidity and mortality. It is often missed or misdiagnosed because of masked or somatic symptoms, delusions, and pseudodementia. At any given time, about 2 per cent of the elderly have major depression and a third to a half of older psychiatric inpatients and outpatients have mood disorders. Aged depressives have more somatization, hypochondriasis, anxiety, retardation, and delusionality but less guilt, loss of libido, and family history of depression than young ones. Both the illnesses common in the elderly and the medicines used to treat them may be etiologically connected with depression. After precipitating causes are remedied, remaining symptoms respond to antidepressant treatment. Medication doses are much lower and side effects more troublesome. ECT or concomitant antipsychotic medication are more likely to be indicated.
Assuntos
Idoso/psicologia , Transtorno Depressivo/diagnóstico , Antidepressivos/efeitos adversos , Delusões/diagnóstico , Transtorno Depressivo/etiologia , Transtorno Depressivo/terapia , Transtornos Autoinduzidos/diagnóstico , Humanos , MasculinoRESUMO
To test the hypothesis that circulating FDP may stem from extravascular proteinolysis of fibrin (fibrinogen), eight patients with a pleural or peritoneal effusion had an intravenous injection of 125I-fibrinogen and a simultaneous intracavitary injection of 131I-fibrinogen. Two days after injection a mean of 12% of intravascularly injected radioactivity was found in the extravascular cavity, whereas 4.8% of the extravascularly administered radioactivity could be recovered in the circulation. Of the activity exchanged in both directions, more than half was protein-bound, and more than a quarter was clottable. The results demonstrate not only a rapid and considerable extravasation but also a definite back-flow of both clottable and unclottable fibrin (fibrinogen) derivatives from the extravascular space into the circulation. Thus, in the presence of pleural or peritoneal effusion, a shortened fibrinogen t1/2 as well as raised levels of FDP should be interpreted with caution. They may be due, at least to some extent, to an exchange between intravascular and extravascular spaces rather than to intravascular coagulation or fibrinolysis, respectively. The demonstration of fibrinogen proteolysis in effusions further emphasizes that conventional compartmental analysis of plasma and urine radioactivity after intravenous radiofibrinogen injection is highly questionable in pathological conditions.
Assuntos
Fibrinogênio/metabolismo , Injeções Intraperitoneais , Injeções Intravenosas , Animais , Coagulação Sanguínea/efeitos dos fármacos , Feminino , Fibrinogênio/administração & dosagem , Fibrinogênio/farmacologia , Humanos , MasculinoRESUMO
Twenty-four patients with major depression were treated in a single-blind design with 25 mg to 75 mg gepirone, a pyrimidinyl piperidinedione analog of buspirone with serotonin1A (5-HT1A) receptor affinity properties. Twenty-four-Item Hamilton Rating Scale for Depression-(HAM-D) scores decreased by 36 percent when mean baseline scores were compared with an endpoint analysis of 6 weeks' gepirone treatment. Several subjects demonstrated marked improvements over baseline. The data are discussed within the context of 5-HT1A receptor desensitization as a potential component of antidepressant treatment.
Assuntos
Ansiolíticos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Pirimidinas/uso terapêutico , Serotonina/fisiologia , Adulto , Idoso , Transtorno Depressivo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação PsiquiátricaRESUMO
Clinical, histological and serological data of 72 patients with antimitochondrial antibodies (AMA) were analyzed. 56 (78%) of the patients exhibited chronic cholestatic hepatopathy; in 30 of these primary biliary cirrhosis (PBC) was diagnosed and in 26 "possible PBC". The remaining 16 patients were subsumed in an "other illness' group. A collagen or autoimmune disease was found in 8 patients of the chronic cholestatic hepatopathy group and in 3 of the "other illness" group. Histological findings were diagnostic for PBC or cirrhotic liver in 90% of the patients with clinical signs, while 64% of the symptomfree patients had unspecific histological liver alterations. In general, increasing serum IgM, alkaline phosphatase, gamma-GT and symptoms paralleled increasing AMA titers, although asymptomatic patients with high AMA titers were also seen. The prevalence of hepatopathies rose with increasing AMA titers, but otherwise no association of AMA titers and diagnosis was observed. Therefore, a positive AMA test bears out suspicion of hepatopathy, but cannot be regarded as specific for PBC when other liver signs are absent.
Assuntos
Autoanticorpos/análise , Doenças Autoimunes/imunologia , Cirrose Hepática Biliar/imunologia , Mitocôndrias Hepáticas/imunologia , Colestase Intra-Hepática/imunologia , Doenças do Colágeno/imunologia , Humanos , Imunoglobulinas/metabolismo , Membranas Intracelulares/imunologia , Testes de Função HepáticaRESUMO
A report is presented on two brothers with erythropoietic protoporphyria (EPP) with massively and moderately elevated RBC-protoporphyrin content respectively. Both exhibited splenic and one also intravascular hemolysis. The mechanism of hemolysis was investigated on the basis of filterability, plasma trapping and osmotic resistance of in vivo RBCs and of incubated, UV-light exposed RBCs. Photodynamic damage to EPP-RBC, leading to increased RBC rigidity, increased splenic trapping and intravascular hemolysis, appears to play a crucial role in the causation of hemolysis in vivo as well as in vitro.
Assuntos
Hemólise , Porfirias/sangue , Adolescente , Criança , Eritropoese , Humanos , Masculino , Porfirias/fisiopatologia , Protoporfirinas/sangue , Baço/fisiopatologiaRESUMO
According to international recommendations, the diagnosis of chronic lymphocytic leukaemia (CLL) is made on the grounds of persistent peripheral lymphocytosis or lymphocytic infiltration of the bone marrow. The appearance of morphologically atypical lymphocytes in low-grade malignant lymphoma (NHL) or CLL is easily overlooked, and is generally not regarded as a diagnostic criterion. We report 12 cases of CLL/NHL who were detected only by morphological screening of routine peripheral blood smears (83,400 blood smears). The diagnosis of CLL/NHL was not suggested by the patients' history, physical or other laboratory findings, and had not been contemplated by the physician in charge. Monoclonality of peripheral lymphocytes was confirmed by immunophenotyping and Southern blotting. The lymphoma was classified histologically according to the International Working Formulation (bone marrow biopsy). A monoclonal lymphatic population was not found by immunophenotyping in the blood of 11 patients whose lymphocytes were morphologically classified as activated-abnormal. However, 3 patients suspected to have NHL/CLL on morphological screening of blood smears had to be classified as benign after immunophenotyping. We conclude that morphological screening of routine blood smears is an inexpensive and easy additional screening method for CLL and low grade malignant NHL.
Assuntos
Citometria de Fluxo/métodos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Linfócitos/patologia , Linfoma/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
A review of recent investigations in the retinoid field is presented. Retinoic acid exerts a prophylactic and a therapeutic effect on chemically induced benign and malignant epithelial tumors in mice. In clinical studies positive therapeutic results have been obtained in patients with preneoplastic and neoplastic epithelial lesions. However, treatment with retinoic acid is limited by serious side effects (hypervitaminosis A syndrome). Therefore, the synthesis of analogs of retinoic acid (retinoids) possessing a more favorable therapeutic ratio has been initiated. Among a large series of synthesized compounds, certain aromatic analogs proved to have a particularly favorable therapeutic ratio. The structure-activity relationship of the most active retinoids is discussed including some biological data concerning prophylaxis and therapy of epithelial tumors. The total synthesis of retinoids according to various building schemes is discussed in detail. Methods for the synthesis of the cyclic end group, of the polyene chain component, and of the full retinoid skeleton are described. Metabolic studies of retinoic acid and of the most active retinoid, as well as the synthesis of some isolated metabolites are outlined. Suggestions concerning the mechanism of action of retinoids are made. Some clinical results on the treatment of acne, psoriasis and precancerous conditions are reported.
Assuntos
Dermatopatias/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Vitamina A/análogos & derivados , Animais , Carcinoma/tratamento farmacológico , Humanos , Neoplasias Experimentais/tratamento farmacológico , Papiloma/tratamento farmacológico , Retinaldeído/uso terapêutico , Dermatopatias/prevenção & controle , Relação Estrutura-Atividade , Tretinoína/análogos & derivados , Tretinoína/metabolismo , Tretinoína/uso terapêutico , Vitamina A/efeitos adversos , Vitamina A/uso terapêuticoRESUMO
Large granular lymphocytes (LGL) proliferation is characterized by expansion of cytotoxic lymphocytes and associated with neutropenia. In a case of CD3+ LGL-proliferation the epinephrine stimulation test (EST) induced a striking elevation of CD3+, CD8+, CD57+ LGL in peripheral blood from 2.7 x 10(9)/l to 20 x 10(9)/l and might be an additional diagnostic tool in patients with normal or low absolute numbers of circulating LGL. After treatment with steroids, plasma elastase--a marker of neutrophil destruction--decreased from 162 to 40 micrograms/l (normal < 47 micrograms/l) which correlated well with a simultaneous increase in peripheral neutrophil counts from 0.14 to 1.0 x 10(9)/l. This finding supports the hypothesis that neutropenia in CD3+ LGL proliferation is due to neutrophil destruction, possibly mediated by LGL.
Assuntos
Complexo CD3/sangue , Epinefrina , Linfocitose/diagnóstico , Elastase Pancreática/sangue , Idoso , Artrite Reumatoide/complicações , Biomarcadores/sangue , Divisão Celular , Feminino , Glucocorticoides/uso terapêutico , Humanos , Contagem de Leucócitos , Linfocitose/complicações , Linfocitose/tratamento farmacológico , Neutropenia/etiologiaRESUMO
The malignant proliferation of natural killer (NK) cells which are morphologically characterized as large granular lymphocytes (LGL) is a well known clinical entity which was named after its morphological appearance as LGL-leukemia/lymphoma. Similar to non-malignant NK-cells, these tumors can be divided into those which express the CD3-T-cell receptor complex and those which do not. The CD3-positive type of LGL-leukemia is immunophenotypologically characterized by the expression of CD16, and variably CD 56 and CD 57, and generally follows a more indolent course. In contrast, malignant proliferations of CD3-negative LGL express either CD16 or CD 56, and only occasionally CD 57 on their cell surface. Clinically, CD3-negative NK-lymphomas tend to progress rapidly. We report here the case of a high grade malignant lymphoma which was characterized by an immunophenotype typical for CD3-negative NK-cells (CD2+, CD3-, CD16+, CD56(+), CD57-). The disease proved to be rapidly fatal despite aggressive chemotherapy. Interestingly, the patient suffered from a high turn over pancytopenia, which also characterizes NK-cell leukemias/lymphomas of the LGL-type. However, our patient's lymphatic cells appeared highly immature, and cytoplasmic granules, characteristic for LGL-cells, could not be discerned either microscopically or electronmicroscopically. Furthermore, the malignant lymphatic population had the T-cell receptor beta-chain rearranged. We therefore concluded that our patient might have suffered from a malignant proliferation of a putative precursor cell intermediate between T-cells and NK-cells.